Bella Adler

Nonfasting Plasma Total Homocysteine Level and Mortality in Middle-Aged and Elderly Men and Women in Jerusalem

The metabolism of homocysteine, a sulfur amino acid, is at the intersection of two metabolic pathways: transsulfuration and remethylation (1). McCully (2) first proposed that severe hyperhomocysteinemia is related to both atherosclerosis and vascular thrombosis. Recent evidence (3-5) has shown an association between mildly to moderately elevated blood concentrations of total homocysteine and vascular disease (including its coronary, cerebral, and peripheral manifestations). Much of the supporting evidence for this association has been obtained from casecontrol studies; reports of prospective studies of cardiovascular disease, however, are inconsistent (6-12). It remains to be established whether this relation is causal and whether reduction of plasma homocysteine level will decrease risk. Most studies have been done in Europe and North America. Only two recent reportsone from the Framingham Study (13) and one on patients with coronary heart disease in Norway (14)have used total mortality as an end point with which to assess health outcomes associated with a modestly elevated homocysteine level. We addressed the question of this relation in a study of nonfasting plasma homocysteine levels and 9- to 11-year all-cause mortality in a cohort of Jewish men and women 50 years of age and older living in Jerusalem. The study sample is ethnically heterogeneous, consisting mainly of persons from central and eastern Europe, northern Africa, and the Middle East who immigrated in the 1950s and 1960s, as well as those born in Israel. Methods Study Sample The third round of examinations of the Kiryat Yovel Community Health Study took place from 1985 to 1987. A neighborhood sample in western Jerusalem was identified by conducting a household census of dwelling units. All identified residents 50 years of age or older were invited for an interview and examination and were asked to give informed consent to participate (15-17). Data Collection A structured interview, administered by trained interviewers during the afternoon, was followed by an examination that included standardized measurements of blood pressure, anthropometric indexes, 12-lead electrocardiography, and a nonfasting blood sample (16, 17). Biochemical Measurements Blood was drawn into plain Vacutainers (Becton Dickinson, Carlsbad, California) and Vacutainers that contained EDTA; 90% of the samples were taken between 1:00 p.m. and 6:00 p.m. The EDTA tubes were immediately refrigerated for up to 2 to 3 hours until centrifugation. Aliquots were stored at 20 C for 9 to 11 years until they were shipped on dry ice to Boston, Massachusetts, for analysis of homocysteine. Plasma total homocysteine, the sum of protein-bound and free homocysteine, was measured by using high-performance liquid chromatography with fluorometric detection, as described by Araki and Sako (18), except for isocratic column elution. Pooled plasma was used for quality control. The interassay and intra-assay coefficient of variation for this method is less than 5%. Serum glucose level, cholesterol level, thiocyanate level, creatinine concentration, blood urea nitrogen level, and albumin level were measured on a Technicon SMAC (Technicon Instruments Corp., Tarrytown, New York). High-density lipoprotein cholesterol level was measured enzymatically (Laboratoires Biotrol, Paris, France) on a Cobas Bio autoanalyzer (F. Hoffman-La Roche Ltd., Basel, Switzerland). Physical Measurements and Interview Data Blood pressure was measured with a mercury sphygmomanometer (16). Body mass index was computed (17). Participants were asked whether a physician had ever told them that they had diabetes. They were also asked, Is your general health at present very good, good, not so good, poor, or very poor? The first two categories were combined as good health, and the last two categories were combined as poor health. Simple self-appraisals, which are common indexes of general health, are correlated with health ratings on the basis of objective measures and are predictors of subsequent death (19-23). Prevalence of cardiovascular disease was defined as typical angina (24) confirmed by a physician, reported history of heart attack, or reported history of stroke. A food-frequency questionnaire included assessment of the usual intake of fruit, fresh vegetables, and cooked vegetables. Follow-up and Causes of Death Deaths that occurred before April 1996 and the underlying cause of death as coded by the Israel Central Bureau of Statistics (International Classification of Diseases, Ninth Revision [ICD-9] codes) were identified by linkage with the national population registry. Statistical Analysis Skewed distribution of plasma homocysteine level was corrected by natural logarithmic transformation. Mean homocysteine levels, when presented, are geometric unless otherwise specified. Associations of homocysteine level with covariates were assessed by age-adjusted partial Pearson correlations and analysis of variance. Kaplan-Meier survival curves were computed for quintiles of homocysteine level after age adjustment by regression. The main analyses used Cox proportional-hazards regression to model survival according to sex-pooled quintiles of homocysteine level, adjusting for possible confounders. In these models, the outcome variable was time to event. Tests for trend were assessed with the logarithm of homocysteine level introduced as a continuous variable. Uniformity in the association of homocysteine level with survival over time was tested by introduction of time-dependent terms. Differences in hazard ratios between the sexes, age groups (<65 years of age and 65 years of age), and ethnic groups were tested by using multiplication terms. Analyses were implemented by using SPSS (SPSS, Inc., Chicago, Illinois). The population attributable fractionthat is, the proportion of all deaths in the population associated with elevated homocysteine levels (cut-off points used elsewhere [25, 26], 13 and 14 mol/L)was computed as Pe (HR 1)/1 + [Pe (HR 1)], where Pe is the proportion of patients with a plasma homocysteine level of at least 13 mol/L or at least 14 mol/L and HR is the respective hazard ratio computed from Cox models. Results Participant Characteristics All 2303 persons identified in 3434 dwelling units in the Kiryat Yovel community who were at least 50 years of age were invited to participate in our study. The response rate for the original census was 96%. A total of 1948 men and women gave informed consent and agreed to participate (85% response rate). Nonrespondents were similar to respondents with regard to age and sex. Plasma total homocysteine was measured in blood samples obtained from 1788 participants (92% of the total); the 160 participants with missing measurements did not differ significantly from those with no missing measurements with respect to age, reported diabetes, or self-appraised health. Covariate data were incomplete for 77 of the 1788 participants in the multivariate-adjusted models. The age distribution of the study sample is shown in Table 1. The mean age was 64.6 years for men and 64.5 years for women (range for both sexes, 50 to 92 years). Table 2 shows the heterogeneity of the sample with respect to place of birth and level of education. Of the 1788 participants, 13% (n=239) reported having received a physicians diagnosis of diabetes, 16% (n=283) had a history of cardiovascular disease, and 30% had hypertension (defined as systolic blood pressure 160 mm Hg, diastolic pressure 95 mm Hg, or current treatment for hypertension). Distributions of smoking and self-appraised health are shown in Table 2. Nineteen percent of men and 41% of women had a total serum cholesterol level of 6.5 mmol/L or greater ( 251 mg/dL) . The prevalence of obesity (body mass index 30.0 kg/m2) was high (32% in women and 16% in men). Table 1. Plasma Total Homocysteine Levels and Number of Deaths during 9- to 11-Year Follow-up, according to Age at Initial Examination (1985-1987) Table 2. Predictors of All-Cause Death during 9- to 11-Year Follow-up Correlates of Total Plasma Homocysteine Level We examined the relation of plasma homocysteine level to the time that had elapsed since food or drink was last consumed. A weak age-adjusted association (r=0.06; P=0.049) was restricted to women. Homocysteine levels increased with age, were higher in men than in women (Table 1), and were not significantly associated with place of birth or level of education (not shown). The strongest age-adjusted correlations were with serum creatinine concentration (r=0.21 in men and r=0.29 in women; P<0.001). The inverse relation with serum glucose level (r= 0.09 in men [P=0.011] and r= 0.15 in women [P<0.001]) was not affected by the amount of time that had passed since the participants last meal. Age- and sex-adjusted mean homocysteine levels were lower among persons who reported that they had diabetes than among those who did not (1.1 mol/L; P<0.001). Homocysteine levels were 1.1 mol/L higher in men who smoked (P=0.004) than in men who did not smoke and were positively correlated with serum thiocyanate level (r=0.12; P<0.001); these associations were weaker and nonsignificant in women. No significant associations were seen with blood pressure, body mass index, or serum lipid levels. Correlations with intake of fruit, fresh vegetables, cooked vegetables, and total vegetables were weak (r= 0.08 [P=0.045], r= 0.10 [P=0.014], r= 0.04 [P>0.2], and r= 0.10 [P=0.015], respectively, in men; r= 0.06, r= 0.04, r= 0.05, and r= 0.04, respectively, in women [for all comparisons P>0.2]). Participants with poor self-appraised health had higher age-adjusted homocysteine levels than participants in fair health or good health (1.8 mol/L and 1.5 mol/L, respectively, for men [P=0.05] and 1.0 mol/L and 0.9 mol/L, respectively, for women [P=0.2]; P=0.012 in the total sample [sex-adjusted]). Homocysteine Level and Death during 9 to 11 Years of Follow-up Among the 1788 participants,

Learning achievement and behavior at school of anemic and non-anemic infants

In a prospective study the learning achievement and behaviour of second grade children who were anemic in infancy (n = 20) was compared with that of non-anemic children (n = 55). All children received preventive care and were under surveillance from birth at the Community Health and Research Center of Hadassah in Jerusalem. The anemic children had a hemoglobin level of less than 10.5 g/dl whereas the comparison group had more than 11.5 g/dl at 9 months of age. The learning achievement score was significantly lower in the anemic group 9.3 S.D. 3.8, than in the non-anemic group 11.5 S.D. 2.9 (P = 0.009). The positive task orientation was also significantly lower in the anemic group, though on additional behavior scores no differences were found. Differences remained significant even after controlling for maternal education and sex of child in a multivariate analysis. It is possible that an iron deficiency state which persists during the critical period of brain development in infancy has long-lasting effects on cognitive functioning. Prevention of iron deficiency may contribute to promotion of child development and better achievement.

Epidemiological studies on head lice infestation in Israel. I. Parasitological examination of children.

ABSTRACT: Of 3,079 children in a medium‐sized community near Jerusalem, 11.2% were found to be infested with living lice and eggs and another 23.4% had only nits. Boys and girls were equally infested. The incidence of infestation was highest among children4–11 years of age. About 78% of the infested children had from one to ten lice. Approximately 80% of the infested children had nits that were 2–5cm away from the scalp. Boys with medium length hair and girls with short hair showed the highest incidence of lice infestation. Children with brown and red hair were more infested than those with black and blond hair. Boys and girls with straight and wavy hair were more infested than those with curly and frizzy hair.

Incidence and impact of childhood and adolescent injuries: a population-based study.

BACKGROUND The study of disabilities, use of health services, and absenteeism of parents among 0- to 17-year-old residents of Jerusalem (n = 432) hospitalized for unintentional injuries. METHODS Telephone interviews with parents, 6 months after hospitalization. Disabilities among 4 to 17 year olds were measured by a 25-item scale derived from the International Classification of Impairments, Disabilities, and Handicaps and by limitations of activities. RESULTS Six months after the injury, limitations ranged from 8.3% (daily activities) to 19.4% (sport activities). About one in three presented at least one disability in the 25-item scale. All disabilities were present in higher proportions among adolescents. The more severe injuries whether to the head or other parts of the body presented higher percentages of disabilities. Burns and traffic crashes were associated with higher proportions of disabilities than other causes and with more frequent work absenteeism by their parents. CONCLUSION A relatively large proportion of children remain with long-term disabilities irrespective of cause and body part injured. Because the sequelae of injuries is multifaceted, rehabilitation should include coordination between health and other services.

Effect of otitis media on development: a community-based study

Otitis media history until age 3 years were recorded for 233 children as part of the surveillance in a Community Program for Promotion of Growth and Development (PROD) conducted in a western neighborhood of Jerusalem. Recurrent otitis media (6 or more episodes) occurred more frequently among children who were of North African or Asian origin, of lower social class and maternal education, and whose duration of breast feeding was less than 26 weeks. Children with recurrent otitis media also failed the 7-month hearing test more frequently than other children. The mean Developmental Quotient score at 2 years and the mean Stanford Binet score at 3 years were statistically significantly lower among children with recurrent otitis media, even after controlling for maternal origin and length of breast feeding. These findings underscore the importance of early identification and early intervention for otitis media.

Hormonal contraception, sexual behaviour and HIV prevalence among women in Cameroon

BackgroundData on the effect of contraceptive methods, other than the condom, on HIV acquisition is not clear. The aim of this study was to describe hormonal contraceptive use, sexual behaviour and HIV prevalence among women in Cameroon in order to provide baseline information for future analytical studies.MethodsThis is a cross-sectional descriptive study based a nationally representative sample of 4486 sexually active women aged 15–49 years who participated in the 2004 Cameroon Demographic and Health Survey.ResultsThe overall HIV prevalence was 7.4% (332/4486). The HIV prevalence was higher in the 25–35 year age group (10.03%), urban residents (9.39%), and formerly married (18.48%), compared to their compatriots. The prevalence was lower in women with five or more living child (3.67%), women in the low wealth index category (3.79%) and women who had no formal education (3.37%). The HIV prevalence was higher among women who had two or more partners in the last 12 months (10.26%) and women who reported to have had four or more partners in their lifetime (12.40%). The prevalence of HIV was higher among current hormonal contraceptive users (6.63%) compared to the current non-users (3.06%), among ever users of hormonal contraception (13.27%) compared to the never users (7.11%).ConclusionWe conclude that the prevalence of HIV among sexually active women in Cameroon varies according to sociodemographic characteristics, sexual behaviour and hormonal contraceptive use. Our findings underscore the need to counsel women using hormonal contraception to be aware that hormonal methods do not protect against HIV infection. Given the biologic plausibility of the link between hormonal contraception and HIV infection, future research should focus on carefully designed prospective studies to establish the temporal relationship and estimate the incidence of HIV infection among women using and not using hormonal contraceptive methods.

A population-based study of hairy cell leukemia in Israel

Abstract:  Objectives: Few population‐based data exist on the incidence and prognosis of hairy cell leukemia (HCL). Our objectives were to study the effect of socio‐demographic factors on this rare disease and the risk of second malignancies occurring in HCL patients. Methods: We measured crude and age‐adjusted incidence rates of HCL based on reporting to the Israel Cancer Registry (ICR) 1991–2001. Using Kaplan–Meier and multivariate analysis, we assessed survival by gender, ethnicity and geographic region. We ascertained additional primary tumors reported in this population and calculated standardized incidence ratios (SIRs) for tumors reported after the diagnosis of HCL. Results: The ICR registered 147 cases of HCL among males and 34 in females between 1991 and 2001. Age‐adjusted incidence rates were 1.62/106/yr for women and 7.97/106/yr for men, with rates 1.5 times higher in Jewish than in non‐Jewish (mainly Arab) men. Mean overall survival also differed by ethnicity. In a multivariate model, increasing age at diagnosis (P < 0.001), as well as Arab origin (P = 0.008) were associated with poorer survival but gender did not significantly affect the survival after controlling for age and ethnicity. Other primary malignancies were reported in 20 (11%) individuals, with a predominance of genito‐urinary tumors (65%) among males. Secondary genito‐urinary tumors were significantly increased above the expected population rates (SIR 3.23, 95% confidence interval: 1.39–6.36, P = 0.008). Conclusions: In the Israeli population, age and ethnicity were associated with prognosis of HCL. Variations in disease characteristics, stage of disease at diagnosis or differential access to treatment may contribute to these findings. Patients with HCL appear to be at increased risk for genito‐urinary malignancies.

A model-based evaluation of a cultural mediator outreach program for HIV+ Ethiopian immigrants in Israel.

This article presents a model-based evaluation of a program designed to reduce HIV transmission from HIV-infected Ethiopian immigrants in Israel. Rather than rely on self-reported variables such as condom use, this study’s approach focuses on pregnancy rate reduction, estimated from administrative periodic reporting data, as a measure of unprotected sexual exposure. The models show that among both HIV+ women and the female sex partners of HIV+ men, the ongoing pregnancy rates estimated during the intervention were significantly lower than the estimated baseline pregnancy rates, suggesting reductions in unprotected sexual exposures among those participating in the program.

THE DEVELOPMENT OF DISABILITY SCALES FOR CHILDHOOD AND ADOLESCENT INJURIES

Scales for the study of injury-induced disabilities among 0-17 year olds were developed. Telephone interviews were conducted among parents of injured children (n = 432) 6 months after hospitalization in the three main hospitals of Jerusalem, about disabilities immediately following and 6 months after the injury. The scale for 4-17 year olds included 25 items derived from the International Classification of Disabilities, Impairments and Handicaps. Factor analysis revealed three dimensions of disability: personal care and daily activities; motor activities; and communication and sensory activities. The scale and the derived subscales on personal care and daily activities, and on motor activities showed high Cronbachs alpha, especially for disabilities immediately after the injury. The scale or subscales are easy to use, related to everyday activities performed by children in all cultures, are not related to the characteristics of the respondents, and have high consistency-reliability and construct validity. They may be used to assess the prevalence of disabilities in population studies.

Blood donors with positive direct antiglobulin tests are at increased risk for cancer.

BACKGROUND: Positive direct antiglobulin tests (DATs) have been associated with both autoimmunity and lymphoproliferative disorders. However, it is unknown whether DAT+ in healthy blood donors is associated with an increased risk of malignancies.