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Biomedical subjects

C L Williams

Publications and source records attributed to C L Williams.

At least 19 recordsLinked to original sources

Fluconazole and itraconazole susceptibilities of Candida spp. isolated from oropharyngeal specimens and blood cultures of paediatric haematology/oncology patients.

This study examined the in vitro susceptibilities to fluconazole and itraconazole of isolates of Candida spp. from surveillance oropharyngeal specimens and blood cultures from paediatric patients with malignancy. The species distribution of 100 isolates from oropharyngeal specimens was C. albicans 86%, C. glabrata 7%, C. lusitaniae 4%, C. parapsilosis 2% and C. tropicalis 1%. From a total of nine isolates from blood cultures the species distribution was C. albicans 33.3%, C. parapsilosis 33.3 % and C. guilliermondii 33.3%. Only three of the oropharyngeal isolates were resistant to fluconazole (MIC > or = 64 mg l(-1)) and only two were resistant to itraconazole (MIC > or = 1 mg l(-1)). None of the blood culture isolates was resistant to either agent. At this centre, C. albicans is the predominant species from oropharyngeal specimens, but non-albicans Candida species predominate in blood cultures. Although resistance to fluconazole and itraconazole is rare at present, continued surveillance is warranted to monitor trends in species distribution and antifungal susceptibility.

Candida↗

Epinephrine administration increases neural impulses propagated along the vagus nerve: Role of peripheral beta-adrenergic receptors.

A significant number of animal and human studies demonstrate that memories for new experiences are encoded more effectively under environmental or laboratory conditions which elevate peripheral concentrations of the hormone epinephrine and in turn, induce emotional arousal. Although this phenomenon has been replicated across several learning paradigms, understanding of how this arousal related hormone affects memory processing remains obscure because epinephrine does not freely enter into the central circulation to produce any direct effects on the brain. This study examined whether epinephrine's actions on the CNS may be mediated by the initial activation of peripheral vagal fibers that project to the brain. The vagus was selected as a candidate for this role since it is densely embedded with beta-adrenergic receptors and the peripheral endings of this nerve innervate a broad spectrum of sensory organs that are directly affected by epinephrine release. Electrophysiological recordings of cervical vagal activity was measured over 110 min in urethane-anesthetized Sprague-Dawley rats given saline, epinephrine (0.3 mg/kg), the peripherally acting beta-adrenergic antagonist sotalol (2.0 mg/kg), or a combination of sotalol followed 15 min later by an injection of epinephrine. Epinephrine produced a significant increase in vagal nerve firing 10 min post-injection (p < .05) relative to controls and neural impulses recorded from the vagus remained significantly elevated for the remaining 55 min collection period. The excitatory actions of epinephrine were not observed in groups given an identical dose of the hormone after peripheral beta-adrenergic receptor blockade with sotalol. These findings demonstrate that neural discharge in vagal afferent fibers is increased by elevations in peripheral concentrations of epinephrine and the significance of these findings in understanding how epinephrine modulates brain limbic structures to encode and store new information into memory is discussed.

Adrenergic beta-Antagonists↗

Fatal adverse pulmonary reaction in calves after inadvertent intravenous vaccination.

Fatal adverse reactions to vaccination are uncommon and poorly documented. To our knowledge, this is the first case report of fatal adverse reaction to an inadvertent intravenous vaccination in three calves vaccinated against respiratory (Somnustar Ph) and clostridial (Tasvax 8) diseases. All three calves had severe acute interstitial pneumonia with multifocal pulmonary hemorrhages that resulted in fatal respiratory failure. Qualitatively, the pulmonary lesions in these calves were similar to those in septicemic/endotoxemic calves; however, the severity and extensity of pulmonary hemorrhages were of a higher degree than those usually observed in clinical septicemia/endotoxemia. In addition, approximately 30% of the arterioles and small arteries were surrounded by hemorrhages, which occasionally extended around adjacent bronchioles. A unilateral peri-jugular hematoma with recent transmural perforation of jugular vein found in all three calves was believed to have been caused by the injection needle during vaccination, and the fatal pulmonary changes were believed to have been secondary to the intravenous injection of vaccine.

Animals↗

Copper-induced hepatotoxicosis with hepatic stellate cell activation and severe fibrosis in North Ronaldsay lambs: a model for non-Wilsonian hepatic copper toxicosis of infants.

Copper-sensitive North Ronaldsay sheep represent a possible model for certain hepatic-overload syndromes of infancy and childhood that are clinically, pathologically and genetically distinct from Wilson's disease. The purpose of this study was to simulate in artificially reared lambs the syndrome produced by copper exposure in susceptible human infants. Twenty four North Ronaldsay lambs were assigned to three groups of eight animals, namely, an unsupplemented control group and two trial groups given milk replacer to which copper (CuSO4) had been added at the rate of 5 mg/litre and 10 mg/litre. Four lambs from each group were killed at 40 or 69 days. Livers were fixed in 10% formalin and analysed for copper by mass spectrometry. Paraffin wax-embedded sections were stained with rhodanine for copper and labelled immunohistochemically for alpha smooth muscle actin (ASMA). At 40 days the maximum amounts of copper in the livers of both copper-supplemented groups was 1466-1605 microg/g dry weight (control group 172-201 microg/g Cu dry weight). Histochemically, copper was demonstrated within hepatocytes, together with marked apoptosis. At 69 days there was a florid pericellular fibrosis complemented by strong ASMA immunolabelling, confirming phenotypic modulation of hepatic stellate cells. Such primary copper-induced fibrogenesis confirms the unique status of this animal model in respect of childhood copper toxicosis.

Animals↗

The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala.

Vagal nerve stimulation (VNS) is known to improve cognitive processing, presumably by affecting activity in central nervous system structures that process recently acquired information. It has long been assumed that these effects are related to stimulation-induced increases of norepinephrine (NE) release in limbic brain structures. The present study examined this hypothesis by administering VNS at an intensity and duration that improves memory and then measuring fluctuations in NE output in the basolateral amygdala (BLA) with in vivo microdialysis. In Experiment 1, VNS caused a 98% increase in NE output relative to baseline. In Experiment 2, methyl atropine was given 10 min before VNS to assess whether stimulation-induced increases in amygdala NE are mediated by afferent or efferent vagal branches. Methyl atropine did not alter NE release in the BLA in comparison with saline. The significance of these findings in understanding how peripheral neural activity modulates limbic structures to encode and store new information into memory is discussed.

Amygdala↗

Formation of the arthrodial membrane in the blue crab, Callinectes sapidus.

In this study the pattern of arthrodial membrane deposition in Callinectes sapidus was determined by histological and ultrastructural examination of tissues from the carpus joint of the cheliped collected during premolt, ecdysis, postmolt, and intermolt. Apolysis in the arthrodial membrane occurs at stage D(0) and is synchronous with apolysis of the calcified cuticle. Epicuticle formation begins at early stage D(1) and is completed in late stage D(1). Procuticle deposition starts at D(2) and continues until ecdysis. Numerous cytoplasmic extensions occur throughout the lamellae. Component fibers of the arthrodial membrane are intimately associated with dense plaques on the apical membrane of the underlying hypodermal cells, suggesting a site for fiber polymerization. Deposition of the arthrodial membrane continues after ecdysis, with most of the cuticle thickening occurring during stage C. When stained with PAS and counterstained with hematoxylin, a difference can be discerned between preecdysial and postecdysial procuticle of the arthrodial membrane, a distinction not made in previous studies. The boundary between the arthrodial membrane and calcified cuticle is thicker than either of the two layers and the layers overlap rather than butting up against one another. This pattern suggests that underlying hypodermal cells have to produce multiple types of cuticle over the molt cycle. A summary of the various molting patterns in C. sapidus suggests that the control of these diverse events may prove to be complex.

Animals↗

Evaluation of protocol using gene capture and PCR for detection of Helicobacter pylori DNA in feces.

The route of transmission of Helicobacter pylori, which is usually acquired in childhood and is one of the most common bacterial infections in humans, remains undetermined. Mapping the distribution of H. pylori genotypes within families could help to determine the routes of transmission and risk factors. Here we describe a noninvasive method for obtaining H. pylori DNA isolates from the feces of children. Children presenting with gastrointestinal symptoms at the Royal Hospital for Sick Children were tested for gastric H. pylori colonization by using the 13C-urea breath test (UBT) and were asked to provide fecal samples, which were tested for H. pylori by using the HpSA fecal antigen test. DNA was purified from fecal samples by using a novel method of gene capture with subsequent H. pylori PCR analysis. Fifteen UBT-positive and 15 UBT-negative children participated in the study. The positive and negative predictive values for the assay were 80 and 100%, respectively. Fecal DNA purification followed by H. pylori PCR analysis is an effective tool for harvesting H. pylori DNA isolates from the feces of children. This technique may be developed to allow the diagnosis and noninvasive genotyping of H. pylori in children and their families.

Antigens, Bacterial↗

Water, water everywhere nor any a sterile drop to rinse your endoscope.

Traditional waterborne infections have been largely controlled in the UK by the provision of clean drinking water. However, water can still cause problems for infection control teams in particular when used in endoscope washer-disinfectors. HTM 2030 states that final rinse water used in washer-disinfectors must not present a microbiological hazard and that there should be no recovery of micro-organisms from the final rinse water. The problems that biofilms may cause in washer-disinfectors, the type of biofilms that may develop, and the nature of the bacteria within them, in particular how biofilm bacteria behave differently to those that are not part of a biofilm (planktonic bacteria), are discussed in this article. Finally, we discuss how knowledge of the growth and control of biofilms may be used to control their growth.

Biofilms↗

Prevention and treatment of childhood obesity.

Obesity has reached epidemic proportions among children and youth in the United States. Surveys indicate that the number of overweight children aged 6 to 17 years has doubled within three decades. In the decade between the late 1970s and the late 1980s, the prevalence of overweight increased from 7.6% to 10.9% for children aged 6 to 11 years, and from 5.7% to 10.8% for adolescents aged 12 to 19 years. Data for 1999 indicates that the epidemic is continuing to increase, so that 13% of 6- to 11-year-old children and 14% of 12- to 19-year- old children are currently overweight (body mass index > or = 95th percentile for age/gender). This article reviews newer concepts related to etiologic factors, comorbidities, and strategies for prevention and treatment.

Adolescent↗

Smooth estimation of the reliability function.

Problems with censored data arise quite frequently in reliability applications. Estimation of the reliability function is usually of concern. Reliability function estimators proposed by Kaplan and Meier (1958), Breslow (1972), are generally used when dealing with censored data. These estimators have the known properties of being asymptotically unbiased, uniformly strongly consistent, and weakly convergent to the same Gaussian process, when properly normalized. We study the properties of the smoothed Kaplan-Meier estimator with a suitable kernel function in this paper. The smooth estimator is compared with the Kaplan-Meier and Breslow estimators for large sample sizes giving an exact expression for an appropriately normalized difference of the mean square error (MSE) of the two estimators. This quantifies the deficiency of the Kaplan-Meier estimator in comparison to the smoothed version. We also obtain a non-asymptotic bound on an expected L1-type error under weak conditions. Some simulations are carried out to examine the performance of the suggested method.

Humans↗

Subject and observer-rated quality of life in schizophrenia.

OBJECTIVE: We aimed to explore the relationship between objectively rated quality of life and subjective measures of social functioning and life satisfaction. METHOD: Participants of the Schizophrenia Care and Assessment Program (SCAP) study at Dandenong in Australia were included in this analysis. Subjective ratings of several domains of social functioning and life satisfaction were taken from the SCAP instrument and comparisons made with data from the Quality of Life scale rated by research staff as well as several psychopathology measures. RESULTS: Subjectively reported life satisfaction was not related to positive or negative symptoms of schizophrenia but did correlate with depressive symptoms. Quality of Life scale measures correlated with negative symptoms on most domains. There was very limited overlap in domain items between the life satisfaction and quality of life measures. CONCLUSION: Life satisfaction and objectively rated quality of life are not closely related and appear to have different determinants in patients with schizophrenia.

Adult↗

Childhood obesity: the health issue.

Overweight and obesity in children is epidemic in North America and internationally. Approximately 22 million children under 5 years of age are overweight across the world. In the United States, the number of overweight children and adolescents has doubled in the last two to three decades, and similar doubling rates are being observed worldwide, including in developing countries and regions where an increase in Westernization of behavioral and dietary lifestyles is evident. Comorbidities associated with obesity and overweight are similar in children as in the adult population. Elevated blood pressure, dyslipidemia, and a higher prevalence of factors associated with insulin resistance and type 2 diabetes appear as frequent comorbidities in the overweight and obese pediatric population. In some populations, type 2 diabetes is now the dominant form of diabetes in children and adolescents. Disturbingly, obesity in childhood, particularly in adolescence, is a key predictor for obesity in adulthood. Moreover, morbidity and mortality in the adult population is increased in individuals who were overweight in adolescence, even if they lose the extra weight during adulthood. Although the cause of obesity in children is similar to that of adults (i.e., more energy in vs. energy utilized), emerging data suggest associations between the influence of maternal and fetal factors during intrauterine growth and growth during the first year of life, on risk of later development of adult obesity and its comorbidities. In addition, recent data suggest that varying biological responses in different racial/ethnic groups differently contribute to overweight, obesity, and their comorbidities. Although differences in gene-nutrient interactions may contribute, the role of varying cultural and socioeconomic variables still needs to be determined to understand these disparities. Novel approaches in the prevention and treatment of childhood overweight and obesity are urgently required. With the strong evidence that a lifecycle perspective is important in obesity development and its consequences, consideration must be focused on prevention of obesity in women of child-bearing age, excessive weight gain during pregnancy, and the role of breast-feeding in reducing later obesity in children and adults. Consideration must be given to family behavior patterns, diet after weaning, and the use of new methods of information dissemination to help reduce the impact of childhood obesity worldwide.

Adolescent↗

Russian-American partners for prevention. Adaptation of a school-based parent-child programme for alcohol use prevention.

BACKGROUND: The Russian-American Partners for Prevention was an adaptation and evaluation of the Slick Tracy Home Team Program which was developed in Minnesota in order to delay the onset of drinking. The Slick Tracy Home Team Program was the first intervention of Project Northland, a large 3 year community trial of the efficacy of a public health intervention for under age drinking. METHODS: The programme was administered through schools, but involved parents using engaging and fun homework activities. The Russian version was implemented in fifth-grade classrooms in 20 Moscow schools with 1,212 students surveyed at baseline. Students were surveyed again after programme implementation (n = 1,182), of whom 980 were present at baseline. Parents of 1,078 students were surveyed by telephone after programme implementation. RESULTS: The results demonstrated the successful recruitment and retention of 20 Moscow schools in a research project, acceptability of programme materials in Russia, high participation rates, changes in students' knowledge about problems associated with under age drinking and some evidence about increases in parent-child communication about alcohol use. As in the USA, no changes in students' alcohol use rates were observed at the end of the first year of the 3 year programme. CONCLUSION: Russian youth, as compared to Americans, began drinking at earlier ages, received fewer prevention messages from their parents, and had fewer prevention programmes in school. The results suggested that carefully implemented and evaluated replications of the US Project Northland interventions might provide effective and appropriate school-based programmes for Russia.

Adolescent↗

How did Project Northland reduce alcohol use among young adolescents? Analysis of mediating variables.

Project Northland is a randomized trial designed to create, implement and evaluate multilevel, community-wide strategies to prevent alcohol use among adolescents. This paper will focus on the mediating outcomes of the early adolescent phase of Project Northland when the students in the study cohort were in Grades 6-8. The project was conducted in 24 school districts and adjacent communities in northeastern Minnesota. The intervention consisted of social-behavioral curricula in schools, peer leadership activities, parental involvement and education, and community-wide activities. At the end of 3 years of intervention, significantly fewer students in the intervention school districts reported alcohol use than students in the reference districts. Mediation analyses were conducted to investigate if the intervention's effects on mediating variables could explain the reduction in alcohol use. Important mediators of Project Northland's effect on alcohol use were: (1) peer influence to use, including normative estimates, (2) functional meanings of alcohol use, (3) attitudes and behaviors associated with alcohol and drug problems like stimulus seeking, rule violations and bad judgement, and (4) parent-child alcohol-related communication around alcohol use. In addition, among those who did not use alcohol at baseline, self-efficacy to refuse offers of alcohol was a significant mediator.

Adolescent↗

Reduced expression of Wnt-1 and E-cadherin, and diminished beta-catenin stability in MCF-7 breast cancer cells that overexpress protein kinase C-alpha.

MCF-7 breast cancer cells stably overexpressing protein kinase C-alpha (MCF-7-PKC-alpha cells) exhibit reduced cell-cell adhesion and increased tumorigenicity in nude mice. We investigated the possibility that alterations in E-cadherin and catenins contribute to the unique phenotype of MCF-7-PKC-alpha cells. Northern and Western blotting indicated that MCF-7-PKC-alpha cells express abnormally low amounts of plakoglobin mRNA and protein, and undetectable levels of E-cadherin mRNA and protein. In contrast, even though MCF-7-PKC-alpha cells express low levels of beta-catenin mRNA, they express undetectable levels of beta-catenin protein, suggesting that post-transcriptional events further diminish beta-catenin expression in these cells. Pulse-labeling of the cells with [35S]methionine showed that the half-life of beta-catenin is less than 15 min in MCF-7-PKC-alpha cells, compared to over 2 h in MCF-7-Vector cells [MCF-7 cells transfected with pSV2M(2)6 vector only]. Incubation with LiCl to inactivate glycogen synthase kinase-3 (GSK-3) significantly prolonged the half-life of beta-catenin in MCF-7-PKC-alpha cells, suggesting that the GSK-3-dependent degradation of beta-catenin contributes to beta-catenin instability in these cells. Northern and Western blotting indicated that Wnt-1, which also inhibits GSK-3 activity, is expressed by MCF-7-Vector cells, but not by MCF-7-PKC-alpha cells. Transfection of (S37A)beta-catenin, which is resistant to GSK-3-dependent degradation, stimulated TCF/LEF-dependent luciferase expression from the pTOPFLASH reporter plasmid by 753-fold in MCF-7-PKC-alpha cells, and by 268-fold in MCF-7-Vector cells. Inactivation of GSK-3 by LiCl stimulated luciferase expression from the pTOPFLASH reporter plasmid by 12.4-fold in MCF-7-PKC-alpha cells, and by 4.8-fold in MCF-7-Vector cells. These results suggest that degradation of beta-catenin by GSK-3 contributes to beta-catenin instability in MCF-7-PKC-alpha cells, diminishing the ability of -catenin to act as a transcriptional co-activator. Reduced Wnt-1 expression by MCF-7-PKC-alpha cells may promote beta-catenin degradation by enhancing GSK-3 activity. Loss of beta-catenin-dependent cell-cell adhesion and transcription may contribute to the aggressive phenotype of MCF-7-PKC-alpha cells.

Animals↗

Memory retention is modulated by acute estradiol and progesterone replacement.

Ovarian hormones alter spine density of hippocampal granule and pyramidal cells in young adult and aging female rats (P. Miranda, C. L. Williams, & G. Einstein, 1999; C. S. Woolley, 1998). The present study used a delayed matching-to-place version of the water maze to investigate a behavioral correlate of these hormone-induced changes in hippocampal connectivity in 3- and 8-month-old female rats. When primed with 10-microg injections of estradiol 72 and 48 hr before testing, the memory retention of ovariectomized rats was improved compared with retention after priming with oil. A single injection of progesterone maintained this enhancement if testing occurred within 8 hr of the progesterone injection but not if testing occurred more than 24 hr after the progesterone injection. These findings indicate that estradiol and progesterone alter memory retention and suggest that these changes may be the result of hormone-induced increases in hippocampal connectivity.

Animals↗