Israel Medical Association Journal

Background: Primary idiopathic pulmonary hypertension is a rapidly progressive disease with a median survival of less than 3 years. Recently its prognosis was shown to dramatically improve with the use of epoprostenol, an arachidonic acid metabolite produced by the vascular endothelium, which increases the cardiac output and decreases the pulmonary vascular resistance and pulmonary arterial pressure. This drug enhances the quality of life, increases survival and delays or eliminates the need for transplantation.

Objective: To review the experience of Israel hospitals with the use of epoprostenol.

Methods: The study group comprised 13 patients, 5 men and 8 women, with an age range of 3–53 years. All patients suffered from arterial pulmonary hypertension. Epoprostenol was administered through a central line in an increased dose during the first 3 months, after which the dose was adjusted according to the clinical syndrome and the hemodynamic parameters.

Results: After 3 months the mean dose was 10 ng/kg/min and the pulmonary artery pressure decreased from 7 to 38%. After one year, the PAP decreased at a slower rate. Two cases required transplantation, three patients died, and seven continued taking the drug (one of whom discontinued). Four episodes of septicemia were observed. Today 10 patients are alive and well and 7 continue to take epoprostenol.

Conclusion: We found that epoprostenol improves survival, quality of life and hemodynamic parameters, with minimum side effects.

Background: Breast cancer is the most common malignancy among women in Israel and throughout the world. Israeli women aged 50–75 years are advised to undergo a mammographic screening examination every 2 years. However, the lack of a structured referral system is reflected in the low utilization rate of mammography.

Objectives: To describe an innovative program in which family physicians in an urban clinic developed a model framework for referrals, coordinated with radiologists and surgeons, aimed at increasing compliance among women referred for mammography.

Methods: A community-based study was conducted, outside of the regular reception hours, in a neighborhood practice with a population of 527 women aged 50–75. A referral system under the supervision of family physicians was designed, and the women received appointments for mammography at specified days and hours. The results of the examination were sent to the physician who used dedicated time to continue the diagnostic and/or therapeutic process, as appropriate. At the physician’s instructions a research assistant contacted the women who did not keep their appointments and scheduled a second appointment.

Results: In 1993, the year prior to the study, when women referred themselves for mammography, the utilization rate was 9%. During the study year the utilization rate was 77%. Women born in Europe or America had higher compliance rates than women born in Asia or Africa (81% vs. 72%, respectively). Married women were more compliant than unmarried women (81% vs. 70%, respectively). No correlation was found between compliance and age, family history of cancer in general, or breast cancer in particular. Six new cases of breast cancer were detected.

Conclusions: The initiative of family physicians increased the utilization of mammography among women under their care. Family physicians allocated time outside of their regular reception hours for the program. A relatively large number of new malignancies were found, but this impression should be confirmed or negated by a large-scale study using the same methods.
 

Background: Most of the published documents proposing teaching objectives for undergraduate clerkships were prepared by expert bodies. Seldom have the clinical teachers, who are critical to the learning process and to the implementationof the  teaching objectives, been the actual proponents of its core content.

Objective: To develop a national-scale proposal of teaching, objectives for the family medicine clerckship in medical school, using a consensus method and the actual, community-based teachers as the expert body.

Method: The Delphi method was chosen for that purpose. In the first round all 189 family medicine teachers in Israeli medical schools were asked to propose five teaching objectives. In the second round the objectives, which were generatedin the first round, were characterized by key words and were send to the participants as a second round for ranking according to their importance.

Results: A total of 116 family medicine teachers (61.38%) responded in the first round and 91 of the 116 (78.5%) in the second round. They formulated 51 teaching objectives listed in order of importance, covering a wide array of themes and including knowledge, attitude and skills objectives. The most important objectives were common problems in primary care, recognition of the biopsychosocial model, and understanding the importance of the doctor-patient relationship. The structure of the list provides a uniqe insight into the relative importance of each objective in the context of the whole core content of the clerkship.

Conclusions: Constructing a proposal for teaching objectives is feasible using the Delphi method and the field instructors as the selecting body. The process and its results can provide faculty with relevant and important suggestions on the content and structure of the family medicine clerkship.
 

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.

Objective: To investigate whether cigarette smoking has an additive effect on the clinical presentation and course of disease in Helicobacter pylori-positive dyspeptic patients.

Patients and Methods: The study group comprised 596 consecutive H. pylori-positive dyspeptic patients (334 males and 262 females, mean age 50.6, range 12--81 years). Following upper gastrointestinal endoscopy, patients were subdivided by diagnosis as follows: Non-ulcer patient group (n=312: gastritis 193, duodenitis 119), gastric ulcer (n=19), and duodenal ulcer (n=265). H. pylori infection was confirmed by histology and/or rapid urease test. In addition, 244 patients had a positive 14C-urea breath test prior to antimicrobial treatment. The patients' medical history and smoking habits were obtained using a detailed questionnaire completed by the patients and their referring physicians.

Results: There were 337 non-smoking patients, 148 current smokers and 111 past smokers. Gastric and duodenal ulcers were significantly less prevalent in non-smokers than in current or past smokers (gastric 1.8%, 4.1%, 6.3%; duodenal 39.8%, 50%, 51.4%, respectively) (P0.05). The incidence of gastrointestinal bleeding was significantly lower in non-smokers than in current or past smokers (7.1%, 8.1% and 20.7%, respectively) (P0.05). Bacterial density, as assessed by the UBT value in 244 patients, was higher in non-smokers (mean 352.3273 units) than in past smokers (mean 320.8199) or current-smokers (mean 229.9162) (P0.05). Logistic regression analysis revealed that male gender, current smoking, and immigration from developing countries were all significant independent risks for developing duodenal ulcer, while only past smoking was associated with a higher rate of upper gastrointestinal bleeding in the past.

Conclusions: In H. pylori-positive dyspeptic patients, current smoking as well as male gender and immigration from developing countries are associated with an increased risk for duodenal ulcer. This effect does not seem to be related to the bacterial density or increased urease activity of H. pylori organisms.

Background: Data regarding the epidemiology of secondary pulmonary hypertension are scanty.

Objectives: To describe the spectrum and relative incidence of background diseases in patients with significant secondary PHT.

Methods: We identified 671 patients with systolic pulmonary artery pressure of 45 mm Hg or more from the database of the echocardiographic laboratory. Their background diseases were recorded and classified into three subgroups: cardiac, pulmonary and pulmonary vascular disease without pulmonary parenchymal disease. Age at the first echocardiographic study, gender and systolic PAP values were recorded. Data between the three subgroups were compared.

Results: The mean age of the patients was 6515 years, mean systolic PAP 6114 mm Hg and female:male ratio 1.21:1. At the time of diagnosis 85% of the patients were older than 50. PHT was secondary to cardiac disease in 579 patients (86.3%), to PVD without PPD in 54 patients (8%) and to PPD in only 38 patients (5.7%). Mean age and mean systolic PAP did not differ significantly among the three subgroups. There was a significantly higher female: male ratio in patients with PVD without PPD compared with cardiac or pulmonary diseases (1.7:1 vs. 1.2:1 and 1.7 vs. 0.8:1 respectively, P0.05).

Conclusions: The majority of patients with significant PHT are elderly with heart disease. PVD without PPD and chronic PPD are a relatively uncommon cause of significant PHT. Since the diagnosis of PHT is of clinical significance and sometimes merits different therapeutic interventions, we recommend screening by Doppler echocardiography for patients with high risk background diseases.

Background: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases.

Objectives: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel.

Methods: We examined the G380R mutation (G>A and G>C transition) and the mutation G375C (G>T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia.

Results: We found the G>A transition at codon 380 in 30 of our patients and the G>C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia.

Conclusions: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

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FGFR3 = fibroblast growth factor receptor 3

Background: In simultaneous pancreas-kidney transplantation, with both organs coming from the same donor, the addition of a pancreas to the kidney transplant does not jeopardize the kidney allograft outcome despite higher postoperative SPK morbidity. Pancreas allograft outcome has recently improved due to better organ selection and more accurate surgical techniques.

Objective: To demonstrate the positive impact of SPK on kidney allograft outcome versus kidney transplantation alone in insulin-dependent diabetes mellitus patients with end-stage renal failure.

Methods: We performed 39 consecutive SPKs in 14 female and 25 male IDDM patients with renal failure after an average waiting time of 9 months. Multi-organ donor age was 30 years (range 12-53). The kidneys were transplanted in the left retroperitoneal iliac fossa following completion of the pancreas transplantation; kidney cold ischemia time was 16±4 hours. Induction anti-rejection therapy was achieved with polyclonal antithymocytic globulin and methylprednisolone, and maintenance immunosuppression by triple drug therapy (prednisone, cyclosporine or tacrolimus, and azathioprine or mycophenolate mofetil). Infection and rejection were closely monitored.

Results: All kidney allografts produced immediate urinary output following SPK. Two renal grafts had mild function impairment due to acute tubular damage but recovered after a short delay. Three patients died from myocardial infarction, cerebrovascular event and abdominal sepsis on days 1, 32 and 45 respectively (1 year patient survival 92%). An additional kidney allograft was lost due to a renal artery pseudo-aneurysm requiring nephrectomy on day 26. Nineteen patients (49%) had an early rejection of the kidney that was resistant to pulse-steroid therapy in 6. No kidney graft was lost due to rejection. Patients with acute kidney-pancreas rejection episodes suffered from severe infection, which was the main cause of morbidity with a 55% re-admission rate. Complications of the pancreas allograft included graft pancreatitis and sepsis, leading to a poor kidney outcome with sub-optimal kidney function at 1 year. Kidney graft survival at one year was 89% or 95% after censoring the data for patients who died with functioning grafts.

Conclusions: Eligible IDDM patients with advanced diabetic nephropathy should choose SPK over kidney transplantation alone from either a cadaver or a living source.

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SPK= simutaneous pancreas-kidney transplatation

IDDM= insulin-dependent diabetes mellitus

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