Israel Medical Association Journal

Background: Most data on the incidence of rheumatic fever come from hospital records. We presumed that there may be cases of RF[1] that do not require hospitalization, especially in countries with high quality community health care. 

Objectives: To explore the incidence and characteristics of RF using community-based data. 

Methods: A retrospective descriptive study was conducted among the members (more than 450,000) of the Clalit Health Services, Central district, during 2000–2005. The electronic medical files of members up to 40 years old with a diagnosis of RF in hospital discharge letters or during community clinic visits were retrieved. Patients with a first episode of RF according to the modified Jones criteria were included.

Results: There were 44 patients with a first episode of RF. All patients were under the age of 29. The annual incidence among patients aged 0–30 years was 3.2:100,000; the highest incidence was among children aged 5–14 years (7.5:100,000), and in males the incidence was 2.26 times higher than in females. The incidence was higher among patients from large families, of non-Jewish ethnicity, and from rural areas. Twenty-five percent of the patients were both diagnosed and treated in an ambulatory care setting.

Conclusions: Although the incidence of RF in the western world and in Israel is low, the disease still occurs and mainly affects children. Any future estimates of disease incidence should take into account that RF is becoming an ambulatorily treated disease.  

Background: Vitamin A and its derivative retinoic acid regulate various aspects of cell behavior as growth, differentiation, and proliferation. Retinoic acid derivatives have been suggested to play a role in processes such as hepatic regeneration and fibrosis.

Objectives: To evaluate the influence of vitamin A on rat liver epithelial cell proliferation.

Methods: We performed common bile duct ligation in rats that had been subjected to differing vitamin A diets and compared their livers to control rats. Proliferation, apoptosis, and retinoic acid receptors were evaluated by histology and immunohistochemistry in bile duct cells and hepatocytes.

Results: Vitamin A deficiency was found to be associated with enhanced proliferation of bile duct epithelial cells following CBD[1] ligation. The proliferation was manifested by increased numbers of ducts, by aberrant extended ductal morphology, and by elevated numbers of nuclei expressing the proliferation marker Ki67. The amount of vitamin A in the rat diet did not affect detectably ductal cell apoptosis. We observed up-regulated expression of the retinoid X receptor-alpha in the biliary epithelium of vitamin A-deficient rats that had undergone CBD ligation, but not in vitamin A-sufficient rats.

Conclusions: We speculate that the mechanism underlying the ductal proliferation response involves differential expression of RXR[2]-alpha. Our observations suggest that deficiency of vitamin A may exacerbate cholestasis, due to excessive intrahepatic bile duct proliferation.

Background: Severe hearing impairment can have devastating effects on social integration and vocational opportunities.

Objectives: To investigate how well – or poorly – individuals who underwent cochlear implantation as children integrated into the general Israeli hearing community.

Method: We sent a questionnaire to the 30 subjects ≥ 18 years old who underwent cochlear implants our department from 1990 to 2004 when they were < 18 years of age and had used their device for at least 3 years before replying.

Results: Eighteen implant users responded (14 males), yielding a 60% response rate. Their mean age was 13.3 ± 7.0 years (range 6–17) at implantation and 21.1 ± 3.6 years (range 18–34) when they filled in the questionnaire. Five were attending rabbinical school (yeshiva students), four were in regular military service, five were university students (three also held jobs), two were attending high school, one was employed (and had a university degree), and one had left the yeshiva and was unemployed when he returned the questionnaire. Fourteen respondents use the oral communication mode for conversation and the other 4 use both oral and sign languages. Longer daily implant use was significantly associated with coping with the difficulties in the setting in which they were currently active, with a higher level of satisfaction with their current lifestyle and with recognition of the implant’s contribution to this satisfaction (P = 0.037, P = 0.019 and P = 0.001, respectively).

Conclusions: Advances in cochlear implant technologies enable profoundly deaf implanted children to integrate well into the Israeli hearing society, albeit with a large inter-subject variability.

Background: Diabetes mellitus is a multi-organ disorder affecting many types of connective tissues, including bone and cartilage. Certain skeletal changes are more prevalent in diabetic patients than in non-diabetic individuals. A possible association of diabetes mellitus and lumbar spinal stenosis has been raised.

Objectives: To compare the prevalence of diabetes mellitus in patients with spinal stenosis, degenerative disk disease or osteoporotic vertebral fractures.

Methods: A cross-sectional analysis was performed of 395 consecutive patients diagnosed with spinal stenosis, degenerative disk disease or osteoporotic vertebral fractures. All the patients were examined by one senior author in the outpatient orthopedic clinic of a large general hospital between June 2004 and January 2006 and diagnosed as having either lumbar spinal stenosis (n=225), degenerative disk disease (n=124) or osteoporotic vertebral fractures (n=46).

Results: The prevalence of diabetes mellitus in the three groups (spinal stenosis, osteoporotic fracture, degenerative disk disease) was 28%, 6.5% and 12.1%, respectively, revealing a significantly higher prevalence in the spinal stenosis group compared with the others (P = 0.001). The higher prevalence of diabetes in the stenotic patients was unrelated to the presence of degenerative spondylolisthesis.

Conclusions: There is an association between diabetes and lumbar spinal stenosis. Diabetes mellitus may be a predisposing factor for the development of lumbar spinal stenosis.

Background: Cancer is a leading cause of mortality worldwide. The most effective way to combat cancer is by prevention and early detection.

Objectives: To evaluate the outcome of screening an asymptomatic population for the presence of benign and neoplastic lesions.

Methods: Routine screening tests for prevention and/or early detection of 11 common cancers were conducted in 300 consecutive asymptomatic, apparently healthy adults, aged 25–77 years. Other tests were performed as indicated.

Results: Malignant and benign lesions were found in 3.3% and 5% of the screenees, respectively, compared to 1.7% in the general population. The most common lesions were in the gastrointestinal tract followed by skin, urogenital tract and breast. Advanced age and a family history of a malignancy were associated with increased risk for cancer with an odds ratio of 9 and 3.5, respectively (95% confidence interval 1.1–71 and 0.9–13, respectively). Moreover, high serum C-reactive protein levels and polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a malignant lesion was extremely high (23.1%; OR[1] 14, 95% CI[2] 2.5–78).

Conclusions: Screening asymptomatic subjects identifies a significant number of neoplastic lesions at an early stage. Incorporating data on genetic polymorphisms in the APC and CD24 genes can further identify individuals who are at increased risk for cancer. Cancer can be prevented and/or diagnosed at an early stage using the screening facilities of a multidisciplinary outpatient clinic.

Background: Secondary thrombocytosis is associated with a variety of clinical conditions, one of which is lower respiratory tract infection. However, reports on thrombocytosis induced by viral infections are scarce.

Objectives: To assess the rate of thrombocytosis (platelet count > 500 x 10⁹/L) in hospitalized infants with bronchiolitis and to investigate its potential role as an early marker of respiratory syncytial virus infection.

Methods: Clinical data on 469 infants aged ≤ 4 months who were hospitalized for bronchiolitis were collected prospectively and compared between RSV[1]-positive and RSV-negative infants.

Results: The rate of thrombocytosis was significantly higher in RSV-positive than RSV-negative infants (41.3% vs. 29.2%, P = 0.031). The odds ratio of an infant with bronchiolitis and thrombocytosis to have a positive RSV infection compared to an infant with bronchiolitis and a normal platelet count was 1.7 (P = 0.023, 95% confidence interval 1.07–2.72). There was no significant difference in mean platelet count between the two groups.

Conclusions: RSV-positive bronchiolitis in hospitalized young infants is associated with thrombocytosis.

Background: The role of alcohol in driver fatalities in Israel is unknown, and monitoring blood alcohol concentration among drivers is not routine. Moreover, over the past decade, self-reported access to and consumption of alcohol in Israel has been on the rise.

Objectives: To use available data to characterize alcohol-related driver fatalities.

Methods: The prevalence of alcohol-related driver fatalities were estimated for 443 drivers, ages 17+ years using data from Israel's National Center for Forensic Medicine for 2000–2004.

Results: Between 8% and 17% of driver fatalities had a BAC[1] ≥ 0.05 g/dl. Most drivers with alcohol exceeding this level were males aged 21–30 years who died on weekends. Recreational and/or medicinal drugs were found in 6%–11% of driver fatalities. Mean BAC among driver fatalities with BAC ≥ 0.05 g/dl was threefold higher than the legal driving limit and appears to be increasing with time.

Conclusions: In light of the evidence suggesting an increasing mean BAC over time as well as reported increasing trends in access to alcohol and consumption, this study should serve as a basis for future research to comprehensively characterize the extent of this problem

Background: According to the Israeli immunization schedule 1 year old babies should receive two concomitant vaccinations: MMR (measles-mumps-rubella), and DTap-Hib-IPV (diphtheria tetanus acellular pertussis-Haemophilus influenzae type b-poliomyelitis). However, about one-third of infants in Israel receive these vaccinations separately. Nurses at a primary care prevention clinic in Israel observed that the separate mode of vaccination is associated with a lower rate of side effects.

Objectives: To validate this observation and determine whether it represents an exception or the rule.

Methods: A nested prospective follow-up study was conducted in a primary care clinic in Israel. The survey included 191 mothers and their offspring born during 2004/2005. The mothers were interviewed over the telephone 2 weeks after the day of vaccination.

Results: The rate of adverse effects in children who received the injections separately was significantly lower than among those who were vaccinated simultaneously (40% vs. 57%).

Conclusions: It may be necessary to reconsider the current vaccination policy regarding concomitant injections.

Background: The incidence of stroke varies among ethnically and culturally diverse groups.

Objectives: To examine the ethnic-geographic patterns of stroke incidence in men and women with coronary heart disease in Israel, focusing on the extent to which this variability can be explained by known differences in risk factors for stroke.

Methods: Patients with documented coronary heart disease were followed for 6–8 years for incident cerebrovascular events. Baseline medical evaluation included assessment of vascular risk factors and measures of blood lipids. Among 15,052 patients, a total of 1110 were identified with any incident ischemic cerebrovascular event by ICD-9 codes, of whom 613 had confirmed ischemic stroke or transient ischemic attack.

Results: A major excess of ischemic cerebrovascular events among Israeli Arab women as compared to males, and an inverse finding among Israeli born Jews, were noted. The high risk in the Arab population in Israel reflected an unfavorable risk profile, since predicted rates by multivariate analysis and observed rates were 69 and 68 per 1000, respectively. High ischemic cerebrovascular event rates were identified among patients born in the Balkan countries and North Africa (89 and 90 per 1000) but unfavorable risk factor levels of these individuals did not explain them. Most trends appeared similar in male and female patients. A comparison of observed and accepted-according-to-risk-profile rates of ischemic cerebrovascular events yielded significant differences (P = 0.04), consistent with an additional role of geographic/ethnic origin, resulting from factors that remain unrecognized,or with variables unassessed in this study.

Conclusions: We identified an ethnic diversity in stroke risk among Israeli born in different parts of the world beyond what could be expected on the basis of differences in known risk factors. These findings call for detailed research aimed at identifying additional differences in the risk profile of patients with atherothrombotic disease exposed to an increased risk of stroke.
 

Background: Patients with hypertrophic cardiomyopathy are prone to ventricular arrhythmias and sudden death. Identifying patients at risk of sudden death is difficult.

Objectives: To determine whether microvolt T-wave alternans detected during exercise or rapid atrial pacing can identify patients with HCM[1] who are at risk of ventricular arrhythmias and sudden death.

Methods: This prospective observational study included 21 patients with HCM: 11 with hypertrophic obstructive cardiomyopathy, 9 with non-obstructive hypertrophic cardiomyopathy, and 1 with apical hypertrophic cardiomyopathy. TWA[2] was measured while the patients were on anti-arrhythmic medication.

Results: TWA was positive in 9 patients (43%) and negative in 12 (57%). Three patients were resuscitated after sudden death before their enrolment in the study and two patients developed ventricular tachycardia and fibrillation respectively during the study period. After combining the endpoint of sudden death from a ventricular arrhythmia and the presence of ventricular arrhythmias on a Holter monitor, there was no significant correlation between the presence of a positive TWA and the presence of ventricular arrhythmias on the Holter monitor or a history of sudden death.  

Conclusion: TWA cannot be used as a non-invasive test for detecting patients with HCM and electrical instability. TWA is not useful for predicting sudden death in patients with HCM.

Background: Familial dysautonomia is a genetic disease that affects the sensory and autonomic nervous systems with varying severity. The deep breath test is one of several measures used to assess the severity of autonomic diseases, but its value in familial dysautonomia has not yet been investigated.

Objectives: To determine the diagnostic value of the DBT[1] in patients with familial dysautonomia.

Methods: Eight patients with familial dysautonomia and eight healthy volunteers were examined by electrocardiography for 1 minute at rest and during forced deep breathing. The following values were recorded: maximum expiratory and minimum inspiratory heart rate and the difference between them (ΔE/I), standard deviation of the heart rate values, interbeat intervals, and E/I[2] ratio. Spectral power analysis of heart rate variability was also performed.

Results: The patients with familial dysautonomia showed a lesser change in heart rate in response to the change in breathing pattern than the controls. Mean values in the study group were significantly higher for minimal inspiratory heart rate and significantly lower for ΔE/I, heart rate standard deviation and E/I ratio, indicating a non-flexible heart response and abnormal parasympathetic function. These findings were supported by power spectral analysis.

Conclusions: Patients with familial dysautonomia have a significantly disturbed response to physiological stimuli. The DBT may serve as a reliable means to quantify autonomic dysfunction in this patient population.

Background: Respiratory syncytial virus bronchiolitis is the single leading cause of pediatric admissions for infants in the first year of life, presenting regularly in epidemic proportions in the winter months and impacting in a major way on pediatric inpatient services.

Objective: To quantitate the burden of RSV[1] disease on a pediatric service with the purpose of providing a database for proper health planning and resource allocation.

Methods: We conducted a prospective 5 year study of documented RSV infections in a single pediatric service. RSV disease was confirmed by direct immunofluorescence testing of nasal swabs from all hospitalized cases of bronchiolitis.

Results: On average, 147 ± 17 cases of RSV bronchiolitis were admitted annually in the November–March RSV season, representing 7%–9% of admissions and 10%–14% of hospital days. There was a consistent male preponderance of admissions (55–64%) and 15–23% of admissions were patients less than 1 month old. In peak months RSV cases accounted for as many of 40% of the hospitalized infants and was the leading cause of over-occupancy (up to 126%) in the pediatric ward during the winter,

Conclusions: RSV infection is a major burden for pediatric inpatient services during the winter season. This recurrent and predictable “epidemic,” which regularly leads to over-occupancy, requires increased manpower (nursing) and resources (beds, pulse oximeters) to facilitate proper care. Since this annual event is not a surprise nor an unexpected peak, but rather a cyclical predictable epidemiological phenomenon, proper planning and allocation of services are crucial.