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Biomedical subjects

J Walsh

Publications and source records attributed to J Walsh.

At least 55 records · Page 3Linked to original sources
PubMed2000

Studies of renal injury III: lipid-induced nephropathy in type II diabetes.

UNLABELLED: Studies of renal injury III: Lipid-induced nephropathy in type II diabetes. BACKGROUND: Nephrotoxicity from elevated circulating lipids occurs in experimental and clinical situations. We tested the hypothesis that lipid-induced nephropathy causes advanced renal failure in rats with type II diabetes and dyslipidemia. METHODS: First generation (F1) hybrid rats derived from the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) and the LA/NIH-corpulent rat (LA/N-fa) were studied for 41 weeks while being on specific diets. Group 1 (14 rats) ingested 11.5% protein, 47.9% fat, and 40.6% carbohydrate. Group 2 (8 rats) ingested 26.9% protein, 16.7% animal fat, and 56.4% carbohydrate, and group 3 (20 rats) ingested 20.2% protein, 40.4% soy and coconut oil, and 39.4% carbohydrate. RESULTS: Hyperglycemia was more severe in rat groups 1 and 2 than in group 3. In contrast, circulating cholesterol and hydroperoxide levels were highest in group 3, intermediate in group 2, and lowest in group 1. Group 3 had severe renal failure secondary to glomerulosclerosis and tubulointerstitial disease, with striking deposition of the lipid peroxidation stress biomarker 4-hydroxynonenal in glomeruli and renal microvessels. Moreover, in group 3, increased arterial wall thickness also connoted vascular injury. In contrast, the glycoxidation stress biomarkers pentosidine and carboxymethyl-lysine were preferentially localized to renal tubules of hyperglycemic rats in groups 1 and 2 and did not segregate with the most severe renal injury. Glomerular and interstitial fibrosis was accompanied by proportional increases in renal transforming growth factor-beta1 levels, which were threefold higher in the hypercholesterolemic rats of group 3 than in the hyperglycemic rats of group 1. CONCLUSIONS: Acquisition of non-nodular glomerular sclerosis and tubulointerstitial disease is dependent on lipoxidation stress in rats with type II diabetes. On the other hand, in the absence of hypercholesterolemia, prolonged glycoxidation stress does not appear to be uniquely nephrotoxic.

Animals↗
PubMed2000

How effective is syndromic management of STDs?: A review of current studies.

BACKGROUND: Studies of the accuracy of syndromic management have demonstrated widely varying results depending upon gender, location of infection, risk group, organisms, among other factors. GOAL: To review current knowledge about syndromic management of sexually transmitted diseases (STDs) and to make recommendations about the strengths and weaknesses of different syndromic management algorithms. STUDY DESIGN: The authors identified articles and abstracts about the syndromic management of STDs. Evaluation of the effectiveness of algorithms for urethral discharge, genital ulcer disease, and vaginal discharge was based primarily on published sensitivity and specificity data. RESULTS: Overall, algorithms for the diagnosis and treatment of urethral discharge and genital ulcer disease in men had high sensitivities or cure rates (urethral discharge, 87-99%; genital ulcer disease, 68-98%). The sensitivities for the algorithms for vaginal discharge ranged from 73% to 93% among women presenting with symptoms of vaginal discharge, and from 29% to 86% among women not presenting with symptoms. Vaginal discharge was not found to be an effective indicator of cervical infection and, therefore, is not an independently effective screening tool to detect women with cervical infection, especially in low-risk or asymptomatic populations. Incorporating risk scores can improve the accuracy of algorithms to detect cervical infection. CONCLUSIONS: Algorithms for urethral discharge and genital ulcer disease can be effective in STDs. The current algorithms for vaginal discharge are not highly effective in detecting gonorrhea and chlamydia in women; risk scores can improve their efficacy, but must be tailored to reflect community risks. Without attention to the qualitative aspects of STD syndromic management, these methods will likely have even less accuracy than the studies reviewed above. There remains an urgent need for the development of an affordable, rapid, and effective diagnostic technique that will improve STD detection in resource-poor settings.

Adolescent↗
PubMed2000

A pilot study examining injuries in elite gaelic footballers.

OBJECTIVES: To quantify injuries in elite gaelic footballers and to determine the nature, sites, and outcome of injuries and the possible risk factors involved. METHODS: Information on injuries was collected from six elite gaelic football teams by a questionnaire. The footballers were asked to recall injuries over the preceding six month period. RESULTS: A total of 88 out of 107 subjects sustained injuries over the study period. Ninety five injuries were recorded, giving an incidence rate of 1.78 injuries per subject per year, of which 35% were recurring. It was found that 35% of injuries were sustained during training sessions. Lower body injuries predominated (77%), the ankle being the most commonly injured anatomic site. Most injuries were soft tissue in nature: muscle, 33%; ligament, 32%; tendon, 16%. The most common situations giving rise to injuries were collision (22%) and twist/turn (19%). Foul play only accounted for about 6% of injuries. Mean time off play as a result of injury was 17.3 days, and hospital admission was necessary for 15% of the injuries. CONCLUSION: Despite the limitations of a retrospective of this nature, the study provides useful and important information on injuries in gaelic footballers.

Adult↗
PubMed2000

Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by acting in the brain.

The site of action of peripheral peptide YY (PYY)-induced inhibition of vagally stimulated gastric acid secretion was studied using immunoneutralization with PYY antibody in urethan-anesthetized rats. Gastric acid secretion (59+/-7 micromol/90 min) stimulated by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368 (14 pmol/rat) was dose-dependently inhibited by 52%, 69%, and 83% by intravenous infusion of 0.25, 0.5, and 1.0 nmol. kg(-1) x h(-1) PYY, respectively. PYY or PYY(3-36) (2.4 pmol/rat) injected intracisternally also inhibited the acid response to intracisternal RX-77368 by 73% and 80%, respectively. Intravenous pretreatment with PYY antibody (4.5 mg/rat), which shows a 35% cross-reaction with PYY(3-36) by RIA, completely prevented the inhibitory effect of intravenously infused PYY (1 nmol x kg(-1) x h(-1)). When injected intracisternally, the PYY antibody (280 microg/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol x kg(-1) x h(-1))-induced inhibition of acid response to intracisternal RX-77368 by 64% and 93.5%, respectively. These results provide supporting evidence that peripheral PYY inhibits central vagal stimulation of gastric acid secretion through an action in the brain.

Animals↗
PubMed2000

Rates of GDP referral of complete dentures to a teaching hospital.

PURPOSE OF STUDY: To identify areas and sites of excessive referral of complete dentures by GDPs, allowing for factors which might distort referral rates. METHODS: Two hundred and six consecutive valid referrals of patients over the age of 50 years with complete dentures to a local dental teaching hospital and originating from the 29 Sheffield electoral wards were audited from the beginning of 1995 to the end of 1997. The referring practitioner and electoral ward were recorded. RESULTS: Referral rates were calculated according to the size of the 50+ population within each ward and were found to be normally distributed, following exclusion of two wards with much higher referral rates than normal (3.5 and 6 SDs [standard deviations] from the mean). After calculating mean numbers referred per full-time equivalent (FTE) GDP for all wards, practices and practitioners originating excessive numbers of referrals within a high-referring ward could be identified. CONCLUSION: After taking into account factors which might permit a high referral rate to be acceptable, practices with inappropriately high referral rates can be identified and remedial teaching need pinpointed.

Aged↗
PubMed2000

Sexual maturation and control issues among sexually abused and non-abused anorexia patients.

OBJECTIVES: To assess the relative salience of the maintenance of control and the avoidance of sexual maturation as sources of motivation for maintaining pathological eating behaviours among sexually abused anorexic patients. DESIGN/METHODS: A two-factor mixed experimental design was employed. Three independent groups (sexually abused anorexics (N = 12); non-abused anorexics (N = 9); non-anorexic/non-abused controls (N = 12)) constituted the between-subjects factor. Allocation to abuse/non-abuse group was dependent upon replies to a questionnaire-based measure of unwanted sexual experience. The within-subjects factor comprised three conditions in which words of various colours were presented to participants for colour-naming (Stroop, 1935). The conditions were represented by lists of neutral words, sexual maturation words, and control-related words. Two trials were carried out in each condition and mean response times were measured. RESULTS: Within-group analyses revealed that interference was greater from sexual maturation words than from control-related words among the sexually-abused anorexics, but of equal magnitude among non-abused counterparts. Between-groups analyses found that abused patients experienced marginally greater cognitive interference from sexual maturation words than the non-abused patients. CONCLUSION: Theoretically, support is offered for elaborated schematic models of cognitive processing. Clinically, treatment interventions may need to pay particular attention to issues of sexual maturation among sexually abused anorexic patients.

Adolescent↗
PubMed2000

Formation and current results of a patient-organized registry for alpha(1)-antitrypsin deficiency.

BACKGROUND: Significant challenges exist to investigating uncommon illnesses because too few patients are seen at any single clinical center to permit appropriate research studies. Recognizing this impediment to clinical research in alpha(1)-antitrypsin deficiency, the Alpha One Foundation, a patient-organized research foundation, has collaborated with clinician-scientists to organize a voluntary registry of individuals with alpha(1)-antitrypsin deficiency. PURPOSE: To facilitate clinical research in alpha(1)-antitrypsin deficiency by organizing a registry of affected individuals willing to be approached to participate in clinical studies. METHODS: Elements of the Alpha One Foundation Research Network Registry include a Medical and Scientific Advisory Committee, composed of physician-investigators and patient advocates, designated clinical resource centers at medical institutions with expertise in the management of individuals with alpha(1)-antitrypsin deficiency, and a data coordinating center with responsibility for database management and analysis. Questionnaires requesting information about demographic features, alpha(1)-antitrypsin phenotype, smoking history, and health-care utilization were distributed to prospective registrants through the following channels: mailings from the Alpha One Foundation; mailings from the clinical resource centers; and distribution by home-care and pharmaceutical companies. Information from this questionnaire formed the basis of the initial registry database. RESULTS: Between May 1997 and June 1999, 7,789 forms were distributed, and forms were returned by 712 unique registrants. Registrants have the following characteristics: mean (+/- SD) age, 49.3+/-13.2 years; women, 47.7%; white, 96.2%; PI*ZZ phenotype, 70.7%; ex-smokers, 73.3%; COPD patients, 87.2% (emphysema patients, 54.2%; chronic bronchitis patients, 33%); and self-reported liver disease, 6.4%. The mean number of physician visits reported by registrants in the preceding 12 months was 7.8+/-9.4, 59% reported currently receiving IV augmentation therapy, and 35% reported using supplemental oxygen at home. Examples of ongoing research studies using this unique database include: (1) a case-control study to evaluate occupational risk factors for obstructive lung disease in individuals with alpha(1)-antitrypsin deficiency and (2) a study to evaluate the health-care costs for affected individuals. CONCLUSIONS: A registry currently including 712 individuals with alpha(1)-antitrypsin deficiency has been organized through a collaboration between physician-investigators and a patient-organized research foundation. Use of the registry has already facilitated studies that were previously difficult because of the paucity of identifiable study subjects. The registry cohort promises to provide an important resource for future clinical and epidemiologic studies.

Clinical Trials as Topic↗
PubMed2000

The clinical enquiry service; benign intracranial hypertension.

Considering how uncommon the condition is (3.3 cases per 100 000 women aged 15 to 44 years) the CEU has received a surprising number of enquiries about contraceptive options for women with a diagnosis of idiopathic benign interacranial hypertension.

Adolescent↗
PubMed2000

Win-win mentoring.

Learn strategies to build and enhance mentor-protégé relationships, expand your experience, and help new nurses develop.

Humans↗
PubMed2000

Recognizing and managing boundary issues in case management.

Much of the literature on worker-client boundaries in clinical practice is based on assumptions that the relationship between the two parties is structured and formal. These assumptions do not always apply in community-based case management practice, where the worker and client interact in a wide variety of settings and circumstances. The relative informality of case management makes the establishment of appropriate worker-client boundaries both critical and difficult. In this article key principles for recognizing and managing boundary issues are presented and discussed.

Case Management↗
PubMed1999

Localization of cells preferentially expressing GAD(67) with negligible GAD(65) transcripts in the rat hippocampus. A double in situ hybridization study.

Two major forms of glutamic acid decarboxylase (GAD) are present in the mammalian brain, a 65-kDa isoform (GAD(65)) and a 67-kDa isoform (GAD(67)), and it is usually assumed that all GABAergic neurons contain both. The two forms have not yet been colocalized to the same neurons, because the GAD(65) protein is found almost exclusively in axon terminals, while GAD(67) is found predominantly in the cell body. Using double in situ hybridization (DISH) with both radioactive [35S] and non-radioactive (digoxigenin, DIG) probes, the distributions of GAD(65) and GAD(67) mRNA have been simultaneously examined in the rat hippocampus. The results suggest that [35S] radioprobes are slightly more sensitive than DIG probes, and that the reversal of labels is necessary in DISH studies to determine whether a neuronal subtype which expresses only one isoform of GAD may be present. The data indicate that the majority of cells (90%) showing labeling were labeled for both GAD(65) and GAD(67) mRNA. In sectors CA1 and CA3 approximately 5-10% of the cells positive for GAD(67) showed little or no detectable GAD(65) mRNA. In the hilus, however, GAD(65) levels were higher, and all cells seem to express both GAD(65) and GAD(67) mRNA. Taken together, these results support the view that most GABAergic neurons in the hippocampus express both GAD(65) and GAD(67). However, it appears that some interneurons in the CA subfields differ from "classic" GABAergic interneurons by preferentially expressing the 67-kDa isoform of GAD under baseline conditions, with GAD(65) mRNA levels very low or absent.

Animals↗
PubMed1999

Oxidation regulates the inflammatory properties of the murine S100 protein S100A8.

The myeloid cell-derived calcium-binding murine protein, S100A8, is secreted to act as a chemotactic factor at picomolar concentrations, stimulating recruitment of myeloid cells to inflammatory sites. S100A8 may be exposed to oxygen metabolites, particularly hypochlorite, the major oxidant generated by activated neutrophils at inflammatory sites. Here we show that hypochlorite oxidizes the single Cys residue (Cys41) of S100A8. Electrospray mass spectrometry and SDS-polyacrylamide gel electrophoresis analysis indicated that low concentrations of hypochlorite (40 microM) converted 70-80% of S100A8 to the disulfide-linked homodimer. The mass was 20,707 Da, 92 Da more than expected, indicating additional oxidation of susceptible amino acids (possibly methionine). Phorbol 12-myristate 13-acetate activation of differentiated HL-60 granulocytic cells generated an oxidative burst that was sufficient to efficiently oxidize exogenous S100A8 within 10 min, and results implicate involvement of the myeloperoxidase system. Moreover, disulfide-linked dimer was identified in lung lavage fluid of mice with endotoxin-induced pulmonary injury. S100A8 dimer was inactive in chemotaxis and failed to recruit leukocytes in vivo. Positive chemotactic activity of recombinant Ala41S100A8 indicated that Cys41 was not essential for function and suggested that covalent dimerization may structurally modify accessibility of the chemotactic hinge domain. Disulfide-dependent dimerization may be a physiologically significant regulatory mechanism controlling S100A8-provoked leukocyte recruitment.

Animals↗
PubMed1999

Making Cairo work.

The 1994 International Conference on Population and Development set broad new goals for family planning and reproductive health. The resources available to fund these much needed programmes, however, are much smaller than was originally calculated. To divide the limited budgets for the maximum health impact, likely resource flows need to be set against the cost of various family planning and reproductive health interventions. Preliminary analysis suggests that selection of cost-effective delivery of family planning services would still meet much of the need for family planning, and that some progress could be made towards improved control of sexually transmitted diseases.

Congresses as Topic↗
PubMed1999

Relationship between tumor extracellular fluid exposure to topotecan and tumor response in human neuroblastoma xenograft and cell lines.

PURPOSE: We have reported a 6-fold difference in the topotecan (TPT) lactone systemic exposure achieving a complete response in the human neuroblastoma xenografts NB-1691 and NB-1643. However, the relationship between tumor extracellular fluid (ECF) exposure to TPT and the antitumor activity in xenograft and in vitro models has not been established. METHODS: TPT was given i.v. to mice bearing NB-1691 and NB-1643 tumors. Prior to dosing, microdialysis probes were placed in tumors of mice bearing NB-1691 and NB-1643 tumors. Plasma and tumor ECF concentrations of TPT lactone were assayed by high performance liquid chromatography. The inhibitory concentration (IC50) was determined for NB-1691 and NB-1643 cell lines in vitro. RESULTS: The TPT AUC(ECF) values determined for NB-1691 (n = 10) and NB-1643 (n = 11) were 7.3 +/- 0.84 and 25.6 +/- 0.76 ng h ml(-1), respectively (P < 0.05). TPT tumor ECF penetration in NB-1691 and NB-1643 was 0.04 +/- 0.04 and 0.15 +/- 0.11 (P < 0.05), respectively. The IC50 values recorded after 6 h of TPT exposure daily for 5 consecutive days for NB-1691 and NB-1643 were 2.7 +/- 1.1 and 0.53 +/- 0.19 ng/ml, respectively (P < 0.05). CONCLUSIONS: NB-1643 was more sensitive in vitro than NB-1691, and at similar plasma TPT exposures, NB-1643 had a greater degree of TPT tumor ECF exposure and penetration as compared with NB-1691. Potential factors affecting tumor TPT ECF disposition include tumor vascularity, capillary permeability, and interstitial pressure. The clinical importance of this study is underscored by the need to select anticancer agents with a high capacity for tumor penetration and to optimize drug administration to increase tumor penetration.

Animals↗