Israel Medical Association Journal

Background: Two recent studies found that the prevalence of cryptosporidiosis among children in Israel was 3.4-7.4%.

Objectives: To assess the cumulative infection rate by testing immunoglobulin A and G seroprevalence for Cryptosporidium in children and adults in Israel.

Patients and Methods: The seroprevalence of IgA and IgG anti-Cryptosporidium antibodies was determined by an enzyme-linked immunosorbent assay procedure in a group of 163 healthy children and adults.

Results: The overall seroprevalence rates for IgG, IgA, both IgA and IgG, and any immunoglobulin were 12.6%, 23%, 30% and 65.6% respectively. Half the children under the age of 12 years were already infected, with seroprevalence increasing to 95.6% in those over age 13 (P<0.05). Seropositivity for IgG or IgA did not significantly increase with age.

Conclusions: These results indicate that a large percentage of healthy children and adults in northern Israel have been infected with Cryptosporidium, and at early ages.

Background: Smoking is the most important preventable cause of chronic disease in the western world. Many smokers want to quit, but have difficulty overcoming the addictive effect of nicotine.

Objectives: To assess the quitting rate of smokers who participated in smoking cessation groups and to characterize predictors of success or failure over a 1-3 year follow-up period.

Methods: We studied 89 participants in 7 groups. Questionnaires were completed at baseline and after a follow-up period of 1 to 3 years. Smoking cessation was determined by self-report and a carbon monoxide breath test.

Results: Of the 89 participants in the support groups 76 (85%) were located. An intention-to-treat analysis was done for these participants. At follow-up 25 (33%) were non-smokers. There was a 95% agreement rate between self-report of smoking status and CO breath analysis. There were no differences between quitters and non-quitters in education level, gender, age at initiation of smoking, previous quit attempts, extent of participation in group meetings, concern about gaining weight, Fagerstrom index, or the number of close friends or relatives who smoke. Belief in one's ability to quit, satisfaction with group meetings, and spouse support were significantly associated with success (P<0.01).

Conclusions: The quit rate was 33%. Self-report is a reliable method for assessing smoking status. Smokers' belief in their ability to quit must be reinforced. Spouse participation in some group meetings may be beneficial, as may the involvement of a dietician and an expert on exercise. Follow-up "booster" meetings may also help.

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CO= carbon monoxide

* In partial fulfilment of the requirements for an MD degree.

Background: Osteoporosis is the most common human bone disease. It affects millions of persons throughout the world and its prevalence will increase as the population ages worldwide.

Objective: To assess Israeli physicians' attitudes and knowledge with regard to management of osteoporosis.

Methods: A questionnaire was mailed to 1,900 Israeli physicians concerning their attitudes to the management of osteoporosis, their prescribing habits, and their knowledge on the pharmacological treatment of the disease.

Results: Replies were received from 19% of the physicians. The respondents encouraged physical activity and cessation of smoking for all women, and prescribed estrogen replacement as the main treatment for 50-year-old women. A relatively low level of knowledge was found regarding the adequate dosage of several of the pharmacological treatments.

Conclusions: The findings of the present study stress the need to provide clear guidelines and to extend physicians' knowledge regarding the management of osteoporosis.

Background: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+T cells of healthy subjects (normal T cells) to ECM components is inhibited in the presence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+T cells to ECM.

Objective: To evaluate chemokine (MIP-1β and RANTES) and tumor necrosis factor α-induced adhesion of CD4+T cells to ECM in a uremic milieu.

Methods: We examined adhesion of normal CD4+T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1β and RANTES) and to TNF-α following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group.

Results: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+T cells to ECM compared to a normal milieu (a peak response of 10–11% vs. 24–29% for soluble chemokines, P<0.001; 12–13% vs. 37–39% for bound chemokines on resting cells, P<0.01; and 18–20% vs. 45–47% for bound chemokines on activated cells, P<0.02). The same pattern of response was noted following stimulation with immobilized TNF-α (7 vs. 12% for resting cells, P<0.05; 17 vs. 51% for activated cells, P<0.01).  Adherence of dialysis patients’ cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15–17% vs. 25–32%, P<0.0000). In contrast, adherence following stimulation by TNF-α was of equal magnitude.

Conclusions: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1β, RANTES and TNF-α. However, whereas reduced adhesion to chemokines was present in both normal CD4+T cells in a uremic environment and in dialysis patients’ T cells, TNF-α-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.

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ECM = extracellular matrix

TNF-α = tumor necrosis factor-a

Background: Previous studies have suggested that prolactin may serve as an indicator of disease progression in breast cancer.

Objectives: To evaluate the use of PRL as a serum tumor marker in patients with breast cancer.

Methods: PRL serum level was determined in 99 breast cancer patients and compared with CA 15-3 serum level.

Results: Elevated serum level of PRL (>20 ng/ml) was found in 8 of 99 patients (8.1%). A stratified analysis of prolactin levels according to therapy revealed that PRL levels was increased in 8 of 55 untreated patients (14.5%), but not in patients who received hormonal or chemotherapy in the 3 months preceding the test (0/42 patients, P=0.009). However, mean PRL level was similar in patients with no evidence of disease activity and in patients with active disease (10.2 vs. 8.2 ng/ml, NS). In comparison, CA 15-3 mean level was significantly lower in patients with no evidence of disease as compared to patients with active disease (18.2 vs. 144.7 units/ml, P<0.001). PRL level was increased in 6 of 60 patients (10%) with no evidence of disease and in 2 of 39 (5.2%) with active disease (NS). In comparison, CA 15-3 level was increased in 3 of 60 patients (5%) with no evidence of disease and in 24 of 39 (61.5%) with active disease (P<0.001).

Conclusions: PRL levels are decreased following hormonal or chemotherapy in patients with breast cancer and there is no correlation between PRL serum level and the state of disease. Further studies are needed to clarify a possible clinical significance of hyperprolactinemia in a subset of patients with breast cancer.

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PRL = prolactin

Background: Spectral analysis of heart rate variability has been shown to be a reliable non-invasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a window reflecting the interaction of sympathetic and parasympathetic tone. Alterations in autonomic function are associated with a variety of physiologic and pathophysiologic processes and may contribute substantially to morbidity and mortality. Our previous study shows that patients with post-traumatic stress disorder have significantly lower HRV compared to controls, reflecting a basal autonomic state characterized by increased sympathetic and decreased parasympathetic tone.

Objectives: To apply this tool to PTSD patients treated with selective serotonin re-uptake inhibitors in order to assess the impact of such treatment on the autonomic dysregulation characterizing these patients.

Methods: Standardized heart rate analysis was carried out in nine PTSD patients treated with SSRI agents and compared to that in a matched control group of nine healthy volunteers and in nine untreated PTSD patients, based on a 15 minute resting electrocardiogram.

Results: Our preliminary results show that the HRV parameters indicating autonomic dysregulation, which characterize PTSD patients at rest, are normalized in responding patients by use of SSRIs. Neither the clinical implications of these findings nor their physiological mechanisms are clear at present, although we presume that they reflect a central effect, since the peripheral autonomic effects of SSRIs are relatively negligible.   

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HRV = heart rate variability

PTSD = post-traumatic stress disorder

SSRI = selective serotonin re-uptake inhibitor

Background: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors.

Objective: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation.

Methods: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring >1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor’s death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts.

Results: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n=13, 9.3%) or DGF (n=25, 17.9%). On regression analysis, donor age >50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors >50 years old, 21 (37.5%) developed either PNF (n=9) or DGF (n=12).

Conclusions: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from “aged” donors may help to choose appropriate donors from that pool.

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PNF = primary graft non-function

DGF = delayed graft function

Background: In trials comparing different formulations of measles vaccine, excess non-specific mortality occurred in female children who received high titer vaccine. These findings suggest a gender-specific effect of measles vaccine.

Objectives: To determine whether gender differences exist in the rates of adverse reactions and morbidity in the month following immunization with measles-containing vaccine, and to evaluate whether there is a gender-specific association between the humoral immune response to measles vaccination and post-vaccination morbidity.

Methods: Parents completed questionnaires on the health status of 755 infants aged 15-20 months, during the month preceding and the month following the measles-mumps-rubella vaccination. Blood samples were tested for measles antibody titers in a subsample of 237 infants.

Results: After controlling background morbidity in the infants, the relative risk of fever and rash following vaccination was 2.35 in females and 1.36 in males. The geometric mean antibody titers against measles were similar in both sexes and there was no significant association between antibody titer and post-vaccination morbidity in either sex.

Conclusions: Our findings demonstrate higher rates of adverse effects in females following vaccination with MMR vaccine, irrespective of the humoral response. This study emphasizes the need to consider possible gender differences when evaluating new vaccines.

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MMR= measles-mumps-rubella

Background: The pattern of diabetes and ischemic heart disease among emigrants from pre-industrialized societies to more developed countries may be explained by both genetic and environmental factors.

Objectives: To describe and interpret the pattern of diabetes and ischemic heart disease among Yemenite immigrants in Israel and their second-generation offspring.

Methods: Medical record charts of adult Yemenites were surveyed in a primary care health center, and the data were compared with prevalence rates derived from a non-Yemenite population.

Results: There was a marked excess of non-insulin dependent diabetes mellitus among Yemenite immigrants over 45 years of age, but not of hypertension or ischemic heart disease. Yemenites with diabetes were far less likely to develop ischemic heart disease than non-Yemenites with diabetes (odds ratio for non-Yemenites compared with Yemenites, 3.5; confidence interval 1.54<OR<7.77).

Conclusions: There was less of an association between diabetes and ischemic heart disease among Yemenites. This finding requires further investigation of the relative roles of genetic and environmental factors. 

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OR= odds ratio

Background: Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM.

Objectives: To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice.

Methods: Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice.

Results: Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83±10.67 vs. 4.44±10.83 mmol/L, P<0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104±27 vs. 151±36 mol/L, P<0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups.

Conclusions: This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.

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IDDM= insulin-dependent diabetes mellitus

NOD= non-obese diabetic