NCI 2014 / 3

ISSN 2148 - 4902

NORTHERN CLINICS OF ISTANBUL • İSTANBUL KUZEY KLİNİKLERİ

Vol. 1 • No. 3 • Year 2014

The correlation between tenascin-c expression, and formation of intestinal stricture • Carpal tunnel syndrome in women working in tea agriculture • Investigation of the efficacy of transobturator

INDEXED IN TURKIYE CITATION INDEX.

tape surgery in stress urinary incontinence • Gastroesophageal reflux symptoms in Turkish people • The knowledge, attitude and behaviour of nurses, working in a state hospital about pharmacovigilance,

adverse drug neaction and event reporting • Effect of botulinum toxin type-A in patients with focal spasticity • Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors • The

evaluation of demographic characteristics and general disease of patients affiliated with Home Health Care Unit of Malatya State Hospital • Cutaneous adverse effects of imatinib mesylate • Marfan syndrome with a

giant noncoronary sinus of Valsalva aneurysm • Aural myiasis • Lidocaine intoxication in axillary block: similar pharmaceutical form, different concentration • General approach to velocardiofacial

anomalies: a pediatric case presenting with Fallot tetralogy • Myoclonusdystonia syndrome • Dramatic response in the dependency to transfusion after low doses of lenalidomide treatment in a 5q-syndrome patient

NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ Editor-in-Chief

Vıce Editors

Bekir Durmus, M.D.

Banu Mesci, M.D. Berna Terzioglu Bebitoglu, M.D. Ender Onur, M.D. Levent Doganay, M.D. Tunc Eren, M.D.

Scientıfıc Commıttee Abdullah Aydın, M.D.

Gencer Meryem, M.D.*

Ali Ihsan Dokucu, M.D.

Gozde Kir Cınar, M.D.

Ali Rıza Odabas, M.D.

Gulendam Kocak, M.D.

Murat Tuncer, M.D.*

Aliye Yıldırım Guzelant, M.D.

H. Muammer Karakas, M.D.

Mustafa Calıskan, M.D.

Asiye Kanbay, M.D.

Hale Akbaylar, M.D.

Mutse Banzragch, M.D.*

Atakan Yesil, M.D.

Haluk Vahaboglu, M.D.

Nazmiye Altintas, M.D.*

Ates Kadioglu, M.D.

Hamit Okur, M.D.

Nusret Acikgoz, M.D.*

Atilla Karaalp, M.D.*

Hanefi Ozbek, M.D.*

Onur S. Goksel, M.D.

Ayse Banu Sarıfakioglu, M.D.

Haydar Sur, M.D.

Orhan Alimoglu, M.D.

Ayse Cikim Sertkaya, M.D.

Hulya Apaydın, M.D.

Ayten Kadanali, M.D.

Hulya Sungurtekin, M.D.

Ozge Ecmel Onur, M.D.

Bekir Atik, M.D.

Huseyin Bayramlar, M.D.

Ozlem Guneysel, M.D.

Birsen Yurugen, M.D.

Ibrahim Akalin, M.D.

S. Tahir Eren, M.D.

Bulent Gumusel, M.D.*

Ibrahim Ikizceli, M.D.

Sabahat Aksaray, M.D.

Canan Agalar, M.D.

Ihsan Karaman, M.D.

Sait Naderi, M.D.

Derya Buyukayhan, M.D.

Ilknur Aktas, M.D.

Semra Sardas, M.D.*

Didem Korular Tez, M.D.

Kamil Ozdil, M.D.

Serhat Citak, M.D.

Dilaver Tas, M.D.

Kaya Sarıbeyoglu, M.D.

Sevki Erdem, M.D.

Duygu Geler Kulcu, M.D.*

Kazim Capaci, M.D.*

Seyhan Hidiroglu, M.D.*

Ebru Zemheri, M.D.

Kemalettin Koltka, M.D.

Suayip Birinci, M.D.

Eren Gozke, M.D.

Lutfullah Orhan, M.D.

Sukran Kose, M.D.

Mahmut Durmus, M.D.

Tayfun Kirazlı, M.D.*

Erturk Levent, M.D.

Mehmet Ali Ozcan, M.D.

Tuba Yavuzsen, M.D.

Eyup Gumus, M.D.

Mehmet Doganay, M.D.

Umut Kefeli, M.D.

Fahri Ovali, M.D.

Mehmet Eren, M.D.

Murat Muhcu, M.D.* *

*

*

*

Osman Ekinci, M.D.* *

*

Eren Ozek, M.D. *

Fatih Saygili, M.D.

Murat Acar, M.D.

Veli Citisli, M.D.*

Mehmet Fatih Ayik, M.D.

Yasar Bukte, M.D.

Fatma Eti Aslan, M.D.

Mehmet Kanbay, M.D.

Yuksel Altintas, M.D.

Ferruh Isman, M.D.

Mehmet Tunca, M.D.

Yurdanur Kilinc, M.D.*

Filiz Akyuz, M.D.

Melek Celik, M.D.

Fugen Aker, M.D.

Metin Kapan, M.D.

Fusun Mayda Domac, M.D.*

Muhammet Fatih Onsuz, M.D.*

*

*

*For the third issue of NCI.

NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ YEAR 2014 VOLUME 1 NUMBER 3

p-ISSN 2148 - 4902

Ownership and Accountability for Contents on behalf of the Istanbul Northern Anatolian Association of Public Hospitals

Kemal Memisoglu, M.D.

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CONTENTS VI IX

INSTRUCTIONS FOR THE AUTHORS EDITORIAL

Vol. 1 • No. 3 • Year 2014

ORIGINAL ARTICLES 127-131 The correlation between tenascin-C expression, and formation of intestinal stricture

E. Erdem, K. Kochan, N. Paker, Y. Gokden, A. Salturk Degirmenci, F. Kocak, C. Gonen 132-136 Carpal tunnel syndrome in women working in tea agriculture

G. Devrimsel, S. Kirbas, M. Yildirim, A. Kucukali Turkyilmaz, N. Sahin 137-140 Investigation of the efficacy of transobturator tape (TOT) surgery in stress urinary incontinence

M. S. Bostanci, S. Ozden, O. Unal, A. S. Cevrioglu, N. Akdemir, M. Albayrak 141-146 Gastroesophageal reflux symptoms in Turkish people: a positive correlation with abdominal obesity in women

S. Karayaka, B. Mesci, A. Oguz, G. Tamer 147-152 The knowledge, attitude and behaviour of nurses, working in a state hospital about pharmacovigilance, adverse drug neaction and event reporting

F. Vural, S. Ciftci, B. Vural 153-157 Effect of botulinum toxin type-A in patients with focal spasticity

E. Selimoglu, S. Turan Turgut, P. Akpinar, Y. Yumusakhuylu, S. Haliloglu, H. S. Baklacioglu, A. Icagasioglu 158-165 Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors

M. Sahin, C. Akbulut, C. Dolapcioglu, E. Ozpolat, R. Dabak, M. Aliustaoglu, E. Ahishali 166-172 Evaluation of demographic characteristics, and general disease state of patients affliated with home health care unit of Malatya state hospital

E. Oksuz, E. Onat, A. Shahzadi, Z. Yazici, C. Cetin

ORIGINAL IMAGES 173

Cutaneous adverse effects of imatinib mesylate M. H. Dogu, I. Sari, S. Hacioglu, A. Keskin

174

Marfan syndrome with a giant noncoronary sinus of Valsalva aneurysm S. Avsar, S. Unal Dayi, A. Kaya, I. L. Ozmutlu, A. Osken

CASE REPORTS 175-177 Aural myiasis: case report

E. Mengi, E. Demirhan, I. B. Arslan 178-181 Lidocaine intoxication in axillary block: similar pharmaceutical form, different concentration

Z. A. Erbesler, G. Karaoren, R. Dagli, V. Cakirtekin 182-186 General approach to velocardiofacial anomalies: a pediatric case presenting with Fallot tetralogy

A. Turkmen Karaagac, A. I. Yildirim 187-190 Myoclonus-dystonia syndrome: case report

E. Oguz Akarsu, R. Surmeli, D. Yalcin 191-193 Dramatic response in the dependency to transfusion after low doses of lenalidomide treatment in a 5q-syndrome patient: a case report

M. H. Dogu, I. Sari, S. Hacioglu, A. Keskin 194

NORTHERN CLINICS OF ISTANBUL INDEX FOR VOLUME 1 (2014)

INSTRUCTIONS FOR THE AUTHORS Northern Clinics of Istanbul

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EDITORIAL

Dear readers of Journal of Northern Clinics of Istanbul, Here comes the 3rd issue of 2014. The first year was full of challenges. We hope that next year will see a rise in NCI's popularity and readership. As we grow, NCI will become a preferred journal among researchers and the quality of articles submitted will be higher.

In this issue of NCI, 8 original articles, 2 original radiological images, and 5 case reports are presented.

The original articles investigate the following topics: The relationship between tenascin-C expression and intestinal stricture formation; carpal tunnel syndrome in women working in tea agriculture; an evaluation of efficacy of the transobturator band in the management of stress urinary incontinence; the relationship between symptoms of gastroesophageal reflux and abdominal obesity in female population of Turkey; knowledge levels, and attitudes of nurses working in a public hospital concerning pharmacovigilance, adverse drug reactions, and event reporting; the effectiveness of botulinum toxin type–A in patients with focal spasticity; endoscopic findings in dyspeptic patients unresponsive to proton pump inhibitors; an evaluation of demographic characteristics and disease states of patients who receive services of Home Health Care Services Unit of Malatya State Hospital. In the section on original clinical manifestations, Marfan’s syndrome, a giant noncoronary sinus Valsalva aneurysm, and skin eruptions as adverse reactions to imatinib mesylate are presented. In the case reports, there are discussions on dramatic response in the dependency of transfusion after low doses of lenalidomide treatment in a 5q-syndrome patient; aural myiasis, local anesthetic intoxication developed in a patient secondary to axillary block with lidocaine; an approach to velocardiofascial anomalies in consideration of a pediatric case presented with Fallot tetralogy, and cases with myoclonus-dystocia.

We congratulate the authors who made valuable contributions to the contents of this issue, and express our gratitude to our reviewers, who gave of their valuable time to evaluating submitted manuscripts.

Hope to see you in the first NCI issue of 2015…

Bekir Durmus, Assoc. Prof. M.D.

Editor-in-Chief

Orıgınal Article

GASTROENTEROLOGY

North Clin Istanbul 2014;1(3):127-131 doi: 10.14744/nci.2014.13008

The correlation between tenascin-C expression, and formation of intestinal stricture Emrullah Erdem1, Koray Kochan1, Nurcan Paker2, Yasemin Gokden1, Ayca Salturk Degirmenci1, Fatin Kocak1, Can Gonen1 Haydarapasa Numune Training and Research Hospital, Istanbul, Turkey;

1

Duzen Laboratory, Istanbul, Turkey

2

ABSTRACT OBJECTIVE: A strong correlation exists between tenascin-C induction, and acute inflammation. Generally increased tenascin-C concentrations are correlated with various inflammatory, and infectious diseases. In patients with diagnosis of Inflammatory Bowel Disease (IBD) presence of tenascin-C in colonic mucosa demonstrates tissue repair, and its mucosal concentrations are correlated with local disease activity Therefore plasma levels of tenascin-C have been demonstrated to be a helpful indicator of the activity of inflammatory bowel diseases. In this study, firstly in the literature, we aimed to display the correlation between tenascin-C expression, and formation of intestinal stricture.

METHODS: A total of 43 patients (male, n=19; 44.2%; and female, n=24, 55.8%) aged between 19, and 63 years, with clinically, endoscopically, radiologically, and histopathologically confirmed definitive diagnosis of Crohn’s disease who were examined, diagnosed, and treated in the Gastroenterology Clinic of Haydarpasa Numune Training and Research Hospital between January 2011, and April 2012 were investigated. Serum tenascin-C levels were measured using commercial sandwich enzyme-linked immunosorbent assay Human Tenascin-C Purified Protein kit (Chemicon, Millipore(R), USA). Study groups were categorized based on the type of the disease as inflammatory (n=17; 39.5%), obstructive (27.2%), and fistule formation (n=10; 23.3%) Crohn’s disease. For statistical analysis SPSS (Statistical Package for Social Sciences) Statistics 15 program was used.

RESULTS: Median tenascin- C value in the obstructive group (6.57 ng/mL; range, 4.26-21.87 ng/mL) was statistically significantly higher than that detected in the inflammatory (1.74 ng/mL; range,1.29-3.16 ng/mL), and fistulizing (1.44 ng/mL; range, 0.74-2.47 ng/mL) groups (p=0.002).

CONCLUSION: Intestinal fibroblasts have an important role in the stricture formation process in CD. Transforming growth factor (TGF)-b1 cytokine is in the center of this process. A strong correlation exists between tenascin-C induction, and acute inflammation. As a known fact, serum tenascin-C levels can be used in the determination of activity of IBD. Starting from this point, serum tenascin-C levels can be useful in the categorization of the Crohn’s disease without the need for invasive methods. In the future, studies with larger patient series investigating use of serum tenascin-C in the prediction of stricturing Crohn’s disease should be conducted.

Key words: Intestinal stricture; tenascin C.

Received: November 22, 2014 Accepted: December 07, 2014 Online: January 24, 2015

??, ????

Correspondence: Dr. Emrullah ERDEM. Haydarpasa Numune Egitim ve Arastirma Hastanesi, Istanbul, Turkey.

Tel: +90 216 - 542 32 32 e-mail: emrullah.erdem@gmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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C

rohn’s disease (CD) occurs as a result of complex interaction among genetic, immunological, and microbial factors. In more than one-third of the patients, fibrostenosing phenotype progressing with recurrent intestinal strictures develops [1]. Because of chronic, transmural inflammation, and dysregulated wound healing, strictures occur as a result of superfluous, and abnormal matrix accumulation [2]. This phenomenon induces reorganization of extracellular matrix, scar formation, tissue distortion, and finally intestinal obstruction [3].

Tenascin was discovered in 1983, and this protein is especially contained in the stroma of gliomas, and thus termed as glioma-mesenchymal extracellular matrix antigen [4]. Studies performed within years have demonstrated diffuse expression of tenascin-C in tendons, ligaments, and extracellular matrix of tumors [5]. Since tenascin-C modulates adhesion of cells on fibronectin, it has anti-adhesive or adhesive characteristics [6]. Apart from classical adhesion proteins, tenascin-C can be adhesive, and promigratory for one type of cells, while on the contrary it can be an inhibitor for the other types of cells. The effect of tenascin-C on a specific type of cells can change dependent on the contact of this

Table 1.

cell with other extracellular matrix proteins [7].

In patients with diagnosis of Inflammatory Bowel Disease (IBD) tenascin-C in the colonic mucosa indicates tissue repair, and their mucosal concentrations are associated with the activity of the local disease. Therefore plasma levels of tenascin-C have been demonstrated to be a beneficial indicator of the activity of the inflammatory bowel diseases [8].

In this study, first time in the literature, we aimed to demonstrate the association between tenascin-C expression, and intestinal stricture formation.

MATERIALS AND METHODS A total of 43 patients (male, n=19; 44.2%;, and female, n=24, 55.8%) aged between 19, and 63 years, with clinically, endoscopically, radiologically, and histopathologically confirmed definitive diagnosis of Crohn’s disease who were examined, diagnosed, and treated in the Gastroenterology Clinic of Haydarpasa Numune Training and Research Hospital between January 2011, and April 2012 were investigated.

After an overnight fasting of 10-12 hours- to eliminate possible lipemic interference- during morning hours, venous blood samples from the patient group

Demographic distribution, and laboratory data of the cases included in the study

Patients, n (%) Age (mean±SD) years Gender Male, n (%) Female, n (%) Laboratory data ESR (mm/s),mean±SD CRP (mg/L), median (IQR) WBC(K/mm3), mean±SD Hemoglobin (g/dL), mean±SD Platelet (K/mm3), mean±SD Tenascin C (ng/mL), median (IQR)

Inflammatory

Obstructive

Fistulizing

P value

17 (39.5) 35.1±12.1

16 (37.2) 40.0±10.7

10 (23.3) 31.5±11.7

0.368* 0.182**

9 (47.1) 8 (52.9)

8 (50.0) 8 (50.0)

2 (20.0) 8 (80.0)

0.210*

38.3±27.2 1.56 (0.43-3.3) 7.7±2.1 11.7±1.9 327±98 1.74 (1.29-3.16)

36.5±17.7 1.44 (1.00-2.75) 7.6±1.8 10.9±2.1 332±136 6.57 (4.26-21.87)

30.9±21.2 2.65 (0.5213.00) 6.7±2.3 12.0±2.0 342±109 1.44 (0.74-2.47)

0.735** 0.560*** 0.473** 0.380** 0.950** 0.002***

*Chi-squared test; **Oneway Anova; ***Kruskal Wallis; IQR, interquartile range; SD, Standard deviations ESH, Erythrocyte Sedimentation Rate; CRP, C-reactive protein.

Erdem et al., The correlation between tenascin-C expression, and formation of intestinal stricture

129

ng/mL 50.00

Tenascin c

40.00 P=0.002

30.00

P=0.004

20.00

10.00

*

*

.00 Inflammatory

Obstructive

Fistulizing

Figure 1. Distribution of tenascin-C levels in inflammatory, obstructive, and fistulizng type groups.

were drawn into tubes containıng EDTA, sodium citrate, and gel (Becton Dickinson, USA) Tubes with gel were left aside for 30 minutes, then centrifuged at 3500 rpm (1300 g) for 10 minutes. After an overnight fasting of 10-12 hours- to eliminate possible lipemic interference- during morning hours, venous blood samples from the patient, and the control groups were drawn into tubes containıng EDTA, sodium citrate, and gel (Becton Dickinson, USA) Blood counts, and measurements of CRP, and ESR were performed without delay. Blood samples of all patients, and the control group in EDTA containing tubes were pipetted out for blood counts, while blood samples preserved in sodium citrate solution were analyzed for ESR measurements using Westergreen method, and Sed Rate Screener 100 (SRS 100, Greiner Bio-one GmbH, Austria) device. CRP measurements were performed from serum samples using nephelometric methods (Immage, Beckmann Coulter, USA).

Serum samples were divided into two portions for the future measurement of tenascin-C levels and awaited at -70oC. Frozen samples were thawed just befors the analysis, and then analyzed. Recurrent freezing, and thawing cycles were avoided. Serum

tenascin- C levels were measured using a commercial Human Tenascin-C Purified Protein kit (Chemicon (Millipore, USA).

Based on the types of the Crohn’s disease the study groups were divided into inflammatory (n=17; 39.5%), obstructive (n=16; 37.2%), and fistulizing (n=19; 23.3%) categories. For statistical analyses of data obtained from this study, SPSS (Statistical Package for Social Sciences) Statistics 15 program was used. The results were evaluated within 95% confidence interval at a statistically significant level of p <0.05.

RESULTS Groups were not different as for the distribution of age, and gender. Demographic characteristics, and laboratory results are indicated in Table 1. Median tenascin- C value in the obstructive group (6.57 ng/ mL;4.26-21.87) was statistically significantly higher than that detected in the inflammatory (1.74 ng/ mL; 1.29-3.16), and fistulizing (1.44 ng/mL; 0.742.47) groups (p=0.002) (Figure 1). Any statistically significant intergroup difference was not detected regarding ESR, CRP, leukocyte, hemoglobin, and platelet values (Table 1)

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DISCUSSION Ulcerative colitis (UC), and CD which are classified as inflammatory bowel diseases discriminate themselves from other many inflammatory diseases which might affect colon in that they reflect a chronic process, and they are characterized by periods of exacerbations, and remissions during their natural courses [9]. Three various phenotypes of Crohn’s disease have been detected. Patients manifest nonstructural, and non-penetrating type (70%) (disease progression only with inflammation), and stricturing type (17-20%) (progressing with fistulas, and abscess formations) [10]. Anatomic location of CD in the gastrointestinal system does not change with time, however its phenotype can alter. The disease usually starts with a inflammatory phenotype, and intractable inflammation transforms with time into a stricturing or penetrating form [10].

Intestinal fibroblasts have a critical role in the development of strictures in CH. Fibroblast migration is a very important component of fibrosis.

Therefore, interest in the role of this phenomenon in the healing process of intestinal wounds, and formation of strictures has increased [11]. During the process of stricture formation in CD, histologically, excessive accumulation of mesenchymal cells in muscularis mucosa, submucosa, and muscularis propria is observed.

Intestinal fibroblasts do not proliferate as a result of stimulation by TGF-b1, but they demonstrate supermigration. Therefore, these mesenchymal cells possibly migrate from seromuscular layer.

[12]. Expression of TGF-b isoforms in intestinal fibroblasts changes dependent on the structure of the affected tissue. Fibroblastas both in normal, and inflamed CD mucosa express both TGF-b1, and TGF-b3 isoforms. Expression of fibroblasts in the fibrotic tissue decreases, but they promote increases in the production of TGF-b1, and TGF-b2 [13].

Tenascin-C is the firstly discovered growth factor which reportedly upregulates mRNA of growth factor TGF-b1. increases proliferation, and production of tenascin-C by osteoprogenitor cells [13].

S.Tanaka et al. indicated that presence of tenas-

North Clin Istanbul – NCI

cin-C is associated with inflammation rather than the disease itself. In their study, they stated the presence of a strong correlation between induction of tenascin-C, and acute inflammation, and reported the existence of a correlation between increased levels of circulatory tenascin-C concentrations, and various inflammatory, and infectious disease. [14].

Riedl S. et al. reported that tenasscin-C is induced by various pro-, and anti-inflammatory cytokines, and de novo expression of tenascin-C is a reliable marker for acute inflammation. Starting from that phenomenon, they indicated that trnascin-C levels can be used in the determination of disease activity of IBD [15].

Intestinal fibroblasts have an important role in the formation process of strictures in CD. Transforming growth factor (TGF)-b1 cytokine has a central place in this process [16]. Both TGF-b1, and its receptors are expressed in abundant amounts in the bowels of the patients diagnosed as CD [16].

When we considered that TGF-β can transform mesenchymal epithelium in a way to produce tenascin-C [16], one can assume that increased serum tenascin-C levels play a role in the development of CD-related strictures.

In summary, stricture formation in Crohn’s disease is regulated by intestinal fibroblasts. Transforming growth factor-β1 (TGF-β1) stimulates synthesis of tenascin-C, and it is very important in the activation of fibroblasts. Starting from this point, serum tenascin-C levels can be said to be helpful in the determination of the type of Crohn’s disease without resorting to invasive methods Studies performed with large patient series should aim to substantiate the use of tenascin-C levels in the prediction of stricturing type Crohn’s disease.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Rieder F, Lawrance IC, Leite A, Sans M. Predictors of fibrostenotic Crohn’s disease. Inflamm Bowel Dis 2011;17:2000-7.

Erdem et al., The correlation between tenascin-C expression, and formation of intestinal stricture

2. Di Sabatino A, Jackson CL, Pickard KM, Buckley M, Rovedatti L, Leakey NA, et al. Transforming growth factor beta signalling and matrix metalloproteinases in the mucosa overlying Crohn’s disease strictures. Gut 2009;58:777-89.

3. Froehlich F, Juillerat P, Mottet C, Pittet V, Felley C, Vader JP, et al. Fibrostenotic Crohn’s disease. Digestion 2007;76:113-5.

4. Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD. Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res 1983;43:2796805.

5. Chiquet M, Fambrough DM. Chick myotendinous antigen. II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits. J Cell Biol 1984;98:1937-46.

6. Chiquet-Ehrismann R, Kalla P, Pearson CA, Beck K, Chiquet M. Tenascin interferes with fibronectin action. Cell 1988;53:383-90.

7. Sage EH, Bornstein P. Extracellular proteins that modulate cellmatrix interactions. SPARC, tenascin, and thrombospondin. J Biol Chem 1991;266:14831-4.

8. Piccinini AM, Midwood KS. Endogenous control of immunity against infection: tenascin-C regulates TLR4-mediated inflammation via microRNA-155. Cell Rep 2012;2:914-26.

9. Scaldaferri F, Fiocchi C. Inflammatory bowel disease: progress and current concepts of etiopathogenesis. J Dig Dis 2007;8:171-8.

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10. Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006;12 Suppl 1:3-9.

11. Rovedatti L, Di Sabatino A, Knowles CH, Sengupta N, Biancheri P, Corazza GR, et al. Fibroblast activation protein expression in Crohn’s disease strictures. Inflamm Bowel Dis 2011;17:1251-3.

12. Alejandre Alcázar MA, Morty RE, Lendzian L, Vohlen C, Oestreicher I, Plank C, et al. Inhibition of TGF-β signaling and decreased apoptosis in IUGR-associated lung disease in rats. PLoS One 2011;6:e26371.

13. Sumioka T, Kitano A, Flanders KC, Okada Y, Yamanaka O, Fujita N, et al. Impaired cornea wound healing in a tenascin Cdeficient mouse model. Lab Invest 2013;93:207-17.

14. Tanaka S, Sumioka T, Fujita N, Kitano A, Okada Y, Yamanaka O, et al. Suppression of injury-induced epithelial-mesenchymal transition in a mouse lens epithelium lacking tenascin-C. Mol Vis 2010;16:1194-205.

15. Riedl S, Tandara A, Reinshagen M, Hinz U, Faissner A, Bodenmüller H, et al. Serum tenascin-C is an indicator of inflammatory bowel disease activity. Int J Colorectal Dis 2001;16:285-91.

16. Geboes K, El-Zine MY, Dalle I, El-Haddad S, Rutgeerts P, Van Eyken P. Tenascin and strictures in inflammatory bowel disease: an immunohistochemical study. Int J Surg Pathol 2001;9:281-6.

Orıgınal Article

PM&R

North Clin Istanbul 2014;1(3):132-136 doi: 10.14744/nci.2014.42714

Carpal tunnel syndrome in women working in tea agriculture Gul Devrimsel1, Serkan Kirbas2, Murat Yildirim1, Aysegul Kucukali Turkyilmaz1, Nilay Sahin3 Department of Physical Medicine and Rehabilitation, Recep Tayyip Erdogan University Faculty of Medicine, Rize, Turkey;

1

Department of Neurology, Recep Tayyip Erdogan University Faculty of Medicine, Rize, Turkey;

2

Department of Physical Medicine and Rehabilitation, Balikesir University Faculty of Medicine, Balikesir, Turkey

3

ABSTRACT OBJECTIVE: The aim of this cross-sectional study was to determine the frequency of carpal tunnel syndrome (CTS) among women using tea leaf scissors and compare it with normal population.

METHODS: Two hundred hands of 100 women using tea leaf scissors (tea leaf scissors group) and 112 hands of 56 healthy women (control group) were clinically and electrophysiologically evaluated for CTS. Women using tea leaf scissors were evaluated with visual analog scale (VAS) for pain and Boston Carpal Tunnel Syndrome Questionnaire for symptoms and functional status.

RESULTS: Carpal tunnel syndrome was diagnosed bilaterally in 62 (62%) and unilaterally in 7 (7%) women using tea leaf scissors, whereas 2 (3.57%) bilateral and 6 (10.71%) unilateral cases of CTS was diagnosed in controls. The differences in demographic factors were not statistically significant. In women with CTS using tea leaf scissors, mean symptom severity, functional status, and VAS scores were 2.73±0.60, 2.42±0.71 and 5.19±1.84, respectively. There was statistically significant difference in the frequency of CTS between women using tea leaf scissors and the control group and the risk of having CTS among women using tea leaf scissors was approximately 12 times greater (p<0.001).

CONCLUSION: In tea agriculture, working with repetitive flexions and extensions of the wrist highly increases the risk of developing CTS. Key words: Carpal tunnel syndrome; occupation; using tea leaf scissors.

C

arpal tunnel syndrome (CTS) is the most common nerve entrapment syndrome and it is more prevalent in middle-aged women [1, 2].

Trauma, diabetes mellitus, rheumatoid arthritis, acromegaly, hypothyroidism and pregnancy were found to be associated with CTS [3]. Symptoms

were numbness and finger movement dysfunction in both hands [4]. In works that involve repeated forced movements of flexion-extension of the wrist and fingers with inappropriate posture and use of vibrating instruments, the risk of CTS increases [5, 6, 7, 8]. The occupations which have increased risk

Received: July 22, 2014 Accepted: December 08, 2014 Online: January 24, 2015 ????

Correspondence: Dr. Nilay SAHIN. Balikesir Universitesi Tip Fakultesi, Fiziksel Tip ve Rehabilitasyon Anabilim Dalı, 42001 Balikesir, Turkey.

Tel: +90 266 - 612 10 10 e-mail: nilaysahin@gmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Devrimsel et al., Carpal tunnel syndrome in women working in tea agriculture

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for CTS include assembly workers in food industry, especially in meat and fish processing section, garment industry, boot and shoe manufacturing, supermarket cashiers, hand-made carpet manufactory, fishnet and railroad workers [9].

The aim of this cross-sectional study was to determine the frequency of CTS among women using tea leaf scissors and compare it with normal population. To the best of our knowledge the present study was the first to investigate the frequency of CTS among women using tea leaf scissors.

MATERIALS AND METHODS Tea leaf scissors are mostly used by women in rural areas of Rize, Turkey. Tea worker women were invited to our polyclinic for physical examination and electrodiagnostic tests. The women (age range 25 to 45 years) were asked to participate in the study investigating the presence of CTS and those who volunteered were included in the study.

One hundred and ninety five women participated in the study. Fifty -four of them having CTS risk factors other than using tea leaf scissors were not included in the study. These risk factors were diabetes mellitus, hypothyroidism, inflammatory rheumatic diseases, renal failure, polyneuropathy, cervical radiculopathy, brachial plexopathy, obesity and wrist trauma. Forty-one women were also excluded from the study because of having occupations with increased CTS risk such as woolen sweater knitters and manual milking besides using tea leaf scissors.

The remaining 100 women having no CTS risk factor other than using tea leaf scissors were evaluated by both electrophysiologically and clinically for the risk of CTS. Fifty-six healthy, voluntary women who had no complaints of CTS and none of the risk factors mentioned above for CTS were studied as a control group.

Demographic and clinical features of the subjects were recorded. Employment history and duration of employment were questioned. Because tea working takes 5 months in a year, duration of working was calculated by multiplying months of employment in a year by total number of years. Numbness, tingling and paraesthesia or pain particularly on

Figure 1. Tea leaf scissors is used with elbows in flexion, wrists in extension and strong handgrip with fingers in flexion.

median nerve innervation area, presence of thenar muscle atrophy or weakness, Tinnel or/and Phallen test results were recorded. All patients were asked to point their severity of pain on Visual Analogue Scale (VAS). VAS is a linear scale 10 cm in length divided in 10 equal parts. Zero indicates no pain, whereas 10 signifies worst pain ever [10]. Patients who were diagnosed as CTS by electromyography also filled Boston questionnaire forms. Boston questionnaire consisted of two parts (symptom severity scale and functional status scale) and includes 11 questions for symptom severity and 8 questions for functional status (Figure 1) [11].

Electrophysiological evaluation All participants underwent electrophysiological examinations. Electrophysiological studies (ES) were performed according to the American Association of Electrodiagnostic Medicine guidelines [3, 12]. All electrodiagnostic tests were done with the patient in the supine position, in a room with the temperature kept at 25째C. All of the studies were performed with a Medtronic Keypoint electromyography instrument (Medtronic Corporation, Minneapolis, MN, USA) in all subjects by the same neurologist.

The filter band-pass was 2 Hz to 3 kHz for motor studies and 20 Hz to 3 kHz for sensory studies.

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The compound muscle action potential (CMAP) was recorded with surface electrodes placed over the abductor pollicis brevis muscle. Median nerve was stimulated 8 cm proximal to the anodal electrode by a hand-held stimulator with 2 cm inter-electrode distance. Duration of stimulus was 0.2 ms, sweep speed was 2 ms/division and amplitude gain was 5 mV. Measurements were done by a tape measure.

Sensory nerve action potentials (SNAP) were obtained orthodromically and recorded by ring electrodes placed at the proximal and distal interphalangeal joints. The distance between the stimulator and recording electrode was 14 cm. Sweep speed was 2 ms/division and gain was 10 μV. An average of ten responses for sensory and five responses for motor evaluation were obtained from each stimulation site. Amplitudes of SNAP and CNAP were measured from peak-to-peak and distal latency from the onset point. Ulnar sensory and motor nerve conductions were also evaluated with the same method. Concentric needle EMG investigations were performed to exclude an additional or alternative disorder. In electrophysiological examination, a distal latency difference of greater than 0.5 msec between median and ulnar sensory nerves were accepted as the hallmark of CTS [9].

Statistical Analysis All data in this study were analyzed using SPSS version 18.0 software (Statistical Package for the Social Sciences Inc. Chicago, IL, USA). Descriptive data were reported as means and standard deviations (SD). Student’s t-tests were performed to determine the demographic factor differences between

Table 1. Clinical findings of women using tea leaf scissors

Mean Min.-Max.

Age (years) Working duration (years) Visual analogue scale score Boston symptom severity score Boston functional status score

38.81 9.58 5.19 2.73 2.42

25-45 6-17 3-10 1.72-4 1-4.62

women using tea leaf scissors and controls. Spearmann’s correlation coefficient was used to confirm the correlation between continuous variables. The prevalence ratios of two groups were compared with chi-square test, and odds ratios (OR) with their estimated 95% confdence intervals (CIs). ES was considered as the gold standard test for CTS diagnosis.

Level of significance was set at p ≤0.05.

All subjects who gave their approval for participation in the study were informed about the study procedure. The study protocol was approved by the local ethics committee.

RESULTS After ES, CTS was diagnosed bilaterally in 62 (62%) and and unilaterally in 7 (7%) women using tea leaf scissors whereas 2 (3.57%) bilateral and 6 (10.71%) unilateral cases of CTS were diagnosed in controls. Among these subjects, 20 (20%) had no complaints, while in women using tea leaf scissors, 67 (67%) had bilateral and 13 (13%) unilateral CTS. Seventy- three of 200 hands (36.5%) were diagnosed as CTS on clinical examination. None of the subjects in the control group had complaints of CTS, while ten hands (17.85%) were diagnosed as CTS on physical examination.

Mean age of the participants was 38.81±0.4 (range 25 to 45) years in women using tea leaf scissors and 38.97±0.67 (range 25 to 45) years in controls. There were no statistically significant differences as for age and BMI between two groups (p>0.05). Mean duration of working was 9.58±5.93 years. In women with CTS in the tea leaf scissors group, mean symptom severity score was 2.73±0.60 points whereas mean functional status score was 2.42±0.71 poimts which were evaluated with Boston questionnaire. However, mean VAS score was 5.19±1.84 (Table 1). Electrophysiologic study findings and comparison between women using tea leaf scissors and controls are shown in Table 2.

There was a statistically significant difference in the frequency of CTS between women using tea leaf scissors and the control group (p<0.001). The risk of having CTS among women using tea leaf scissors was approximately 12 times greater compared to the

Devrimsel et al., Carpal tunnel syndrome in women working in tea agriculture

135

Table 2. Electrophysiologic study findings and comparison between women using tea leaf scissors and controls

mSNCV mSDL mMNCV mMDL mSNAP mCMAP D4M-D4U

Women using tea leaf scissors

Controls

P-value

46.06±10.49 3.09±0.80 55.92±7.26 4.31±1.35 22.89±11.77 6.54±2.35 0.43±0.17

54.89±7.38 2.49±0.37 57.28±5.37 3.31±0.46 29.47±12.60 6.82±1.63 0.24±0.11

<0.0001 <0.0001 0.098 <0.0001 <0.0001 0.263 <0.0001

mSNCV: median nerve sensory nerve conduction velocity; mSDL: median nerve sensory distal latency; mMNCV: median nerve motor nerve conduction velocity; mMDL: median nerve sensory distal latency; SNAPa: median nerve sensory nerve action potential amplitude; mCMAPa: median nerve compound muscle action potential amplitude; D4M-D4U: the difference between median and ulnar sensory distal latencies to the fourth digit.

control group (OR:11.77; 95% CI=5.68-24.39).

There were no significant correlations between number of years worked and symptom severity and functional status evaluated by Boston questionnaire (r=0.07, p>0.05, r=0.05, p>0.05, respectively). In addition electrophysiologic study findings did not correlate with the number of years worked (p>0.05).

DISCUSSION Diagnosis of CTS is mainly established with clinical and electrophysiological examinations. Clinically, thenar atrophy, pain and paresthesia along the area innervated by median nerve which increase in severity with repetitive movements and relief of symptoms with changing position of the hand are seen. Tinel and/or Phalen tests are generally positive [13]. In the present study, high VAS and Boston Questionnairre scores indicated that clinical symptoms negatively affected the daily life of women using tea leaf scissors.

In this study we found that the risk of having CTS among women using tea leaf scissors was approximately 12 times greater compared with the controls. Kutluhan et al. [9] reported that CTS was 11.4 times higher in women manually milking cows compared to controls.

It was suggested that prolonged and highly repetitive movements of flexion and/or extension of

the wrist increase the risk of CTS, especially when allied with a forceful grip [14]. It was first discovered in 1947 that CTS was related to occupation, when Brian et al. reported approximately 6 cases of work-related CTS in jobs requiring repetitive flexions, and extensions of the wrists [15]. CTS has been listed since 2003 in the European Union’s list of occupational disease [16].

In the study by Mondell M et al. [17] a high occurrence of CTS among floor cleaners was found which was attributed to repetitive movements of the wrists. Barnhart et al. [18] reported CTS in 15.4% of ski manufacturing workers indulging in repetitive tasks. Kim et al. [19] reported the highest prevalence (73.9%) of CTS workers in meat and fish processing plants, and Punnet et al. [20] found a higher prevalence of CTS (%60) among garment workers. Margolis and Kraus found [21] a prevalence of 62.5% for symptoms consistent with CTS in female supermarket workers.

The latter prevalence rate is very close to ours (62.5% versus 69%, respectively). Increased frequency of CTS was also found among dairy workers, vineyard workers and poultry-processing workers however this study was first to investigate prevalence of CTS among women using tea leaf scissors. In tea working, repetitive flexions and extensions of the wrist may increase carpal tunnel

136

pressure which may presumably lead to ischemia and direct mechanic injury of the median nerve.

Until today limited number of studies have investigated the relationship between presence of CTS and duration of working. De Krom et al.

[22] reported that risks increased 5-to 8-fold when the self-reported time spent in activities with the wrist flexed or extended was ≥20 h/week, while in the study by Nordstrom et al. the risk of CTS doubled for those who work more than 3.5h/day among frozen-food packers. Wieslander et al. [23] found that the risk was doubling after one year in a work requiring repetitive flexions and extensions of the wrists. In the present study we could not find a correlation between the duration of working with symptom severity, functional status and electrophysiologic study findings.

In conclusion, in tea agriculture, working with repetitive flexions and extensions of the wrist highly increases the risk of developing CTS. Further studies are needed to confirm these results and evaluate increases in the risk of CTS development with working time.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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7. Becker J, Nora DB, Gomes I, Stringari FF, Seitensus R, Panosso JS, et al. An evaluation of gender, obesity, age and diabetes mellitus as risk factors for carpal tunnel syndrome. Clin Neurophysiol 2002;113:1429-34.

8. Aroori S, Spence RA. Carpal tunnel syndrome. Ulster Med J 2008;77:6-17.

9. Kutluhan S, Tufekci A, Kirbaş S, Erten N, Koyuncuoglu HR, Ozturk M. Manuel milking: A risc factor for carpal tunnel syndrome. Biomedical Research 2009;20:21-4 10. Wewers ME, Lowe NK. A critical review of visual analogue scales in the measurement of clinical phenomena. Res Nurs Health 1990;13:227-36.

11. Levine DW, Simmons BP, Koris MJ, Daltroy LH, Hohl GG, Fossel AH, et al. A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am 1993;75:1585-92.

12. Kummel BM, Zazanis GA. Shoulder pain as the presenting complaint in carpal tunnel syndrome. Clin Orthop Relat Res 1973;92:227-30.

13. Simovic D, Weinberg DH. The median nerve terminal latency index in carpal tunnel syndrome: a clinical case selection study.

Muscle Nerve 1999;22:573-7.

14. Palmer KT, Harris EC, Coggon D. Carpal tunnel syndrome and its relation to occupation: a systematic literature review. Occup Med (Lond) 2007;57:57-66.

15. Brain RW, Wright AD, Wilkinson M. Spontaneous compression of both median nerves in the carpal tunnel; six cases treated surgically. Lancet 1947;1:277-82.

16. Giersiepen K, Spallek M. Carpal tunnel syndrome as an occupational disease. Dtsch Arztebl Int 2011;108:238-42.

17. Mondelli M, Grippo A, Mariani M, Baldasseroni A, Ansuini R, Ballerini M, et al. Carpal tunnel syndrome and ulnar neuropathy at the elbow in floor cleaners. Neurophysiol Clin 2006;36:245-53.

18. Barnhart S, Demers PA, Miller M, Longstreth WT Jr, Rosenstock L. Carpal tunnel syndrome among ski manufacturing workers. Scand J Work Environ Health 1991;17:46-52.

19. Kim JY, Kim JI, Son JE, Yun SK. Prevalence of carpal tunnel syndrome in meat and fish processing plants. J Occup Health 2004;46:230-4.

20. Punnett L, Robins JM, Wegman DH, Keyserling WM. Soft tissue disorders in the upper limbs of female garment workers.

Scand J Work Environ Health 1985;11:417-25.

21. Margolis W, Kraus JF. The prevalence of carpal tunnel syndrome symptoms in female supermarket checkers. J Occup Med 1987;29:953-6.

22. de Krom MC, Kester AD, Knipschild PG, Spaans F. Risk factors for carpal tunnel syndrome. Am J Epidemiol 1990;132:1102-10.

23. Wieslander G, Norbäck D, Göthe CJ, Juhlin L. Carpal tunnel syndrome (CTS) and exposure to vibration, repetitive wrist movements, and heavy manual work: a case-referent study. Br J Ind Med 1989;46:43-7.

Or覺g覺nal Article

OBSTETRICS&GYNECOLOGY

North Clin Istanbul 2014;1(3):137-140 doi: 10.14744/nci.2014.30085

Investigation of the efficacy of transobturator tape (TOT) surgery in stress urinary incontinence Mehmet Suhha Bostanci, Selcuk Ozden, Orhan Unal, Arif Serhan Cevrioglu, Nermin Akdemir, Mustafa Albayrak Sakarya University Faculty of Medicine, Training and Research Hospital, Sakarya, Turkey

ABSTRACT OBJECTIVE: To evaluate the safety and efficacy of transobturator vaginal tape (TOT) in the management women with stress urinary incontinence (SUI) and to analyze functional results and subjective cure rates at follow- up visits.

METHODS: Eighty-three consecutive women with SUI underwent TOT procedure. Data related to operative time, pre- and post-operative complications were collected. Subjective cure was defined as the absence of any urine loss on physical activity.

RESULTS: Mean age of the patients was 53.2 years, and 66.3% of the patients had pure SUI. The mean operative time was 24.96 min in cases of isolated SUI treatment. The mean hospital stay was 1.53簣0.68 days. At a mean follow-up of 32.8 months, the median subjective cure rate was 68.7 percent. Bladder injury (8.4%) was the only short and long term complication of this procedure.

CONCLUSION: TOT is a safe and effective procedure for SUI with a low rate of long- term complications.

The short -term complication like bladder perforation may develop based on the experience of the surgeons or concomitant pelvic surgery.

Key words: Complication; stress urinary incontinence, transobturator vaginal tape (TOT).

S

tress urinary incontinence (SUI) can be described as an involuntary urine loss, which has become a social problem. In this condition, increased intra-abdominal pressure causes urine leakage on effort, exertion, on sneezing or coughing when the support structures of the pelvic floor and the urinary system are stretched, damaged, or

defective [1]. The prevalence of SUI in women has been estimated to be between 10% and 40%, and it has a severe course in about 3% to 17% of women [2]. Factors that may increase the risk of developing incontinence include obesity, straining at stool, heavy manual labor, chronic obstructive pulmonary disease, and smoking [3, 4]. Incidence increases with

Received: September 23, 2014 Accepted: December 08, 2014 Online: January 24, 2015 ? ??, ????

Correspondence: Dr. Mehmet Suhha BOSTANCI. Saglik Bakanligi Sakarya Universitesi Egitim Arastirma Hastanesi, Kadin Dogum Klinigi, Sakarya, Turkey.

Tel: +90 264 - 255 21 06 e-mail: msuhha@gmail.com 穢 Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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age [3, 4]. Numerous surgical methods for stress incontinence have been described. To date, several tape procedures with various modifications have been introduced into female SUI treatment. Tension-free vaginal tape (TVT) was introduced for the treatment of SUI by Ulmsten more than a decade ago, with a success rate ranging from 85% to 95% [5, 6].

This procedure involves the insertion of two needles passed through the retropubic space blindly from vagina to abdomen or from abdomen to vagina.

Cystoscopy is recommended to detect any perforation of the bladder or urethra [5]. In 2001, Delorme reported a transobturator vaginal tape (TOT) approach which consisted of placing a mesh through the obturator foramen behind the mid-urethra [7].

Surgical correction of SUI with TOT is the procedure of choice because of a shorter surgical time and a lower complication rate compared with TVT [8].

We focused on the morbidity and efficacy of the TOT procedure, including peri-, and post operative complications, and subjective results.

MATERIALS AND METHODS This is a retrospective analysis on patients who underwent SUI surgery since 2009. Patients were operated on between January 2009 and September 2013 in the Gynecology and Obstetrics Department of Sakarya University Training and Research Hospital.

Eighty-three patients were analyzed and examination results obtained during preoperative, perioperative, early postoperative periods, and at each follow- up visit were recorded. Findings were taken from patients files. Preoperatively, patientsâ&#x20AC;&#x2122; medical history, physical examination findings, voiding diary notes, and their responses to the questions in the quality-oflife survey forms were evaluated. All participants had normal neurological findings. All had clinical signs of urethral hypermobility, with an abnormal cotton swab test (greater than 30 degrees) and a bladder capacity of at least 250 ml. All the patients received intravenous antibacterial prophylaxis (cefazolin, 2 g) at the beginning of surgery, while no vaginal preparation was necessary the day before the surgery. Transobturator approach was performed as described by Delorme in 2001 using a curved tunneler inserted from the

North Clin Istanbul â&#x20AC;&#x201C; NCI

outside entrance point to adjust the tape without any tension [3]. Prolene light mesh (condensed monofilament non- absorbable polypropylene) was used as mesh material. A piece of polypropylene mesh (1.01.2 cm in width 20 cm in length) was cut by the surgeon from condensed monofilament non-absorbable polypropylene (TAHA Prolene Polypropylene mesh, Altaylar Bilim, Turkey). Patients were operated by several surgeons who routinely performed TOT procedures including residents in training as our department is an academic teaching centre. Routinely, cystoscopic examinations were not performed excepting the cases with complications of bladder injury. The incidence of perioperative and postoperative complications, febrile morbidity, analgesic requirements, and length of the postoperative hospital stay were recorded. Residual urine volume was evaluated after withdrawal of the Foley catheter. Voiding difficulties were defined as a residual urine volume of 150 mL or more, checked by postvoid catheterization. We recorded effectiveness and complications taking into account not only continence but overall well-being of the patients. Complications included adjacent organ injuries, hemorrhage, hematoma formation, urinary retention, and newly-developed urinary incontinence.

Early postoperative complications were defined as those occurring during the first postoperative 7 days, and late postoperative complications as those that persisted or were diagnosed more than 7 days after the operation. Patients were clinically followed after one week, one month and one year after surgery. They were considered as cured when they did not present any stress urine leakage during a cough test with a full bladder and without the need of any continent pad during the past month. An improvement was registered when patients judged themselves as improved with less frequent use of urinary protective devices and/or pads during daily activities. Subjective cure was defined as women not experiencing any urine loss on physical activity. All other cases were recorded as subjective failures.

RESULTS In this study, a total of 83 patients who underwent SUI were assessed. The median age of the patients

Bostanci et al., Investigation of the efficacy of transobturator tape (TOT) surgery in stress urinary incontinence

was 53.20 years (range 30-74 years) with a median body mass index (BMI) of 24.6 kg/m2 (18–37).

Characteristics of women undergoing TOT procedures were shown in Table 1. The mean operative time was 24.96 min (17–35) in cases of isolated SUI treatment. Twelve patients (14.5%) had previously undergone incontinence surgery including Burch colposuspension, and Kelly plication. Thirty-two patients had undergone combined vaginal procedures (hysterectomy, n=32; rectocele repair, n=13; cystocele repair, n=24, and sacrospinofixation, n=21). All procedures were performed under general or regional anesthesia. No significant blood loss occurred in any cases. The mean hospital stay was 1.53±0.68 days (range, 1-4 days). No bleeding and no nerve, bowel, ureteral, or vascular injuries were reported. Bladder injury was observed in seven women (8.4%), necessitating indwelling catheter for seven days. All bladder injuries occurred during the first pass of the tunneler. None of them occurred during passage of the mesh or during other simultaneously performed manipulations. Cystoscopic controls were performed in these patients and no surgical repair was made because of the presence of a small perforation site less than 1cm. None of the patients had long term complications like urethral erosion, vaginal erosion or extrusion. Median followup period was 32.86 months (range, 6-52 months).

The overall subjective cure rate was 68.7%. Patients’ complaints resolved in 27.7% of the study subjects.

Only 3.6% of the patients indicated persistence of complaints after the TOT procedure (Table 2).

DISCUSSION The main goal of the surgical treatment of SUI is to restore a perfect continence with minimal morbidity. Surgical procedures to remedy stress incontinence generally aim to lift and support the urethrovesical junction but in the last decade the emphasis has been on suburethral support at the mid urethral level [9]. Although it is effective and easy to perform, the retropubic placement of suburethral TVT has been associated with a number of periand post-operative complications including mesh erosion, urinary retention, de novo overactive blad-

139

Table 1. Characteristics of women undergoing TOT procedure

Mean Age (year)±SD Mean parity±SD BMI±SD Stress Incontinence Mixed Incontinence Mean time of Incontinence (year)±SD

53.20±10.19 3.65±1.45 24.66±4.11 66.3% 33.7% 7.11±6.12

Table 2. Characteristics of TOT operation and subjective cure rates

Mean operative time (min)±SD Mean hospital stay (day)±SD Complications No complication Bladder Injury Mean follow-up (month)±SD Subjective cure rates No cure Improvement Cure

24.96±3.59 1.53±0.68 91.6% 8.4% 32.86±14.87 3.6% 27.7% 68.7%

der, vascular injury, bowel and bladder injuries [10, 11]. Most complications appear to be related to the blind upward vaginal passage of the trocars into the retropubic space [7, 9].

Delorme et al. described the transobturator approach as an excellent alternative to the retropubic approach that reduces complications [7]. Shortly after the introduction of the transobturator approach a similar operation was described which allows the passage of a tape through the obturator foramina, from inside to outside [12]. In our cases, trocars were placed from outside- in as described by Delorme. Subjective cure is usually regarded as the absence of incontinence during cough stress test.

Surgical correction of SUI with TOT is the procedure of choice because of its shorter surgical time and a lower complications rate compared with TVT. According to published data any significant

140

difference between TOT and TVT as for the subjective cure rates does not exist during midterm follow-up [13]. Angioli reported a 62% subjective cure rate in 37 patients during 5 years after TVT [14].

Houwert reported a cure rate of 72% in 93 patients after TVT and 69% after TOT at 2–4 years [15].

In our cases cure rate of 68.7% and improvement rate of 27.7% were detected. We found similar satisfaction rates with other studies but subjective cure rate detected in our study was a bit lower in comparison with other studies [9, 14, 16, 17].

Bladder perforation occurred in 15% of women in this report which was higher than that reported by others. All our patients were treated with an indwelling catheter for seven days and no long- term complications were encountered. Concomitant pelvic surgery may have contributed to higher bladder injury rate. The complications like nerve, bowel, urethral, or vascular injuries did not occur. Also long- term complications like urethral erosion, vaginal erosion, or vaginal extrusion did not develop during the follow- up period.

In conclusion, short-term complication of bladder perforation occurs at an unexpectedly high rate.

This might be related to the technique as well as the experience of the surgeons or concomitant pelvic surgery. TOT procedure is a very effective treatment of SUI with low morbidity. The fact that the tape provides more firm support than a suspension of the urethra might explain the low rate of complications.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 2010;29:4-20.

2. Botlero R, Urquhart DM, Davis SR, Bell RJ. Prevalence and incidence of urinary incontinence in women: review of the literature and investigation of methodological issues. Int J Urol 2008;15:230-4.

North Clin Istanbul – NCI 3. Foldspang A, Mommsen S, Lam GW, Elving L. Parity as a correlate of adult female urinary incontinence prevalence. J Epidemiol Community Health 1992;46:595-600.

4. Kirss F, Lang K, Toompere K, Veerus P. Prevalence and risk factors of urinary incontinence among Estonian postmenopausal women. Springerplus 2013;2:524.

5. Ulmsten U, Henriksson L, Johnson P, Varhos G. An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 1996;7:81-6.

6. Nilsson CG, Falconer C, Rezapour M. Seven-year follow-up of the tension-free vaginal tape procedure for treatment of urinary incontinence. Obstet Gynecol 2004;104:1259-62.

7. Delorme E. Transobturator urethral suspension: mini-invasive procedure in the treatment of stress urinary incontinence in women. [Article in French] Prog Urol 2001;11:1306-13. [Abstract] 8. Ward KL, Hilton P; UK and Ireland TVT Trial Group. Tensionfree vaginal tape versus colposuspension for primary urodynamic stress incontinence: 5-year follow up. BJOG 2008;115:226-33.

9. Barber MD, Kleeman S, Karram MM, Paraiso MF, Walters MD, Vasavada S, et al. Transobturator tape compared with tensionfree vaginal tape for the treatment of stress urinary incontinence: a randomized controlled trial. Obstet Gynecol 2008;111:611-21.

10. Peyrat L, Boutin JM, Bruyere F, Haillot O, Fakfak H, Lanson Y. Intestinal perforation as a complication of tension-free vaginal tape procedure for urinary incontinence. Eur Urol 2001;39:603-5.

11. Hermieu JF, Messas A, Delmas V, Ravery V, Dumonceau O, Boccon-Gibod L. Bladder injury after TVT transobturator. [Article in French] Prog Urol 2003;13:115-7. [Abstract] 12. de Leval J. Novel surgical technique for the treatment of female stress urinary incontinence: transobturator vaginal tape insideout. Eur Urol 2003;44:724-30.

13. Park YJ, Kim DY. Randomized controlled study of MONARC® vs. tension-free vaginal tape obturator (TVT-O®) in the treatment of female urinary incontinence: comparison of 3-year cure rates. Korean J Urol 2012;53:258-62.

14. Angioli R, Plotti F, Muzii L, Montera R, Panici PB, Zullo MA. Tension-free vaginal tape versus transobturator suburethral tape: five-year follow-up results of a prospective, randomised trial. Eur Urol 2010;58:671-7.

15. Houwert RM, Renes-Zijl C, Vos MC, Vervest HA. TVT-O versus Monarc after a 2-4-year follow-up: a prospective comparative study. Int Urogynecol J Pelvic Floor Dysfunct 2009;20:1327-33.

16. Abdel-fattah M, Ramsay I, Pringle S, Hardwick C, Ali H. Evaluation of transobturator tapes (E-TOT) study: randomised prospective single-blinded study comparing inside-out vs. outside-in transobturator tapes in management of urodynamic stress incontinence: short term outcomes. Eur J Obstet Gynecol Reprod Biol 2010;149:106-11.

17. But I, Faganelj M. Complications and short-term results of two different transobturator techniques for surgical treatment of women with urinary incontinence: a randomized study. Int Urogynecol J Pelvic Floor Dysfunct 2008;19:857-61.

Or覺g覺nal Article

INTERNAL MEDICINE

North Clin Istanbul 2014;1(3):141-146 doi: 10.14744/nci.2014.44154

Gastroesophageal reflux symptoms in Turkish people: a positive correlation with abdominal obesity in women Sergul Karayaka1, Banu Mesci2, Aytekin Oguz2, Gonca Tamer3 Department of Family Medicine, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey;

1

Department of 2nd Internal Medicine Clinic, Istanbul Medeniyet University, Goztepe Training and Research Hospital,

2

Istanbul, Turkey; Department of Endocrinology, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey

3

ABSTRACT OBJECTIVE: Metabolic syndrome (MetS) is increasing around the world due to abdominal obesity with altered eating habits and decreased physical activity. The aim of this study was to determine the risk factors for gastroesophagial reflux disease (GERD) symptoms and the prevalence of GERD in patients with MetS. METHODS: Five hundred patients (MetS, n=300 and the control group, n=200) were enrolled in the study. A detailed questionnaire reflux symptoms and behavioral habits was performed.

RESULTS: Sixty percent of the subjects were with MetS. GERD rate was significantly higher in the group with MetS compared to subjects without MetS (50.7% vs. 26%). Women were more likely to have GERD in both groups (62.6% of women and 28.6% of men 覺n the MetS group while corresponding rates were 37% vs. 16.7% in the control group). Waist circumferences were found to be higher in female MetS patients with GERD. CONCLUSION: GERD is present approximately in every one of the two patients with MetS. Every patient who has MetS should be evaluated in terms of GERD symptoms.

Key words: Abdominal obesity; gastroesophageal reflux; metabolic syndrome; obesity; Turkish population.

G

astroesophagial reflux disease (GERD) is frequently observed together with MetS [1].

Prevalence of metabolic syndrome (MetS) is increasing around the world due to abdominal obesity with altered eating habits and decreased physical activity. GERD worsens quality of life, and may cause diseases involving esophagus such as esophagitis,

Barret esophagus, adenocarcinoma, and many additional diseases such as laryngitis, morning hoarseness and aspiration syndrome as a result of regurgitation of the stomach contents into the pharynx and the mouth [2, 3]. These kinds of chronic complications can be prevented with active questioning of GERD symptoms in patients with MetS.

Received: October 27, 2014 Accepted: December 07, 2014 Online: January 24, 2015 ? ??, ????

Correspondence: Dr. Banu MESCI. Istanbul Medeniyet Universitesi, Goztepe Egitim ve Arastirma Hastanesi, 2. Dahiliye Klinigi, Istanbul, Turkey.

Tel: +90 216 - 416 03 45 e-mail: banualpaslan@gmail.com 穢 Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

142

North Clin Istanbul – NCI

Table 1. Demographic data of the patients

MetS group

Control group

67.9%

50.7%

Mean±SD

Mean±SD

p

52.83±9.85 32.43±4.88 107.89±10.45

51.86±12.71 23.42±2.69 82.86±7.88

0.21 0.001 0.001

Female

Age BMI (kg/m2) Waist circumference (cm)

The aim of the present study was to determine the risk factors and the prevalence of GERD symptoms in patients with MetS. MATERIALS AND METHODS The study was conducted in Goztepe Training and Research Hospital outpatient clinics between 2008 and 2009. Five hundred patients (MetS, n=300 and the control group, n=200) were enrolled in the study. MetS was identified according to the criteria of The International Diabetes Federation (IDF) [4].

Exclusion criteria were pregnancy, hormone replacement therapy, history of gastric surgery. The study protocol was designed in accordance with the relevant criteria of Helsinki Declaration and was approved by the local ethics committee of Goztepe Training and Research Hospital. Subjects provided their written informed consent. Demographic and clinic data were recorded. Their physical examina-

Table 2. Reflux prevalence in groups

Reflux + -

MetS n

%

Control n

%

p

152 50.7 52 26.0 0.001** 148 49.3 148 74.0

tion was performed; height, weight, and waist circumference measurements were performed. Body mass index (BMI) was calculated by dividing weight in kg by height in m2. Systolic and diastolic blood pressures (BP) were recorded. Waist circumferences were measured at the plane between anterior superior iliac spines and lower costal margins at the narrowest part of the waistline while patients were standing during slight expiration. Waist circumferences >80 cm for women and >94 cm for men were accepted as abdominal obesity according to IDF. A detailed questionnaire asking reflux symptoms and behavioral habits was performed. GERD symptoms were defined as a ‘yes’ response to all three of the following components: the presence or absence of heartburn, indigestion or pain in your stomach, a tender point palpated on the upper abdomen and relief with antacid. Related risk factors such as tobacco smoking, alcohol intake, eating habits, physical activity and the sleeping position were investigated in both groups.

Statistical analysis NCSS (Number Cruncher Statistical System), 2007&2008 Statistical Software PASS (Utah, USA) program were used. Student’s t test was used for comparison of descriptive statistical data (mean, standard deviation, frequency) as well as quantitative parameters showing normal distribution of data between groups. The chi-square test was used to compare qualitative data.

143

Karakaya et al., Gastroesophageal reflux symptoms in Turkish people

Table 3. Reflux prevalence in groups according to the gender of the patients

Reflux

MetS

Control group

Female n

Male

%

n

+p

%

+ 122 62.6 30 28.6 0.001** – 73 37.4 75 71.4 + –

34 37.0 18 16.7 0.001** 58 63.0 90 83.3

Table 4. Reflux prevalence according to waist circumference

Reflux

Waist circumference (women) <80 cm (31.5 in) 80-88 cm (31.5-34.6 in) >88 cm (34.6 in) Waist circumference (men) <94 cm (37 in) 94-102 cm (37-40.2) >102 cm (40.2)

+

– p

n

%

n

%

34 5 117

21.8 3.2 75.0

58 0 73

44.3 0 55.7

0.001**

18 7 23

37.5 14.6 47.9

90 21 54

54.5 12.7 32.7

0.100

RESULTS The study was completed with 500 patients (213 M, 287 F). Sixty percent of the subjects were diagnosed with MetS (Table 1). GERD rate was significantly higher in the group with MetS as compared to the group without MetS (50.7% vs 26%) (Table 2). Women were more likely to have GERD in both groups (MetS, and the control groups, women: 62.6 vs 37% and men, 28.6 vs 16.7%) (Table 3). Waist circumferences were found to be higher among female MetS patients with GERD (Table

4). Smoking rate was lower in the group with MetS. GERD prevalence was found to be higher in nonsmokers. Alcohol consumption rates were similar between subjects with and without GERD. Subjects with GERD were found out to eat larger sized meals. A habit of eating three hours before bedtime was associated with GERD. Physical activity level at work was not correlated with GERD while lesser physical activity during leisure times was significantly correlated with GERD. There was no relation between the type of lying position and GERD (Table 5).

144

North Clin Istanbul â&#x20AC;&#x201C; NCI

Table 5. Reflux prevalence in groups according to daily habits

Reflux

Smoking status Nonsmoker Irregular smoker Former smoker Current smoker The number of cigarettes smoked <5 5-20 >20 Alcohol consumption + - The size of meals Small Medium Large Eating 3 hours before bedtime Never Rare Often Very often Physical activity at work Minimal Average Heavy Physical activity at leisure time Minimal Average Heavy Sleeping position Right side Left side Supine position Prone position

+ n

%

â&#x20AC;&#x201C; p n

%

123 46.4 142 53.6 37 36.3 65 63.7 25 30.9 56 69.1 19 36.5 33 63.5 daily by current smokers (n=52) 4 80.0 1 20.0 12 30.8 27 69.2 3 37.5 5 62.5 5 33.3 10 66.7 199 41.0 286 59.0

0.045*

0.098

0.550

43 81 80

27.7 112 72.3 41.1 116 58.9 0.001** 54.1 68 45.9

34 99 56 15

23.6 110 76.4 40.2 147 59.8 0.001** 59.6 38 40.4 93.8 1 6.3

64 41,8 89 58.2 108 44.1 137 55.9 32 31.4 70 68.6

0.086

128 56.6 98 43.4 67 32.1 142 67.9 0.001** 9 13.8 56 86.2 130 47 12 15

DISCUSSION This study showed that waist circumference is the most important factor for GERD in female patients

43.0 39.5 34.3 34.1

172 72 23 29

57 60.5 65.7 65.9

0.542

with MetS. It is well documented that obesity increases the risk of GERD [5, 6]. With the growing interest in MetS similar recent studies were performed on coexistence between GERD and MetS

145

Karakaya et al., Gastroesophageal reflux symptoms in Turkish people

[1]. In a study conducted with 2457 people in Korea, abdominal obesity was found as a more important factor in the development of erosive gastritis than body mass index [7]. In another study, MetS and increased insulin resistance were found to increase the risk of development of erosive esophagitis [8].

Visceral obesity increases intragastric pressure and leads to reflux esophagitis. Visceral fat is metabolically active and it has been associated with low serum levels of protective cytokines, such as adiponectin, and high levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 [9, 10].

In the present study, GERD prevalence was found to be higher in women in contrast to the prevalence rates reported for a Japanese cohort [1].

In a large cross-sectional study on abdominal obesity, GERD symptoms and ethnicity of 80110 members of a health organization were investigated.

It was found that increased abdominal circumference adjusted for BMI, was an independent risk factor for reflux symptoms (OR, 1.85; 95% CI, 1.552.21) in the white population but not among blacks and Asians which was not influenced by gender [11]. Higher GERD prevalence in Turkish women with MetS in the present study as compared to Japanese women [12] can be related to higher waist circumference of the former group.

Cigarette smoking and alcohol consumption are well known risk factors for GERD [13-16].

We did not find a correlation with smoking or alcohol consumption and GERD, possibly because of higher nonsmoking rate in subjects with MetS and very limited alcohol consumption in our population.

Although eating larger- sized meals and eating especially three hours before bedtime were associated with GERD in accordance with the results of other studies [10], we haven’t observed any correlation between GERD and physical activity level at work and observed a negative correlation between GERD, and the intensity of leisure time activity.

Accumulating information about GERD indicates that GERD coexists with vigorous rather than moderate exercise [17, 18]. Since gastric fullness in-

creases the possibility of GERD [19], leisure time is more convenient for exercises. Investigating sleeping position, any of lying position did not show association with GERD. Present study is based on a questionnaire survey.

An endoscopic evaluation of the study population would be more enlightening.

Conclusion: GERD is present approximately in every one of the two patients with MetS. Every patient who have MetS should be evaluated in terms of GERD symptoms.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Moki F, Kusano M, Mizuide M, Shimoyama Y, Kawamura O, Takagi H, et al. Association between reflux oesophagitis and features of the metabolic syndrome in Japan. Aliment Pharmacol Ther 2007;26:1069-75.

2. Vaira D, Gatta L, Ricci C, Castelli V, Fiorini G, Kajo E, et al.

Gastroesophageal reflux disease and Barrett’s esophagus. Intern Emerg Med 2011;6:299-306.

3. Heidelbaugh JJ, Gill AS, Van Harrison R, Nostrant TT. Atypical presentations of gastroesophageal reflux disease. Am Fam Physician 2008;78:483-8.

4. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006;23:469-80.

5. Anand G, Katz PO. Gastroesophageal reflux disease and obesity.

Gastroenterol Clin North Am 2010;39:39-46.

6. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med 2005;143:199-211.

7. Kang MS, Park DI, Oh SY, Yoo TW, Ryu SH, Park JH, et al.

Abdominal obesity is an independent risk factor for erosive esophagitis in a Korean population. J Gastroenterol Hepatol 2007;22:1656-61.

8. Park JH, Park DI, Kim HJ, Cho YK, Sohn CI, Jeon WK, et al. Metabolic syndrome is associated with erosive esophagitis.

World J Gastroenterol 2008;14:5442-7.

9. Cnop M, Landchild MJ, Vidal J, Havel PJ, Knowles NG, Carr DR, et al. The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes 2002;51:1005-15.

10. Festi D, Scaioli E, Baldi F, Vestito A, Pasqui F, Di Biase AR, et al.

146 Body weight, lifestyle, dietary habits and gastroesophageal reflux disease. World J Gastroenterol 2009;15:1690-701.

11. Corley DA, Kubo A, Zhao W. Abdominal obesity, ethnicity and gastro-oesophageal reflux symptoms. Gut 2007;56:756-62.

12. Kozan O, Oguz A, Abaci A, Erol C, Ongen Z, Temizhan A, et al. Prevalence of the metabolic syndrome among Turkish adults.

Eur J Clin Nutr 2007;61:548-53.

13. Dennish GW, Castell DO. Inhibitory effect of smoking on the lower esophageal sphincter. N Engl J Med 1971;284:1136-7.

14. Dua K, Bardan E, Ren J, Sui Z, Shaker R. Effect of chronic and acute cigarette smoking on the pharyngoglottal closure reflex.

Gut 2002;51:771-5.

15. Mohammed I, Nightingale P, Trudgill NJ. Risk factors for gastro-oesophageal reflux disease symptoms: a community study.

North Clin Istanbul â&#x20AC;&#x201C; NCI Aliment Pharmacol Ther 2005;21:821-7.

16. Wang JH, Luo JY, Dong L, Gong J, Tong M. Epidemiology of gastroesophageal reflux disease: a general population-based study in Xiâ&#x20AC;&#x2122;an of Northwest China. World J Gastroenterol 2004;10:1647-51.

17. Schoeman MN, Tippett MD, Akkermans LM, Dent J, Holloway RH. Mechanisms of gastroesophageal reflux in ambulant healthy human subjects. Gastroenterology 1995;108:83-91.

18. Clark CS, Kraus BB, Sinclair J, Castell DO. Gastroesophageal reflux induced by exercise in healthy volunteers. JAMA 1989;261:3599-601.

19. Emerenziani S, Zhang X, Blondeau K, Silny J, Tack J, Janssens J, et al. Gastric fullness, physical activity, and proximal extent of gastroesophageal reflux. Am J Gastroenterol 2005;100:1251-6.

Orıgınal Article

HEALTH SERVICES

North Clin Istanbul 2014;1(3):147-152 doi: 10.14744/nci.2014.41636

The knowledge, attitude and behaviours of nurses about pharmacovigilance, adverse drug reaction and adverse event reporting in a state hospital Fisun Vural1, Seval Ciftci2, Birol Vural3 Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey;

1

Golcuk Necati Celik State Hospital, Kocaeli, Turkey;

2

Kocaeli University, School of Medicine, Kocaeli, Turkey

3

ABSTRACT OBJECTIVE: With the use of any drug comes the possibility of unintended consequences which when harmful are referred to as adverse drug reactions (ADRs). The development of national pharmacovigilance systems is the responsibility of all health workers. The aim of this study was to investigate the knowledge of nurses about pharmacovigilance and attitudes about ADR and adverse event reporting.

METHODS: This descriptive-cross sectional study was performed in 112 nurses working in a public hospital. The questionnaire was applied about pharmacovigilance and adverse drug reactions. The knowledge, attitudes and practices about adverse drug reactions were asked.

RESULTS: The 74.1% of the nurses definition of “severe adverse effect” of drug therapy. The ratio of participants who knew that ADRs are reported to contact person responsible from pharmacovigilance was 34.9%. Although 70.5% of nurses knew the necessity of ADR reporting, the 8% of the nurses knew Turkish Pharmacovigilance Center (TÜFAM). Only 8% of nurses reported ADRs in their professionality.

CONCLUSION: Although most of the participants knew the importance of ADR event reporting, event reporting was low. Thiese results showed that there is a lack of knowledge about pharmacovigilance. Futher studies with different settings and healthcare staff are needed to improve awareness about pharmacovigilance.

Key words: Drug reactions; drug safety; pharmacovigilance.

T

he World Health Organization (WHO) defined adverse drug reaction (ADR) as harmful, and unwanted reaction of a drug when used in normal doses for human beings. Pharmacovigilance was

defined as a branch of science and related activities interested in the determination, evaluation of drug safety, and taking necessary relevant measures [1-3].

At the beginning of 1900s German scien-

Received: September 11, 2014 Accepted: December 01, 2014 Online: January 24, 2015 ?, ????

Correspondence: Dr. Fisun VURAL. Haydarpasa Numune Egitim ve Arastirma Hastanesi, Istanbul, Turkey.

Tel: +90 216 - 414 45 24 e-mail: fisunvural@yahoo.com.tr © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

148

tist Paul Elrich defined the ideal drug as “a magic bullet”which directly reaches the region of the disease, and does not cause any harm to healthy tissues.” Drugs exert their effects on diseased region, and also harm healthy tissues as well [1]. Firstly in the year 1848, chloroform used during operation performed for the extraction of an ingrown toe nail in a pediatric patient named Hannah Greener induced development of atrial fibrillation ensuing in death of the patient. From then on, potential fatal adverse effects of the drugs attracted widespread attention [4] However, priorly in 1893 Lancet started to record adverse effects of the drugs [5]. In 1906, FDA laid down the rules stating that drugs should be formulated in their pure forms ie. free from other chemical substances. In the year 1936 sulphanilamide dissolved in ethylene glycol caused the death of 107 patients. This tragic event led the way to enact pharmacovigilance laws [4]. At the end of 1950s, emergence of cases with phocomelia secondary to thalidomide prescribed as a sedative in pregnant women shocked the whole world. Especially Germany where the drug first marketed was especially affected from harmful effects of the drug, and nearly 10.000 fetuses worldwide were exposed to teratogenic effects of the drug [6]. Though priorly, cases with phocomelia were thought to develop because of environmental teratogens, firstly in 1961 the cases with phocomelia caused by thalidomide were published in Lancet which led to enactment of the drug safety law [7]. Legal regulations known as Kefauer-Harris amendments banned the use of unsafe drugs whatever was their effectiveness would be [6]. These dramatic events experienced related to drug safety emphasized the importance of pharmacovigilance systems and Phase IV studies, and initiated the establishment of pharmacovigilance systems in the whole world [8].

From 2000s on, morbidity, and mortality related to drug use has become the most important health problem in the whole world, and in some developed countries. Besides in some developed countries mortality rates due to unwanted drug reactions have taken the 4th, and 6th place among allcause deaths which constituted 15-20% of health care expenditures and necessitated establishment of

North Clin Istanbul – NCI

pharmacovigilance systems [4, 9]. Every year nearly ten thousand people lost their lives because of adverse effects of the drugs, and even with the use of registered drugs unwanted, and unexpected adverse effects can be seen [4].

World Health Organization has pointed out to the differences in diseases seen, and prescription routines among countries. These differences involve a wide spectrum of genetic, dietary, and sociocultural variations. Because of differences in the production, dispension, and use of drugs, and also herbal medicinal products which can lead to various toxicological problems among countries, each country should establish its unique national pharmacovigilance system [9]. In Turkey, Turkish Drug, and Medical Device Institution of Turkish Republic (TITCK), Ministry of Health, and Social Welfare, and Turkish Pharmacovigilance Center (TÜFAM) enacted a Regulation Regarding the Monitoring and Assessment of Medicinal Products for Human Use. Our national pharmacovigilance system gained a corporate identity [9]. For effective realization of activities of national pharmacovigilance system, as one of the most important point, all health care professionals should be conscious about the fact that pharmacovigilance is a responsibility which should be shared by all health care professionals [4, 5].

Before marketing a drug for the first time, pharmacological properties, and efficacy of the drug are analyzed, and the drug passes through comprehensive, and detailed toksicological, and safety tests.

However information about adverse drug reactions can be acquired after postmarketing experience, sophisticated clinical experiments, meta-analyses, and reports of health care professionals about adverse reactions are entered into national, and international databases [9]. As reported in the literature, health care professionals encounter adverse drug reactions at an incidence rate of 1.6-41.4%, and in developed countries, nurses have been playing effective roles in reporting adverse events [10]. Since nurses are the main appliers of human medicinal products in clinics, they are in a position to detect unwanted effects which might develop during the treatment process.

Drug safety are among the priority issues in medicine [11-16]. In developed countries, pharma-

Vural et al., The knowledge, attitude and behaviour of nurses, working in a state hospital

covigilance studies have gained momentum, however in our country only a few studies have pointed out to deficiencies on this issue [17-20]. Ours is a pilot study which was planned with the aim to imvestigate knowledge, attitude and behaviour of the nurses working in a state hospital about pharmacovigilance, adverse drug reaction and event reporting MATERIALS AND METHODS This descriptive, and cross sectional study was performed with nurses working in Kocaeli Gölcük Necati Çelik State Hospital between January, and March 2013. Approval for the study was obtained from the Ethics Committee of Kocaeli University.

The objective of the study was explained to 160 nurses, and among them 112 nurses who gave their consent for participation were included in the study.

The questions in the survey were prepared based on “Rational Drug Use Questionnaire -2012” forms issued by Ministry of Health, and Wellfare.

The following items were investigated in the questionnaire: 1. Personal, and professional characteristics (age, professional seniority, the unit she/he is working) 2. What is his/her definition of an adverse effect? a) life-threatening effect b) fatal side-effect c) any side effect of the drug which prolongs hospital stay or necessitates in-hospital treatment d) any side effect which induces congenital anomalies e) all of them 3. How do you react when you encounter an adverse effect? a) I inform the physician or b) the charge nurse c) I fill up safety assessment or d) adverse effect reporting forms.

4. To what authority do you communicate the adverse effects? a) Chief Physician b) The Directorate of the Hospital c) Quality Management Unit d) Authority in Charge of the Pharmacovigilance.

5. To what official organ is notified about your adverse effect report? a) Provincial Directorate of Health b) Ministry of Health c) TÜFAM. 6. What are the minimal adverse effect reporting criteria? a) Name of the person who reported

149

Table 1. Personal, and professional characteristics of the nurses who participated in the study

Age groups 18-25 26-35 36-50 51-64 Gender Female Male Educational levels Lycée High school Faculty Doctorate/post-graduate Professional life span 1-3 years 4-10 years 11-15 years 16-19 years ≥20 years

n

%

6 55 48 3

5.3 49.1 42.8 2.8

105 7

93.7 6.3

15 57 38 2

13.4 50.9 33.9 1.8

8 19 33 26 26

7.1 17.0 29.5 23.2 23.2

adverse effect b) The name of the patient who used the drug c) The human medicinal product applied d) Name of at least one adverse effect e) The name of the prescribing physician f ) The drugs used by the patient g)All of them 7. Have you ever reported any adverse effect?

For the statistical analysis SPSS 14.0 (Statistical Package for Social Sciences) for Windows 97 program was used. Evaluation of data was performed using descriptive statistical methods. All analyses were evaluated within 95% confidence interval, and using two-way ANOVA test.

RESULTS Nearly 91.9% of the study participant nurses were in the 26-50 age group. The study population consisted of 93.7% female participants, and 98.2% of them were high school or university graduates.

Nearly 75.9% of the survey participants had 10

150

North Clin Istanbul â&#x20AC;&#x201C; NCI

8%

report

82%

Figure 1.

ADR reporting rates of the nurses during their professional lives.

or more than 10 years of professional experience.

Study participants were outpatient clinic (n=40; 35.7%), service (internal medicine, n=35; surgical clinics, n=25), or charge nurses (n=12; 10.7%). Sociodemographic characteristics of the study participants are given in Table 1.

Eighty-three (74.1%) nurses who participated in the survey study accurately defined serious side effect. Most of the (70.5%) participants knew that they should report any unwanted drug effects they observed during their practice. Thirty percent of the participants indicated that they should inform the prescribing physician about the adverse effect, and 39.2% of them knew that they should complete the side effect report form. Half of the participants were knowledgeable about minimum reporting criteria.

Although 70.5% of the nurses acknowledged the

necessity of reporting drug adverse effects, only 8% of these nurses reported drug adverse effects during their professional life (Figure 1). The knowledge levels of the participants about pharmacovigilance are given in Table 2.

Thirty-nine (34.9%) participants knew that adverse effect reporting should be addressed to the responsible pharmacovigilance authorities, while 25% of the nurses thought that adverse effects had been communicated to the quality management units.

When the knowledge level of the participants about the authorities whom they communicate adverse event reports was inquired, they named City Health Administratives (n=56; 50%), Ministry of Health (n=6; 5.4%), TĂ&#x153;FAM (n=9; 8%), and quality management onit (n=1; 0.9%). While 40 (35.7%) participants indicated that they had not known where to address their adverse event reports.

DISCUSSION Since drug-related mortality rates are quiet high worldwide, drug safety is among priorities in medicine [11-16]. Raising awareness about pharmacovigilance, and generalizing adverse effect reporting will not only ensure safe drug use, but also assure determination of specific adverse effects with resultant development of effective treatment modalities [5].

This is a descriptive study investigating awareness, and attitudes of nurses working in the clinics of a state hospital about necessity of ADR reporting.

The outcomes of this study have demonstrated that

Table 2. The knowledge levels of the participants about pharmacovigilance

Number (%) of participants who knew The defnition of ADR Necessity of ADR reporting Necessity for completing ADR report forms Knowledge level of minimum criteria of reporting Number of participants who knew that ADR reports should be communicated to the pharmacovigilance regulatory authorities Number of participant who knew TĂ&#x153;FAM

n

%

83 79 44 61

74.1 70.5 39.2 50

39 9

34.9 8

Vural et al., The knowledge, attitude and behaviour of nurses, working in a state hospital

despite awareness of ADR reporting was acknowledged, event reporting rates were still relatively low, and authorities to be addressed were not known.

Many investigations have been performed worldwide on the issue of pharmacovigilance, however nowadays the state of pharmacovigilance in our country has been revealed in only limited number of studies [17-20]. As reported in the literature, health professionals encounter adverse drug reactions at incidence rates varying between 1.6, and 41.4 percent [10]. Outcomes of the studies realized on the awareness for pharmacovigilance demonstrate variations among countries [21-24] The necessity of ADR reporting was recognized by different percentages of nurses participating in studies performed in China (1.6%) [22], Nigeria (35%) [23], and India (75%).

Although awareness of pharmacovigilance is improved in developed countries, still importance of educational activities has been emphasized in order to increase event reporting rates [10]. Ekman et al. performed a survey study with nurses in Switzerland, and reported event reporting rate as 14%, while this rate climbed to 30% among those receiving training on pharmacovigilance [21]. In this study, 74.1% of the nurses knew the unfavourable drug reactions, and 70% of them were cognizant that they should report adverse effects. However in their professional past, event reporting rates were found to be relatively lower. In three different studies in our country apart from ours, similar, and lower event reporting rates were indicated [18-20]. Sencan et al. realized a educational, and questionnaire survey study in a private hospital with 15 participants, and found that only 60% of the participant had defined adverse drug reactions correctly [19]. In the study performed by Sencan et al., 60% of the study participants encountered adverse drug reactions in their professional lives, but their event reportng rates were relatively lower [19]. Majority of our study population were of female gender in the 26-50 age group with an educational level of high school, and higher.

Besides they had a professional life of at least 10 years, and they were working in services.

In this investigation, though necessity for reporting adverse drug reactions was already acknowledged in 70.1% of the study participants, only 9% of them

151

reported adverse events. Sencan et al. [19], and Alan et al. [20] indicated incidence of event reporting as, 60, and 65%, respectively. Besides, in our study only 8% of the study participants were aware of the presence of TÜFAM which achieved a corporate identity. Besides only 8% of our study participants were aware of the the presence of TÜFAM which gained its corporate identity in 2005. In a survey study of Alan et al. in Adana region only 1.2% of the participants heard the name of TÜFAM [20]. In another study performed among pharmacists in Istanbul, even though 89 of the pharmacists believed the importance of reporting adverse drug effects, only 7% of them reported adverse effects to TÜFAM [18].

This is a pilot study conducted with the intention to determine awareness of the nurses working in a state hospital about pharmacovigilance so as to shed light on future studies to be performed.

Single-centered design of the study precludes making generalizations. According to the results of this investigation, deficiencies in adverse effect reporting, and lack of knowledge about authorities to be addressed implicate that we are still at the bottom of the ladder.

For the establishment of a national pharmacovigilance system, first of all, awareness should be raised among health care professionals about this issue. In our country, drug side effects are not recorded attentively. However, studies on this issue appear to be promising for the future. Further investigations on pharmacovigilance and especially those concerning causes of deficiencies in adverse event reporting should be performed.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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2. Lindquist M, Edwards IR. The WHO Programme for International Drug Monitoring, its database, and the technical support of the Uppsala Monitoring Center. J Rheumatol 2001;28:1180-7.

3. Edwards IR. The WHO World Alliance for Patient Safety: a new

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4. Çakır N. Deney Tüpünden Eczane Rafına: Bir Antimikrobiyal Nasıl Geliştirilir? ANKEM Derg 2010;24:174-81.

5. Routledge P. 150 years of pharmacovigilance. Lancet 1998;18:1200-1.

6. Botting J. The History of Thalidomide. Drug News Perspect 2002;15:604-611.

7. Waller P. An introduction to pharmacovigilance. In:What is Pharmacovigilance and How has it Developed? Wiley online publication. 2009;1-10. DOI: 0.1002/9781444316766.ch1 8. Edwards R. Advers Drug Reactions. In: Drug Benefits and Risks: International Textbook of Clinical Pharmacology. Boxtel CH, Santoso B, Edwars R. Eds, London, John Wiley &Sons ltd 2007:195-211.

9. Akılcı A, Dağıstanlı S, Aydınkarahaliloğlu D, Şardaş S. Ulusal Farmakovijilans Sistemi. Türk Farmakoloji Derneği Klinik Farmakoloji Çalışma Grubu Elektronik Bülteni 2005;3:19-22. www.tdf.org.tr 10. Shepherd M. Adverse reactions: know the risks. Nurs Times 2011;107:20.

11. Lesar T, Mattis A, Anderson E, Avery J, Fields J, Gregoire J, et al.

Using the ISMP Medication Safety Self-Assessment to improve medication use processes. Jt Comm J Qual Saf 2003;29:211-26.

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13. Barker KN, Flynn EA, Pepper GA, Bates DW, Mikeal RL. Medication errors observed in 36 health care facilities. Arch Intern Med 2002;162:1897-903.

14. Kayaalp S. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. 12.

Baskı, Ankara, 2009.

15. Akici A, Oktay S. Rational pharmacotherapy and pharmacovigilance. Curr Drug Saf 2007;2:65-9.

North Clin Istanbul – NCI 16. Sodha M, McLaughlin M, Williams G, Dhillon S. Nurses’ confidence and pharmacological knowledge: a study. Br J Community Nurs 2002;7:309-15.

17. Soyalan M, Demirdamar R, Toklu HZ, Gümüşel B. Kuzey Kıbrıs Türk Cumhuriyeti’nde ulusal farmakovijilans sistemi ve mevcut uygulamalar. Marmara Pharmaceutical Journal 2012;16:159-63.

18. Toklu HZ, Uysal MK. The knowledge and attitude of the Turkish community pharmacists toward pharmacovigilance in the Kadikoy district of Istanbul. Pharm World Sci 2008;30:556-62.

19. Şencan N, Altınkaynak M, Ferah I, Özyıldırım A, Ceylan E, Clark P. The Knowledge and Attitudes of Physicians and Nurses Towards Advers Event Reporting and the Effect of Pharmacovigilance Training: A Hospital Experience. Hacettepe University Journal of the Faculty of Pharmacy 2010;30:24-40.

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21. Ekman E, Petersson G, Tågerud S, Bäckström M. Awareness among nurses about reporting of adverse drug reactions in Sweden. Drug Healthc Patient Saf 2012;4:61-6.

22. Li Q, Zhang SM, Chen HT, Fang SP, Yu X, Liu D, et al. Awareness and attitudes of healthcare professionals in Wuhan, China to the reporting of adverse drug reactions. Chin Med J (Engl) 2004;117:856-61.

23. Fadare JO, Enwere OO, Afolabi AO, Chedi BA, Musa A. Knowledge, attitude and practice of adverse drug reaction reporting among healthcare workers in a tertiary centre in Northern Nigeria. Trop J Pharm Res 2011;10:235-42.

24. Rehan HS, Sah RK, Chopra D. Comparison of knowledge, attitude and practices of resident doctors and nurses on adverse drug reaction monitoring and reporting in a tertiary care hospital. Indian J Pharmacol 2012;44:699-703.

Orıgınal Article

P&ME

North Clin Istanbul 2014;1(3):153-157 doi: 10.14744/nci.2014.43531

Effect of botulinum toxin type-A in patients with focal spasticity Esra Selimoglu1, Selin Turan Turgut2, Pinar Akpinar3, Yasemin Yumusakhuylu4, Sema Haliloglu5, Hatice Sule Baklacioglu6, Afitap Icagasioglu4 Erenkoy Physical Medicine and Rehabilitation Hospital, Istanbul, Turkey;

1

Department of Physical Medicine and Rehabilitation, Karaman Government Hospital, Karaman, Turkey;

2

Department of Physical Medicine and Rehabilitation, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey;

3

Department of Physical Medicine and Rehabilitation, Istanbul Medeniyet University, Goztepe Training and Research Hospital,

4

Istanbul, Turkey; Department of Physical Medicine and Rehabilitation, Istanbul Occupational Disease Hospital, Istanbul, Turkey;

5

Department of Physical Medicine and Rehabilitation, Bakirkoy Prof. Dr. Mazhar Osman Psychology and Neurology Hospital,

6

Istanbul, Turkey

ABSTRACT OBJECTIVE: To investigate the effect of botulinum toxin type-A (BTX-A) on spasticity and function in patients with focal spasticity.

METHODS: Patients attended to the outpatient clinic of physical medicine and rehabilitation department with a diagnosis of focal spasticity and had BTX-A injections because of spasticty were evaluated for the study.

Demographic data, exercise status, orthoses, drugs used for spasticity, functional status, stages of spasticity of muscles before and after 1st and 3rd months of BTX-A injection according to Modified Ashworth Scale (MAS) were evaluated retrospectively. MedCalc 11.6 statistical program was used for statistical analyses. Statistical significance was defined as p<0.05.

RESULTS: Forty-nine patients with focal spasticity were recruited for the study (35 men, 14 women). Mean age of the patients was 21.59±20.09 years. The patients had cerebral palsy (CP, n=28), 19 had hemiplegia (n=19) and paraplegia (n=2). Forty-three patients were using orthoses and exercising regularly. Mean Pediatric Functional Independence Measurement (WeeFIM) scores of the patients with CP was 54.82±28.91 and according to the Gross Motor Function Classification System (GMFCS) the patients were in stages 2 (14%), 3 (46%), 4 (11%) and 5 (29%). Mean Functional Independence Measure (FIM) of hemiplegic and paraplegic patients was 80.80±20.88.

Brunnstrom staging scores for upper extremity (3.52±0.96), hands (2.68±0.82), lower extremity (4.57±1.01) were calculated. MAS muscles demonstrated statistically significant decrease in spasticity at the end of first and third months (p<0.05).

CONCLUSION: We saw a significant decrease in the spasticity of upper and lower extremities in patients with focal spasiticity who received BTX-A injections. We suggest that if BTX-A injections are supported with orthoses and exercise programs, then functional status of the patients would be better.

Key words: Botulinum toxin type-A; cerebral plasy; hemiplegia; spasticity.

Received: September 11, 2014 Accepted: November 18, 2014 Online: January 24, 2015 ??? ??, ????

Correspondence: Dr. Esra SELIMOGLU. Erenkoy Fizik Tedavi ve Rehabilitasyon Hastanesi, Istanbul, Turkey.

Tel: +90 216 - 411 80 11 e-mail: esselimoglu@gmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

154

S

pasticity arises as a result of destructive changes in medulla spinalis or serebrum caused by trauma, stroke, hypoxia, inflammatory, and demyselinizing diseases, degenerative or familial diseases or compression by mass lesions. Muscle contraction amplitude decreases, muscle tone, and rigidity increases, and velocity dependent resistance during passive joint movements occur because normal inhibition of lower motor neurons which is required for the maintenance of physiological muscle tone is not achieved resulting in predominancy of upper motor neuron functions [1-3].

Spasticity is a complex disorder which may lead to serious disability [4]. Primary aim in its treatment is to achieve functional improvement. Among treatment targets increasing mobility, decreasing pain, and spasms, increasing ROM of joints, facilitating use of ortheses, and positioning, providing cosmetic benefit, prevention or postponing surgery can be enumerated [5, 6]. Nowadays prophylactic treatment modalities applied for the treatment of spasticity include appropriate positioning, stretching, and exercises, physical therapy, oral antispastic drugs (baclofen, diazepam, tizanidine, and dantrolene), neuromuscular blockade with phenol or BTX-A, intratechal baclofen, and surgical interventions [7, 8].

BTX-A is the most potent neurotoxin produced

by Clostridium botulinum. Via inhibition of acetylcholine release from presynaptic terminals of peripheral cholinergic nerves BTX-A prevents nervous signal transmission [9, 10]. Nearly two or three moınths later, new nerve terminals develos through axonal budding, and nervous signal transmission resumes. Various studies have demonstrated that recovery of neuromuscular transmission, and secretion of acetylcholine are achieved nearly 91 days after BTX-A injection. It exerts its effect within the first week which peaks at 4.-6. weeks, and disappears generally within 3-4 months [11]. Thanks to its long-term, but reversible effect, ease of its application, appropriateness, and established safety, in addition to its favourable side effect profile, BTX-A has become the first choice in the pharmacological treatment of focal spasticity [12].

In this study the effect of BTX-A injections on

North Clin Istanbul – NCI

spasticity in patients with focal spasticity has been retrospectively investigated.

MATERIALS AND METHODS After retrieval of the ethics committee approval, the patients who were followed up, and received BTX-A injections in the outpatient clinic of Physical Medicine, and Rehabilitation Department with the diagnosis of focal spasticity were retrospectively evaluated. The patients with generalized spasticity, and those who developed contractures were excluded from the study. Patients’ demographic data, their compliance to exercise therapy, orthoses, and antispastic drugs used, and their functional status were retrieved, and recorded via screening their medical files, The severity of spasticity evaluated for BTX-A injected muscle groups were evaluated before, and 1, and 3 months after injections MAS criteria’ 0: No increase in muscle tone 1: Slight increase in muscle tone 1: Minimal resistance at the end of the range of motion (ROM) of the affected mucle when the affected part(s) is moved in flexion or extension 2: More marked, but still slight increase in muscle tone; Minimal resistance felt throughout less than half of the ROM of the joint 3: Considerable increase in the muscle tone, difficulty during passive movements 4: Affected muscle part(s) are rigid in flexion or extension [7].

Study population consisted of the patients who received BTX-A injections, and diagnosed as focal spasticity, cerebral palsy (CP), hemiplegia, and paraplegia. Disease severity of CP patients according to Pediatric Functional Independence Measure (WeeFIM) scores, and their Gross Motor Function Classification levels, and also Functional Independence Measure (FIM), and Brunnstrom staging scores of the hemiplegic, and paraplegic patients were recorded, and all patients were included in the rehabilitation program.

For statistical Analysis MedCalc 11.6 statistical

Selimoglu et al., Effect of botulinum toxin type-A in patients with focal spasticity

Table 1. Demographic data

Gender Female Male Diagnosis Cerebral Palsy Hemiplegia Paraplegia Orthoses Users Nonusers Antispastics Users Nonusers Exercise program Compliants Noncompliants

n

%

14 28.57 35 71.42 28 51.14 19 38.77 2 4.08 43 87.75 6 12.24 18 36.73 31 63.26 43 87.75 6 12.24

program was used. p<0.05 was accepted as the level of significance.

RESULTS A total of 49 patients were included in the study.

Demographic characteristics of the patients are demonstrated in Table 1. The study population consisted of 35 male, and 14 female patients. Mean

155

age of the patients was 21.59±20.09 years. The patients were followed up with diagnosis of CP (n=28), hemiplegia (n=19), and paraplegia (n=2).

Forty-three patients were using orthoses, and exercising to maintain their positioning or range of motion, and functionality of the affected joint.

Mean WEEFIM score of the patients with CP was 54.82±28.91. GMFCS. scores of the patients with CP are shown in Graphic 1. Mean FIM score of patients with hemiplegia, and paraplegia was 80.80± 20.88 Mean Brunnstrom staging scores of the patients were 3.52±0.96 for the affected upper extremity, 2.68±0.82 for the hand, and 4.57±1.01 for the lower extremity. Pre-, and post-treatment 1.

(T1), and 3. (T3) month- MAS scores of the patients were also evaluated. Pre-, and post-treatment T1 spasticity levels were statistically significantly different (p<0.05). Besides, post-treatment 1 (T1), and 3. (T3) month spasticity scores were also statistically significantly different (p<0.05) (Table 2).

DISCUSSION This retrospective study was performed to demonstrate the effect of BTX-A injection on patients with focal spasticity 1, and 3 months after injection.

The results have demonstrated that BTX-A injection prominently decreased muscle tone.

Spasticity is a complex disorder which might lead to serious disability. BTX-A is used for multifocal, and focal spasticities. For the determina-

Table 2. BTX-A injected muscles, and their MAS (Modified Ashworth Scale) values Muscles (n)

Onset of treatment MEAN±SD

1. Month MEAN±SD

3. Month MEAN±SD

p

Biceps 18 Flexor carpi radialis 14 Flexor carpi ulnaris 13 Flexor digitorum superficialis 12 Flexor digitorum profundus 11 Adductor muscles of the hip 18 Hamstring Gastrosoleus 35

2.4±0.61 2.42±0.85 2.61±0.5 2.58±0.51 2.63±0.5 2.38±0.69 2.38±0.65 2.48±0.56

1.5±0.7 1.35±0.84 1.46±0.77 1.5±0.75 1.63±0.67 1.33±0.76 1.33±0.76 1.48±0.61

1.94±0.63 1.71±1.06 1.69±0.75 1.75±0.45 1.72±0.46 1.72±1.01 2.23±0.92 1.94±0.72

<0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05

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0.0% 11% 14%

46% 29%

Level Level Level Level Level

1 2 3 4 5

Figure 1.

Distribution of the patients with cerebral palsy based on their GMFCS (Gross Motor Function Classification) scores.

tion of spasticity, and evaluation of its progression, physical, quantitative, and standardized scales have been used. Quantitative methods are preferred in randomized studies. Among them MAS is the most frequently used scale [8]. Slovek et al. injected a median dose of 255 IU botox to 18 stroke patients with upper extremity spasticity, and detected a significant regression in MAS values [13]. Simpson et al. investigated effectiveness of BTX-A on upper extremity spasticities in their randomized doubleblind, placebo controlled studies, and compared BTX-A 75/150/300 IU doses with placebo. The authors detected significant decrease in muscle tone 6 weeks after application of higher doses of BTXA [14]. In their randomized controlled studies, Scholtes et al. demonstrated the effect of BTX-A on muscle length, and walking parameters, and decrease in spasticity starting from the first week after injection. [15]. Brashear et al. injected 200-240 U botulinum toxin into wrist, and finger flexors of 126 patients who developed post-stroke spasticity, and detected significant regression in MAS values, improvement in hygiene, and also movements done during wearing clothes, and pain relief without any side effects [16]. Hesse et al. applied 400 units BTX-A to 12 patients with chronic lower extremity extensor spasticity, and and detected a significant regression of MAS values of 10 patients within 2 weeks [17]. Karaçam et al. analyzed 15 patients who developed post-stroke focal spasticity, and measures of spasticity (MAS), muscle strength score, disabil-

ity scale, visual analogue scale, and Barthel index scores obtained at control visits performed at 1., and 3. months were compared With this study they obtained a serious decrease in MAS, and disability scores. Another striking feature of the study is that effectiveness of BTX-A still continued at 3. month controls [7]. In some literature studies decrease in the effectiveness of BTX-A was reported at. 3. month controls, and this phenomenon was associated with severity of spasticity, inadequate doses, and inability to comply regularly with the rehabilitation program [3, 13, 18]. In this study, decreases in the severity of spasticity were detected at 1, and 3. months based on MAS values of the patients who received BTX-A injections to their upper, and lower extremities, At 3. month controls of the patients, persistence of BTX-A effects can be associated with compliance of most of the patients to their exercise programs, and usage of appropriate doses.

Physical therapy applications, therapeutic exercises, use of orthoses or plastering, electrical stimulation of BTX-A injected muscles, and biofeedback can be used after BTX-A injections [19]. Therapeutic exercises include traction/ stretching of BTX-A injected muscles, if active movements were noticed, then strength of antagonistic muscles were strenghtened, and neurofascilitative exercises were prescribed. Our patients were prescribed stretching exercises for BTX-A injected muscles, and if active muscle movements were noted, then these patients were included in the antagonistic muscle- strenghtening programs. Our 43 patients completed their exercise program.

CONCLUSION Because of adverse effects of oral agents, in recent years for the treatment of spasticity, BTX-A injections have been used. Though various viewpoints have been proposed about effectiveness, and duration of BTX-A treatment, consensus opinion asserts that its effect is not sustainable Whatever the treatment choice for spasticity is, it should be supported by a neurohabilitative program.

Conflict of Interest: No conflict of interest was declared by the authors.

Selimoglu et al., Effect of botulinum toxin type-A in patients with focal spasticity

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Simpson DM. Clinical trials of botulinum toxin in the treatment of spasticity. Mayer NH, Simpson DM (eds). Spasticity: Etiology, Evaluation, Management and the Role of Botulinum Toxin.

New York: We Move, 2002:125-30.

2. Little JW, Massgli TL. Spasticity and associated abnormalities of muscle tone. DeLisa JA, Gans BM (eds). Rehabilitation Medicine: Principles and Practice. Philadelphia: Lippincott-Raven Publishers 1998:997-1013.

3. Ozcakir S, Sivrioglu K. Botulinum toxin in poststroke spasticity.

Clin Med Res 2007;5:132-8.

4. Gracies JM. Pathophysiology of spastic paresis. I: Paresis and soft tissue changes. Muscle Nerve 2005;31:535-51.

5. Burke D. Spasticity as an adaptation to pyramidal tract injury.

Adv Neurol 1988;47:401-23.

6. Umphred DA, McCormack GL. Classification of common facilitatory and inhibitory treatment techniques. In: Umphred DA (ed). Neurological Rehabilitation. Missouri: Mosby 1990:11161.

7. Karaçam M, Selçuki D. İnme sonrası gelişen spastisite tedavisinde botulinum toksin A intramusküler enjeksiyonu etkinliği.

Turk Norol Derg 2010;16:133-40.

8. Coban A, Matur Z, Hanagasi HA, Parman Y. Iatrogenic botulism after botulinum toxin type A injections. Clin Neuropharmacol 2010;33:158-60.

9. Mayer NH. Clinicophysiologic concepts of spasticity and motor dysfunction in adults with an upper motoneuron lesion. Muscle Nerve Suppl 1997;6:1-13.

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10. Denny-Brown D. The cerebral control of movement. Liverpool: Liverpool University Press 1966:124-43, 171-84.

11. Coffield J, Comsidine RV, Simpson LL. The site and mechanism of action of botulinum neurotoxin. In: Jankovic J, Hallett(eds).

Therapy with botulinum toxin. Marcel Dekker 1994:3-13.

12. Farmer SF, Harrison LM, Ingram DA, Stephens JA. Plasticity of central motor pathways in children with hemiplegic cerebral palsy. Neurology 1991;41:1505-10.

13. Slawek J, Bogucki A, Reclawowicz D. Botulinum toxin type A for upper limb spasticity following stroke: an open-label study with individualised, flexible injection regimens. Neurol Sci 2005;26:32-9.

14. Simpson DM, Alexander DN, O’Brien CF, Tagliati M, Aswad AS, Leon JM, et al. Botulinum toxin type A in the treatment of upper extremity spasticity: a randomized, double-blind, placebocontrolled trial. Neurology 1996;46:1306-10.

15. Scholtes VA, Dallmeijer AJ, Knol DL, Speth LA, Maathuis CG, Jongerius PH, et al. Effect of multilevel botulinum toxin a and comprehensive rehabilitation on gait in cerebral palsy. Pediatr Neurol 2007;36:30-9.

16. Brashear A, McAfee AL, Kuhn ER, Fyffe J. Botulinum toxin type B in upper-limb poststroke spasticity: a double-blind, placebo-controlled trial. Arch Phys Med Rehabil 2004;85:705-9.

17. Hesse S, Lücke D, Malezic M, Bertelt C, Friedrich H, Gregoric M, et al. Botulinum toxin treatment for lower limb extensor spasticity in chronic hemiparetic patients. J Neurol Neurosurg Psychiatry 1994;57:1321-4.

18. Ward A, Roberts G, Warner J, Gillard S. Cost-effectiveness of botulinum toxin type a in the treatment of post-stroke spasticity.

J Rehabil Med 2005;37:252-7.

19. The We Move Spasticity Study Group. Mayer NH, Simpson DM (eds). Spasticity: Etiology,evaluation and management of spasticity, and the role of botulinum toxin. 2002;1-174.

Orıgınal Article

GASTROENTEROLOGY

North Clin Istanbul 2014;1(3):158-165 doi: 10.14744/nci.2014.54227

Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors Mestan Sahin1, Canan Akbulut2, Can Dolapcioglu3, Eyup Ozpolat1, Resat Dabak2, Mehmet Aliustaoglu1, Emel Ahishali3 Department of Internal Medicine, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey;

1

Department of Family Medicine, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey;

2

Department of Gastroenterology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey

3

ABSTRACT OBJECTIVE: To evaluate the endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors (PPIs) and analyze if there is any correlation between these findings and dyspeptic symptoms via predetermined inquiry.

METHODS: Patients between 18 and 45 years of age were selected among those referred to our unit for upper GI endoscopy due to failure to achieve improvement in dyspeptic complaints with PPI. Patients who consent to participate in and eligible for the study were questioned for their symptoms using questionnaires.

RESULTS: A total of 446 patients with female preponderance (60%) were included in the study. Endoscopic results were listed as: 147 (32.9%) normal, 16 (3.6%) gastric ulcer, 36 (8.1%) duodenal ulcer, 216 (48.4%) gastritis, 7 (1.5%) duodenitis and 24 (5.4%) esophagitis. A total of 122 patients were classified as functional dyspepsia.

While incidence of persistent bloating was distinctly higher in patients with gastritis compared to those with normal endoscopic findings (p:0.000), but its incidence was comparable between ulcer and normal patients. No statistical difference was detected between gastritis, ulcer and normal endoscopy patients considering incidence of early satiety. Compared to those with normal endoscopy patients, incidence of epigastric pain was significantly higher among patients with gastritis and ulcer (p: 0.002 and p: 0.000 respectively). Incidence of heartburn was higher in patients with gastritis compared to those with normal endoscopy findings, but it was similar to those with ulcer.

CONCLUSION: Most (67.1%) of the patients between 18 and 45 years of age with no alarm symptoms had diagnoses that required use of a PPI. Hence, the patients should be carefully evaluated before referring for endoscopy.

Key words: Dyspepsia; esophagogastroduodenoscopy; proton pump inhibitor- treatment.

D

yspepsia is a discomfort felt over the upper abdomen, and epigastrium. Dyspepsia is a group of symptoms including pain, bloating, early satiety, postprandial upper abdominal fullness, nausea, loss

of appetite, pyrosis, regurgitation, and belching.

Dyspepsia is an important clinical problem in that it is very frequently seen in the commuınity which is also one the reasons for seeking medical help. Be-

Received: November 26, 2014 Accepted: December 04, 2014 Online: January 24, 2015 ??? ??, ????

Correspondence: Dr. Emel AHISHALI. Dr. Lütfi Kirdar Kartal Egitim ve Arastirma Hastanesi, Istanbul, Turkey.

Tel: +90 216 - 441 39 00/1176 e-mail: emelahishali@yahoo.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Sahin et al., Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors

cause of recurrent complaints in half of the patients, patient’s quality of life, and social life is affected directly or indirectly [1, 2]. In addition to medical services used for dyspeptic patients, loss of labour, and productivity lead to considerable financial burden.

In Western countries estimated prevalence of dyspepsia among adults ranges between 10, and 20%, and it constitutes 5% of referrals to outpatient clinics, and nearly 40-70% of the consultations for gastrointestinal complaints [3, 4]. In studies performed in various parts of the world, the prevalence of dyspepsia has been reported to vary between 14.5, and 45 percent [5-10]. In a few studies carried on in our country the prevalence of dyspepsia was revealed to fluctuate between 30.8, and 39 percent [11, 12, 13].

Patients without alarm symptoms and history of chronic disease, GIS operation, thyroid dysfunction, accidental intake of corrosive material, and diseases causing gastroesophageal symptoms as scleroderma, cases who didn’t use non-steroidal anti-inflammatory drugs, steroids or routine aspirin users, and those refractory to 8 weeks of treatment with proton pump inhibitors (PPIs) were considered to have dyspepsia unresponsive to PPI treatment. In our study, upper gastrointestinal system (GIS) endoscopic findings of the patients with PPI-refractory dyspeptic symptoms.were evaluated.

The purpose of the study was to investigate if any correlation exists between findings of upper GIS endoscopic examination performed with the indication of initial diagnosis of dyspepsia, and dyspeptic symptoms using a preprepared questionnaire forms MATERIALS AND METHODS Patients without alarm symptoms and history of chronic disease, GIS operation, thyroid dysfunction, accidental intake of corrosive material, and diseases causing gastroesophageal symptoms as scleroderma, cases who didn’t use non-steroidal anti-inflammatory drugs, steoids or routine aspirin users, and those refractory to 8 weeks of treatment with proton pump inhibitors (PPIs) were considered to have dyspepsia unresponsive to PPI treatment. Our study population was selected among patients aged 18-45 who were referred to our en-

159

doscopy unit for endocopic GIS examinations with the indication of dyspepsia unresponsive to PPIs. One week after endoscopic examinations, patients were called for a control in the polyclinics, and faceto-face interviews. Among patients who gave their consent for participation in the study, cases without any alarm symptoms, accidental corrosive substance intake, but with complaints priorly suggestive of dyspepsia (individuals describing heartburn and/ or regurgitation were excluded), and those without history of chronic diseases (diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic renal failure, chronic renal failure or chronic hepatic failure), thyroid dysfunction, and scleroderma which might induce gastroesophageal symptoms, cases who didn’t routinely use non-steroidal anti-inflammatory drugs, steroids or aspirin were included in the study. Patients whose first degree relatives had been diagnosed as gastric and/or esophageal cancer, and underwent endoscopic procedures for diagnostic purposes, cases with Barrett’s esophagus, gastric, and esophageal tumors who were endoscopically monitored, and those with metastases who were screened for primary tumor foci were not included in the study.

Patients who volunteered for the participation in the study filled up informed consent forms, and responded to the questions in questionnaire forms we prepared to evaluate symptoms. Questionnaire form is shown in Table 1. Following completion of questionnaire forms, heights, and weights of the patients were measured. Approval of the Ethics Committee of our hospital was obtained for the conduction of this study.

Endoscopic findings of the study participants were evaluated as normal, gastric ulcer, duodenal ulcer, gastritis, duodenitis, and esophagitis (suspect cases with short-segment Barret’s esophagus were evaluated as esophagitis) Cases with esophagitis were classified based on Modified Los Angeles Classification.

A total of 579 patients were called by phone for polyclinic controls, and 517 of them attended the follow-up visits. Among 468 eligible patients, 21 of them did not want to participate in the study. One patient with GIS tumor detected during endoscop-

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Table 1. Questionnaire form Department of Gastroenterology, Dr. Lutfi Kirdar Kartal Training and Research Hospi̇ tal Evaluation of the Patients who Underwent Endoscopic Examinations with the Indication of Dyspepsia The first, and the last name of the patient: Date: Age: Male Female Alcohol use: cc/day Type of alcoholic drink: Smoking status: cigarettes/day Body weight: Kg Height: cm

□

□

Duration: Duration:

year year

1. Within the last 3 months, how often have you felt disturbing abdominal bloating after eating a normal amount of food?

0. Never 1. 8-20 days a month 2. Every day 2. How long have you had this disturbing bloating?

0. No bloating 1. For the last 1 -6 months 2. For more than 6 months 3. Within the last 3 months how often have you stopped eating your meal because of your stomach problems?

0. Never 1. 8-20 days a month 2. Every day 4. How long have you had problems of stopping eating your meal because of your stomach problems?

0. Early satiety is absent 1. For the last 1-6 months 2. For more than 6 months 5. Within the last 3 months, how often have you felt pain on the middle of your abdomen (not on your chest)?

0. Never 1. 8-20 days a month 2. Every day 6. How long have you had this pain?

0. Never 1. For the last 1 -6 months 2. For more than 6 months 7. Is this pain related to eating a meal?

0. It does not change with eating?

1. The pain worsens after eating a meal?

2. The pain decreases after eating a meal?

8. Within the last 3 months, how often have you felt a burning pain at the middle of your abdomen (not on your chest)?

0. Never 1. For the last 1 -6 months 2. For more than 6 months 9. How long have you had complaints of burning pain?

0. Never 1. For the last - 6 months 2. For more than 6 months 10. Is this pain related to eating a meal?

0. It does not change with eating?

1. It worsens after eating .

2. It decreases after eating 11. Within the last year how often have you used a PPI (omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole etc.)?

0. 1-3 times a day 1. Every day 2. Whenever I had complaints 12. How often have you had treatment for “Helicobacter pylori” infection?

0. Never 2. Twice 1. Once 3. Thrice 13. Have you ever undergone an endoscopic examination?

0. None 2. Twice 1. Once 3. Thrice

Sahin et al., Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors

Table 2. Frequency of bloating

None 8-20 days a month Every day

Table 3. Duration of complaints of bloating

Patients (n=446)

%

11 2.4 135 30.3 300 67.3

Table 4. Frequency of early satiety

None 8-20 days a month Every day

Patients (n=446)

%

185 41.4 187 42.0 74 16.6

None 8-20 days a month Every day

Patients (n=446)

None 1-6 months ≥6 months

Patients (n=446)

%

11 36 399

2.4 8.0 89.6

Table 5. Duration of early satiety symptoms

Table 6. Frequency of abdominal pain

161

None 1-6 months ≥6 months

Patients (n=446)

%

185 93 168

41.4 20.8 37.8

Table 7. Duration of complaints of abdominal pain %

9 2.0 141 31.6 296 66.4

ic examination was not included in the study. The study was completed with 446 patients.

RESULTS A total of 446 patients (women, n=267; 60%, and men, n=179; 40%) with a mean age of 35.73±8.13 years were included in the study. Mean body heights, and weights of the patients were 168±8.51) cm, and 73.75 (±10.14) kg, respectively. Mean BMI (body mass index) of the patients was 26.18±3.8 kg/m2 Among a total of 446 patients, 193 (53.2%) smokers, and 104 (23.3%) alcohol users were detected.

None 1-6 months ≥6 months

Patients (n=446)

%

9 37 400

2.0 8.4 89.6

In the questionnaire form the item which questioned “bloating symptoms” was responded affirmatively by 435 (97.5%) patients. The responses to the question which inquired the frequency of bloating are shown in Table 2, while the patients’ answers to duration of bloating are given in Table 3. Two hundred and sixty-one (58.6%) patients indicated that they had felt early satiety in response to the item of “early satiety” included in the questionnaire form. Frequency, and duration of early satiety indicated by the patients are shown in Tables 4, and 5.

Frequency, and duration of the abdominal pain are shown in Tables 6, and 7. When the correlation of this complaint with meals was investigated, among

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Table 8. Presence, and duration of complaints of

Table 9. Duration of complaints of epigastric burning

epigastric pain

Patients (n=446)

None For 8-20 days Every day

%

12 2.7 125 28.0 309 69.3

Epigastric burning is absent Complaints of epigastric burning for 1-6 months Complaints of epigastric burning for more than 6 months

Patients (n=446)

%

12

2.7

36

8.1

398

89.2

Table 10. The frequency of PPI use by patients

Patients (n=446)

1-3 times a week Every day Whenever I had complaints

105 149 192

% 23.5 3.,5 43.0

Table 11. Number of endoscopic examinations Number of upper GIS endoscopic examinations None Once Twice Thrice

Patients (n=446)

%

362 81.2 52 11.6 22 5.0 10 2.2

Table 12. The number of patients who received treatment for “Helicobacter pylori” infection

HP-treatment naive patients HP treatment, once HP treatment, twice HP treatment, thrice

*

Patients (n=446)

%

277 103 42 24

62.1 23.0 9.5 5.4

436 patients who were complaining of ‘stomach pain’ indicated that the intensity of their pains worsened with meals (51. 8% of the patients) or did not change (40.6%). Number of patients who described epigastric burning, and duration of their pains are shown in Tables 8, and 9. Frequency of PPI use, application of endoscopic procedures, and treatment for Helicobacter pylori infection are shown in Tables 10, 11, and 12, respectively.

Endoscopic findings of the patients are shown in Figure 1. During endoscopic examinations esophaghitis (n=18; 4%; Grade A, n=13; Grade B, n=5),

and a suspect cases of short-segment (< 2 cm) Barret’s esophagus (n=6; 1.3%) were detected.

The patients with normal endoscopic findings were classified according to their responses, and within the frame of Rome III diagnostic criteria, the diagnosis of functional dyspepsia (FD) was sought for. FD was detected in 122 (83%) out of 147 patients with normal endoscopic findings Bloating symptoms, and endoscopic findings were evaluated, and higher rates of bloating were observed in patients with pathological endoscopic findings (p=0.015). Among 435 patients with bloating, gastritis was detected in 218 (48.9%) patients. Bloating complaints were more frequently experienced every day by patients with normal endoscopic findings or gastritis. (p=0.000). Any difference was not found in the frequency of bloating complaints in patients with and without ulcer.

Still a significant difference was not found between patients whose endoscopies demonstrated normal

Sahin et al., Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors

Normal n:147 Gastric ulcer n:16 Duodenal ulcer n:36 Gastritis n:216 Duodenitis n:7 Esophagitis n:24

Figure 1. Endoscopic findings of the patients.

GIS, gastritis or ulcer. Epigastric burning was more frequently observed in patients with endoscopically detected ulcer or gastritis when compared with those normal GIS. (p=0.000, and p=0.002, respectively). Epigastric burning was more frequently experienced by patients with endoscopically detected gastritis relative to those with normal GIS (p=0.002). Frequency of epigastric burning did not differ between patients with normal endoscopic findings, and those with ulcer.

In our study any correlation between obesity, and dyspepsia was not found. Scarce number of patients in our study were smokers or using alcoholic beverages, so we couldnâ&#x20AC;&#x2122;t establish any correlation between them, and dyspeptic symptoms.

DISCUSSION Due to its chronic and /or recurrent nature, and its harmful effects on routine daily life of the patients, dyspepsia generally is an indication for endoscopic evaluation. Nearly 20% of our study participants had undergone upper GIS endoscopy at least once because of prolonged duration of their symptoms more than 6 months. In our study, upper GIS endoscopic findings of dyspeptic patients unresponsive to PPI treatment were evaluated. In previous studies where dyspeptic complaints, and endoscopic findings were analyzed, 15-26.7% of endoscopic findings were not indicative of gastritis. [14, 15, 16]. In our study its rate was 17.1 percent. We think that because of exclusion of the patients with alarm symptoms, and those older than 45 years of age from our assessments, our rate was lower than cited in the literature.

163

Dyspeptic symptoms of the patients were evaluated using our questionnaire forms. In 83% of the patients with normal endoscopic findings, FD was detected based on Rome III criteria. Park et al. [17] detected median FD rate as 40.9% in patients with chronic dyspeptic complaints according to Rome III criteria. In a population-based study performed in Japan, median FD rate was found to be 14.2% in patients with dyspeptic symptoms based on Rome III criteria [18]. In a study realized in Asia prevalence of FD was detected within a wide spectrum ranging between 7.4, and 70% [19, 20]. However, these studies were evaluated based on different criteria, and a heterogenous distribution of patientsâ&#x20AC;&#x2122; ages was reported. Therefore, incidence of FD differed widely in these studies.

In our study similar rates of bloating (87.6%), epigastric pain (98%), and epigastric burning (97.3%) were detected. In studies performed in Europe, and Asia rates of epigastric pain were detected as 36.6-66.3%, and 25-44.5%, respectively [18, 21, 22]. In studies realized in Turkey epigastric pain was reported at an incidence rate of 77.9-95%, and frequency of epigastric burning was indicated as 95% [11, 23, 24]. We think that, our relatively higher rate of dyspeptic complaints is related to our evaluation of young-middle aged group of patients, PPI-unresponsive dyspeptic cases, and those without alarm symptoms. Symptoms of early satiety in studies on dyspepsia have demonstrated variations between 9.1, and 67.5 percent [21, 22, 25]. Studies realized in our country reported its incidence as ranging between 36.8, and 45 percent [11, 24]. In our study symptoms of early satiety was the least (58.8%) encountered complaint relative to the frequencies of other 3 symptoms.

Apart from other studies, in our questionnaire survey we evaluated the association between frequency of dyspeptic complaints, and endoscopic findings. Significantly higher number of patients with gastritis complained of bloating, epigastric pain or burning every day (p=0.000, p=0.002, and p=0.002, respectively). In cases with ulcer, as a striking finding, epigastric pain was felt every day. (p=0.000). These outcomes suggest that in patients complaining of dyspeptic symptoms in general,

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gastritis may be present, and GIS ulcer may be detected in individuals suffering frequently from epigastric pain.

In our study, endoscopic examinations of dyspeptic patients unresponsive to PPIs revealed the presence of gastritis in half, normal findings in onethird, gastric ulcer or esophagitis in nearly one-fifth of the these cases. In 83% of the patients with normal endoscopic findings FD was detected. Great majority of the patients with FD can not benefit only from PPI treatment, however in the treatment of other diagnoses PPI has been used. In nearly 70% of the dyspeptic patients younger than 34 years of age without alarm symptoms, upper GIS endoscopy reveals diagnoses requiring PPI treatment. Therefore, before ordering endoscopy, the patients should be evaluated in detail to disclose problems which may arise from disuse or misuse of the drug Besides in our study we evaluated frequency of dyspeptic complaints, and endoscopic findings, and detected higher number of patients with gastritis among those who had dyspeptic complaints every day.

Median BMI value of the study participants was 26.1 kg/m2. In a TEKHARF survey study where the prevalance of obesity in Turkey was investigated, median BMIs in the age group of 30-79 years of age were found to be 26.85 kg/m2 in men, and 29.22 kg/m2 in women [26]. In our study, a correlation between obesity, and dyspepsia was not found.

However, in our study, we had scarce number of obese patients, and median BMI of our patients was lower than that estimated for Turkish population.

In conclusion, in dyspeptic patients without alarm symptoms younger than 45 years of age and unresponsive to PPIs, upper GIS endoscopy detects diagnosis which necessitates high doses of PPIs, Besides the incidence of gastritis is higher in patients experiencing dyspeptic symptoms every day. Therefore patients’ complaints, and findings should be meticulously evaluated.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

North Clin Istanbul – NCI

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3. Camilleri M, Dubois D, Coulie B, Jones M, Kahrilas PJ, Rentz AM, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study. Clin Gastroenterol Hepatol 2005;3:54352.

4. Ford AC, Forman D, Bailey AG, Axon AT, Moayyedi P. Initial poor quality of life and new onset of dyspepsia: results from a longitudinal 10-year follow-up study. Gut 2007;56:321-7.

5. Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ 3rd. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology 1992;102:1259-68.

6. Drossman DA, Li Z, Andruzzi E, Temple RD, Talley NJ, Thompson WG, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci 1993;38:1569-80.

7. Tougas G, Chen Y, Hwang P, Liu MM, Eggleston A. Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: findings from the DIGEST study. Domestic/International Gastroenterology Surveillance Study. Am J Gastroenterol 1999;94:2845-54.

8. Moayyedi P, Forman D, Braunholtz D, Feltbower R, Crocombe W, Liptrott M, et al. The proportion of upper gastrointestinal symptoms in the community associated with Helicobacter pylori, lifestyle factors, and nonsteroidal anti-inflammatory drugs. Leeds HELP Study Group. Am J Gastroenterol 2000;95:1448-55.

9. Kay L, Jørgensen T. Epidemiology of upper dyspepsia in a random population. Prevalence, incidence, natural history, and risk factors. Scand J Gastroenterol 1994;29:2-6.

10. Shah SS, Bhatia SJ, Mistry FP. Epidemiology of dyspepsia in the general population in Mumbai. Indian J Gastroenterol 2001;20:103-6.

11. Bektaş M, Çetinkaya H, Çalışkan D, Öztaş E, Akdur R, Özden A. Park Sağlık Ocağı bölgesinde 15 yaş üstü nüfusta dispepsi prevalansı. Akademik Gastroenteroloji Dergisi 2007;6:120-6.

12. Arslan H, Türkay C, Yönem Ö, Sadioğlu ÖD. Cumhuriyet Üniversitesi genelinde ve Tıp Fakültesi öğrencilerinde dispepsi prevelans çalışması. Güncel Gastroenteroloji 2002;6:29-34.

13. Özaydın ANG, Çalı Ş, Türkyılmaz AS, Hancıoğlu A. Marmara Sağlık Eğitim ve Arastırma Vakfı. TURHEP Türkiye Helikobakter Pilori Prevalans Arastırması 2003 Arastırma Raporu. İstanbul: Eray Basım Hiz. Tic. Ltd. Sti; 2007.

14. Talley NJ, Vakil NB, Moayyedi P. American gastroenterological association technical review on the evaluation of dyspepsia. Gastroenterology 2005;129:1756-80.

15. Shiota S, Murakami K. Endoscopic findings of dyspeptic patients. Clinical Gastroenterology 2010;51:467-70.

Sahin et al., Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors

16. Ford AC, Marwaha A, Lim A, Moayyedi P. What is the prevalence of clinically significant endoscopic findings in subjects with dyspepsia? Systematic review and meta-analysis. Clin Gastroenterol Hepatol 2010;8:830-7.

17. Park JM, Choi MG, Cho YK, Lee IS, Kim JI, Kim SW, et al.

Functional Gastrointestinal Disorders Diagnosed by Rome III Questionnaire in Korea. J Neurogastroenterol Motil 2011;17:279-86.

18. Kinoshita Y, Chiba T; FUTURE Study Group. Characteristics of Japanese patients with chronic gastritis and comparison with functional dyspepsia defined by ROME III criteria: based on the large-scale survey, FUTURE study. Intern Med 2011;50:2269-76.

19. Ghoshal UC, Singh R, Chang FY, Hou X, Wong BC, Kachintorn U. Epidemiology of uninvestigated and functional dyspepsia in Asia: facts and fiction. J Neurogastroenterol Motil 2011;17:235-44.

20. Adibi P, Behzad E, Shafieeyan M, Toghiani A. Upper functional gastrointestinal disorders in young adults. Med Arh 2012;66:89-91.

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2010;105:565-71.

22. Xiao YL, Peng S, Tao J, Wang AJ, Lin JK, Hu PJ, et al. Prevalence and symptom pattern of pathologic esophageal acid reflux in patients with functional dyspepsia based on the Rome III criteria.

Am J Gastroenterol 2010;105:2626-31.

23. Sayın I, Oğuz AK, Değertekin H. Fonksiyonel dispepsinin değerlendirilmesinde klinik yaklaşım. Akademik Gastroenteroloji Dergisi 2008;7:91-5.

24. Bor S, Endoscopic and pathologic findings in patients with dyspepsia in Turkey: Multicenter prospective study (DISPEN).

Sözlü bildiri, 28. Ulusal Gastroenteroloji Haftası, 2011. Turk J Gastroenterol 2011;22:(suppl 1):96.

25. Hongo M, Harasawa S, Mine T, Sasaki I, Matsueda K, Kusano M, et al. Large-scale randomized clinical study on functional dyspepsia treatment with mosapride or teprenone: Japan Mosapride Mega-Study ( JMMS). J Gastroenterol Hepatol 2012;27:62-8.

26. Onat A, Keleş İ, Sansoy V, Ceyhan K, Uysal Ö, Çetinkaya A, et al. Yetişkinlerimizin 10-yıllık Takibinde Obezite Göstergeleri Artışta: Beden Kitle İndeksi Erkeklerde Koroner Olayların Bağımsız Öngördürücüsü. Türk Kardiyol Derneği Arşivi 2001;29:430-3.

Orıgınal Article

HEALTH SERVICES

North Clin Istanbul 2014;1(3):166-172 doi: 10.14744/nci.2014.14633

Evaluation of demographic characteristics, and general disease state of patients affiliated with home health care unit of Malatya State Hospital Ersoy Oksuz1, Elif Onat1, Andleeb Shahzadi2, Zeliha Yazici2, Cumali Cetin3 Department of Home Health Service, Malatya State Hospital, Malatya, Turkey;

1

Department of Medical Pharmacology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey;

2

Departmen of Infectious Diseases, Malatya State Hospital, Malatya, Turkey

3

ABSTRACT OBJECTIVE: Home Health Care Unit a unit provides health services for elderly, bedridden and individuals with chronic diseases at home along within the frame of the diagnosis, and treatments of the relevant experts.

Therefore, it is intended to reduce the probable physical and emotional burden related to the patient that arise by commuting to the hospital, to increase the number of empty beds for other patients and to improve the living standard by reducing the risk of hospital infection. In this study, the demographic characteristics of housebound patients, their general disease and its relationship with age and gender was investigated.

METHODS: The following study was performed on 626 active patients of Malatya State Hospital Home Health Care Unit from January to November 2014. Data were analyzed using Microsoft Excel Program.

RESULTS: The study included 60.5% (n=379) female and 39.5% (n=247) male patients. The highest group consisted of patients with 80 years or above 37.7% (n=236). Cerebrovascular disease (CVD) (n=95; 25.0%), senility (n=56; 14.8%) and Alzheimer’s disease (n=50; 13.2%) were commonly observed in women. Male patients had CVD (n=54; 21.8%), femur fracture or gonarthrosis which required surgery (n=28; 11.3%), and fracture due to trauma or traffc accidents (n=28; 11.3%), senility and Alzheimer’s disease (n=218.5%).

CONCLUSION: In recent years home health care units became even more important after the gradual increase in the elderly population and injuries due to accidents. This study can help to provide home health care units in a more effcient manner by educating the staff and relatives who take care of the patients.

Key words: Alzheimer; cerebrovascular disease; home heatly care; senility.

H

ealth care units at home provide necessary psychosocial, and medical support for elderly, and disabled individuals, patients with chronic dis-

eases after their discharge from the hospital in their living environment, increase their standard of living, ensure more peaceful life for them, and alleviate the

Received: December 01, 2014 Accepted: December 18, 2014 Online: January 24, 2015?? ??, ????

Correspondence: Dr. Ersoy OKSUZ. Malatya Devlet Hastanesi, Firat Mahallesi, Hastane Caddesi, Cosnuk Semt Poliklinigi Malatya, Turkey.

Tel: +90 422 - 326 15 69 e-mail: drugoksuz@hotmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Oksuz et al., Home health care unit of Malatya State Hospital

work burden of patient’s relatives [1].

Home health care units were firstly implemented in the year 2005 with the release of a regulation

by Ministry of Health entitled “Provision of Home Health Care Services”, and published in the Turkish Official Gazette (issue #25751) [2]. In compliance with the regulation released in the year 2010 the task of these units has been described as “The task of this unit is not to make a diagnosis, but to offer services of physical examination, analysis, medical care, and rehabilitation at home of the patient within the frame of the diagnosis made, and treatment planned previously by the specialists of the relevant branches. Besides it facilitates prescription of medical board reports for the drug(s) which should be used for a long time, and release of the reports for medical device, and materials. It also informs the patient, and his/her family about the tasks they would assume during the disease process, and provide training, and counselling about the disease, health care procedures, appropriate use of medical devices, and equipments that should be used at home [3].

Home health care units especially offer services to elder patients with chronic diseases, completely or partially bedridden patients at their home. By this means, it is aimed to obviate from material, and moral constraints which originate from frequent commuting between home, and the hospital, increase number of empty beds in the hospital, decrease the hospitalization expenditures, and the risk of nosocomial infection by early discharge of the patients from the hospital, provide moral support for the patients by their earlier return to their family environment, and raise their standard of living to its peak level, and protect them from contracting secondary diseases [4].

In Turkey, elder population and life span of people are increasing gradually. In the year 2005, 5%, and in 2010 7.9% of the Turkish population consisted of elderly people. In the year 2025, it is estimated to rise to 10 percent [5, 6]. With the increase in the elder population, the number of individuals who need health care services at home will increase. With aging, incidence of chronic diseases also increases. In 90% of the individuals over the age of 65, presence of one or more than one disease states have been reported. According to The World

167

Health Organization (WHO) 60% of all deaths in the world are caused by chronic diseases. Among these deaths, cardiovascular diseases lead the way followed by cancer-related deaths. Among fatal diseases for people over the age of 60, ischemic heart disease, and cerebrovascular diseases take the first, and the second place, respectively [6]. Cerebrovascular disease (CVD) occupies an important place as for home health care units. In a report released

by WHO in 2005, CVD is also responsible for 12.0% of all disease-related deaths. Besides CVD is responsible for 85% of all deaths caused by neurological diseases [7, 8]. In a study performed in 2011 in Ordu University Training and Research Hospital within the context of Health Care Services At Home, CVD was detected as the most frequently seen disease [9]. Regarding their higher incidence, and also requirement for long-term health care, treatment, and rehabilitation of these patients by health care services at home gain gradually increasing importance.

One of the other two important problems is that in recent years the number of bedridden patients have increased because of ever increasing rate of traffic accidents and necessitated fulfilling the needs of disabled individuals in the community. As an important issue, since many of these patients are young individuals, they should be reintigrated into society, their hospital stays, and treatment costs should be decreased.

A study performed in 2002 revealed that 4.0% of disabled individuals in the community required health care services at home. Nearly 10.0% of them had reportedly a chronic disease [10, 11].

The objective of this study was to evaluate age, and gender of the patients, and diseases seen in patients who received active services in Malatya State Hospital Home Health Care Unit between January, and November 2014.

MATERIALS AND METHODS For this study required approvals have been obtained from The Ethics Committee of Clinical Researches, and hospital administration of Yüzüncü Yıl University. Home Health Care Unit of Malatya State provide services from 2008 on. The patients who died

168

North Clin Istanbul – NCI

Table 1.

Number (%) of patients according to age groups

Age groups

≤49 50-59 60-69 70-79 ≥80

Women n=379 (60.5) n

%

Men n=247 (39.5) n

%

Total (n=626) n

%

35 9.2 54 21.8 89 14.2 25 6.6 22 8.9 47 7.5 44 11.6 33 13.4 77 12.3 108 28.5 69 28.0 177 28.3 167 44.0 69 28.0 236 37.7

since 2008 were excluded from the study, and medical files of 2800 patients who received services from this unit were screened. The patients whose death was reported during the study period, patients temporarily confined to bed (cases with bone fractures because of traffic accident or trauma, patients operated for various indications whose wounds were dressed or their injections were made), and completely cured patients who did not receive the services of the unit any more were excluded from the study, and demographic characteristics, and diseases of the remaining 991 patients were classified. The patients (226 female, and 139 male) who received the services of this unit before the year 2014 were not included in the study. A total of 626 active patients who were visited by the staff of the unit at their home, and received health care services were included in the study. This was a retrospective, and descriptive study which enrolled all patient groups who consulted to Malatya State Hospital the Home Health Care Unit within the year any sampling was not constructed.

Statistical analysis All data were evaluated in the Microsoft Excel program. All data were entered in a computerized system, then percent changes of each group were calculated based on total number of study participants, and separately for male, and female patients Limitation of the study The study included active patients who had received

services within the year 2014. Although, higher number of patients were included in our study, exclusion of the patients who were thought to be bedridden as understood from screening of patients’medical files, but couldn’t receive the services of the Unit is a limitation of our study.

RESULTS A total of 626 (female, n=379, 60.5%, and male, n=247; 39.5%) patients were included in the study.

Based on the age groups, number, and percentages of the female, and male patients are given in Table 1. Patients aged ≥80 constituted the group with the highest number of patients (n=236; 37.7%). The diseases seen in the patients who received health care services at home were prioritized, and classified as diseases, and disease groups which would confine the patients to bed. Secondly, concomitant diseases were evaluated separately. In female patients cerebrovascular diseases (CVDs) (n=95; 25.0%), senility (n=56; 14.8%), and Alzheimer’s disease (n=50; 13.2%) were detected in respective number, and percentage of female patients as indicated in parentheses. Among male patients, cases with CVD (n=54; 21.8%), operations with the indications of femoral fracture, or gonarthrosis (n=28; 11.3%), patients with fractures caused by traumatic events or traffic accidents (n=28; 11.3%), finally Alzheimer’s disease, and senility (n=21; 8.5%) were detected (Table 2). Although, the patients in the advanced age group were mostly confined to bed because of chron-

Oksuz et al., Home health care unit of Malatya State Hospital

169

Table 2. Diseases seen in patients who were benefiting from home health care service units Diseases

Women

Men %

n

Total

n

%

n

%

Cerebrovascular diseases Senility Alzheimer Femur fracture, gonarthrosis, osteoporosis CHF Oncological diseases Spastic disability, MR or cerebral palsy Trauma-Fracture following TA Multiple sclerosis Amiotrophic lateral sclerosis Epilepsy, psychosis, parkinsonism Myopathy, neuropathy Encephalitis as a result of MI COPD CRF Obesity SSPE, GB, TBC, PAD, ELP, LDH

95 25.0 54 21.8 149 23.8 56 14.8 21 8.5 77 12.3 50 13.2 21 8.5 71 11.3 41 10.8 28 11.3 69 11.0 41 10.8 17 6.9 58 9.3 23 6.0 21 8.5 44 7.0 19 5.0 22 8.9 41 6.5 12 3.0 28 11.3 40 6.4 8 2.0 2 0.8 10 1.6 - - 3 1.2 3 0.5 6 1.5 8 3.2 14 2.2 4 1.0 7 2.3 11 1.7 1 0.25 5 2.0 6 0.9 6 1.5 6 2.4 12 1.9 6 1.5 1 0.4 7 1.1 6 1.5 - - 6 0.9 5 1.25 3 1.2 8 1.2

ELP: Elephantiasis; GB: Gullain-Barré syndrome; CRF: Chronic renal failure; CHF: Chronic heart failure; COPD: Chronic obstructive pulmonary disease; LDH: Lumbar discal hernia; MI: Myocardial infarction; MR: Mentally retarded; PAD: Peripheral artery disease; SSPE: Subacute sclerosing panencephalitis; TBC: Tuberculosis; TA: Traffic accident.

ic diseases, in the group aged 49 years or younger, more frequently the patients with congenital anomalies, congenital diseases or patients who experienced traumatic events, and traffic accidents were confined to bed. Majority of the young men who received services of the Unit had fractures secondary to traumatic events or traffic accidents (female 12, and male 28).

Distribution (%) of CVD, senility, and Alzheimer’s disease seen in individuals benefiting from the Home Health Care Unit is seen in Table 3. CVD was most frequently seen in the age group of 70-79 years (43.0%), then in patients aged 80 and above (34.9%). Female patients with left hemiplegia (52.6%) were more numerous than those with right hemiplegia. However among men the rates of left, and right hemiplegia were equal (46.2%). Senility as a cause of confinement to bed was seen mostly in patients aged 80 and over (83.1%). In 52.5% (n=42) of the patients, any chronic disease was not detected

excepting senility. As chronic disease, hypertension was detected in 16 (28.6%) female, and 8 (38.0%) male patients. Alzheimer’s disease was mostly seen in patients aged 80, and over (64.8%). Forty-four (65.0%) patients had only Alzheimer’s disease without any other chronic disease. Concomitant HT was present in 13 female, and 7 male patients.

As asecondary chronic diseases, hypertension (n=196; 31.3%), and diabetes mellitus (n=86; 13.7%) were seen. Decubitus ulcer which is the most important health problem in bedridden patients was seen in 48 (7.6%) patients.

DISCUSSION Most of our study population were elder, and chronic patients. Patients’ requirement for care, and health services increases with age. A study performed in Eskişehir, revealed that people in need of care constituted 3.7% of the total population of the city. While

170

North Clin Istanbul – NCI

Table 3. Distribution, and rates of CVD, senility, and Alzheimer’s disease among age groups seen in patients who were benefiting from home health care servives Disease (Gender)

≤49 n

n

%

60-69

70-79

≥80

n

%

n

%

n

Left hemiplegia (Female)

8

16.0

20

40.0

Left hemiplegia (Male)

1

4.0

4

16.0

10

40.0

Right hemiplegia (Female)

2

5.3

6

15.8

16

Right hemiplegia (Male) 1

4.0

1

4.0

4

16.0

16

Tetraplegia (Female)

14.3

2

28.6

1

14.3

2

50.0

1

%

50-59

Tetraplegia (Male) Total

Total %

n

%

22

44.0

50

52.6

10

40.0

25

46.2

42.1

14

36.8

38

40.0

64.0

3

12.0

25

46.2

1

14.3

2

28.6

7

7.3

1

25.0

1

25.0

4

7.4

2 1.3 6 4.0 25 16.8 64 43.0 52 35.0 149 23.8

Senility (women)

1

1.8

8

14.3

47

83.9

56

14.8

Senility (men)

1

4.7

3

14.3

17

81.5

21

8.5

Total

2 2.6 11 14.3 64 83.1 77 12.3

Alzheimer’s disease (Female)

5

10.0

12

24.0

33

66.0

50

13.2

Alzheimer’s disease (Male)

1

4.8

7

33.2

13

62.0

21

8.5

Total

6 8.5 19 27.8 46 64.8 71 11.3

people aged above 65, comprised 53.2% of the total population of the city [11]. In a study performed both in 1997, and 2004 in Austria, median age of the male, and female population benefiting from health care units in the years 1997, and 2004 was detected as 72 vs. 76, and 79 vs 81 years, respectively [12]. In the year 2011, in the study performed by Home Health Care Service Unit of Ordu University Training and Research Hospital most frequently (38.4%) patients aged 80 years, and above were detected [9]. We also obtained similar results in our study. Most of our study population were aged 80, and above (37.7%). In a study performed in Austria, female patient population (71.1%) was indicated to be more numerous than male patients [12]. Similarly in a study performed by the Home Health Care Unit of a Turkish public hospital, female patients were observedly higher (63.8%) in number [13]. In a study performed in Ordu University Training and Research Hospital, male patient population was reportedly more numerous (58.4%) than female patients [9]. In compliance with the other two studies mentioned above, in our study, the percentage of fe-

male patients were 21.0% higher than male patients.

Although the number of male, and female patients in a study performed in the year 2011 in Mamak district were nearly the same to what we detected in our study, number of patients in age groups differred. In this study the highest number of patients were reported in the 45-60 age group, then in the 35-40 age group [10].

In patients receiving health services at home, more frequently cardiac, orthopedic, respiratory problems, and DM were encountered [11, 14]. Based on the data provided by local health authority of Eskişehir, Alzheimer’s disease, dementia, and cerebrovascular diseases were reported in 50% of those receivimg health care at home [11]. In a study conducted in Austria, mostly central nervous system (CNS), musculoskeletal (degenerative, posttraumatic), and cardiovascular diseases were observed [12]. Similar outcomes have been also revealed in a study performed in Ordu University Training and Research Hospital. In their study most frequently CVD was seen, followed by Alzheimer’s disease [9]. Our outcomes were similar to this data. CNS-related CVD,

Oksuz et al., Home health care unit of Malatya State Hospital

Alzheimer’s diseases, operated femoral fracture, gonarthrosis, osteoporosis, and CHF consisted 4 of 5 most frequently seen diseases. Our study differs from others, in that senility was the most frequently seen condition after CVD. Nearly, half of these patients any chronic disease was not found.

CVD is responsible for 14.5%, and 15.7% of the mortalities among men, and women, respectively [7]. CVD is the most important disease which causes restriction of mobility in individuals above 40 years of age. Ischemic stroke is more frequently seen in elder women. Since life span of women is longer, they appear to have higher risk of dying from an ischemic disease, and risk of stroke during their life time [15, 16, 17]. The outcomes of our study are compatible with these findings. CVD is the most frequently seen disease, especially in women. Beginning from the age group of 50-59, its incidence increased in both genders. Only one female, and one male patient were younger than 50 years of age. In men it is most often seen in the age group of 70-79 years, while its incidence decreased almost 50 percent in the age group of 80 and above. In women it is most often seen in the age group of 80 and above.

Five female patients aged above 90, were followed up with the diagnosis of CVD, while none of our male patients were older than 90 years of age.

Alzheimer’s disease increases with age. In a study performed with patients above 50 years of age prevalence of Alzheimner’s disease was detected as 11.0 percent [18, 19]. In another study Alzheimer’s disease was found in 30.4% of the people aged 75 years, and above [20]. In our investigation, Alzheimer’s disease ranked third among our patients. In our study, the rates of Alzheimer’s disease increased with age. Alzheimer’s disease was mostly seen in patients aged 80, and above. In both genders, number of patients aged 80, and above were significantly higher than those seen in younger patients.

Decubitus ulcer is an important health problem which can emerge in bedridden patients. Decubitus ulcer increases mortality, and morbidity, and decreases quality of life of the patients. It also increases frequency of long-term immobility [21].

In another study, decubitıus ulcer was reported in 12.0% of the patients receiving health care services

171

at home [9]. However in our study lesser number (7.6%) of our patients had decubitus ulcer. Because of frequent provision of health care services to these patients, they have a special place as for home health care units. The staff of the Home Health Care Unit visit these patients at their homes, and dress their wounds every other day which have an important place in the Unit’s workload not mentioning economic burden as for the utilization of material, cost of drugs used, and wound care expenditures. Therefore, as an important issue, Health Care Service Units should train the patient’s household about applications against occurrence of decubitus ulcer.

In this study where demographic characteristics, and diseases seen in the patients who were receiving home care were evaluated, generally outcomes similar to those seen in other studies have been obtained. In our study, the need for health care services at home is especially crucial for bedridden patients with cardiovascular diseases, senility, Alzheimer’s Disease, and musculoskeletal diseases. Structuring home health care service units, and training their staff so as to ensure treatment, and rehabilitation of these patients who need long-term care can be realized at their home environment will be an appropriate approach.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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9. Enginyurt Ö, Öngel K. Evde bakım hizmeti kapsamındaki hastaların sosyodemografik özellikleri ve tıbbi durumları. Smyrna Tıp Dergisi 2011;45-8.

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11. Arslantaş D. Halk Sağlığı Bakışıyla Evde Bakım Hizmetleri; Durum Tespiti. Halk Sağlığı Uzmanları Derneği Yaşlı sağlığı: sorunlar ve çözümler 2012;1:80-6.

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original ımages

HEMATOLOGY

North Clin Istanbul 2014;1(3):173 doi: 10.14744/nci.2014.88597

Cutaneous adverse effects of imatinib mesylate Mehmet Hilmi Dogu, Ismail Sari, Sibel Hacioglu, Ali Keskin Department of Hematology, Pamukkale University Faculty of Medicine, Denizli, Turkey

Figure 1.

Right lateral image of

patient.

Figure 2. tient.

Right leg image of pa-

A 52-year -old female patient was found to have elevated white blood cell count (WBC) on routine physical examination. Her WBC count was 67.260/ uL, hemoglobin was 8.3 gm/dL, hematocrit was 26.1% and platelet count was 133,000/uL. Bone marrow reveled myeloid hyperplasia and the Philadelphia chromosome was positive. Patient was diagnosed as chronic myeloid leukemia (CML) and imatinib mesylate treatment began in August 2011. The patient did not receive any concomitant treatment. On the 5th month of imatinib treatment, the patient was admitted because of pruritus and grade 4 generalized skin rashes. Erythematous lesions and scaly plaques were noted (Figure 1, 2). At that time, imatinib was discontuined and topical corticosteroid was given with oral an antihistaminic.

Her pruritus resolved and skin lesions improved. Imatinib was replaced by dasatinib (100 mg/day) and her treatment is still ongoing. Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of one–two cases per 100,000 adults and accounts for nearly 15% of newly diagnosed cases of leukemia in adults.

CML is characterized by a balanced ge-

netic translocation, t(9;22)(q34;q11.2).

This rearrangement is known as the Philadelphia chromosome. Imatinib mesylate was the first TKI to receive approval by the Food and Drug Administration (FDA) for the treatment of patients with CML-CP. Cutaneous reactions to imatinib are common. The reported frequency varies across studies (rash, 32%-39%, severe rash 3%4%; pruritus, 6%-10%, severe pruritus <1%; severe cutaneous reactions, <1%, and photosensitivity 0.1%-1%). The median onset of severe skin reaction is about 1-2 months after the start of treatment but it may be delayed. Management of dermatologic adverse events is generally confined to discontinuation or reduction of imatinib dose, and administration of oral and/or topical corticosteroid and antihistamines use. In our patient due to the grade 4 skin reactions, molecular response has not been achieved yet. As we know, in clinical trials with 2nd generation TKIs significantly deeper and faster responses have been reported, however their impact on long-term survival remains to be determined. In accordance with this clinical studies we replaced imatinib with dasatinib at daily doses of 100 mg.

Received: October 29, 2014 Accepted: December 01, 2014 Online: January 24, 2015 ? ??, ????

Correspondence: Dr. Mehmet Hilmi DOGU. Pamukkale University, Faculty of Medicine. Fahri Goksin Oncology Center 20070 Denizli, Turkey.

Tel: +90 444 0 728 e-mail: mhdogu@yahoo.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

original 覺mages

CARDIOLOGY

North Clin Istanbul 2014;1(3):174 doi: 10.14744/nci.2014.43043

Marfan syndrome with a giant noncoronary sinus of Valsalva aneurysm Sahin Avsar, Sennur Unal Dayi, Adnan Kaya, Ibrahim Levent Ozmutlu, Altug Osken Dr. Siyami Ersek Cardiovascular Surgery Hospital, Istanbul, Turkey

A

B

C

D

Figure 1.

(A) Transthoracic echocardiogram in the apical four-chamber view showing a giant noncoronary sinus of Valsalva aneurysm (SVA). (B, C, D) Cardiac computed tomography images. (B) Axial image showing noncoronary SVA compressing all pulmonary veins (PV) and the LA. The dissection flap in the descending thoracic aorta is also seen between the false (FL) and true (TL) lumens. (C) Coronal image showing noncoronary SVA compressing the RA. Arrow indicates the mechanical aortic valve. (D) Sagittal image showing noncoronary SVA. LV: Left ventricle; RV: Right ventricle.

Once presented in 2011 by Dayi SU et al. our case is a 30-year-old woman with Marfan syndrome who had undergone aortic valve replacement due to severe aortic regurgitation secondary to dilatation of the aortic root in 2000 and supracoronary aortic replacement due to Stanford type A dissection in 2002 with subsequent dilatation of sinus of Valsalva. When described by Dayi SU et al. the size of the aneurysm was noted to be 6x6.5x6.5 cm in dimensions and it was formed from noncoronary sinus of Valsalva. At this time conservative follow- up was found to be the appropriate therapy because high risk of redo surgery. Three years later the same patient was observed in echocardiography laboratory with a rapid progression of the same aneurysm of sinus of Valsalva to 8.3x9.3x8.2 cm in size (Figure 1A). Moderate mitral and tricuspid regurgitation with prolapse of valves and normal function of mechanical aortic valve were observed.

Computed tomography angiography also confirmed enlargement of the aneurysm to 91.9x91.8 in size (Figures 1B, C, and D). Herein, we would like to draw attention to the clinical presentation and progression of Marfan syndrome.

Received: October 01, 2014 Accepted: November 24, 2014 Online: January 24, 2015 ?? ??, ????

Correspondence: Dr. Sahin AVSAR. Dr. Siyami Ersek Hastanesi, Tibbiye Caddesi, No: 13, Istabul, Turkey.

Tel: +90 216 - 542 44 44 e-mail: avsarsahin@gmail.com 穢 Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Case Report

ENT

North Clin Istanbul 2014;1(3):175-177 doi: 10.14744/nci.2014.96967

Aural myiasis: case report Erdem Mengi1, Erhan Demirhan2, Ilker Burak Arslan2 Department of Otolaryngology, Maltepe State Hospital, Istanbul, Turkey;

1

Department of Otolaryngology, Tepecik Training and Research Hospital, Izmir, Turkey

2

ABSTRACT Myiasis is the infestation of live vertebrates with dipterous larvae. Aural myiasis involves infestation of the external ear and/or middle ear. It is a rare clinical state that usually occurs in patients who have mental or physical disabilities. Although myiasis is a self-limiting disease, it can be associated with fatal complications like penetration within the central nervous system. We present a 87-year-old patient suffering from Alzheimer’s disease with aural myiasis and also discuss the clinical presentation and efective therapies with a review of the literature.

Key words: Alzheimer’s disease; aural myiasis; otorrhagia.

T

he myiasis, derived from the ancient Greek word ‘myia’ which means fly, is an infestation of the tissues and organs caused by fly (diptera) larvea [1]. Although life cycle of a fly depends on species and types of exposure, usually infestation onsets with flies leaving their ova on intact skin, wound or necrotic tissue. Larvae hatching from the ova pass into adjacent tissues, and complete their life cycles, and transform into adult forms. Myiasis can encounter us in various forms in clinical practice. They are classified as ecologically obligatory, facultative or accidentally localized parasites. Anatomically they are classified according to the location of the larvae in the host [2]. Aural myiasis or automyiasis is the infestation of external ear and/ or middle ear with dipterous larvae. This very rarely encountered clinical condition is generally seen in children, in individuals with predisposing factors as

mental retardation or impaired personal hygiene.

In this article an Alzheimer’s disease patient with automyiasis will be presented after approval of the patient, and their relatives.

CASE REPORT A 87-year-old bedridden woman for 6 months who followed due to severe dementia and monitored in neurology clinic with the diagnosis of Alzheimer’s disease, was consulted to our clinic because of pruritus and bleeding of her left ear. She was suffering from itching in her left ear for nearly a month and bleeding for 2 days. On her physical examination, left external ear canal was completely occluded with mobile larvae (Figure 1). Then the patient was brought into the operating room for otomicroscopic examination External ear canal was irrigated with

Received: September 25, 2014 Accepted: October 22, 2014 Online: January 24, 2015 Correspondence: Dr. Erdem MENGI. Altaycesme Mahhallesi, Cam Sok., No: 26-28, 34843 Maltepe, Istanbul, Turkey.

Tel: +90 216 - 459 77 70 e-mail: zerbesler@gmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

North Clin Istanbul â&#x20AC;&#x201C; NCI

176

Figure 2. Appearance of live larvae.

Figure 1.

Mobile larvae completely obstructing left external ear canal.

10% lidocaine spray, and 70% ethanol to restrict the movements of larvae. Under microscopic guidance, 7 white-colored, thick, and segmented larvae with a mean length of 10-15 mm were extracted from inside the external ear canal with the aid of an aspirator, and alligator clamps (Figure 2). Secretions, and granulation tissue within the external ear canal were removed. An area of perforation on the posterior quadrant of the tympanic membrane was observed.

External ear canal, and middle ear were irrigated with physiologic saline. Larvae were not encountered in the middle ear. Topical antibiotherapy was initiated with a mixture of hydrogen peroxide and boric acid solution One week later larvae were not encountered within her external ear canal. Because of her advanced age, and mental health state tympanoplasty operation was not conceived.

DISCUSSION Myiasis can be seen in various regions, skin, body cavities, and organs. Aural myiasis can manifest itself in various forms including ophthalmomyiasis, nasal myiasis, urogtenital myiasis, intestinal myiasis, and cutaneous myiasis [3-6]. Only one species

of dipterous larva can involve more than one anatomical region or different species can be seen in the same region [2].

Otomyiasis is quiet rarely seen in healthy people [7]. Literature reviews have detected its presence generally in children, people with poor hygiene or those having predisposing factors. Among these predisposing factors mental retardation, immobilization, immunosuppression, and diabetes mellitus can be enumerated [8]. Besides chronic otorrhea is considered as a risk factor in healthy, and ambulatory patients [7]. Our case was a bedridden patient for nearly 6 months with a limited interaction with her environment.

Complaints of otomyiasis can manifest differences based on the patientâ&#x20AC;&#x2122;s mental health state.

These patients can present with complaints of sensation of foreign substance in the ear, aural itching, pain, bleeding, tinnitus, hearing loss, and vertigo [8, 9]. In our case, the most important symptom was itching in the ear. However aural pruritus was not considered as an important symptom by her relatives, and the patient was not consulted to an ENT specialist till her left ear bled. This otorrhagic symptom was thought to be related to frequent scratchings, and the patient was fastened to her bed. Since in cases with otomyiasis early diagnosis is thought to be very important, especially in patients with predisposing factors, persistent ear itching should lead

Mengi et al., Aural myiasis

the physician to be suspicious of otomyiasis, and the patients should be evaluated with meticulous otoscopic examination.

In literature reviews, the most frequently encountered species of parasites in cases with aural myiasis are cochliomyia hominivorax, wohlfahrtia magnifica, chrysomya bezziana, chrysomya megacephala, and parasarcophaga crassipalpis [2]. In our case segmented larvae measuring approximately 10-15 mm covered with bands of irregularly, and retrogradely arrayed spinous processes. With these characteristics, these larvae were determined to be consistent with wohlfahrtia magnifica species.

Otomyiasis is generally a self limiting disease.

Larvae usually leave the host when they become adult larvae. However during this period because of both mechanical effects of larvae, and collagenases they secrete, they induce many complications in the patient. These complications can include perforation of the tympanic membrane, destruction of the middle ear, and mastoid cavity, and fatal central nervous system invasion [10]. Mortality rates of otomyiasis combined with nasal myiasis climb to 8 percent [2]. The most important point in the prevention of complications is early diagnosis, and eradication of the larvae as soon as possible.

The treatment of otomyiasis is basically mechanical cleaning of the airway. This procedure should be performed under microscope is especially important in the evaluation of the middle ear in cases with tympanic membrane perforation. Following mechanical cleaning irrigation of the ear canal with 70% ethanol, 10% chloroform or physiologic saline, urea, dextrose, creatinine, and topical ivermectin is recommended so as to get rid of the remaining larvae. In addition, in cases with suspect furuncle or secondary infection, topical antibiotherapy can be prescribed [8-10].

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In conclusion, persistent ear itching, and pain, and irritability especially in patients with predisposing factors as mental retardation, dementia, and immunosuppression, oto myiasis should be kept in mind. A simple autoscopic examination may be a life-saving procedure.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Hope FW. On insects and their larvae occasionally found in the human body. Trans. R. Entomol. Soc. Lond 1840;256-71.

2. Francesconi F, Lupi O. Myiasis. Clin Microbiol Rev 2012;25:79105.

3. Arora S, Sharma JK, Pippal SK, Sethi Y, Yadav A. Clinical etiology of myiasis in ENT: a reterograde period--interval study. Braz J Otorhinolaryngol 2009;75:356-61.

4. Eyigör H, Dost T, Dayanir V, Başak S, Eren H. A case of naso-ophthalmic myiasis. Kulak Burun Bogaz Ihtis Derg 2008;18:371-3.

5. Aydin E, Uysal S, Akkuzu B, Can F. Nasal myiasis by fruit fly larvae: a case report. Eur Arch Otorhinolaryngol 2006;263:1142-3.

6. Karabiber H, Oguzkurt DG, Dogan DG, Aktas M, Selimoglu MA. An unusual cause of rectal bleeding: intestinal myiasis. J Pediatr Gastroenterol Nutr 2010;51:530-1.

7. Hatten K, Gulleth Y, Meyer T, Eisenman DJ. Myiasis of the external and middle ear. Ann Otol Rhinol Laryngol 2010;119:436-8.

8. Güler S, Sağıt M, Sarı K, Somdaş MA. An Aural Myiasis on the Grounds of Chronic Otitis Media: Case Report. KBB ve BBC Dergisi 2011;19:172-5.

9. Karaman E, Samasti M, Saritzali G, Ozdemir S, Halil MC, Isildak H. Otomyiasis by Wohlfahrtia magnifica. J Craniofac Surg 2009;20:2123-4.

10. Werminghaus P, Hoffmann TK, Mehlhorn H, Bas M. Aural myiasis in a patient with Alzheimer’s disease. Eur Arch Otorhinolaryngol 2008;265:851-3.

Case Report

ANESTHESIOLOGY&REANIMATION

North Clin Istanbul 2014;1(3):178-181 doi: 10.14744/nci.2014.46320

Lidocaine intoxication in axillary block: similar pharmaceutical form, different concentration Zeynel Abidin Erbesler1, Gulsah Karaoren2, Recai Dagli1, Vedat Cakirtekin3 Department of Anesthesiology, Ahi Evran University, Training And Research Hospital, Kirsehir, Turkey;

1

Department of Anesthesiology, Umraniye Training and Research Hospital, Istanbul, Turkey;

2

Department of Anesthesiology, Prof. Dr. Celal Ertug Etimesgut Hospital, Ankara, Turkey

3

ABSTRACT Local anesthetic intoxication is a medical emergency with high mortality. These drugs have not spesific antidotes, quick differential diagnosis and supportive treatment required in the case of exposure to toxic doses. We report the complications and anesthetic management of a patient who was scheduled for right carpal tunnel syndrome surgery under regional anesthesia, but mistakenly received injection of 140 mg procaine added to 10% 10 mL lidocaine (10 mL=1000mg) instead of 2% lidocaine (10mL=200 mg) as part of an axillary plexus blockade.

Key words: Axillary blokage; intoxication; lidocaine.

T

oxic reactions are among the most prevalent causes of medical emergencies [1]. Development of regional techniques, introduction of new long-acting local anesthetics into clinical use in the practice of anesthesia within the last 20 years, raised awareness among physicians, and patients about the use of regional anesthesia have resulted in increased popularity, and applicability of regional anesthesia.

Despite technologies which widen safety margins of regional anesthesia including use of bedside ultrasound which reveals the anatomy of the site of application, and use of peripheral nerve stimulator which directly determines the nerve to be targeted, still intoxications related to local anesthetics in applications of regional anesthesia can be seen as a serious,

and important adverse effects with incidence rates ranging between 0.01, and 0.2% of the cases [2].

Local anesthetics used in the practice of regional anesthesia have usually an amide component, and they induce Na channel blockade in cell membranes, and thus prevent transmission of impulses by way of axons. Lidocaine is an amide group local anesthetic which is preferred in relatively shorter surgical interventions, infiltration anesthesia, extremity blocks, topical anesthesia, and regional intravenous anesthesia (RIVA) with its higher potency, rapid onset, and termination of its action. Its intoxications when used in local anesthesia, emerge frequently during inadvertent intravenous administration of the drug

Received: September 18, 2014 Accepted: November 14, 2014

Online: January 24, 2015 ?? ??, ????

Correspondence: Dr. Zeynel Abidin ERBESLER. Ahi Evran Universitesi Egitim Arastirma Hastanesi, Kervansaray Mahhallesi, 2019. Sokak, No:1, Kirsehir, Turkey.

Tel: +90 386 - 213 45 15 e-mail: zerbesler@gmail.com Š Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Erbesler et al., Lidocaine intoxication in axillary block

in applications of central or peripheral blockade, unnecessarily higher drug dosage, and rapid systemic absorption of the drug. Though central nervous system is firstly, and most frequently affected in local anesthesic intoxications, mortality rates increase due to cardiovascular system involvement.

Cardiovascular effects can manifest themselves as enlarged QRS complex due to prolonged Na channel blockade in diastole, prolonged PR interval, AV blocks, and related dangerous arrhytmias. However its central effects appear secondary to cortical stimulation. Early manifestations of cortical stimulation including relatively mild symptoms as metallic taste in the mouth, numbness, disorientation, tinnitus, paresthesia, ataxia, dysarthria, nystagmus, and dose related serious symptoms of cortical stimulation as convulsions, respiratory system depression, serious arrhytmias, deep cardiovascular collapse, and coma can develop [2, 3].

In our article, complications and anesthetic management of a patient who was scheduled for right carpal tunnel syndrome surgery under regional anesthesia, and mistakenly received injection of 140 mg procaine added to 10% 10 mL lidocaine (10 mL=1000mg) instead of 2% lidocaine (10mL=200 mg) as part of an axillary plexus blockade.

CASE REPORT A 57-year-old-male patient 165 cm tall, and weighing 68 kg in the ASA 1 risk group because of numbness of his left wrist. The biochemical parameters of the patient who was scheduled for operation under regional anesthesia with the diagnosis of carpal tunnel syndrome were as follows; Hb:14.0 mg/ dL, Htc:43.0%, Plt:229000/mm3, WBC:6000/ mm3, FBG:100 mg/dL, BUN:2817 mg/dL, Creatinine:0.7 mg/dL, AST:20.72 mg/dL, and ALT:12.45 mg/dL. His electrocardiogram (EKC) revealed a HR of 70 bpm with normal sinus rhythm.

Preoperatively the patient was informed about axillary nerve blockade, and his written informed consent was obtained. He didn’t receive any preoperative premedication, and in the operating room, his standard EKG, peripheral O2 saturation (SpO2), and noninvasive blood pressure (NIBP) were monitores. Using a 18 G branule a vein on the back of his left hand was punctured, and 0.09%NaCl infusion

179

at a rate of 200 ml/hr was initiated. Right arm to be operated was positioned at 90o abduction with the torso, and forearm was flexed 90o. After cleansing the surgical field with a sterile antibacterial solution, the site was covered with sterile drape, and a single injection was made with a 22 G x 50 mm needle (Stimuplex® Braun, Melsungen, Germany). Retrograde blood was not observed during negative aspiration.

Using a peripheral nerve stimulator (Stimuplex A; B.Braun Melsungen AG, B.Braun Medical AG CH-6021, Germany) at an intensity of 1.5 mA the nerve was localized. When the intensity of the electrical current was reduced to 0.5 mA, nervous stimuli were observed which made us to think that we were on the innervation site of the nerve to be blocked. Then 40 mL anesthetic solution preprepared by anesthesia technician which we thought to be our routinely used mixture i.e. [20 mL 1% lidocaine (2 ampoules of 2% lidocaine, and 10 mL NaCl 0.09%) and 20 mL 1% prilocaine (10 mL 2% prilocaine, and 10 mL0,09% NaCl)] was injected to the patient with negative suctions after each application of 5 mL. Injection site was compressed for 5 minutes. Nearly 10 minutes later the patient felt numbness on his tongue, irritability, restlessness, agitation, he uttered meaningless words, and moved his arms, and legs senselessly. Decreased peripheral oxygen saturation and presence of peripheral cyanosis led us to make an initial diagnosis of methemoglobinemia, and supportive O2 therapy was initiated via oxygen mask at a rate of 6 lt per minute.

We couldn’t measure methemoglobin levels because of lack of necessity facilities. Arterial blood gas measurements were as follows. pH: 7.43 pO2:60.1, and pCO2:44.0. Respiratory distress of the patient increased, and deepened, with a drop in his SpO2 to 76, was intubated under 1 mg/kg propofol, 1 µ/ kg fentanyl, and 0.5 mg.kg‾¹ rocuronium anesthesia to enjure the patency of his airway. For the postintubation maitenance of anesthesia 50 oxygen – nitrogen, and 1 mac sevoflurane were used. Following induction of anesthesia, hypotension (NIBP: 60/40 mmHg), and bradycardia (HR:40 bpm) developed which required administration of 0.5 mg atropin, and intermittent IV injections of ephedrine (total dose 30 mg). When his health state was stabilized, NIBP values improved, and his HR dropped to 70 bpm with SpO2: 95%, he was amenable for surgery. At the end of the operation which lasted

180

for nearly half an hour, the patient was awakened with injections of 10 µg/kg atropine, and 40 µg/kg neostigmine. Thoughy the patient still continued to articulate meaningless words, and make senseless movements, since he was more cooperative we transferred the patient into the intensive care unit.

When we discerned that in place of 2% lidocaine ampoule which we always requested as a local anesthetic from the pharmacy, 10% lidocaine ampoule was sent, and anesthetic mixture was prepared without checking whether it was 2% lidocaine, we made the diagnosis of local anesthetic intoxication related to wrong formulation of lidocaine rather than methemoglobinemia During 24-hour monitorization in the intensive care unit his hemodynamic parameters were stable, and his complaints resolved. Then the patient was traansferred to his service with relevant recommendations.

DISCUSSION Ninety-eight percent of systemic reactions that might develop against local anesthetic agents are related to higher plasma concentrations of the drugs used. Higher plasma concentrations can be observed when doses higher than the maximum daily doses are used or in cases of unwanted intravascular injections during central or peripheral nerve blocks [4]. Lidocaine is a local anesthetic with a amide component which induces Na channel blockade in nerve cell membranes. Because of its higher potency, lesser systemic toxic reactions, its safety in IV use unless toxic doses are not exceeded, lidocaine is frequently used local anesthetic in anesthesia practice.

Lidocaine at doses exceeding 4 mg/.kg, and doses above 7.5 mg/kg of its combined form with adrenaline used in local anesthesia have toxicity effects [1].

In CNS toxicity relaated to local anesthetics, firstly excitatory, then depressive symptoms become evident. Presence of hypoxia, hypercapnia, and acidosis further facilitates development of convulsion.

Besides cardiovascular collapse can be seen because of the impact of local anesthetic on vascular smooth muscle resulting in vasodilation, and bradycardia due to its direct effect on myocardium. Symptoms of cardiac toxicity are more frequently seen in patients with a history of cardiovascular disease [5].

North Clin Istanbul – NCI

In our case occurrence of mild hypoxia, and cyanosis at the onset made us to think of the development of methemoglobinemia related to prilocaine injection. Regression of cyanosis after delivery of 100% O2 made us to drift away from the diagnosis of methemoglobinemia.

Local anesthetics can be marketed in many pharmaceuıtical forms as cream, gel, lyposomal capsule, tablet, and spray. Tablet formulation of mexyletine, and tocainide which is a derivative of lidocaine have been used in antiarrhytmic,a nd neuropathic pains. Besides, 10% solution of lidocaine (Xylocain® pump spray) is used as an aerosol, and each puff contains 10 mg lidocaine. In topical anesthesia EMLA® (2.5% lidocaine, 2.5% prilocaine) cream has been applied.

Lidocaine solution is marketed in ampoules each containing 2%, or 10% concentrations. Similar appearance of ampoules can easily result in erroneous applications. Injections of higher doses of lidocaine are one of the most frequent erroneous drug applications. Packaging of bolus, and concentrated dosage forms of these types of drugs is still problematic [6]. In our case, instead of injecting 2% lidocaine formulation which is used routinely for the purpose of peripheral blockade, the ampoule with similar appearance except for an extra yellow line on the neck of the ampoule which contained 10% lidocaine was inadvertently prepared for injection, and our patient received 5-fold higher dose than our estimate.

Kudo et al. [7] presented a 76-year-old patient with known paroxysmal ventricular dysrhytmia who was injected 5 ml 10% lidocaine (599 mg) instead of 2.5 ml 2% lidocaine (50 mg) for the treatment of his dysrhytmia. They reported tonic-clonic convulsions immediately after high doses of lidocaine injection, then cardiac arrest developed. Despite initiation of resuscitation without delay the patient died.

Ludot et al. [8] planned knee surgery using posterior lumbar plexus block in a 13-year-old patient, and at 15. minute of lidocaine,and ropivacaine injection heart rate of the patient increased up to 150 bpm, and ventricular tachycardia with a wide QRS complex emerged. Preoperatively measured arterial blood pressure (88/45 mmHg) rised up to 12/92, while SpO2 dropped from 99% to 92 percent.The patient was given 150 ml IV (3mg/kg) 20% lipid emulsion (Medialipid 20%, Braun, Germany) with

Erbesler et al., Lidocaine intoxication in axillary block

the initial diagnosis of local anesthesic intoxication. At 2nd minute of the infusion, her heart rate regressed to 100 bpm, and arterial blood pressure to 100/48 mm Hg, and SpO2 increased to 97 percent.

After stabilization of her vital signs, and inability to detect any additional sign, we proceeded with the operation. The patient was discharged on postoperative 2. day without any sequalae.

Safe use of lipid emulsions in intoxications of local anesthetics was reported by Rosenblatt et al.

[9] in the year 2006. In this presentation, brachial plexus blockade was applied using bupivacaine, and mepivacaine combination. After the blockade, cardiac arrest was developed in the patient, and cardiopulmonary resuscitation was initiated. The patient didn’t respond to 20 minutes of resuscitation, then 100 ml 20% Intralipid® fat emulsion (Fresenius kabi, Uppsala, Sweeden) was administered through intravenous route, a little while after initiation of lipid therapy her hemodynamic parameters started to return to normal levels.

In the practice of anesthesia, lipid emulsions are marketed as total parenteral nutrition solutions and in formulations with propofol. However in the literature, clear-cut information about effective, and safe use of these emulsions in lipid rescue treatment is lacking [10]. In our case in consideration of potential beneficial effects of lipid solutions, we urgently requested these solutions from the pharmacy of our hospital, but we were unable to use them for the patient because of difficulties in its procurement.

Anesthesic pharmacotherapy requires constant care, and it is not exempt from erroneous applications. Erroneous applications, and unnecessarily higher doses can frequently lead to serious adverse effects, besides confusing infusion, and single dose applications, and dosage calculation errors can be also frequently seen. Blendon et al. [11] investigated faulty drug applications, reported physicians or family members (35%), civilians (42%) for these erroneous usage of drugs.

Even though literature information does not absolutely support, we think that in pharmacy departments of hospitals where day-care surgeries, and regional techniques are frequently applied, lipid solutions should be available for immediate use so as to protect the patients from adverse outcomes of drug use.

181

CONCLUSION Finally, we think that preventive measurements including standardization, separation of different forms of the drugs (intrathecal, topical, and intravenous), drugs used in different dosages should be marketed in different coloured, and sized ampoules, controlled application of the drugs at every step of their usage, regular, meticulous, and updated pharmacological training of health personnel should be developed.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Morgan GE. Clinical anesthesiology. Third edition. McGrawHill Companies 2002;297-8.

2. Ökten F. Hasdoğan M. Tarhan A. What is the importance of bupivacaine cardiotoxicity. Anestezi Dergisi 2010;18:189-93.

3. Bigger JT, Hoffman DF. Anti arrhythmic drugs.in: Gillman AG, Rall TW, Nies AS. Goodmanand Gillman: The pharmacologial basis of therapeutics 8th ed. Newyork: Pergamonpres; 1990. p.

857-61.

4. Miller RD. Local anaesthetics. Anesthesia Fourth edition.

Chuchill Livingstone 1994;510-6.

5. Alfano SN, Leicht MJ, Skiendzielewski JJ. Lidocaine toxicity following subcutaneous administration. Ann Emerg Med 1984;13:465-7.

6. Tokgöz O, Beyaz SG, Arıkanoğlu Z. Toxic reaction related to high dose lidocaine secondary to intravenous regional anesthesia.

J ClinExpInvest 2010;1:119-21.

7. Kudo K, Nishida N, Kiyoshima A, Ikeda N. A fatal case of poisoning by lidocaine overdosage--analysis of lidocaine in formalin-fixed tissues: a case report. Med Sci Law 2004;44:266-71.

8. Ludot H, Tharin JY, Belouadah M, Mazoit JX, Malinovsky JM. Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg 2008;106:1572-4.

9. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006;105:217-8.

10. Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity: proof of clinical efficacy. Anesthesiology 2006;105:7-8.

11. Blendon RJ, DesRoches CM, Brodie M, Benson JM, Rosen AB, Schneider E, et al. Views of practicing physicians and the public on medical errors. N Engl J Med 2002;347:1933-40.

Case Report

PEDIATRICS

North Clin Istanbul 2014;1(3):182-186 doi: 10.14744/nci.2014.04695

General approach to velocardiofacial anomalies: a pediatric case presenting with Fallot tetralogy Aysu Turkmen Karaagac1, Ayse Inci Yildirim2 Department of Pediatrics, Kartal Kosuyolu Training and Research Hospital, Istanbul, Turkey;

1

Department of Pediatric Cardiology, Kartal Kosuyolu Training and Research Hospital, Istanbul, Turkey

2

ABSTRACT Velocardiofacial syndrome (VCFS), also known as “Shprintzen syndrome” or “22q11.2 deletion syndrome” is an autosomal dominant genetic disorder with a wide range of phenotypical findings. It is majorly characterized by cleft palate, dysmorphic face, conotruncal cardiac anomalies, growth retardation, neurologic disorders and learning disabilities. Our case was the first child of her family and she had a cleft palate, dysmorphic face, tetralogy of Fallot (TOF), growth retardation and a mild neuromotor developmental delay. It is important to recognize this syndrome and inform the family about the probable future health problems of their babies as early as possible. Genetic counselling is crucial for the subsequent pregnancies. Therefore, we wanted to review the literature about the differential diagnosis and genetics of velocardiofacial anomalies.

Key words: Conotruncal cardiac anomaly; dysmorphic face; genetic counselling; 22q11 deletion.

V

elocardiofacial anomalies are related to the microdeletions on the long arm of chromosome 22 and characterized by several different combinations of clinical features as cleft palate, dysmorphic facial appearance, conotruncal cardiac anomalies, ophtalmic disorders, ear problems, immunologic deficiencies, hematologic and/or renal abnormalities, musculoskeletal problems, neurologic and psychologic disorders [1, 2]. The frequency of Velocardiofacial syndrome (VCFS) among all surviving newborns in the United States is about 1:2000 [3].

CASE REPORT Z.T. was a 11-month-old female baby. She was born at the 37th week of gestation weighing 2650 gr, and delivered by a cesarean section. She was followed in the neonatal intensive care unit for 2 weeks due to the respiratory insufficiency, cleft palate and feeding difficulty. At the first hospital visit after her discharge, pulmonary valvular stenosis and tetralogy of Fallot (TOF) were diagnosed on her echocardiograms. Balloon valvuloplasty was performed

Received: October 10, 2014 Accepted: December 03, 2014 Online: January 24, 2015 ??, ????

Correspondence: Dr. Aysu TURKMEN KARAAGAC. Denizer Caddesi, Cevizli Kavsagi, No: 2, Kartal, Istanbul, Turkey.

Tel: +90 216 - 500 15 00 e-mail: aysukaraagac@gmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Turkmen Karaagac et al., General approach to velocardiofacial anomalies

Figure 1.

Facial

dysmorphism

in

velocardiofacial

syndrome.

when she was 4 month- old. She was referred to our hospital for the surgical correction of her cardiac anomalies at the 11 months. On her physical examination in our clinic, her body weight was 6300 gr. (<3 percentile), height 62 cm. (<3 percentile) and head circumference, 41 cm. (<3 percentile). She had a wide forehead, low nasal bridge, cleft palate, micro/retrognathia, hypoplastic maxilla and hypertelorism (Figure 1). Her heart rate was 130 bpm, respiratory rate was 32 breaths per minute with an oxygen saturation of 82% while breathing room air and her systemic blood pressure was 80/50 mmHg. She had bilateral sibilant rales and 2/6 systolic murmur at the pulmonic area on auscultation. Her liver was 3 cm. palpable below the subcostal margin and the spleen was nonpalpable. She had 3 hemangiomas with the diameters of 3 to 5 cm on her back.

Her musculoskeletal and the genital examinations were within normal limits.

The mother of Z.T. was 26 and the father was 28 years old. There was no consanguinity between them and they had no dysmorphic facial appearance or any systemic illnesses. The mother had not received regular medical follow- ups during her pregnancy. She had never used tobacco or alcohol.

There was no history of drug use or exposure to Xray after she became pregnant. She had no history

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of infection, abortus or stillbirth, either. Their first degree relatives had not any congenital anomalies.

Biochemical and microbiological examinations of Z.T. showed mild infection with a white blood cell count of 13500/mm3, C reactive protein level of 2 mg/dl and 64% neutrophil dominancy (63%) on the peripheral blood smear, iron deficiency anemia and hypocalcemia with a serum calcium level of 7.3 mg/dl. Her 25 OH-D level was low (10 ng/ml), parathyroid and thyroid hormone levels were normal (15.2 pg/ml and 2.1 IU/ml, respectively). After treatment with calcium and vitamin D, her serum calcium levels have sustained within normal ranges.

Serologic test results for toxoplasma, rubella and cytomegalovirus (TORCH) were negative. Her cardiothoracic ratio increased and the cardiac apex was elevated on the chest X-ray. On her echocardiogram, there was perimembranous ventricular septal defect, pulmonary stenosis, straddling tricuspid valve with a moderate degree of incompetence, patent ductus arteriosus, 50% dextroposition of aorta, tetralogy of Fallot and coronary arterial fistula on the ventricular septum. Abdominal ultrasonograms were normal except for a mild hepatomegaly.

As there were two afebrile seizure attacks in her neonatal history, electroencephalography (EEG) was performed. EEG reports indicated that there were sharp wave activities on the frontocentral, centrooccipital and temporooccipital regions of the left serebral hemisphere in relation with the centrooccipital region of the right cerebral hemisphere.

Ophthalmic and audiological examinations of Z.T. were unremarkable. Cranial and spinal magnetic resonance examinations (MRI) showed mild dilatation of the lateral ventricules and a lipoma on the philum terminale.

The karyotype analysis of our case was reported as 46, XX. On her fluorescence in situ hybridization (FISH) analysis performed using DG (22q11) probe, deletion of band 11 on the long arm of chromosome 22 was detected.

After a successful total correction of TOF, tricuspid valvuloplasty and PDA ligation operations, she was discharged from our hospital on the twentieth postoperative day. We informed the family about the necessity of multidisciplinary approach for the children with VCFS to deal with their gastrointestinal, neurological, hematological, endocrinological,

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ophthalmic and the psychological problems in the future. We directed them for genetic counseling for the subsequent pregnancies. Z.T. underwent a plastic surgery for the correction of her cleft palate. She is 2 years old now and healthy.

The written consent of the family was taken for the publication of this case.

DISCUSSION Shprintzen and colleagues first described the VCFS in 1981 and Scambler defined the microdeletions on the long arm of 22nd chromosome as its main pathology in 1992. VCFS may present with several different combinations of phenotypical and clinical features [1, 4].

VCFS is also known as “DiGeorge syndrome”, however the severity of immune deficiency differs between rhese two entities. In “complete DiGeorge syndrome”, there are recurrent, severe upper/lower tract infections due to the abscence of thymus and hypocalcemic convulsions may take place as a result of parathyroid aplasia [2, 3]. Our case had a thymus gland and no history of recurrent severe respiratory tract infections. She had a mild hypocalcemia, but her parathyroid hormone level was normal. Several studies have shown that 36% of the children with VCFS have severe growth retardation (weight and height below 3rd percentile) [2]. Furthermore, congestive heart failure secondary to the congenital cardiac anomalies may lead to the development of edema on the small bowel surface and malabsorption, which results in nutrient deficiency in these children [5]. Our case also had a severe growth retardation, vitamin D deficiency, iron deficiency and hypocalcemia as a result of feeding difficulty due to the cleft palate, congestive heart failure and malabsorption. After administration of anticongestive therapy, antibiotherapy, fluid and nutritional support, our patient started to gain weight of 20-30 gr/ day and her vitamin D and calcium levels returned to normal.

Wang and colleagues performed phenotypical analysis of the children with VCFS by using three dimensional computed tomography and reported that 95% of these children had facial, gnathial and/ or palatal abnormalities. Palatal anomalies seen in 70% of these children were mostly the cleft palate

North Clin Istanbul – NCI

of complete type and rarely of submucosal type together with a bifid uvula and velopharyngeal insufficiency [6]. Our case had a submucosal cleft palate, bifid uvula, micro/retrognathia, wide prominent forehead, low nasal bridge and hypertelorism. We directed the family to a plastic surgery clinic and a palatal obturator was provided until accomplishment of her cardiac surgery. As the children with velopharyngeal insufficiency have short soft palate and hypotonic velopharyngeal muscles, they have difficulty in speaking and swallowing, which create a tendency to aspiration and speech disorders [7].

Our case also had a short soft palate, difficulty in speaking and swallowing and her endoscopic examination in the ear-nose and throat clinic (ENT) showed velopharyngeal insufficiency. Ha and colleagues reported that the repair of the cleft palate after 18 months of age would lead to a higher risk of developing articulatory speech problems resulting in the need for more speech therapy [8]. Therefore, the children with VCFS should be consultated with plastic surgeons, orthodontists, ENT specialists and speech therapists for the monitorization and resolution of their facial and velopharyngeal problems as early as possible [6, 7, 8]. The cleft palate of our case was corrected in the fifteenth postnatal month and she has being followed by ENT specialists and speech therapists in a university hospital since then.

Conotruncal cardiovascular anomalies diagnosed in 75% of the VCFS cases, especially in those with 22q11 deletion, are the main causes of morbidity and mortality. The most common cardiac anomalies are aortic arch anomalies (28%), pulmonary atresia and ventricular septal defect (23%), ventricular septal defect (21%), tetralogy of Fallot (15%) and truncus arteriosus (13%) [1, 9]. Rouch and colleagues screened 217 cases with aortic arch anomalies and found 22q11.2 deletions in patients with subclavian artery anomalies (n=38/47; 81%), right (n=24/52; 46%), and left aortic (n=35/118; 30%) arches [10].

Fallot tetralogy is not a common cardiac pathology in VCFS with 22q11 deletion. Maeda and colleagues examined 212 patients with TOF and found 22q11 deletion only in 28 (13%) of VCFS patients [11].

Our case had tetralogy of Fallot, perimembra-

Turkmen Karaagac et al., General approach to velocardiofacial anomalies

nous ventricular septal defect, pulmonary stenosis, straddling tricuspid valve with a moderate degree of incompetence, patent ductus arteriosus, 50% dextroposition of aorta, and coronary arterial fistula on the ventricular septum. These anomalies were corrected by total correction of TOF, tricuspid valvuloplasty and PDA ligation operations.

Amelswoort and colleagues performed quantitative MRI studies and reported that the VCFS cases had differences in their brain anatomies affecting the midline structures (septum pallicidum, corpus callosum), the cerebellum, white and grey matters of the temporal and left frontal regions. Fusion in the cervical vertebra, and narrowing of the spinal canal may also be detected. These abnormalities may partially explain the cognitive profile and the neuropsychiatric problems encountered in VCFS cases. Therefore, it is necessary to perform cranial and spinal MRIs of the people with VCFS [12, 13].

As our case had two afebrile seizure attacks in the neonatal period with a mild neurodevelopmental delay, we performed cranial and spinal MRI and the EEG studies. We informed the family about the possible future problems of their child as neuromotor retardation, learning disability, speech disorder and psychiatric problems (psychosis, schisophrenia). They have been attending to a neurologist, a psychiatrist, a psychologist and a speech therapist since then.

On their urogenital system examinations, 35% of the children with VCFS showed urinary system abnormalities such as renal agenesis, multicystic kidneys, urolithiasis, horseshoe kidneys, hydronephrosis, vesicoureteral reflux or double collecting system, Besides they had 20-30% inguinal hernia (20-30%), hypospadias (8%), and undescended testicle(s)(6%) [2, 3]. Therefore, the urogenital system examinations should be carefully made and the urinary ultrasonography should be performed in the children with VCFS. The urogenital system examination of our case was normal as well as her urinary system ultrasonography.

The microdeletions on the long arm of chromosome 22, leading to VCFS, are usually sporadic and affect a region containing 30 genes in 90% of the cases. However, in 7-8% of VCFS cases microdeletions may take place in smaller regions containing 20-25 genes, which explain the high phenotypical

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variations of VCFS cases [14, 15]. It is important to perform genetic analysis of both parents of a child with VCFS even if they don’t have facial dysmorphism or history of a cardiovascular disease. As the VCFS is an autosomal dominant disorder, a deletion in the chromosome of any parent will increase the risk of VCFS with more dramatical clinical presentations in the subsequent pregnancies [16]. The FISH analysis of our case revealed 22q11 deletion, so we directed the family to a university hospital for genetic counselling. The FISH analysis results of the parents were normal and they were informed about the importance of amniocentesis for the subsequent pregnancies.

As a result, VCFS requires a multidisciplinary approach to deal with multiple systemic anomalies.

Therefore, it is vital to recognize the syndrome and inform the family as early as possible to get good results from the necessary interventions.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Digilio M, Marino B, Capolino R, Dallapiccola B. Clinical manifestations of Deletion 22q11.2 syndrome (DiGeorge/Velo-Cardio-Facial syndrome). Images Paediatr Cardiol 2005;7:23-34.

2. Shprintzen RJ. Velocardiofacial Syndrome. In: Cassidy SB, Allanson JE (eds). Manag of Genetic Syndr. New Jersey: WilleyLiss 2005:615-31.

3. Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study.

Dev Disabil Res Rev 2008;14:3-10.

4. Ütine EG, Şimşek Kiper PÖ, Boduroğlu K. Microdeletion Syndromes (Review). Turkish Journal of Pediatrics 2012;55:42-51.

5. Leitch CA. Growth, nutrition and energy expenditure in pediatric heart failure. Prog Pediatr Cardiol 2000;11:195-202.

6. Wang K, Yang Y, Shen F, Tao J, Xu H, Portnof JE, et al. Utilization of three-dimensional computed tomography for craniofacial phenotypic analysis in children with velocardiofacial syndrome. J Craniofac Surg 2009;20:2013-9.

7. Widdershoven JC, Stubenitsky BM, Breugem CC, MinkvanderMolen AB. Outcome of velopharyngoplasty in patients with velocardiofacial syndrome. Arch Otolaryngol Head Neck Surg 2008;134:1159-64.

8. Ha KM, Cleland H, Greensmith A, Chong D, Macgill K, Verhoeven A, et al. Submucous cleft palate: an often-missed diagnosis.

J Craniofac Surg 2013;24:878-85.

186 9. Carotti A, Digilio MC, Piacentini G, Saffirio C, Di Donato RM, Marino B. Cardiac defects and results of cardiac surgery in 22q11.2 deletion syndrome. Dev Disabil Res Rev 2008;14:35-42.

10. Rauch R, Rauch A, Koch A, Zink S, Kaulitz R, Girisch M, et al. Laterality of the aortic arch and anomalies of the subclavian artery-reliable indicators for 22q11.2 deletion syndromes? Eur J Pediatr 2004;163:642-5.

11. Maeda J, Yamagishi H, Matsuoka R, Ishihara J, Tokumura M, Fukushima H, et al. Frequent association of 22q11.2 deletion with tetralogy of Fallot. Am J Med Genet 2000;92:269-72.

12. van Amelsvoort T, Daly E, Robertson D, Suckling J, Ng V, Critchley H, et al. Structural brain abnormalities associated with deletion at chromosome 22q11: quantitative neuroimaging study of adults with velo-cardio-facial syndrome. Br J Psychiatry 2001;178:412-9.

North Clin Istanbul â&#x20AC;&#x201C; NCI 13. Ricchetti ET, Hosalkar HS, Gholve PA, Cameron DB, Drummond DS. Advanced imaging of the cervical spine and spinal cord in 22q11.2 deletion syndrome: age-matched, double-cohort, controlled study. J Child Orthop 2008;2:333-41.

14. Firth HV, Hurst JA. Deletions and duplications. Chapter 5: Chromosomes, In: Firth HV, Hurst JA (eds).Oxford Desk Reference Clinical Genetics. New York: Oxford Un. Pres 2005:520-22.

15. Nazlican H, Zeschnigk M, Claussen U, Michel S, Boehringer S, Gillessen-Kaesbach G, et al. Somatic mosaicism in patients with Angelman syndrome and an imprinting defect. Hum Mol Genet 2004;13:2547-55.

16. Kitsiou-Tzeli S, Kolialexi A, Fryssira H, Galla-Voumvouraki A, Salavoura K, Kanariou M, et al. Detection of 22q11.2 deletion among 139 patients with Di George/Velocardiofacial syndrome features. In Vivo 2004;18:603-8.

Case Report

NEUROLOGY

North Clin Istanbul 2014;1(3):187-190 doi: 10.14744/nci.2014.28247

Myoclonus-dystonia syndrome: case report Emel Oguz Akarsu1, Reyhan Surmeli2, Destina Yalcin2 Department of Neurology, Ersin Aslan State Hospital, Gaziantep, Turkey;

1

Department of Neurology, Umraniye Training and Research Hospital, Istanbul, Turkey

2

ABSTRACT Myoclonus-dystonia syndrome (MDS) is a rare disease manifesting myoclonus as the only neurological symptom which may be accompanied by dystonia. It usually starts in the first or second decade of life. It has a benign course with spontaneous remissions but can cause functional disability in some patients. In this paper, we report a patient diagnosed as probable MDS on the basis of clinical and electrophysiological features who showed marked improvement under levetiracetam treatment.

Key words: Myoclonus; dystonia; treatment.

M

yoclonus-dystonia syndrome (MDS) is a rare, sometimes sporadically encountered autosomal dominant hereditary disease occasionally manifesting symptoms of isolated myoclonus potentially accompanied with dystonia, and frequently seen in the first two decades of life [1]. Myoclonic contractions mostly, and predominantly involve upper extremities, and especially their proximal parts.

Alcohol intake typically suppresses myoclonic jerks [1, 2]. Dystonic episodes (storms) of mild-moderate severity can accompany myoclonic jerks [1].

For 覺ts symptomatic treatment, benzodiazepines, anticholinergics, levodopa, dopamine agonists, amantadine, serotonergic agents, beta blockers, neuroleptics, and antiepileptic agents have been tried. In some patients, with myoclonic seizures favourable responses to levetiracetam, piracetam, and zonisamide have been obtained [3, 4]. In refractory

cases, deep brain stimulation constitutes an alternative treatment option [5].

In our article, we have presented a case with a probable diagnosis of MDS based on clinical, and electrophysiologic examinations who also responded to levetiracetam therapy.

CASE REPORT A-14-year-old female patient with a right hand dominancy consulted to us with complaints of involuntary jerks of her left arm especially when she were moving her arm or writing something. Her complaints started when she was 7 years of age, and her complaints continued without demonstrating any progression. Her complaints worsened especially when she tried to write with her left hand, and consequently she consulted to a neurologist in her

Received: July 09, 2014 Accepted: October 16, 2014 Online: January 24, 2015 ?? ??, ????

Correspondence: Emel OGUZ AKARSU. Ersin Arslan Devlet Hastanesi, Gaziantep, Turkey.

Tel: +90 342 - 221 07 00 e-mail: emeloguz@yahoo.com 穢 Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

North Clin Istanbul – NCI

188

home city who referred the patient to us without initiating any therapy. Her medical history was unremarkable. Her family history revealed only consanguineous marriage with a third-degree relative.

Neurological examination detected presence of only involuntary movements without any other pathologic finding. Involuntary movements were characterized by brief, focal dysrhythmic jerks worsened by certain postures, and movements involving all along the affected left arm, but being more predominant at the distal part of this extremity. Biochemical analysis couldn’t detect any significant characteristic. Her electroencephalographic (EEG) examination did not demonstrate cortical discharges associated with myoclonic jerks. On her electromyograms (EMGs) myoclonic activities correlated with clinically observed involuntary movements with varying monophasic or polyphasic amplitudes recurring at irregular intervals were noted (Figure 1). During examination of her somatosensory evoked potentials (SEPs) tibial SEP was evaluated as within normal limits. On examination of median SEP, SEPs with relatively longer latency, and higher amplitude were detected (Figure 2). C reflex was absent. With these findings, we thought that our patient were experiencing myoclonic jerks of subcortical origin. Then she was evaluated based on the criteria suggested by Grunewald et al., and diagnosis of probable MDS was made. The patient was started on escalating levetiracetam therapy (1000 mg/day). At the control visit in our outpatient clinic, a marked decrease in her myoclonic episodes were observed.

DISCUSSION Myoclonus can be physiologic, central or peripheral or it can emerge during the course of many different disease states. Clinical findings, imaging modalities, and electrophysiologic examinations aid in the determination of etiology of myoclonus.

MDS is a rare, sometimes sporadically encountered, generally autosomal dominant hereditary disease manifesting symptoms of isolated myoclonus potentially accompanied with only dystonia, and frequently seen in the first two decades of life which also dramatically alleviates with alcohol intake [1, 2].

In the year 2008 yılında Grunewald et al. classified MDS as definite MDS (early-onset myoclo-

Figure 1.

EMG during involuntary movement.

A

B

Figure 2. (A) Right median SEP response (B) Left median SEP response.

nus, and dystonia episodes or isolated myoclonus occurring predominantly in the upper extremity with a positive family history for myoclonus and /or dystonia), probable MDS (early-onset myoclonus, and dystonia or isolated myoclonus occurring predominantly in the upper extremity), possible MDS (cervical dystonia or isolated jolting movements involving various parts of the body or dystonia and/or myoclonus affecting lower half of the body or alcohol unresponsive–MDS). MDS manifesting before 26 years of age is considered as early-onset MDS [6]. In 2009 Kinugava et al. proposed five diagnostic criteria for definite MDS based on available clinical data, and comprehensive literature review: 1) Age of onset ≤20 years; 2) Myoclonus with or without dystonia, 3) Positive family history, 4) Absence of any other neurological comorbidity 5)

Oguz Akarsu et al., Myoclonus-dystonia syndrome

Normal cerebral magnetic resonance imaging finding [1]. According to Kinugava classification our patient did not meet definite MDS criteria due to lack of any positive family history, and she was included in probable MDS category based on Grunewald classification.

In some cases diagnosed as autosomal dominant hereditary MDS, mutations in the epsilon-sarcoglycan gene (SGCE) was identified at locus 7q21 on the long arm of the 7. chromosome. Grunewald et al. identified SCGE mutations in patients with diagnosis of definite (6/10; 60%), and probable (3/15; 2%) MDS [6]. Carrecchio et al. (2013) also detected. SCGE mutations in patients diagnosed as definite (7/23; 30.4%), and probable MDS (8/52; 15.4%). In the study performed by Carrecchio et al. more than half of the patients with mutations had not positive family history for MDS. Lack of positive family history was correlated with reduced penetrance of SCGE gene, and existence of de novo mutations [7]. Similarly, Ritz et al. couldn’t demonstrate presence of mutations in half of their patients diagnosed as definite MDS [8]. Because of our restricted facilities, we couldn’t perform genetic tests on our patient whose family history was unremarkable for MDS Studies performed hitherto have demonstrated that criteria defined for MDS are not 100% sensitive, and specific for SCGE mutations.

On the other hand, in some patients with SCGE mutation atypical phenotype (adult-onset, lower extremity involvement, predominant dystonia) has been observed [9].

In MDS, myoclonic contractions predominantly affect upper extremities. More rarely, lower extremity, face, and vocal chord can be involved. DMS tends to affect proximal parts of the extremities, however, as is seen in our patient, cases of myoclonuc jerks predominantly affecting distal parts of the extremities have been also reported [1, 2]. Isolated cases of myoclonus can be seen or mild or moderate degrees of dystonia can accompany myoclonic episodes.

Dystonia is more frequently seen as writer’s cramp, and cervical dystonia [10]. In our patient, myoclonus manifested itself as irregular, brief, focal jerks which increase in frequency with change of posture, and movement, and observed all along the left arm, but being more predominant at the distal part of the extremity. Repetitive neurological examinations

189

performed on our hospitalized patient during her hospital stay, and follow-up period did not reveal any evidence of dystonia.

Records of myoclonic episodes, and neurophysiologic examinations including EEG, and SEP aid in the diagnosis of MDS. On EMG, myoclonic discharges each lasting for 25-250 ms are recorded during resting, and tonic contractions.. Myoclonic contractions have a dysrhythmic pattern with a frequency not exceeding 10 Hz [1, 2]. On EEG examination of cortical myoclonus, frequently negative waves are observed before onset of myoclonic jerks. In subcortical myoclonus, any EEG activity is not seen. During recording of SEPs, giant somatosensory evoked potentials are not accompanied by C-reflex. On our patient’s EMG, we observed occasional mono-, or polyphasic myoclonic activities of different amplitudes recurring at irregular intervals which also correlated with clinically observed involuntary movements. During EEG examination cortical discharges associated with myoclonic activities were not observed. On SEP examination, giant somatosensory evoked potentials were not observed and also C-reflex was not recognized. In the light of all these data myoclonic contractions of our patient were interpreted as nonepileptic subcortical myoclonus. Within this context, when patient’s age at the onset of the disease, normal cranial magnetic resonance imaging (MRI) findings, and persistence of isolated myoclonus as the only neurological pathology affecting solely her upper extremity during 7 years of the disease process were taken into consideration, juvenile Huntington disease (Westphal variant), early-onset Parkinson’s disease, Wilson’s Disease, and pantothenate -kinsase associated neurodegeneration which are contemplated in the differential diagnosis of the disease were ruled out.

Pathophysiology of the disease is not completely understood. However in some studies, primary dysfunction of basal ganglions have been implicated in its pathophysiology. Nonobservance of C-reflex, premyoclonic critical discharges, and giant somatosensory evoked potentials on EEG, indicates subcortical origin of myoclonic jerks [3, 11]. Dramatic response obtained with deep brain stimulation (DBS) applied on globus pallidus internus (GPI) in patients with MDS suggests involvement of GPI among subcortical structures [5].

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Nowadays, a definitive treatment for MDS does not exist. Wide spectrum of symptomatic pharmacological treatment modalities have been tried including benzodiazepines, anticholinergics, L-dopa, dopamine agonists, amantadine, neuroleptics, serotonergic agents, and beta-blockers [3, 4]. Apart from oral medications, botulinum toxin is being used for the treatment of dystonic posture [12, 13].

In refractory cases leading to serious disabilities, DBS which targets GPI is a treatment alternative [5]. Effectiveness of antiepileptic drugs as levetiracetam, piracetam, and zonisamide in symptomatic treatment of MDS has been demonstrated [1, 2, 14]. In our case levetiracetam at daily oral doses of 1000 mg provided marked symptomatic relief.

MDS is a rarely seen disease with a potential of causing serious disabilities. Antiepileptic levetiracetam can achieve symptomatic improvement, and raise quality of life of some patients. In the 21th century where genetic evaluation methods have been revolutionized, we foresee gene therapy as an effective treatment alternative for MDS. Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Kinugawa K, Vidailhet M, Clot F, Apartis E, Grabli D, Roze E. Myoclonus-dystonia: an update. Mov Disord 2009;24:479-89.

2. Roze E, Apartis E, Clot F, Dorison N, Thobois S, GuyantMarechal L, et al. Myoclonus-dystonia: clinical and electrophysiologic pattern related to SGCE mutations. Neurology 2008;70:1010-6.

North Clin Istanbul – NCI 3. Obeso JA, Rothwell JC, Lang AE, Marsden CD. Myoclonic dystonia. Neurology 1983;33:825-30.

4. Quinn NP. Essential myoclonus and myoclonic dystonia. Mov Disord 1996;11:119-24.

5. Kuncel AM, Turner DA, Ozelius LJ, Greene PE, Grill WM, Stacy MA. Myoclonus and tremor response to thalamic deep brain stimulation parameters in a patient with inherited myoclonusdystonia syndrome. Clin Neurol Neurosurg 2009;111:303-6.

6. Grünewald A, Djarmati A, Lohmann-Hedrich K, Farrell K, Zeller JA, Allert N, et al. Myoclonus-dystonia: significance of large SGCE deletions. Hum Mutat 2008;29:331-2.

7. Carecchio M, Magliozzi M, Copetti M, Ferraris A, Bernardini L, Bonetti M, et al. Defining the epsilon-sarcoglycan (SGCE) gene phenotypic signature in myoclonus-dystonia: a reappraisal of genetic testing criteria. Mov Disord 2013;28:787-94.

8. Ritz K, Gerrits MC, Foncke EM, van Ruissen F, van der Linden C, Vergouwen MD, et al. Myoclonus-dystonia: clinical and genetic evaluation of a large cohort. J Neurol Neurosurg Psychiatry 2009;80:653-8.

9. Hartmann CJ, Leube B, Wojtecki L, Betz B, Groiss SJ, Bauer P, et al. A novel mutation of the SGCE-gene in a German family with myoclonus-dystonia syndrome. J Neurol 2011;258:1186-8.

10. Koukouni V, Valente EM, Cordivari C, Bhatia KP, Quinn NP. Unusual familial presentation of epsilon-sarcoglycan gene mutation with falls and writer’s cramp. Mov Disord 2008;23(:1913-5.

11. Marelli C, Canafoglia L, Zibordi F, Ciano C, Visani E, Zorzi G, et al. A neurophysiological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome. Mov Disord 2008;23:2041-8.

12. Costa J, Borges A, Espírito-Santo C, Ferreira J, Coelho M, Moore P, et al. Botulinum toxin type A versus botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev 2005;1:CD004314.

13. Costa J, Espírito-Santo C, Borges A, Ferreira JJ, Coelho M, Moore P, et al. Botulinum toxin type A therapy for cervical dystonia. Cochrane Database Syst Rev 2005;1:CD003633.

14. Matur Z, Bebek N, Gürses C, Baykan B, Gökyiğit A. Miyoklonus-distoni sendromu: Olgu sunumu Epilepsi 2007;13:94-6.

Case Report

HEMATOLOGY

North Clin Istanbul 2014;1(3):191-193 doi: 10.14744/nci.2014.36036

Dramatic response in the dependency to transfusion after low doses of lenalidomide treatment in a 5q-syndrome patient: a case report Mehmet Hilmi Dogu, Ismail Sari, Sibel Hacioglu, Ali Keskin Department of Hematology, Pamukkale University Faculty of Medicine, Denizli, Turkey

ABSTRACT 5q-syndrome is a special subgroup of myelodysplastic syndrome in terms of follow-up and treatment. Lenalidomide is an immunomodulatory drug that is frequently used in the treatment of multiple myeloma. Some clinical studies have shown that lenalidomide treatment is effective in 5q syndrome and significantly decreases the transfusion dependency in these patients. In this paper, we would like to share a dramatic response of lowered transfusion dependency after treatment with low-dose lenalidomide in a patient who received myelodysplastic syndrome diagnosis and isolated 5q anomaly in our clinic.

Key words: del(5q); Lenalidomide; myelodysplastic syndrome.

M

yelodysplastic syndrome (MDS) is a progressive heterogeneous bone marrow deficiency that is characterized by variable degrees of leukopenia and anemia which can transform into acute leukemia. Besides, dysplastic changes and ineffective erythropoiesis during the maturation phase of bone marrow progenitor cells may be observed [1].

Cytogenetic anomalies are used as a criteria to determine prognosis of myelodysplastic syndrome [2, 3]. “5q syndrome” is a subgroup of cytogenetically isolated 5q anomalies that are not accompanied with a blast increase in the bone marrow, while it

manifests typical dismegakaryopoietic symptoms, thrombocytosis and severe anemia [4, 5]. In clinical studies it has been shown that treatment with lenalidomide which is an immunomodulatory drug and frequently used in multiple myeloma, is effective in 5q-syndrome significantly decreasing transfusion dependency in these patients [6].

In this paper, we would like to share dramatic response of lowered transfusion dependency after treatment with low-dose lenalidomide in a patient who was diagnosed in our clinic as myelodysplastic syndrome with isolated 5q anomaly.

Received: October 29, 2014 Accepted: November 28, 2014

Online: January 24, 2015 ?? ??, ????

Correspondence: Dr. Mehmet Hilmi DOGU. Pamukkale University, Faculty of Medicine, Fahri Goksin Oncology Center 20070 Denizli, Turkey.

Tel: +90 444 0 728 e-mail: mhdogu@yahoo.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

North Clin Istanbul â&#x20AC;&#x201C; NCI

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CASE REPORT A 78-year-old woman presented with weakness, fatigue and hemoglobin of 8.3 g/dL, to another clinic in September, 2009, and she was given erythrocyte suspension replacement. She had regression in her existing complaints with blood replacement therapy, but after one month, same complaints reappeared with a low hemoglobin value and she was referred for further investigation to the outpatient clinic of hematology of our university faculty of medicine. Her hematologic parameters ar that time were as follows: white blood cell count of 6390/ mm3, neutrophils 3785/mm3, hemoglobin 8.1 g/ dL, mean corpuscular volume (MCV) 95 fL, and platelets 211.000/mm3. With the provisional diagnosis of myelodysplastic syndrome due to an isolated anemia unrelated to nutritional status, bone marrow aspiration biopsy was performed. Her bone marrow aspiration showed normal cellularity; and biopsy revealed increase in the number of megakaryocytes, signs of dismegakaryopoiesis, minimal dysplasia in erythroid series, and normal morphology in myeloid series. Upon conventional cytogenetical studies she was diagnosed with 5q-syndrome.

She had given erythrocyte suspension and scheduled for follow-up. She had been lost-to-follow up for approximately a year and during that time she had received a total of 4 units of erythrocyte suspension, and erythropoietin treatment was started.

However, erythropoietin treatment discontinued because she did not respond to the maximum dose of 10.000 IU three times a week. She did not attend 16 14 12 10 8 6

Hgb(gr/dL)

4 2 Ap ril

Ju ly Au gu Se st pt em be r O ct ob No er ve m bb er De ce m be r Ja nu ar y Fe br ua ry M ar ch

0

Figure 1. Hemoglobin monitoring after lenalidomide use.

to her follow-up visits regularly and in the mean time she had transfusions monthly at another clinic.

Since her transfusion dependency increased, she was considered for lenalidomide treatment in April, 2013. Lenalidomide at daily doses of 10 mg was started in May, 2013. After 10 days of treatment, her liver enzymes increased more than 3 times of normal values and she had thrombocytopenia (platelet count: 38.000/mm3) Then her treatment was postponed for two weeks She restarted lenalidomide treatment at daily doses of 5 mg after liver enzymes and platelet counts returned to normal.

During further follow-up, increase in liver enzymes and severe thrombocytopenia were not detected; her hemoglobin value increased and transfusion dependency was not observed (Figure 1).

DISCUSSION In myelodysplastic syndrome, interstitial deletion in the long arm of chromosome 5 is a common cytogenetical abnormality seen in 16-28% of the patients.

Isolated 5-q syndrome is a subgroup with different clinical and pathological characteristics. It is characterized by hypoproliferative anemia and normal megakaryocytes with hypolobated nuclei or increased dysplastic megakaryocytes in bone marrow [7, 8]. Anemia is observed with normal or increased number of thrombocytes in peripheral blood. Most of the patients are transfusion-dependent because endogen erythropoietin production is usually increased [7]. One of the major problems during the progression of the disease in transfusion-dependent MDS patients is the iron overload secondary to transfusion and the dependency for chelation therapy to treat iron overload. The immunomodulatory drug lenalidomide that has additional benefits in the regulation of erythropoiesis, inhibition of angiogenesis, and reorganization of erythroid production, targets the MDS clone directly [9, 10].

This syndrome is rarely seen; therefore, there is not enough data about isolated 5q-syndrome as well as lenalidomide therapy in our country. Isolated 5qsyndrome presents with normal or increased thrombocyte counts in peripheral blood and anemia with frequent transfusion replacement dependency. In clinical studies, it has been shown that lenalidomide therapy decreases transfusion dependency [11]. Lenalidomide provided long term blood transfusion

Dogu et al., Dramatic response after low doses of lenalidomide treatment in a 5q-syndrome

independency and erythroid response in patients with low- risk del(5q) and without del(5q) [12]. In a phase II study of low- risk del(5q) patients; after 24 weeks, evaluation of erythrocyte response showed that 67% of the patients with 5q deletion who were treated with lenalidomide became transfusion independent [13]. In low- risk 5q deletion MDS patients, daily doses of 10 mg for 21 days are used, and repeated with 28 day-intervals that can be modified if needed. In order to evaluate the response, treatment should be continued at least for 4 months [13, 14]. Lenalidomide treatment has a tolerable adverse event profile, besides decreasing transfusion dependency. Adverse events can be easily overcome with dose modifications. In clinical studies, thrombocytopenia and leukopenia are frequently observed but these adverse reactions usually appear during the first 8 weeks of treatment [15]. Therefore, weekly clinical follow-up at the beginning of the therapy is recommended. Less often adverse events of fatigue, rash and diarrhea can be noted [16].

In conclusion, in isolated 5q-syndrome which is a MDS subgroup and characterized by transfusion dependency; lenalidomide can decrease transfusion dependency with a tolerable adverse event profile that can be overcome with dose modifications.

Therefore lenalidomide can be considered as a treatment option. Assessment of all prevalent cases in our country will be helpful to reveal the efficacy and adverse event profile of lenalidomide.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med 2009;361:1872-85.

2. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079-88.

3. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero

193

G, Solé F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120:2454-65.

4. Giagounidis AA, Germing U, Wainscoat JS, Boultwood J, Aul C. The 5q- syndrome. Hematology 2004;9:271-7.

5. Germing U, Lauseker M, Hildebrandt B, Symeonidis A, Cermak J, Fenaux P, et al. Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study. Leukemia 2012;26:1286-92.

6. Fenaux P, Giagounidis A, Selleslag D, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del 5q. Blood 2011;118:3765-76.

7. Giagounidis AA, Germing U, Haase S, Hildebrandt B, Schlegelberger B, Schoch C, et al. Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. Leukemia 2004;18:113-9.

8. Bernasconi P, Klersy C, Boni M, Cavigliano PM, Calatroni S, Giardini I, et al. Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution. Leukemia 2005;19:1424-31.

9. Eisenmann KM, Dykema KJ, Matheson SF, Kent NF, DeWard AD, West RA, et al. 5q- myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics. Oncogene 2009;28:3429-41.

10. Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, et al.

Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36.

11. Giagounidis AA, Germing U, Aul C. Biological and prognostic significance of chromosome 5q deletions in myeloid malignancies. Clin Cancer Res 2006;12:5-10.

12. Kurtin SE, List AF. Durable long-term responses in patients with myelodysplastic syndromes treated with lenalidomide. Clin Lymphoma Myeloma 2009;9:E10-3.

13. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355:1456-65.

14. Mallo M, Del Rey M, Ibáñez M, Calasanz MJ, Arenillas L, Larráyoz MJ, et al. Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations. Br J Haematol 2013;162:74-86.

15. List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549-57.

16. List AF, Baker AF, Green S, Bellamy W. Lenalidomide: targeted anemia therapy for myelodysplastic syndromes. Cancer Control 2006;13 Suppl:4-11.

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NORTHERN CLINICS OF ISTANBUL SUBJECT INDEX FOR VOLUME 1 (2014)

Abdominal obesity see 2014;1(3):141-146 Adefovir dipivoxil see 2014;1(1):26-32 Aging see 2014;1(3):166-172 Alzheimer see 2014;1(3):166-172 disease see 2014;1(3):175-177 Anemia see 2014;1(2):84-88 Anencephaly see 2014;1(2):78-83 Anesthetics see 2014;1(1):39-44 Annular lesions see 2014;1(2):114-116 Annular sarcoidosis see 2014;1(2):114-116 Anxiety see 2014;1(1):6-12 Arrhythmia see 2014;1(1):6-12 Aural myiasis see 2014;1(3):175-177 Avascular necrosis see 2014;1(2):117-120 Axillary blokage see 2014;1(3):178-181 Axillary nerve block see 2014;1(1):39-44

BI-RADS 4 see 2014;1(1):1-5

safety see 2014;1(3):147-152 Dysmorphic face see 2014;1(3):182-186 Dyspepsia see 2014;1(3):158-165 Dystonia see 2014;1(3):187-190

Electrocardiogram see 2014;1(1):6-12 Esophagogastroduodenoscopy see 2014;1(3):158-165 ESWT see 2014;1(1):33-38 Extracorporeal shockwave see 2014;1(2):117-120

Femoral head see 2014;1(2):117-120 Fetal anomaly see 2014;1(2):78-83 Fibromyalgia see 2014;1(1):6-12 see 2014;1(2):89-94 Flatfoot see 2014;1(1):57-64 Flexible see 2014;1(1):57-64 Foot problem see 2014;1(1):57-64

Biological markers see 2014;1(2):95-100 Botulinum toxin type-A see 2014;1(3):153-157 astroesophageal reflux Brachial plexus see 2014;1(1):39-44 see 2014;1(3):141-146 Genetic counselling see 2014;1(3):182-186 annabis see 2014;1(2):121-126 Gensini score see 2014;1(2):65-70 Carpal tunnel syndrome see 2014;1(3):132-136 CB1 see 2014;1(2):121-126 ealth care professional see 2014;1(2):71-77 Cerebral plasy see 2014;1(3):153-157 Hematocolpos see 2014;1(1):45-48 Cerebrovascular disease see 2014;1(3):166-172 Hematologic parameters see 2014;1(1):19-25 Chiari see 2014;1(2):78-83 Hemiplegia see 2014;1(3):153-157 Child see 2014;1(1):49-52 Hemorrhage see 2014;1(2):101-105 Children see 2014;1(1):57-64 Home medicare see 2014;1(3):166-172 Chronic disease see 2014;1(2):84-88 nfection see 2014;1(1):13-18 Chronic hepatitis B see 2014;1(1):26-32 Inflammation see 2014;1(2):95-100 Cigarette see 2014;1(1):19-25 Intestinal stricture see 2014;1(3):127-131 Communication see 2014;1(2):71-77 Intoxication see 2014;1(3):178-181 Complication see 2014;1(3):137-140 Iron deficiency see 2014;1(2):84-88 Conotruncal cardiac anomaly Ischemia see 2014;1(2):101-105 see 2014;1(3):182-186 Conservative oint hypermobility see 2014;1(2):89-94 see 2014;1(2):117-120 treatment see 2014;1(1):33-38 -asparaginase see 2014;1(1):49-52 Coronary artery disease Lateral epicondylitis see 2014;1(1):33-38 see 2014;1(2):65-70 Lenalidomide see 2014;1(3):191-193 see 2014;1(2):95-100 Leukemia see 2014;1(1):49-52 Cutaneous tuberculosis see 2014;1(1):53-56 Lidocaine see 2014;1(3):178-181 Local see 2014;1(1):39-44 el(5q) see 2014;1(3):191-193 Lupus vulgaris see 2014;1(1):53-56 Depression see 2014;1(1):6-12 ammography see 2014;1(1):1-5 Depression see 2014;1(2):89-94 Metabolic syndrome see 2014;1(3):141-146 Disseminated lupus vulgaris Multiple sclerosis see 2014;1(2):109-113 see 2014;1(1):53-56 Myelodysplastic syndrome Drug reactions see 2014;1(3):147-152 see 2014;1(3):191-193

G

C

H

I

J L

D

M

Myoclonus see 2014;1(3):187-190 Myofacial pain see 2014;1(2):89-94

Obesity see 2014;1(3):141-146

Occupation see 2014;1(3):132-136 Otorrhagia see 2014;1(3):175-177

P-wave dispersion see 2014;1(2):65-70

Pain see 2014;1(2):89-94 Patient satisfaction see 2014;1(2):71-77 Pegylated interferon alpha 2a see 2014;1(1):26-32 Pelvic mass see 2014;1(1):45-48 Pes planus see 2014;1(1):57-64 Pharmacovigilance see 2014;1(3):147-152 Polychondritis see 2014;1(2):106-108 Prenatal ultrasonography see 2014;1(2):78-83 PRES see 2014;1(1):49-52 Progestin see 2014;1(1):45-48 see 2014;1(2):95-100 Proton pump inhibitor- treatment see 2014;1(3):158-165

Recurrent tonsillopharyngitis

see 2014;1(1):13-18 Relapsing see 2014;1(2):106-108

Sarcoidosis see 2014;1(2):114-116

Sensorineural hearing loss see 2014;1(2):106-108 Sleep disorder see 2014;1(2):89-94 Spasticity see 2014;1(3):153-157 Stable angina pectoris see 2014;1(2):65-70 Stress urinary incontinence see 2014;1(3):137-140 Stroke see 2014;1(2):101-105 Subcategories 4A see 2014;1(1):1-5 Sudden sensorineural hearing loss see 2014;1(2):109-113 Synthetic cannabinoid see 2014;1(2):121-126

Tenascin C see 2014;1(3):127-131

Thrombosis see 2014;1(1):49-52 Transobturator vaginal tape (TOT) see 2014;1(3):137-140 Treatment see 2014;1(3):187-190 Turkish population see 2014;1(3):141-146

Using tea leaf scissors see 2014;1(3):132-136 Vitamin D see 2014;1(1):13-18 Young man see 2014;1(1):19-25

NCI AUTHOR INDEX FOR VOLUME 1 (2014)

195

NORTHERN CLINICS OF ISTANBUL AUTHOR INDEX FOR VOLUME 1 (2014)

Abaci O (see Akin F et al.) 2014;1(2):65-70

Acmaz G (see Tutus S et al.) 2014;1(2):78-83 Ahishali E (see Sahin M et al.) 2014;1(3):158-165 Akbulut C (see Sahin M et al.) 2014;1(3):158-165 Akdemir N (see. Bostanci MS et al.) 2014;1(3):137-140 Akin F, et al. see 2014;1(2):65-70 Akin MA (see Tutus S et al.) 2014;1(2):78-83 Akin S, et al. see 2014;1(2):84-88 Akpinar P (see Selimoglu E et al.) 2014;1(3):153-157 Albayrak M (see. Bostanci MS et al.) 2014;1(3):137-140 Alimoglu O (see Leblebici IM et al.) 2014;1(1):1-5 Aliustaoglu M (see Akin S et al.) 2014;1(2):84-88 Aliustaoglu M (see Sahin M et al.) 2014;1(3):158-165 Alpat SN (see Korkmaz P et al.) 2014;1(1):26-32 Alpsoy S (see Sarifakioglu B et al.) 2014;1(1):6-12 Arslan IB (see Mengi E et al.) 2014;1(3):175-177 Atik A (see Sahin N et al.) see 2014;1(2):89-94 Atik A, et al. see 2014;1(1):57-64 Avci F (see Bakacak M et al.) see 2014;1(1):45-48 Avsar S, et al. see 2014;1(3):174 Ay D, et al. see 2014;1(2):95-100 Ayca B (see Akin F et al.) see 2014;1(2):65-70 Aydin U (see Ay D et al.) 2014;1(2):95-100 Ayhan A (see Kartal V et al.) 2014;1(1):49-52

Bakacak M, et al. see 2014;1(1):45-48

Bakacak Z (see Bakacak M et al.) see 2014;1(1):45-48 Bakan N (see Yanli Y et al.) 2014;1(1):39-44 Baklacioglu HS (see Selimoglu E et al.) 2014;1(3):153-157 Bayram K, et al. 2014;1(1):33-38 Bilgin Badur N (see Memetoglu OG et al.) 2014;1(2):101-105 Bilici R see 2014;1(2):121-126 Bostanci MS (see Bakacak M et al.) see 2014;1(1):45-48 Bostanci MS, et al. see 2014;1(3):137-140 Bozaykut A (see Collak A et al.) 2014;1(1):13-18 Bozkurt S (see Leblebici IM et al.) 2014;1(1):1-5

Cakiroglu Y (see Vural F et al.) 2014;1(2):71-77

Cakirtekin V (see Erbesler ZA et al.) 2014;1(3):178-181 Cam OH (see Tekin M et al.) 2014;1(2):109-113 Can B (see Zafer Turkoglu Z et al.) 2014;1(2):114-116 Can B, et al. see 2014;1(1):53-56 Cavus B (see Inal B et al.) 2014;1(1):19-25 Cetin C (see Oksuz E et al.) 2014;1(3):166-172 Cevrioglu AS (see. Bostanci MS et al.) 2014;1(3):137-140 Ciftci S (see Vural F et al.) 2014;1(2):71-77 Ciftci S (see Vural F et al.) 2014;1(3):147-152 Collak A, et al. see 2014;1(1):13-18

Dabak R (see Sahin M et al.) 2014;1(3):158-165

Dagli R (see Erbesler ZA et al.) 2014;1(3):178-181 Demir A (see Ay D et al.) 2014;1(2):95-100 Demir H (see Inal B et al.) 2014;1(1):19-25 Demirel B (see Collak A et al.) 2014;1(1):13-18 Demirhan E (see Mengi E et al.) 2014;1(3):175-177 Demirkuru F (see Derin S et al.) 2014;1(2):106-108 Derin S, et al. see 2014;1(2):106-108 Devrimsel G, et al. see 2014;1(3):132-136 Dogan E (see Bayram K et al.) 2014;1(1):33-38 Dogan E (see Sahin N et al.) see 2014;1(2):89-94 Dogru M (see Collak A et al.) 2014;1(1):13-18 Dogu MH, et al. see 2014;1(3):173 Dogu MH, et al. see 2014;1(3):191-193 Dolapcioglu C (see Sahin M et al.) 2014;1(3):158-165

Erben N (see Korkmaz P et al.) 2014;1(1):26-32

Erbesler ZA, et al. see 2014;1(3):178-181 Ercan O (see Bakacak M et al.) see 2014;1(1):45-48 Erdem E, et al. see 2014;1(3):127-131 Erdolu B (see Ay D et al.) 2014;1(2):95-100 Eren TT (see Leblebici IM et al.) 2014;1(1):1-5 Ergin E (see Akin S et al.) 2014;1(2):84-88 Ersanli M (see Akin F et al.) see 2014;1(2):65-70

Firatli I (see Akin F et al.) see 2014;1(2):65-70 Gokden Y (see Erdem E et al.) 2014;1(3):127-131 Gonen C (see Erdem E et al.) 2014;1(3):127-131 Gurmen T (see Akin F et al.) see 2014;1(2):65-70

Hacioglu S (see Dogu MH et al.) 2014;1(3):173

Hacioglu S (see Dogu MH et al.) 2014;1(3):191-193 Hac覺bekiroglu T (see Inal B et al.) 2014;1(1):19-25 Haliloglu S (see Selimoglu E et al.) 2014;1(3):153-157 Hanege FM (see Tekin M et al.) 2014;1(2):109-113

Icagasioglu A (see Selimoglu E et al.) 2014;1(3):153-157 Inal B, et al. see 2014;1(1):19-25

Kalyoncuoglu M (see Akin F et al.) see 2014;1(2):65-70 Karaagac AT, et al. see 2014;1(3):182-186 Karadag B (see Inal B et al.) 2014;1(1):19-25 Karaoren G (see Erbesler ZA et al.) 2014;1(3):178-181 Karayaka S, et al. see 2014;1(3):141-146 Kartal ED (see Korkmaz P et al.) 2014;1(1):26-32 Kartal V, et al. see 2014;1(1):49-52 Katkat F (see Akin F et al.) see 2014;1(2):65-70 Kavala M (see Can B et al.) 2014;1(1):53-56

196 Kavala M (see Zafer Turkoglu Z et al.) 2014;1(2):114-116 Kaya A (see Avsar S et al.) 2014;1(3):174 Kazan S (see Akin S et al.) 2014;1(2):84-88 Keskin A (see Dogu MH et al.) 2014;1(3):173 Keskin A (see Dogu MH et al.) 2014;1(3):191-193 Keskin Tukel N (see Akin S et al.) 2014;1(2):84-88 Kilic Aydin D (see Akin S et al.) 2014;1(2):84-88 Kirbas S (see Devrimsel G et al.) 2014;1(3):132-136 Kocak F (see Erdem E et al.) 2014;1(3):127-131 Kochan K (see Erdem E et al.) 2014;1(3):127-131 Korkmaz P, et al. see 2014;1(1):26-32 Kostu B (see Bakacak M et al.) see 2014;1(1):45-48 Kucukali Turkyilmaz A (see Devrimsel G et al.) 2014;1(3):132-136 Kucukoglu S (see Akin F et al.) see 2014;1(2):65-70

Leblebici IM, et al. see 2014;1(1):1-5 Memetoglu OG, et al. see 2014;1(2):101-105

Mengi E, et al. see 2014;1(3):175-177 Mesci B (see Karayaka S et al.) 2014;1(3):141-146 Musaoglu Z (see Inal B et al.) 2014;1(1):19-25

Oguz A (see Karayaka S et al.) 2014;1(3):141-146

Oguz Akarsu E, et al. see 2014;1(3):187-190 Oksuz E, et al. see 2014;1(3):166-172 Onat E (see Oksuz E et al.) 2014;1(3):166-172 Oran A (see Derin S et al.) 2014;1(2):106-108 Osken A (see Avsar S et al.) 2014;1(3):174 Ozbilen Acar G (see Tekin M et al.) 2014;1(2):109-113 Ozdemir M (see Yanli Y et al.) 2014;1(1):39-44 Ozden S (see. Bostanci MS et al.) 2014;1(3):137-140 Ozemir IA (see Leblebici IM et al.) 2014;1(1):1-5 Ozgonenel L, et al. see 2014;1(2):117-120 Ozgunes I (see Korkmaz P et al.) 2014;1(1):26-32 Ozmutlu IL (see Avsar S et al.) 2014;1(3):174 Ozpolat E (see Sahin M et al.) 2014;1(3):158-165 Ozyurek S (see Atik A et al.) 2014;1(1):57-64 Ozyurt S (see Tutus S et al.) 2014;1(2):78-83

Paker N (see Erdem E et al.) 2014;1(3):127-131 Sagiroglu J (see Leblebici IM et al.) 2014;1(1):1-5

Sahin M, et al. see 2014;1(3):158-165 Sahin N (see Devrimsel G et al.) 2014;1(3):132-136 Sahin N (see Sarifakioglu B et al.) 2014;1(1):6-12 Sahin N, et al. see 2014;1(2):89-94 Salturk Degirmenci (see Erdem E et al.) 2014;1(3):127-131 Sari I (see Dogu MH et al.) 2014;1(3):173 Sari I (see Dogu MH et al.) 2014;1(3):191-193 Sari M (see Akin F et al.) see 2014;1(2):65-70 Sarifakioglu B, et al. see 2014;1(1):6-12 Selimoglu E, et al. see 2014;1(3):153-157 Seren LG (see Collak A et al.) 2014;1(1):13-18 Serin S (see Bakacak M et al.) see 2014;1(1):45-48

North Clin Istanbul â&#x20AC;&#x201C; NCI Sezer RG (see Collak A et al.) 2014;1(1):13-18 Shahzadi A (see Oksuz E et al.) 2014;1(3):166-172 Surmeli R (see Oguz Akarsu E et al.) 2014;1(3):187-190

Tamer G (see Karayaka S et al.) 2014;1(3):141-146 Taraktas A (see Memetoglu OG et al.) 2014;1(2):101-105 Tekce M (see Akin S et al.) 2014;1(2):84-88 Tekin M, et al. see 2014;1(2):109-113 Timur C (see Kartal V et al.) 2014;1(1):49-52 Tiryakioglu O (see Ay D et al.) 2014;1(2):95-100 Topaloglu Demir F (see Can B et al.) 2014;1(1):53-56 Topaloglu Demir F (see Zafer Turkoglu Z et al.) 2014;1(2):114-116 Topcu B (see Sarifakioglu B et al.) 2014;1(1):6-12 Turgut ST (see Selimoglu E et al.) 2014;1(3):153-157 Turkoglu Z (see Can B et al.) 2014;1(1):53-56 Tutus S, et al. see 2014;1(2):78-83

Ucar S (see Derin S et al.) 2014;1(2):106-108 Ulucay V (see Can B et al.) 2014;1(1):53-56 Unal Dayi S (see Avsar S et al.) 2014;1(3):174 Unal O (see. Bostanci MS et al.) 2014;1(3):137-140 Unlu Ozkan F (see Memetoglu OG et al.) 2014;1(2):101-105 Unsal C (see Sarifakioglu B et al.) 2014;1(1):6-12 Usluer G (see Korkmaz P et al.) 2014;1(1):26-32

Vural AH (see Ay D et al.) 2014;1(2):95-100 Vural B (see Vural F et al.) 2014;1(2):71-77 Vural B (see Vural F et al.) 2014;1(3):147-152 Vural F, et al. see 2014;1(2):71-77 Vural F, et al. see 2014;1(3):147-152

Yalcin D (see Oguz Akarsu E et al.) 2014;1(3):187-190 Yanli Y, et al. see 2014;1(1):39-44 Yazici Z (see Oksuz E et al.) 2014;1(3):166-172 Yesil H (see Bayram K et al.) 2014;1(1):33-38 Yesil H (see Ozgonenel L et al.) 014;1(2):117-120 Yesil M (see Ozgonenel L et al.) 014;1(2):117-120 Yigit Z (see Akin F et al.) see 2014;1(2):65-70 Yildirim AI (see Karaagac AT et al.) 2014;1(3):182-186 Yildirim Guzelant A (see Sarifakioglu B et al.) 2014;1(1):6-12 Yildirim M (see Devrimsel G et al.) 2014;1(3):132-136 Yilmaz E (see Tutus S et al.) 2014;1(2):78-83 Yilmaz S (see Kartal V et al.) 2014;1(1):49-52 Yoruk A (see Kartal V et al.) 2014;1(1):49-52 Yumun G (see Ay D et al.) 2014;1(2):95-100 Yumusakhuylu Y (see Selimoglu E et al.) 2014;1(3):153-157

Zafer Turkoglu Z, et al. see 2014;1(2):114-116 Zara Z (see Kartal V et al.) 2014;1(1):49-52 Zemheri E (see Zafer Turkoglu Z et al.) 2014;1(2):114-116 Zindanci I (see Can B et al.) 2014;1(1):53-56 Zindanci I (see Zafer Turkoglu Z et al.) 2014;1(2):114-116