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: 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: Tuberculosis is the most common opportunistic infection among people infected with human immunodeficiency virus and its first cause of morbidity and mortality.

Objectives: To analyze the characteristics of a population in Israel with both tuberculosis disease and HIV[1] infection in order to identify factors that contribute to outcome.

Methods: The study group comprised patients hospitalized in the Pulmonary and Tuberculosis Department of Shmuel Harofeh Hospital during the period January 2000 to December 2006. They were located by a computer search in the hospital registry and the pertinent data were collected.

Results: During the study period 1059 cases of active tuberculosis disease were hospitalized; 93 of them were co-infected with HIV. Most of them came from endemic countries (61.2% from Ethiopia and 20.4% from the former Soviet Union; none of them was born in Israel). Ten percent of the cases were multiple-drug resistant and 32% showed extrapulmonary involvement. The response rate to the treatment was good, and the median hospitalization time was 70 days. The mortality rate was 3.2%.

Conclusions: Despite the high prevalence of pulmonary disease in our group, the short-term outcome was good and the Mycobacterium was highly sensitive to first-line drugs. These encouraging results can be attributed to the fact that tuberculosis patients in Israel are identified early and treated continuously and strictly, with early initiation of antiretroviral therapy, which ensures that the development of drug resistance is low.

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.