Israel Medical Association Journal

Background: Familial Mediterranean fever is a genetic disorder manifested by recurrent attacks of peritonitis, pleuritis and arthritis, and characterized by clinical, histological and laboratory evidence for localized and systemic inflammation. Colchicine treatment usually prevents the attacks and the associated inflammation. Inflammation of atherosclerosis and ischemic heart disease.

Objective: To study the effect of inflammation and its prevention on occurrence of IHD, using FMF as a model.

Methods and Patients: We studied the presence of IHD and its risk factors in 290 FMF patients aged 40 years or more, and in two control groups – 233 spouses of the FMF patients’ and 126 patients with inflammatory diseases obtained from other outpatient clinics. FMF patients were also compared with age and gender-matched individuals from the population reference data of the Israel Ministry of Health.

Results: The prevalence of IHD in FMF patients was significantly lower than in the group of controls from other outpatient clinics (15.5% vs. 30.2% P< 0.05) and comparable with their spouses (11.2%) and with the matched general population in Israel (16%).

Conclusion: These findings suggest that despite the evidence of recurrent inflammation, colchicines-treated FMF patients are not more predisposed to IHD than the normal population.

Objective: To evaluate the feasibility of using combined clinical and histomorphometric features to construct a prognostic score for the individual patient with localized renal cell carcinoma.

Patients and Methods: We studied 39 patients with pT1 and pT2 RCC who underwent radical nephrectomy between 1974 and 1983. Univariate and multivariate analyses were used to determine the association between various prognostic features and patient survival.

Results: The most important and independent predictors of survival were tumor angiogenesis (P=0.009), nuclear DNA ploidy (P=0.0071), mean nuclear area (P=0.013), and mean elongation factor (P=0.0346). Combination of these variables enabled prediction of outcome for the individual patient at a sensitivity and specificity of 78% and 89% respectively.

Conclusion: Our results indicate that no single parameter can accurately predict the outcome for patients with localized RCC. Combination of neovascularity, DNA content and morphometric shape descriptors enabled a more precise stratification of the patients into different risk categories.
 

Objective: To investigate whether cigarette smoking has an additive effect on the clinical presentation and course of disease in Helicobacter pylori-positive dyspeptic patients.

Patients and Methods: The study group comprised 596 consecutive H. pylori-positive dyspeptic patients (334 males and 262 females, mean age 50.6, range 12--81 years). Following upper gastrointestinal endoscopy, patients were subdivided by diagnosis as follows: Non-ulcer patient group (n=312: gastritis 193, duodenitis 119), gastric ulcer (n=19), and duodenal ulcer (n=265). H. pylori infection was confirmed by histology and/or rapid urease test. In addition, 244 patients had a positive 14C-urea breath test prior to antimicrobial treatment. The patients' medical history and smoking habits were obtained using a detailed questionnaire completed by the patients and their referring physicians.

Results: There were 337 non-smoking patients, 148 current smokers and 111 past smokers. Gastric and duodenal ulcers were significantly less prevalent in non-smokers than in current or past smokers (gastric 1.8%, 4.1%, 6.3%; duodenal 39.8%, 50%, 51.4%, respectively) (P0.05). The incidence of gastrointestinal bleeding was significantly lower in non-smokers than in current or past smokers (7.1%, 8.1% and 20.7%, respectively) (P0.05). Bacterial density, as assessed by the UBT value in 244 patients, was higher in non-smokers (mean 352.3273 units) than in past smokers (mean 320.8199) or current-smokers (mean 229.9162) (P0.05). Logistic regression analysis revealed that male gender, current smoking, and immigration from developing countries were all significant independent risks for developing duodenal ulcer, while only past smoking was associated with a higher rate of upper gastrointestinal bleeding in the past.

Conclusions: In H. pylori-positive dyspeptic patients, current smoking as well as male gender and immigration from developing countries are associated with an increased risk for duodenal ulcer. This effect does not seem to be related to the bacterial density or increased urease activity of H. pylori organisms.

Background: Tumor necrosis factor is associated with various local and systemic inflammatory sequelae following snakebite. Xanthine oxidase is a principal mediator of remote tissue injury (e.g., lungs, heart, liver).

Objective: To investigate in a snakebite-like animal model the as yet unexplored role of TNF and XO in mediating organ damage following snakebite.

Methods: Sprague-Dawley rats were injected intramuscularly with a non-lethal 500 g/kg dose of Vipera aspis venom (n=10) or saline (n=10). Blood pressure and heart rate were continuously monitored, TNF- was measured in the blood, and total XO + xanthine dehydrogenase activity was assessed in various tissues. Lung histology and permeability indices were analyzed.

Results: Venom injection caused a significant (P0.05) reduction in both heart rate and invasive arterial pressure. The blood circulating TNF levels were significantly higher in the intoxicated group (P0.05 vs. saline group), with changes seen at 30 minutes from intoxication in both groups. Total XO + XDH activity in the kidney, lung and liver of the venom-injected group was significantly (P0.05) higher than in the saline group, while the activity in the heart was similar.

Conclusions: The mediation of remote organ and hemodynamic changes following intramuscular injection of a non-lethal dose of Vipera aspis venom can be attributed partly to TNF and partly to XO. More research is needed to better understand the role of either compound and the time frame of their activity before specific antagonists can be introduced for snakebite management.
 

Background: The degree to which serum total cholesterol predicts cariovascular disease is uncertain. While most authors have placed TC among the most powerful risk indicators of CVD, some have claimed that it predicted CVD in women only, or even not at all.

Objective: To determine the predictive value of serum total cholesterol relative to diabetes, smoking, systolic blood pressure and body mass index (kg/m2), for cardiovascular disease mortality in 3,461 occupationally active Israeli males.

Methods: A prospective follow-up was carried out for the years 1987-1998 to determine the effect of age, smoking habits, a history of diabetes, SBP, BMI and TC, at entry, on CVD mortality.

Results: There were 84 CVD deaths during a total of 37,174 person-years follow up. The hazard ratios (95% confidence intervals) for CVD mortality with respect to variables at entry were: diabetes 5.2 (2.1-13.2), age 2.2 (1.7-2.9), smoking 1.3 (1.0-1.8), SBP 1.4 (1.1-2.0), TC 1.5 (1.0-2.1) and BMI 1.2 (0.7-2.2). Among non-obese, non-diabetic, normotensive subjects the hazard ratio of TC adjusted for age and smoking was 1.16 (1.09-1.22) per 10 mg/dl. In the remaining subjects it was 1.04 (0.98-1.12) only. There was a significant interaction between TC and diabetes, hypertension or obesity (P=0.003).

Conclusions: In this population of Israeli males we found an interaction between TC and other risk indicators for CVD. Confirmation is required for the unexpected finding that the predictive value of TC for CVD mortality among non-diabetic, non-obese and normotensive subjects exceeded that among subjects with either of these risk factors.
 

Background: Data regarding the epidemiology of secondary pulmonary hypertension are scanty.

Objectives: To describe the spectrum and relative incidence of background diseases in patients with significant secondary PHT.

Methods: We identified 671 patients with systolic pulmonary artery pressure of 45 mm Hg or more from the database of the echocardiographic laboratory. Their background diseases were recorded and classified into three subgroups: cardiac, pulmonary and pulmonary vascular disease without pulmonary parenchymal disease. Age at the first echocardiographic study, gender and systolic PAP values were recorded. Data between the three subgroups were compared.

Results: The mean age of the patients was 6515 years, mean systolic PAP 6114 mm Hg and female:male ratio 1.21:1. At the time of diagnosis 85% of the patients were older than 50. PHT was secondary to cardiac disease in 579 patients (86.3%), to PVD without PPD in 54 patients (8%) and to PPD in only 38 patients (5.7%). Mean age and mean systolic PAP did not differ significantly among the three subgroups. There was a significantly higher female: male ratio in patients with PVD without PPD compared with cardiac or pulmonary diseases (1.7:1 vs. 1.2:1 and 1.7 vs. 0.8:1 respectively, P0.05).

Conclusions: The majority of patients with significant PHT are elderly with heart disease. PVD without PPD and chronic PPD are a relatively uncommon cause of significant PHT. Since the diagnosis of PHT is of clinical significance and sometimes merits different therapeutic interventions, we recommend screening by Doppler echocardiography for patients with high risk background diseases.

Background: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases.

Objectives: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel.

Methods: We examined the G380R mutation (G>A and G>C transition) and the mutation G375C (G>T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia.

Results: We found the G>A transition at codon 380 in 30 of our patients and the G>C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia.

Conclusions: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

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FGFR3 = fibroblast growth factor receptor 3