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: Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN[1] is characterized by neutrophil count < 500 ml and a benign self-limiting course. Detecting specific antibodies against the polymorphic human neutrophil antigen usually confirms the diagnosis. Current available tests, however, are expensive and inapplicable in many laboratories as they require the use of isolated and fixed granulocytes obtained from donors pretyped for their distinct HNA[2] alloform.

Objectives: To assess the performance of a modified test to identify by FACS-analysis granulocyte-specific antibodies in the sera of neutropenic children.

Methods: We evaluated 120 children with a clinical suspicion of AIN, whose sera were analyzed by flow cytometry for the presence of autoantibodies using the indirect granulocyte immunofluorescence test. In contrast to the traditional tests, the sera were tested against randomly selected untyped neutrophils derived from a batch of 10 anonymous healthy subjects, presumably including the common HNA alloforms. Control sera samples were from patients with chemotherapy-induced, familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded.

Results: Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods.

Conclusions: The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective aiding tool for clinical decision making.

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: The prevalence of Parkinson's disease varies among ethnic and geographic groups around the world, being very low in China and high in Argentina. While the main etiology of the disease has yet to be determined, environmental, occupational and genetic factors seem to play important roles.

Objectives: To estimate the prevalence of PD in an Arab Muslim population in Israel, using the drug tracer approach.

Methods: We studied a Muslim Arab population living in a well-defined geographic area in Israel, with the majority located in two towns and two large villages. Of the approximately 115,000 residents, about 38% are under the age of 15 and 7.75% are older than 65. Drug tracer methodology was applied in this study. All those who were on anti-PD[1] medication were identified and examined by a neurologist to confirm the diagnosis.

Results: The overall crude prevalence of PD in this population was low, 43.24/100,000, while the prevalence in the age group above 65 years was 477.32/100,000. Below this age, the prevalence was very low, 12.29/100,000. PD prevalence was higher in males than in females (ratio 1.17); 63% of male patients smoked cigarettes. The prevalence was found to be twice as high among the residents of rural areas, where most inhabitants work in agriculture.

Conclusions: The prevalence of PD among the Arab population in Israel is considered low and comparable to that reported in other Arab countries.

Background: The incidence of congenital heart defects, reported to be 5–8/1000 in term infants, is not well established in very low birth weight infants.

Objectives: To establish the incidence of congenital heart defects in VLBW[1] infants in the neonatal intensive care unit of our institution.

Methods: A retrospective analysis of the population in the NICU[2] at our institution was performed. VLBW (BW ≤ 1500 g) infants born between 2001 and 2006 who survived more than 48 hours were included in the study. Infants with clinical signs of heart disease underwent echocardiography.

Results: During the study period 437 VLBW live-born infants met the inclusion criteria. Of these, 281 (64.3 %) underwent echocardiography. CHD[3] was detected in 19 infants (4.4%, 95% confidence interval 2.4–5.4%), significantly higher than the incidence of 5–8/1000 in the general population (P < 0.0001). In the subgroup of 154 infants with BW < 1000 g there were 10 (6.5%) with CHD. In the subgroup of 283 infants with BW 100–-1500 g there were 9 (3.2 %, P = 0.19 vs. VLBW) with CHD.

Conclusions:  Our observations show an increased incidence of CHD in VLBW neonates, as compared to the general population. Since not all infants underwent echocardiography, and minor cardiac defects may have been missed in our VLBW infants, the true incidence may be higher than reported here.

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: Parallel to increased life expectancy, the number of very elderly patients hospitalized in internal medicine departments is growing rapidly, although clinical data on hospital care are lacking.

Objectives: To investigate the sociodemographic data, hospitalization characteristics and outcomes of nonagenarian patients, as these measures are necessary for evaluating prognostic information and predictors of mortality.

Methods: We reviewed the medical records of all patients aged ≥ 90 hospitalized in our institute's Department of Internal Medicine. The data comprised 482 admissions of 333 patients hospitalized over a one year period.

Results: Half of the study patients were residents of nursing institutions. A high rate of atrial fibrillation was documented (106 patients, 32%). Acute infectious diseases constituted the leading diagnosis (276/482 admissions, 57%), followed by acute coronary syndrome (17% of admissions). In-hospital mortality occurred in 74 patients (22%). Chronic therapy with statins or acetylsalicylic acid was inversely related to mortality (P < 0.05). The main predictors for in-hospital death of nonagenarians were pressure sores, older age, atrial fibrillation, malignant disease, and admission due to an acute infection, especially Clostridium difficile-associated diseases. In addition, mental decline, permanent urinary catheter, leukocytosis, renal failure and hypoalbuminemia predicted post-discharge mortality. Admission due to an infectious disease but not acute coronary syndrome was significantly correlated to in-hospital and post-discharge mortality (P < 0.001).

Conclusions: Hospitalized nonagenarians comprise a growing group with distinct characteristics and increasing significance in the daily practice of internal medicine departments. Comprehensive assessment of the elderly at admission together with identification of the above clinical and laboratory risk factors for mortality will help determine in-hospital management, discharge planning and rehabilitation programs.

Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations. The consortium reviewed known lifestyle risk habits and genetic causes, screening methodologies used and available in Israel. Overall, there are about 600 new patients per year, with the highest incidence occurring in Jewish men of European birth (age-standardized rate 8.11/10⁵ for 2003–06). The 5 year survival is about 5%. The consortium concluded that screening will be based on endoscopic ultrasonography. Pancreatic cancer patients and families at risk will be enrolled, demographic and lifestyle data collected and a cancer pedigree generated. Risk factors will be identified and genetic tests performed as required. This concerted national program to identify persons at risk, recommend which environmental risk factors to avoid and treat, and perform endoscopic ultrasound and genetic screening where appropriate, might reduce their incidence of invasive pancreatic cancer and/or improve its prognosis