Israel Medical Association Journal

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.

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.

Only one case of a cow infected with bovine spongiform encephalopathy has been reported in Israel. Its publication, in 2002, caused both public and professional concern. The inevitable health policy question raised was whether or not to recommend against consuming beef and what public health measures should be taken. In this article we describe the prion diseases among animals and humans, their interaction and the precautionary procedures that were carried out by the state Veterinary Services and the Ministry of Health since 1988. The BSE[1] case (a 10 year old dairy cow) is believed to be the result of local consumption of infected food with mammalian meat and bone meal more than a decade earlier. The risk assessment took into consideration that no cases of vCJD (a new variant of Creutzfeldt-Jacob disease) have ever been diagnosed in Israel, as well as the low risk of contamination of the meat due to the religious method of slaughtering performed in the country. The policy decision was to implement a contingency plan prepared in advance. Israel was reclassified from the level II category of geographic risk where BSE is unlikely but not excluded in the herds, to level III, where BSE is likely but not confirmed, or confirmed at a lower level. No undue damage to the meat industry has occurred. By the end of 2002, despite the examination of more than 3,800 brains from slaughtered cows older than 3 years, no other cases of BSE have been detected.

Background: The Arterial Revascularization Therapies Study was a multicenter, randomized trial designed to compare percutaneous coronary intervention with stenting versus coronary artery bypass graft surgery in 1,205 patients with multivessel coronary artery disease. The most appropriate type of treatment for these patients is still a matter of considerable debate.

Objectives: To evaluate the clinical characteristics of patients enrolled in the ARTS[1] trial in Israel in comparison to those worldwide, and to assess the 1 year outcome in these patients.

Methods: Between April 1997 and June 1998, a total of 1,205 patients with multivessel coronary artery disease, who were considered to be equally treatable with both modalities, were randomized to either stenting (n=600) or CABG[2] (n=605) at 67 centers around the world. In Israel, 53 patients at four participating medical centers underwent randomization to either PCI[3] with stents (n=27) or CABG (n=26).

Results: Clinical and angiographic characteristics were similar in the two groups, except for a significantly higher incidence of diabetic patients in Israel who were randomized to CABG, compared to those worldwide (35% vs. 16%, P = 0.01). Also, there were more patients with unstable angina in Israel (63 vs. 37%, P = 0.006). At 1 year follow-up, overall mortality and cerebrovascular accident rates were similar between the two groups and equivalent to results obtained around the world. There was a significantly higher incidence of myocardial infarction rates in patients randomized to stenting in Israel compared to patients worldwide (7.4 vs. 5.3%, P = 0.01) or to patients randomized to CABG in Israel (7.4 vs. 0%, P = 0.006). Similar to the overall ARTS results, there was a higher incidence of repeat revascularization procedures in patients assigned to the PCI with stenting arm (22.2 vs. 3.8%, P = 0.004) compared to those randomized to CABG, respectively.

Conclusions: The results of this analysis of the Israeli ARTS population indicate that coronary stenting and bypass surgery yield similar findings with regard to mortality and stroke and are comparable to those obtained in the whole study group. Likewise, coronary stenting was associated with an increased incidence of repeat revascularization procedures as compared to CABG. However, patients in Israel randomized to stenting had a higher rate of myocardial infarctions as compared to the overall results and to patients who underwent CABG in Israel. The present analysis provides important data for the safety and efficacy of either stenting or bypass surgery in treating patients with multivessel disease in Israel.

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Progressive neurodegenerative disorders share common mechanisms of cell death, and in all likelihood multiple factors are involved in every disease. Therefore, several neuroprotective agents are being investigated with the purpose of slowing or preventing further deterioration of cell loss. These include experimental animal and clinical studies on the neuroprotective effects of caspase inhibitors, antioxitands, glutamate antagonists, anti-inflammatory agents and trophic factors in several neurodegenerative diseases. At present there is limited clinical evidence for direct neuroprotective effects against these diseases, but much effort is being invested in research on novel technologies and compounds.

Background: Decreased elasticity of the aorta is associated with aging and several risk factors of atherosclerosis. The data regarding this phenomenon in patients with familial hypercholesterolemia are rather sparse.

Objectives: To evaluate non-invasively the elasticity of the proximal ascending aorta of 51 heterozygous FH[1] patients compared to 42 normal age and gender-matched controls.

Methods: Aortic elasticity was estimated by transthoracic echocardiography using the “pressure-strain” elastic modulus and aortic strain formulas.

Results: The elastic modulus score was higher in the FH group than in the controls (1.12 ± 0.91 10⁶ dynes/cm² vs. 0.65 ± 0.46 10⁶ dynes/cm² respectively, P = 0.01). This was consistent in both the pediatric (0.5 ± 0.2 10⁶ dynes/cm² vs. 0.4 ± 0.1 10⁶ dynes/cm² respectively, P = 0.009) and adult subgroups (1.3 ± 1.0 10⁶ dynes/cm² vs. 0.8 ± 0.5 10⁶ dynes/cm² respectively, P = 0.0004). Aortic strain was significantly lower in patients with FH than in controls (6 ± 4% vs. 9 ± 5% respectively, P = 0.0002). These findings reflected decreased elasticity of the proximal ascending aorta in the FH patients. In multivariate analysis, age, serum cholesterol level and serum triglycerides level were the independent predictors of the elastic modulus score, whereas age was the predictor of aortic strain.

Conclusions: The elasticity of the proximal ascending aorta is decreased in heterozygous FH patients.

Background: Technetium-99m sestamibi scintigraphy has become one of the most popular techniques for localization of the parathyroid gland after failure of primary neck exploration.

Objective: To examine the efficacy of sestamibi with the hand-held gamma ray detecting probe for the identification of parathyroid adenomas during revision parathyroidectomy.

Methods: We reviewed six cases of probe-assisted neck exploration for parathyroid lesions following unsuccessful primary exploration.

Results: In all cases, the pathologic glands were successfully detected and removed.

Conclusions: With careful planning, a gamma ray detecting probe can be used optimally at 2–3 hours after technetium-99m sestamibi injection. The probe is efficient, easy and convenient to use.
 

Background: The osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or early-onset blindness. Other manifestations include muscular hypotonia, ligamentous laxity, mild mental retardation and seizures. The gene responsible was recently identified to be the low density lipoprotein receptor-related family member LRP5 on chromosome 11q11-12.

Objective: To measure bone density in two siblings with the OPPG[1] syndrome as well as in their family members (parents and siblings).

Methods: Bone mineral density was determined in the lumbar spine (antero-posterior), femoral neck, two-thirds distal forearm (>95% cortical bone) and ultradistal forearm (predominantly trabecular bone) by dual-energy X-ray absorptiometry.

Results: The studies revealed osteoporotic changes both in the patients and the carriers.

Conclusion: The findings demonstrate that OPPG carriers have reduced bone mass, which is a risk factor for development of early osteoporotic changes.

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Background: Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel cystinuria is especially common among Libyan Jews who suffer from non-type I disease.

Objectives: To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls.

Methods: Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls.

Results: Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients’ urinary pH. Eleven of the unaffected Libyan Jewish controls were found heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584+3 del AAGT mutation was not found in any of the Libyan Jewish controls.

Conclusion: Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.