Israel Medical Association Journal

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.
 

Objective: To gain an insight into the forces behind these changes, we compared the trends in hospital utilization in Israel with those in 21 developed countries with available data.

Materials and Methods: Our data were derived from The "Hospitals and Day Care Units, 1995" report by the Health Information and Computer Services of the Israel Ministry of Health, and the Organization for Economic Cooperation and Development Health Data, 98. We examined the numbers of acute care hospital beds, of patients on dialysis and of doctors' consultations, health expenditures and age structure of the population in 1995 or closest year with available data, as well as changes in DRs, HDs and ALOS between 1976 and 1995.

Results: In Israel the DRs increased from 130 in 1976 to 177 in 1995 (36%), HDs declined from 992 to 818 (18%), and ALOS declined from 7.60 to 4.51 days (41%). Relative to other countries, in 1995 Israel had the lowest ALOS; low HDs similar to those in the UK, Portugal, Spain, the USA and Sweden; and intermediate DRs similar to those in Belgium, Germany, Sweden and Australia. The number of acute care beds per 1,000 population was directly related to HDs (r=0.954, P=0.000) and to DRs (r=0.419, P=0.052). Health expenditures (% of the gross national product) correlated with the number of patients on dialysis per 1,000,000 population (r=0.743, P=0.000). Between 1976 and 1995, HDs and ALOS declined in most countries, however the trends in DRs varied from an increase by 119% in the UK to a decline by 29% in Canada.

Conclusions and hypotheses: The increase in DRs in Israel from 1976 to 1995 was shared by many but not all countries. This variability may be related to differences in trends in local practice norms and in available hospital beds. If the number of patients on dialysis is a valid index for use of expensive treatment modalities, the correlation of health expenditures with the number of patients on dialysis suggests that the use of expensive technology is a more important determinant of health care costs than the age of the population or hospital utilization. Since the use of expensive technology is highest during the first few days in hospital, decisions about health care policy should consider the possibility that the savings incurred by a further decline in HDs and ALOS may be offset by a possible increase in per diem hospital costs and in health care expenditures after discharge from hospital.

Background: Although influenza is usually a mild self-limiting disease it can cause serious complications in high risk groups. The economic costs of influenza are large due to the burden on the health system and absenteeism from work. There is evidence that the vaccine is underused in groups targeted for vaccination.

Objectives: To estimate: a) the compliance rate with the influenza vaccination in Israel during the winter seasons of 1998/1999 and 1999/2000, b) the role of health care personnel and the media in influencing compliance, and c) the reasons for lack of compliance in the elderly.      

Methods: Two national population-based random telephone surveys of 1,500 households were performed during October 1999 and January 2000 to survey influenza vaccination compliance prior to the winters of 1998/1999 and 1999/2000 respectively. Each survey was performed during four successive evenings. The response rate was 78.1% for the first survey and 79.1% for the second.

Results: Vaccination compliance was similar in both surveys. The average rate of vaccination was 6% for the population under 65 years and 50% for the population of 65 years and above. The overall vaccination rate was around 10%. The family physician was the main authority to recommend the vaccination, followed by the community nurse. Absence of recommendation and lack of faith in the efficacy of the vaccine were the main reasons for non-compliance.

Conclusion: Compliance rates with influenza vaccine in targeted groups in Israel remain relatively low. Health care personnel should be more involved in promoting the vaccine.
 

Background: The degree to which serum total cholesterol predicts cariovascular disease is uncertain. While most authors have placed TC among the most powerful risk indicators of CVD, some have claimed that it predicted CVD in women only, or even not at all.

Objective: To determine the predictive value of serum total cholesterol relative to diabetes, smoking, systolic blood pressure and body mass index (kg/m2), for cardiovascular disease mortality in 3,461 occupationally active Israeli males.

Methods: A prospective follow-up was carried out for the years 1987-1998 to determine the effect of age, smoking habits, a history of diabetes, SBP, BMI and TC, at entry, on CVD mortality.

Results: There were 84 CVD deaths during a total of 37,174 person-years follow up. The hazard ratios (95% confidence intervals) for CVD mortality with respect to variables at entry were: diabetes 5.2 (2.1-13.2), age 2.2 (1.7-2.9), smoking 1.3 (1.0-1.8), SBP 1.4 (1.1-2.0), TC 1.5 (1.0-2.1) and BMI 1.2 (0.7-2.2). Among non-obese, non-diabetic, normotensive subjects the hazard ratio of TC adjusted for age and smoking was 1.16 (1.09-1.22) per 10 mg/dl. In the remaining subjects it was 1.04 (0.98-1.12) only. There was a significant interaction between TC and diabetes, hypertension or obesity (P=0.003).

Conclusions: In this population of Israeli males we found an interaction between TC and other risk indicators for CVD. Confirmation is required for the unexpected finding that the predictive value of TC for CVD mortality among non-diabetic, non-obese and normotensive subjects exceeded that among subjects with either of these risk factors.
 

Background: The frequent coexistence of two or more sexually transmitted diseases in one patient has been reported in non-dermatological literature, mostly in languages other than English. Identification of Ureaplasma urealyticum, Chlamydia trachomatis and Mycoplasma hominis in men with other STDs is important, since these bacteria have been implicated in a variety of diseases such as non-gonococcal urethritis, premature rupture of fetal membranes, and infertility in female sexual partners of these patients.

Objective: To assess the frequency of concomitant STD, particularly urethral colonization of U. urealyticum, C. trachomatis and M. hominis, in men consulting for suspected STD-related symptoms.

Methods: All patients attending our dermatology clinic for STD-related symptoms during a 12 month period in 1996–97 underwent systematic clinical and laboratory screening for syphilis, gonorrhea, NGU, prostatitis, genital herpes simplex infection, Condyloma acuminatum, urethral carriage of U. urealyticum, C. trachomatis and M. hominis, as well as serological screening for HIV, and hepatitis B and C infections.

Results: A total of 169 men with STD-related symptoms were enrolled in the study. The following clinical diagnoses were established: NGU in 109 men, C. acuminatum in 40, genital herpes simplex in 10, prostatitis in 7, latent syphilis in 6, primary syphilis in 1, and Behcet’s disease in 1. No clinical evidence of STD was found in 13 patients. Of the 169 patients, 39 (23%) had two or more concomitant STDs, of whom 27 (69%) had C. acuminatum associated with one or more of the urethral pathogens. A positive U. urealyticum culture was found in 67.5% (27/40) of the men with C. acuminatum as compared to 42% (40/96) among the patients with NGU who did not have C. acuminatum (P=0.004, X² test). Conversely, the prevalence of C. acuminatum among patients positive for U. urealyticum was significantly higher than the prevalence among those who were negative – 27/75 (36%) vs. 13/94 (14%), P<0.0009, X² test. About half of the U. urealyticum-positive patients with C. acuminatum had no clinical signs or symptoms of urethritis.

Conclusion: Our findings suggest that patients with C. acuminatum should be assessed for U. urealyticum carriage and, when identified, their sexual contacts should be actively sought and treated.

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* Dr. Zvulunov is now with the Department of Pediatrics, Joseftal Hospital, Eilat, Israel.

STDs = sexually transmitted diseases

NGU = non-gonococcal urethritis