Israel Medical Association Journal

Background: A high total plasma homocysteine level is an independent risk factor for cardiovascular and cerebrovascular disease, but the evidence connecting plasma tHcy level with hypertension is inconsistent.

Objective: To determine the association between plasma tHcy level and some common risk factors for cerebrovascular disease (recurrent  stroke, diabetes mellitus, hypertension, ischemic heart disease and hyperlipidemia) in patients presenting with primary or recurrent acute ischemic strokes.

Methods: This retrospective cross-sectional chart analysis was conducted in a university-affiliated referral hospital. During an 18 month period we identified 113 acute ischemic stroke patients (mean age 71.2), 25 of whom had a recurrent stroke. Plasma tHcy[1] level, obtained 2–10 days after stroke onset, was determined by the high performance liquid chromatography method with fluorescence detection. A multivariate logistic regression model was used to determine the independent relationship between each potential risk factor and tHcy level above or below the 75th percentile.

Results:  Hypertension was more frequent among patients with plasma tHcy level above than below the 75th percentile (51.7% vs. 80.8%, respectively, P = 0.012). After adjusting for demographic and clinical variables, the odds ratio for recurrent stroke and hypertension, with tHcy above or below the 75th percentile, was 3.4 (95% confidence interval 1.01–10.4, P = 0.037) and 4.02 (95% CI[2] 1.2–13.9, P = 0.028), respectively.

Conclusions: A high plasma tHcy level is associated with history of hypertension and recurrent stroke among patients presenting with acute ischemic stroke. These results were independent of other risk factors such as atrial fibrillation, diabetes and hyperlipidemia. Hypertensive stroke patients with hyperhomocysteinemia should be identified as high risk patients as compared to non-hypertensive stroke patients, and may warrant more vigorous measures for secondary prevention.

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: 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.

Background: An organ sharing system should achieve fairness and optimal graft longevity. Balancing between social and utilitarian considerations is a sensitive ethical, public and medical issue that requires a means to examine the consequences of any allocation policy or planned changes thereof.

Objective: To evaluate the performance and applicability of a computerized simulation model by examining the impact of two opposing organ allocation policies (social or utilitarian) on predicted organ distribution regarding age, waiting time, recipient sensitization measured by panel reactive antibody level and overall donor-recipient tissue matching (measured by the number of HLA antigen mismatches).

Methods: Using a computerized simulation model, virtual donors and recipients were emulated and organs were allocated according to either social algorithms or utilitarian policies. The resulting number of HLA mismatches, PRA[1], age, and waiting time distributions were compared between allocation strategies.

Results: Simulating allocation of 7,000 organs to 17,000 candidate recipients and implementing social policies yielded donor-recipient compatibility comparable to utilitarian policies (0–1 mm: 19.4% vs. 28%) while allocating 66.7% of organs to long waiters (>48 months).

Conclusion: This computerized simulation model is a valuable tool for decision-makers establishing or modifying organ allocation policies.

Background: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.

Objectives: To study the impact of combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. 

Methods: Between September 1997 and January 2000, 129 patients underwent living related (n=80) or unrelated (n=49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF[1] with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.

Results: LUD[2] recipients were older (47.8 vs. 33.6 years) with higher number of re-transplants (24.5% vs. 11.2% in LRD[3] recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 year graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.

Conclusions: Despite HLA[4] disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Background: Acute myocardial infarction is rare in people under the age of 30.

Objective: To determine the clinical features and outcome in young patients presenting with AMI.

Methods: All patients aged 30 years and younger hospitalized with AMI during a period of 8 years (1993–2000) were evaluated for clinical features and outcome.

Results: Of the 3,758 patients with AMI, 15 were 30 years old or younger (0.4%). The mean age was 28 (range 21–30 years) and all were male. Eight had normal coronary arteries on angiogram; seven had obstructive coronary artery disease. Patients with OCA[1] had more classical risk factors for coronary disease. A complete diagnostic work-up was abnormal in four patients with NCA[2]: thrombophilia in two patients, spasm due to alcohol withdrawal and hyperthyroidism in one patient each. All patients presented with typical new-onset chest pain. None had a previous history of angina. All patients with OCA received reperfusion therapy as compared to one patient with NCA. Peak creatine phosphokinase in NCA and OCA was 504 ± 547 and 1,328 ± 440 respectively (P < 0.01). All patients with NCA had good left ventricular function on follow-up echocardiography, compared to only three in the OCA group (P = 0.02). There was one death due to cardiogenic shock in a patient with OCA. Follow-up of 4 ± 2 years demonstrated recurrent acute coronary syndromes in four of seven patients with OCA versus none in the NCA patients (P = 0.02).

Conclusions: AMI is rare in very young patients, and more than half have NCA. A thrombophilic tendency or spasm should be considered. Young patients with NCA have an excellent prognosis.

The relevance of central neurotransmission to aggressive and impulsive behavior has become more evident due to extensive research in humans and in animals. Among other findings, there are abundant data relating low serotonergic activity – as measured by low cerebrospinal fluid 5-hydroxyindolacetic acid, and a blunted response of prolactin to fenfluramine – to impulsive behavior. Many studies on testosterone activity show a relation between high plasma levels and a tendency towards aggression. It is hypothesized that the interaction between low serotonin and high testosterone levels in the central nervous system has a significant effect on the neural mechanisms involved in the expression of aggressive behavior. It seems that testosterone modulates serotonergic receptors activity in a way that directly affects aggression, fear and anxiety. Our survey reviews the main findings on serotonin, testosterone and the possible interaction between them with regard to these behavioral phenomena.