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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 73 records · Page 4Linked to original sources

AIDS and AIDS-treatment neuropathies.

AIDS and AIDS-treatment neuropathies are common in individuals infected with HIV. As patients live longer due to improved antiretroviral therapies, the impact of painful neuropathy on patients' lives may increase. Several antiretroviral medications are known to cause toxic neuropathy in AIDS patients; but this may be outweighed by the beneficial effects of viral suppression. Current theories on the pathogenesis of AIDS neuropathies include mitochondrial toxicity secondary to gamma-DNA polymerase inhibition and subsequent abnormal mitochondrial DNA synthesis. Treatment of AIDS neuropathies is directed toward relief of symptoms, however, new evidence suggests that aggressive antiretroviral therapy may also be effective.

Acquired Immunodeficiency Syndrome↗

Comparison of drug substance impurity profiles generated with extended length columns during packed-column SFC.

The current study assesses the effect of extending column length during gradient packed column sub/supercritical fluid chromatography (PCSFC) experiments on the detection of known and unknown impurities in a drug substance sample. Quantitative drug substance impurity profiles were generated and compared using multiple column PCSFC and HPLC conditions. Also, chromatographic figures of merit were estimated and compared for components of a standard mixture during PCSFC experiments, which used one column, four columns, and six columns in series.

Chromatography, High Pressure Liquid↗

Integumental disease in invertebrates.

The necessarily truncated discussion of integumental neoplasia in invertebrates, given the lack of investigation of such lesions involving individual animals, shows how invertebrate veterinary medicine has a long way to go before reaching the levels of diagnosis and therapeutics of vertebrate exotic species. Nevertheless, the importance of a disease such as varoosis in a species such as the honey bee, which has a massive influence through pollination quite beyond its relevance as a honey producer, shows the importance of never excluding invertebrates from discussion of disease in exotic species. It is therefore commendable that this issue of the Veterinary Clinics of North America: Exotic Animal Practice seeks wherever possible to include invertebrates in its discussion.

Animals↗

A (1-->3)-beta-D-linked heptasaccharide is the unit ligand for glucan pattern recognition receptors on human monocytes.

Glucans are fungal cell wall polysaccharides which stimulate innate immune responses. We determined the minimum unit ligand that would bind to glucan receptors on human U937 cells using laminarin-derived pentaose, hexaose, and heptaose glucan polymers. When U937 membranes were pretreated with the oligosaccharides and passed over a glucan surface, only the heptasaccharide inhibited the interaction of glucan with membrane receptors at a K(d) of 31 microM (95% CI 20-48 microM) and 100% inhibition. However, the glucan heptasaccharide did not stimulate U937 monocyte NFkappaB signaling, nor did it increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger and more complex glucan polymer (M(w) = 7700 g/mol), only partially inhibited binding (61 +/- 4%) at a K(d) of 2.6 microM (99% CI 1.7-4.2 microM) with characteristics of a single binding site. These results indicate that a heptasaccharide is the smallest unit ligand recognized by macrophage glucan receptors. The data also indicate the presence of at least two glucan-binding sites on U937 cells and that the binding sites on human monocyte/macrophages can discriminate between glucan polymers. The heptasaccharide and laminarin were receptor antagonists, but they were not receptor agonists with respect to activation of NFkappaB-dependent signaling pathways or protection against experimental sepsis.

Animals↗

New insight into RNase P RNA structure from comparative analysis of the archaeal RNA.

A detailed comparative analysis of archaeal RNase P RNA structure and a comparison of the resulting structural information with that of the bacterial RNA reveals that the archaeal RNase P RNAs are strikingly similar to those of Bacteria. The differences between the secondary structure models of archaeal and bacterial RNase P RNA have largely disappeared, and even variation in the sequence and structure of the RNAs are similar in extent and type. The structure of the cruciform (P7-11) has been reevaluated on the basis of a total of 321 bacterial and archaeal sequences, leading to a model for the structure of this region of the RNA that includes an extension to P11 that consistently organizes the cruciform and adjacent highly-conserved sequences.

Base Sequence↗

Suppression of aromatase (estrogen synthetase) by red wine phytochemicals.

Estrogen promotes the proliferation of breast cancer cells. Aromatase is the enzyme that converts androgen to estrogen. In tumors, the expression of aromatase is upregulated compared to surrounding non-cancerous tissue. In this study, we found that wine contains phytochemicals that are capable of suppressing aromatase. Red wine was shown to be much more effective than white wine in the suppression of aromatase activity. Whole wine, lyophilized wine, and heat-treated extracts were examined for aromatase inhibition in a human placenta microsomal assay. C18 Sep-Pak cartridge (Waters Co.) separation of red wine extracts under an increasing acetonitrile (ACN) gradient found that the most active components were in the 20% ACN fraction, in that they inhibited the wild-type human placenta aromatase, wild-type porcine placenta and blastocyst aromatase in a dose-dependent fashion. The 20% ACN active fraction was heat stable and inhibited aromatase in a non-competitive manner. The aromatase-inhibitory action of red wine extracts was also examined with a transgenic mouse model in which aromatase is over-expressed in the mammary tissues. It was found that the intake of the 20% ACN fraction by gavage completely abrogated aromatase-induced hyperplasia and other changes in the mammary tissue. This is the first report demonstrating that wine, especially red wine, contains phytochemicals that can inhibit aromatase.

Animals↗

Preferential prescribing of oral corticosteroids in Irish male asthmatic children.

AIMS: To determine if there is a gender difference in the prescription of oral corticosteroids in asthmatic children (< 15 years). METHODS: 8072 asthmatics were identified on the basis that they received a prescription for either an inhaled beta-adrenoceptor agonist, an inhaled corticosteroid, inhaled cromoglycate/nedocromil sodium, oral xanthines or leukotriene antagonist. Odds ratios (OR) and 95% confidence intervals (CI) were determined for the different asthma treatments for males compared with females. RESULTS AND CONCLUSIONS: Male asthmatic children were more likely (OR = 1.37, 95% CI = 1.21,1.55, P < 0.001) to receive a prescription for an oral corticosteroid compared with their female counterparts suggesting a possible increased severity of their condition, rather than a different management of their disease. Male asthmatic children were less likely to be prescribed an antibiotic over the study period (OR = 0.85, 95% CI = 0.77, 0.93, P < 0.001).

Administration, Oral↗

Lack of symptom benefit following presumptive Helicobacter pylori eradication therapy in primary care.

BACKGROUND: Helicobacter pylori eradication regimens have failure rates under 10%, however little information is available on the effect of treatment success in reducing the subsequent prescription of anti-ulcer medications in primary care. AIMS: To determine, using a large prescription database in eastern Ireland, the success of presumptive eradication therapy in improving symptoms of dyspepsia in primary care, as judged by a reduction in the subsequent prescription of anti-ulcer medications. METHODS: In a cross-sectional study, we identified 3847 patients who received a prescription for eradication therapy for Helicobacter pylori, including 826 who were followed for 9-11 months. Those who subsequently received anti-ulcer medications were deemed failures to obtain symptom relief. RESULTS: For 3847 patients with a median follow-up of 8 months, the failure rate was 49%. Of 826 patients, followed for a longer period (9-11 months), the overall failure rate was 56% (range 44-62% depending on the eradication regimen used). Age over 65 years (hazard ratio=1.57, 95% confidence interval= 1.29-1.91, P < 0.001), prior use of anti-ulcer medications (hazard ratio=1.97, 95% confidence interval=1.63-2.37, P < 0.001) and prior use of aspirin/NSAIDs (hazard ratio=1.43, 95% confidence interval=1.18-1.73, P < 0.001) all predicted failure to obtain relief of symptoms of dyspepsia from eradication therapy. CONCLUSIONS: Such high failure rates of eradication therapy in reducing the subsequent consumption of anti-ulcer medications have both clinical and economic implications for the use of eradication therapy for Helicobacter pylori in primary care.

Adult↗

Universal vs. selective services: the case of British health visiting.

AIMS: This paper discusses whether there should be universal or selective provision of health visiting services. The aim is to show the central relevance of the work of the late epidemiologist, Geoffery Rose, to arguments advocating the retention of a universal health visiting service. BACKGROUND: In the United Kingdom (UK), health visiting moved, in the early years of the twentieth century, from being focused on the needs of poor families to becoming a universally provided service. Recent debates about the future of British health visiting have again raised the issue of whether health visiting remains a universal service, or should be targeted only on the most needy. STRUCTURE: Following an exposition of Rose's work, two kinds of problems with which health visitors are concerned, depression and child abuse, are used to illustrate the ways in which Rose's approach can be applied to health visiting. CENTRAL THESIS: Rose argued that the bulk of problems in society arise in the many who are not at especially high risk, rather than in the few who are at high risk. This is because of a very large number of people who are not at especially high risk. Consequently, following Rose, this paper argues that in relation to such problems as depression or child abuse, to target health visiting services only on those at high risk would be to leave untouched a vast burden of health and social problems. In the context of identifying people who are at greatest risk, Rose argued that no screening instrument can ever be sufficiently precise to accurately identify those most likely to suffer problems. In corroboration of Rose's argument, this paper illustrates the pitfalls of health visitors' attempts to screen for families at greatest risk through the use of such instruments as checklists of risk factors. CONCLUSIONS: It is concluded that it is neither possible to screen accurately for those at greatest risk, nor desirable to target services only on those at greatest risk. Therefore, it is advocated that health visiting should remain a universal service. However, it is recognized that within a universally provided service, some clients will require a greater intensity of input than others. In assessing the need for services, it is argued that the professional judgements of health visitors are crucial.

Child↗

Xanthogranulomatous pyelonephritis in childhood.

PURPOSE: Demographic data, clinical presentation, associated abnormalities, and radiologic findings were evaluated to outline diagnostic criteria that may lead to the diagnosis of xanthogranulomatous pyelonephritis in children. METHODS: Eleven boys and 8 girls with a mean age of 3.4 +/- 1.7 years were classified into obstructive xanthogranulomatous pyelonephritis (n = 13), which was associated with nephrolithiasis and nonobstructive (n = 6), which mimicked Wilms' tumor. RESULTS: Twelve children with obstructive diffuse involvement of the renal parenchyma, 1 with left-sided obstructive focal involvement in a horseshoe kidney (group 1), and 6 with nonobstructive diffuse xanthogranulomatous pyelonephritis (group 2) showed a male to female ratio of 1.2:1 and 2:1, respectively. Mean age was 4.1 +/- 1.2 years in group 1 versus 1.8 +/- 1.5 years in group 2; P =.001. The common features were renal mass, hematuria, and anemia (100%; P =.07) and leucocytosis (77% v 83%; P =.097). Main differences between the 2 groups were acute inflammatory syndrome (0 v 33%; P =.01), recurrent urinary infection (54% v 17%; P =.05), isolation of Proteus mirabilis as a pathogen (69% v 0; P =.001), and renal stones (100% v 0; P =.001). Preoperative diagnosis was accurate in all 13 (100%) children with obstructive xanthogranulomatous pyelonephritis. Radiologic features that were not consistent with Wilms' tumor in group 2 were absence of sharp definition and encapsulation of the mass, ill-defined margins with inflammatory infiltration of the perinephric fat and focal inflammatory tissue destruction. Nephrectomy was technically difficult because of extensive adhesions to the retroperitoneum, psoas muscle, and surrounding structures in both groups. CONCLUSIONS: Xanthogranulomatous pyelonephritis must be considered in the differential diagnosis of a child presenting with a renal mass, anemia, and elevated inflammatory markers. Treatment by nephrectomy is curative. J Pediatr Surg 36:598-601.

Age Distribution↗

Diagnostic issues in unusual asphyxial deaths.

Upper airway occlusion may be due to a variety of causes and may result from accidents, suicides or homicides. Underlying natural diseases may also predispose to lethal choking episodes. A series of nine cases is reported to illustrate a range of circumstances that resulted in fatal upper airway compromise. These included suicide from upper airway obstruction due to an impacted blanket, and accidental deaths due to inhalation of soil, a rock, and a video cassette sticker. One death resulted from glottic obstruction due to a mucosal cavernous haemangioma, another from an enlarged tonsil, and two deaths were precipitated by underlying organic disease in the form of dementia and insulin-dependent diabetes mellitus. The manner of death was not clear cut in two cases where there was evidence of possible accidental death or suicide.

Journal Article↗

An assessment of the potential value of endoscopic ultrasound as a cost-minimizing tool in dyspeptic patients with persistent symptoms.

STUDY AIMS: To quantify resource utilization in dyspeptic patients with persistent symptoms and to determine whether using both the endoscopic and ultrasound capabilities of endoscopic ultrasound could reduce costs. METHODS: Consecutive patients with persistent dyspepsia, after a minimum 1-month trial of acid suppression, underwent endoscopic ultrasound (EUS) and upper endoscopy using the GF-UM20 echo endoscope. Assuming EUS could replace imaging tests which had been requested in addition to upper endoscopy, the hypothetical costs of the EUS-based and upper endoscopy-based strategies were compared. RESULTS: 116 patients with persistent dyspepsia underwent EUS, of whom 64.6 % had > or = 2 imaging procedures, most commonly computed tomography (CT) (70.6 %) and abdominal ultrasound (64.7 %). The number of tests did not correlate strongly with any demographic variables. The fiberoptic echo endoscope provided an adequate endoscopic and ultrasound examination but was damaged by retroflexion. Direct hospital costs were lowest for the EUS-based strategy. Total avoidable cost for 116 patients was $ 4137 to $ 14 121 (or $ 36 to $ 122 per patient), depending on whether upper endoscopy was performed in the non-EUS strategies. CONCLUSIONS: Patients with persistent dyspepsia may undergo multiple abdominal imaging procedures. Clinical variables do not predict the need for additional testing. An EUS-based strategy may reduce overall costs if it prevents additional testing.

Cost-Benefit Analysis↗

Synthesis of peptide-oligonucleotide conjugates: application to basic peptides.

Efficient methods of synthesis of peptide-oligonucleotide conjugates are badly needed for studies of uptake into cells in culture. We describe improvements to the procedures involved in "native ligation" conjugation in solution to extend the method to basic peptides. Further, we describe progress in development of a total solid-phase synthesis approach that makes use of a L-homoserine linker as the key reagent for growing of oligonucleotide and peptide chains on a single solid support.

Amino Acid Sequence↗

The impact of a worksite health promotion program on short-term disability usage.

This study examined the impact of a worksite health promotion program on short-term disability (STD) days in a large telecommunications company. The evaluation used a quasi-experimental, multiple time-series design with between-group comparison of workdays lost due to STD to determine impact. The study period was 3 years and included 1628 employees on STD leave. Self-selected program participants were compared with non-participants on net days lost at three assessment points: the year before the launch of the program, and each of 2 years post-launch. A comprehensive health promotion program was developed to reduce health care costs, improve employee satisfaction, and enhance the employer's image. Key features of the program included reimbursement for employees participating in the Health Risk Assessment and in wellness or fitness activities. Other features included occupational health services, targeted interventions for high-risk employees, self-care materials, and a nurse advice line. Results revealed no significant differences at baseline between participants and non-participants for net days lost while on STD leave. At the post-program launch, non-participants' net days lost significantly increased from 33.2 to 38.1 when controlled for age, gender, job type, tenure, and STD category, whereas the participant group average net days lost decreased from 29.2 to 27.8. After adjusting for baseline differences, we found a 6-day difference between groups, which represented a 20% program impact. This study found that participation in a health promotion reimbursement program had a significant impact on average net days lost for employee STD absence. These findings represented potential savings in excess of $1,371,600 over a 2-year period. Future program evaluation efforts will address the impact on medical care costs related to program participation.

Absenteeism↗

Flow instabilities in a graft anastomosis: a study of the instantaneous velocity fields.

The major cause of arterial bypass graft failure is intimal hyperplasia. Fluctuating wall shear stresses in the graft, which are associated with disturbed flow, are believed to be important factors in the development and localization of intimal hyperplasia. This study, based upon water as the working fluid, has investigated the flow structure inside a 30 degree Y-junction with different fillet radii at the intersection between the graft and the host artery at various Reynolds numbers and distal outlet segment (DOS) to proximal outlet segment (POS) flow ratios. The structure of the flow has been investigated experimentally using particle image velocimetry (PIV). The two-dimensional instantaneous velocity fields confirm the existence of a very complex flow, especially in the toe and heel regions for the different fillet radii and clearly identify features such as sinks, sources, vortices and strong time dependency.

Anastomosis, Surgical↗

Stress and illness in low-income women: the roles of hardiness, John Henryism, and race.

This study examines the stress-illness relationship in a biracial group (African-American and Caucasian-American) of low-income women. Two personality constructs, hardiness and John Henryism, were studied for their possible moderating influences on the stress-illness relationship. One hundred women, with family incomes below the poverty line, completed questionnaires of stress, illness, hardiness, and John Henryism. Hierarchical regression models indicated that hardiness moderated the stress-illness relationship, with high stress, low hardy women having higher levels of illness. In addition, race also moderated the effect of stress, with high stress, Caucasian women having higher levels of illness. However, John Henryism had no effect on stress-related illness in these low-income women. Analyses of additional stress measures indicated that hardy women perceive their external environments as less stressful, although high and low hardy women have similar levels of network stress. Correlational analyses indicated that life-event stress, network stress and low-income concerns were all associated with illness scores. Thus, a range of stress measures are linked to physical illness in low-income women; furthermore, hardiness and being African-American both buffered the effects of stress on illness.

Adaptation, Psychological↗

Effects of risperidone on aberrant behavior of persons with developmental disabilities: I. A double-blind crossover study using multiple measures.

The efficacy of the atypical antipsychotic risperidone was evaluated in the treatment of aberrant behavior (e.g., aggression, self-injury) in 20 individuals with developmental disabilities. A double-blind, crossover design was used to compare risperidone with placebo in a 22-week trial with a 6-month follow-up phase. Based on a 50% reduction in mean Aberrant Behavior Checklist--Community total scores, 50% of the participants were identified as responders. Naturalistic observations of a subset of five individuals showed that for 4 out of 5 participants, risperidone was effective in reducing aberrant behavior. Side effects included weight gain (84% of participants) and sedation (40% of participants). The advantages of conducting a comprehensive analysis of the effects of medication on aberrant behavior are discussed.

Adolescent↗