Israel Medical Association Journal

The screening program in Israel for Tay-Sachs disease has proven very successful, giving Jewish couples a choice not to have affected children. The technology of carrier detection is now possible in several other severe genetic diseases that are relatively frequent among Jews. Due to the current confusion, a policy is needed to determine how the TSD screening program should be continued in the Israeli Jewish population. We propose that such a screening program include only mutations agreed by consensus as causing a disease severe enough to warrant the possibility of therapeutic abortion. We also propose that general screening include only mutations that are relatively frequent, taking into account the carrier frequencies in the Israeli Jewish population.

Background: Many medications used for children have not undergone evaluation to assure acceptable standards for optimal dose, safety and efficacy. As a result, the majority of children admitted to hospital wards receive medications outside the terms of their license (off-label) or medications that are not specifically licensed for use in children (unlicensed). The extent of unlicensed and off-label medication use in ambulatory children is unknown.

Objective: To determine the extent of unlicensed and off-label medication use in a general pediatrics ambulatory hospital unit in Israel.

Patients and Methods: We conducted a retrospective analysis of the medical records of 132 outpatient children treated in the General Pediatrics Ambulatory Unit of the Soroka Medical Center, Beer Sheva, in November–December 1998.

Results: The children’s ages ranged from 1 month to 18 years (mean ± SD 50±58 months). Of the 222 prescriptions given to these children, one-third were unlicensed (8%) or unlabeled (26%). Different dose and age were the most common categories of off-label medication use. All 18 cases of unlicensed use were due to modifica-tion of licensed drugs (tablets were crushed to prepare suspensions). Altogether, 42% of children received medicines that were off-label and/or unlicensed.

Conclusions: More off-label than unlicensed medications were used. Further investigations are required to establish the extent of unproved drug use in both hospitalized and ambulatory pediatric patients in Israel. Recommendations recently issued by the Ministry of Health’s National Council for Child Health and Pediatrics constitute a first step in the Israeli contribution to the international effort demanding testing of medications for children.

Background: A previous study on Hodgkin's lymphoma in southern Israel found that Bedouin patients had an increased rate of Epstein-Barr virus expression in their tumor cells.

Objectives: To determine the influence of the patients' communities on the pattern of disease in HL.

Methods: We compared the clinical features, demographic data, stage at diagnosis, treatment modality and outcome, as well as laboratory findings, in four community-based subgroups. These groups comprised kibbutz residents (n=11), Bedouin (n=19), new immigrants from the former USSR (n=22), and town-dwellers (n=82).

Results: The Bedouin patients differed significantly from the new immigrants and town-dwellers, particularly regarding the rate of EBV sequences in the tumor tissues, and a poorer response to treatment. The kibbutz patients did not differ significantly from the other populations regarding most of the parameters studied, but showed an intermediate expression of EBV antigens compared to Bedouin patients and the rest of the cohort.

Conclusions: This study indicates that HL may behave differently in different population groups in a given geographic area. Notably, the Bedouin patients showed markedly different clinical and biological patterns of this malignancy. 

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HL= Hodgkin's lymphoma

EBV= Epstein-Barr virus

Background: The reasons that patients consult the clinic physician for common minor symptoms are not clearly defined. For seasonal epidemic events such as flu-like symptoms this characterization is relevant.

Objectives: To identify the factors that prompt patients to seek medical attention, and correlate patient behavior with different demographic and disease variables.

Methods: A random sample of 2,000 enrolled people aged 18–65 years and registered with eight primary care clinics located throughout Israel were asked to report whether they had had flu-like symptoms within the previous 3 months.  Those who responded affirmatively (n=346) were requested to complete an ad hoc questionnaire evaluating their treatment-seeking behavior.

Results: A total of 318 patients completed the questionnaire (92% response rate), of whom 271 (85%) consulted a physician and 47 (15%) did not. Those who sought medical assistance had more serious symptoms as perceived by them (cough, headache and arthralgia) (P<0.05), and their main reason for visiting the doctor was “to rule out serious disease.”  Self-employed patients were more likely than salaried workers to visit the clinic to rule out serious disease (rather than to obtain a prescription or sick note or to reassure family). They also delayed longer before seeking treatment (P=0.01).

Conclusion: In our study the majority of individuals with flu symptoms tended to consult a physician, though there were significant variations in the reasons for doing so, based on a combination of sociodemographic variables. We believe these findings will help primary care physicians to characterize their practices and to program the expected demand of flu-like symptoms.

Background: Previous studies have suggested that prolactin may serve as an indicator of disease progression in breast cancer.

Objectives: To evaluate the use of PRL as a serum tumor marker in patients with breast cancer.

Methods: PRL serum level was determined in 99 breast cancer patients and compared with CA 15-3 serum level.

Results: Elevated serum level of PRL (>20 ng/ml) was found in 8 of 99 patients (8.1%). A stratified analysis of prolactin levels according to therapy revealed that PRL levels was increased in 8 of 55 untreated patients (14.5%), but not in patients who received hormonal or chemotherapy in the 3 months preceding the test (0/42 patients, P=0.009). However, mean PRL level was similar in patients with no evidence of disease activity and in patients with active disease (10.2 vs. 8.2 ng/ml, NS). In comparison, CA 15-3 mean level was significantly lower in patients with no evidence of disease as compared to patients with active disease (18.2 vs. 144.7 units/ml, P<0.001). PRL level was increased in 6 of 60 patients (10%) with no evidence of disease and in 2 of 39 (5.2%) with active disease (NS). In comparison, CA 15-3 level was increased in 3 of 60 patients (5%) with no evidence of disease and in 24 of 39 (61.5%) with active disease (P<0.001).

Conclusions: PRL levels are decreased following hormonal or chemotherapy in patients with breast cancer and there is no correlation between PRL serum level and the state of disease. Further studies are needed to clarify a possible clinical significance of hyperprolactinemia in a subset of patients with breast cancer.

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PRL = prolactin

Background: Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins.

Objectives: To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease.

Methods: Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera.  Cutoff values for the test were performed using logistic regression and receiver operating curves analysis.

Results: An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18±0.19 optical density for controls, and 1.65±1.14 for patients with celiac disease (P<0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively.

Conclusions: A tissue transglutaminase-based ELISA test is both sensitive and specific for  detection of celiac disease.

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AEA = anti-endomysial antibody

Background: According to studies from different countries, the prevalence of natural rubber latex sensitization in healthcare workers ranges from 2.9 to 17%.

Objective: To estimate the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel.

Methods: Three hundred healthcare workers, mostly from a major pediatric tertiary care facility, and 15 non-healthcare workers completed a questionnaire on signs and symptoms of NRL allergy and other respiratory and food allergies. NRL-specific IgE antibodies were assayed with the DPC AlaSTAT-ELISA method.

Results: Seventy of the 300 workers (23.3%) reported symptoms of NRL allergy: hand eczema and pruritus in 63, upper respiratory tract and ocular symptoms in 10, shortness of breath in 2, and generalized rash in 6. None had anaphylaxis due to latex exposure. There was a significant correlation of symptoms of NRL allergy with atopy and job category (nurses, laboratory technicians, nurse assistants and dental medicine workers), but not with gender, age, or years of employment. The in vitro tests for specific IgE antibodies against NRL were positive (≥0.70 IU/ml) in five workers (1.66%).

Conclusions: This is the first study of the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel. Our 1.66% sensitization rate is much lower than that reported for healthcare workers in other countries. This difference may be due to our inclusion of a study population with a relatively low exposure to latex gloves (pediatricians compared to surgeons). Further studies are needed in this and other high risk populations in Israel.  

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NRL = natural rubber latex

Objective: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy.

Methods: We retrospectively studied 51 patients (34 males, 17 females), aged 2–18 years, from several medical centers in Israel.

Results: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3–6 MU/m²). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P<0.05).

Conclusions: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B. 

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HBV = hepatitis B virus

IFN = interferon

HBeAg = hepatitis B e antigen

Background: There is an increasing number of reports of pertussis among older children and adults. The development and licensure of an acellular pertussis vaccine offer the possibility of adult vaccination against the disease. Information on immunity to pertussis in this age group is needed before any vaccination policy can be considered.

Objectives: To study the seroepidemiology of pertussis antibodies in a random sample of adolescents.

Methods: Serum IgG antibodies to whole-cell lysate of Bordetella pertussis were measured by enzyme-linked immunosorbent assay in sera of 533 Israeli military recruits aged 17–18 years. Epidemiologic variables were collected by a questionnaire and analyzed for correlation with pertussis antibodies.  

Results: Of the sera tested 58.6% were positive for pertussis IgG antibodies, while 35.4% were negative and 6% were borderline. The seropositivity rate was significantly higher among females and non-smokers than among males and smokers. Serum samples of subjects found negative to Bordetella pertussis on recruitment were tested again, using the same ELISA assay, 2–3 years later.  Seroconversion during the 3 year military service was detected in 12.5% of 40 subjects. Using the pertussis toxin as the antigen in a subsample of 160 sera, the seroprevalence was lower than that detected by the whole-cell lysate on the same sera (45% vs. 58%).

Conclusions: A significant part of the adolescent population in Israel has low titer of serum IgG antibodies to the multiple antigens of B. pertussis. The relatively low concentration of anti-pertussis antibodies, together with the serological evidence of exposure to the disease indicates that booster immunization with the acellular pertussis vaccine of military recruits should be considered after more information on the incidence of clinical cases of pertussis will be available.

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ELISA = enzyme-linked immunosorbent assay

Background: The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial.  

Objectives: To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency.  

Methods: Logistic regression models were formulated to predict successful outcome.  

Results: Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level.

Conclusions: Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide useful guidelines for counseling women with preexisting renal disease about their prospects for a successful pregnancy in terms of immediate and long-term maternal and neonatal outcome.
 

Methods: We attempted to investigate plasma oxidation and plasma and erythrocyte glutathione and glutathione enzymes in 20 patients with NIDDM, compared with euglycemic matched controls. Plasma oxidation was analyzed both basally (without) and as induced by 2,2'-azobis,2-amidopropane hydrochloride measured by the generation of thiobarbituric acid reactive substances and lipid peroxides.

Results: There was a significant increase in oxidation both basally (without) and as induced by AAPH. Plasma glutathione was lowered by 50% (P<0.01) and erythrocyte glutathione peroxidase, glutathione s-transferase and glutathione reductase activities were lower by 30%, 27% and 46%, respectively (P<0.01) in the patients with NIDDM.

Conclusions: Confronted by increased oxidation, patients with NIDDM show an abnormal plasma and erythrocyte antioxidative capacity, which may result in an accelerated rate of complications.

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NIDOM= non-insulin-dependent diabetes mellitus

Objectives: To present a case series of foyr patients with phenytion-induced severe CDRs, including toxic epidermal necrolysis (2 patients), exanthematous eruption (1 patient) and hypersensitivity syndrome (1 patient). In all patients the reactions appeared following the combined intake of phenytion, corticosteroids and H2 blockers.

Conclusions: Our case series may imply the role of drug interactions between phenytion, corticosteroids and H2 blockers in the induction of severe CDRs.