Israel Medical Association Journal

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: Ion Channel Innovations has developed a gene transfer product, ftMaxi-K, and has begun clinical trials to investigate the effect of increased expression of Maxi-K channels in the smooth muscle of the penis or bladder in patients with erectile dysfunction and those with overactive bladder. The primary function of K channels is to modulate Ca⁺⁺ influx through Ca-channels (i.e., L-type, voltage-dependent). The amount of Ca⁺⁺ that enters the cell through these channels is a major determinant of the free intracellular calcium levels inside the smooth muscle cell, which in turn determines the degree of smooth muscle cell contraction. Increased Maxi-K channel activity is associated with smooth muscle cell relaxation, resulting in, for example, penile erection and detrussor muscle relaxation. A phase I clinical trial that used dMaxi-K has been completed and a similar trial to assess safety of the transfer for overactive bladder is about to begin.

Objectives: To assess the safety and tolerability of escalating dMaxi-K doses by clinical evaluations and laboratory tests, and to measure efficacy objectives by means of the International Index of Erectile Function scale.

Methods: In the erectile dysfunction trial 11 patients with moderate to severe erectile dysfunction were given a single-dose corpus cavernosum injection of dMaxi-K, a "naked" DMA plasmid carrying the human cDNA encoding for the gene for the a, or pore-forming, subunit of the human smooth muscle Maxi-K channel, hSIo. Three patients each were given 500,1000, and 5000 pg and two patients were given 7500 pg doses of ftMaxi-K and followed for 24 weeks. Patient responses were validated by partner responses.

Results: There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of dMaxi-K had apparent sustained improvements in erectile function as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 (jg and one given 7500 [jg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study.
Conclusions: Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that ftMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access

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.

The human papillomavirus family of viruses causes a variety of benign, premalignant and malignant lesions in men and women. All cervical cancers are caused by HPV[1]. It is the leading cause of death from cancer in women in developing countries; every year some 493,000 women develop cervical cancer and 230,000 women die every year of this disease. The vaccine against HPV includes virus-like particles, composed of the major viral capsid protein of HPV without the carcinogenic genetic core. Large-scale studies have shown that the vaccine is tolerated well, leads to high antibody levels in both men and women, and prevents chronic HPV infection and its associated diseases. To achieve effective coverage the vaccine should be given prior to sexual debut. Introduction of the vaccine into specific countries, particularly Israel, should take into account the local incidence of cervical cancer as well as the increasing incidence of precancerous cervical lesions and genital warts, which reduce quality of life and are associated with considerable costs.

Eponyms are titles of medical disorders named for individuals who originally described the condition. They also help us remember and identify the disorder. Medicine is replete with them, and changing them or eradicating them, for whatever reason, is not simple. But when there is a moral issue involved – for example, the research conducted under overwhelming unethical conditions – we believe it wrong to perpetuate and thus “reward” the memory of the individual for whom the disorder is named. The name of a syndrome should thus be discontinued if described by an individual whose research used extreme or who was involved in atrocities against humanity. Ethical considerations should be introduced into medical nosology just as they exist in patient care and research. This article details a group of notable eponyms, the names of which are associated with overt crimes of the medical community during the Nazi era, and provides alternative medical nomenclature. In addition, examples are provided of eponyms named after Nazi era victims, eponyms of those who protested such injustices, and eponyms of those who had to flee discrimination and death. These should be remembered and even strengthened, as opposed to those of the perpetrators, which should be obliterated. Since the greatest accolade a physician can earn is praise from his colleagues as expressed in an eponym entrenched in one's name, the medical profession should remove any honor given to physicians involved in crimes to humanity.

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: Healthcare behavior occurs within the context of the family unit. Little research has investigated the influences among adult family members regarding their use of medical care services.

Objectives: To investigate the effects of maternal attendance patterns and maternal self-assessed health status on those of adult children.

Methods: This study was a retrospective cohort, analyzing both patient records for physician visits and mailed self-administered questionnaires regarding subjective health assessment. We evaluated a unique study group of multi-generational families with free and equal access to medical services at a primary care kibbutz clinic in Israel. This enabled an exclusive focus on the association between the use of healthcare by mothers and their grown children.

Results: Controlling for the subjects' age, gender and number of chronic diagnoses, a significant association exists between the family physician visit rates of a mother and those of her grown offspring (P = 0.03). Low self-health assessment is associated with higher levels of physician utilization (P = 0.003). Maternal self-health evaluation is associated with her adult children's own self-health evaluation (odds ratio 5.9, P = 0.04) and their rates of physician utilization (one additional offspring visit per year for low maternal self-health, P = 0.02).

Conclusions: A mother’s behavior patterns measured via self-rated health status and physician visit rates serve as a proxy for maternal attitudes regarding healthcare, and these attitudes are possibly imparted to her children for life. This study provides unique evidence for a maternal health behavior effect on grown children, and enables a more complete understanding of families attending the primary care clinic.
 

Background: In 2003 a total of 43 soldiers in the Israel Defense Forces committed suicide; only 20% of them were known to the IDF[1] mental health services. Somatic symptoms are often the only presentation of emotional distress during the primary care visit and may be the key to early identification and treatment.

Objectives: To examine whether the information in the medical records of soldiers can be used to identify those suffering from anxiety, affective or somatoform disorder.

Methods: We conducted a case-control study using the information in the electronic medical records of soldiers who during their 3 year service developed affective disorder, anxiety, or somatoform disorder. A control group was matched for recruitment date, type of unit and occupation in the service, and the Performance Prediction Score. The number and reasons for physician visits were collated.

Results: The files of 285 soldiers were examined: 155 cases and 130 controls. The numbers of visits (mean SD) during the 3 and 6 month periods in the case and control groups were 4.7 ± 3.3 and 7.1 ± 5.0, and 4.1 ± 2.9 and 5.9 ± 4.6 respectively. The difference was statistically significant only for the 6 month period (P < 0.05). The variables that remained significant, after stepwise multivariate regression were the Performance Prediction Score and the presenting complaints of back pain and diarrhea.

Conclusions: These findings may spur the development of a computer-generated warning for the primary care physician who will then be able to interview his or her patient appropriately and identify mental distress earlier.