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.

Objectives: To identify patients with PPD and to describe their consultation patterns with primary care physicians for themselves and their babies.

Methods: Using a telephone survey and the Edinburgh Postnatal Depression Scale questionnaire we identified PPD in a sample of women who gave birth in HaEmek Medical Center. We also assessed the extent to which the women consulted with family physicians, gynecologists and/or pediatricians.

Results: The survey included 574 women, of whom 9.9% were diagnosed with PPD. There was a higher rate of PPD among Arab compared to Jewish women, among women with a prior history of depression, among women whose pregnancy was unplanned, among those who described the course of pregnancy as “difficult,” and among women who described their general health as “not good.” Women with PPD consulted more with family physicians and pediatricians. The reasons for the consultations are physical and emotional. There were cases of somatization manifested directly by the mother or indirectly through the baby.

Conclusions: Women with PPD have higher consultation rates than those without. By asking a few simple questions it is possible to identify a significant proportion of women with PPD.

Endometrial polyps are a frequent finding in infertile patients. Little is known about the true prevalence of polyps in infertile patients. It is unproved whether polyps are causative of infertility, or whether surgical polypectomy by hysteroscopy improves the likelihood of successful conception. This article reviews endometrial polyps in reproductive-age fertile and infertile women.

Background: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement, under the assumption that the condition is due to excessive menstrual blood loss.

Objectives: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia.

Methods: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes.

Results: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 ± 15 years and their mean hemoglobin level 9.3 ± 2.3 g/dl. Twenty‑eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts.

Conclusions: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi‑directional endoscopic evaluations of the gastrointestinal tract.

Objectives: To evaluate trends in the incidence of hip fractures in this population.

Methods: The study was based on two surveys done approximately 20 years apart. It included women and men 50 years and older with radiographic evidence of a new hip fracture caused by low impact trauma. Only fractures that resulted from low or moderate trauma were considered for the current study. Incidence rates were calculated based on population data obtained from the official Central Bureau of Statistics.

Results: There was an overall twofold increase in the incidence rate of hip fractures. However, this increase occurred almost exclusively in the over-75 year old age groups (2.5-fold increase, both in women and men). The mean (and median) age of patients with hip fractures increased significantly over the study period, corresponding with the increase in longevity between the two periods.

Conclusions: There was a marked secular increase in the incidence of proximal hip fractures in both genders, primarily because of an increase in the fracture rate in the very old. The increase in median age of fracture patients suggests that the observed increase in fracture rate can be attributed mainly to aging of the population rather than to deterioration in bone quality over the generations.

Objective: To assess the prevalence of diabetes in an Arab community, the contribution of obesity to diabetes development, and the therapeutic potential of a preventive program.

Methods: Data were obtained from the medical files of diagnosed diabetes patients attending a primary care clinic in an Arab village in northern Israel.

Results: Type 2 diabetes was diagnosed in 323 patients of whom 63% were women. The prevalence of diabetes below age 65 years was significantly higher among women than men. Diabetic women were younger than men at diagnosis (48.27 vs. 59.52 respectively) and were found to have higher body mass index (34.35 vs. 30.04 respectively) at diagnosis. The age at diagnosis of diabetes was strongly correlated with BMI[1] (r = 0.97, P < 0.0001).

Conclusions: Women of Arab origin are at higher risk of developing type 2 diabetes compared to men. Obesity in women seems to be associated with higher diabetes risk as well as earlier appearance of the disease. Therefore, they will have the disease for longer and, consequently, a higher risk for complications.

Endometriosis is a chronic disease characterized by ectopic deposits of endometrial glands and stroma located outside the uterus. Women with symptomatic endometriosis may experience premenstrual bleeding or staining, pain and other physical sensations, as well as other symptoms dependent upon the stage and location of the endometrial implants. We discuss the particular implications of these symptoms for women who observe the part of Jewish law known as hilkhot niddah. The laws of niddah, also known as taharat hamishpahah (family purity), dictate the timing of the physical relationship between a married couple. These laws proscribe any physical contact between the couple during the time that the wife has the status of niddah. This status is obtained by any uterine bleeding that is not caused by injury. Menstruation is the most common cause of the niddah status, but niddah and menstruation are not synonymous. Since, to the best of our knowledge, there is no written discussion of the specific implications of endometriosis for this population, we discuss the relevant halakhic and medical literature and hope that such analysis will facilitate efforts to assist the observant couple in gaining regular niddah-free segments of time.

Objective: To describe the experience of our CF[1] center in the management of CF pregnant woman from 1977 to 2004.

Methods: We analyzed 27 years of records (1977–2004) of the national CF registry of all CF women who wished to conceive and became pregnant.

Results: Eight CF women (mean age 24 ± 4.5 years) who wished to conceive had 11 pregnancies and delivered 12 neonates. The pregestational results of forced expiratory volume per 1 second varied significantly among patients (59 ± 23%), yet most (10/11) stayed stable throughout the pregnancy course. Maternal deterioration in CF condition occurred in only one mother, necessitating cesarean section. In 9 of the 11 pregnancies the women were pancreatic-insufficient. Of the 11 pregnancies, 2 CF women had diabetes mellitus and 3 developed gestational diabetes. One pregnancy occurred in a mother with a transplanted lung. Of the 12 neonates, 3 were preterm and one was born with esophageal atresia. No miscarriages, terminations or neonatal mortalities occurred. Although most of the CF mothers had FEV_1[2] below 55% before pregnancy, the maternal and neonatal outcome was favorable and lung function tests generally remained stable.

Conclusions: We conclude that pregnancy in CF is feasible with a positive maternal and neonatal outcome. Early participation of the CF physician in the wish of the CF woman to reproduce is required. The integration of an intensive multidisciplinary approach during pregnancy, which includes close follow-up of maternal and fetal condition by the various specialists, should ensure an optimal outcome.

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[1] CF = cystic fibrosis

[2] FEV₁ = forced expiratory volume per 1 sec

Background: Until recently trimethoprim-sulfamethoxazole was the drug recommended in the Leumit Health Fund for the empiric treatment of uncomplicated urinary tract infection in women. However, due to increased uropathogen resistance to this drug, the fund has designated nitrofurantoin as its new drug of choice.

Objectives: To evaluate the potential economic impact of implementing this new pharmaco-policy.

Methods: Using data derived from the electronic patient records of the Leumit Health Fund we identified all non-recurrent cases of women aged 18–49 with a diagnosis of acute cystitis or UTI[1] without risk factors for complicated UTI and empirically treated with antibiotics throughout 2003. The final sample comprised 5,489 physician-patient encounters. The proportion of cases treated with each individual drug was calculated, and the excess expenditure due to non-adherence to the new guideline from the perspective of the health fund was evaluated using 5 days of therapy with nitrofurantoin as the reference treatment.

Results: Ofloxacin was the most frequently prescribed drug (30.24%), followed by TMP-SMX[2] (22.43%), cephalexin (15.08%), and nitrofurantoin (12.59%). The observed net aggregate drug expenditure was 2.3 times greater than expected had all cases been treated with nitrofurantoin according to the guideline duration of 5 days. The cost of treatment in 53% of the cases exceeded the expected cost of the guideline therapy.

Conclusions: Successful implementation of the new drug policy will likely improve quality of care and reduce costs to the health fund.

Background: Oral contraceptive users are at increased risk for both arterial and venous thrombosis, some of which can be fatal. Studies are consistent with the existence of a synergism between cigarette smoking and OC[1] use in the pathogenesis of myocardial infarction in young women.

Objectives: To study the relationship between OC use, cigarette smoking and other cardiovascular risk factors among young women.

Methods: A systematic sample of military personnel, upon discharge from service in the Israel Defense Forces, was asked to complete a research questionnaire. Body weight and height were measured and body mass index computed.

Results: Overall, 16,258 questionnaires were collected and analyzed during this 20 year study. There was a gradual, significant increase in OC use until the mid-1980s, from approximately 45% to 60% (P < 0.001), followed by steady rates of 58–64% since then. In contrast, the rates of smoking decreased significantly in the mid-1980s, from approximately 42% to a nadir of 22% in 1991. Since then, the rate of smoking has increased slowly but steadily, to reach a level of 35% in 1999. The OC users were more often of western (Ashkenazi) origin and came from families with more education and fewer siblings. They were more often smokers than non-OC users, and started smoking at a younger age. They had significantly lower BMI[2] than non-users. OC use was nearly identical in groups with or without multiple cardiovascular risk factors (smoking, obesity, family history).

Conclusions: Smoking and OC use are strongly associated. Other cardiovascular risk factors (smoking, obesity, family history) do not prevent OC users from smoking or smokers to use OC. We suggest that primary care physicians discourage smoking among adolescent females who wish to start using OC. A thorough medical history should be obtained to recognize all risk factors for cardiovascular disease and to provide for appropriate contraception counseling.

Background: In Israel, preventive services for mothers and children are provided mainly by the Ministry of Health through a network of Maternal and Child Health clinics, and partly by municipalities and health maintenance organizations. Utilization of the MCH[1] clinics for prenatal care has declined during the last decades.

Objective: To study the utilization and satisfaction with prenatal care services following the introduction of the National Health Insurance Law.

Methods: The study population comprised a national sample of Jewish and Arab women who were interviewed by telephone regarding the following: main service utilized for prenatal care, physician and nursing visits, satisfaction with care, and demographic and other characteristics. The response rate was 92% among Jewish women and 88% among Arab women.

Results: Twenty percent of the Jewish and 52% of the Arab women selected MCH clinics as the main service for prenatal care. The great majority of the study population attended the HMO[2] services (clinics, independent physicians, women’s health centers), while 7% of the Jewish and 4% of the Arab women visited a private clinic. The predisposing factors affecting the women's choice were educational level, ethnic group, religiosity, district of residence, and type of HMO. The mean number of physician visits was more than the eight visits recommended. Forty percent of the sample visited with three or more physicians at different services. More than 50% of the women had no appointment with a nurse, mainly those who chose the services of an HMO clinic, independent physician, or private physician. Satisfaction with the physician, nurse, and physical structure of the main service chosen for prenatal care was high.

Conclusions: Since the majority of women preferred the HMO services, the merging of prenatal care with curative care provided by the HMOs has to be considered. Public health nurses should be integrated in the service, and their specific role needs to be defined.

Background: Prior studies have suggested that women are at higher risk for morbidity and mortality during coronary angioplasty, although long-term prognosis is similar after successful procedures.

Objectives: To examine the role of gender in coronary stenting, including immediate procedural success as well as early and late outcomes.

Methods: The study group comprised 560 consecutive patients (119 women and 441 men) who had undergone stenting over a 3 year period.

Results: The indications for coronary stenting were similar among women and men, and stents were successfully deployed at similar rates without complications (92 vs. 90% respectively). Cardiac death or myocardial infarction within 30 days of the procedure was observed in 5% of women and men, whereas none of the women, compared to 1.4% of men, had early revascularization. Bleeding complications occurred in 4% of women and 2% of men. During 10 ± 2.8 months of follow-up, 58% of women and men underwent repeat cardiac catheterization, revealing similar rates of restenosis, 36 vs. 32% respectively. During the study period, 3.3% of women as compared to 0.9% of men had a cardiac death (not significant). Cardiac death or myocardial infarction was observed in 7% of women and 8% of men, and the combined endpoint of death, myocardial infarction or revascularization, was noted in 24% and 26% respectively. Multivariate Cox analyses of the clinical, angiographic and procedural characteristics revealed that multiple stent deployment was the only predictor of major adverse cardiac event among men, whereas none of these characteristics predicted outcome in women.

Conclusion: Coronary stenting is performed with similar success rates among women and men, with similar restenosis rates, as well as early and late major adverse cardiac events.