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Biomedical subjects

M A Williams

Publications and source records attributed to M A Williams.

At least 19 recordsLinked to original sources
PubMed1992

The accumulation and metabolism of glycosphingolipids in primary kidney cell cultures from beige mice.

In the normal C57BL/6J male mouse a specific subset of the kidney glycosphingolipids which is associated with multilamellar bodies of lysosomal origin and represents about 10% of the total kidney glycolipids, is excreted into the urine each day. This excretion is blocked and glycosphingolipids accumulate in the kidney of bgJ/bgJ mutants of this strain. To examine this process in vitro, glycosphingolipid metabolism and excretion were studied in beige mouse kidney cell cultures. Primary kidney cell cultures from male C57BL/6J control and bgJ/bgJ beige mutants were grown in D-valine medium and glycosphingolipids labeled with [3H]palmitate. As we have shown previously, the giant lysosomes of altered morphology were maintained in cultures of the beige kidney cells. Beige-J and control cells synthesized the same types of glycosphingolipids, but the mutant cells had quantitatively higher levels of these compounds than control cells, as determined by high performance liquid chromatography. Beige-J cells incorporated more [3H]palmitate into glycosphingholipids than control cells on a cpm/mg protein basis and the specific activity (cpm/pmole glycosphingolipid) was lower in beige cells. Medium from beige-J cells accumulated more glycosphingolipids than that from control cells in a 24 h period. The glycosphingolipids released into the medium as determined by HPLC were primarily non-lysosomal types and both control and mutant cells retained the glycosphingolipids associated with lysosomal multilamellar bodies excreted in vivo. The elevated levels of lysosomal glycosphingolipids and the dysmorphic lysosomes in primary cultures of beige cells, then, are not caused by a mutant block in secretion of lysosomes.

Animals↗
PubMed1992

Cigarettes, coffee, and preterm premature rupture of the membranes.

Premature (prior to 37 completed weeks of gestation) rupture of the membranes (preterm PROM) is one of the most common underlying causes of preterm delivery. However, there have been few epidemiologic studies of this obstetric complication. The authors studied the relation of maternal cigarette smoking and coffee consumption to both preterm PROM and spontaneous preterm labor not complicated by premature rupture of the membranes (preterm NONPROM) in a large cross-sectional data base. The 307 preterm PROM and 488 preterm NONPROM cases who delivered during 1977-1980 at the Boston Hospital for Women were compared with 2,252 randomly selected women who delivered at term at that institution. Multiple logistic regression techniques were used to derive maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). After confounders had been adjusted for, the relative risk of preterm PROM for women who reported ever having smoked during pregnancy, as compared with nonsmokers, was 1.6 (95% CI 1.1-2.4). However, no gradient between the number of cigarettes smoked per day and the risk of preterm PROM was observed. Similar results were observed for preterm NONPROM. Women who consumed three or more cups of coffee daily during the first trimester had a 2.2-fold greater risk of preterm PROM than did women who drank two or fewer cups (95% CI 1.5-3.3). Among coffee drinkers, there was some evidence of a linear trend in the risk of preterm PROM as coffee consumption increased. Consumption of three or more cups of coffee per day was less strongly associated with the occurrence of preterm NONPROM (adjusted OR = 1.4, 95% CI 1.0-1.9).

Adolescent↗
PubMed1992

Long-term effects of desmotomy of the accessory ligament of the deep digital flexor muscle in standardbreds: 23 cases (1979-1989).

Desmotomy of the accessory ligament of the deep digital flexor muscle (inferior check desmotomy) permitted Standardbred foals affected with flexural deformities to reach their full athletic potential. Long-term effects of inferior check desmotomy were examined in 23 Standardbreds over a 10-year period. Six of 11 foals that were treated surgically either raced 6 times and obtained a race record or were training sound (if yearlings). All 12 horses with flexural deformity that did not receive an inferior check desmotomy had an unfavorable outcome (no race record). Foals that had surgery performed at a younger age apparently had a better chance of racing or training sound because no foals treated surgically after 8 months of age had a favorable outcome and only 1 foal that was older than 5 months at the time of surgery had a favorable outcome. In 5 foals that had surgery with an unsuccessful outcome, 3 were greater than or equal to 1 year old at the time of surgery and were lame when training was started on the limb(s) with the desmotomy.

Animals↗
PubMed1992

Impact of chronic oral H2-antagonist therapy on left ventricular systolic function and exercise capacity.

It has been suggested that H2-antagonists may adversely affect left ventricular systolic function. To assess the effects of cimetidine, famotidine, and ranitidine on exercise capacity and left ventricular systolic function, the authors conducted a randomized, double-blind, four-way crossover study in 15 healthy male volunteers with placebo control. Each subject underwent a maximal upright treadmill exercise test, aerobic metabolic assessment, and two-dimensional stress echocardiography on six separate occasions. The initial two treadmill exercise tests with aerobic metabolic assessment and stress echocardiography were performed to minimize the learning effect. In the final four evaluations, subjects were randomized to receive 7 days of oral treatment with cimetidine 400 mg twice daily, famotidine 40 mg daily, ranitidine 150 mg twice daily, and placebo. A comparison of exercise tests, aerobic metabolic assessment, and stress echocardiography results found no significant differences between any of the H2-antagonists and placebo. In addition, there were no significant differences in test results between cimetidine, famotidine, and ranitidine. Specifically, exercise treadmill time, maximal oxygen consumption, respiratory quotient, maximal exercise systolic and diastolic blood pressure, maximal exercise heart rate, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, and ejection fraction were not different between treatments. The authors conclude that 7 days of oral treatment with cimetidine, famotidine, or ranitidine has no deleterious effect on exercise capacity or left ventricular systolic function in healthy subjects.

Administration, Oral↗
PubMed1992

Elevated maternal serum alpha-fetoprotein levels and midtrimester placental abnormalities in relation to subsequent adverse pregnancy outcomes.

OBJECTIVE: Unexplained elevations of maternal serum alpha-fetoprotein levels in the second trimester of pregnancy are associated with adverse pregnancy outcomes, including intrauterine growth retardation, preterm delivery, preeclampsia, and abruptio placentae. In addition, elevations of maternal serum alpha-fetoprotein have been associated with placental lesions detected during second-trimester ultrasonographic evaluations. We examined the relationship between adverse pregnancy outcomes and unexplained elevations of maternal serum alpha-fetoprotein and placental abnormalities in the second trimester of pregnancy. STUDY DESIGN: During the period from January 1989 to March 1991 we conducted a cohort study of 201 women with an elevated maternal serum alpha-fetoprotein (> or = 2.0 multiples of the median) and a second-trimester ultrasonographic evaluation at Swedish Hospital Medical Center and 211 women with normal maternal serum alpha-fetoprotein levels who had also undergone ultrasonographic evaluation at the same institution. All women in this investigation had singleton pregnancies without fetal anomalies. RESULTS: Elevated maternal serum alpha-fetoprotein was associated with the following adverse pregnancy outcomes: low birth weight (adjusted risk ratio 3.7), preterm delivery (adjusted risk ratio 3.6), intrauterine growth retardation (adjusted risk ratio 4.0), preeclampsia (adjusted risk ratio 3.8) and abruptio placentae (adjusted risk ratio 4.8). Placental abnormalities detected during second-trimester ultrasonographic evaluations were also associated with adverse pregnancy outcomes: low birth weight (adjusted risk ratio 2.0), preterm delivery (adjusted risk ratio 2.3), intrauterine growth retardation (adjusted risk ratio 1.4), and abruptio placentae (adjusted risk ratio 9.0). A joint positive history of second-trimester elevations of maternal serum alpha-fetoprotein and placental abnormalities was more strongly associated with the following adverse infant outcomes: low birth weight (adjusted risk ratio 6.9), preterm delivery (adjusted risk ratio 5.6), and intrauterine growth retardation (adjusted risk ratio 5.3). CONCLUSIONS: Unexplained elevated levels of maternal serum alpha-fetoprotein and placental abnormalities detected in the second trimester of pregnancy are associated with particularly poor pregnancy outcome. Careful examination for placental abnormalities should be part of the evaluation of elevated maternal serum alpha-fetoprotein.

Birth Weight↗
PubMed1992

Prevention of preterm delivery and low birth weight associated with asymptomatic bacteriuria.

Since the first report of an association between asymptomatic bacteriuria and low birth weight (less than 2,500 g) in 1962, greater than 30 other studies on the same subject have been published. Some of these confirmed this association while others disputed it. Now, however, by using meta-analysis (a technique considered valid by many but not all statisticians) one may conclude with increased certainty that true associations between asymptomatic bacteriuria and preterm delivery (less than 37 weeks of gestation) and asymptomatic bacteriuria and low birth weight do exist. Because asymptomatic bacteriuria in pregnancy remains prevalent and preventable, a review of this important subject is relevant at this time.

Bacteriuria↗
PubMed1992

Estimating the time of death in stillborn fetuses: I. Histologic evaluation of fetal organs; an autopsy study of 150 stillborns.

OBJECTIVE: To determine whether the autopsy histology of fetal tissues can determine the time of death of stillborn fetuses. METHODS: Hematoxylin and eosin slides from autopsies of 150 stillborn fetuses with well-timed deaths were evaluated retrospectively. Fetuses were divided into a learning set (100 fetuses) and a test set (50 fetuses). RESULTS: From assessment of the 100 fetuses in the learning set, 23 histologic features were identified with possible temporal associations with fetal death. When those histologic features were randomly and blindly assessed in the 50 test fetuses, ten features performed well as diagnostic tests (sensitivity, specificity, and positive predictive values at or above 0.875), correctly classifying 43 of 50 fetuses (86%) with respect to the time of death. The ten histologic features and their predicted death-to-delivery intervals were: loss of nuclear basophilia in individual cells in renal cortical tubules (4 hours), liver (24 hours), inner half of the myocardium (24 hours), outer half of the myocardium (48 hours), bronchial epithelium (96 hours), and tracheal cartilage (1 week); and loss of nuclear basophilia of all cells in the liver (96 hours), gastrointestinal tract (1 week), adrenal (1 week), and kidney (4 weeks). The development of these histologic changes appeared to be accelerated by fetal hydrops and a delivery-to-autopsy interval exceeding 24 hours and decelerated by fetal gestational age under 25 weeks. CONCLUSION: Histologic changes identifiable in hematoxylin and eosin-stained fetal tissue may be useful for estimating the time of death in many stillborn fetuses.

Autopsy↗
PubMed1992

Low birth weight and preterm delivery in relation to early-gestation vaginal bleeding and elevated maternal serum alpha-fetoprotein.

OBJECTIVE: To determine whether early-gestation vaginal bleeding and elevated maternal serum alpha-fetoprotein (MSAFP) are independent risk factors for adverse infant outcomes. METHODS: We conducted a cohort study of 201 women with an elevated MSAFP (at least 2.0 multiples of the median [MOM]) and a second-trimester ultrasound evaluation at Swedish Hospital Medical Center between January 1989 and March 1991, and 211 women with MSAFP levels below 2.0 MOM who had also undergone ultrasound evaluations during the same period. RESULTS: Stratified analyses demonstrated that early-gestation bleeding and elevated MSAFP were independent risk factors for the delivery of both preterm and low birth weight infants. Compared with women with no history of early-gestation bleeding or elevated MSAFP, women with early-gestation bleeding alone had a relative risk (RR) of preterm delivery of 4.3 (95% confidence interval [CI] 1.5-12.1); non-bleeders with elevated MSAFP had an RR of 4.6 (95% CI 1.9-10.9). A combined history of early-gestation bleeding and elevated MSAFP was associated with an almost sixfold increased risk of preterm delivery (RR 5.8; 95% CI 2.2-15.6). Analyses restricted to women with normal-appearing appearing placentas by second-trimester ultrasound evaluations yielded similar results. CONCLUSIONS: These findings support an earlier report documenting the independence of early-gestation bleeding and elevated MSAFP as predictors of adverse infant outcomes.

Cohort Studies↗
PubMed1992

Measuring change in surgical practice.

We reviewed the work of a single general surgical firm over six years--about 11,500 patient episodes. Although the workload remained approximately constant, a severe reduction in the number of available beds was accompanied by a marked change towards shorter duration of stay. This affected particularly the elective cases. Previous authors, when trying to predict requirement of hospital beds, have accepted that duration of stay and number of beds available are independent variables; this was not what we observed.

Bed Occupancy↗
PubMed1991

Risk factors for abruptio placentae.

The authors studied the relation of sociodemographic, medical, and life-style factors and abruptio placentae in a large cross-sectional data base. The 143 cases of abruption identified in the Delivery Interview Program, conducted in Boston from 1977 to 1980, were compared with 1,257 randomly selected controls. The authors used multiple logistic regression techniques to derive maximum likelihood estimates of the adjusted odds ratios and 95% confidence intervals as measures of the association between exposure factors and abruption. A history of chronic hypertension was associated with a threefold increase in risk (odds ratio (OR) = 3.1, 95% confidence interval (Cl) 1.1-8.4), but pregnancy-induced hypertension was not associated with abruption. Excess risk was associated with advanced maternal age (OR = 2.3, 95% Cl 1.3-3.9), low prepregnancy body mass index (OR = 2.3, 95% Cl 1.3-4.1), a history of prior stillbirth (OR = 3.5, 95% Cl 1.8-7.0), and at least weekly use of marijuana during pregnancy (OR = 2.8, 95% Cl 1.2-6.6). Overall, the association with cigarette smoking during pregnancy was of only borderline significance (OR = 1.5, 95% Cl 1.0-2.2), although there appeared to be a dose-response relation between the number of cigarettes smoked and risk of abruption.

Abruptio Placentae↗
PubMed1991

Pharmacologic treatment of priapism in two horses.

Benztropine mesylate was used successfully to treat priapism that developed during anesthesia in 2 horses. After IV injection, there was a rapid resolution of signs in both horses, and no side effects were observed. The choice of an effective method to treat priapism is challenging because precise causes in most patients have not been well-defined. Benztropine mesylate is a synthetic compound resulting from the combination of the active portions of atropine and diphenhydramine, and is believed effective because of its central acetyl-choline-antagonizing properties.

Anesthesia, General↗
PubMed1991

Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility.

Female fertility declines with advancing age. To establish whether this age-related reproductive failure results from diminished oocyte quality or uterine/endometrial inadequacy we investigated ovum donation in 35 infertile women, aged 40 years or older (mean 42.7 [SE 0.3]) who had failed at attempts at conception with their own (self) oocytes. Oocytes were donated by 29 young individuals (mean age 33.4 [0.7]) undergoing in-vitro fertilisation (IVF). 8 (5.3%) pregnancies were achieved in 150 cycles of ovulation induction with self-oocytes and 2 (3.3%) in 60 such cycles by in-vitro fertilisation (IVF), but none attained viability. By contrast in 50 cycles with donated oocytes 28 (56%) pregnancies and 15 (30%) deliveries were realised (p less than 0.005). The rate of implantation per embryo transferred was higher (14.7%) with donated oocytes than that with self-oocytes (3.3%) (p less than 0.01). To further elucidate the contribution of age to reproductive outcome, pregnancy results were compared between the young donors and older recipients. Both donors and recipients shared oocytes from the same induced cohort. Rates for clinical pregnancy and delivery did not differ between donors (33% and 23%) and recipients (40% and 30%). Our data suggest that the age-related decline in female fertility is attributable to oocyte quality and is correctable by ovum donation. The uterus can adequately sustain pregnancies even when reproductive potential is artificially prolonged into the late 40s.

Adult↗
PubMed1991

Predicting the behaviour and selectivity of fluorescent probes for lysosomes and related structures by means of structure-activity models.

Cultured rat fibroblasts were exposed to 50 fluorescent probes of varied physicochemical characteristics. Probe concentrations, fluorochrome excitation wavelength and period of illumination, and cell-probe contact time were varied. Structure-activity relationships defining a number of classes of fluorescent probes for lysosomes and related processes and compartments were demonstrated. Numerical specifications are now available for several familiar classes of probes: (a) acidotropic weak bases, used as markers for low pH compartments; (b) markers of adsorptive pinocytosis, involving non-specific protein binding; (c) markers for fluid phase pinocytosis; and (d) viability stains involving intralysosomal enzymic activity. Two novel classes of probes have also been specified numerically: (a) acid-precipitated weak acids, as markers for low pH compartments; and (b) lipid-binding markers of adsorptive pinocytosis. Overall, these structure-activity models provide a tool for predicting whether or not compounds enter cells; and whether they accumulate in lysosomes and related compartments. Pathways of entry are also predicted. This tool should permit design and selection of improved probes, and provide a better understanding of existing reagents. Moreover these models are expected to be applicable to interactions between any non-polymeric xenobiotic with lysosomes and related compartments.

Animals↗
PubMed1991

Cigarette smoking during pregnancy in relation to placenta previa.

To evaluate the relationship between cigarette smoking and the occurrence of placenta previa, we used interview and medical record data to conduct a case-control analysis of 69 placenta previa cases and 12,351 controls. The unadjusted relative risk estimate of placenta previa for women reported to have "ever smoked" during pregnancy relative to nonsmoking mothers was 1.9 (95% confidence interval, 1.2 to 3.0). The risk rose after adjusting for potential confounders (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.5). In contrast to a previous report, the duration of smoking was not an independent risk factor for placenta previa. These results suggest that cigarette smoking during pregnancy is a determinant of placenta previa. Carbon monoxide hypoxemia, which is one possible mechanism for this association, may result in compensatory placental hypertrophy. Placentas with increased surface areas are more likely to cover the cervical os, causing placenta previa.

Adult↗
PubMed1991

Subfertility and the risk of low birth weight.

OBJECTIVE: We evaluated the association between subfertility and low birth weight infants. DESIGN: Women in this analysis participated in a cross-sectional investigation of maternal risk factors for adverse pregnancy outcomes. SETTING: Medical and obstetric history and life style information were obtained from women who delivered at the Boston Hospital for Women, 1977 to 1980. PATIENTS, PARTICIPANTS: Our analysis was restricted to nondiabetic married women who planned their pregnancies and subsequently delivered viable singletons (3,622). The 644 "subfertile" women (no conception during a year of unprotected intercourse) were compared with 2,978 "fertile" women (conception within 1 year). MAIN OUTCOME MEASURE(S): The relative risk of low birth weight was estimated using the cumulative incidence risk ratio. RESULTS: After adjusting for confounding, the relative risk of delivering a low birth weight infant (less than 2,500 g) for subfertile women versus fertile women was 1.9 (95% confidence interval [CI], 1.3 to 2.8). The adjusted relative risk of delivering a term low birth weight (intrauterine growth retarded) infant was 2.3 (95% CI, 1.2 to 4.4). CONCLUSIONS: In these data, subfertility is a predictor for low birth weight. The association may result from endocrinological, immunological, cervical, or other factors that interfere with optimal fetal growth.

Coffee↗
PubMed1991

Delirium/acute confusional states: evaluation devices in nursing.

Characteristics of instruments developed by nurses for use in evaluating delirium/acute confusional states include relative emphasis on observable behavior and the need to impose low respondent burden. Two instruments that have been most used by nurse researchers are described: The Confusion Rating Scale and the NEECHAM Confusion Scale. The former is based on observable behavior; the latter incorporates vital function and oxygen saturation measurements that may serve as early warning signs of impending delirium.

Aged↗