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Biomedical subjects

J D Kark

Publications and source records attributed to J D Kark.

At least 91 records · Page 5Linked to original sources

A Rift Valley fever vaccine trial: 2. Serological response to booster doses with a comparison of intradermal versus subcutaneous injection.

A booster dose of a formalin-inactivated, cell culture-propagated Rift Valley fever vaccine (TSI-GSD-200) was administered without significant reactogenicity to 60 volunteers 18 months after they received a three dose primary series. Blood was drawn for serological testing prior to boosting and 10, 49, and 180 days thereafter. Neutralizing antibody response was prompt, being maximum on day 10 and considerably higher than the peak titres obtained on day 42 after the initial series. A marked decline in antibody titres was evident by day 180, as seen for the primary series, but residual titres were substantially higher. The initial series was given in doses of 1.0, 0.5, 0.3, or 0.1 ml and the immune status achieved with these injections was a major determinant of the response to boostering. Secondary responses were highly dependent in magnitude and duration on the prior immune status of the recipient. Evaluation of dose and route of recall inoculation showed 1.0 ml given subcutaneously (SC) to be equivalent to 0.1 ml administered intradermally (ID), though inference should be guarded due to the small sample size. Although 0.1 ml SC dose was inferior to either, it was modestly effective. Intradermal administration of vaccine may be useful for extending the small reserve of vaccine available for use in emergency.

Adult↗

Serum cholesterol and primary brain tumours: a case-control study.

The objective of this study was to test the hypothesis that a positive relationship exists between high levels of serum cholesterol and primary brain tumours. A record-based case-control study was performed on male Jewish residents of Israel who were hospitalized at the Hadassah Ein Karem hospital in the years 1978-1982. A record check identified 37 cases of brain tumour who fulfilled the criteria for inclusion in the study and whose hospital files included the necessary data. For each case two controls were chosen randomly from all patients with inguinal hernia who met the respective matching criteria of age and year of hospitalization. The mean cholesterol value of the cases with brain tumours was 22 mg dl-1 higher than that of the controls. This difference was statistically significant (P = 0.007). Controlling for weight, region of birth, season of year, social class, medications and length of hospitalization before the measurement of cholesterol did not reduce the cholesterol difference, and in some instances increased it.

Adult↗

Coronary heart disease risk factors among religious groupings in a Jewish population sample in Jerusalem.

The hypothesis that plasma lipids, blood pressure, smoking and dietary intake differed according to degree of religiosity was examined in a sample of Jewish residents of Jerusalem. Religiosity was classified according to the subject's self-ranking of his perceived degree of religiosity. Prevalence of smoking, and plasma levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol were higher in secular participants than in the orthodox group. No differences in blood pressure and in high-density lipoprotein cholesterol were observed. Secular subjects consumed more total fat, more saturated fatty acids and less carbohydrate than religious subjects. These differences in nutrient intake among the religious groups reflected differences in their food selection, notably consumption of dairy products. These findings of parallel differences in plasma lipids and in dietary intake are consistent with the differing incidence of myocardial infarction in the religious groups which has been shown in the Israeli population.

Adolescent↗

Family history of myocardial infarction as an independent risk factor for coronary heart disease.

The hypothesis that a family history of heart attack before the age of 60 years is an independent risk factor for coronary heart disease was examined in a random sample of 1044 men aged 40-70. Data on personal and family history, smoking, weight, height, plasma lipid and lipoprotein concentrations, blood pressure, and resting and exercise electrocardiograms were collected according to the standard Lipid Research Clinics protocol. A history of heart attack in first degree relatives was ascertained by interviewing the participants. Evidence of coronary heart disease was found in 123 men (reported heart attack in 20, electrocardiographic findings of ischaemic heart disease at rest in 40, and electrocardiographic findings during heart rate limited exercise in 63). Subjects with coronary heart disease had considerably higher concentrations of total cholesterol, higher blood pressures, and lower concentrations of high density lipoprotein cholesterol than those without. Twenty nine per cent of the subjects with coronary heart disease reported a history of heart attack in a first degree relative before 60 years of age compared with 19% of those without. In a multivariate logistic model, the coefficients for age, cholesterol concentrations, and hypertension were all positive and statistically significant. The coefficient for HDL cholesterol concentration was negative and significant. A family history of heart attack showed a significant positive association, indicating a relation with coronary heart disease that is independent of the other variables in the model. The relation persisted in apparently asymptomatic patients with coronary heart disease.

Adult↗

Serological hepatitis A virus infections and ratio of clinical to serological infections in a controlled trial of pre-exposure prophylaxis with immune serum globulin.

Seroconversion to hepatitis A virus was studied in a sub sample of 802 Israeli military recruits (611 men and 191 women) who were taking part in a randomised controlled trial of pre-exposure immune serum globulin (ISG) for the prevention of viral hepatitis. On intake into the service 35% of the men and 47% of the women were negative to hepatitis. A virus antibody (anti-HAV). After three years 7 of 71 men (9.9%) who had not received pre-exposure ISG had become positive to anti-HAV compared to 2 of 83 (2.4%) who had received it; the statistical significance of this difference was p = 0.052. At two years 2 of 30 women (6.7%) who had not received ISG had converted compared to 1 of 43 (2.3%) who had received ISG (p = 0.37). Pooling the sexes gave conversion rates of 8.9% in those not immunised and 2.4% in those immunised (p = 0.029). The sex adjusted odds ratio was 4.0 (95% confidence limits 1.3-19.0). The morbidity rates for clinical non B hepatitis over the three year period among 12 835 men were 7.2 per 1000 in those not immunised and 3.6 per 1000 in those immunised (p = 0.004). Point estimates of the ratio of clinical hepatitis to seroconversion in men ranged from 0.25 to 0.30. It is concluded that pre-exposure administration of ISG effectively prevented clinical expression of viral hepatitis, apparently reduced seroconversion, and did not induce passive-active immunisation.

Clinical Trials as Topic↗

Variability of plasma lipids and lipoproteins: the Jerusalem Lipid Research Clinic Study.

We examined the variability of lipid and lipoprotein concentrations in plasma from a population sample from the Jerusalem Lipid Research Clinic study. Coefficients of variation of about 8% for plasma cholesterol, 11% to 15% for low- and high-density-lipoprotein cholesterol, and about 30% for triglyceride were reported, both for 17-year-olds and adults examined twice, with a median period of two months between measurements. Stability was similar in a subsample of adults who had an additional measurement a median of 28 months later. Within-assay analytical variation (CV) was 1.9-2.0% for cholesterol, 1.5-2.3% for triglyceride, and 4.5% for high-density-lipoprotein cholesterol. Between-assay variation was 3-5% for cholesterol and triglyceride and 10% for high-density-lipoprotein cholesterol. The lower stability of the lipoprotein fractions of cholesterol than of total cholesterol emphasizes the need for repeated measurements of these fractions for more accurate characterization of subjects, especially those with extreme values, both for clinical use and for predicting outcome in follow-up studies.

Adolescent↗

Treadmill exercise testing in a middle-aged Jerusalem population sample. The Jerusalem Lipid Research Clinic Prevalence Study.

We studied determinants of the exercising physical capacity of 1,640 subjects (1,043 men and 597 women) using the Bruce protocol as modified by Sheffield. These participants represented a sample of parents of 17-year-old adolescents living in Jerusalem. Apparently healthy participants underwent a graded treadmill exercise test (88% of the men and 87% of the women). Exercise was terminated when the subject achieved a heart rate of 85 to 90% of the predicted maximal heart rate or could not continue for other reasons, mainly fatigue or weakness. Exercise performance was assessed according to time on the treadmill. On univariate analysis, duration of exercise was related in both sexes to age, country of origin, reported physical exercise, resting heart rate, systolic and diastolic blood pressure, body mass index and plasma lipids and lipoproteins. In multivariate analysis, time was related to age, body mass index, heart rate and habitual physical exercise in both men and women, and to systolic and diastolic blood pressure in men only. Cigarette smoking and plasma lipid levels were not independently related to time on the treadmill in either sex. Ethnic differences were observed.

Age Factors↗

Validity of maternal reporting of breast feeding history and the association with blood lipids in 17 year olds in Jerusalem.

The validity of mothers' reporting of the breast feeding history of their children more than 20 years after their birth was studied in a Jerusalem population. Among 74 study subjects, duration of breast feeding as ascertained from an interview was well correlated with that recorded in mother and child health clinic charts. Concordance was of similar magnitude in subgroups of ethnicity, mother's education, family size, and sex of child. Duration of breast feeding in 101 youngsters was inversely associated with plasma cholesterol in 17 year old girls, though not in boys, which was statistically significant on univariate analysis and of borderline significance on multivariable analysis. Among 17 year old boys, though not in girls, a statistically significant inverse association for plasma triglyceride was apparent on multivariable analysis. Reported breast feeding history derived from interview of mothers may be a useful instrument for study of possible long term effects of breast feeding in their adolescent or adult progeny.

Adolescent↗

Admixture analysis of plasma cholesterol levels in a Jewish population sample in Jerusalem.

The frequency distribution of total plasma cholesterol levels (TC) in 17-year-old Jerusalem youngsters and their parents (n = 6,170) was examined for evidence of admixture of normal distributions. Probability plots indicated bimodality of age-adjusted TC in both sexes. Using a maximum likelihood procedure, two normal distributions fitted the age- and sex-adjusted data significantly better than 1, with 0.9% males and 1.2% females coming from a lower distribution 2-3 standard deviations below the major mode and 0.2% males and 1.1% females belonging to the higher distribution. These results suggest that single genes may determine high as well as low cholesterol levels, but are open to other interpretations, and thus require confirmation by segregation analysis. Jews originating from Europe showed the highest TC levels followed by those from Israel, Asia, and Africa. Adjustment of TC for ethnicity did not alter the above estimates. Analysis of bimodality within countries of origin showed greater separation of the distributions in Asian and Israeli origin groups than in European and North African groups, in whom there was less evidence for admixture.

Adolescent↗

Prevalence of diabetes among ethnic groups in Jerusalem. The Kiryat Hayovel Community Health Study.

The prevalence of diabetes was determined in a community health survey in the Kiryat Hayovel neighborhood of west Jerusalem. The prevalence rates of diabetes among 4,938 people aged greater than or equal to 15 years were 5.8% in men and 4.6% in women, with a male/female age-adjusted ratio of 1.15. One-third of the diabetics were first diagnosed in this study. In both sexes, the rates increased steeply with age. A higher prevalence rate of diabetes was found in Jews of North African origin, especially in men, than in the other ethnic origin groups. These ethnic differences in men do not appear to be explained by differences in body mass.

Adolescent↗

Determinants of thyroid hormone and thyroid-lipid interrelationships in Jerusalem.

In a study of 652 boys and 556 girls, aged 17, and 1,020 men and 575 women from the Jerusalem Lipid Research Clinic, serum thyroxine was higher in females than in males and higher in 17-year-old boys than in men. In most age- and sex groups, thyroxine was highest in Israelis originating from Asian and other Middle Eastern countries and lowest in immigrants or children of immigrants from Western countries. As in other population-based studies, we found a statistically significant negative correlation between thyroxine and triglyceride in adult males and negative correlations between thyroxine and high-density lipoprotein-cholesterol in all age- and sex groups. No associations between thyroxine and low-density lipoprotein-cholesterol or very low-density lipoprotein-cholesterol were observed.

Adolescent↗

Frozen stored Leishmania tropica vaccine: the effects of dose, route of administration and storage on the evolution of the clinical lesion. Two field trials in the Israel Defense Forces.

The first field trial of frozen vaccine against cutaneous leishmaniasis yielded a 100% take rate and a high ulceration rate at a dose of four million units. Two further trials were designed to investigate differences in response rates on the basis of duration of storage, sex of vaccinee, vaccination dose and method of administration. 257 soliders (151 males and 106 females) were inoculated in 1978 with an isolate of Leishmania tropica major that had been stored at the temperature of liquid nitrogen for 11 months before use. Those inoculated with an intradermal jet injector and those receiving half a million units by conventional injection yielded very low take rates. For those receiving two million and one million units, no difference in response was demonstrated between males and females or between doses. The over-all take rate for these groups after six months of follow-up was 71.6% with an ulceration rate of only 23.7%. In a subsequent trial in 1979, 131 men were inoculated with one of two frozen isolates of L. tropica major that had been stored for 11 and 18 months, respectively, at doses of either two million or four million units. The take rate after 12 months of follow-up was 91% and 93% for the four and two million units dose, respectively. The corresponding ulceration rates were 39.5% and 25%. The lesions produced by the higher dose developed more rapidly than those produced by the lower dose. The ability of the parasites to produce lesions rapidly with high ulceration rates appears to decline during prolonged storage, even in the frozen state.

Adolescent↗

The cellular and humoral immune response in subjects vaccinated against cutaneous leishmaniasis using Leishmania tropica major promastigotes.

In vitro lymphocyte transformation was studied in 24 subjects 12 months after vaccination with live Leishmania tropica major vaccine, in 10 normal control subjects and in three controls residing in an endemic area. The vaccines had lesions in various stages of clinical development. Lymphocytes from all the subjects were studied for their response to stimulation with L. tropical major promastigotes. Lymphocytes of vaccinated subjects responded to low concentrations of antigen whereas the lymphocyte response of the controls tended to be depressed by the same concentration of the antigen. Serum from each subject was subjected to a study of the humoral antibody titre against L. tropica major and L. donovani using indirect immunofluorescence. A humoral response to L. donovani was present in a majority of vaccinees who had developed a positive lesion whereas no such responses was present in any of the controls. The data suggest that high humoral responses were accompanied by relatively low cell-mediated responses and vice versa. No significant humoral response to L. tropica major could be demonstrated in any of the subjects. A combination of both the cell-mediated and humoral mechanisms may participate in the immune response although their usefulness in the assessment of the protectivity of leishmania vaccines has not been established.

Antibody Formation↗

Admixture analysis of high density lipoprotein cholesterol distribution in a Jerusalem population sample.

The distribution of high density lipoprotein cholesterol values (HDL-C) in 2003 nuclear families (including both parents and one child aged 17) participating in the Jerusalem Lipid Research Clinic survey, were analyzed by a maximum-likelihood procedure for evidence of bimodality. HDL-C was age-sex adjusted by the mean-variance method to 17 year old male levels. After covariance adjustment for Quetelet's index, season, education and social class, when using untransformed data a mixture of two distributions fitted the data significantly better than one distribution in both sexes. The results indicated that 4.7% of males and 14.1% of females came from an upper distribution with mean values of 2.15-3.15 standard deviations above the major mode. We next applied the MacLean et al. (1976) method of transformation and used a maximum-likelihood method in which the skewness parameter was estimated jointly with the other parameters of the model. When the data were transformed the mixture of two distributions fitted the data significantly better than one for males only. We tested a mixture of three normal distributions and estimated that 6% of both males and females belonged to a higher distribution, while 1% came from a lower distribution. This model did not provide a significantly better fit to the data than a mixture of two distributions. Our findings imply that in the Israeli population there is evidence for an admixture in the distribution of HDL-cholesterol. Segregation analysis is necessary in order to determine whether a major gene or some environmental factors are responsible for the commingling detected.

Adolescent↗

Pre-exposure prophylaxis of viral hepatitis with immune serum globulin in an endemic area. A trial in field units of the Israel Defence Forces.

Field units in the Israel Defence Forces represent a high risk group for type A infectious hepatitis. Very large scale post-exposure prophylaxis with immune serum globulin (ISG) has been successfully employed for the past decade with a reduction in incidence and an elimination of overt epidemic cycles. The use of pre-exposure prophylaxis in an indigenous population in whom approximately 70% have antibody to HAV at age 18 was compared in a field trial with the routine post-exposure method. Units were randomized into an intervention group (A) in which all subjects were to receive ISG (79% were in fact immunized), a second group (B) in which 50% of subjects were to be immunized (36% were actually immunized) and a non-immunized control group (C). During the trial incidence rates in the non-immunized study population dropped well below predicted levels. The incidence rates were zero in group A, 1.31/1000 in group B (0.61/1000 among the immunized and 1.72/1000 among the non-immunized) and 2.49/1000 in group C over the 6-month follow-up. Pre-exposure ISG afforded excellent protection and even at the low rate of incidence was cost-effective. The possibility of herd immunity is discussed.

Antibodies, Viral↗

Cigarette smoking as a risk factor for epidemic a(h1n1) influenza in young men.

We studied an outbreak of A(H1N1) influenza in an Israeli military unit of 336 healthy young men to determine the relation of cigarette smoking to the incidence of clinically apparent influenza and to the influenza-antibody response. Of 168 smokers, 68.5 per cent had influenza, as compared with 47.2 per cent of nonsmokers (P less than 0.0001). Influenza was also more severe in the smokers; 50.6 per cent of the smokers lost work days or required bed rest, or both, as compared with 30.1 per cent of the nonsmokers. The proportion of all influenza in smokers that was attributable to smoking was 31.2 per cent (95 per cent confidence intervals, 16.5 to 43.1 per cent). For severe influenza, the attributable risk in the smokers was 40.6 per cent (95 per cent confidence intervals, 21.6 to 54.8 per cent). A quarter of all severe morbidity from influenza in the overall study population was attributable to smoking. Antibody levels to A/USSR/90/77(H1N1) antigen were higher in smokers but not markedly so. We conclude that smoking is a major determinant of morbidity in epidemic influenza and may contribute substantially to incapacitation in outbreaks in populations that smoke heavily.

Adolescent↗

Serum retinol and the inverse relationship between serum cholesterol and cancer.

Several human studies have shown an inverse relation between vitamin A intake (and serum concentrations of retinol and carotene) and cancer. Serum cholesterol concentrations have also been reported in inverse relation to cancer. In a study of 3102 people in Evans County, Georgia, who were followed for over 12-14 years to assess the incidence of cancer there was an inverse association between the risk of cancer and both serum retinol and serum cholesterol concentrations. The data also showed an unexpectedly strong correlation between serum retinol and total cholesterol concentrations. The inverse relationship with cancer was stronger with serum retinol than with cholesterol, which suggested that the association with cholesterol might be secondary. This suggestion may also explain the cholesterol-cancer association reported in several other cohort studies. Further studies of the relation between serum concentrations of cholesterol, retinol, and carotene and the incidence of cancer are needed.

Cholesterol↗