Israel Medical Association Journal

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: 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: Upper respiratory tract illnesses have been associated with an increased risk of morbidity and mortality.

Objective: To assess the influence of vaccination against influenza on the risk of hospitalization in internal medicine and geriatric wards, and the risk of death from all causes during the 2000–2001 influenza season.

Methods: A historical cohort study was conducted using computerized general practitioner records on patients aged 65 years and above, members of “Maccabi Health Care Services” – the second largest health maintenance organization in Israel with 1.6 million members. The patients were divided into high and low risk groups corresponding to coexisting conditions, and were studied. Administrative and clinical data were used to evaluate outcomes.

Results: Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline, vaccinated subjects were sicker and had higher rates of coexisting conditions than unvaccinated subjects. Vaccination against influenza was associated with a 30% reduction in hospitalization rates and 70% in mortality rates in the high risk group. The NNT (number needed to treat) measured to prevent one hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk group). When referring to length of hospitalization, one vaccine was needed to prevent 1 day of hospitalization among the high risk group. Analyses according to age and the presence or absence of major medical conditions at baseline revealed similar findings across all subgroups.

Conclusions: In the elderly, vaccination against influenza is associated with a reduction in both the total risk of hospitalization and in the risk of death from all causes during the influenza season. These findings compel the rationale to increase compliance with recommendations for annual influenza vaccination among the elderly.

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.

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.

Background: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known.

Objectives: To evlauate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters.

Methods: Jewish Israeli prostate cancer patients (n=224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters.

Results: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner.

Conclusions: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.