Israel Medical Association Journal

Patients with graft-versus-host disease suffer from xerostomia, oral infections and mucosal pathologies. The continuous increase in the number of patients treated worldwide with bone marrow transplants, combined with improved survival statistics result in a concomitant increase in the number of GVHD[1] patients. the pathogenesis of GVHD is based on donor graft T lymphocytes that recognize antigenic disparities between donor and recipient, and on the disregulation of a broad panel of cytokines. Consequently, various tissues and organs, including the mucosa of the oral and gastrointestinal tract, are damaged via cytotoxicity caused by infiltrating T cells. Since the salivary glands are a known major target of GVHD and their secretions significantly contribute to preserving mucosal integrity, this mucosal insult is further enhanced by the reduced quantity and altered quality of saliva. GVHD occurs in 40–70% of patients treated by bone marrow and peripheral blood stem cell transplantation. limited studies suggest that a large percentage of GVHD patients are affected and that the induced salivary dysfunction occurs rapidly following transplantation, affecting both major and minor salivary glands and reflecting the severity of the disease. Moreover, profound sialochemical alterations may be diagnostic of GVHD. an additional reason for the vast amount of research is that GVHD, as an autoimmune-like disease, seems to be an appropriate model for studying a much more prevalent, well-known and studied autoimmune disease involving salivary glands, namely, sjögren’s syndrome. The present review describes the GVHD-related sialometric and sialochemical data available in the literature for both major and minor salivary glands in both human and rodent models, and discusses a possible mechanism.

The Israel Health Ministry is preparing legislation that would allow a person to receive monetary compensation in exchange for donating a kidney for a lifesaving transplant. Such a bill would be the first of its kind, and would seem to establish a policy that is in contrast with both existing international professional ethics and major Christian and Islamic religious ethics. In an attempt to investigate the extent to which such a bill would be consistent with traditional Jewish ethics, we reviewed the opinions of major traditional Jewish ethicists/halakhists, with emphasis on contemporary opinions, and found that compensating an organ donor for his or her time, discomfort, inconvenience, and recovery is fully consistent with traditional Jewish law and ethics.  While non-altruistic sale of kidneys might be theoretically ethical from a Jewish perspective, ultimately its ethical status is inextricably connected to solving a series of pragmatic issues, such as creating a system that insures that potential vendors/donors are properly informed and not exploited; controlling and supervising medical screening and support of the donors to insure that their health is not permanently endangered; protecting minors and incompetents; and regulating payments so that they reasonably reflect compensation for pain and suffering.

The complexity of medical problems is a well-recognized phenomenon. In the presence of economic and cultural restrictions, medical decision-making can be particularly challenging. This paper outlines a system of analysis and decision-making for solving such problems, and briefly describes a case study in which the method was used to analyze the case of antibiotic overprescribing in a large health maintenance organization. The purpose of the study was to determine if a technique for problem-solving in the field of engineering could be applied to the complex problems facing primary care. The method is designated Systematic Inventive Thinking and consists of a three-step procedure: problem reformulation, general search-strategy selection, and an application of idea-provoking techniques. The problem examined is the over-prescribing of antibiotics by general practitioners working in Maccabi Healthcare Services, an HMO[1] serving one and a half million patients in Israel. The group of healthcare professionals involved in the discussions generated 117 ideas for improving antibiotic use. Six of these ideas were then implemented in a national campaign in the winter of 2000/1 and 2001/2. During this period, a significant reduction in per-visit antibiotic purchasing was observed for influenza visits (from 79.2 per 1,000 to 58.1 per 1,000, P < .0001), but not for other categories of visits. The SIT[2] methodology is a useful technique for problem-solving and idea generation within the medical framework.

Background: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke.

Objectives: To assess the feasibility and safety of rt-PA[1] therapy for reperfusion in routine clinical practice in Israel, in a setting of a dedicated stroke unit.

Methods: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography eligible patients were treated with intravenous rt-PA (0.9 mg/kg; maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Re-canalization was assessed by serial transcranial Doppler.

Results: The study group comprised 16 patients, mean age 61 years (range 47–80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6–24). They were treated within a mean door-to-CT time of 39 minutes (range 17–62 min), door-to-drug time 101 minutes (range 72–150), and stroke onset-to-drug time 151 minutes (range 90–180). There was an early improvement within 24 hours (of ≥ 4 points in the NIHSS[2] score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study.

Conclusion: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Background: Iodine intake is necessary to maintain normal thyroid function and prevent iodine deficiency disorders. In 1990, a resolution calling for universal salt iodination to eliminate iodine deficiency worldwide was taken by the World Health Organization and endorsed by some 130 countries. As of today, very little is known about iodine intake and the prevalence of iodine deficiency disorders in Israel, and iodine enrichment of regular salt has not been authorized.

Objectives: To assess the current level of iodine intake in an unselected group of residents from the Israeli costal area.

Methods: Spot urine samples were collected from three groups: Group A comprising 51 pregnant women attending the Women s Health Clinic at our institution, with a mean age of 32 years and at gestational week 28; group B consisting of 35 healthy subjects, mean age 38; and group C consisting of 16 euthyroid subjects harboring nodular goiters. Tap drinking and mineral water were also analyzed for iodine content. Iodine concentration was measured using the catalytic reduction of ceric ammonium sulfate method.

Results: When considering all groups together the median urinary iodine concentration was 143 µg/L, with 27% of the study population having concentrations under 100 µg/L and 7.8% under 50 µg/L. Values were distributed similarly between sites of residency, and no significant differences were seen between groups. The mean iodine concentration for tap drinking water was 22.8 µg/L (range 0.5–53.5 µg/L) and for mineral water 7 µg/L (range 0–15 µg/L).

Conclusions: Overall, iodine intake appeared to be satisfactory in our study population, however mild deficiency may exist in up to 26% of this group. A nationwide survey is needed to better determine the status of iodine intake in Israel, allowing for recommendations on salt-iodine enrichment in the future.

Background: Unexplained pulmonary hypertension is assumed to occur mainly in young adults.

Objectives: To describe the features of the disease in older patients and compare them to those in PHT[1] patients of all ages.

Methods: We conducted a retrospective evaluation of the files of patients over 65 years of age in whom UPHT[2] was diagnosed between 1987 and 1999 at two PHT centers serving a population of 4 million. Patients were followed for survival until March 2003. Clinical variables of the study patients were compared to those in PHT patients of all ages.

Results: The study group included 14 patients, 10 females and four males, with a mean age of 70.5 ± 6.7 years. The calculated mean annual incidence of UPHT for the study population was one new case per year per million persons. Seven patients (50%) had systemic hypertension. The mean interval from onset of symptoms to diagnosis was 8.3 months. At diagnosis, 64% of patients had functional capacity of III-IV according to the New York Heart Association classification, and 43% had right heart failure. Mean systolic pulmonary artery pressure was 80 ± 21 mmHg, peripheral vascular resistance 11.7 ± 7 mmHg/L/min, cardiac index 2.16 ± 0.81, and mean right atrial pressure 10.5 ± 5.9 mmHg. Median survival time was 43 months; survival rates for 1 year, 3 years and 5 years were 92.6%, 50%, 40%, respectively. Compared to data from the U.S. National Institute of Health Registry, UPHT in older patients is more common in females, but the incidence as well as clinical, hemodynamic and survival parameters are similar to those in PHT patients at any age.

Conclusions: UPHT occurs in the elderly more frequently than previously thought, with similar features in PHT patients of all ages. The coexistence of systemic and pulmonary hypertension warrants further investigation.

Background: Hypovitaminosis D is an important risk factor for osteoporosis and its complications. Previous studies found that the incidence of hypovitaminosis D among patients in an internal medicine ward reached up to 57%.

Objectives: To determine the prevalence and determinants of hypovitaminosis D among patients in internal medicine wards in a sunny country.

Methods: We measured 25-hydroxyvitamin D, parathyroid hormone and various other laboratory parameters, and assessed the amount of sun exposure, dietary vitamin D intake and other risk factors for hypovitaminosis D in 296 internal medicine inpatients admitted consecutively to the Soroka University Medical Center, which is situated in a sunny region of Israel.

Results: We found hypovitaminosis D (serum 25-HO-D[1] <15 ng/ml) in 77 inpatients (26.27%). The amount of sunlight exposure, serum albumin concentration, being housebound or resident of a nursing home, vitamin D intake, ethnic group, cerebrovascular accident and glucocorticoid therapy were all significantly associated with hypovitaminosis D. Multivariate analysis showed a significant association between hypovitaminosis D and Bedouin origin, sun exposure, vitamin D intake, and stroke. Hypovitaminosis D was also found among inpatients who reported consuming more than the recommended daily amount of vitamin D. Parathyroid hormone levels were significantly higher in patients with 25-OH-D levels below 15 ng/ml. In a subgroup of 74 inpatients under 65 years old with no known risk factors for hypovitaminosis D, we found 20.3% with hypovitaminosis D.

Conclusions: Hypovitaminosis D is common in patients hospitalized in internal medicine wards in our region, including patients with no known risk factors for this condition. Based on our findings, we recommend vitamin D supplementation during hospitalization and upon discharge from general internal medicine wards as a primary or secondary preventive measure.

Background: Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition associated with inflammatory bowel disease. PG[1] occurs rarely in IBD[2] patients and there are insufficient data on the clinical manifestations of this disease with IBD.

Objective: To determine the incidence, clinical manifestations and treatment of PG in patients with IBD and the connection to IBD, its activity and extent.

Methods: All patients hospitalized with IBD at a university hospital during a 20 year period were evaluated for the occurrence of PG.

Results: Of 986 patients hospitalized for IBD 6 suffered from PG (0.6% incidence). Their average age was 37 with equal sex distribution and equal distribution of Crohn’s disease and ulcerative colitis. PG appeared 6.5 years on average after diagnosis of IBD in all patients. The development of PG correlated with significant clinical exacerbation of IBD, the majority having active colitis at the onset of the PG. Extra-intestinal manifestations of IBD occurred in half the patients (sacroiliitis, peripheral arthritis and erythema nodosum). Pathergy was not elicited in any patients. Four patients had multiple skin lesions, frequently on the lower extremities. Diagnosis was made by skin biopsy in four patients. There was little correlation between amelioration of IBD and the skin lesions. Treatment consisted of high dose steroids and immunomodulatory drugs (cyclosporine, azathioprine and dapsone) in conjunction with topical treatment.

Conclusions: PG is a rare extra-intestinal manifestation of IBD that coincides with the exacerbation of the intestinal disease but does not always respond to treatment of the bowel disease.