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M L Williams

Publications and source records attributed to M L Williams.

At least 73 records · Page 4Linked to original sources
PubMed1998

A cluster analysis of not-in-treatment drug users at risk for HIV infection.

The purpose of the analysis described here was to classify not-in-treatment drug users participating in the National Institute on Drug Abuse (NIDA)-sponsored Cooperative Agreement study into several "homogeneous" HIV risk groups using cluster analysis. Data for this analysis (N=17,778) were collected at 19 study sites in the United States and Puerto Rico. Measures selected for the cluster analysis were limited to (a) current drug use and HIV risk behaviors, (b) mutually exclusive behaviors, (c) behaviors directly related to HIV risk, and (d) behaviors that were not statistically rare. Eight homogeneous HIV risk clusters were produced. Crack cocaine use was the most distinguishing feature of three clusters. Another three clusters were distinguishable by drug injection and needle use practices. Two additional clusters could not be grouped with either the crack- or the injection-dominant clusters. Prostitution was the most distinguishing risk behavior of one of these clusters, and extremely high drug injection frequencies and relative rates of risky needle use characterized the other. Composition of the clusters varied significantly by gender, race/ethnicity, educational attainment, and drug use characteristics. In addition, perceptions and behaviors initiated to reduce the chances of becoming infected with HIV varied by cluster. Subjects in the crack-predominant clusters reported low perceptions of the chances of getting AIDS. Perceptions of the chances of becoming infected with HIV among subjects in the injection-predominant clusters were strongly related to injection frequency. Seroprevalence was also related to cluster. Higher rates of HIV infection were evident among the injection-predominant clusters, and higher rates were related to frequency of injection and the rate of risky needle use. Among the crack-predominant clusters, the relationship between drug use and sexual behaviors and HIV infection was less clear.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Educate ICU assistive personnel.

Many institutions use assistive personnel in intensive care units (ICUs) to provide more cost-effective nursing care. One ICU uses a comprehensive, competency-based orientation program to help fulfill the assistive personnel's unique orientation needs.

Competency-Based Education↗
PubMed1997

Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the development of the fetal epidermal permeability barrier.

Members of the superfamily of nuclear hormone receptors which are obligate heterodimeric partners of the retinoid X receptor may be important in epidermal development. Here, we examined the effects of activators of the receptors for vitamin D3 and retinoids, and of the peroxisome proliferator activated receptors (PPARs) and the farnesoid X-activated receptor (FXR), on the development of the fetal epidermal barrier in vitro. Skin explants from gestational day 17 rats (term is 22 d) are unstratified and lack a stratum corneum (SC). After incubation in hormone-free media for 3-4 d, a multilayered SC replete with mature lamellar membranes in the interstices and a functionally competent barrier appear. 9-cis or all-trans retinoic acid, 1,25 dihydroxyvitamin D3, or the PPARgamma ligands prostaglandin J2 or troglitazone did not affect the development of barrier function or epidermal morphology. In contrast, activators of the PPARalpha, oleic acid, linoleic acid, and clofibrate, accelerated epidermal development, resulting in mature lamellar membranes, a multilayered SC, and a competent barrier after 2 d of incubation. The FXR activators, all-trans farnesol and juvenile hormone III, also accelerated epidermal barrier development. Activities of beta-glucocerebrosidase and steroid sulfatase, enzymes previously linked to barrier maturation, also increased after treatment with PPARalpha and FXR activators. In contrast, isoprenoids, such as nerolidol, cis-farnesol, or geranylgeraniol, or metabolites in the cholesterol pathway, such as mevalonate, squalene, or 25-hydroxycholesterol, did not alter barrier development. Finally, additive effects were observed in explants incubated with clofibrate and farnesol together in suboptimal concentrations which alone did not affect barrier development. These data indicate a putative physiologic role for PPARalpha and FXR in epidermal barrier development.

Animals↗
PubMed1997

A Queensland family with ciguatera after eating coral trout.

Ciguatera (poisoning caused by eating fish contaminated with algal toxins) is usually diagnosed clinically. We describe a Queensland family of four (including a pregnant woman) with ciguatera, confirmed by bioassay of the implicated fish for ciguatoxin. All four recovered, illustrating the effectiveness of treatment with intravenous mannitol. At birth, the infant appeared to suffer no adverse effects attributable to ciguatera; to our knowledge, this is the first report of the effect of severe ciguatera in the first trimester of pregnancy.

Adult↗
PubMed1997

Unanticipated lessening of the rise in extracellular potassium during ischemia by pinacidil.

BACKGROUND: The efflux of potassium (K) through the ATP-sensitive K channel is considered an important cause of the rise in extracellular K ([K+]e) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K+]e. METHODS AND RESULTS: We studied the effects of 10 and 25 mumol/L pinacidil, and ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K+]e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 mumol/L unexpectedly lessened the rise in [K+]e and the activation delay in both preparations. Pinacidil 10 mumol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K+]e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage. CONCLUSIONS: Our results indicate that the rise in [K+]e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K+]e by pinacidil reflects the balance of its effects on these several parameters.

Adenosine Triphosphate↗
PubMed1997

Atypical squamous cells of undetermined significance: correlative histologic and follow-up studies from an academic medical center.

The diagnosis of ASCUS (atypical squamous cells of undetermined significance) was introduced in the 1988 Bethesda System for reporting cervical/vaginal cytologic findings. Outcome and appropriate management of patients with this diagnosis is not presently established. Criteria defining ASCUS are nuclear enlargement (2.5-3.0 times normal intermediate cell nucleus), mild nuclear hyperchromasia, smooth nuclear outlines with mild variation in nuclear size and shape, or else two, but not all three, cytologic criteria for human papilloma virus (HPV) cytopathic effect. All 668 cases reported as ASCUS from February 1992-December 1993 from our cytology laboratory were reviewed. These ASCUS cases represented 4.5% of all gynecologic cases diagnosed in that same time period. Of these, 284 (41%) had a subsequent colposcopic biopsy and/or endocervical curettage. The biopsied cases included 101 (36%) with condylomata, 38 (13%) with cervical intraepithelial neoplasia (CIN) I, 17 (6%) with CIN II, and 9 (3%) with CIN III. No cases of carcinoma were detected. Of patients with a cytologic diagnosis of ASCUS and subsequent cervical biopsy, 49% had low-grade cervical intraepithelial neoplasia (LGSIL), either condyloma or CIN I. Nine percent had high-grade cervical intraepithelial neoplasia, either CIN II or CIN III. These findings indicate that ASCUS defines cytologically a group of patients who may have either a concurrent or subsequent development of a squamous intraepithelial lesion (SIL). This forms a high-risk group. The management of cases with a cytologic diagnosis of ASCUS should be at least as aggressive as that of LGSIL.

Adolescent↗
PubMed1997

Powerlessness and HIV prevention among people who trade sex for drugs ('strawberries').

Researchers and members of the drug culture have employed the term 'strawberries' to describe African American women who trade sex for drugs. Data from six US cities participating in a community-based drug research project were analysed to examine the determinants of trading sex for drugs. As shown by our data, some African American women match the street description commonly attributed to 'strawberries'. However, our results also show that trading sexual favours for drugs is not limited to African American women, nor solely to women. Rather, trading sex for drugs is an economic behaviour that occurs among women and men of any race/ethnicity who use crack cocaine. Trading sex for drugs is closely related to conditions of poverty and homelessness, conditions that especially affect many crack smokers. The discussion urges educators and researchers to be alert for 'strawberry behaviours' exhibited by drug-users of any racial/ethnic background or gender.

Adult↗
PubMed1997

Epidermal steroid sulfatase and cholesterol sulfotransferase are regulated during late gestation in the fetal rat.

Lipids in the stratum corneum (SC) are organized into lamellar membrane unit structures that provide the permeability barrier. Cholesterol sulfate, a SC membrane lipid, is synthesized by cholesterol sulfotransferase (CSTase) in the lower epidermis and hydrolyzed to cholesterol by steroid sulfatase (SSase) in the SC. To determine whether these enzymes are induced during barrier ontogenesis, we examined their activity in epidermis of fetal rats before (gestational day 17), during (day 19), and after (day 21) barrier formation. CSTase activity increased approximately 10-fold between day 17 and day 19, then declined between day 19 and day 21. In contrast, SSase activity reached its peak activity on day 21, increasing >5-fold. Fetal rat skin explants develop a SC and barrier over the same time course in vitro as in utero. Likewise, CSTase and SSase activities during in vitro ontogenesis precisely mirrored those obtained in utero. Moreover, hormones that accelerate barrier ontogenesis (e.g. glucocorticoids, thyroid hormone, and estrogen) accelerated the increase in CSTase and SSase activities during in vitro ontogenesis. mRNA levels of SSase increased in parallel with enzymatic activity, suggesting that these developmental changes are regulated at the genomic level. Finally, addition of exogenous cholesterol sulfate to explants in vitro did not accelerate either SC development or barrier formation. These studies suggest that induction of the cholesterol sulfate cycle enzymes during SC ontogenesis is a component of the fetal epidermal differentiation program and that the synthetic and degradative enzymes of this pathway are differentially regulated.

Aging↗
PubMed1997

Acceleration of barrier ontogenesis in vitro through air exposure.

Immaturity of the epidermal barrier in the preterm infant may have serious clinical consequences. However, regardless of the degree of prematurity, the barrier rapidly matures such that by 2 wk all infants display a competent barrier. To determine whether the change from an aqueous (intrauterine) to a xeric environment might be the stimulus for this accelerated maturation, we examined the effects of air exposure on cutaneous barrier formation in vitro. Skin explants from d 17 fetal rats were incubated either submerged or at the air-medium interface. As previously reported, a competent barrier formed under submerged conditions after 3-4 d, precisely mirroring the time course of maturation in utero. In contrast, barrier maturation was accelerated in air-exposed explants, with functional, histologic, and structural markers of barrier formation observed after only 2 d of incubation. A water-impermeable membrane blocked the acceleration of barrier formation, resulting in a developmental time course comparable to that for submerged explants. In contrast a water vapor-permeable membrane did not block the acceleration. Glucocorticoids and thyroid hormone, which accelerate barrier formation in utero or in vitro under submerged conditions, did not further accelerate barrier formation in the air-exposed model. These data indicate that: 1) air exposure accelerates barrier ontogenesis, suggesting that water flux may be an important signal for the accelerated barrier formation that occurs in premature infants; and 2) factors which accelerate barrier formation in utero may not further accelerate barrier formation in neonates.

Air↗
PubMed1997

Hypothyroidism delays fetal stratum corneum development in mice.

The epidermal permeability barrier, required for terrestrial life, is localized to lipid-enriched lamellar membranes in the extracellular spaces of the stratum corneum (SC). Immaturity of the SC is a significant contributor to morbidity and mortality in premature infants. Previous studies have shown that supraphysiologic concentrations of thyroid hormone accelerate epidermis/SC ontogenesis. Here we studied SC development in Hyt/Hyt mice who are genetically hypothyroid due to a mutation in the TSH receptor. In control mice on d 18 of gestation (term 19.5 d), only focal areas displayed a mature SC membrane pattern. By 19 d of gestation there was a mature multilayered SC with lamellar unit structures filling the extracellular spaces similar to that seen in mature mice. In Hyt/Hyt mice SC development was delayed at both 18 and 19 d of gestation. In both strains of mice, within the first day after birth there were no differences in epidermal or SC appearance, and the SC was fully mature. These findings indicate that thyroid hormone plays a physiologic role during normal intrauterine development of the SC. However, normal SC maturation ultimately occurs, indicating that thyroid hormone is not absolutely essential. Previous studies have shown that glucocorticoids accelerate SC development in euthyroid rats, and in the present study we demonstrate that glucocorticoids also accelerate SC ontogenesis in euthyroid mice. In contrast, in Hyt/Hyt mice glucocorticoids did not accelerate or normalize SC development, indicating that the glucocorticoid effect on SC maturation requires a euthyroid state or that glucocorticoids act via thyroid hormone. These studies demonstrate that thyroid hormone status is an important regulator of fetal SC development.

Animals↗
PubMed1997

Introduction of HIV into drug injector networks outside AIDS epicentres.

Injection drug users (IDUs) continue to be at risk for HIV infection despite high levels of knowledge about how human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is transmitted. Yet, among not-in-treatment injection drug users, the chances of becoming infected with HIV vary substantially. Information regarding the factors that facilitate the introduction of HIV into networks of drug injectors in low HIV seroprevalence cities is urgently needed. This study examines the factors related to HIV seroprevalence in a large (n=9492), multi-site sample of IDUs recruited in 11 low seroprevalence cities. Univariate and multivariate associations between drug injection and sexual behaviours and travel to an AIDS epicentre were examined. Results show that, next to male-to-male sexual contact, having sex at least twice in an AIDS epicentre was the strongest predictor of HIV infection. Also associated with higher odds of being HIV-positive were racial/ethnic characteristics, daily drug injection, and injecting drugs in an AIDS epicentre. These results confirm that travelling to an AIDS epicentre and having sex or injecting drugs play a large role in the introduction of HIV into drug injector networks in low seroprevalence cities.

Adult↗
PubMed1997

Glucosylceramide metabolism is regulated during normal and hormonally stimulated epidermal barrier development in the rat.

Glucosylceramides, delivered to the stratum corneum interstices by exocytosis of lamellar body contents, are enzymatically hydrolyzed to ceramides, which are major components of the lipid lamellar bilayers that mediate epidermal barrier function. Because this conversion is critical for permeability barrier homeostasis in the adult animal, in this study we measured the changes in activities of the enzymes responsible for the synthesis of glucosylceramide and its conversion to ceramide, UDP-glucose:ceramide glucosyltransferase (GC synthase) and beta-glucocerebrosidase (beta-GlcCer'ase), respectively, during fetal barrier formation. In epidermis from rats of gestational age 17-21 days, GC synthase activity peaked on day 19, prior to barrier competence, whereas beta-GlcCer'ase activity rose throughout barrier formation, exhibiting a 5-fold increase over this time period. beta-GlcCer'ase protein rose in parallel with activity, as did mRNA levels. Enzyme activities in skin explants from 17-day fetal rats, incubated up to 4 days in hormone- and serum-free media, paralleled those measured at corresponding time points in utero. Incubation with hormones that accelerate barrier development had minimal effects on GC synthase activity, whereas beta-GlcCer'ase activity was significantly increased after 1 or 2 days in culture. Finally, inhibition of beta-GlcCer'ase with conduritol B epoxide prevented barrier development in vitro and was accompanied by abnormalities in the lamellar bilayer ultrastructure of the stratum corneum. These data indicate that both synthesis and hydrolysis of glucosylceramide are regulated during fetal development. Furthermore, the enzymatic hydrolysis of glucosylceramide to ceramide is essential for fetal barrier ontogenesis.

Animals↗
PubMed1997

Workplace violence. Prevalence, prevention, and first-line interventions.

Workplace violence is increasing, but through education, prevention, and man aging escalating crises, critical care nurses can help to minimize the negative consequences of violence. Critical care nurses are particularly prone to acts of aggression and acts of violence due to the stressful environment for them, their families, and their patients. Developing violence prevention skills and interpersonal communication skills, not always highly valued in a critical care environment, are important steps in deterring workplace violence. Although not all incidents of workplace violence can be prevented, recognizing the individual at risk for violence and intervening on the behalf of all involved is a responsibility of every employee including the critical care nurse.

Adult↗
PubMed1996

Transglutaminase 1 delivery to lamellar ichthyosis keratinocytes.

Therapeutic gene delivery in severe genetic skin disease may require production of a uniformly corrected population of cells capable of regeneration of normal skin elements when returned to the host. To achieve this, we have used lamellar ichthyosis (LI), a disorder of epidermal differentiation recently associated with defects in keratinocyte transglutaminase (TGase1), as a prototype. We have used a high-efficiency retroviral delivery approach to uniformly restore normal levels of TGase1 expression to primary keratinocytes from severely affected LI patients previously lacking TGase1. Delivered TGase1 was correctly targeted to membrane association and restored patient cell transglutaminase activity levels to normal. Corrected primary LI patient keratinocytes also demonstrated restoration of previously defective involucrin cross-linking and in vitro measures of cornification to levels found in normal cells. These results indicate that efficient TGase1 delivery to early passage keratinocytes can produce a population of corrected LI patient cells. The capability to produce such cells may provide a basis for future efforts at gene therapy for genetic skin disease.

Cells, Cultured↗
PubMed1996

Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat. Acceleration by estrogen and delay by testosterone.

Previous studies have shown that ontogeny of the epidermal permeability barrier and lung occur in parallel in the fetal rat, and that pharmacologic agents, such as glucocorticoids and thyroid hormone, accelerate maturation at comparable developmental time points. Gender also influences lung maturation, i.e., males exhibit delayed development. Sex steroid hormones exert opposite effects on lung maturation, with estrogens accelerating and androgens inhibiting. In this study, we demonstrate that cutaneous barrier formation, measured as transepidermal water loss, is delayed in male fetal rats. Administration of estrogen to pregnant mothers accelerates fetal barrier development both morphologically and functionally. Competent barriers also form sooner in skin explants incubated in estrogen-supplemented media in vitro. In contrast, administration of dihydrotestosterone delays barrier formation both in vivo and in vitro. Finally, treatment of pregnant rats with the androgen antagonist flutamide eliminates the gender difference in barrier formation. These studies indicate that (a) estrogen accelerates and testosterone delays cutaneous barrier formation, (b) these hormones exert their effects directly on the skin, and (c) sex differences in rates of barrier development in vivo may be mediated by testosterone.

Animals↗
PubMed1996

An assessment of the risks of syphilis and HIV infection among a sample of not-in-treatment drug users in Houston, Texas.

The research presented in this paper details the results of an assessment of the risk factors associated with having a positive syphilis or HIV serology. The study was conducted using a sample of not-in-treatment drug users volunteering to participate in an HIV risk reduction intervention. The sample was composed of individuals who had injected drugs within 30 days or smoked crack cocaine 48 hours prior to participation in the study. Study participants were approximately 75% male and 66% African-American. All participants provided a blood sample to be tested for HIV and syphilis. Analysis of risk was conducted using univariate and multivariate statistical methods. Multivariate analysis of blood results showed that women, African-Americans, and those having a positive blood test for HIV were at higher odds of having a positive syphilis test. Analysis also showed that being a gay or bisexual male, having a history of drug injection, having less than a high-school education, having a history of trading sex for money, being African-American, and having a positive blood test for syphilis significantly increased the odds of a positive HIV test. Implications for HIV and STD prevention are discussed.

Adult↗