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Biomedical subjects

A Walsh

Publications and source records attributed to A Walsh.

At least 55 records · Page 3Linked to original sources
PubMed1998

The problem-based medical audit program: influence on family practice residents' knowledge and skills.

BACKGROUND AND OBJECTIVES: Family physicians need to possess the skills to conduct audits in their own clinical settings to ensure that their patients receive exemplary clinical care. Residency offers an important opportunity for physicians to develop these auditing skills. This study describes the introduction of a problem-based medical audit program at three teaching units in the Department of Family Medicine at McMaster University and the program's effect on learner knowledge, skills, and attitudes toward the practice audit. METHODS: A survey designed to assess residents' self-rated knowledge, skills, and attitudes toward practice audits was distributed before and after residents participated in the audit program. RESULTS: Forty-three residents were surveyed; 33 (76.7%) completed the initial questionnaire and follow-up questionnaire. Residents reported significant improvements in their understanding of the relevance of audits, ability to develop a practice audit question, skills in designing methodology, and skills needed to conduct an audit independently. Residents also reported a moderate increase in their knowledge of statistics needed to complete an audit. CONCLUSIONS: The practice audit program at McMaster University uses a problem-based model to introduce learners to the concept of the clinical audit. The practice audit program successfully improved the residents' self-reported ability to conduct an audit and heightened their understanding of the importance and relevance of the audit process.

Commission on Professional and Hospital Activities↗
PubMed1998

Teaching behavioral science to family medicine residents: integrating training into the family practice unit.

The teaching of behavioral science is an integral part of the education of family physicians. This paper presents a model of a program that integrates the teaching of behavioral science with residents' daily activities in their clinical placement. It outlines the format of the program, the curriculum, teaching methodologies, evaluation and funding. The authors stress the importance of collaboration between family physician and psychiatrist in planning and implementing the program.

Behavioral Sciences↗
PubMed1997

Cell damage induced by Angiovist-370 and 308nm excimer laser radiation.

BACKGROUND AND OBJECTIVE: Radiographic contrast media containing iodine-labeled organic compounds can be present in the irradiated field during laser angioplasty using 308 nm excimer laser radiation. These compounds absorb light at 308 nm and may undergo photochemical reactions that produce products that damage cells. STUDY DESIGN/MATERIALS AND METHODS: This study was undertaken to determine whether photoproducts that damage human lymphocytes in vitro are formed when Angiovist 370 (AV), a contrast medium containing triiodinated aromatic compounds, is exposed to 308 nm radiation. RESULTS: The absorption spectrum of AV developed a new peak at 360 nm that extended to wavelengths greater than 500 nm when dilute AV solutions were exposed to 308 nm radiation indicating that photoproducts were formed. Irradiating dilute AV solutions above a layer of human lymphocytes caused a dose-dependent decrease in thymidine incorporation using fluence rates between 5.2 x 10(6) and 1.0 x 10(8) W/cm2. Decreased DNA synthesis was independent of the pulse length (10 ns vs. 230 ns) but was lower, at a given dose, when the highest fluence rate was used. Incubation of lymphocytes with preirradiated AV solutions also decreased incorporation of thymidine in a radiation dose-dependent manner. The cell damaging photoproducts in preirradiated AV solutions were unstable; within 15 min, the effectiveness had decreased by approximately 85%. CONCLUSIONS: These results indicate that exposure of AV to 308 nm excimer laser radiation produces photochemical products that damage human cells in vitro.

Angioplasty, Balloon, Laser-Assisted↗
PubMed1997

A new method for bronchial-provocation testing in asthmatic subjects using a dry powder of mannitol.

We developed a bronchial provocation test (BPT) with a dry powder preparation of mannitol. The mannitol was inhaled from gelatin capsules containing 5, 10, 20, or 40 mg to a cumulative dose of 635 mg, and was delivered via an inhalator, Halermatic, or Dinkihaler device. We studied the airway sensitivity to inhaled mannitol, the repeatability of the response, and the recovery after challenge in 43 asthmatic subjects 18 to 39 yr of age who had a 20% decrease in FEV1 in response to inhaling a 4.5% NaCl. We compared this with the airway response to methacholine in 25 subjects. The geometric mean (GM) for the dose of dry mannitol required to reduce the FEV1 by 15% of the baseline value (PD15) was 64 mg, with a 95% confidence interval (CI) of 45 to 91. Subjects responsive to mannitol had a PD20 to metacholine of < 7.8 mumol, with a GM of 0.7 mumol (CI: 0.4 to 1.2). For the first of two challenges to mannitol the PD15 was 59 mg (CI: 36 to 97) and for the second the PD15 was 58 mg (CI: 35 to 94) p = 0.91 (n = 23). Spontaneous recovery to within 5% of baseline occurred within 60 min and within 10 min after 0.5 mg terbutaline sulfate was inhaled. Arterial oxygen saturation (SaO2) remained at 93% or above during mannitol challenge. Subjects tolerated the inhalation of the mannitol well. A dry powder preparation of mannitol may be suitable to develop for bronchial provocation testing.

Administration, Inhalation↗
PubMed1997

The effect of inhaling a dry powder of sodium chloride on the airways of asthmatic subjects.

Wet aerosols of 4.5% sodium chloride (NaCl) are often used to assess the bronchial responsiveness associated with asthma. We questioned whether dry NaCl could be used as an alternative. Dry powder NaCl was inhaled from capsules containing either 5, 10, 20 or 40 mg to a cumulative dose of 635 mg. The powder was delivered via an Inhalator or Halermatic. The airway sensitivity to the dry and wet NaCl was compared in 24 patients with asthma aged 19-39 yrs. All subjects responded to both preparations and the geometric mean (95% confidence intervals) for the provocative dose of NaCl causing forced expiratory volume in one second (FEV1) to fall 20% from baseline (PD[20,NaCl]) for dry NaCl was 103 mg (68-157) versus 172 mg (102-292), p<0.03 for the wet NaCl. The response to dry NaCl was reproducible and on repeat challenge the PD20 was 108 mg (75-153). The mean maximum fall in FEV1 was approximately 25% on each of the two test days. Spontaneous recovery occurred within 60 min after challenge with dry NaCl and within 5 min after bronchodilator. There were no serious side-effects requiring medical attention, however some patients coughed on inhalation of the 40 mg dose and three gagged. Arterial oxygen saturation remained within normal limits. We conclude that a suitably prepared dry powder of sodium chloride could potentially replace wet sodium chloride to assess bronchial responsiveness in patients with asthma, but further studies are required to establish the long-term stability of the dry powder preparation.

Administration, Inhalation↗
PubMed1996

Human cholesteryl ester transfer protein gene proximal promoter contains dietary cholesterol positive responsive elements and mediates expression in small intestine and periphery while predominant liver and spleen expression is controlled by 5'-distal sequences. Cis-acting sequences mapped in transgenic mice.

The plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of high density lipoprotein cholesteryl esters to other lipoproteins and appears to be a key regulated component of reverse cholesterol transport. Earlier studies showed that a CETP transgene containing natural flanking sequences (-3.4 kilobase pairs (kbp) upstream, +2.2 kbp downstream) was expressed in an authentic tissue distribution and induced in liver and other tissues in response to dietary or endogenous hypercholesterolemia. In order to localize the DNA elements responsible for these effects, we prepared transgenic mice expressing six new DNA constructs containing different amounts of natural flanking sequence of the CETP gene. Tissue-specific expression and dietary cholesterol response of CETP mRNA were determined. The native pattern of predominant expression in liver and spleen with cholesterol induction was shown by a -3.4 (5'), +0.2 (3') kbp transgene, indicating no major contribution of distal 3'-sequences. Serial 5'-deletions showed that a -570 base pairs (bp) transgene gave predominant expression in small intestine with cholesterol induction of CETP mRNA in that organ, and a -370 bp transgene gave highest expression in adrenal gland with partial dietary cholesterol induction of CETP mRNA and plasma activity. Further deletion to -138 bp 5'-flanking sequence resulted in a transgene that was not expressed in vivo. Both the -3.4 kbp and -138 bp transgenes were expressed when transfected into a cultured murine hepatocyte cell line, but only the former was induced by treating the cells with LDL. When linked to a human apoA-I transgene, the -570 to -138 segment of the CETP gene promoter gave rise to a relative positive response of hepatic apoA-I mRNA to the high cholesterol diet in two out of three transgenic lines. Thus, 5'-elements between -3,400 and -570 bp in the CETP promoter endow predominant expression in liver and spleen. Elements between -570 and -370 are required for expression in small intestine and some other tissues, and elements between -370 and -138 contribute to adrenal expression. The minimal CETP promoter element associated with a positive sterol response in vivo was found in the proximal CETP gene promoter between -370 and -138 bp. This region contains a tandem repeat of a sequence known to mediate sterol down-regulation of the HMG-CoA reductase gene, suggesting either the presence of separate positive and negative sterol response elements in this region or the use of a common DNA element for both positive and negative sterol responses.

Animals↗
PubMed1996

Increased prebeta-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes.

Human plasma phospholipid transfer protein (PLTP) circulates bound to high density lipoprotein (HDL) and mediates both net transfer and exchange of phospholipids between different lipoproteins. However, its overall function in lipoprotein metabolism is unknown. To assess the effects of increased plasma levels of PLTP, human PLTP transgenic mice were established using the human PLTP gene driven by its natural promoter. One line of PLTP transgenic mice with moderate expression of PLTP mRNA and protein was obtained. The order of human PLTP mRNA expression in tissues was: liver, kidney, brain, small intestine > lung > spleen > heart, adipose tissue. Western blotting using a human PLTP monoclonal antibody revealed authentic human PLTP (Mr 80 kD) in plasma. Plasma PLTP activity was increased by 29% in PLTP transgenic mice. However, plasma lipoprotein analysis, comparing PLTP transgenic mice to control littermates, revealed no significant changes in the plasma lipoprotein lipids or apolipoproteins. Since previous studies have shown that human cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase only function optimally in human apoAI transgenic mice, the human PLTP transgenic mice were cross-bred with human apoAI transgenic mice. In the human apoAI transgenic background, PLTP expression resulted in increased PLTP activity (47%), HDL phospholipid (26%), cholesteryl ester (24%), free cholesterol (37%), and apoAI (22%). There was a major increase of apoAI in prebeta-HDL (56%) and a small increase in alpha-HDL (14%). The size distribution of HDL particles within alpha- and prebeta-migrating species was not changed. The results suggest that PLTP increases the influx of phospholipid and secondarily cholesterol into HDL, leading to an increase in potentially antiatherogenic prebeta-HDL particles.

Animals↗
PubMed1996

Alternative splicing of the human cholesteryl ester transfer protein gene in transgenic mice. Exon exclusion modulates gene expression in response to dietary or developmental change.

The plasma cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl ester from high density lipoprotein to other lipoproteins. The human DETP gene produces two forms of mRNA, with or without exon 9 (E9)-derived sequences. To study the function and regulation of alternative splicing the CETP gene, transgenic mice were prepared 1) with the metallothionein (mT) promoter driving an E9-deleted construct (mT.CETP(-E9) transgene), and 2) with the natural flanking regions (NFR) controlling expression of genomic sequences which permit alternative splicing of E9 (NFR.CETP(+/-E9) transgene). With zinc induction, the mT.CETP(-E9) transgene gave rise to abundant E9-deleted CETP mRNA in liver and small intestine, but only relatively small amounts of E9-deleted protein were found in plasma. The E9-deleted form of CETP was inactive in lipid transfer and produced no changes in plasma lipoprotein profile. The NFR.CETP(+/-E9) transgene gave rise to full-length (FL) and E9-deleted forms of CETP mRNA in liver and spleen. In response to hypercholesterolemia induced by diet and breeding into an apoE gene knock-out background, the FL CETP mRNA was induced more than the E9-deleted mRNA, resulting in a 2-fold increase in ratio of FL/E9-deleted mRNA. The expression of CETP mRNA was found to be developmentally regulated. In NFR.CETP(+/-E9) transgenic mice CETP mRNA levels were markedly increased in the liver and small intestine in the perinatal period and decreased in adult mice, whereas CETP mRNA in the spleen was low in perinatal mice and increased in adults. The developmental increase in CETP mRNA in the liver and spleen was preceded by an increased ratio of FL/E9-deleted forms. Thus, the E9-deleted mRNA appears to be poorly translated and/or secreted, and the cognate protein is inactive in lipid transfer and lipoprotein metabolism. CETP gene expression was found to be highly regulated in a tissue-specific fashion during development. Increased CETP gene expression during development or in response to hypercholesterolemia is associated with preferential accumulation of the full-length CETP mRNA.

Alternative Splicing↗
PubMed1996

Profound induction of hepatic cholesteryl ester transfer protein transgene expression in apolipoprotein E and low density lipoprotein receptor gene knockout mice. A novel mechanism signals changes in plasma cholesterol levels.

The plasma cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key regulated component of reverse cholesterol transport. Dietary hypercholesterolemia results in increased hepatic CETP gene transcription and higher plasma CETP levels. To investigate the mechanisms by which the liver senses hypercholesterolemia, mice containing a natural flanking region CETP transgene (NFR-CETP transgene) were bred with apo E or LDL receptor gene knockout mice (E0 or LDLr0 mice). Compared to NFR-CETP transgenic (Tg) mice with intact apo E genes, in NFR-CETP Tg/E0 mice there was an eightfold induction of plasma CETP levels and a parallel increase in hepatic CETP mRNA levels. Other sterol-responsive genes (LDL receptor and hydroxymethyl glutaryl CoA reductase) also showed evidence of altered regulation with decreased abundance of their mRNAs in the E0 background. A similar induction of plasma CETP and hepatic CETP mRNA levels resulted from breeding the NFR-CETP transgene into the LDL receptor gene knockout background. When placed on a high cholesterol diet, there was a further increase in CETP levels in both E0 and LDLr0 backgrounds. In CETP Tg, CETP Tg/E0, and CETP Tg/LDLr0 mice on different diets, plasma CETP and CETP mRNA levels were highly correlated with plasma cholesterol levels. The results indicate that hepatic CETP gene expression is driven by a mechanism which senses changes in plasma cholesterol levels independent of apo E and LDL receptors. Hepatic sterol-sensitive genes have mechanisms to sense hypercholesterolemia that do not require classical receptor-mediated lipoprotein uptake.

Animals↗
PubMed1996

Long-term benefits of aggressive treatment for primary colorectal cancer.

The long-term follow up of 128 colorectal cancer patients is reported. Seventy-nine percent (101/128) of the patients had curative resections: 70 patients had radical lymphadenectomies with wide removal of tumor-adjacent nodes, and 31 patients had standard resections. The 5-year overall survival rates for Dukes' stage B and C patients and for all rectosigmoid cancer patients significantly favored radical resection (60% vs. 38%, 57% vs. 29%, respectively, P < 0.05). Tumor-free survival rates were also higher after radical lymphadenectomy but did not reach statistical significance. Eleven percent (14/128) of the patients required multiorgan resections, and/or preoperative radiation to render fixed cancers resectable, and these patients had a 10-year tumor-free survival rate of 45%, compared to zero % 5-year survival for the 27 patients who underwent palliative procedures (P < 0.01). These results confirm that many colorectal cancer patients will be cured with aggressive treatment and they support the need for a controlled trial for evaluation of lymphadenectomy for this disease.

Adult↗
PubMed1996

An outbreak of cutaneous aspergillosis in a tertiary-care hospital.

A cluster of four cases of surgical and burn wound aspergillosis occurred in a 900-bed, adult, tertiary-care hospital. The source was traced to the outside packages of dressing supplies, which had become contaminated during construction in the central Inventory Control area. This resulted in patients with large exposed surface areas being inoculated directly with Aspergillus spores.

Adult↗
PubMed1995

Cerebral oxygen supply and utilization during infant cardiac surgery.

The survival of infants with congenital heart disease has improved dramatically. However, the incidence of neurological injury in infants surviving cardiac surgery remains considerable. These neurological sequelae are attributable at least in part to hypoxia-ischemia/reperfusion, which inevitably accompanies infant heart surgery with deep hypothermia, cardiopulmonary bypass, and circulatory arrest. To begin to identify mechanisms of brain injury during infant cardiac surgery, we used near-infrared spectroscopy to study the relationship between cerebral intravascular (hemoglobin) and mitochondrial (cytochrome aa3) oxygenation in 63 infants (aged 1 day to 9 months) undergoing deep hypothermic repair of congenital heart defects, throughout the intraoperative period. Moreover, we assessed the effect of postnatal age on these changes. The cerebral concentration of oxidized cytochrome aa3 decreased from the onset of deep hypothermic cardiopulmonary bypass, despite apparent abundant intravascular oxygenation manifested by a simultaneous increase in the cerebral concentration of oxyhemoglobin. During this interval infants older than 2 weeks had a greater decrease in oxidized cytochrome aa3 than did infants 2 weeks old or younger. During deep hypothermic circulatory arrest, cerebral levels of oxidized cytochrome aa3 remained depressed while those of oxyhemoglobin declined. With reperfusion following circulatory arrest, the recovery of oxidized cytochrome aa3 was delayed, despite a rapid recovery of intravascular oxygenation (HbO2). After rewarming and 60 minutes of reperfusion, only 46% of infants recovered to the baseline level of cerebral oxidized cytochrome aa3. These findings demonstrate a paradoxical dissociation of changes in intravascular and mitochondrial oxygenation during hypothermic cardiopulmonary bypass; a pronounced decrease of mitochondrial oxygenation is established during induction of hypothermia and a delay in recovery of mitochondrial oxygenation occurs following circulatory arrest. These effects were more pronounced in infants older than 2 weeks than in younger infants. The data suggest potentially deleterious impairments of intrinsic mitochondrial function or of delivery of intravascular oxygen to the mitochondrion or both, effects previously undetected and apparently influenced by cerebral maturation.

Brain↗
PubMed1995

The effect of nutritional status on the cytokine and acute phase protein responses to elective surgery.

Weight loss and impaired nutritional status are associated with increased complications following surgery. This study aimed to assess the effect of nutritional status on the magnitude of the acute phase protein response, and determine if this is associated with changes in the magnitude of the related cytokine responses. Nineteen patients (10 wellnourished, 9 malnourished on the basis of body composition) undergoing major abdominal surgery were studied by frequent blood sampling in the early postoperative period. There was a significant reduction in the plasma C-reactive protein response in the malnourished group, but no difference between the groups in the responses of alpha 1-antitrypsin, alpha 1-acid glycoprotein, or in the trace elements iron or zinc, which reflect induction of ferritin and metallothionein. There was an early increase in IL-6, soluble receptors of TNF, and in IL-1 receptor antagonist in both groups, but no detectable increase in plasma IL-1 or TNF. There was no difference between the wellnourished and malnourished group for any of these markers of activation of the cytokine network. Weight loss is therefore associated with a reduction in aspects of the acute phase response, but this is due to impaired effectiveness rather than reduced magnitude of the cytokine response.

Acute-Phase Proteins↗
PubMed1995

Biochemical and behavioural effects of acute tryptophan depletion in abstinent bulimic subjects: a pilot study.

We studied the effect of acute tryptophan (TRP) depletion in a group of eight abstinent bulimic (BN) subjects and in 12 healthy female controls. Despite being free of episodes of binge-eating and vomiting for a prolonged period, the abstinent BN subjects still appeared to practice dietary restrain as judged by their food intake in a test meal. In addition, their plasma TRP concentrations were significantly lower than those of the controls. Administration of a TRP-free amino acid load (52 g) significantly lowered plasma total and free TRP. However, compared to a balanced amino acid load, this procedure did not have significant effects on mood, appetite or food intake in either the abstinent BN subjects or the healthy controls.

Adult↗
PubMed1995

The effect of ivermectin treatment of late pregnant dairy cows in south-west Victoria on subsequent milk production and reproductive performance.

A total of 498 dairy cows in 5 predominantly pasture-fed herds were allocated to pairs. One cow in each pair was treated with a single dose of ivermectin during the dry period. Treated and untreated cows were managed as a single group throughout the trial. Most cows calved between 45 and 115 days after treatment. When data from all herds were pooled, treated cows produced an extra 74 L of mild over the first 100 days of the subsequent lactation (95% confidence interval 20 to 128). Means were greater among treated groups relative to untreated groups in all 5 herds. However, when analysed individually, differences were statistically significant (P < 0.05) in 1 herd only. Over the complete lactation, mean milk volume for treated cows was 86 L greater than for untreated cows (95% confidence interval of difference -57 to 229; P = 0.24). Untreated cows produced 2473 L and 5883 L for the first 100 days of lactation and for the complete lactation, respectively. Milk production responses to treatment did not vary significantly with parity, body condition score, previous production index, calving date category or with plasma pepsinogen concentrations or faecal egg count at the time of treatment. Faecal egg counts and plasma pepsinogen concentrations were low at the start of the study. The interval from calving to conception was 4.8 days less in treated cows (95% confidence interval 1.2 to 8.2) relative to untreated cows when data from all 5 herds were pooled. Differences within individual herds were not statistically significant.

Animals↗