Israel Medical Association Journal

Background: Extensive necrosis is rare in primary renal cell carcinoma. This finding may reflect the biological characteristics of the carcinoma and therefore could be of prognostic and clinical value.

Objectives: To assess the incidence of necrosis in renal cell carcinoma and its potential prognostic value.

Methods: We conducted a consecutive retrospective study of 173 patients after radical nephrectomy for renal cell carcinoma. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database.

Results: Extensive necrosis was found in 31 tumor specimens (17.9%). Univariate analysis showed that the specimens with extensive necrosis were significantly larger and manifested more perirenal and venous extension than the tumors without necrosis. The size of the renal tumor was the only parameter that remained significant in multivariate analysis (P=0.0001). Overall disease-free survival did not differ significantly between patients with necrotic tumors and those without (68% and 66% respectively).

Conclusions: The finding of extensive necrosis in renal cell carcinoma specimens does not seem to be related to tumor biology but rather may reflect the relation between size and vascularity of the tumor.

Objectives: To assess mortality causes and trends over time and identify target groups with excessive mortality rates among Israeli youth aged 10-24, in order to formulate an intervention policy for prevention of adolescent mortality.

Methods: Mortality data for Israeli residents aged 10-24 were extracted from the Central Bureau of Statistics compu­terized death certificate file for the period 1984-95. Trends were evaluated by cause of death and demographic char­acteristics.

Results: The crude mortality rate among Israeli youth aged 10-24, during 1993-1995, was 39.6 per 100000. Rates were 2.7 times higher among males, increased with age, and reached a peak among 18-21 year olds. Rates were 1.4 times higher among Arabs than among Jews. The sharp increase in mortality among Jewish males of military service age (18-21 years) was due mainly to motor vehicle crashes and suicide. Although overall mortality decreased by 9.4% from 1984-86 to 1993-95, the gap between the subgroups increased. MVC­related mortality increased over time by 100% among Arab males. The rate of completed suicide among Jewish males increased by 110%. Although injury-related mortality is lower in Israel compared with the U.S., similar demographic differen­tials and trends were found in both countries.

Conclusions: Suicide among Jewish males of military service age, as well as MVC fatalities among Arab males, present a growing public health issue. Intervention strategies should therefore be targeted towards these subgroups in order to minimize the rates of preventable death.

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.

Sex steroid hormones (estrogens, progestagens and androgens) have been associated with healthy and neoplastic pancreatic biology, although the precise significance of the findings has not been well established. Receptors for the three different types of SSH are expressed in normal and tumoral pancreatic tissue with varying profiles related to cell origin (exocrine or endocrine), to type of neoplasm. and probably even to tumoral behavior. The activity of specific enzymes involved in the synthesis and transformation of SSH are increased in some neoplastic pancreatic tissues, which may influence the circulating concentrations of these hormones, such as the low serum testosterone: dihydrotestosterone ratio described in male patients with pancreatic carcinoma. Different patterns of age and gender-related incidence and growth of neoplasms have been identified. Experimental studies have shown that pancreatic carcinogenesis is promoted or inhibited by SSH. At present, the data supporting hormonal manipula­tion for the treatment of these tumors are non-conclusive. Normal and tumoral pancreatic tissues may be regarded as a target for SSH and an additional site of biosynthesis. The influence of these hormones on physiological activities is not well known but should be further explored. The study of SSH in pancreatic neoplasms will provide clues about its origin, development, tumoral behavior, prognosis and more specific hormonal therapy. We review here the evidence favoring the role of SSH and their possible clinical implications in pancreatic function.

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.
 

Background: The transfer of therapeutic genes into malignant brain tumors has been the subject of intense pre­clinical and clinical research in recent years. Most approaches have used direct intratumoral placement of a variety of vectors and genes, such as retroviruses or adenoviruses carrying drug-susceptibility genes, modified replication-competent herpes virus, and several vectors carrying tumor suppressor genes such as the p53 gene. However, clinical results have so far been disappointing, mainly due to the limited ability to effectively distribute the genetic material into the target cell population. Accordingly, alternative delivery approaches into the central nervous system, e.g., intravascular, are under investigation. Genetic vectors administered intravascularly are unlikely to penetrate the blood-brain barrier and transfer a gene into brain or tumor parenchyma. However, intravascular delivery of vectors may target endothelial cells lining the blood vessels of the brain. Since endothetial cells participate in a variety of physiological and pathological processes in the brain, their modulation by gene transfer may be used for a variety of therapeutic purposes. Angiogenically stimulated endothelial cells within tumors replicate rapidly and hence may become targets for retroviral-mediated gene transfer.

Objective: To assess the anti-tumor effect of transferring a drug-susceptibility gene into endothelial cells of the tumor vasculature.

Methods: As a model for this approach we delivered concentrated retroviral vectors carrying a drug-susceptibility gene via the internal carotid artery of rats with malignant brain tumors. The safety and efficacy of this approach, without and with subsequent treatment with a pro-drug (ganciclovir). was evaluated.

Results: No acute or long-term toxicity was observed after intraarterial infusion of the vector. Treatment with ganciclovir resulted in variable hemorrhagic necrosis of tumors, indicating preferential transduction of the angiogenically stimulated tumor vasculature. This was accompanied by severe toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in vascular territories shared by the tumor and adjacent brain.

Conclusion: The data indicate that endothelial cells can be targeted by intraarterial delivery of retroviral vectors and can be used for devising new gene therapy strategies for the treatment of brain tumors.