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: Increased levels of high density lipoprotein (over 60 mg/dl) are considered to be a risk factor for ischemic heart disease. However, some patients with high HDL[1] still develop cardiovascular diseases.

Objective: To find out why patients with very high HDL still suffer from cardiovascular diseases.

Methods: We analyzed several risk factors, such as increased lipid peroxidation, hyperhomeocysteinemia and increased release of inflammatory molecules that could be related to the development of vascular disease in patients with high serum HDL levels. Patients with HDL cholesterol levels above 75 mg/dl were selected for this study and were separated into two groups based on the presence of atherosclerotic vascular disease, i.e., those with vascular disease (patients) and those without (controls).

Results: Plasma isolated from the patient group exhibited significantly increased lipid peroxidation by 21% and decreased total antioxidant status by 17%, but there were no differences regarding their serum or their paraoxonase activity. Moreover, both groups exhibited similar levels of serum C-reactive protein, fibrinogen and homocysteine, enabling us to eliminate these risk factors in the etiology of cardiovascular disease in the patient group.

Conclusion: Increased oxidative stress could be one of the factors leading to cardiovascular diseases in patients with high serum HDL levels.

Background: Previously reported results of total hip arthroplasty in patients younger than 30 years of age indicate a high complication rate and questionable durability.

Objectives: To estimate the results of THA[1] in extremely young patients.

Methods: We report the results of 69 THA procedures in 56 patients who were under the age of 30 at the time of surgery (mean age 23.23 ± 4.31 years) and were followed-up postoperatively for 2–23 years (mean 7.4 ± 3.79 years).

Results: Loosening of the cup (11/69) and early traumatic dislocation (5/69) accounted for the majority of complications.

Conclusion: The final average Harris hip scores of 90.59 ± 9.36 in these patients indicated that THA is a successful and durable treatment modality for young patients with disabling diseases affecting the hip joint. However, due to the likelihood of complications it should be used with caution in this patient group. Efforts should be made to diminish the complication rate.

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.

Background: Dizziness and vertigo can be a complaint in various psychiatric conditions, where it usually constitutes only one of the features of the syndrome. Lately, a somatoform disorder characterized by almost mono-symptomatic dizziness and unsteadiness has been described. Since phobic postural vertigo usually presents without anxiety or other psychological symptomatology, patients with this condition seek help at neurologic and otolaryngologic clinics where they are often misdiagnosed as suffering from organic vertigo.

Objectives: To present the clinical features of 55 consecutive patients diagnosed with phobic postural vertigo at our clinic during 1998–2002.

Methods: We conducted a retrospective review of patients’ medical records and report two typical cases as illustration.

Results: The patients presented with complaints of unsteadiness with or without dizziness, and attacks of sudden veering that caused them to grasp for support. Accompanying anxiety was admitted by only 5% and vegetative symptoms were reported in 18%. In 16% the symptoms resulted in avoidance behavior. A stressful life event or an unrelated somatic disease triggered the onset of PPV[1] in 35% of patients, whereas a vestibular insult preceded the symptoms in 13%. The mean duration of symptoms was 26.7 ± 39.1 months (range 0.5–20 years). In 72% of patients the symptoms resolved after the psychological mechanism of their symptoms were explained to them; 24% improved with antidepressant treatment (selective serotonin reuptake inhibitors or tricyclic antidepressants), and only in 4% did the symptoms persist.

Conclusions: Since PPV is a frequently encountered diagnosis at some specialized dizziness clinics, familiarity with this entity resulting in early diagnosis can avoid unnecessary examinations and lead to effective treatment.