Israel Medical Association Journal

Background: Familial nephritis is a heterogeneous group of disorders caused by several genetic conditions such as Alport syndrome, glomerulonephritic syndromes, and unclas­sified nephritis without deafness or ocular defects.

Objectives: To describe a family of Iraqi Jewish origin, several of whose members suffer from non-syndromic renal failure without deafness or ocular defects and where transmis­sion is by autosomal dominant inheritance. We present the case histories of four family members and describe the molecular analysis performed in order to seek a possible linkage to one of the genes causing Alport or Alport-like syndromes.

Methods: We investigated all family members over the age of 18 for evidence of renal failure. We also extracted DNA and carried out molecular linkage analysis with polymorphic markers in each of the known loci involved in Alport and Alport­like syndromes.

Results: Histology of the renal biopsy specimens showed non-specific findings. Linkage was excluded for all the Alport and Alport-like syndrome loci.

Conclusions: The condition suffered by several members of this family seems to represent a unique autosomal dominant type of progressive hereditary nephritis, characterized by hypertension and progressive renal failure without significant hematuria or proteinuria. The main histological changes are non-specific in the early stage of the disease. Our study rules out all the currently known genes that cause Alport syndrome as being responsible for the basic defect in this type of nephritis.

Background: Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.

Objectives: To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.

Methods and Results: We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n=26), a 17% reduction n homocysteine was detected in the group treated with bezafibrate (n=12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.

Conclusions: These results indicate that an increase In plasma homocysteine levels following administration of flbrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.
 

Background: Classic Kaposi's sarcoma is a rare tumor with an indolent behavior. Local therapy is not applicable in disseminated cutaneous disease. Patients with advanced disease are usually treated with systemic chemotherapy.

Objectives: To assess the effectiveness and toxicity of  single-agent vinblastine in the treatment of disseminated and recurrent Kaposi's sarcoma.

Methods: Ten patients with wide cutaneous spread of classic Kaposis sarcoma were treated with single-agent vinblastine, 6 mg/m² intravenously once every 2 weeks. Vinblastine was continued for 2 months after achieving a maximal response.

Results: The male:female ratio was 2.3:1, and median age 64 years (range 50-79 years). The median number of involved nodules in the skin was 34. The overall response rate was 90%, 5 with complete response (50%) and 4 with partial response (40%). Complete responders had a longer duration of response than partial responders: 41.2 vs. 14.8 months. The median survival of all patients was 33 months. Side effects were minimal and tolerable.

Conclusions: Vinblastine is very effective in the treatment of extensive classic Kaposi's sarcoma, and results in a high response rate, long survival and disease-free survival with tolerable toxicity.

Background: Congenital subependymal pseudocysts are incidental findings that are found in 05-5.2% of neonates during postmortem examination or head ultrasonography. In our institution we detected 10 neonates with CSEPC.

Objective: To investigate associated etiological factors, morphologic characteristics and outcome of CSEPC.

Methods: We performed a meta-analysis of the literature on CSEPC (1967-98), including our 10 cases.

Results: A total of 256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC 48.8% were bilateral and 53.4% were located in the caudothalamic groove or head of caudate nucleus. Altogether, 93.5% resolved during 1-12 months of ultrasonographic follow-up. Compared to the general neonatal population, the following features were more prevalent in the CSEPC population: prematurity, maternal vaginal bleeding, preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal cytomegalovirus and rubella infec­tions, congenital malformations, chromosomal aberrations, infant mortality, and neurodevelopmental handicap. The risk for neurodevelopmental handicap was significantly higher when CSEPC were associated with fetal infections, IUGR, malformations and chromosomal aberrations, or persistence of CSEPC during follow-up. CSEPC infants without any of these four conditions had a low risk for neurodevelopmental handi­cap.

Conclusions: CSEPC are morphologic features of various underlying conditions encountered in the fetus. Association of CSEPC with IUGR, fetal infections, malformations and chromosomal aberrations or persistence of CSEPC indicates a higher risk for future neurodevelopmental handicaps, probably because of the deleterious effects on the fetal brain that are inherent in these conditions. A favorable outcome is expected in the absence of these risk factors.
 

Objectives: To compare risk behavior between subjects attending anonymous and confidential clinics for human immunodeficiency virus testing, and to assess whether anonymous testing results in a higher accrual of persons at risk for HIV.

Methods: An anonymous questionnaire that addressed sociodemographic and risk behavior aspects was administered to 140 subjects attending an anonymous clinic and 124 attending a confidential clinic in the Tel Aviv area. A logistic regression analysis was used to compare the effects of various behavioral factors on the probability of attending each clinic.

Results: Chronological age, age at first sexual intercourse and the percent of married subjects were similar in both clinics. However, there was a significant difference in the sex ratio and in educational attainment (85.0% versus 55.6% were males, P< 0.001 and 58% vs. 34% had over 12 years of education, P<0.001, in the anonymous and confidential clinics respectively).

There was a striking difference between the two clinics with regard to sexual experience characteristics: of the subjects reaching the anonymous clinic 21.4% were homosexual and 10.0% bisexual versus a total of 2.6% in the confidential clinic. A logistic regression analysis, comparing the effects of various behavioral factors on the probability of attending each clinic showed that gender (male), high education, homosexuality, number of partners and sexual encounter with sex workers were the strongest predictors for selecting anonymous HIV examination.

Conclusions: Individuals at high risk for HIV, such as homosexuals and bisexuals, prefer to attend an anonymous clinic.
 

Cancer is a multi-step disease involving a series of genetic alterations that result in the loss of control of cell proliferation and differentiation. Such genetic alterations could emerge from the activation of oncogenes and the loss or malfunctioning of tumor suppressor gene activity. Our understanding of cancer has greatly increased through the use of DNA tumor viruses and their transforming proteins as a biological tool to decipher a cascade of events that lead to deregulation of cell proliferation and subsequent tumor formation. For the past ten years our laboratory has focused on the molecular biology of the human neurotropic papovavirus, JCV. This virus causes progressive multifocal Ieukoencephalopathy, a fatal neuro­degenerative disease of the central nervous system in immunocompromised patients. JCV is a common human virus that infects more than 80% of humans but does not induce any obvious clinical symptoms. The increased incidence of acquired immune deficiency syndrome and the use of immunosuppressive chemotherapy have dramatically raised the incidence of PML. The coincidental occurrence of malignant astrocytes and oligodendrocytes in PML patients, coupled with the induction of glioblastoma in JCV-intected non­human primates, provides intriguing speculation on the association between JCV and CNS malignancies. In this report we discuss clinical data and laboratory observations pointing to the direct involvement of JCV in cancer.