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: Appropriateness of hospital admission has both clinical and economic relevance, especially in light of the growing pressure for increased efficiency of health services utilization. In Israel, the number of referrals and use of the emergency room continue to rise along with an increase in hospital admissions and the number of inappropriate admis­sions. Using evaluation protocols, such as the Pediatric Appropriateness Evaluation Protocol, international studies have shown that 10-30% of hospital admissions are medically unnecessary. Inappropriate hospitalizations have an economic impact as well as medical and psychological effects on the child and the family.

Objectives: To assess the extent and characteristics of inappropriate pediatric admissions to a tertiary care facility in Israel.

Methods: We conducted a prospective study using chart review of pediatric admissions to Soroka University Medical Center on 18 randomly selected days in 1993, and evaluated the appropriateness of admissions using the PAEP.

Results: Of the 221 pediatric admissions 18% were evaluated as inappropriate. The main reason for such an evaluation was that the problem could have been managed on an ambulatory basis. Inappropriate admissions were asso­ciated with hospital stays of 2 or less days, children older than 1 year of age, Jewish children, and self-referrals to the pediatric emergency room.

Conclusions: The assessment and identification of characteristics of inappropriate hospital admissions can serve as indicators of problems in healthcare management and as a basis for improving quality of care and developing appropriate medical decision-making processes.

Objective: To explore the putative effect of cardiac rehabilitation programs on the health-related quality of life’ and ‘return to work’ in pre-retirement patients one year after coronary artery bypass grafting.

Methods: Of the 2085 patients aged 45-4 who survived one year after CABG and were Israeli residents, 145 (6.9%) had participated in rehabilitation programs. Of these, 124 (83%) who answered QOL questionnaires were individually matched with 248 controls by gender, age within 5 years. and the time the questionnaire was answered. All patients had full clinical follow-up including a pre-operative interview. The Short Form-36 QOL questionnaire as well  as a specific questionnaire were mailed to surviving patients one year after surgery. Study outcomes included the scores on eight scales and two summary components of the SF-36, as well as return to work’ and ‘satisfaction with medical services’ from the specific questionnaire. Analysis was done for matched samples.

Results: Cardiac rehabilitation participants had signifi­cantly higher SF-36 scores in general health, physical functioning, and social functioning. They had borderline significant higher scores in the physical summary component of the SF-36. The specific questionnaire revealed significantly better overall functioning, higher satisfaction with medical care. and higher rate of return to work. While participants in cardiac rehabilitation and their controls were similar in their socio­-demographic and clinical profiles, participating patients tended to be more physically active and more fully employed than their controls.

Conclusions: Rehabilitation participants had a self-per­ception of better HRQOL, most significantly in social function­ing. Our findings of more frequent return to work and higher satisfaction with medical care should induce a policy to encourage participation in cardiac rehabilitation programs after CABG.
 

Background: The modest clothing that Orthodox Jewish women wear exposes very little of their skin to sunlight. Under these conditions they may develop vitamin D deficiency, even in sunny Israel.

Objectives: To determine and compare the vitamin D nutritional status in Jewish orthodox mothers to that of non-orthodox mothers who live in the same metropolitan area in Israel.

Methods: 25-Hydroxyvitamin D was measured by compe­titive protein-binding radioassay in the sera of 341 Jewish Israeli mothers (156 orthodox and 185 non-orthodox). The sera were obtained 48-72 hours after childbirth during the late summer of 1998 and the spring of 1999.

Results: The mean (SD) serum concentration of 25-OHD was significantly (P<0.002) lower (13.5 ± 7.5 ng/ml) in the orthodox than in the non-orthodox mothers (18.6 + 9.6 ng/ml). Vitamin D deficiency (<5 ng/ml) and insufficiency (<10 ng/ml) were more common in the orthodox mothers (5.1% and 32.7% respectively) than in the non-orthodox mothers (2.7% and 13%, respectively). In subgroups of mothers supplemented with 400 units of vitamin D daily during pregnancy, vitamin D deficiency and insufficiency were less common (2.2% and 13%, respectively) in orthodox and non-orthodox mothers (0% and 8.1%, respectively). Vitamin D insufficiency was more common in the winter than in the summer only among non­orthodox mothers.

Conclusions: The high prevalence of vitamin D deficiency and insufficiency in Israeli mothers raises the question whether vitamin D supplements should be given to pregnant women in Israel, at least to orthodox mothers.
 

Background: On 1 January 1995 a new mandatory National Health Insurance Law was enacted in Israel, The new law fostered competition among the four major Israeli healthcare providers (HMO5 or sick funds) already operating in the market due to the possibility that an unlimited number of patients and the relative budget share would shift among the HMOs. This led them to launch advertising campaigns to attract new members.

Objectives: To examine newspaper advertising activities during the early stages of healthcare market reform in Israel.

Methods: Advertising efforts were reviewed during a study period of 24 months (July 1994 to June 1996). Advertisements were analyzed in terms of marketing strategy, costs and quality of information.

Results: During the study period 412 newspaper adver­tisements were collected. The total advertising costs by all HMOs was approximately US$4 million in 1996 prices. Differences were found in marketing strategy, relative adver­tising costs, contents and priorities among the HMOs.

Conclusions: The content of HMO5 newspaper advertis­ing was consistent with their marketing strategy. The mes­sages met the criteria of persuasive advertising in that they cultivated interest in the HMOs but did not provide meaningful information about them. Future developments in this area should include consensus guidelines for advertising activities of HMOs in Israel, instruction concerning the content of messages, and standardization of criteria to report on HMO performance.

Background: Patients who feel involved in their treatment have better outcomes than those who do not.

Objective: To identify determinants of perceived patient involvement in obstetric care.

Methods: A retrospective study was undertaken in 1,452 (83%) of 1,750 women sampled in November 1995 from maternity wards of 14 general hospitals in Israel. A postal and telephone survey using a self-administered questionnaire included the following variables: hospital (identity number), patients' age, self-reported complications, previous deliveries, education, ethnicity, and number of obstetric interventions performed and/or considered. The main outcome measured was the reported involvement in decisions for obstetric interventions.

Results: Reported full involvement varied from 72% for epidural analgesia to 13% for forceps/vacuum extraction. Factor analysis identified two dimensions of perceived involvement: one for routine” interventions (enema, monitor­ing, IV line and episiotomy), which are performed in Israel mostly by midwives, and another for "special" interventions (forceps/vacuum extraction, epidural or other analgesia, and cesarian section) performed by physicians. Logistic regression identified hospitals, younger age, number of interventions, and Arab ethnicity as correlates of a perceived non-involvement in decisions for "special" interventions.

Conclusions: Clinical setting, age and ethnicity affected patient perception of involvement in decisions for obstetric interventions.

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.
 

Trophic factors such as nerve and fibroblast growth factors are important modulators of 13 cell physiology. These two factors induce the extension of neurite-Iike processes in primary cultures of adult rat 13 cells. Moreover, both NGF and FGF enhance glucose-induced insulin secretion. Since â cells synthesize NGF and pancreatic islet cells produce FGFs, it is possible that autocrine/paracrine interactions may be major regulators of insulin secretion, and impairment of these interactions could lead to pathological states such as diabetes mellitus.

The formerly prevalent concept that intact autoantibodies could not penetrate into viable cells has been defeated by a large amount of experimental findings and clinical observations that indicate otherwise. The penetration of autoantibodies into living cells seems to participate in the pathogenesis of diverse autoimmune diseases, but it may also play a physiological role in healthy individuals. Although the fine mechanisms of the phenomenom remain to be elucidated, the potential use of penetrating autoantibodies as vectors to deliver molecules into cells, with diverse therapeutic purposes, has gained growing interest during the last few years.

Background: Inflammatory mediators, including cytokines and reactive oxygen species. are associated with the pathology of chronic liver disease. Hepatocytes are generally considered as targets but not producers of these important mediators.

Objectives: To investigate whether cells of hepatocellular lineage are a potential source of various cytokines we estimated the expression and secretion of tumor necrosis factor alpha, transforming growth factor beta 1 and interleukins I beta, 6 and 8 in the culture of well-differentiated human HepG2 cells treated for 24 hours with ethanol, acetaldehyde and lipopolysaccharide. Lipid peroxidation damage, glutathione content and glutathione perox­idase, catalase and superoxide dismutase activity were also determined.

Methods: HepG2 cells were treated for 24 hours with ethanol (50 mM), acetaldehyde (175 ìM) and LPS (1 ìg/ml). TNF-á, TGF­-â, L-1â, IL-6 and IL-8 mRNA were determined by reverse transcriptase polymerase chain reaction and secretion by en­zyme-linked immunoassay. Lipid peroxidation damage, glutathione content and antioxidant enzyme activities were determined spectrophotometrically.

Results: Exposure to ethanol for 24 hours induced the expression of TNF-á and TGF- â1. secretion of IL-1â and TGF-â₁ and decreased catalase activity. Acetaldehyde markedly increased TNF-á and IL-8 expression, stimulated IL-1â and IL-8 secretion, increased lipid peroxidation damage and decreased catalase activity, while LPS exposure induced the expression of TNF-á. TGF- â₁, IL-6 and IL-8, the secretion of TGF-â₁, IL-1â, IL-6 and IL-8, and a decrease in catalase activity. No change in GSH, GSHPx or SOD was found in any experimental condition.

Conclusions: The present studies confirm and extend the notion that hepatocytes respond to ethanol, acetaldehyde and LPS-producing cytokines. Oxidative stress produced by the toxic injury plays an important role in this response through up­regulation of inflammatory cytokines.

Objective: To evaluate the feasibility of using combined clinical and histomorphometric features to construct a prognostic score for the individual patient with localized renal cell carcinoma.

Patients and Methods: We studied 39 patients with pT1 and pT2 RCC who underwent radical nephrectomy between 1974 and 1983. Univariate and multivariate analyses were used to determine the association between various prognostic features and patient survival.

Results: The most important and independent predictors of survival were tumor angiogenesis (P=0.009), nuclear DNA ploidy (P=0.0071), mean nuclear area (P=0.013), and mean elongation factor (P=0.0346). Combination of these variables enabled prediction of outcome for the individual patient at a sensitivity and specificity of 78% and 89% respectively.

Conclusion: Our results indicate that no single parameter can accurately predict the outcome for patients with localized RCC. Combination of neovascularity, DNA content and morphometric shape descriptors enabled a more precise stratification of the patients into different risk categories.
 

Background: Human chorionic gonadotropin, the pregnancy hormone, is synthesized by trophoblast cells which make up the placenta.

Objective: To determine whether antibody to hCG can be used to specifically detect living trophoblast in vitro by binding to the external membrane.

Methods: Trophoblast was isolated from fresh placentas of women undergoing termination of pregnancy in the first trimester and incubated with monoclonal antibody to hCG. Anti-mouse immunoglobulin G with a fluorescent marker was then added.

Results: Syncytiotrophoblast stained positive on the external surface of the cell, while controls of leukocytes, endometrial cells and hepatocytes were negative.

Conclusion: The hCG monoclonal antibody may be used to specifically detect hCG on the surface of living trophoblast in vitro.