Israel Medical Association Journal

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: There are several treatment options for simple bone cysts, with treatment depending mainly on the experience and preference of the surgeon and the extension and location of the cyst.

Objectives: To assess our experience with the surgical treatment of bone cyst lesions in pediatric patients at one institution by the same group of surgeons.

Methods: The study group comprised 60 patients (43 boys, 17 girls) treated surgically for monostatic lesions between January 2002 and July 2007. The mean age at surgery was 11.8 years (range 4–17 years). Mean follow-up was 4.2 years. Most of the lesions were located at the proximal humerus. Patients were divided into five groups according to treatment method: a) corticosteroids (methylprednisolone 40-80 mg) (n=26); b) curettage and bone grafting (fibula or iliac crest) (n=16); c) aspiration of the bone cavity and subsequent bone marrow transplantation (n=10); d) internal preventive fixation using an elastic stable intramedullary nail (n=5); and e) curettage and implantation of a synthetic cancellous bone substitute (pure beta-tricalcium phosphate substitute, ChronOS®, Synthes, Switzerland) (n=3).

Results: Treatment success was evaluated by the Capanna criteria. Successful results were observed in 68% (18 complete healing, 23 healing with residual radiolucent areas), 30% recurrence rate, and no response to treatment in one patient (2%). We recorded recurrence in 50% of the children treated by corticosteroid injection, and one child did not respond to treatment.

Conclusions: The best results were achieved in children treated by curettage and the subsequent use of an osteoconductive material, and in children treated with elastic intramedullary nail fixation. Despite our limited experience with calcium-triphosphate bone substitute, the treatment was mostly successful. Because of the short follow-up, further observation and evaluation are necessary.

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: 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: Professional drivers have been found to be at high risk for developing low back pain. However, the exact reasons are poorly understood.

Objectives: To assess the prevalence of LBP[1] among Israeli professional urban bus drivers, and evaluate the association between LBP in drivers and work-related psychosocial and ergonomic risk factors.

Methods: A total of 384 male full-time urban bus drivers were consecutively enrolled to this cross-sectional study. Information on regular physical activity and work-related ergonomic and psychosocial stressing factors was collected during face-to-face interviews. The prevalence of LBP was assessed using the Standardized Nordic Questionnaire.

Results: From the total cohort, 164 bus drivers (45.4%) reported experiencing LBP in the previous 12 months. Ergonomic factors associated with LBP were uncomfortable seat (odds ratio 2.6, 95% confidence interval 1.4–5.0) and an uncomfortable back support (OR[2] 2.5, 95% CI[3] 1.4–4.5). In the group of drivers with LBP, 48.5% reported participation in regular physical activities vs. 67.3% in the group without LBP (P < 0.01). The following psychosocial stressing factors showed significant association with LBP: “limited rest period during a working day” (1.6, 1.0–2.6), “traffic congestion on the bus route” (1.8, 1.2–2.7), “lack of accessibility to the bus stop for the descending and ascending of passengers” (1.5, 1.0–1.5), and “passengers' hostility” (1.8, 1.1–2.9).

Conclusions: Work-related ergonomic and psychosocial factors showed a significant association with LBP in Israeli professional urban bus drivers. Prevention of work-related stress, organizational changes targeted to reduce stressful situations, improvement in seat comfort, and encouraging regular sports activity need to be evaluated as prevention strategies for LBP in professional bus drivers.

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: 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.