Israel Medical Association Journal

Objective: To establish the frequency of A. haemolyticum in throat cultures in a northern Israeli population and to estimate the clinical significance of this pathogen in patients with sore throat.

Methods: We examined suspected colonies for A. haemolyticum by gram stain, catalase test and reverse CAMP test in 518 throat cultures sent to the microbiologic laboratory of HaEmek Medical Center.

Results: Of the throat cultures tested, A. haemolyticum was recovered from one patient (0.2%). In contrast, group A Streptococcus (Streptococcus pyogenes) was recovered from 135 patients (26%).

Conclusion: A. hemolyticum is an uncommon pathogen implicated in acute pharyngitis, therefore routine screening in throat swabs is not required.

Background: During ingestible capsule endoscopy, video images are recorded throughout the device's natural propulsion through the digestive system. Shortening the transit time of the wireless video capsule through the stomach and small bowel could reduce the time needed to read and analyze the resultant images, utilize more effectively the short life of the capsule battery (7 ± 1 hours) and make it possible to image the entire small bowel.

Objective: To measure gastric and small bowel transit times, with and without preparation, using capsule endoscopy.

Methods: Capsule transit times through the stomach, small bowel and colon were evaluated by analysis of the videos generated during the capsule's passage. The study group included 62 patients with small and large bowel pathologies (e.g., iron deficiency anemia, Crohn's disease). The patients were divided into three groups: prepared with polyethylene glycol (Group A, n = 9), prepared with sodium phosphate (Group B, n = 13), and with no preparation (Group C, n = 40).

Results: The gastric emptying times were 20.4 ± 15.2 minutes in group A, 55.7 ± 45.1 in group B, and 48.3 ± 28.7 in group C (P = 0.01). The capsule produced views of the cecum in only 49 of the 62 patients. The mean small bowel transit time for these 49 patients was 238.8 ± 82.1 minutes, making the mean times for the groups (A,B,C) 148.9 ± 32.6, 289.4 ± 77.2 and 249.3 ± 73.9 minutes respectively (P = 0.0001).

Conclusion: Compared to both SP[1] and no preparation, preparation of the colon with PEG[2] significantly shortened the transit time of the capsule through the stomach and small bowel.

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or “homing receptors.” Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL[1] patients.

Methods: Expression of adhesion molecules belonging to different families was studied in CD19-positive cells isolated from the blood of 42 patients by dual color flow cytometry. The families included: immunoglobulin superfamily (CD54, CD58), integrin family (β1, β2 and β3 chains, CD11a, CD11c CD49d), selectin family (L-selectin), and lymphocyte homing receptor family (CD44).

Results: The average percentage of leukemic cells expressing CD11c in the 23 patients with stage II(S) was 25.7 compared with 13.2% in the 14 patients with stage 0 disease (P = 0.047). The average percentage of leukemic cells expressing CD44 in patients with stage II(S) was 90.5 compared with 77.2% in patients with stage 0 (P = 0.007) and 80% in patients with stages 0 and I together (n=19, P = 0.008). Other adhesion molecules tested did not show a statistically significance difference in expression between the different disease stages.

Conclusions: The higher expression of CD44 and CD11c in cells of CLL patients with predominantly splenic manifestations may account for the tendency of their lymphocytes to home to the spleen.

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent attacks of fever and serositis. The disease is caused by mutations in the MEFV gene, presumed to act as a down-regulator of inflammation within the polymorphonuclear cells.

Objectives: To present the results of 412 FMF patients genotyped for three MEFV mutations, M694V, V726A and E148Q.

Results: The most frequent mutation, M694V, was detected in 47% of the carrier chromosomes. This mutation, especially common among North African Jewish FMF[1] patients, was not found in any of the Ashkenazi (East European origin) patients. Overall, one of the three mutations was detected in 70% of the carrier chromosomes. M694V/M694V was the most common genotype (27%), followed by M694V/V726A (16%). The full genotype could be assessed in 57% of the patients, and one disease-causing mutation in an additional 26%. Only one patient with the E148Q/E148Q genotype was detected despite a high carrier rate for this mutation in the Jewish population, a finding consistent with a low penetrance of this genotype. The M694V/M694V genotype was observed in 15 patients with amyloidosis compared to 4 amyloidosis patients with other genotypes (P < 0.0001).

Conclusions: Because of low penetrance and as yet other undetermined reasons, mutation analysis of the most common MEFV mutations supports a clinical diagnosis in only about 60% of patients with definite FMF.

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Micronutrient deficiencies have reoccupied the center stage of public health policy with the realization that folic acid deficiency results in neural tube defects and possibly other birth defects as well as ischemic heart disease. These, in turn, have raised an older debate on food fortification policy for the elimination of iodine, iron and vitamin D deficiencies. Data from the First Israeli National Health and Nutrition Survey (MABAT 2000) provided an impetus to develop an active national nutrition policy aimed to improve the nutritional status of iodine, iron, vitamins A and D and B-vitamins, including folate. In this paper we examine some of the MND[1] issues in Israel and their implications for public health, and suggest options for the formulation of policy.

Background: Genes that confer mild or moderate susceptibility to breast cancer may be involved in the pathogenesis of sporadic breast cancer, modifying the phenotypic expression of mutant BRCA1/BRCA2 alleles. An attractive candidate is the insulin-like growth factor I, a known mitogen to mammary ductal cells in vivo and in vitro, whose serum levels were reportedly elevated in breast cancer patients.

Objective: To evaluate the contribution of the IGF-1 gene polymorphism to breast cancer risk by genotyping for a polymorphic allele size in breast cancer patients and controls.

Methods: We analyzed allele size distribution of the polymorphic CA repeat upstream of the IGF-I gene in 412 Israeli Jewish women: 268 women with breast cancer (212-sporadic and 56 carriers of either a BRCA1:or BRCA2 mutation), and 144 controls. Genotyping was accomplished by radioactive polymerase chain reaction of the relevant genomic region and size fractionation on polyacrylamide gels with subsequent auloradiography,

Results: Among women with breast cancer, with or without BRCA germline mutations, 196 and 198 basepair alleles were present in 4.7% (25/536 alleles), compared with 9% (26/288) controls (P = 0.02). This difference was more pronounced and significant in the non-Ashkenazi population. Conversely, the smaller size allele (176 bp) was present in the breast cancer group only {3/536, 0.6%).

Conclusions: The IGF-I polymorphism may serve as a marker for breast cancer risk in the general Jewish population, in particular non-Ashkenazi Jews, but extension and confirmation of these preliminary data are needed.
 

Background: One of the measures adopted in Israel since 1959 as part of the tuberculosis control program was screening children aged 12–13 years old. The screening comprised single-step tuberculin skin testing using the Mantoux method.

Objective: To assess the efficacy of tuberculin skin screening for TB[1] in schoolchildren in southwestern Israel as well as the compliance to treatment for latent tuberculosis infection.

Methods: We retrospectively reviewed the records of children in the Ashkelon region who underwent a tuberculin skin test during the period 1995–99.

Results: Of the 28,016 eligible children, 27,232 were tested. In 923 children, mostly from the former USSR and Ethiopia, an induration of 10 mm or more was found. Only 52 Israeli-born children tested positive. Tuberculosis was found in seven children with a positive test, five of whom were from Ethiopia. All children who tested positive were referred to the local TB clinic; only 266 children (28.8%) presented. Only 151 completed the recommended treatment of isoniazid for 6 months. Thus, although screening included most of the targeted children aged 13, only a third of them presented to a TB clinic, of whom only about half completed treatment of latent infection.

Conclusions: Our results indicate that the current policy of screening for latent TB in our region is ineffective in terms of implementation of the recommended treatment. We suggest that only high risk groups be screened, and that a concerted effort be made to implement treatment.

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Background: Low birth weight has been shown to be strongly related to hypertension in adult life.

Objective: To determine whether blood pressure is higher in children with intruterine growth retardation than in control subjects.

Methods: Blood pressure was measured in 58 children aged 4-6 years with IUGR and in 58 age-matched controls. The control children, whose birth weight was appropriate for gestational age, were also matched for gestational age.

Results: The children with IUGR had significantly higher mean values of systolic (p<0.05) and diastolic blood pressures (p<0.05) and mean arterial pressure (p<0.05). Significant differences in blood pressure values were found between preterm IUGR (n=21) and preterm controls (p<0.05).

Conclusion: These data indicate that children with IUGR may be at higher risk of hypertension already in childhood.

Background: Chickenpox is a highly contagious childhood infection caused by varicella zoster virus, a virus of the herpes family. Although a mild and self-limiting disease in otherwise healthy children, chickenpox can be a complicated and even life-threatening disease in adults, pregnant women and immunosuppressed individuals. Among infants whose mothers had varicella during the first trimester of pregnancy, 2-3% will develop a congenital VZV syndrome that includes a combination of scarring, limb deformation, central nervous system impairment and ocular injury. In 1974, a live attenuated virus vaccine against VZV was developed in Japan and has been thoroughly tested for safety, efficacy and long-term effects. In March 1995 the vaccine was licensed in the U.S. for use in healthy children only.

Objectives: To determine the rate of immunity to VZV in young Israeli adults.

Methods: On the assumption that a randomly picked sample of 18-year-old army recruits in Israel is representative of the general Jewish population, 900 sera samples were taken for 3 years (1985,1988,1992). The sera were analyzed for IgG to VZV with a commercial ELISA kit using microwells coated with VZV antigens.

Results: A total of 98% of the samples tested positive for VZV antibodies. The difference in serologic values between the recruitment years was not statistically significant.

Conclusion: The majority of the Israeli population reaches adulthood already immunized against VZV, with immigrants having slightly lower immunity rates. Nonetheless, a few dozen cases of chickenpox are diagnosed in the IDF annually. These data should be taken into account when a vaccination program is devised. Should such a program be implemented, it would be interesting to repeat the serosurvey for comparison. A shift in the peak occurrence age might necessitate the administration of a booster vaccine at an older age.

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VZV= varicella zoster virus

IDF= Israel Defense Forces

Background: The pathogenesis of neurological symptoms, the most common extraintestinal complication ofchildhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role.

Objectives: To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R.

Methods: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate.

Results: In our animal model of Shigella related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection.

Conclusions: Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.