Israel Medical Association Journal

Background: Type 2 diabetes, an extreme state of glucose intolerance, has been found to be associated with cancer mortality; less is known about impaired glucose tolerance and cancer incidence.

Objectives: To examine the association between fasting and post-load plasma glucose and insulin, and the 20 year incidence of cancer.

Methods: We followed a sample of the Jewish Israeli population (n=2780), free of cancer at baseline,

from 1977-1980 to 1999 for cancer incidence and mortality. Baseline fasting and 1 and 2 hour post-load plasma glucose levels were recorded, as was insulin in 1797 of them.

Results: During 20 years, 329 individuals (11.8%) developed cancer. Cancer incidence for all sites differed between men and women (13.0% and 10.7%, P = 0.03), and among different glucose tolerance status groups (P = 0.01). Cancer incidence hazard ratio, by glucose status adjusted for gender, age, ethnicity, smoking and body mass index, was 1.24 (95%CI 0.96–1.62, P = 0.10) for impaired fasting glucose or impaired glucose tolerance, and 1.32 (95%CI 0.96–1.81, P = 0.09) for type 2 diabetes mellitus, compared to those who were normoglycemic at baseline. Fasting insulin and cancer incidence were not associated.

Conclusions: An increased long-term cancer risk for individuals with impaired fasting glucose or glucose tolerance, or diabetes, is suggested. Even this modest association could have substantial public health consequences.
 

Background: The cognitive impairment (frontal, parietal) in many patients with multiple sclerosis does not correlate with the degree of neurological disability and disease duration. Frontal/prefrontal cognitive impairment requires neuropsychological diagnostic tools.

Objectives: To evaluate the clinical effect of IFNβ-1b[1] (Betaferon®) treatment on cognitive function and event-related potential as compared to the clinical course (EDSS[2]) in MS patients during 1 year of follow-up.

Methods: This prospective open-label design study included 16 consecutive patients with relapsing forms of MS attending the MS outpatient clinic. Mean EDSS score was calculated prior to starting treatment. Parietal lobe event-related potential P300 was elicited using an auditory physical stimulus to an alert subject. Mean P300 amplitude and latency were calculated for the group before treatment. The Wisconsin Card Sorting Test, which measures frontal lobe functions, was performed before the treatment. After 1 year of treatment a second P300 and Wisconsin Card Sorting Test were performed and the mean change between visit 1 and baseline was calculated for each parameter. Correlation between the change in P300 and the Wisconsin Card Sorting Test score at baseline was measured using the paired t-test.

Results: There was a significant reduction in P300 amplitude and latency after 1 year of treatment with IFNβ-1b: from 20.3 ± 8.3 μv to 13.1 ± 10.6 μv (P = 0.026) for amplitude, and from 312.9 ± 15.6 msec to 302.0 ± 17.0 msec (P = 0.002) for latency. The Perseverative Response (raw score) and the Perseverative Response U.S. Census age-matched standard score showed a significant improvement – from 20.7 ± 30.7 to 13.1 ± 10.6 (P = 0.001) and 96.7 ± 15.7 to 100.1 ± 11.1 (P = 0.0025) respectively – after 1 year of treatment. A mild but not significant improvement was observed on the EDSS after 1 year of treatment: 2.9 ± 0.5 to 2.8 ± 1.1.

Conclusions: A cognitive decline in MS patients may have a negative impact on the quality of life, affecting all active daily living domains. IFNβ-1b, a disease-modifying therapy, has demonstrated a positive therapeutic effect on cognitive dysfunction, unrelated to its effect on the EDSS score and course of the disease.

Background: Numerous studies have shown an association between asthma and mental disorders. While elevated rates of asthma have been noted among psychiatric patients with anxiety disorders and post-traumatic stress disorder, several studies have found elevated rates of mental disorders among asthma patients. Such studies, however, have generally relied upon questionnaires and assessment by non-specialist physicians to diagnose mental disorders and asthma.

Objectives: To examine a possible association between asthma and psychiatric diagnoses in Israeli military recruits and soldiers.

Methods: In this cross-sectional study we compared the prevalence of mental diagnoses in asthmatic recruits and soldiers to that in non-asthmatic recruits and soldiers. A total of 195,903 recruits and soldiers were examined by Israel Defense Forces recruiting offices and fitness boards. Diagnoses of asthma were based on a pulmonologist's diagnosis, including spirometry at rest and exercise testing as indicated; diagnoses of mental disorders were based on examination by a psychiatrist.

Results: The prevalence of asthma was found to be 7.8% (current) and 9.8% (lifetime). The prevalence of mental disorders was 13.4%. Current asthma was associated with an increased likelihood of any mental disorder (OR = 1.20, 95% CI = 1.15–1.26), and specifically with mood and anxiety disorders (1.31, 1.19–1.46), introvert personality disorders (1.20, 95% 1.12–1.28) and adjustment disorder (1.43, 1.26–1.62). Lifetime asthma was associated with an increased likelihood of the same disorders, but the association was not as powerful.

Conclusions: The results validate the previously documented association between asthma and mental disorders, using a sample of unprecedented size and improved methodology. A multidisciplinary approach to asthma that incorporates mental health professionals in the treatment of poorly controlled asthma and perhaps of asthma in general is recommended.
 

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: Radiofrequency ablation has been suggested as first-line therapy in the management of accessory pathways. There are limited data on the results of ablation over years of experience.

Objectives: To assess the results and complications following RFA[1] of APs[2] performed in our institution over a 14 year period.

Methods: RFA was performed using deflectable electrode catheters positioned at the mitral or tricuspid annulus. The site of the AP was localized by electrophysiological study and radiofrequency energy was applied via the tip of the catheter

Results: The study cohort comprised 508 consecutive patients (64.2% males, mean age 33.6 ± 15.1 years) who underwent 572 RFA procedures for ablating 534 APs. A single AP was found in 485 (95.5%) patients while multiple APs were noted in 23 patients (4.5%). The APs were manifest, concealed or intermittent in 46.8%, 44.4% and 8.8% of cases, respectively. AP distribution was as follows: left free wall (56.6%), posteroseptal (23%), right anteroseptal (7.9%), right free wall (6.2%), midseptal (3.4%) and right atriofascicular (3.0%). Acute successful rates for a first or multiple ablation attempts were 93.1% and 95.3%, respectively. At a first ablation attempt, acute success and failure rates were the highest for midseptal (100%) and right atriofascicular (12.5%) APs respectively. Right anteroseptal APs were associated with the highest rate (23.9%) of discontinued or non-attempted procedures. Recurrent conduction in an AP after an initial successful ablation was observed in 9.9% of cases; it was the highest (24.2%) for right free wall APs and the lowest (5.0%) for left free wall APs. During follow-up (85 ± 43 months), definite cure of the AP was achieved in 94.9% of cases following a single or multiple procedures: midseptal (100%), left free wall (98%), right free wall (97%), posteroseptal (92.7%), right atriofascicular (87.5%) and right anteroseptal (78.5%). A non-fatal complication occurred in 18 patients (3.5%), more frequently in females (6.6%) than in males (1.8%) (P < 0.01). The two major complications (pericardial effusion and myocardial ischemic events) mainly occurred during RFA of a left free wall AP using a retrograde aortic approach. Catheter-induced mechanical trauma to APs was observed in 56 cases (10.5%). Mechanical trauma mainly involved right atriofascicular (43.8%) and right anteroseptal (38.1%) APs and contributed to the low success rate of RFA at these AP locations. During the 14 year period, our learning curve was achieved quickly in terms of success rate, although the most significant complications were observed at the beginning of our experience.

Conclusions: The results of this study confirm the efficacy and safety of RFA and suggest that it is a reasonable first-line therapy for the management of APs at any location.

Background: There is little published information on the coronary risk characteristics of Palestinian women. However, there are documented lifestyle differences as well as socioeconomic inequalities between Arab and Jewish women in Israel.

Objectives: To compare the risk factor characteristics of coronary heart disease patients in Palestinian and Israeli women.

Methods: This study included 546 women (444 Jews and 102 Arabs) aged 35-74, all residents of Jerusalem, who underwent cardiac catheterization at the Hadassah-Hebrew University Medical Center between 2000 and 2003, and were confirmed to have coronary artery disease; Data on multiple risk factors were obtained from patient interviews and files.

Results: Compared with Jewish women, Arab women had a higher prevalence of diabetes, had borne more children/were younger, had a lower socioeconomic status, consumed jess alcohol and more olive oil, suffered more passive smoking and were less physically active. On the other hand, fewer Arab women had dyslipidemia, used hormone replacement therapy and had a family history of CHD.

Conclusions: Compared to Jewish women, Palestinian Arab women in Jerusalem appear to have more diabetes and exhibit lifestyle factors that generally increase the risk for CHD. Greater attention to primary prevention in this ethnic group is needed. This study suggests the need to investigate determinants of the metabolic syndrome and the possible role of passive smoking in Arab women as well as modes of intervention via health promotion and risk factor management in this population.
 

Background: Most Israeli males aged 16–17 undergo a thorough medical examination prior to recruitment into the army. During the last 50 years, extensive data have been gathered enabling a study of time trends in the prevalence of common diseases in this age group.

Objectives: To examine the current prevalence of common diseases, compare the results with those of previous cohorts, and assess the influence of the massive immigration during the 1990s.         

Methods: The health examination at the recruitment centers includes a medical history, complete physical examination, and review of medical documentation provided by the family physician. If needed, additional tests and referral to specialists are ordered. The prevalence of selected diseases and severity was drawn from the computerized database of the classification board. Two cohorts, 1992–94 and 2003–04, were examined and compared with three previous cohort studies in 1957–61, 1977–78 and 1982–84. Data were stratified according to origin and country of birth.

Results: The prevalence of asthma increased dramatically during the years from 10.2 per 1000 examinees in 1957–61 to 111.6 per 1000 examinees in 2003–04. The prevalence of tuberculosis declined and then increased from 0.6 per 1000 adolescents in 1982–84 to 2.4 per 1000 adolescents in 2003–04. The prevalence of type 1 diabetes mellitus increased from 0.2 cases per 1000 examinees in 1957–61 to 0.8 cases in 1977–78 and 1982–84 and 0.9 cases per 1000 examinees in 2003–04. The prevalence of severe heart defects and severe epilepsy declined in the last 20 years (1.4 and 1.7 cases per 1000 examinees in the 1982–84 cohort to 0.4 and 0.3 cases per 1000 examinees in the 2003–4 cohort respectively). The patterns of disease prevalence were different for immigrants: tuberculosis was more common while asthma and allergic rhinitis were less prevalent.

Conclusions: The prevalence of common diseases among adolescents in Israel has changed over the last 50 years. There is a different pattern for immigrants and for those born in Israel.

Rembrandt van Rijn (1606–1669) left behind the largest collection of self-portraits in the history of art. These portraits were painted over a period of 41 years, using a realistic technique. To evaluate Rembrandt's aging process we studied 25 uncontested Rembrandt oil self-portraits by means of objective and descriptive techniques. By measuring brow position changes through the years, we demonstrated that brow descent started in the second half of the third decade and began to level out in the fourth decade. Based on Rembrandts' aging physiognomy, from age 22 to 63, we believe that Rembrandt did not suffer from temporal arteritis, hypothyroidism, rosacea, or rhynophima and that no other facial signs of systemic diseases are evident, contrary to the opinions expressed by other medical professionals. We suggest that Rembrandt suffered from melancholia or mild depression, and propose the possibility of chronic lead poisoning as a theoretical illness that he might have had.

Background: Decreased lacrimal gland output may cause dry eye syndrome. Using a rat model, we examined the feasibility of transplanting lacrimal gland cells from newborns.

Objectives: To restore lacrimal gland function in eyes with compromised tear production.

Methods: A model of dry eye in adult rats was developed by unilateral surgical removal of the main lacrimal gland. Tear secretion in both eyes was then assessed by masked Schirmer's test. Lacrimal gland tissue from newborn rats was transplanted into the fibrous connective tissue in which the lacrimal gland had been embedded. Masked Schirmer's test was repeated 4, 8 and 12 weeks after transplantation.

Results: Schirmer's test performed in 13 rats 10 days after unilateral lacrimal gland excision revealed significantly less wetting on the side with excised gland compared with the normal side (P < 0.003). The lack of secreting cells on the operated side was verified histologically. The reduction in tear secretion on the operated side remained significant for 8 weeks on average. In the six rats with transplanted lacrimal gland tissue however, there were no differences in tear reduction between the two eyes at 4, 8 or 12 weeks after the operation (P = 0.81, 0.56 and 0.8, respectively).

Conclusions: Transplantation of lacrimal gland tissue from newborn rats effectively restored eye wetting in this new model. Further research is needed to evaluate this new approach for treating lacrimal gland dysfunction. Using this model might also facilitate evaluation of potential clinical treatments for dry eyes.
 

Inherited forms of proteinuria constitute a rare and heterogeneous group of diseases, the most prominent of which is glomerular dysfunction, which leads to proteinuria. Investigation of the genetic background underlying these diseases has provided significant data on the normal operation of the glomerular filter. Among the different components of the glomerulus, the podocyte slit diaphragm is considered the main source for genetically derived protein alteration, which leads in turn to proteinuria. Investigation of the different proteins revealed that the lack of nephrin and podocin is the leading cause of several inherited forms of proteinuria. It was also proposed that the lack of podocin is linked to cardiac anomalies. This review suggests that the absence of slit diaphragm proteins and the open zipper phenomenon are associated with cardiac anomalies.