Israel Medical Association Journal

Background: The frequency of performing percutaneous endoscopic gastrostomy in demented older people has increased in recent years. Several reports indicate flaws in the criteria for performing PEG[1] and in the decision-making process, raising concerns about the adequacy of the consent.

Objectives: To examine knowledge and attitudes of referring doctors and gastroenterologists, and to evaluate attitudes and feelings of family members concerning PEG insertion.

Methods: We conducted a survey of 72 doctors who referred 126 demented patients for PEG, as well as 126 family members and 34 gastroenterologists. Closed-ended questionnaires were designed for each study group, completed by the participants, and computer analyzed.

Results: Approximately 50% of family members expressed dissatisfaction with the decision-making process. Referring physicians reported that PEG insertion was often dictated by the need to transfer patients to a nursing home, with 50% admitting institutional pressure. Most of the referring physicians believed that PEG improved quality of life and longevity, whereas gastroenterologists did not expect an improved quality of life and thought that administrative demands should not intervene in the decision to insert PEG.

Conclusions: The decision-making process in the patient's families regarding PEG insertion for their demented relative is unsatisfactory, often takes place under pressure, and does not provide sufficient information about the procedure or its complications. Interpersonal communication between the patient's family and the medical team need to be improved and institutional demands should not play a major role in the medical decision to insert PEG. Gastroenterologists should take a more active role in the deliberations regarding PEG.

Background: Pulmonary tuberculosis continues to be a major cause of mortality, particularly in developing countries. Despite modern anti-TB[1] treatment, the elderly and immigrants from TB-endemic countries are at risk. Multidrug resistance has yet to be resolved..

Objectives: To determine the mortality rate and predictors of mortality among patients hospitalized with TB in Israel.

Methods: We evaluated the medical records of 461 patients with active pulmonary TB who were hospitalized in the department of respiratory care during the 5 year period 2000–2004. Data included demographic, clinical, laboratory and radiological findings, drug resistance as well as adverse reactions to anti-TB treatment.

Results:| Three main ethno-geographic groups were observed: 253 patients from the former USSR, 130 from Ethiopia, and 54 of Israeli origin (as well as 24 residents of other countries). Of the 461 patients 65 patients (13%) died in hospital. The factors that were best predictors of mortality were older age, ischemic heart disease, cachexia, prior corticosteroid treatment, hypoalbuminemia and pleural effusion (P < 0.005 for all). The ethno-geographic factor and the presence of multidrug-resistant bacteria had no significant effect on mortality in our study group.

Conclusions: The mortality rate in our study was relatively low, and there was no significant difference between the three ethno-geographic groups.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

Background: Patients with end-stage renal disease are at high risk of mycobacterial infection.

Objectives: To analyze the difficulties in reaching an accurate diagnosis of tuberculosis in dialysis patients.

Methods: We conducted a retrospective follow-up of patients who attended our peritoneal and hemodialysis units during the 10 year period 1995–2005.

Results: Our dialysis unit diagnosed 10 cases of tuberculosis caused by Mycobacterium tuberculosis and 9 cases of Mycobacterium other than tuberculosis. In the former group, five patients had mycobacterium in the sputum, which was diagnosed by intraabdominal mass biopsy in one, culture of the gastric juices in one, and pleural fluid culture or pleural biopsy in three. One of these patients was suffering from pleural TB[1] as well as Potts disease. Of the patients with Mycobacterium other than tuberculosis, five were diagnosed by sputum cultures, three by urine cultures and one in peritoneal fluid. Differences in treatment and outcome were also reviewed.

Conclusions: The diagnosis of TB in dialysis patients should be approached with a high index of suspicion. It is clear that extensive diagnostic procedures are required to ensure an accurate diagnosis of the disease. Tuberculosis incurs a significant added burden due to the need for isolation of infected patients within the dialysis unit. Treatment of patients with Mycobacterium other than tuberculosis should be addressed individually.

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

Background: Despite improved management of heart failure patients, their prognosis remains poor.

Objectives: To characterize hospitalized HF[1] patients and to identify factors that may affect their short and long-term outcome in a national prospective survey.

Methods: We recorded stages B-D according to the American College of Cardiology/American Heart Association definition of HF patients hospitalized in internal medicine and cardiology departments in all 25 public hospitals in Israel.

Results: During March-April 2003, 4102 consecutive patients were recorded. Their mean age was 73 ± 12 years and 57% were males; 75.3% were hypertensive, 50% diabetic and 59% dyslipidemic; 82% had coronary artery disease, 33% atrial fibrillation, 41% renal failure (creatinine ³ 1.5 mg/dl), and 49% anemia (hemoglobin £ 12 g/dl). Mortality rates were 4.7% in-hospital, 7.6% at 30 days, 18.7% at 6 months and 28.1% at 12 months. Multiple logistic regression analysis revealed that increased 1 year mortality rate was associated with New York Heart Association III–IV (odds ratio 2.07, 95% confidence interval 1.78–2.41), age (for 10 year increment) (OR[2] 1.41, 95% CI[3] 1.31–1.52), renal failure (1.79, 1.53–2.09), anemia (1.50, 1.29–1.75), stroke (1.50, 1.21–1.85), chronic obstructive pulmonary disease (1.25, 1.04–1.50) and atrial fibrillation (1.20, 1.02–1.40).

Conclusions: This nationwide heart failure survey indicates a high risk of long-term mortality and the urgent need for the development of more effective management strategies for patients with heart failure discharged from hospitals.

Background: Heart failure with preserved systolic left ventricular function is a major cause of cardiac disability.

Objectives: To examine the prevalence, characteristics and late clinical outcome of patients hospitalized with HF-PSF[1] on a nationwide basis in Israel.

Methods: The Israel nationwide HF survey examined prospectively 4102 consecutive HF patients admitted to 93 internal medicine and 24 cardiology departments in all 25 public hospitals in the country. Echocardiographic LV function measurements were available in 2845 patients (69%). The present report relates to the 1364 patients who had HF-PSF (LV ejection fraction ≥ 40%).

Results: Mortality of HF-PSF patients was high (in-hospital 3.5%, 6 months 14.2%, 12 months 22.0%), but lower than in patients with reduced systolic function (all P < 0.01). Mortality was higher in patients with HF as the primary hospitalization diagnosis (16.0% vs. 12.5% at 6 months, P = 0.07 and 26.2% vs. 18.0% at 12 months, P = 0.0002). Patients with HF-PSF who died were older (78 ± 10 vs. 71 ± 12 years, P < 0.001), more often female (P = 0.05) and had atrial fibrillation more frequently (44% vs. 33%, P < 0.01). There was also a relationship between mortality and pharmacotherapy: after adjustment for age and co-morbid conditions, mortality was lower in patients treated with angiotensin-converting enzyme inhibitors (P = 0.0003) and angiotensin receptor blockers (P = 0.002) and higher in those receiving digoxin (P = 0.003) and diuretic therapy (P = 0.009).

Conclusions: This nationwide survey highlights the very high late mortality rates in patients hospitalized for HF without a decrease in systolic function. The findings mandate a focus on better evidence-based treatment strategies to improve outcome in HF-PSF patients.

Background: The etiology of chest pain with normal epicardial coronary arteries (cardiac syndrome X) seems to be related to endothelial cell dysfunction. Multiple factors are implicated in the pathophysiology, including evelated levels of homocysteine in the blood. Mutations in the MTHFR gene are associated with evelated levels of homocysteine.

Objectives: To test whether abnormal homocysteine metabolism is associated with syndrome X.

Methods: Forty-two women with chest pain, positive stress test and normal coronary arteries (syndrome X) and 100 asymptomatic women (controls) were studied for the C677T mutation. Vitamin B12, folic acid, and plasma levels of homocysteine were also measured. Endothelial cell function was studied in 10 patients with syndrome X and homozygosity for C677T mutation, and in 10 matched healthy controls. Folic acid (5 mg daily) was prescribed to syndrome X patients after initial measurements of ECF[1]. Following 13 weeks of treatment, ECF and blood tests were repeated and compared to baseline measurements.

Results: Homozygosity for C677T mutation was doubled in syndrome X vs. control (33%, 14/42 vs. 16%, 16/100, P < 0.02), and homocysteine levels were increased (9.16 ± 2.4 vs. 8.06 ± 2.6 μmol/L, P = 0.02). In the 10 homozygous patients, homocysteine levels decreased significantly after treatment with 5 mg/day folic acid (10 ± 3.3 vs. 5.4 ± 1.1 µmol/L, P = 0.004). Abnormal baseline ECF improved after treatment with folic acid: flow-mediated dilatation was greater (11.3 ± 7.9% vs. 0.7 ± 4.5%, P < 0.002), as was nitroglycerin-mediated dilatation (15.2 ± 9.0% vs. 5.6 ± 6.4%, P < 0.003). Frequency of chest pain episodes was significantly reduced after 13 weeks of folic acid treatment.

Conclusion: Our findings establish the association between the C677T mutation, endothelial cell dysfunction and cardiac syndrome X, and provide a novel and simple therapy for a subset of patients with syndrome X and homozygosity for the C677T mutation.

Background: Despite significant advances in the therapy of heart failure, many patients still do not receive optimal treatment.

Objectives: To document the standard of care that patients hospitalized with HF[1] in Israel received during a 2 month period.

Methods: The Heart Failure Survey in Israel 2003 was a prospective 2 month survey of patients admitted to all 25 public hospitals in Israel with a diagnosis of HF.

Results: The mean age of the 4102 patients was 73 years and 43% were female. The use of angiotensin-converting enzyme/angiotensin receptor blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6% for ACE[2]-inhibitor/ARB[3] and 64.1% to 52.9% for beta blockers, P < 0.001 for comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or ARB and a beta blocker at hospital discharge also declined from NYHA class I to IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being discharged with an ACE-inhibitor or ARB was the use of these medications at hospital admission. Negative predictors for their usage were age, creatinine, disease severity class, and functional status.

Conclusions: Despite the dissemination of guidelines many patients did not receive optimal care for HF. Reasons for this discrepancy need to be identified and modified.

Background: The prevalence and incidence of blindness in Israel appear to be comparable to other western countries. Comparisons are difficult because of different definitions of blindness, and the uniqueness of the Israeli registry for the blind.

Objective: To characterize the population who were registered as Blind in Israel in the years 1998–2003 and estimate the prevalence and incidence of blindness by age and causes of blindness.

Methods: A retrospective review of the annual report of the National Registry for the Blind in Israel between 1998 and 2003 identified 21,585 blind persons who received a certificate for blindness. Blind persons are identified by ophthalmologists throughout Israel and referred to the Registry of the Blind if they have a visual acuity of 3/60 or worse, or a visual field loss of < 20 degrees in their better eye. This report includes prevalence data on 21,585 persons enrolled in this review still alive and living in Israel in 2003. We estimated the prevalence rate of blindness nationwide and the incidence rate for each cause of blindness for every year.

Results: The main leading causes of blindness in Israel in 1998 were (in percent of the total number of newly registered patients): age-related macular degeneration (20.1%), glaucoma (13.8%), myopic maculopathy (12%), cataract (10.4%), diabetic retinopathy and maculopathy (10.1%), and optic atrophy (7.9%), and in 2003, 28%, 11.8%, 7.4%, 6.5%, 14.4% and 6.5% respectively.

Conclusions: The results indicate that the incidence of age-related macular degeneration, diabetic retinopathy and maculopathy in Israel is increasing, while that of glaucoma, myopic maculopthy, optic atrophy and cataract is decreasing.