Israel Medical Association Journal

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.

Background:  One of the major reasons for the shortage of organs for transplantation in Israel is the failure to identify potential donors. According to the World Health Organization, the expected number of potential donors in Israel is 300 per year. In recent years an average of only 200 donors (2/3) has been identified.

Objective: To identify the reasons for the gap between the potential and the actual number of organ donors.

Methods: We reviewed the medical records of all potential donors at the Soroka University Medical Center between October 1997 through September 1999.

Results: The total of 183 death records was consistent with the minimal inclusion criteria for potential organ donation, of which 41 were suspected to be potential brain death (PBD) In 31 cases an ad hoc committee had declared brain death, and the patients were evaluated for organ donation. However, in 10 cases no committee was formed. We found that 24.4% (10/41) of the potential donors had not been designated as such by their medical team.

Conclusion: We believe that a comprehensive education program for medical and nursing staff might increase awareness for organ donation and may eliminate the gap between the potential and actual number of organ donors.

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: Vaginal symptoms are a leading reason for a patient to visit her gynecologist. Little is known about the prevalence of the different causes of vaginitis and the risk factors for this entity in Israel.

Objective: To determine the prevalence in a gynecologic practice in Israel of the main forms of vaginitis: vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis.

Methods: We evaluated 208 patients presenting with vaginal symptoms to a gynecologic clinic; 100 asymptomatic women who attended the clinic for routine check-up served as controls. Demographic, medical and gynecologic histories were obtained, and a pelvic examination was performed in all patients. Vaginal specimens were tested for pH and amine reaction, smeared for Gram-staining and cultured for yeasts and Trichomonas vaginalis. Bacterial vaginitis was diagnosed using the Nugent scoring system. candida infection was diagnosed by microscopic examination and by culture.

Results: Candida spp. was the most common pathogen, documented by microscopy and culture in 35.5% of symptomatic women and 15% of asymptomatic controls (P < 0.001). Detection by culture only (negative microscopy) was documented in 18.7% of symptomatic patients and 15% of controls (P = 0.5). Bacterial vaginosis (Nugent score ≥ 7) was diagnosed in 23.5% of patients and 13% of controls (P = 0.04). Trichomoniasis was present in 8.1% of symptomatic women and 4% of controls (P = 0.1). The main risk factors were antibiotic use for candidiasis and lack of use of oral contraception and condom use for trichomoniasis.

Conclusion: Candida was by far the most common pathogen detected in our population. A statistically significant difference between patients and controls was noted for the prevalence of microscopically diagnosed candidiasis and bacterial vaginosis.
 

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.

Background: Onchocerciasis results from infestation by the nematode Onchocerca volvulus, and is characterized clinically by troublesome itching, skin lesions and eye manifestations. Since 1992, approximately 9,000 immigrants have arrived in Israel from the Kuwara province of northwest Ethiopia where the prevalence of onchocerciasis is particularly high.

Objectives: To determine whether onchocerciasis is the cause of cutaneous and ocular symptoms among recent immigrants from the Kuwara province in Ethiopia

Methods: We examined 1,200 recent immigrants from the Kuwara province residing at the Mevasseret Zion immigration center outside Jerusalem. Among them, patients with cutaneous signs suggestive of onchocerciasis underwent a skin-snip biopsy and a thorough eye examination.

Results: In the detailed skin examination performed in 83 patients, the most common skin finding was chronic papular onchodermatitis, found in more than 46 patients (55%);depigmentation and atrophy was found in 13 (15%) and 12 (14%), respectively. In 40 patients (48%), living microfilaria were detected in their skin snips. Of the 65 patients who underwent a thorough eye examination, 45 patients (66%) had ocular complaints. Corneal abnormalities were found in 55 of the 130 eyes (42%), active anterior segment intraocular inflammation and live microfilariae were found in 4 eyes (3%) and lens changes in 16 eyes (1 %). Eleven eyes (9%) showed retinal or choroidal changes.

Conclusions: Skin and eye manifestations associated with onchocerciasis are prevalent among symptomatic Ethiopian immigrants to Israel from the Kuwara province.

Diffuse idiopathic skeletal hyperostosis is often incorporated into osteoarthritis. Although DISH[1] often coexists with OA, patients affected by this disorder differ from patients with primary OA in several aspects: prevalence in the general population, gender distribution, anatomic site of primary involvement, magnitude and distribution in the spine and the peripheral joints. DISH is a distinct clinical entity. Its recognition as such should stimulate clinicians and researchers to focus on its pathogenesis, treatment and prevention.

Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30–50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Activated protein C, an endogenous vitamin K-dependent anticoagulant, plays a major role in the down-regulation of the procoagulant arm. It also possesses anti-inflammatory properties. Endothelial damage during sepsis impairs the endothelium-dependent activation of protein C, thus shifting the balance towards thrombosis. This shift may contribute to the development of sepsis-related multi-organ failure. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients. Indeed, a recent randomized controlled trial demonstrated a reduction in overall mortality in patients with severe sepsis treated with APC[1]. In this review we discuss the pathogenesis of the coagulopathy of sepsis, as well as the new therapeutic approaches aimed at correcting the defects in the coagulation system.