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Biomedical subjects

M A Williams

Publications and source records attributed to M A Williams.

At least 73 records · Page 4Linked to original sources
PubMed2001

Report of the Council on Scientific Affairs: methadone maintenance and needle-exchange programs to reduce the medical and public health consequences of drug abuse.

Extensive evaluation studies show that methadone maintenance therapy (MMT) reduces heroin use and associated problems in a cost-effective manner, without negative public health impact. MMT is limited by inadequate funding and understanding of relevant research, extensive regulation, and limits on the freedom of physicians to provide methadone in a variety of medical settings. Broad-based medical, public health, and scientific support exists for expansion of MMT with greater emphasis on consistency and quality, and provision of ancillary services. Programs for the exchange, free distribution, and legal pharmacy sale of needles and syringes reduce injection drug use and prevent the spread of bloodborne pathogens; drug abuse treatment and other services are important components. Neither strategy increases existing drug use nor leads to drug use initiation. The scientific literature supports assertions that drug abuse issues should be treated primarily as medical and public health rather than criminal justice issues. The effectiveness of both strategies warrants increased support for services, easing of federal and state restrictions governing their availability, and advocacy in their support.

Community Mental Health Services↗
PubMed2001

Technical note: Artificial vagina vs a vaginal collection vial for collecting semen from rams.

The time required to train rams to an artificial vagina (AV) makes collecting semen from large numbers of rams difficult. To manage this problem, we developed a glass, round-bottomed, 1.9-cm i.d. x 9.8-cm long vaginal collection vial (VCV). Three experiments were conducted to determine whether the VCV affected 1) semen volume per collection, 2) percentage of motile spermatozoa, 3) forward progressive motility score before and after extension and after freezing and thawing, and 4) our ability to collect semen from untrained rams. A soft rubber cap with a hole in the center was used to cover the VCV. A VCV was inserted into the vagina of an estrual ewe, and a monofilament line attached to the VCV was clipped to the wool near the vulva. Rams were joined with unrestrained ewes in a pen until they ejaculated into the VCV. In Exp. 1, five rams trained to an AV were used in a switchback design with four collection periods. During each period (1 d), semen was collected with an AV and a VCV. Immediately after collection, semen volume and sperm motility were quantified. Semen was extended with an aloe vera gel-based diluent at a 1:4 dilution rate, motility was quantified again, and semen was frozen. At 1 h after freezing, semen was thawed and sperm motility was quantified. Ejaculate volume (mean = 0.7 mL) and all measures of motility after collection were similar (P > 0.05) for the two collection methods. In Exp. 2, 10 rams trained to an AV were used in a switchback design with five collection periods (period = 3 d). On d 1 and 3 of each period, an AV and a VCV were used to collect semen. Collection method did not affect (P > 0.05) ejaculate volume (mean = 1.0 mL), percentage of motile cells, or forward progressive motility score. In Exp. 3, 51 untrained rams were used in a switchback design with a single collection period (2 d). Semen was collected with an AV and a VCV. Ability to collect an ejaculate and time required for collection were recorded. The likelihood of collecting semen from untrained rams was greater (P < 0.01) using a VCV (mean = 31.4%) than using an AV (mean = 9.8%). Collection method did not affect (P > 0.05) ejaculate volume (mean = 0.8 mL), percentage of motile cells, or forward progressive motility score. We concluded that a VCV could be used to collect semen from rams that are not trained for semen collection without decreasing ejaculate volume or sperm motility.

Animals↗
PubMed2001

Ventriculopleural shunt obstruction and positive-pressure ventilation. Case report.

The authors report an unusual case of a patient with low-pressure hydrocephalus and a ventriculopleural shunt, in whom routine respiratory management performed using positive-pressure ventilation caused shunt obstruction and coma. While the patient received positive-pressure ventilation with external cerebrospinal fluid (CSF) drainage at subatmospheric pressure, the ventricles returned to normal size and the coma rapidly reversed. After the authors' recognition of the effect of positive-pressure ventilation on intrapleural pressure and ventriculopleural shunt function, and the subsequent removal of positive-pressure ventilation, CSF flow through the shunt resumed and the patient's coma resolved.

Cerebrospinal Fluid Shunts↗
PubMed2001

Prenatal care utilization and foetal outcomes at Harare Maternity Hospital, Zimbabwe.

OBJECTIVES: To examine the association between adverse infant outcomes and maternal under utilization of prenatal care, among women delivering at Harare Maternity Hospital. DESIGN: Hospital based, cross sectional study. SETTING: Harare Maternity Hospital, Harare, Zimbabwe. SUBJECTS: A random sample of 3,864 pregnant women. MAIN OUTCOME MEASURES: Prenatal care utilization, maternal socio-demographic information, as well as birth weight and other neonatal outcome characteristics. RESULTS: Of the total number of women who participated in this study 3,491 (90%) had at least one prenatal care visit. Women receiving no prenatal care, were more likely to be younger, unmarried and to have been transferred for delivery as compared with women receiving prenatal care. Women receiving no prenatal care were seven times more likely to deliver an infant weighing less than 1,500 grams, adjusted odd ratio (OR) = 7.22; 95% confidence interval (CI) 4.58 to 11.39 as compared with those who booked for care. Newborns of unbooked mothers were more likely to have a low apgar score at birth, adjusted OR = 1.71; to have been admitted to the neonatal intensive care unit, adjusted OR = 2.14, and to require intubation, adjusted OR = 3.35. A large proportion of women (31.4%) initiated prenatal care after 30 weeks gestation. CONCLUSIONS: There were significant differences between maternal characteristics and foetal outcomes in relation to booking status. Under utilization of prenatal care was associated with sub-optimal foetal outcomes. Improving the socio-economic status of women, their education and access to health care, and family planning methods are all strategies that should contribute to the reduction of adverse foetal outcomes.

Female↗
PubMed2000

Genetic characterization of strain differences in the ability to mediate CD40/CD28-independent rejection of skin allografts.

Simultaneous blockade of the CD40 and CD28 T cell costimulatory pathways effectively promotes skin allograft survival in C3H/HeJ mice, extending median survival times (MSTs) beyond 100 days. This strategy is markedly less effective in C57BL/6 mice, with MSTs ranging between 20 and 30 days. In this study, we investigate the underlying genetic causes of these distinct phenotypes. Using H-2 congenic mice, we show that the genetic basis for the varied responses between these two strains is independent of the H-2 locus and T cell precursor frequency. C57BL/6 mice treated with costimulation blockade are able to generate allospecific CTL- and IFN-gamma-producing T cells within 3-4 wk posttransplant, whereas mice with a C3H background generate neither CTL- nor IFN-gamma-producing cells. Thus, differences appear to be in the generation of the immune response and not T cell homing. Strain differences in costimulation blockade-induced hyporesponsiveness persist in the absence of CD4(+) T cells, implying a direct effect on CD8(+) T cells. We demonstrate that genetic differences are important in cells of hemopoietic origin and that the costimulation blockade-resistant phenotype is dominant. Analysis of BXH recombinant inbred strains indicates that multiple loci contribute to the phenotype, and that the blockade resistance loci are preliminarily linked to 17 markers on four chromosomes. We conclude that strain variation in allograft MSTs following CD40/CD28 blockade results from the ability of CD8(+) T cells in some strains to use alternative modes of costimulation to mount an effective alloresponse.

Abatacept↗
PubMed2000

Addition of non-genomically encoded nucleotides to the 3'-terminus of maize mitochondrial mRNAs: truncated rps12 mRNAs frequently terminate with CCA.

The 3'-termini of maize mitochondrial RNAs were characterized by ligation of an anchor oligonucleotide, reverse transcription and amplification. DNA sequence analysis of cDNA clones for tRNA(Ser) and 18S rRNA confirmed the expected 3'-terminal nucleotides and demonstrated the accuracy and fidelity of the protocol. Analysis of cDNAs for rps12, cox2 and atp9 indicated that non-genomically encoded nucleotides were present at the 3'-terminus. rps12 cDNAs exhibited the highest degree of modification, with 94% of 35 cDNA clones analyzed containing one to four non-genomically encoded C or A residues; 83% of these cDNAs terminated with the trinucleotide CCA. DNA sequence and transcript mapping analyses demonstrated that four positions exhibited modified 3'-termini within a small region of the 3' flank of rps12 transcripts. These transcript termini represented low abundance, truncated forms of rps12 mRNAs which may be intermediates in degradation. cox2 mRNAs are also modified at a truncated position. Sixty percent of the cox2 cDNAs were modified with 1-5 nt that most frequently included A and C residues, but also included a few G and T residues. Non-genomically encoded nucleotides were detected in 27% of the atp9 cDNAs as a single C or A residue.

3' Untranslated Regions↗
PubMed2000

Detection of Kaposi's sarcoma-associated herpesvirus in oral and genital secretions of Zimbabwean women.

Kaposi's sarcoma-associated herpesvirus (KSHV) in oral and genital secretions of women may be involved in horizontal and vertical transmission in endemic regions. Nested polymerase chain reaction assays were used to detect KSHV DNA sequences in one-third of oral, vaginal, and cervical specimens and in 42% of peripheral blood mononuclear cell (PBMC) specimens collected from 41 women infected with human immunodeficiency virus type 1 who had Kaposi's sarcoma (KS). KSHV DNA was not detected in specimens from 100 women without KS, 9 of whom were seropositive for KSHV. A positive association was observed between KSHV DNA detection in oral and genital mucosa, neither of which was associated with KSHV DNA detection in PBMC. These data suggest that KSHV replicates in preferred anatomic sites at levels independent of PBMC viremia. Detection of genital-tract KSHV only among relatively immunosuppressed women may provide an explanation for infrequent perinatal transmission of KSHV.

AIDS-Related Opportunistic Infections↗
PubMed2000

Methylenetetrahydrofolate reductase 677 C --> T polymorphism, plasma folate, vitamin B(12) concentrations, and risk of preeclampsia among black African women from Zimbabwe.

We conducted a case control study at Harare Maternity Hospital, Zimbabwe. We genotyped a total of 171 cases with preeclampsia or eclampsia and 185 normotensive control subjects for the methylenetetrahydrofolate reductase (MTHFR) 677 C --> T genotype. The wild-type allele frequency among cases and controls was 91.2 and 91.3%, respectively. Only one subject (0.3%) was homozygous for the 677 C --> T MTHFR genotype and this subject had preeclampsia. After adjustment for confounding factors, there was statistically no significant association between maternal MTHFR genotype and risk of preeclampsia (adjusted odds ratio = 1.0; 95% CI, 0.5-1.9). In addition, plasma homocyst(e)ine, vitamin B(12), and folate concentrations were not statistically different between normotensive control subjects with wild-type genotype as compared with normotensive subjects who were heterozygous for the mutant allele. Conversely, there was a strong graded association between maternal plasma folate concentration and risk of preeclampsia. Women with plasma folate concentrations less than 5.7 nmol/L experienced a 10. 4-fold increase in risk of preeclampsia. There was no clear pattern of preeclampsia risk and vitamin B(12) concentrations.

Adolescent↗
PubMed2000

Respiratory distress syndrome and maternal birth weight effects.

OBJECTIVE: To study traditional risk factors and the intergenerational risk factor maternal low birth weight (LBW) for respiratory distress syndrome (RDS) in infants in multiple ethnic groups. METHODS: The population-based database consists of hospital records linked to Washington state maternal and infant vital records. Four racial-ethnic groups were studied, whites, blacks, Native Americans, and Hispanics. Poisson regression models were used to estimate relative risks of various factors for RDS. RESULTS: Rates for RDS were whites 1.2%, blacks 1.9%, Native Americans 1.3%, and Hispanics 1.0%. Maternal LBW was associated with increased relative risk (RR) for RDS in whites (2.6, 95% confidence interval [CI] 1.6, 4.2) and blacks (3.3, 95% CI 1.9, 5.6) for infants born vaginally. Compared with mothers of normal infants, birth weights of mothers of infants with RDS and delivered vaginally were significantly lower in whites, blacks, and Native Americans. The association of maternal LBW with RDS persisted in blacks even when multiple risk factors were added to the model (RR 2.4; 95% CI 1.1, 5.1). CONCLUSION: The association of maternal LBW with RDS is probably due in part to the association of maternal LBW with infant LBW and preterm birth. The strong persistent association of maternal LBW with RDS in blacks suggests that improvement of perinatal outcomes in that group will require improvement of long-term birth weight distribution.

Adult↗
PubMed2000

Cytokine modulated cell-membrane bound tumour necrosis factor expression is associated with enhanced monocyte-mediated killing of human leukaemic targets.

Cytokines such as interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) activate monocytes both in vitro and in vivo. We therefore studied whether the anti-leukaemic activity of monocytes could be augmented by IL-3 alone or in combination with GM-CSF. Using normal human monocytes stimulated with IL-3, GM-CSF, LPS or combinations of growth factor and LPS, we studied their cytotoxic activity against leukaemic cell-lines and primary AML blasts. IL-3 like GM-CSF, augmented the expression and secretion of TNF but did not prime for further expression and secretion of TNF in response to LPS. Neither GM-CSF or IL-3 increased the expression or secretion of TNF receptor p55 (TNF-Rp55), although both agents increased expression of TNF receptor p75 (TNF-Rp75). Monocyte-mediated cytotoxicity (MMC) against K562 and U937 cell-lines was increased by both GM-CSF and IL-3 stimulation, and both cytokines primed monocytes for increased killing of K562 and KG-1 cell-lines as well as primary AML blasts in response to LPS. The mechanism of action of MMC was largely confirmed to be via surface-bound TNF, although other TNF-independent mechanisms must have been involved.

Cytotoxicity, Immunologic↗
PubMed2000

Tumor necrosis factor-alpha soluble receptor p55 (sTNFp55) and risk of preeclampsia in Peruvian women.

We conducted a large case-control study to assess the risk of preeclampsia with elevated sTNFp55 concentrations (markers of excessive TNF-alpha release) in Peruvian women. A total of 125 women with preeclampsia and 179 normotensive women were included in a study conducted during the period, June 1997 through January 1998. Antepartum (third-trimester) plasma sTNFp55 was measured by enzyme linked immunosorbent assay. Mean plasma sTNFp55 concentrations were 32.4% higher among preeclampsia cases (920.1+/-30.4 pg/ml) as compared with controls (694.8+/-15.0 pg/ml, Student's t-test P<0.001). There was a strong linear increase in risk of preeclampsia with increasing concentrations of sTNFp55 (linear trend P-value <0. 001). After adjusting for confounding factors, women in the highest quartile experienced a 10-fold increased risk of preeclampsia as compared with women in the lowest quartile (adjusted odds ratio, 10.3; 95% confidence interval, 4.1-25.9). Compared with women in the highest quartile, women in the second and third quartiles experienced a 3-fold or greater increased risk of preeclampsia (adjusted odds ratios were 3.1 and 3.8, respectively). Excessive TNF-alpha release (as measured by the detection of the soluble receptor sTNFp55 in maternal plasma collected before delivery) is increased in pregnancies complicated by preeclampsia as compared with normotensive pregnancies. These findings are consistent with most previous studies.

Adolescent↗
PubMed2000

Activities of daily living among heart transplant candidates: neuropsychological and cardiac function predictors.

BACKGROUND: The ability of patients to perform day-to-day tasks (e.g., medication management, dietary regulation) is an important concern of transplant teams. METHODS: We studied a clinical series of 75 heart transplant candidates and 38 controls to examine the predictive validity of demographic, neuropsychologic, and cardiac function variables to a performance-based measure of instrumental activities of daily living (IADL) capacity (i.e., Everyday Problems Test, EPT). RESULTS: Multiple regression analyses, controlling for education and race, indicated that neuropsychologic tests accounted for between 34% and 67% of the variance across IADL domains (e.g., cooking, household chores, medication management). The IADL capacity was most consistently predicted by long-standing verbal ability (Shipley Institute of Living Scale-Vocabulary, SILS-VOC) and psychomotor speed and mental flexibility (Trail Making Test-Part B, TMT-B). Similarly, SILS-VOC and TMT-B also tended to show the best operating characteristics (i.e., sensitivity, specificity, positive predictive power, negative predictive power) for detection of dependence across IADL domains. In contrast, cardiac function measures (e.g., cardiac output, mean atrial pressure) were largely unrelated to the patient's performance on the paper-and-pencil EPT task. CONCLUSIONS: Long-standing intellectual ability, and a measure of speeded information processing and mental flexibility are the best predictors of IADL capacity.

Activities of Daily Living↗
PubMed2000

A molecular description of the gelation mechanism of konjac mannan.

A molecular level description of the time course of the gelation of the polysaccharide konjac mannan (KM) is presented and the role of alkali addition is considered in detail. NMR relaxometry is utilized as a complementary methodology to mechanical spectroscopy in order to probe events occurring as a prelude to network formation, and high-resolution NMR is used to follow the deactetylation process. It is shown that the addition of alkali plays an important solubilizing role in addition to facilitating the deacetylation of the chain. Deacetylation is important both in reducing the inherent aqueous solubility of the polymer and in progressively negating the alkali-induced polyelectrolytic nature of the polysaccharide chain via reaction induced pH changes. It is proposed that observed induction periods following alkali addition (during which the elastic modulus does not rise) are not simply deacetylation delays but are related to the aggregation kinetics of the deacetylated material.

Algorithms↗
PubMed2000

Monocyte-macrophage system as targets for immunomodulation by intravenous immunoglobulin.

Pooled human intravenous immunoglobulin (IVIg) has been used successfully to treat or ameliorate the clinical manifestations of humoral immune deficiencies, haematological disorders, HIV infection and many other diseases states. However, the mechanism of action of IVIg remains unclear. Several mechanisms of action of IVIg have been proposed. These include Fcy receptor blockade, accelerated clearance of endogenous pathogenic auto-antibodies, inhibition of components of the complement cascade, neutralization of super-antigens and bacterial toxins as well as anti-cytokine and anti-idiotype effects. A major contributor to host immunity and immune surveillance against infection, tissue or cell damage and malignancy is the monocyte/macrophage system. Monocyte-directed inflammation is a desirable consequence of microbiological or malignant challenge. However, monocyte hyperactivity may contribute to certain pathological conditions. These include the systemic inflammatory response syndrome (SIRS), septic shock, other dysregulated inflammatory disorders and auto-immunity. Novel therapies that can suppress the hyperactive state or correct monocyte/macrophage dysfunction without compromising normal host cell-mediated immunity are desirable. In this review, we discuss the immunomodulatory effects of IVIg focussing particularly upon the monocyte/macrophage system in pertinent disease states.

Adjuvants, Immunologic↗
PubMed2000

Maternal birth weight and cesarean delivery in four race-ethnic groups.

OBJECTIVE: We hypothesized that maternal birth weight was associated with the risk of cesarean delivery for nulliparous women. STUDY DESIGN: In a population-based cohort study, maternal birth data were linked to a Washington State database, including the birth certificates of 18,905 first-born singleton infants (1987-1995). RESULTS: Among non-Hispanic white subjects, maternal birth weight of 2500 to 3999 g was associated with a 20.9% risk of cesarean delivery, which was the lowest risk, compared with 24.5% for a maternal birth weight <2500 g (P <.05) and 24.0% for a maternal birth weight > or =4000 g (P <.05). Similar patterns of risk were noted among Hispanic and Native American subjects, although the associations did not reach statistical significance. Risk of cesarean delivery was not associated with maternal birth weight among African American subjects. Among non-Hispanic white subjects, the risk of cesarean delivery was 3.23 times greater with a maternal birth weight <2500 g and an infant birth weight > or =4000 g compared with pregnancies with both maternal and infant birth weights between 2500 and 3999 g (P <. 001). Adjustment for socioeconomic factors did not alter these results. CONCLUSION: Low and high maternal birth weights exert an intergenerational risk of cesarean delivery in nulliparous non-Hispanic white women.

Adult↗