Israel Medical Association Journal

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.

Objectives: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2.

Methods: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008.

Results: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder, consistent with an autosomal dominant trait.

Conclusions: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.
 

Background: Cardiac patients express elevated levels of B-type natriuretic peptide and the amino terminal segment of its prohormone (NT-proBNP). However, there are non-cardiac causes of NT-proBNP level elevation.

Objectives: To determine the upper limit of NT-proBNP for pediatric patients with acute non-cardiac disease.

Methods: We compared NT-proBNP concentrations in healthy children and children with acute non-cardiac, mostly febrile, and acute cardiac disease. We used the Student t-test and Mann-Whitney test for group comparisons, and Pearson's and Spearman's correlation coefficients to test relationships between variables. 

Results: In 138 patients with acute non-cardiac diseases (mean age 3.7 years, 53% male), median NT-proBNP concentration was 162 pg/ml, upper limit (95% percentile) 1049 pg/ml. The level did not vary significantly by disease category; was negatively correlated with weight, weight percentile, age and hemoglobin level; and positively correlated with creatinine level. Multivariant analysis showed weight to be the only factor influencing NT-proBNP level. Levels were higher in children with acute non-cardiac diseases versus healthy children (median 88 pg/ml, P < 0.001, n= 59), and lower than levels in patients with acute cardiac disease (median 29,986 pg/ml, P < 0.001, n=29). Receiver operating characteristic analysis showed good NT-proBNP performance for differentiation between children with acute cardiac versus non-cardiac disease (area under the curve 0.958), at a cutoff of 415 pg/ml.

Conclusions: NT-proBNP levels are higher in children with acute non-cardiac diseases than in healthy children, but lower than in children with acute cardiac disease. NT-proBNP negatively correlated with weight and weight percentile.
 

Background: The rate of infection with Clostridium difficile colitis and its associated mortality have been increasing in the last decade. The molecular epidemiology of C. difficile in Israel has as yet not been studied.

Objectives: To screen for the existence of the 027 and 078 ribotypes and determine the longitudinal molecular epidemiology of the circulating clinical C. difficile isolates in a large hospital in central Israel.

Methods: Polymerase chain reaction (PCR) ribotyping was performed on C. difficile isolates obtained from hospitalized patients from November 2003 to May 2004 (first study period) and September 2009 (second study period). Isolates with PCR[1] ribotype patterns, unlike those of the available reference strains (078 and 027), were labeled with letters. Forty-six isolates from the first study period and 20 from the second were analyzed.

Results: PCR strain typing of C. difficile isolates yielded approximately 26 unique ribotypes. During the first study period, ribotype A and B accounted for 30% and 28%, respectively, whereas ribotype E and K accounted for 6.5% for each. During the second study period, ribotypes A, E and K disappeared, and the incidence of ribotype B decreased from 28% to 15%. One isolate (1/20, 5%) emerged during the second period and was identified as ribotype 027. Moxifloxacin resistance was found in 93% of ribotype A isolates, 81% of the ribotype B group, and in 44% of other ribotypes.

Conclusions: The predominant ribotypes circulating in our institution were diverse and changing. This is the first report on the emergence of the 027 ribotype in Israel.

Background: Acute renal failure (ARF) is a common complication in critically ill children. It is known as an important predictor of morbidity and mortality in this population. Data on the factors affecting the choice of renal replacement therapy (RRT) modality and its impact on mortality of children with ARF[1] are limited.

Objectives: We retrospectively studied 115 children with ARF necessitating RRT[2] during the period 1995–2005 to evaluate the effect of several prognostic factors as well as RRT type on their immediate outcome.

Methods: The data collected from charts included demographics, primary disease, accompanying medical conditions, use of vasopressor support, indications for dialysis, RRT modality, and complications of dialysis. Categorical variables were analyzed using chi-square or Fisher’s exact tests. Variables associated with mortality (P < 0.1) at the univariable level were studied by a multivariable logistic regression model.

Results: The most common cause of ARF was congenital heart disease (n=75). RRT modalities included peritoneal dialysis (PD) (n=81), hemodialfiltration (HDF) (n=31) and intermittent hemodialysis (IHD) (n=18). Median RRT duration was 4 days (range 1–63 days). Overall mortality was 52.2%. IHD[3] was associated with the best survival rate (P < 0.01 vs. PD[4] and HDF[5]), while children treated with HDF had the worse outcome. Hemodynamic instability and systemic infections were associated with greater mortality, but the rate of these complications did not differ between the study groups.

Conclusions: Our results suggest that IHD[6] when applied to the right patient in an appropriate setting may be a safe and efficient RRT modality in children with ARF. Randomized prospective trials are needed to further evaluate the impact of different RRT modalities on outcome in children with ARF.

Background: Concomitant human immunodeficiency virus and human papillomavirus infection increases both HPV[1] persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV[2]-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer.

Objectives: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center.

Methods: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed.

Results: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%).

Conclusions: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.

Background: The TANTALUS^™ System (MetaCure Ltd.) is a minimally invasive implantable device for the treatment of type 2 diabetes. The system detects food intake by sensing gastric electrical variations and applies electrical stimulation to the gut synchronized to natural gastric activity. The system is commercially available in Europe and Israel and is in clinical trials in the United States. It has been tested in 132 patients worldwide to date.

Objectives: To re-analyze previously reported data from different studies. This retrospective analysis of the type 2 diabetes subpopulation analyzed the expected benefit and characterize the significance of baseline A1c in the determination of the expected clinical outcome.

Methods: From the total cohort of 132 patients implanted with the TANTALUS device in 10 different centers in Europe and the U.S., 50 subjects (27 females, 23 males) who were obese with uncontrolled T2DM[1] on a stable regime of oral medication for 3 months prior to implant were identified. This population had similar inclusion/exclusion criteria as well as treatment protocols and were all treated for at least 24 weeks. The analysis was based on the A1c change compared to baseline.

Results: Data after 24 weeks demonstrate a reduction in A1c in 80% of the patients with average drop in A1c of 1.1 ± 0.1%. The average weight loss was 5.5 ± 0.7 kg.

Conclusions: The results suggest that the TANTALUS stimulation regime can improve glucose levels and induce moderate weight loss in obese T2DM patients.

Background: Insulin-dependent diabetes mellitus is dominated by a Th1 response whereas atopic diseases such as asthma, eczema and allergic rhinitis are characterized by a Th2 response. Because it is known that Th1 and Th2 cells reciprocally counteract each other, it can be speculated that the prevalence of Th2-mediated diseases is lower in patients with a Th1-mediated disease.

Objectives: To compare the prevalence of atopic diseases among children with IDDM[1] and age-matched controls.

Methods: The study group comprised 65 children with IDDM attending the pediatric endocrinology clinic at the Wolfson Medical Center. The control group consisted of 74 non-diabetic children who presented at the emergency room due to an acute illness (burns, abdominal pain, fever, head trauma). Patients were asked to complete a detailed questionnaire on their history of personal and familial atopic and autoimmune diseases. In addition, a total serum immunoglobulin E concentration and the presence of IgE[2] antibodies to a panel of relevant inhalant allergens were analyzed.

Results: Children with IDDM and their first-degree relatives had a significantly higher prevalence of other autoimmune diseases such as thyroiditis and celiac as compared to controls. The two groups had a similar prevalence of atopic diseases with respect to history, total serum IgE, or the presence of IgE antibodies to a panel of relevant inhalant allergens.

Conclusions: The prevalence of atopic diseases in IDDM patients was similar to that in the normal population. Our results suggest that the traditional Th1/Th2 theory to explain the complexity of the immune response is oversimplified.