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Biomedical subjects

J Walsh

Publications and source records attributed to J Walsh.

At least 145 records · Page 8Linked to original sources

Peptide YY immunoneutralization inhibits meal-induced absorption in vivo.

BACKGROUND: Plasma peptide YY (PYY) levels rise after a meal and have recently been shown to increase small bowel-absorption. The purpose of this study was to determine whether immunoneutralization of PYY would block postprandial absorption in vivo. METHODS: Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm) were created in six mongrel dogs. After a 2-week recovery luminal perfusion with an isotonic buffer, containing [14C]-polyethylene glycol as a volume marker, was used to analyze water and sodium flux after an oral meal. Each meal was accompanied by either intravenous anti-PYY (0.5 mg.kg-1.h-1) or nonspecific immunoglobulin IG (control). PYY antibody binding was determined by radioimmunoassay. RESULTS: Displacement studies showed complete PYY neutralization. In control experiments feeding increased absorption of sodium and water in both segments. PYY immunoneutralization had no effect on jejunal absorption but significantly diminished ileal absorption (p < 0.05). CONCLUSIONS: These results suggest that PYY acts selectively in the ileum to increase postprandial fluid and electrolyte absorption after a meal. Agents directed at PYY-stimulated absorption may prove to be of therapeutic benefit in patients with malabsorptive conditions.

Animals↗

The social networks of seriously mentally ill persons receiving case management services.

Social network characteristics, or the patterning of one's social ties, are an important indicator of social support for persons with serious mental illness. Yet relatively few studies have been done on the particular network characteristics of clients receiving case management services in community settings. An understanding of the range of potential and actual social network contacts for persons with serious mental illness is important for targeting interventions to enhance their community supports. In this study, 125 clients of two urban community treatment teams were surveyed by case managers to determine their overall social network size, personal or support network size, and participation in any of 11 network clusters. Results of the study are presented with implications for the social functioning of persons with serious mental illness and suggestions for case manager interventions toward network expansion.

Adult↗

Changing physician prescribing patterns: evaluation of an educational strategy for acute diarrhea in Mexico City.

This paper presents the results of an intervention strategy designed to decrease drug prescription and increase the use of oral rehydration therapy (ORT) in the treatment of acute diarrhea aimed at family medicine practitioners in two primary health care units of the Mexican Social Security Institute. The intervention consisted of six successive stages: 1) Baseline study of prescribing practices by all 69 physicians in both clinics; 2) Training workshop attended by 36 physicians, including a critical analysis of relevant up-to-date literature, review of results of stage I, discussion of a previously designed treatment algorithm for acute diarrhea, and modification of it according to participant's experience; 3) Post-workshop evaluation; 4) Establishment of a peer review committee to discuss the treatment behavior of participating physicians; 5) Mid-term evaluation for 2 months after the committee stopped functioning; 6) Long-term evaluation at 6, 12 and 18 months, of 20 physicians who received the complete intervention (study group) and 20 physicians who received none (control group). The treatment behaviors of the study and control groups were similar on baseline, but differed significantly (P < 0.01) in the post-workshop evaluation. The study group showed a reduction in the use of antibiotics (from 78.8% to 39.3%) and restrictive diets (47.3% to 12.4%), and increased the use of ORT (31.4% to 58.4%) for children younger than 5 years old with acute diarrhea. In the mid-term evaluation, the use of antibiotics by the study group decreased to 27.6%, prescription of restrictive diets decreased to 6.4%, and use of ORT increased to 73.8% (P < 0.01, in all cases). In the long-term evaluation, persistent positive prescribing behavior was still present in the study group, with a significant difference (P < 0.05) compared to the control group, where no modification was found in the prescribing behavior throughout the study. The average proportion of cases treated according to the algorithm by the study group increased in 29.2% (31.3 to 60.5%) after the workshop, and 45.2% (31.3 to 76.5%) after peer review committee. This behavior was maintained during 18 months after the intervention (74%). The control group showed no significant modification in the average proportion of cases treated according to the algorithm during the study (2 years 7 months). The active participation of physicians in the workshop and in the peer review committee was identified as the key to the short and long-term success of the educational strategy.

Acute Disease↗

Sudden unexpected cardiac death among Tasmanian men.

OBJECTIVE: To examine sudden unexpected cardiac death (SUCD) in Tasmanian men and to assess the contribution of these deaths to differences in rates of mortality from ischaemic heart disease (IHD) between regions within Tasmania. DESIGN AND SETTING: Descriptive epidemiological study based in the community. SUBJECTS: Male residents of Tasmania aged 30 to 69 years who died from IHD suddenly and unexpectedly between 1987 and 1989. MAIN OUTCOME MEASURES: Rates and proportions of sudden cardiac death in men who had no prior overt signs of IHD, validated by necropsy and information from the attending doctors. RESULTS: SUCD accounted for approximately 24% of deaths from IHD among men aged 30 to 69 years in Tasmania. The ratios of observed to expected numbers of deaths occurring among manual and nonmanual workers were similar whereas there was an excess of events among men aged less than 65 years who were not working. Examination of data from necropsy reports revealed that 32% of cases showed evidence of previous "silent" myocardial infarction and 63% showed severe coronary artery disease in two or more vessels, with a further 28% having severe single vessel disease. The contribution of SUCD to total mortality from IHD varied from 20% in the north-west region to 25% in the south and 26% in the north, but the limited number of events makes it uncertain whether the variation in the rate of SUCD is significantly different from that for total mortality from IHD. CONCLUSIONS: The proportion of deaths from IHD among men in Tasmania which are sudden and unexpected and the associated necropsy findings are consistent with those described in other population based studies of sudden cardiac death. Non-participation in the workforce was a risk factor in SUCD. As yet, we cannot distinguish whether the higher mortality rates from IHD among men in northern regions of Tasmania (P < 0.01) were due to differences in SUCD or whether the same rate of SUCD obtains in all regions of the State and the differences in mortality from IHD reflect variation in non-sudden deaths and deaths in people with overt IHD.

Adult↗

Immunochemical and immunohistochemical characterization of a synaptic membrane protein that binds the competitive antagonists of NMDA receptors.

An approximately 54-kDa protein that has binding sites for the competitive N-methyl-D-aspartate (NMDA) receptor antagonists 3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) and (+-)-(E)-2-amino-4-propyl-5-phosphonopentenoic acid (CGP 39653) was purified from rat brain synaptic membranes. Polyclonal antibodies to this protein reacted specifically with an approximately 54-kDa protein in synaptic membranes and immunoextracted approximately 60% of [3H]CGP 39653 binding sites associated with solubilized membrane proteins. The antibodies also labeled antigenic sites in the perikaryon and apical and basilar dendrites of pyramidal neurons of the hippocampus and cerebral cortex.

2-Amino-5-phosphonovalerate↗

Specimen-orientated radiography helps define excision margins of malignant lesions detected by breast screening.

Eighty patients with impalpable breast lesions detected by mammographic screening underwent hookwire-guided wide local excision. Excision specimens were orientated with Ligaclips and submitted to radiography; if, on the specimen radiograph, the mammographic lesion crossed any visible margin, further tissue was excised. Clear histological margins were obtained on the initial excision in 52 (68 per cent) of 77 carcinomas. After inspection of the orientated specimen radiograph, further tissue was excised from 22 patients; this significantly increased the rate of complete excision to 86 per cent (P < 0.01). Significantly more patients with invasive cancer had a complete excision than those with ductal carcinoma in situ (52 of 57 versus 14 of 20, P < 0.02).

Breast↗

Microdissection of proximal mouse chromosome 6: identification of RFLPs tightly linked to the ob mutation.

In a previous report, the ob mutation was mapped to a position 5 cM distal to Met on murine Chromosome (Chr) 6 in tight linkage to Cpa. In order to identify additional RFLPs in the region of ob, we have made use of chromosome microdissection of a 6:16 Robertsonian chromosome. In total, 19 RFLPs were used to type 131 progency of a B6D2 ob/ + x B6 spretus ob/ + intercross. Fifteen of the RFLPs mapped to Chr 6, one of which, D6Rck13, was tightly linked to ob. For refinement of the genetic map around ob, 350 obese progency of a B6 Mus castaneus ob/ + intercross were characterized. DNAs from these animals were typed for microsatellite markers from Chr 6 that flank ob. Recombinants were then typed for D6Rck13. D6Rck13 was nonrecombinant among all the progency of both crosses corresponding to 831 meioses. This probe will be of use as an entry point for physical mapping of the ob mutation.

Animals↗

Electrical current paths in acute pericarditis.

The electrocardiographic changes accompanying pericarditis consist of ST elevation in most of the leads of the 12-lead electrocardiogram. The source of this ST elevation is thought to be local inflammatory changes in the epicardium underlying the inflamed pericardium. The current from this area of ST elevation must return to some unaffected region of the heart and this should be associated with a region of ST depression. This current path from the external epicardial surface has been postulated to flow back into the endocardium through the great vessels and atria. To test this hypothesis, 18 patients with pericarditis were studied by body surface potential mapping and inverse epicardial potential distributions were computed. The resultant maps were compared to those of normal people and patients with acute anterior infraction. Epicardial maps from patients with pericarditis showed a region of current flow into the heart over the great vessels and atria in all 18 patients. This pattern was not seen in normal patients or infarction patients and was consistent with the mechanism resulting in ST elevation in pericarditis being one of current flowing from the epicardium out into the thorax and back into the heart through the great vessels and atria.

Acute Disease↗

Beam profile analysis using GafChromic films.

GafChromic film dosimetry techniques were used to evaluate the beam profiles for each collimator of the Leksell Gamma Knife at the University of Kentucky Medical Center. At the conclusion of acceptance testing, representatives from Leksell exposed conventional films for beam profile processing and analysis in Sweden. At the same time, an inhouse technique using GafChromic films was utilized in the analysis of the beam profiles. GafChromic films were irradiated to 100 Gray to provide data in each of the three planes for each collimator size. The films were analyzed using a scanning helium-neon laser densitometer with a small aperture of 5-10 microns. The digitized density profiles were curve-fitted using a PC plotting algorithm. The curve-fitted density profiles were converted to relative dose using a standard calibration curve determined with a conventional cobalt-60 teletherapy beam. The results are in excellent agreement with the conventional film analysis reported by Leksell. The GafChromic method has proven to be an accurate and rapid method of analysis and could be easily incorporated into a quality assurance program.

Calibration↗

A tissue equivalent phantom for stereotactic radiosurgery localization and dose verification.

A tissue equivalent head phantom was utilized in the stereotactic localization and dose verification of radiosurgery procedures with the Leksell Gamma Knife Unit at the University of Kentucky Medical Center. A radiation dose-dependent color-doped gel target was positioned within the head phantom and stereotactically localized using either angiography, CT, or MR techniques. Utilizing standard Gamma Knife treatment procedures, the head phantom was irradiated, which resulted in a color change of the gel tumor at the position of the treatment isocenter and thereby confirmed the localization procedure. Additionally, a radiation dosimeter (thermoluminescent dosimetry--TLD) was positioned within the head phantom and localized using an angiography frame and a standard radiation therapy simulator. The phantom skull measurements and the dosimeter coordinates were entered into the Leksell Gamma Knife dose planning computer (KULA) and an irradiation time for 40 Gy using the 18-mm collimator was determined. The TLD dose evaluations were relatively determined using a cobalt-60 calibration curve. The experimental dose verification results agreed well (+/- 4%) with computer dose estimates.

Algorithms↗

Variable expression of platelet-derived growth factor family proteins in acute lung injury.

During acute lung injury, there is an outpouring of growth factors into the alveolar space that drive local repair and fibrosis. During the remodeling that follows the instillation of bleomycin via the trachea into the adult rat, at least two platelet-derived growth factor (PDGF)-like peptides are released sequentially into lung lining fluid. Groups of four to five animals were killed at 3, 6, 15, and 26 days after exposure to bleomycin and lungs lavaged with isotonic saline. PDGF-like peptides in epithelial lining fluid (ELF) were partially purified by cation exchange chromatography and concentrated. Isolated peptides were analyzed by immunoblotting to determine their molecular weight and immunologic identity. Western blots were probed with polyclonal antibodies to PDGF-BB and PDGF-AA. PDGF-like peptides of two distinct size classes (38-40 kD and 29 kD) were present in alveolar fluid from all rats with lung injury induced by bleomycin. No PDGF-like peptides were found in comparably prepared ELF from control animals. The 38-40 kD peptide was detected only with anti-PDGF-BB antibody; the 29 kD peptide was detected only with anti-PDGF-AA antibody. The presence of these two peptides varied independently with time after exposure to bleomycin. The 38-40 kD peptide was at peak levels at 3 to 6 days. In contrast, the 29 kD peptide was present at all times following injury but with far less variation over time. In parallel with these immunoassays for PDGF-like molecules, there was abundant growth-promoting activity for fibroblasts present in concentrated ELF during the course of injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Determining the site of airway collapse in obstructive sleep apnea with airway pressure monitoring.

Twenty patients with obstructive sleep apnea (OSA) underwent complete polysomnography and simultaneous upper airway pressure monitoring with a custom-made, soft silicone-covered catheter measuring 2.3 mm in diameter. The catheter had four solid-state microtip pressure sensors positioned in the posterior nasopharynx, immediately caudal to the tip of the uvula, at the level of the hyoid bone, and in the midesophagus. The level(s) of airway collapse was determined by changes in the pressure patterns between transducers. In 14 of the 20 patients, airway collapse was confined or initiated at the oropharyngeal region. The obstruction extended to the base of tongue in 7 and to the entire collapsible upper airway in 2 patients. Four patients had collapse at the base of the tongue and 2 had collapse at the hypopharynx. The site of airway collapse remained fairly constant through various sleep stages and positions. Uvulopalatopharyngoplasty (UPPP) and postoperative polysomnography were performed in 4 patients (2 with hypopharyngeal, 1 with base of tongue, and 1 with oropharyngeal airway collapse). Two patients had a favorable response to UPPP.

Female↗

Acid secretion and serum gastrin in normal subjects and patients with duodenal ulcer: the role of Helicobacter pylori.

OBJECTIVES: To compare gastric secretory function in patients with duodenal ulcer and in healthy volunteers with and without Helicobacter pylori infection. METHODS: Basal acid output, peak acid output, meal-stimulated acid output, fasting and meal-stimulated serum gastrin concentrations were measured in 136 healthy volunteers (63 H. pylori positive, 73 H. pylori negative) and 52 duodenal ulcer patients, all but one of whom were H. pylori positive. RESULTS: By multivariate linear regression analysis, H. pylori infection was a significant negative predictor of basal acid output and a positive predictor of fasting and meal-stimulated gastrin concentrations. When compared to truly normal (i.e., H. pylori-negative) control subjects, duodenal ulcer patients had elevated basal acid output, peak acid output, fasting and meal-stimulated gastrin concentrations. CONCLUSIONS: Our results show that in patients with duodenal ulcer disease, hypergastrinemia is largely related to gastric H. pylori infection, whereas acid hypersecretion is due to factors other than H. pylori.

Adult↗

Regional variation in coronary mortality within Tasmania.

OBJECTIVE: To measure regional rates of mortality from ischaemic heart disease (IHD) within Tasmania and to analyse factors associated with regional differences. DESIGN: Descriptive epidemiological study. SETTING: Community-based study. SUBJECTS: Male residents of Tasmania aged 30-69 years dying from IHD between 1986 and 1989. MAIN OUTCOME MEASURES: Coronary death as coded by the Australian Bureau of Statistics and place of death validated by hospital and community data. RESULTS: This study identifies substantial differences in coronary death rates among the three Health Regions of Tasmania. These differences are real and are not caused by variations in diagnostic or coding practices between regions. The two northern Health Regions, which represent approximately 52% of the total population, account for 98% of the excess mortality from IHD in Tasmania compared with the national rate. More detailed analysis of these differences suggests that variation in the number of deaths occurring in hospital contributes significantly to the regional differences in death rate from IHD. CONCLUSION: Rates of coronary mortality in Tasmania have been significantly higher than in all other Australian States for much of the past decade because of a higher death rate within the population of the northern half of Tasmania. Differences in mortality rates between regions in Tasmania provide a focus for further study into the causes of the unacceptably high rates of death from IHD in Tasmania and underline the need for the funding of a coronary register in Tasmania.

Adult↗