Israel Medical Association Journal

Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division – CDKN2A and cyclin-dependent kinase 4 (CDK4) – have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.

Background: Gallium scintigraphy is frequently used in the evaluation of fever of unknown origin, although its utility has been addressed in only a few studies.

Objectives: To evaluate the utility of gallium scintigraphy in the evaluation of patients with FUO[1] in our department.

Methods: We reviewed the charts of all patients from our department who had undergone gallium scintigraphy during the years 1995–2002 for the evaluation of FUO and who met the criteria for the definition of FUO. Demographic, clinical and laboratory data in addition to the results of gallium scintigraphy were documented. The patients were divided into two groups: those with a normal gallium study (group 1) and those with an abnormal gallium study (group 2). The second group was further divided into two groups: those whose gallium study results contributed to the diagnosis of the cause of FUO (group 2A) and those whose gallium study results did not (group 2B).

Results: A total of 102 patients met the study criteria. The male: female ratio was 54:48 and the mean age ± SD was 62.4 ± 20 years. A final diagnosis had been reached in 63 patients (62%), among whom the etiology was infectious in 54%, neoplastic in 19% and immunologic/rheumatic in 16%. Forty-one patients (40% of all the patients) (Group 2) had an abnormal gallium scintigraphy, and in only 21 patients (21% of all the patients) (Group 2A) did the gallium study results contribute to the diagnosis of the cause of FUO. However, in only two patients from Group 2A (2% of all the patients in our study) was the contribution of gallium study considered significant or crucial to the diagnosis of the cause of FUO.

Conclusions: The utility of gallium scintigraphy in the evaluation of FUO is very limited.

Background: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients.

Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment.

Methods: In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B₆ daily and one monthly injection of 200 µg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 µg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy[1] levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR[2] alleles were analyzed, as were activated protein C resistance, von Willebrand factor and lupus anticoagulant.

Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects (33.8 ± 4.3 vs. 4.5 to 14.0 mmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in group A and 18.6 ± 1.4 mmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5) was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 mmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 mmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable.

Conclusions: Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor.

The complexity of medical problems is a well-recognized phenomenon. In the presence of economic and cultural restrictions, medical decision-making can be particularly challenging. This paper outlines a system of analysis and decision-making for solving such problems, and briefly describes a case study in which the method was used to analyze the case of antibiotic overprescribing in a large health maintenance organization. The purpose of the study was to determine if a technique for problem-solving in the field of engineering could be applied to the complex problems facing primary care. The method is designated Systematic Inventive Thinking and consists of a three-step procedure: problem reformulation, general search-strategy selection, and an application of idea-provoking techniques. The problem examined is the over-prescribing of antibiotics by general practitioners working in Maccabi Healthcare Services, an HMO[1] serving one and a half million patients in Israel. The group of healthcare professionals involved in the discussions generated 117 ideas for improving antibiotic use. Six of these ideas were then implemented in a national campaign in the winter of 2000/1 and 2001/2. During this period, a significant reduction in per-visit antibiotic purchasing was observed for influenza visits (from 79.2 per 1,000 to 58.1 per 1,000, P < .0001), but not for other categories of visits. The SIT[2] methodology is a useful technique for problem-solving and idea generation within the medical framework.

Background: Ovarian vein embolization was recently suggested as the preferred treatment for chronic pelvic pain syndrome.

Objective: To evaluate the technical feasibility, complications and early clinical and radiographic results of ovarian vein embolization in women with pelvic pain syndrome.

Methods: Percutaneous transcatheter ovarian vein embolization with coils was performed in six patients aged 27–53 years who presented with pelvic pain syndrome. All had lower abdominal pain, and pelvic varicosities were found on Doppler ultrasound and retrograde ovarian vein venography. Embolization was done unilaterally in three patients (on the left side) and bilaterally in three. Mean follow-up by telephone questionnaire was 7.3 months.

Results: The procedure was technically successful in all patients. Two patients reported partial relief of symptoms (33.3%) and three had complete relief (50%), for a total of 5 patients (83.3%) with some measure of improvement. There were no complications following the procedure.

Conclusions: Percutaneous transcatheter ovarian vein embolization seems to be safe and feasible for the treatment of pelvic pain syndrome. The procedure is performed on an outpatient basis and is well tolerated by patients.

Background: Among the various new technologies in the field of parathyroid surgery are intraoperative quick parathormone measurements.

Objectives: To evaluate the contribution of QPTH[1] measurements during parathyroidectomy to the achievement of higher success rates. 

Methods: QPTH assay using Immulite Turbo Intact PTH[2] was measured in 32 patients undergoing parathyroidectomy: 30 for primary and 2 for secondary hyperparathyroidism.  QPTH levels were measured at time 0 minutes (before incision) and at 10, 20, and 30 minutes after excision of the hyperfunctioning gland.  Only a drop of 60% or more from the 0’ level was considered to be a positive result.

Results: The mean QPTH level at time 0’ for PHPT[3] patients was 38.12 ± 25.15 pmol/L (range 9.1–118 pmol/L).  At 10 minutes post-excision of the hyperfunctioning gland (or glands), QPTH dropped by a mean of 73.80% to 9.89 ± 18.78 pmol/L. 

Conclusions: Intraoperative QPTH level measurement is helpful in parathyroid surgery.  A drop of 60% or more from 0’ level indicates a successful procedure, and further exploration should be avoided.

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.

Background: Treatment of hyperlipidemia is important for secondary prevention in patients suffering from coronary heart disease. It has been proven that “young elderly” (patients aged 65–75 years) can benefit from the treatment at least as much as younger patients.

Objective: To assess the adequacy of treatment as part of secondary prevention in “young elderly” and younger patients.

Methods: In this prospective study, 389 patients discharged from the hospital with the diagnosis of coronary heart disease were divided according to age groups. Data were collected regarding lipid profile examinations, dietary and drug therapy, and results of lipid profiles.

Results: Less than one-third of the patients achieved target low density lipoprotein levels. More patients in the older age group achieved the treatment goals. The goals were achieved despite the fact that the percentage of patients treated with lipid-lowering drugs was lower in the older age group.

Conclusion: The percentage of patients treated for hyperlipidemia as part of a secondary prevention plan in Israel is similar to that in other developed countries. The fact that more “young elderly” patients achieve adequate lipid profiles compared to younger patients indicates that there is no age discrimination towards this patient group. The finding that less than one-third of the patients reach the treatment goals should prompt physicians to treat hyperlipidemia more aggressively.