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Biomedical subjects

R Quinn

Publications and source records attributed to R Quinn.

At least 19 recordsLinked to original sources
PubMed2002

Gastric bypass model in the obese rat to study metabolic mechanisms of weight loss.

A rat model replicating gastric bypass with Roux-en-Y (GB) as used in morbidly obese patients, evolved in our laboratory in stages, using the Zucker rat as an obese model (GB) is presented. In the final model, a 20% gastric fundic pouch to limit the gastric reservoir was created using two staple lines (Ethicon). A 4- to 5-mm end-to-side gastrojejunostomy and a 6- to 8-mm jejunojejunostomy, at 10 cm length of the Roux-en-Y limb, placed 16 cm below the ligament of Treitz, was hand sewn to create a limited area of nutrient digestion and absorption. Controls underwent sham operation. Rats were divided into: (i) sham-op ad lib-fed (Control); (ii) GB; and (iii) sham-op pair fed (PF) in two experiments. In Experiment 1, 24 Zuckers (control n = 8; GB n = 8; PF n = 8) were studied to assess the effectiveness of the model for weight loss. In Experiment 2, 24 Zuckers (8/group) were studied to confirm the effects of the operation on weight loss and on metabolic parameters. Boost was given for 4 days starting 24 h postop and then ground chow was given. Daily food intake (FI), meal size (MZ), meal number (MN), and body weight (BW) were measured. Rats were sacrificed on Day 20 in Experiment 1 and on Day 10 in Experiment 2. Serum metabolites and body fat weight were measured. Data were evaluated using Student's t test. Controls steadily gained BW (5.2-6.1 g/day), reaching approximately 500 g. In GB: FI, MZ, MN, BW, glucose, free fatty acids, insulin, and body fat decreased (P < 0.05). In PF: BW, insulin, triglycerides, and body fat decreased. A dependable, reproducible gastric bypass with Roux-en-Y obesity model was developed. This permits the study of biochemical and eventually molecular mechanism(s) of weight loss resulting from the operation.

Adipose Tissue↗
PubMed2001

CREB regulates hepatic gluconeogenesis through the coactivator PGC-1.

When mammals fast, glucose homeostasis is achieved by triggering expression of gluconeogenic genes in response to glucagon and glucocorticoids. The pathways act synergistically to induce gluconeogenesis (glucose synthesis), although the underlying mechanism has not been determined. Here we show that mice carrying a targeted disruption of the cyclic AMP (cAMP) response element binding (CREB) protein gene, or overexpressing a dominant-negative CREB inhibitor, exhibit fasting hypoglycaemia [corrected] and reduced expression of gluconeogenic enzymes. CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo. Overexpression of PGC-1 in CREB-deficient mice restored glucose homeostasis and rescued expression of gluconeogenic genes. In transient assays, PGC-1 potentiated glucocorticoid induction of the gene for phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in gluconeogenesis. PGC-1 promotes cooperativity between cyclic AMP and glucocorticoid signalling pathways during hepatic gluconeogenesis. Fasting hyperglycaemia is strongly correlated with type II diabetes, so our results suggest that the activation of PGC-1 by CREB in liver contributes importantly to the pathogenesis of this disease.

Adenoviridae↗
PubMed2001

Predicting the risk of death from heart failure after coronary artery bypass graft surgery.

UNLABELLED: Heart failure is the most common cause of death among coronary artery bypass graft (CABG) patients. In addition, most variation in observed mortality rates for CABG surgery is explained by fatal heart failure. The purpose of this study was to develop a clinical risk assessment tool so that clinicians can rapidly and easily assess the risk of fatal heart failure while caring for individual patients. Using prospective data for 8,641 CABG patients, we used logistic regression analysis to predict the risk of fatal heart failure. In multivariate analysis, female sex, prior CABG surgery, ejection fraction <40%, urgent or emergency surgery, advanced age (70-79 yr and >80 yr), peripheral vascular disease, diabetes, dialysis-dependent renal failure and three-vessel coronary disease were significant predictors of fatal postoperative heart failure. A clinical risk assessment tool was developed from this logistic regression model, which had good discriminating characteristics (receiver operating characteristic clinical source = 0.75, 95% confidence interval: 0.71, 0.78). IMPLICATIONS: In contrast to previous cardiac surgical scoring systems that predicted total mortality, we developed a clinical risk assessment tool that evaluates risk of fatal heart failure. This distinction is relevant for quality improvement initiatives, because most of the variation in CABG mortality rates is explained by postoperative heart failure.

Aged↗
PubMed2001

Integrating public health into medical education: community health projects in a Primary Care Preceptorship.

Physicians must integrate care of populations with the care of individual patients to function optimally in today's health care environment. With this understanding, medical school curricula are increasingly addressing the skills and knowledge of public health along with those of clinical medicine. The University of Utah School of Medicine in 1997 revised its four-year curriculum to increase the teaching of topics needed by future physicians, including public health. This report describes one course in the curriculum, the Primary Care Preceptorship (PCP), a fourth-year, six-week required rotation that assists students in learning about the health needs of a community along with providing primary care for its individual residents. Students in the PCP spend approximately 60% of their time in clinical primary care and 40% completing a community health project. In the first year of the PCP, 32 students completed projects on clinical problems, 27 on community health needs assessment, 26 on patient education, and 15 on epidemiology.

Community Health Services↗
PubMed2001

Intra-operative quality assessment of coronary artery bypass grafts.

Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery.

Anastomosis, Surgical↗
PubMed2000

Improved stable isotope dilution-gas chromatography-mass spectrometry method for serum or plasma free 3-hydroxy-fatty acids and its utility for the study of disorders of mitochondrial fatty acid beta-oxidation.

BACKGROUND: Disorders of fatty acid oxidation (FAO) are difficult to diagnose, primarily because in many of the FAO disorders measurable biochemical intermediates accumulate in body fluids only during acute illness. Increased concentrations of 3-hydroxy-fatty acids (3-OH-FAs) in the blood are indicative of FAO disorders of the long- and short-chain 3-hydroxy-acyl-CoA dehydrogenases, LCHAD and SCHAD. We describe a serum/plasma assay for the measurement of 3-OH-FAs with carbon chain lengths from C(6) to C(16). METHODS: We used stable isotope dilution gas chromatography-mass spectrometry (GC-MS) with electron impact ionization and selected ion monitoring. Natural and isotope-labeled compounds were synthesized for the assay. RESULTS: The assay was linear from 0.2 to 50 micromol/L for all six 3-OH-FAs. CVs were 5-15% at concentrations near the upper limits seen in healthy subjects. In 43 subjects, the medians (and ranges) in micromol/L were as follows: 3-OH-C(6), 0.8 (0.3-2.2); 3-OH-C(8), 0.4 (0.2-1.0); 3-OH-C(10), 0.3 (0.2-0.6); 3-OH-C(12), 0.3 (0.2-0.6); 3-OH-C(14), 0.2 (0.0-0.4); and 3-OH-C(16), 0.2 (0.0-0.5). 3-OH-FAs were increased in infants receiving formula containing medium chain triglycerides. Two patients diagnosed with LCHAD deficiency showed marked increases in 3-OH-C(14) and 3-OH-C(16) concentrations. Two patients diagnosed with SCHAD deficiency showed increased shorter chain 3-OH-FAs but no increases in 3-OH-C(14) to 3-OH-C(16). CONCLUSION: Measuring blood concentrations of the 3-OH-FAs with this assay may be a valuable tool for helping to rapidly identify deficiencies in LCHAD and SCHAD and may also provide useful information about the status of the FAO pathway.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

How do General Practitioners learn of their patient's deaths?

OBJECTIVES: To investigate the methods by which General Practitioners learn, or do not learn, of their patients deaths, when the deaths occur in an institution in which the General Practitioner has no direct role in their care. DESIGN: Using a semi-structured telephone questionnaire the relevant General Practitioners were asked of the method, if any, by which they had learned of their patients deaths, and their views on this. SETTING: Sligo, Ireland. RESULTS: In 6 (16%) of the 37 cases, the GP was informed of the death within one working day by hospital staff. In 22 (59%) of the cases, the GP had learned of the death through other means. In 9 (26%) of the cases the GP had not learned of the death. In 28 (75%) of the cases, the GPs were dissatisfied with either the fact that they did not know of the death, or even if they did know, the method by which they learned of the patients death. CONCLUSION: General Practitioners, for a variety of reasons, wish to learn of their patient's deaths within a short length of time of such deaths occurring. When deaths occur in an institution in which the GP has no direct role in the care of their patients, the information is not forwarded to the GP within a reasonable length of time in the vast majority of cases. Such institutions need to realise the importance of this simple act, and to make it routine to forward the information.

Attitude of Health Personnel↗
PubMed1997

Use of the internal mammary artery graft in Northern New England. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: There is evidence that patients who receive an internal mammary artery graft (IMA) during coronary artery bypass surgery have increased long-term survival. However, an IMA is not used in all patients. METHODS AND RESULTS: We studied the use of IMA grafts among 7944 patients undergoing initial, isolated coronary artery bypass surgery in Maine, New Hampshire, and Vermont from 1992 to 1995. Overall, the IMA graft was used in 82% of patients; of these, 97.2% had left IMA grafts. The use of the IMA graft varied considerably by patient and disease factors. Women received an IMA graft significantly less often (76% versus 85% in men, P<.01). Older patients (> or =75 years) were less likely to receive an IMA graft (67% versus 86%, P<.001). Smaller BSA was also associated with lower rates of IMA grafts in both sexes; however, men and women with BSA <1.8 m2 received an IMA graft at about the same rate. In general, more sick and more urgent patients had lower rates of IMA use. Patients with left ventricular ejection fraction <40% received an IMA less often than those with an ejection fraction > or =60% (77% versus 85%, P<.01). Patients with a greater number of diseased coronary vessels received an IMA more often (one, 78%; two, 82%; three, 85%). IMA use varied significantly by priority of surgery, with elective patients receiving an IMA 88% of the time, urgent 83%, and emergent 51% (Ptrend<.01). The use of the IMA graft varied from 42% to 95% among individual surgeons. Surgeons were consistent in their patterns of IMA graft use for specific risk groups. All surgeons had lower rates of IMA use among older patients, lower rates of IMA among women, and lower rates of IMA use among emergent or urgent patients. However, "low-use" surgeons had consistently lower rates of use within these patient groups. The overall rate of IMA graft use increased from 76% in 1992 to 86% in 1995 (Ptrend<.001). IMA graft use increased in all five centers and in all patient subgroups. The largest increases in use were seen among women (from 69% to 83%), among patients older than 75 years (from 55% to 75%), and in emergent patients (from 40% to 72%). CONCLUSIONS: This regional prospective study of IMA graft use in initial coronary artery bypass surgery describes substantial variability in patient groups receiving an IMA as well as increasing IMA graft use over time. It also suggests that the practice patterns of surgeons are an important determinant of IMA use. These data indicate that even more patients could benefit from the use of this technique.

Aged↗
PubMed1996

Undetectable IgE responses after respiratory syncytial virus infection.

Sequential nasopharyngeal secretions were collected from 81 infants from one day to three months after admission to hospital with respiratory syncytial virus (RSV) infection. Samples from 21 infants were assayed for anti-RSV IgE in an antigen capture ELISA assay. No IgE antibodies were detected although an assay of IgA antibodies carried out in parallel by a similar technique detected IgA antibodies in the secretions of all patients tested. Neither prior absorption of IgA or IgG, concentration of the secretions by freeze drying, nor enzyme amplification of the assay revealed any virus specific IgE. Using an antibody capture ELISA with a sensitivity of 0.85 IU/ml, IgE could be detected in sequential secretions of only one of the 81 RSV infected infants studied. Further testing of the secretions from 12 of these patients and those of a further 15 using an enzyme amplified assay with a sensitivity of 0.1 IU/ml revealed no further positives. Low concentrations of IgE were found in the sera of the majority of infants with RSV infection but they did not differ from those of virus negative children of a similar age collected between RSV epidemics. No rise in mean serum IgE concentrations between acute and convalescent samples was observed. No virus specific IgE was detected in the sera of any infant using the enzyme amplified antigen capture ELISA.

Antibodies, Viral↗
PubMed1994

General practice vocational training and public health medicine: a novel collaboration.

The incorporation of a module of public health teaching into a general practice vocational training programme is described. This programme is itself innovative in that in addition to the 2 years of hospital-based training, it provides 2 years of community-based training. While the curriculum of the public health module is evolving with time, the objectives have remained the same, and are being met. The module has been appraised by external observers, and has been evaluated by participating trainees. The public health module is now an established feature of the Sligo general practice training programme.

Community Medicine↗
PubMed1994

Sacral insufficiency fractures in the elderly.

Sacral insufficiency fractures are not uncommon in elderly patients. We have diagnosed 20 cases in a five-year period, and have reviewed the clinical records, radiographs, CT and bone scans. We also assessed the degree of osteoporosis by measuring bone density using dual-energy X-ray absorptiometry and bone histomorphometry, and monitored the patients' functional outcome. Bone scans were positive in all 20 patients, CT showed a fracture or sclerosis in 7 of 12 patients and was useful in excluding malignancy. Plain radiographs were the least helpful, showing sclerosis in only 4 of the 20 patients. Involutional osteoporosis with a reduced bone formation rate was the most common underlying cause. Seventeen patients had complete resolution of pain within nine months, and no patient lost independence in daily activities. Increased awareness of these fractures may help to avoid unnecessary investigation and treatment. Bedrest and analgesia followed by rehabilitation provide good relief of symptoms.

Absorptiometry, Photon↗
PubMed1993

Simulations of the Viking Gas Exchange Experiment using palagonite and Fe-rich montmorillonite as terrestrial analogs: implications for the surface composition of Mars.

Simulations of the Gas Exchange Experiment (GEX), one of the Viking Lander Biology Experiments, were run using palagonite and Fe-rich montmorillonite as terrestrial analogs of the Martian soil. These terrestrial analogs were exposed to a nutrient solution of the same composition as that of the Viking Landers under humid (no contact with nutrient) and wet (intimate contact) conditions. The headspace gases in the GEX sample cell were sampled and then analyzed by gas chromatography under both humid and wet conditions. Five gases were monitored: CO2, N2, O2, Ar, and Kr. It was determined that in order to simulate the CO2 gas changes of the Viking GEX experiment, the mixture of soil analog mineral plus nutrient medium must be slightly (pH = 7.4) to moderately basic (pH = 8.7). This conclusion suggests constraints upon the composition of terrestrial analogs to the Mars soil; acidic components may be present, but the overall mixture must be basic in order to simulate the Viking GEX results.

Aluminum Silicates↗
PubMed1993

A double blind randomised trial of low power laser treatment in rheumatoid arthritis.

OBJECTIVES: To define the value of low power laser treatment in small joint rheumatoid arthritis. METHODS: Twenty five women with active disease were recruited. The metacarpophalangeal and proximal interphalangeal joints of one hand were treated with 12 J/cm2 for 30 s with a gallium-aluminium-arsenate laser. The other hand received a sham laser treatment designed so that neither therapist nor patient could distinguish the active laser from the sham laser. Each patient received 12 treatments over four weeks. The following parameters were measured: pain as assessed by visual analogue scale; range of joint movements; grip strength; duration of early morning stiffness, joint circumference, Jebsen's hand assessment; drug usage; total swollen joint counts; Arthritis Impact Measurement Scales; three phase bone scans; haematological and serological tests. RESULTS: A total of 72% of patients reported pain relief but this reduction was reported equally in both hands. No significant changes were seen in other clinical, functional, scintigraphic, or laboratory features. Neither patients nor staff were able to detect which hand was treated with the active laser. CONCLUSION: When this specific laser and dose regimen was used, low power laser treatment had no objective effect on patients with rheumatoid arthritis. It did appear to produce analgesia through a powerful placebo effect.

Adult↗
PubMed1992

Distinct hemagglutinin and neuraminidase epitopes involved in antigenic variation of recent human parainfluenza virus type 2 isolates.

A panel of fourteen neutralizing anti-HN monoclonal antibodies (mAbs) to the prototype Greer strain of human parainfluenza virus type 2 (PI2) was used to determine the extent of antigenic variation in recent virus isolates. Competitive binding analysis with the mAbs indicated the presence of at least five distinct antigenic sites (I to V) on the HN glycoprotein molecule. MAbs recognizing different antigenic sites were found to be associated with the hemagglutinin (sites I, IV and V), hemagglutinin and neuraminidase (site II), or neuraminidase (site III) activities. The location of two distinct epitopes identifying the neuraminidase sites (II and III) was further verified from the generation of escape mutants. Antibodies directed to sites I and III failed to show any detectable binding or neutralizing activity against a number of natural PI2 virus isolates collected in Texas between 1986 and 1987. Interestingly, these natural variants, unlike the prototype virus, did not show any detectable neuraminidase activity with fetuin as a substrate and the enzyme activity was only detected with N-acetylneuramin-lactose as an alternative substrate. Despite the observed variation in the antigenic sites, primary infection with the prototype virus or the natural variants generated a protective immune response against challenge infection with the other virus strains.

Animals↗
PubMed1989

Zidovudine-induced fever.

Zidovudine (3'-azido-3'deoxythymidine, AZT, Retrovir) is the first antiretroviral drug to demonstrate clinical efficacy for symptomatic human immunodeficiency virus infection. In a large, placebo-controlled trial, nausea and hematologic toxicity, but not fever, occurred more frequently in zidovudine- than in placebo-treated patients. However, in an open label study, fever severe enough to halt zidovudine administration occurred in 10% of 70 acquired immune deficiency syndrome (AIDS) patients receiving the drug. We now describe three AIDS patients with severe zidovudine-induced fever in whom other causes of fever were excluded. Zidovudine-induced fever was confirmed in each case by drug rechallenge. Using an enzyme immunoassay, we detected IgM antibodies directed against a zidovudine-serum protein conformational determinant in one of these three patients. Neither IgG nor IgM anti-zidovudine antibodies were present in sera from the other two patients with zidovudine fever, from four AIDS patients who discontinued zidovudine for reasons other than fever, or from five AIDS patients who never received zidovudine. Zidovudine may cause fever as a severe adverse effect in patients with AIDS. Either type III or type IV hypersensitivity may mediate this reaction.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Monoclonal antibodies against spore antigens of Bacillus anthracis.

A murine monoclonal antibody produced against heat inactivated spores of Bacillus anthracis Ames, reacted with live or inactivated spores of several anthrax strains in indirect immunofluorescence (IF) tests. The reactive anthrax strain gave only a moderate degree of reaction. No staining of anthrax vegetative cells was observed. The monoclonal did not react with spores of non-anthrax Bacillus strains that gave cross reactions with mouse hyperimmune antiserum raised against Ames spores. The staining of individual spores in B. anthracis preparations was more heterogeneous with the monoclonal antibody than with the hyperimmune serum. Evidence is produced that the epitope for this monoclonal is not stable during long-term storage of inactivated spore preparations, and is not fully available for reaction with antibody until late in spore maturation. The monoclonal did not react by immunoblotting (Western blotting) of spore extracts. A monoclonal antibody produced against Ames spore extracts reacted with about 1% of Ames spores in IF tests, but not reproducible reactions with other anthrax strains were recorded. This monoclonal interacted with three bands in Western blots of anthrax spore extracts.

Animals↗