Israel Medical Association Journal

Background: In trials comparing different formulations of measles vaccine, excess non-specific mortality occurred in female children who received high titer vaccine. These findings suggest a gender-specific effect of measles vaccine.

Objectives: To determine whether gender differences exist in the rates of adverse reactions and morbidity in the month following immunization with measles-containing vaccine, and to evaluate whether there is a gender-specific association between the humoral immune response to measles vaccination and post-vaccination morbidity.

Methods: Parents completed questionnaires on the health status of 755 infants aged 15-20 months, during the month preceding and the month following the measles-mumps-rubella vaccination. Blood samples were tested for measles antibody titers in a subsample of 237 infants.

Results: After controlling background morbidity in the infants, the relative risk of fever and rash following vaccination was 2.35 in females and 1.36 in males. The geometric mean antibody titers against measles were similar in both sexes and there was no significant association between antibody titer and post-vaccination morbidity in either sex.

Conclusions: Our findings demonstrate higher rates of adverse effects in females following vaccination with MMR vaccine, irrespective of the humoral response. This study emphasizes the need to consider possible gender differences when evaluating new vaccines.

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MMR= measles-mumps-rubella

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.
 

Background: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown.

Objectives: To study the effect of cisapride on TPN-induced cholestasis in a rat model.

Methods: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups.

At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct.

Results: At the end of the third hour, TPN caused a significant reduction in bile flow (P<0.02) and bile salt secretion rate (P<0.001) (61.24 vs. 50.74 µl/min/kg, and 1.173 vs. 0.799 µmol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN.

Conclusions: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

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TPN= total parenteral nutrition
 

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: Extensive cleaning of homes in Israel before Passover may result in increased exposure of children to cleaning substances.

Objectives: To evaluate the potential danger of Passover cleaning to children, and to study the risk factors in order to identify areas for prevention.

Methods: All cases of poison exposure in Jewish and Arab children under the age of 15 years reported to the Israel Poison Information Center during 1990–95 (n= 5,583) were analyzed for the 6 weeks before and 6 weeks after Passover. Poison exposures in Jewish children <15 years old were studied in seven pediatric emergency rooms for the 2 weeks before and 6 weeks after Passover (n=123).

Results: The IPIC data showed a highly significant 38% increase in the average weekly poison exposure rate for the 2 weeks before Passover compared with the remaining 10 weeks.  Data recorded by the pediatric emergency rooms showed a twofold increase in cleaning substance poisoning during the 2 weeks before Passover compared with the following 6 weeks. The rise in exposures to cleaning substances was observed among children from secular, religious and ultra-orthodox families. In these exposures, the substance was found in open containers in 70% of cases. 

Conclusions: The extensive cleaning of homes among Jewish families in preparation for Passover poses the danger to young children of cleaning substance poisoning. Increasing public awareness, closer observation of children, and keeping these substances in closed containers should increase children’s safety during this annual cleaning.    

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IPIC = Israel Poison Information Center

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

Background: Streptococcal pharyngotonsillitis remains a common illness in children and can lead to serious complications if left untreated.

Objective: To evaluate the diagnostic and management approach of a sample of primary care physicians in the largest sick fund in Israel to streptococcal pharyngotonsillitis in children.

Methods: A questionnaire was mailed to all physicians who treat children and are employed by the General Health Services (Kupat Holim Klalit) in the Jerusalem District. The questionnaire included data on demographics, practice type and size, and availability of throat culture and rapid strep test; as well as a description of three hypothetical cases followed by questions relating to their diagnosis and treatment.

Results: Of the 188 eligible physicians, 118 (62.5%) responded, including 65 of 89 pediatricians (73%) and 53 of 99 family and general practitioners (53.5%). Fifty-six physicians (47.4%) had more than 18 years experience, and 82 (70%) completed specialization in Israel.  Mean practice size was 950 patients. Fifty-three physicians (43%) worked in Kupat Holim community clinics, 25 (21%) worked independently in private clinics, and 40 (34%) did both. A total of 91 (77%) had access to laboratory facilities for daily throat culture. The time it took for the results to arrive was 48 to 72 hours.  For the three clinical scenarios, 90% of the physicians accurately evaluated case A, a 1-year-old with viral pharyngotonsillitis, and 100 (85%) correctly diagnosed case C, a 7-year-old with streptococcal infection.  As expected, opinions were divided on case B, a 3-year-old child with uncertain diagnosis.  Accordingly, 75 (65.3%) physicians did not recommend treatment for case A, compared to 109 (92.5%) for case C.  For case B, 22 (19%) said they would always treat, 43 (36%) would sometimes treat, and 35 (30%) would await the result of the throat culture.  For 104 (88%) physicians the antibiotic of choice for case C was penicillin, while only 9 (7.5%) chose amoxicillin. However, the recommended dosage regimens varied from 250 to 500 mg per dose, and from two to four doses daily.  For case C, 110 physicians (93%) chose a 10 day duration of treatment.

Conclusions: The primary care physicians in the sample (pediatricians, general practitioners and family physicians) accurately diagnosed viral and streptococcal pharyngotonsillitis. However, there was a lack of uniformity regarding its management in general, and the dosage regimen for penicillin in particular.
 

Background: Protruding aortic atheromas are a potential source of stroke and systemic emboli. The single modality currently available for their detection has been transesophageal echocardiography. However, TEE does not allow full visualization of the upper part of the ascending aorta and proximal aortic arch.

Objectives: To investigate whether double helical computerized tomography- both with and without contrast injection - may represent a useful technique for noninvasive detection of PAA in stroke patients.

Methods: Forty consecutive patients ≥50 years of age who sustained a recent ischemic stroke and/or systemic emboli (within 15 days after the onset of the event) were enrolled in the study and underwent TEE and DHCT without contrast injection using thin slice acquisition (3.2 mm thickness and 1.5 mm reconstruction increment). In addition, the last eight consecutive patients, after obtaining an unenhanced scan, underwent a contrast-enhanced DHCT following peripheral intravenous injection of a small amount of contrast material (15 ml of diatrizoate).

Results: PAAs were demonstrated by TEE in 18 patients (45%); in 16 of them (89%) the atheromas were recognized by DHCT. Of the 22 patients without PAA on TEE, DHCT confirmed their absence in 18 (82%). DHCT yielded a sensitivity of 89%, a specificity of 82%, and an overall accuracy of 85%. The total number of protruding plaques detected by TEE was 43, of which 41 (95%) were correctly identified by DHCT. The mean thickness of the plaques was 5.6±2.4 mm on TEE, and 5.4±2.3 on DHCT (P=NS), with a good correlation between the modalities (γ=0.84). Contrast-enhanced DHCT scans demonstrated absolute equivalence to TEE in aortic areas defined as "clearly visualized by TEE." DHCT detected PAA between the distal ascending aorta and the proximal arch in seven patients; these atheromas were not included in the comparative analysis. In these "occult" areas, DHCT may be superior to TEE.

Conclusions: DHCT without contrast injection using thin slice acquisition may become a useful modality for rapid noninvasive detection of PAA. Contrast-enhanced DHCT scans significantly improve imaging quality and may be superior to TEE in the upper ascending aorta and the proximal arch (areas not well visualized by TEE).

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TEE= transesophgeal echocardiography

PAA= protruding aortic atheroma

DHCT= dual helical computerized tomography
 

Background: Previous studies have published controversial results regarding a connection between Helicobacter pylori infection and colorectal cancer. One possible mechanism is increased gastrin secretion in subjects infected with H. pylori, insofar as gastrin is known to be a trophic factor for the colonic mucosa.

Objectives: To investigate a possible role of gastrin secretion in H. pylori infection associated with colorectal cancer, and determine whether H. pylori infection is a factor in this disease.

Methods: The serum gastrin levels and the presence of H. pylori IgG antibodies were measured in 51 colorectal cancer patients and 51 control subjects. The cancer patients were also tested for carcinoembryonic antigen and CA 19-9.

Results: H. pylori IgG antibodies were found in the serum of 41 (80.4%) of the cancer patients compared to 32 (62.7%) of the control subjects (P=0.05). A significant correlation was found between CA 19-9 (γ=0.3432, n=49, P=0.01) and seropositive H. pylori IgG antibodies in the serum of the cancer patients (odds ratio 2.43, and 95% confidence limit 0.99-5.95), but none between CEA and H. pylori IgG antibodies nor between the serum gastrin level and the presence of colorectal cancer.

Conclusions: The results of this study indicate a significant association between seropositive H. pylori IgG antibodies and elevated CA 19-9 in colorectal cancer patients, but no correlation between the serum gastrin level and the presence of this cancer. H. pylori seropositivity is more prevalent in patients with colorectal cancer.
 

Objectives: To evaluate the diagnostic yield of gastroscopy, colonoscopy and fecal occult blood testing of hospitalized IDA patients, plus follow-up.

Methods: IDA was defined as hemoglobin <12.5 g/dl (men) and 11 g/dl (women), and serum iron <50 g/dl. The study group comprised 90 patients (42% male) with a mean age of 65±15 years and mean Hb 8.1 g/dl.

Results: Gastroscopy and colonoscopy revealed a bleeding source in 28.8% and 14.4% respectively. Gastrointestinal symptoms were found in 23% of patients with diseases of the upper gastrointestinal tract and in 15.3% of the lower. The sensitivity of fecal occult blood tests in detecting lesions in the lower and upper GI tracts was 100% and 30.7% respectively. Forty-four patients (48.9%) were discharged from the hospital with IDA of unknown origin. Over the following year, 20 of the 44 patients required further hospitalization, and of these, 13 were found to have anemia. Of the remaining 24 patients who were not hospitalized again, 15 had anemia. Four patients (9%) had significant gastrointestinal lesions and two died during the follow-up.

Conclusions: Fecal occult blood is a sensitive examination for lower but not for upper GI tract lesions.

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IDA= iron deficiency anemia

Objective: To evaluate the contribution of computerized tomography to the diagnosis of Takayasu's arteritis.

Methods: A retrospective analysis of the diagnostic process was recently conducted in three consecutive patients diagnosed over the last 3 years.

Results: Three females of Arab origin with Takayasu's arteritis were recently identified by CT. In two of the three patients the imaging procedure was performed for different working hypotheses, and the radiological findings (wall thickening, perivascular edema, and segmental intraluminal obliteration of the aorta and its major branches) were unexpected. In these two patients, repeated physical examination following the imaging procedure disclosed initially missed findings that could have led to an earlier consideration of Takayasu's arteritis (bruits above the epigastrium, subclavian and carotid arteries, and absent brachial pulses). Retrospective analysis of the patients' symptoms following CT revealed the true nature of the patients' misinterpreted complaints (e.g., typical abdominal angina replaced a faulty obtained history compatible with renal colic or dyspepsia). In the third patient CT was performed for the evaluation of an epigastric bruit associated with constitutional complaints. The diagnosis of aortitis, based upon the presence of diffuse aortic wall thickening and edema of the surrounding fat, without intraluminal narrowing, could have been missed by angiography, the traditional "gold standard" diagnostic procedure. All three patients complained of ill-defined epigastric abdominal pain and had epigastric tenderness during examination.

Conclusions: CT has the potential for detecting Takayasu's disease and may be superior to angiography, particularly at the early non-obliterative stage. Since the diagnosis of Takayasu's disease is rarely considered, the expanding use of CT and MRI technologies may reveal missed cases that are evaluated for other plausible diagnoses. The true incidence of Takayasu's arteritis in Israel may be much higher than reported, particularly in the Arab population. Our findings suggest that epigastric tenderness, originating from active inflammatory reaction in the abdominal aortic wall, should be considered as a diagnostic criterion of Takayasu's aortitis.