Israel Medical Association Journal

Background: It has been argued that arginine replacement in locus16 (Arg16) of ß₂ adrenergic receptor with glycin (Gly16) increases asthma severity, while glutamin replacement in locus 27 (Gln27) with glutamic acid (Glu27) decreases it. In addition, ethnic dependency of these polymorphisms has been described, but few studies investigated its relation to asthma severity in a non-anglosaxic population.

Objectives: To investigate non-anglosaxic ethnic influences on ß₂AR[1] polymorphisms and its correlations to asthma severity.

Methods: Sixty-six Israeli Jewish and Arab asthmatics who had near-fatal asthma and/or severe nocturnal asthma and/or steroid-dependency were investigated for genetic polymorphisms of ß₂AR and compared to matched controls. The Jewish patients included both Ashkenazi (of East European origin) and non-Ashkenazi (originating from the Middle East or North Africa). The results were compared with those of ethnically matched 113 non-asthmatic Israelis, and of non-asthmatic Anglo-Saxons described in the literature.

Results: We found no significant genetic differences between the asthmatics and their controls or between the various ethnic groups of our population. However, the prevalence of Glu27 was significantly lower in non-asthmatic Israelis compared to non-asthmatic Anglo-Saxons.

Conclusions: The genetic distribution of ß₂AR polymorphisms in severe Israeli asthmatics is not different from that of non-asthmatic Israelis and therefore its clinical impact on asthma is probably minimal.

Background: In lipid oxidation kinetics studies, prevalent cardiovascular disease has been associated with shortened lag phase, the length of time preceding the onset of oxidation.

Objectives: To examine, in vitro, copper-induced lipid oxidation kinetics in unfractionated serum from hemodialysis patients and to determine differences in kinetic parameters between patients with and without a history of CVD[1].

Methods: Of the 76 patients enrolled in a study of oxidative stress in hemodialysis (44/76 with prevalent CVD, 53/76 males), 9 males with a history of myocardial infarction were selected and matched for age, diabetes and smoking status with 9 males from the non-CVD group. The kinetics of lipid oxidation was studied. Blood chemistry determinations including serum lipids, lipoproteins, hemostatic factors and serum malondialdehyde were obtained. Variables were compared using the t-test for independent samples with history of MI[2] entered as the categorical variable.

Results: Tmax, the oxidation kinetic parameter defined as the time at which the rate of absorbing product accumulation was maximal, was significantly shorter in dialysis patients with a history of MI than in those without (115.2 ± 38.5 vs. 162.7 ± 48.9 minutes, P = 0.04). Further, Tmax and MDA[3] were negatively correlated to one another (r = -0.47, P = 0.04). Odds ratios indicate that each 1 minute increase in Tmax was associated with a 3% decrease in odds that a subject had a history of MI.

Conclusions: These findings indicate the presence of increased oxidative stress in hemodialysis patients with a history of MI.

Background: The Israeli Blood Pressure Control program was initiated to enhance the control of modifiable risk factors among high risk hypertensive patients followed by general practitioners in Israel.

Objective: To report the baseline results of the state of the treatment regarding blood pressure management, lipid and glucose control as well as obesity and smoking cessation among the patients.

Methods: Hypertensive patients were screened in 30 general practice clinics supervised by family medicine specialists seeing 1,000–5,000 patients each. Between 50 and 250 hypertensive patients were diagnosed at each participating clinic. Blood pressure levels, body mass index, lipid and glucose levels, as well as target organ damage and medications were recorded for all patients.

Results: Of the 4,948 patients registered, 2,079 were males (42%). Mean age was 64.8 ± 12. Blood pressure control was achieved in only 33.1% of total hypertensive patients. Low density lipoprotein control was achieved in 31.1% of all patients, and glucose control in only 28.5%% of diabetic patients (glucose < 126 mg/dl); 20.7% of the diabetics had glucose levels above 200 mg/dl. In this group of patients 38.9% were obese (BMI[1] >30 kg/m²). While there were more obese females than males (48.0% vs. 35.6%), no difference was found in blood pressure, lipid or glucose control between the genders.

Conclusion: Risk factor management of hypertensive patients attending general practice clinics in Israel is not optimal, especially among those with diabetes or in need of secondary prevention measures. A long-term intervention program for high risk patients in the community is needed to improve the current situation.

Background: Cardiac surgery is being performed with increasing frequency in patients aged 80 years and older.

Objectives: To examine the long and short-term results of surgery in this age group.

Methods: We retrospectively investigated 202 consecutive patients aged 80 years or older who underwent cardiac surgery between 1991 and 1999. Ninety-six operations (48%) were urgent.

Results: The study group comprised 140 men (69%) and 62 women (31%) with a mean age of 82.1 years (range 80–89). Preoperatively, 120 patients (59%) had unstable angina, 37 (18%) had left main coronary artery disease, 22 (11%) had renal failure, 17 (8.5%) had a history of stroke, and 13 (6.5%) had previous cardiac surgery. Hospital mortality for the whole group was 7.4%. Postoperative complications included: re-exploration for bleeding in 15 (7.4%), stroke in 8 (4%), sternal wound infection in 3 (1.5%), low cardiac output in 17 (8.4%), new Q wave myocardial infarction in 5 (2.5%), renal failure in 17 (8.5%), and atrial fibrillation in 71 (35%). The actuarial survival for patients discharged from the hospital was 66% at 5 years and 46% at 8 years. The type of surgical procedure was significantly associated with increased early mortality (coronary artery bypass grafting only in 2.9%, CABG[1] + valve in 16.1%, valve only in 16.7%; P = 0.01). Significant predictors (P < 0.05) for late mortality included type of surgical procedure, congestive heart failure, and postoperative low cardiac output.

Conclusions: When appropriately applied in selected octogenarians, cardiac surgery can be performed with acceptable mortality and good long-term results.

Background: Sulfur mustard and VX are potent chemical warfare agents that penetrate rapidly through the skin, causing severe prolonged injuries and sometimes death.

Objectives: To develop a topically applied pretreatment that will act as a barrier and prevent the absorption of these agents through the skin, reducing morbidity and saving life.

Methods: Several formulations were developed and tested in preclinical animal studies in pigs. The protecting cream was applied as a single application (0.5–1 ml/100 cm²) prior to exposure (10 minutes to 12 hours) to sulfur mustard or VX. Assessment of sulfur mustard-induced skin damage was based on clinical and histologic evaluations. When tested against VX, clinical signs and blood cholinesterase activity were monitored. At the final stage of development, safety studies were conducted in animals and in human volunteers.

Results: The formulation that gave the best results, coded IB1 (under patent application), provided significant protection against a 1 hour exposure to sulfur mustard (droplets or vapor). All the pigs pretreated with IB1 cream survived a 1–4 hour challenge of 2xLD₅₀ VX and did not exhibit any overt clinical signs. Protection was exhibited even when the cream was applied 12 hours (single application) prior to exposure. IB1 was found to be non-irritating in animals and humans. No adverse effects were found in a Phase I clinical study in young healthy volunteers when the cream was applied to around 20% of the skin surface (results presented elsewhere).

Conclusions: IB1 cream has been shown to be a safe and effective topical skin protectant against the chemical warfare agents sulfur mustard and VX.

Tremor is extremely common and often functionally disabling. When tremor becomes medically intractable, surgery is a good and safe option for appropriate candidates. Both stereotactic thalamotomy and thalamic deep brain stimulation by means of an implanted electrode offer very high rates of success with an acceptably low complication rate.