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Biomedical subjects

M Garland

Publications and source records attributed to M Garland.

At least 19 recordsLinked to original sources
PubMed2000

Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania.

BACKGROUND: Observational studies suggest that poor nutritional status among HIV-infected pregnant women is associated with a higher risk of vertical transmission of HIV. METHODS: We randomized 1083 pregnant women infected with HIV-1 in a double-blind, placebo-controlled trial to examine the effects of supplements of vitamin A and/or multivitamins (excluding vitamin A) using a 2-x-2 factorial design. We report the effects of the supplements on HIV infection defined using polymerase chain reaction (PCR), or death up to 6 weeks postpartum. RESULTS: Of babies in the multivitamin arm 38, (10.1%) were HIV-positive at birth compared with 24 (6.6%) in the no-multivitamin arm (relative risk [RR] = 1.54; 95% CI, 0.94-2.51; p = .08). Of babies born to mothers in the vitamin A arm, 38 (10.0%) were HIV-positive at birth compared with 24 (6.7%) in the no-vitamin A arm (RR, 1.49; 95% CI, 0.91-2.43; p = 0.11). Neither multivitamins nor vitamin A had an effect on HIV status at 6 weeks among those who were HIV-negative at birth (RR = 1.04; 95% CI, 0.65-1.66; p = 0.88) and (RR = 1.30; 95% CI, 0.80-2.09; p = .29, respectively). Similarly, neither supplement was associated with being either HIV-infected or dead at birth (RR, 0.98; 95% CI, 0.76-1.27; p = .89 and RR, 1.01; 95% CI, 0.78-1.31; p = .95, respectively. A beneficial effect of multivitamins on birth weight was limited to babies who were HIV-negative at birth; babies in the multivitamin arm weighed +94 g more compared with those in the no-multivitamin arm (p = .02). Among babies who were HIV-positive at birth, the corresponding difference was -31 g (p = .82). CONCLUSIONS: Vitamin A and multivitamins did not affect the risk of vertical transmission of HIV in utero nor during the intrapartum and early breastfeeding periods. Multivitamins resulted in a significant improvement in birth weight of babies who were HIV-negative at birth but had no effect among those who were HIV-positive. The effect of vitamin supplements on HIV transmission through breastfeeding and on clinical progression of HIV disease is yet to be ascertained.

Adult↗
PubMed2000

Total serum cholesterol in relation to psychological correlates in parasuicide.

BACKGROUND: Low cholesterol may act as a peripheral marker for parasuicide. AIMS: To examine the relationship between total serum cholesterol and psychological parameters in parasuicide. METHOD: Total serum cholesterol and self-rated scores for impulsivity, depression and suicidal intent were measured in 100 consecutive patients following parasuicide, pair-matched with normal and psychiatric control groups. RESULTS: Backward, stepwise multiple regression analysis revealed a significantly lower mean cholesterol in the parasuicide population (P < 0.01). Across all groups there was an independent significant (P < 0.01) negative correlation between cholesterol and self-reported scores of impulsivity. No correlation existed between cholesterol and scores for depression or suicidal intent. CONCLUSIONS: The data confirm previous reports of low cholesterol in parasuicide. This is the first reported investigation of the construct of impulsivity in relation to cholesterol. We hypothesise that the reported increased mortality in populations with low cholesterol may derive from increased suicide and accident rates consequent on increased tendencies to impulsivity in these populations.

Adolescent↗
PubMed1999

Gestational age related changes in cardiac dynamics of the fetal baboon.

To provide insight into the maturation of neural mechanisms governing fetal heart rate and rate variability, seven chronically instrumented fetal baboons were monitored under steady state conditions between 120 and 165 days gestation (term 175 d). Forty records of 24 h duration (5-7 records/fetus) were evaluated. For each fetus, heart rate decreased with gestational age (mean+/-SD, r = -0.530+/-0.324, P <0.05). In contrast, there were increases with age in markers of various components of autonomic control of fetal R-wave to R-wave interval (RRi) variability as reflected in a positive correlation with age for all fetuses of SD RRi (r = 0.656+/-0.347, P < 0.01), root mean squared differences in RRi (r = 0.686+/-0.223, P <0.05), and power at low frequency in the RRi spectrum (r = 0.800+/-0.161 P < 0.01). In each of the seven fetuses, scatter plots of RRi as a function of the prior RRi (Poincare plots) had increased dispersion around the median with gestational age (0.605+/-0.371, P<0.05). Additional measures of variability evaluated changes in RRi from one interval to the next (deltaRRi). The incidence of sustained deltaRRi changes, either decelerations or accelerations, rose with gestation (r = 0.920+/-0.057, P < 0.001) while the incidence of no detected deltaRRi changes (<+/-1 ms) diminished (r = - 0.649+/-0.364, P <0.05). Sequential decreases in fetal heart rate, increases in RRi variability and increases in changes in RRi and deltaRRi with age imply an overall maturation in autonomic cardio-regulatory control processes. Increases with gestation in measures of high frequency components of variability are compatible with enhanced parasympathetic modulation of fetal heart rate.

Animals↗
PubMed1999

Diurnal rhythms of fetal and maternal heart rate in the baboon.

To investigate the organization of diurnal rhythmicity during gestation, the relationship between daily cycles of maternal and fetal heart rate were measured in long-term studies of healthy chronically instrumented pregnant baboons. In each of six pregnancies, hourly mean values over a 168 h time series were obtained during a 7 to 10 day interval between 135 and 160 days of gestation. Data were modeled by a least squares fit to a cosine function with a period of 24 h. Hourly mean heart rate in the fetus ranged from 161 to 172 bpm (167.9+/-0.6 bpm), and the mother from 105 to 125 bpm (107.9+/-1.4 bpm). The amplitude of the daily fluctuations were 15 to 25 bpm for the fetuses and 25 to 60 bpm for the mothers. The relation between time series data and model estimates were significant (P < 0.001) in all cases with aggregate r2 = 0.747 for fetuses and 0.737 for the mothers. On average the time of day of the peak in fetal heart rate (15:05+/-0.3 h) was about 45 min after the maternal peak (14:21+/-0.4 h). This phase delay was significant (t = 2.63, P < 0.05). There was significant (P < 0.01) diurnal periodicity for each of six parameters used to assess different aspects of fetal heart rate variability with peak variability at night (23:00 to 2:00). Thus, during the latter third of pregnancy in both the maternal and fetal baboon 24 h periodicities of heart rate are present with peak rates in the midafternoon. The daily rhythms in fetal heart rate are linked with periodicities in maternal heart rate with a phase delay in the majority of cases. The synchrony of 24 h fluctuations in rate with parameters of rate variability is consistent with diurnal input into the fetal autonomic nervous system.

Amniotic Fluid↗
PubMed1999

Alcohol consumption in relation to breast cancer risk in a cohort of United States women 25-42 years of age.

We evaluated current and past alcohol consumption prospectively in relation to breast cancer risk among 116,671 women ages 25-42 years old at enrollment in 1989. During 6 years of follow-up, 445 cases of invasive breast cancer were identified. For alcohol consumption in the previous year, the multivariate relative risk associated with more than 20 g/day (approximately 10 drinks/week) was 1.23 (95% confidence interval, 0.68-2.21); the P for trend was 0.85. For average lifetime alcohol consumption, the multivariate relative risk associated with consumption of 10 or more drinks/week was 1.20 (95% confidence interval, 0.69-2.11); the P for trend was 0.18. We examined drinking in several time periods of life; only drinking at ages 23-30 was significantly positively associated with risk. Although this may represent a chance finding, it merits further study. Because drinking levels in this population were low, we had limited information on heavier drinking. Our results suggest that there is unlikely to be a large effect of moderate alcohol consumption on breast cancer risk among young women, although a modest effect cannot be excluded. The association between alcohol consumption and breast cancer is unlikely to be substantially stronger among premenopausal women than among postmenopausal women.

Adolescent↗
PubMed1998

Implications of the kinetics of zidovudine in the pregnant baboon following oral administration.

Zidovudine (ZDV) therapy in pregnancy reduces mother-to-child transmission of HIV. The action of ZDV in the fetus is thought to be an important contributor to efficacy. Previous research in primates has demonstrated that continuous infusion of ZDV to the mother leads to sustained plasma concentrations in the fetus; however, it has not been determined what concentrations of ZDV are achieved in the fetus following oral administration. The pharmacokinetics of drug distribution to the fetus following oral administration of a 100-mg dose of ZDV to the mother are reported from 6 chronically catheterized baboons. The first order elimination half-life of ZDV from both the mother and fetus was approximately 1.2 hours. The area under the concentration-time curve for the fetus was 77% (r2 = 0.98; p < .001) that of the mother and the estimated peak drug levels in the fetus were 52% (r2 = 0.83; p < .01) those in the mother. The rapid transfer and short half-life of ZDV leads to a drug concentration-time profile that would not sustain levels in the fetus with dosing every 4 hours. After comparing these findings with existing data from pregnant and nonpregnant humans, it seems likely that current dose recommendations for ZDV in pregnancy would not maintain levels of the active intracellular metabolite of ZDV in all fetuses. This may explain in part the 8% failure rate of ZDV prophylaxis. The correlation between fetal and maternal plasma concentrations of ZDV would allow titration of dose based on maternal drug levels to achieve fetal levels within the therapeutic range.

Administration, Oral↗
PubMed1998

Menstrual cycle characteristics and history of ovulatory infertility in relation to breast cancer risk in a large cohort of US women.

Menstrual cycle characteristics and ovulatory infertility were evaluated in relation to breast cancer risk among 116,678 women in the Nurses' Health Study II, a prospective cohort study of female registered nurses who were aged 25-42 years and living in 14 US states at enrollment in 1989. During 396,299 person-years of follow-up between return of the baseline questionnaire and June 1993, 251 cases of breast cancer were identified in this cohort. The multivariate relative risk (RR) associated with age at menarche > 13 years compared with age < or = 12 years was 0.66 (95% confidence interval (CI) 0.44-0.99). Short and long menstrual cycle lengths at ages 18-22 years were associated with reduced risk. Compared with menstrual cycle length 26-31 days, the multivariate relative risks (95% CIs) for more extreme cycle lengths were: < 26 days, 0.50 (0.25-0.98); 32-39 days, 0.81 (0.51-1.28); and > 39 days or too irregular for estimation of a usual cycle length, 0.41 (0.18-0.94). The multivariate relative risk associated with a history of ovulatory infertility, compared with no such history, was 0.41 (95% CI 0.18-0.93). These results are consistent with the hypothesis that reduced exposure to ovulatory menstrual cycles provides a protective effect against breast cancer.

Adult↗
PubMed1998

Diurnal rhythm of fetal behavioral state.

To test for the presence in utero of diurnal periodicity in the amount of time spent in organized behavioral states, seven records of 24-hour duration were obtained from each of five chronically instrumented fetal baboons between 144 and 158 days gestation (term = 175 days). Concordance of fetal breathing activity, heart-period variability, and electroencephalographic parameters were used to define two distinctive patterns of fetal physiological activities. One pattern was characterized as EEG activity dominated by tracé alternant, reduced heart-period variability, and fewer breaths in epochs of fetal breathing. This fetal behavioral state (1FB) is analogous to quiet sleep in infants. A second pattern was characterized by the relative absence of tracé alternant, increased heart-period variability, and fetal breathing activity. This fetal behavioral state (2FB) is analogous to active sleep. Cycles of these states were present 29% of time, with a duration of approximately 26 minutes and a 1.7:1 predominance of 2FB/1FB. Cosinor analysis across fetuses revealed a significant (p < .01) 24-hour periodicity of the time spent by the fetus in organized behavioral states, with a peak around 1400 (lights-on 0700 to 1900) and a peak-nadir fluctuation of 15%. These periodicities in the incidence of organized state were significant (p < .01) in three fetuses, and approached significance (< .09) in the two others. Data demonstrate a diurnal rhythmicity in fetal behavioral states, with less time spent in organized state at night than during the day.

Animals↗
PubMed1998

Pharmacology of drug transfer across the placenta.

The effect of drugs in the fetus can be thought of in terms of the dose-response based on a knowledge of the general principles by which drug is transferred from the mother to the fetus. Fetal drug concentration, which determines the fetal response, is a function of the maternal concentration, the placental permeability, the fetal drug clearance, and differences in protein binding and ionization between the maternal and fetal plasma.

Animals↗
PubMed1998

The relation between dietary intake and adipose tissue composition of selected fatty acids in US women.

We compared fatty acid amounts in adipose tissue with fatty acid intake calculated from 2 separate weeks of diet recording and two food-frequency questionnaires for 140 participants in the Nurses' Health Study. Our results showed that the amounts of polyunsaturated and trans fatty acids in adipose tissue reflect dietary intake and confirm those of previous studies. The correlation between the polyunsaturated fatty acid content of adipose tissue and polyunsaturated fatty acid intake from the average of the two food-frequency questionnaires was 0.40; this correlation for trans fatty acids was also 0.40. Linolenic acid amounts in adipose tissue were also moderately correlated with intake from the average of the food-frequency questionnaires (r = 0.34). An estimate of trans fatty acid intake from vegetable sources correlated much more strongly with adipose trans fatty acids than did an estimate of trans fatty acids from animal sources. Adipose tissue aspirates can be used to indicate intake of exogenous fatty acids.

Adipose Tissue↗
PubMed1998

Placental transfer and fetal metabolism of zidovudine in the baboon.

Zidovudine (azidothymidine, AZT) is used in pregnancy to reduce mother to infant transmission of HIV. Understanding the disposition of AZT in the fetus is necessary to optimize therapeutic regimens directed toward the fetus. Recent studies in primates found similar steady-state levels of the glucuronide metabolite of AZT (AZT-glu) in the fetus to those in the mother, raising the question of whether the metabolite was of fetal or maternal origin. The objective of this study was to determine whether glucuronidation occurred in the fetal compartment and to quantify the placental and fetal clearances of AZT using the two-compartment model at steady state. Steady-state concentrations were obtained after paired maternal and fetal infusions of AZT in chronically catheterized pregnant baboons. During maternal infusion, the mean (+/-SE) fetal to maternal ratio of AZT was < 1 (0.84 +/- 0.06, p < 0.02), suggesting clearance of AZT in the fetus. Mean total maternal clearance of AZT was 725 +/- 49 mL/min and placental clearance was 36 +/- 4 mL/min, or approximately 5% of maternal clearance. Fetal clearance of AZT was estimated at approximately 15% of placental clearance. This suggests fetal nonplacental clearance is minimal compared with that in the mother, but does not preclude the fetus from actively contributing to the metabolite in the fetal circulation. During infusion of AZT to the fetus, the concentration of AZT-glu in the fetus was 7.0 +/- 0.8 times that in the mother. This is compelling evidence that glucuronide can be formed in the fetal compartment. Thus, fetal metabolism has an impact on the concentration of both AZT and AZT-glu in the fetal circulation.

Amniotic Fluid↗
PubMed1997

Effect of zidovudine on blood composition of the pregnant and fetal baboon.

OBJECTIVE: Our purpose was to assess the effect of intravenous zidovudine on placental function and fetal well-being. STUDY DESIGN: Eighteen chronically instrumented third-trimester pregnant baboons and their fetuses were studied after 4- to 48-hour infusions of zidovudine to 14 mothers (0.8 to 2.0 mg/kg/hr) and 6 fetuses (0.2 to 0.22 mg/kg/hr of maternal weight). Fetal and maternal pH and blood gases, hematocrit, blood cell counts, clinical chemistries, electrolytes, and hormones were measured before and after the infusions. RESULTS: In both mother and fetus no significant differences were found between values in the control periods and those after infusions of zidovudine in any of the index values measured. CONCLUSION: Administration of zidovudine from 4 to 48 hours in the baboon was associated with no significant change in any biochemical index values in the mother or fetus. Thus comparable exposure of the human fetus to zidovudine during labor is not expected to affect these index values of placental function and fetal well-being.

Acid-Base Equilibrium↗
PubMed1997

Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases.

A common deletion polymorphism in the gene coding for the glutathione S-transferase class mu (the GSTM1 gene) results in a decreased ability to detoxify carcinogenic epoxide intermediates and has been associated with increased breast cancer risk in some small studies. We studied the GSTM1 gene deletion polymorphism (conferring the null genotype) in 243 women who had prevalent breast cancer and 245 women without breast cancer, who were among the 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. In the prevalent case series, the null genotype was slightly more common among cases (58%) than among controls (51%; age-adjusted odds ratio = 1.30; 95% confidence interval, 0.91-1.86). Among cases, the prevalence of the GSTM1 deletion increased with duration of survival [68% for > or = 8 years since diagnosis; 57% for 4-8 years; 51% for < 4 years; P (trend) = 0.04]. In an incident case series of 240 women who were diagnosed with breast cancer following blood collection and prior to June of 1992 and compared with age-matched controls, the GSTM1 deletion was not associated with an elevation in risk (relative risk, 1.08; 95% confidence interval, 0.74-1.57). No significant interaction with cigarette smoking was evident. Thus, there was no significant increase in risk of incident breast cancer associated with the GSTM1 null genotype; however, the gene deletion polymorphism appeared to confer improved survival. These data suggest that odds ratios based upon prevalent cases in molecular epidemiologic studies may be biased due to differential survival. Further studies are required to determine whether this polymorphism is associated with improved breast cancer prognosis.

Adult↗
PubMed1996

Toenail trace element levels and breast cancer: a prospective study.

The associations between toenail levels of five trace elements and breast cancer risk were studied among a cohort of 62,641 US women who provided toenail clippings and were free from diagnosed breast cancer in 1982. Among 433 cases of breast cancer identified during 4 years of follow-up and their matched controls, the odds ratios comparing the highest with the lowest quintiles and adjusted for established breast cancer risk factors were as follows: for arsenic, 1.12 (95% confidence interval (CI) 0.66-1.91); for copper, 0.91 (95% CI 0.59-1.42); for chromium, 0.96 (95% CI 0.61-1.52); for iron, 0.89 (95% CI 0.56-1.40); and for zinc, 1.09 (95% CI 0.70-1.70). Among postmenopausal women, a marginally significant positive association was observed between toenail chromium levels and breast cancer risk (odds ratio = 1.71, 95% CI 0.87-3.35) (p for trend = 0.07). However, the association between chromium and breast cancer risk was inverse among premenopausal women. Although data on the validity of toenail levels of certain of these elements are limited, these results do not provide evidence for an important effect of arsenic, copper, chromium, iron, or zinc on breast cancer risk.

Adult↗
PubMed1996

Zidovudine kinetics in the pregnant baboon.

The devastating impact of human immunodeficiency virus (HIV) infection during pregnancy has made the pharmacologic evaluation of potentially therapeutic agents of high priority. The results presented here are the maternal pharmacokinetics from a series of experiments to delineate more clearly the complex maternal-fetal pharmacokinetics and the effects of AZT in the chronically instrumented maternal and fetal baboon during both steady state intravenous infusion and oral bolus dosage regimens. Two results of major clinical importance were found. First, during pregnancy, both the clearance and volume of distribution of AZT were increased. Plasma clearance in the pregnant animals was 51 +/- 10 ml/min/kg compared with 37 +/- 2 ml/min/kg in the nonpregnant animals, and steady state volume of distribution was 3.7 +/- 1.21/kg compared with 2.2 +/- 0.61/kg. Second, with continuous intravenous infusion plasma drug concentrations were easily maintained in the therapeutic range, whereas with oral administration plasma concentration fell below therapeutic levels within 2 h of the dose being given. Because maternal plasma concentrations are a major determinant of drug concentration achieved in the fetus, an understanding of drug kinetics in pregnancy is of vital importance when making recommendations regarding optimal drug therapy during pregnancy to maximize the beneficial effect--the prevention of HIV infection in children.

Absorption↗