Israel Medical Association Journal

Background: Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes were proposed to be involved in osteoporosis, but the precise genes and their relative contribution remain unknown.

Objectives: To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986s in the calcium-sensing receptor gene.

Methods: We analyzed 86 Jewish Israeli patients with LBMD[1]: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR[2] gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986s polymorphism in the CaSR[3] gene was performed using the denaturing gradient gel electrophoresis technique.  

Reaults: In LBMD women the distributions of VDR alleres in Apal polymorphism were AA=7/28, Aa=16/28 and aa=5/28; in TaqI polymorphism TT=10/31, Tt=16/31 and tt=5/31; and in BsmI polymorphism BB=7/32, Bb=14/32 and 11/32. In LBMD men the distributions were AA=17/39, Aa=21/39 and aa=1/39; in TaqI polymorphism TT=12/42, Tt=23/42 and tt=7/42; and in BsmI polymorphism BB=12/41 Bb=18/41 and bb=11/41. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986s polymorphism, compared with 40 of 203 controls (19.7%) (P=0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD[4] between homozygotes and heterozygotes (P=0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD.

Conclusions: In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

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Intractable forms of autoimmune diseases follow a rapid course, with a significantly shortened life expectancy sometimes comparable to that of malignant diseases. Immunoablative therapy, including high dose cytotoxic agents and hematopoietic autologous stem cell rescue, was recently introduced as an aggressive approach to treat autoimmune diseases that have a rapid course and are resistant to conventional therapy. The most frequent indication for this type of treatment is multiple sclerosis, seconded by systemic sclerosis. The results of immunoablative treatment with documented responses in both diseases are encouraging. The data are mature enough to begin comparative randomized studies of immunoablative versus conventional treatment to validate the benefit of the aggressive approach. A randomized trial involving SSc[1] was recently launched (ASTIS) and a trial involving MS[2] is under preparation. Considerably less experience with immunoablative treatment has been gained in systemic lupus erythematosus, rheumatoid arthritis, and other disorders with an autoimmune pathophysiology. Autologous hematopoietic stem cell transplantation in humans offers more long-lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic transplantation may replace the whole immune system. However, this attractive approach is still associated with considerable morbidity and mortality and is not yet justified for treatment of automimmune diseases. Non-myeloablative allogeneic transplantation and sub-myeloblative high dose cyclophosphamide without stem cell support are alternative approaches that could be explored in pilot studies.

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Background: The bladder tumor antigen stat is a simple and fast one-step immunochromatographic assay for the detection of bladder tumor-associated antigen in urine.

Objectives: To evaluate the BTA[1] stat in non-bladder cancer patients in order to identify the categories contributing to its low specificity.

Methods: A single voided urine sample was collected from 45 patients treated in the urology clinic for conditions not related to bladder cancer. Each urine sample was examined by BTA stat test and cytology.

Results: The overall specificity of the BTA stat test was 44%, which was significantly lower than that of urine cytology, 90%. The false positive rates for BTA stat test vary among the different clinical categories, being highest in cases of urinary tract calculi (90%), and benign prostatic hypertrophy (73%). Exclusion of these categories from data analysis improved BTA stat specificity to 66%.

Conclusions: Clinical categories contributing to low BTA stat specificity can be identified, and their exclusion improves the specificity of this test.

Background: Trauma is viewed by many as a global problem. The phenomenon of similar outcomes within differing healthcare delivery systems can illuminate the strengths and weaknesses of various trauma systems as well as the effects of these characteristics on patient outcome.

Objectives: To compare and contrast demographic and injury characteristics as well as patient outcomes of two urban/suburban trauma centers, one in Israel and the other in the United States.

Methods: Study data were obtained from the trauma registries of two trauma centers. Demographic variables, injury characteristics and outcomes were compared statistically between registries.

Results: Significant differences between the registries were found in demographic variables (age), injury characteristics (Injury Severity Score and mechanism of injury), and outcome (mortality and length of stay). Age and Injury Severity Score were found to be significant predictors of outcome in both registries. The Glasgow Coma Score was found to contribute to patient outcomes more than the ISS[1]. Differences were found in the relative impact of injury and demographic factors on outcomes between the registries. After including the influence of these factors on patient outcomes, significant differences still remained between the outcomes of the trauma centers.

Conclusions: Despite possible explanations for these differences, true comparisons between centers are problematic.

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Background: Previous studies have demonstrated myocardial salvage by basic fibroblast growth factor administration following chronic myocardial ischemia or acute myocardial infarction.

Objectives: To study the effect of bFGF[1] on left ventricular morphometry following coronary occlusion and reperfusion episode in rats.

Methods: bFGF (0.5 mg) or placebo was continuously administered for a period of one week using an implanted osmotic pump. Animals were sacrificed 6 weeks after surgery and myocardial cross-sections were stained with Masson-trichrome and with anti-proliferating cell nuclear antigen antibody.

Results: LV[2] area, LV cavity diameter, LV cavity/wall thickness ratio, and injury size were unchanged compared with control animals. Proliferating endothelial cells were significantly more abundant in injured compared with normal myocardium, but with no differences between animals treated or not treated with bFGF.

Conclusions: One week of systemic bFGF administration following coronary occlusion and reperfusion had no additional effect on LV geometry or cellular proliferation in rats.

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[1] bFGF = basic fibroblast growth factor

[2] LV = left ventricular

Background: Each winter influenza activity is a major cause of morbidity and mortality both in Israel and worldwide.

Objectives: To identify the influenza viruses active in Israel during the winter season and to assess the extent of influenza morbidity.

Methods: Information was collected on a population of 18,684 individuals enrolled in two community clinics in central Israel. It included the total number of visits for acute respiratory infection – including influenza and influenza-like illness (ARI/flu-like) – during a 20 week surveillance period (23 November 1997 to 27 March 1998) and the percent of influenza virus isolates in nasopharyngeal specimens from a sample of patients with ARI/flu-like collected on a weekly basis during the same period.

Results: A total of 5,947 visits for ARI/flu-like were recorded among 18,684 enrolled patients in two community clinics (18.1%). The progressive increase in the number of visits for ARI/flu-like reached a peak on week 2/98 with 597 visits and a rate of 31.95 visits per 1,000 population. After this, a decrease to the initial values was evident by week 12/98. Most affected patients were in the age groups 5–14 and 65 years and over, with a rate of 733.5 and 605.3 visits per 1,000 population, respectively. Influenza virus was isolated from 92 of the 426 nasopharyngeal specimens (21.6%). The most commonly detected strain was A/Sydney/5/97(H₃N₂) like (77.2%). The peak rate of isolates was recorded at the beginning of January (01/98).

Conclusions: A/Sydney/5/97(H₃N₂) like-strain was the dominant influenza virus. Its presence did not prevent the simultaneous activity of influenza A/H₁N₁ virus. The dynamic of the clinical disease as expressed by the weekly visit rate for ARI/flu-like was similar to the temporal pattern of the virological findings. The extent of morbidity suggests moderate epidemic activity.
 

Background: Migration leads to changes in almost all areas of life including health. But how far are health beliefs also preserved, and how far are they affected by the process of acculturation to the host society?

Objectives: To examine the difference between behavior and attitudes towards conventional and traditional medicine among elderly Yemenite immigrants.

Methods: A community-based study was conducted in the Yemenite neighborhoods in the city of Rehovot. All inhabitants of Yemenite origin over the age of 70 were identified from the population register, excluding those who were institutionalized or demented. Social work students interviewed them at home. The questionnaire inquired after health problems in the preceding month. For each of these problems, the respondent was asked whether any mode of treatment had been employed – Yemenite folk remedies, conventional medical care, or other. Their attitudes towards Yemenite folk medicine and conventional medicine were recorded. Socioeconomic data included their current age, age at immigration, year of immigration, marital status, gender, religiosity, and education.

Results: A total of 326 elderly people were identified who fulfilled the selection criteria, of whom 304 (93%) agreed to be interviewed. Of these, 276 (91%) reported at least one health problem in the preceding month, providing 515 problems of which 349 (68%) were reported to a conventional medical doctor while 144 (28%) were treated by popular folk remedies. Fifty-nine problems (11.5%) were treated by specifically Yemenite traditional remedies, mostly by the respondents themselves (38/59) rather than by a traditional healer. Immigrants who arrived in Israel over the age of 30 years, as compared to respondents who immigrated at an earlier age and grew up in Israel, were more likely to use traditional Yemenite remedies (24.4% vs. 8.2%, P<0.005).

Conclusion: Aged Yemenite Jews in Israel prefer modern medicine. The earlier the immigrant arrived in Israel, the more positive the attitude towards modern medicine and the less use made of traditional Yemenite healing.

Background: Familial Mediterranean fever is a genetic disease in which some characteristic gene mutation have been found.

Objective: To analyze the phenotype-genotype correlations in North African Jews and Armedians with FMF.

Methods: We studied MEFV gene mutations and phenotype-genotype correlations in North African Jews and Armedians with Familial Mediterranean Fever living in France.

Results: M694V mutation was the most common mutation in Jews and in Armenians. Patients with M6801 homozygosity or M6801/M694V compound heterozygosity had a phenotype as severe as patients with M694V homozygosity.

Conclusions: This study characterizes the phenotype-genotype in specific ethnic groups of patients with FMF.

Background: A beneficial effect was observed in patients with psoriasis vulgaris following balneotherapy with Dead Sea bath salt.

Objectives: To evaluate the possible role of trace elements in the effectiveness of balneotherapy. 

Methods: Serum levels of 11 trace elements were analyzed in 23 patients with psoriasis vulgaris who participated in a double-blind controlled study of balneotherapy, with either Dead Sea bath salt (12 patients) or common salt (11 patients). Thirteen healthy volunteers served as controls.

Results: The mean pre-treatment serum levels of boron, cadmium, lithium and rubidium were significantly lower in patients compared to controls, whereas the mean pre-treatment serum level of manganese was significantly higher in patients compared to controls. Balneotherapy with Dead Sea bath salt resulted in a significant decrease (P = 0.0051) in the mean serum level of manganese from 0.10 ± 0.05 mmol/L to 0.05 ± 0.02 mmol/L. The mean reduction in the serum level of manganese differed significantly (P = 0.002) between responders (% Psoriasis Area and Severity Index score reduction ³ 25) and non-responders (% PASI score reduction < 25). Following balneotherapy with Dead Sea bath salt the mean serum level of lithium decreased in responders by 0.01 ± 0.02 mmol/L whereas its level in non-responders increased by 0.03 ± 0.03 mmol/L. (P = 0.015).
Conclusions: Manganese and lithium may play a role in the effectiveness of balneotherapy with Dead Sea bath salt for psoriasis.

Background: The exact value of follow-up ultrasonogra­phy and computed tomography in the non-operative manage­ment of blunt splenic injuries is not yet defined. Although follow-up studies have been recommended to detect possible complications of the initial injury, evidence shows that routine follow-up CT scans usually do not affect management of these patients.

Objective: To determine whether follow-up imaging influences the management of patients with blunt splenic injury.

Methods: Between 1995 and 1999, 155 trauma patients were admitted with splenic trauma to a major trauma center. Excluded from the study were trauma patients with penetrating injuries, children, and those who underwent immediate laparotomy due to hemodynamic instability or associated injuries. The remaining trauma patients were managed conservatively. Splenic injury was suspected by focused abdominal sonography for trauma, upon admission, and confirmed by CT scan. The severity of splenic injury was graded from I to V. The clinical outcome was obtained from medical records.

Results: We identified 32 adult patients (27 males and 5 females) with blunt splenic injuries who were managed non-operatively. In two patients it was not successful, and splenectomy was performed because of hemodynamic dete­rioration. The remaining 30 stable patients were divided into two groups: those who had only the initial ultrasound and CT scan with no follow-up studies (n= 8), and those who under­went repeat follow-up ultrasound or CT scan studies (n = 22). The severity of injury was similar in both groups. In the second group follow-up studies showed normal spleens in 2 patients, improvement in 11, no change in 8, and deterioration in one. All patients in both groups were managed successfully with good clinical outcome.

Conclusion: In the present series the follow-up radiologi­cal studies did not affect patient management. Follow-up imaging can be omitted in clinically stable patients with blunt splenic trauma grade I-III.