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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 109 records · Page 6Linked to original sources

Cryptosporidium meleagridis from humans: molecular analysis and description of affected patients.

OBJECTIVES: To genetically characterize an unusual genotype of Cryptosporidium from the stools of humans with diarrhoea and to identify risk factors in the affected patients. METHODS: DNA was extracted from human faeces where Cryptosporidium oocysts were detected by light microscopy. Cryptosporidial gene fragments from six different loci were analysed by PCR alone, PCR/RFLP and by DNA sequencing. Oocysts were characterized by light and immunofluorescence microscopy and epidemiological data was collected from the affected patients. RESULTS: Analysis of the Cryptosporidium oocyst wall protein (COWP) gene amplified from > 2000 human faecal samples identified 19 patients all of which produced an unusual RFLP profile. Subsequent DNA sequence analysis of this and an additional four genetic loci (including 18S rRNA sequences) confirmed these as a homogeneous group which was genetically distinct from Cryptosporidium parvum. The isolates were identified as Cryptosporidium meleagridis since the gene sequences were identical to those from this species recovered from birds. Conventional microscopy showed oocysts indistinguishable from C. parvum and reacted strongly with two different commercially available anti-oocyst monoclonal antibodies. None of the patients showed risk factors unusual for cryptosporidiosis; however, ten of the cases occurred during the summer/autumn, six had a history of foreign travel, four were co-infected with Giardia, two were HIV positive, and six were without identifiable immunocompromising factors. CONCLUSIONS: This study further confirms that C. meleagridis, in addition to C. parvum, is involved in human disease. The study also highlights the lack of basic information on the host range of this genus of parasites, the complexity of the transmission routes involved in human cryptosporidiosis, and the value of molecular techniques in identify hitherto unrecognised differences in Cryptosporidium from human faeces.

Adolescent↗

An investigation of psychological distress in patients who have been treated for head and neck cancer.

There is now ample evidence that psychological distress is common in patients with head and neck cancer and that psychology has a role in reducing this distress. In this study, the prevalence, nature, and correlates of distress were investigated, in 18 patients who were no longer being actively treated but were attending a follow-up clinic or support group (n= 9 each). Four of the patients had appreciable psychological distress and four each had anxiety or depression of at least borderline importance. The degree of depression and distress decreased with increasing age and there were trends for depression to decrease with time after the onset of the illness and to be slightly less common among those attending the support group (2/9 compared to 4/9). Numerous psychosocial difficulties were reported and perceptions of support available from friends and family were mixed. There are implications for services, and in particular, patients need to be given clear information about the resources available to give them psychosocial support.

Adult↗

Crack smokers' intention to use condoms with loved partners: intervention development using the theory of reasoned action, condom beliefs, and processes of change.

Prevalence rates of HIV infection acquired through heterosexual contacts have risen steadily since 1982. Crack cocaine smokers are at particular risk of HIV infection due to heterosexual exposure. HIV risk reduction interventions seeking to increase condom use among drug users have met with minimal success, and there is a need for interventions to be strongly grounded in psychosocial models of behaviour change. This study presents the results of an investigation of predictors of intention to use condoms and related therapy processes among heterosexual drug users. Data were analyzed from 586 crack smokers recruited in Washington, DC, Miami, Florida, and Collier County, Florida who reported having both primary and casual sex partners. Participants responded to items derived from the theory of reasoned action, the theory of planned behaviour and the transtheoretical model of change. Condom use beliefs and therapy processes used to initiate and maintain condom use were assessed. Outcome expectancies and normative beliefs were the strongest predictors of intention to use condoms with a primary sexual partner. In turn, beliefs that condoms inhibit sexual romance and decrease sexual pleasure strongly predicted outcome expectancies. Therapy processes found to be associated with these constructs included: self-liberation, counter conditioning and stimulus control/reinforcement. Results suggest that HIV risk reduction interventions using a group format and targeting condom beliefs related to sexual romance and pleasure will decrease negative outcome expectancies about condom use. Also, reinforcing attempts to use condoms with intimate partners should increase positive outcome expectancies and intention to initiate or maintain condoms with a primary sexual partner.

Adolescent↗

Internalizing the impossible: anorexic outpatients' experiences with women's beauty and fashion magazines.

A growing body of research has linked the readership of women's beauty and fashion magazines with the development and perpetuation of anorexic behaviors in some young women. Although we know the link exists, little is known about the actual cognitive processes and the ways in which at risk women "use" these magazines to internalize the impossible thin ideal that appears to drive the illness. To understand this phenomenon and the process of internalization in greater depth, the authors conducted qualitative, semi-structured interviews with 28 outpatients at an eating disorder treatment facility in the western United States. Using a grounded theory approach, the authors' analysis provides a detailed description drawn from the patients' personal accounts of how the magazines have influenced their lives and eating-disordered behaviors.

Journal Article↗

Cardiovascular disease risk factors and diet of Fulani pastoralists of northern Nigeria.

BACKGROUND: The Fulani of northern Nigeria are seminomadic pastoralists who consume a diet rich in saturated fats, do not use tobacco, are lean, and have an active lifestyle. Little is known about their serum lipid profiles and corresponding risk of cardiovascular disease. OBJECTIVE: We measured serum lipid, homocysteine, folate, and vitamin B-12 concentrations in Fulani men and women and assessed the nutrient content of their diet. DESIGN: Blood samples from 42 men (18-64 y old) and 79 women (15-77 y old) living in the Jos Plateau of Nigeria were analyzed for cholesterol (total, HDL, and LDL), triacylglycerol, homocysteine, folate, and vitamin B-12 serum concentrations. Body composition was determined by bioelectrical impedance analysis. Dietary information was obtained with use of a 7-d dietary recall and a food-frequency questionnaire. Results were compared with US referent ranges. RESULTS: The mean energy content of the Fulani diet was relatively low (men, 6980 kJ; women, 6213 kJ) and the mean protein content was high (men, 20% of energy; women, 16% of energy). Nearly one-half of energy was provided by fat, and one-half of that was derived from saturated fatty acids. The diet provided marginal to adequate amounts of vitamins B-12, B-6, and C but only one-third of the US recommended dietary allowance for folate. The mean total cholesterol, HDL-cholesterol, and triacylglycerol concentrations of Fulani adults were within the referent ranges; the mean LDL-cholesterol concentration of Fulani adults below the range; and the mean serum homocysteine concentration of Fulani men above the range. Homocysteine and folate concentrations were inversely correlated for both men and women. CONCLUSIONS: Despite a diet high in saturated fat, Fulani adults have a lipid profile indicative of a low risk of cardiovascular disease. This finding is likely due to their high activity level and their low total energy intake.

Adolescent↗

Do physiological changes in pregnancy change defibrillation energy requirements?

Resuscitation during pregnancy is uncommon, with approximately 70 deaths occurring during pregnancy in the UK per annum. Physiological changes during pregnancy may affect transthoracic impedance (TTI), which determines transmyocardial current. Increased blood volume, cardiomegaly, haemodilution, changes in lung volume and changes in thoracic volume may alter impedance in ways that are difficult to predict. We measured TTI at term and after delivery once physiological changes had resolved. Mean (SD) TTI was 91.3 (15.8) Omega at term and 91.6 (11.8) Omega 6-8 weeks after delivery; the difference was not statistically significant. We conclude that current energy requirements for adult defibrillation are appropriate for use during pregnancy.

Adult↗

Beta-adrenergic growth regulation of human cancer cell lines derived from pancreatic ductal carcinomas.

Exocrine ductal carcinoma of the pancreas has been associated with smoking, and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) causes this cancer type in laboratory rodents. Current knowledge on the growth regulation of this malignancy is extremely limited. Recent studies have shown overexpression of cyclooxygenase 2 (COX 2) and 5-lipoxygenase (5-lipox) in exocrine pancreatic carcinomas, suggesting a potential role of the arachidonic acid (AA) cascade in the regulation of this cancer type. In support of this interpretation, our data show high basal levels of AA release in two human cell lines derived from exocrine ductal pancreatic carcinomas. Both cell lines expressed m-RNA for beta2-adrenergic receptors and beta1-adrenergic receptors. Radio-receptor assays showed that beta2-adrenergic receptors predominated over beta1-adrenergic receptors. beta2-Adrenergic antagonist ICI118,551 significantly reduced basal AA release and DNA synthesis when the cells were maintained in complete medium. DNA synthesis of the cell line (Panc-1) with an activating point mutation in codon 12 of the ki-ras gene was significantly stimulated by NNK when cells were maintained in complete medium and this response was inhibited by the beta-blocker ICI118,551, the COX-inhibitor aspirin, or the 5-lipox-inhibitor MK-886. The cell line without ras mutations (BXPC-3) did not show a significant response to NNK in complete medium. When the assays were conducted in serum-free medium, both cell lines demonstrated increased DNA synthesis in response to NNK, an effect inhibited by the beta2-blocker, aspirin, or MK-886. Panc-1 cells were more sensitive to the stimulating effects of NNK and less responsive to the inhibitors than BXPC-3 cells. Our findings are in accord with a recent report which has identified NNK as a beta-adrenergic agonist and suggest beta-adrenergic, AA-dependent regulatory pathways in pancreatic cancer as a novel target for cancer intervention strategies.

Adenocarcinoma↗

Use of a simulation model and ecosystem flux data to examine carbon-water interactions in ponderosa pine.

Drought stress plays an important role in determining both the structure and function of forest ecosystems, because of the close association between the carbon (C) and hydrological cycles. We used a detailed model of the soil-plant-atmosphere continuum to investigate the links between carbon uptake and the hydrological cycle in a mature, open stand of ponderosa pine (Pinus ponderosa Dougl. ex Laws.) at the Metolius river in eastern Oregon over a 2-year period (1996-1997). The model was parameterized from local measurements of vegetation structure, soil properties and meteorology, and tested against independent measurements of ecosystem latent energy (LE) and carbon fluxes and soil water content. Although the 2 years had very different precipitation regimes, annual uptake of C and total transpiration were similar in both years, according to both direct observation and simulations. There were important differences in ratios of evaporation to transpiration, and in the patterns of water abstraction from the soil profile, depending on the frequency of summer storms. Simulations showed that, during periods of maximum water limitation in late summer, plants maintained a remarkably constant evapotranspirative flux because of deep rooting, whereas changes in rates of C accumulation were determined by interactions between atmospheric vapor pressure deficit and stomatal conductance. Sensitivity analyses with the model suggest a highly conservative allocation strategy in the vegetation, focused belowground on accessing a soil volume large enough to buffer summer droughts, and optimized to account for interannual variability in precipitation. The model suggests that increased allocation to leaf area would greatly increase productivity, but with the associated risk of greater soil water depletion and drought stress in some years. By constructing sparse canopies and deep rooting systems, these stands balance reduced productivity in the short term with risk avoidance over the long term.

Carbon↗

Critical care unit design: a nursing perspective.

The task of designing a new critical care unit is best accomplished with the input of people representing multiple disciplines including architects, engineers, physicians, nurses, and equipment manufacturers. It is imperative that the critical care nursing staff and management take an active role in planning the layout of the unit and patient rooms, as the nurses will be the bedside providers 24 hours a day. The new unit should be designed to offer efficient patient care as well as a healing, comfortable environment for both the patients and their families.

Attitude of Health Personnel↗

Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections.

OBJECTIVE: To investigate the reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. METHOD: The 1986 version of the KSADS was modified and expanded to include onset and offset of each symptom for both current and lifetime episodes, expanded prepubertal mania and rapid cycling sections, and categories for attention-deficit/hyperactivity disorder and other DSM-IV diagnoses. To optimize diagnostic research, skip-outs were minimized. Subjects participated in the ongoing "Phenomenology and Course of Pediatric Bipolar Disorder" study. Mothers and children were interviewed separately by research nurses who were blind to diagnostic group status. In addition, ratings of off-site child psychiatrists, made from the narrative documentation given for each WASH-U-KSADS item, were compared with research nurse ratings. This work was performed between 1995 and 2000. RESULTS: There was 100% interrater reliability, five consecutive times, as both interviewer and observer after 10 to 15 trials. The kappa values of comparisons between research nurse and off-site blind best-estimate ratings of mania and rapid cycling sections were excellent (0.74-1.00). High 6-month stability for mania diagnoses (85.7%) and for individual mania items and validity against parental and teacher reports were previously reported. CONCLUSIONS: The WASH-U-KSADS mania and rapid cycling sections have acceptable reliability.

Affective Disorders, Psychotic↗

Adult psychosocial outcome of prepubertal major depressive disorder.

OBJECTIVE: To compare adult psychosocial functioning (PSF) of subjects with prepubertal major depressive disorder (PMDD) to a normal comparison (NC) group. METHOD: PSF of subjects with PMDD (n = 72) and of NC subjects (n = 28) was compared after prospective follow-up to adulthood. These 100 subjects were 90.9% of the baseline 110 subjects who participated in the "Nortriptyline in Childhood Depression: Follow-up Study." Research nurses who were blind to group status conducted telephone interviews using the Longitudinal Interval Follow-up Evaluation (LIFE) to obtain PSF data. RESULTS: At follow-up, the PMDD group was 20.7+/-2.0 and the NC subjects were 20.9+/-2.2 years old. The PMDD subjects were 10.3+/-1.5 years old at baseline. Time between baseline and follow-up was 9.9+/-1.5 years. In the PMDD group, subjects with MDD, bipolar disorder, or substance use disorders during the previous 5 years had significantly worse PSF than NC subjects. These PSF impairments included significantly worse relationships with parents, siblings, and friends; significantly worse functioning in household, school, and work settings; and worse overall quality of life and global social adjustment. CONCLUSIONS: Although combined treatments for PMDD have little scientific basis, multimodality regimens seem prudent until definitive treatment data become available.

Adaptation, Psychological↗

CXCR2 regulation of tumor necrosis factor-alpha adherence-dependent peroxide production is significantly diminished after severe injury in human neutrophils.

BACKGROUND: Primed neutrophils are thought to play a key role in inflammatory pathology. We have shown though in vitro studies that interleukin (IL)-8 and growth-related oncogene-alpha (GROalpha) (CXCR2-specific chemokines) regulate the respiratory burst via the CXCR2 receptor. We have also shown in vivo, CXCR2 receptors are down-regulated in severely injured patients. Our hypothesis is that regulation of the respiratory burst by CXCR2 is lost after severe injury. METHODS: Patient neutrophils were studied within 24 hours of admission to the hospital; excluded were severe head injury and patients with Injury Severity Score < 16. Patient and normal neutrophils were isolated by Ficoll-Hypaque centrifugation after dextran sedimentation. Neutrophils were plated with buffer, 50 nmol/L IL-8 or GROalpha on fibronectin-coated plates for 15 minutes, then stimulated with 10 ng/mL of TNFalpha. CXCR2 expression was measured by flow cytometry. Receptor function was assessed by calcium mobilization. RESULTS: One female and 10 male patients with an average age of 37 +/- 3 and Injury Severity Score of 24 +/- 5 suffered blunt injury. CXCR2 showed a 32% +/- 7% loss, whereas CXCR1 showed 15% +/- 6% reduction. GROalpha stimulation of patient neutrophils showed 60% +/- 16% decrease in calcium mobilization, whereas IL-8 showed no decline. At 40 minutes, IL-8 and GROalpha significantly inhibited TNFalpha adherence-dependent peroxide production in normal neutrophils (35% +/- 4% and 45% +/- 3%, respectively; p < 0.05). Both IL-8 and GROalpha lost the ability to suppress the respiratory burst in severely injured patients, but GROalpha had a significantly greater loss of this suppression (p = 0.004). CONCLUSION: IL-8 and GROalpha lose the ability to regulate the TNFalpha-induced respiratory burst. This may contribute to neutrophil dysregulation after injury and result in organ injury.

Adult↗

Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data.

Adrogolide (ABT-431; DAS-431) is a chemically stable prodrug that is converted rapidly (<1 min) in plasma to A-86929, a full agonist at dopamine D1 receptors. In in vitro functional assays, A-86929 is over 400 times more selective for dopamine D1 than D2 receptors. In rats with a unilateral loss of striatal dopamine, A-86929 produces contralateral rotations that are inhibited by dopamine D1 but not by dopamine D2 receptor antagonists. Adrogolide improves behavioral disability and locomotor activity scores in MPTP-lesioned marmosets, a model of Parkinson's disease (PD), and shows no tolerance upon repeated dosing for 28 days. In PD patients, intravenous (i.v.) adrogolide has antiparkinson efficacy equivalent to that of L-DOPA with a tendency towards a reduced liability to induce dyskinesia. The adverse events associated with its use were of mild-to-moderate severity and included injection site reaction, asthenia, headache, nausea, vomiting, postural hypotension, vasodilitation, and dizziness. Adrogolide can also attenuate the ability of cocaine to induce cocaine-seeking behavior and does not itself induce cocaine-seeking behavior in a rodent model of cocaine craving and relapse. In human cocaine abusers, i.v. adrogolide reduces cocaine craving and other cocaine-induced subjective effects. The results of animal abuse liability studies indicate that adrogolide is unlikely to have abuse potential in man. Adrogolide has also been reported to reverse haloperidol-induced cognitive deficits in monkeys, suggesting that it may be an effective treatment for the cognitive dysfunction associated with aging and disease. Adrogolide undergoes a high hepatic "first-pass" metabolism in man after oral dosing and, as a result, has a low oral bioavailability (approximately 4%). This limitation may potentially be circumvented by oral inhalation formulations for intrapulmonary delivery that greatly increase the bioavailability of adrogolide. As the first full dopamine D1 receptor agonist to show efficacy in PD patients and to reduce the craving and subjective effects of cocaine in cocaine abusers, adrogolide represents an important tool in understanding the pharmacotherapeutic potential of dopamine D1 receptor agonists.

Androstenes↗

An investigation of condom use by frequency of sex.

OBJECTIVES: To examine the association between condom use and frequency of sex across sexual partner types. METHODS: Data were collected from African American drug users residing in Washington, DC. Participants were asked to provide the first name of the last three partners with whom they had had vaginal sex, to define the type of relationship, the number of times they had had vaginal sex in the last 30 days with each partner, and whether they had used a condom during their last sexual encounter with each partner. Condom use was examined by frequency of sex in the past 30 days controlling for partner type. RESULTS: Frequency of sexual encounters varied by partner type. The largest number of sexual encounters was with casual partners, followed by commercial and primary partners, respectively. Within partner types, participants had sex most frequently with primary partners. Condom use was lowest within primary partner relationships. Regardless of partner type, condom use varied consistently depending on the frequency of sex with the same partner. CONCLUSIONS: Condom use is related to the frequency of sex between partners when partner type is controlled. The association between frequency of sex and condom use is independent of partner type, suggesting that partner type may become less influential in determining condom use as the frequency of sex increases. This finding suggests that contextual factors determining condom use go beyond partner type designations and include other relationship variables.

Adult↗

Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder.

OBJECTIVE: The authors' goal was to conduct an adult follow-up of subjects who had participated in a study of nortriptyline for childhood depression. METHOD: The study group represented 100 (90. 9%) of the original 110 subjects and included 72 subjects who had a prepubertal diagnosis of major depressive disorder and 28 normal comparison subjects. Subjects were assessed with semistructured research interviews given by research nurses who were blind to the subjects' original diagnoses. RESULTS: In the original study, the mean age of the children with prepubertal major depressive disorder was 10.3 years (SD=1.5); at adult follow-up the mean age of these subjects was 20.7 years (SD=2.0). At follow-up, significantly more of the subjects who had prepubertal diagnoses of major depressive disorder (N=24 [33.3%]) than normal comparison subjects (none) had bipolar I disorder. Subjects who had prepubertal diagnoses of major depressive disorder also had significantly higher rates of any bipolar disorder than normal subjects (48.6% [N=35] versus 7.1% [N=2]), major depressive disorder (36.1% [N=26] versus 14.3% [N=4]), substance use disorders (30.6% [N=22] versus 10.7% [N=3]), and suicidality (22.2% [N=16] versus 3.6% [N=1]). Parental and grandparental mania predicted bipolar I disorder outcomes. CONCLUSIONS: High rates of switching to mania have implications for the treatment of depressed children. The authors discuss the reasons for their finding a higher rate of bipolar disorder in this outcome study than was found in the one other adult outcome study of prepubertal major depressive disorder.

Adolescent↗

One-year recovery and relapse rates of children with a prepubertal and early adolescent bipolar disorder phenotype.

OBJECTIVE: The study examined 1-year recovery and relapse rates for mania in subjects who met criteria for a prepubertal and early adolescent bipolar disorder phenotype. METHOD: Outpatients identified by consecutive new-case ascertainment were assessed by means of separate child and parent interviews, consensus conferences, and blind best estimates. The definition of the prepubertal and early adolescent bipolar disorder phenotype was DSM-IV mania with elation and/or grandiosity as one criterion. RESULTS: Of 93 subjects seen at baseline, 89 were seen at 1 year (95.7% retention). The rate of recovery from mania was 37.1%, and the rate of relapse after recovery was 38.3%. No covariates were significantly associated with recovery or relapse. CONCLUSIONS: The low recovery and high relapse rates supported the study hypothesis of poor outcomes, which was made on the basis of similarity between the characteristics of the prepubertal and early adolescent bipolar disorder phenotype (long episode duration and high prevalence of mixed mania, psychosis, and rapid cycling) and those of severe bipolar disorder in adults.

Adolescent↗

Know your heart.

In this article in our Concepts in Anatomy series, Mriga Williams joins John Clancy and Andrew McVicar in an examination of the heart, identifying and describing its component parts, its relationship to the circulatory system and some of the abnormalities it might develop. The article includes a range of activities readers may carry out to test and improve their knowledge. The series is based on the text by John Clancy and Andrew McVicar, Physiology and Anatomy--a homeostatic approach, Arnold, London (in print September 2001).

Cardiovascular Physiological Phenomena↗