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Biomedical subjects

C McCarthy

Publications and source records attributed to C McCarthy.

At least 37 records · Page 2Linked to original sources
PubMed2000

Does user satisfaction relate to adoption behavior?: an exploratory analysis using CPRS implementation.

User satisfaction is commonly assessed in evaluations of information systems as a proxy for user adoption. However few studies actually report directly assessing the relationship between the two constructs. In this study the relationship between four user satisfaction measures and five adoption behaviors were explored in the context of the implementation of the Veteran's Health Administration Computerized Patient Record System 1.0. Findings suggest that the relationship is modest and depends on the measurement system used. Specifically, direct reports of affect and judgements of specific task efficacy related to behavior more often than usability and a general user satisfaction instrument.

Attitude to Computers↗
PubMed1999

Influence of microenvironment on mammary epithelial cell survival in primary culture.

Mammary epithelial cells cultured on Engelbreth-Holm-Swarm (EHS) matrix form multicellular structures termed mammospheres, in which cells and matrix become arranged around a central luminal space. In the presence of lactogenic hormones, cells within mammospheres become polarized, form tight intercellular junctions, and secrete milk proteins vectorially into the luminal space. This study examined the mechanism of lumen formation. Histological examination of developing mammospheres showed that cavitation was associated spatially and temporally with the appearance of fragmented nuclear material in apoptotic bodies, and with the presence of cells positively labeled by terminal deoxynucleotide transferase-mediated deoxyuridine nick end-labeling (TUNEL). Analysis of [(32)P]-deoxynucleotide end-labeled genomic DNA by electrophoresis and autoradiography showed DNA laddering indicative of apoptosis. A transient increase in laddering coincided with both lumen formation and the presence of TUNEL-positive cells. Lumen formation, DNA laddering, and detection of TUNEL-positive cells were all accelerated when matrix composition was altered. They were also impaired coordinately when caspase inhibitor was present during the first two days of culture. Therefore, lumen formation in mammosphere cultures is due to selective apoptosis of centrally located cells. Mammosphere cavitation was accompanied by redistribution of matrix constituents to the mammosphere periphery. Western blotting and Western ligand blotting of culture medium showed that lumen formation was also associated with a transient increase in insulin-like growth factor binding protein-5 (IGFBP5), a factor implicated in mammary apoptosis in vivo. We propose that epithelial cell survival during mammosphere development is induced selectively through stabilization by basement membrane constituents, which may act directly on the epithelial cell or confer protection against autocrine apoptotic factors.

Animals↗
PubMed1998

Selective endothelin A receptor antagonists. 3. Discovery and structure-activity relationships of a series of 4-phenoxybutanoic acid derivatives.

The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated. These include hypertension, ischemic diseases, and atherosclerosis. In earlier publications we have outlined the discovery and structure-activity relations of two moderately potent series of nonpeptide ETA receptor antagonists. In this paper, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these two series of compounds to be merged into a single class of 4-phenoxybutanoic acid derivatives. The subsequent optimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)b utanoi c acid (12m). This compound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity over the ETB receptor. Data are presented to demonstrate that 12m is orally bioavailable in the rat and is a functional antagonist in vitro and in vivo of ET-1-induced vasoconstriction.

Administration, Oral↗
PubMed1998

Selective endothelin A receptor antagonists. 4. Discovery and structure-activity relationships of stilbene acid and alcohol derivatives.

This publication describes the synthesis and optimization of a novel series of stilbene endothelin antagonists. Analysis of the SAR established for previous papers in this series prompted the design and synthesis of (Z)-4-phenyl-5-(3-benzyloxyphenyl)pent-4-enoic acid 3 which was found to be a moderately active inhibitor of the binding of [125I]ET-1 to ETA receptors with an IC50 of 6 microM. More interestingly, the intermediate compound (E)-2-phenyl-3-(3-benzyloxyphenyl)propenoic acid 5 was equiactive with 3. Optimization of 5 resulted in the preparation of (E)-2-phenyl-3-(2-cyano-5-(thien-3-ylmethoxy))phenylprope noic acid 18 (RPR111723) which had an IC50 in the binding assay of 80 nM on the ETA receptor and a pKB of 6.5 in the functional assay, measured on rat aortic strips. Reduction of the acid group of 5 gave the first nonacidic ETA antagonist in our series, (E)-2-phenyl-3-(3-benzyloxyphenoxy)prop2-enol 6 with an IC50 of 20 microM. Optimization of 6 resulted in the preparation of 2-(2-methylphenyl)-3-(2-cyano-5-(thien-3-ylmethyl)phenyl)pro p-2-enol 33 with an IC50 of 300 nM on the ETA receptor.

Animals↗
PubMed1998

Detection of coronary artery disease using dobutamine stress echocardiography in patients with an abnormal resting electrocardiograph.

PURPOSE: We assessed the value of dobutamine stress echocardiography for the detection of coronary artery disease in patients with chest pain and an abnormal resting electrocardiograph (ECG). METHODS: Dobutamine stress echocardiography was performed in a standard fashion. Significant coronary artery disease was defined as a >50% luminal diameter stenosis on coronary angiography. RESULTS: The sensitivity, specificity, positive and negative predictive value of dobutamine stress echocardiography for the detection of coronary artery disease in 218 patients were 89, 50, 95 and 32%, respectively. The sensitivity for detection of multi-, double- and single vessel disease were 97, 82 and 81%, respectively. The sensitivity for the detection of coronary artery disease in a subgroup of 69 patients by treadmill exercise testing was 37%. CONCLUSION: Dobutamine stress echocardiography is better than exercise ECG for the detection of significant coronary artery disease. The negative predictive value of dobutamine stress echocardiography in this patient group is low.

Aged↗
PubMed1998

[Quality of life of women with stress urinary incontinence with or without pollakiuria].

OBJECTIVES: Assess improvement in quality of life using a validated scale in women with urge incontinence or pollakiuria treated with oxybutynine. PATIENTS AND METHODS: A prospective open multicentric trial was conducted in 1701 women aged 20 to 60 years (mean 47.6) with the last 2 months. Quality of life was assessed on the Ditrovie scale before and after a 3-month treatment with oxybutynin (7.5 to 15 mg/day). RESULTS: Patient compliance was good (97%) and side effects rare (8%) (mainly dry mouth). There was a significant symptom improvement (p < or = 0.0001) between day 0 and day 90 after treatment: 48% of the women no longer had incontinence with a safety interval of more than 15 minutes compared with 0.2% prior to treatment; urge incontinence disappeared in 75% of the 81% affected women; 82% of the women had an intermictional interval longer than 2 hours after treatment compared with 33% prior to treatment. There was a significant improvement in the quality of life scores after treatment (p < 0.0001), as assessed by the overall score and subscores (daily life, emotional impact, self-image, sleep, well-being). CONCLUSION: These findings demonstrate the efficacy of oxybutynine in improving urge incontinence and pollakiuria in women, both in terms of symptom relief and quality of life.

Adult↗
PubMed1998

Correlation of myocardial histologic changes in hibernating myocardium with dobutamine stress echocardiographic findings.

OBJECTIVE: The objective of this study was to correlate histologic changes in hibernating myocardium with dobutamine stress echocardiography (DSE). METHODS: Patients (n = 8) with anterior regional wall motion abnormalities in the seven echocardiographic segments representing the territory supplied by a significantly stenosed left anterior descending coronary artery had preoperative DSE performed (yielding 56 segments for analysis). Two transmural biopsy specimens were taken from the anterior wall of the left ventricle during coronary artery bypass grafting. RESULTS: Morphometric histologic analysis of biopsy specimens showed significantly less fibrosis in segments demonstrating inotropic reserve (p < 0.05) and significantly less fibrosis in segments demonstrating improvement in wall motion on echocardiography 3 months after revascularization (p < 0.05). DSE had a sensitivity of 100% and a specificity of 62% for detection of hibernating myocardial segments. Percent fibrosis was inversely correlated with percent nucleated cells (r = 0.66, p < 0.01) and directly correlated with cytoplasmic clearance (r = 0.76, p < 0.01). CONCLUSION: Inotropic response during DSE correlates with histologic evidence of hibernating myocardium.

Cardiotonic Agents↗
PubMed1998

Three-year prospective study of 3228 clinical BPH patients treated with alfuzosin in General Practice.

Objectives: To investigate (a) the magnitude and durability of symptom score reduction and HRQL score improvement (including sexual drive); (b) adverse outcomes; and (c) progression to acute urinary retention and prostate surgery up to three years of treatment with alfuzosin. Methods: Three thousand two hundred and twenty-eight BPH-patients out of 812 centers were included in a prospective three-year open-labelled study and treated with alfuzosin (immediate release formulation) at the recommended dosage. A symptom score (Boyarsky modified) and a 20-item BPH specific HRQL score including three questions of sexuality (Urolife(TM) BPH QoL 20) were self-administered at baseline, 3, 6, 12, 18, 24, 30, and 36 months. Results: Two thousand five hundred and seventy-nine patients (79.9%) completed the study at the end of three years. Symptom score was significantly reduced by 54% at 3 months and this reduction was maintained up to 36 months (-48.4%); HRQL score was significantly improved by 45.4% at 12 months and this improvement was maintained up to 36 months (+43.4%). Alfuzosin was well tolerated: the quantitative and qualitative distribution of adverse events was similar to that previously observed in placebo-controlled studies (vertigo/dizziness: 2.1%). Adverse events accounted for 4.2% of the drop-outs. 120 patients (3.7%) were operated on for BPH and nine patients (0.3%) experienced acute urinary retention. Conclusion: This medical outcomes study confirms the long-term safety profile of alfuzosin in the naturalistic conditions of general practice and highlights the need to measure HRQL in the context of patient's preferences.

Journal Article↗
PubMed1998

Long-term clinical outcome following coronary artery bypass grafting for isolated stenosis of the left anterior descending coronary artery.

AIMS: To detail the clinical and angiographic profile, and long-term outcome in consecutive patients with isolated stenosis of the left anterior descending coronary artery undergoing bypass surgery. METHODS: A retrospective study of all patients (n = 301) (January 1984-December 1990) and undergoing coronary artery bypass grafting for isolated left anterior descending disease, in the Irish Republic, was performed. Survival was compared with that of an exact age- and gender-matched cohort. RESULTS: Mean age was 53 (+/- 9.3) years. There were 238 (79%) males. In 241 (80%) patients an internal thoracic arterial bypass graft was used. Operative mortality was 1.3%. Of the 280 (93%) patients alive (16 cardiac deaths) at 7.1 (+/- 1.9) years, 105 (35%) had angina, 26 (9%) suffered an interval myocardial infarction, and repeat revascularization was required on 29 (10%). Female gender (P = 0.002), pre-operative myocardial infarction (P = 0.02), significant diagonal disease (P = 0.04) and postoperative myocardial infarction (P = 0.0001) were independently associated with survival. Females were more likely to develop congestive cardiac failure (P = 0.01) or postoperative angina (P = 0.03) than their male counterparts. CONCLUSIONS: Survivorship (97%) and event-free survival (96%) at 5 years following coronary artery bypass grafting for isolated left anterior descending coronary artery disease is excellent and equivalent to an age-matched and gender-matched cohort.

Adult↗
PubMed1998

Sustained-release alfuzosin, finasteride and the combination of both in the treatment of benign prostatic hyperplasia. European ALFIN Study Group.

OBJECTIVES: To assess the additive benefit of combining an alpha1-blocker and a 5alpha-reductase inhibitor. METHODS: This European, randomized, double-blind, multicenter trial involved 1.051 patients with lower urinary tract symptoms related to benign prostatic hyperplasia. Patients received sustained release (SR) alfuzosin (n = 358), a selective alpha1-blocker given at a dose of 5 mg twice daily without dose titration; finasteride (n = 344), 5 mg once daily, or both drugs (n = 349), for 6 months. Primary efficacy criteria were symptomatic improvement (International Prostate Symptom Score: I-PSS) and maximum flow rate (Qmax). Safety was assessed by monitoring adverse events. RESULTS: Symptomatic improvement was significantly higher from the 1st month of treatment with SR alfuzosin, alone or in combination; mean changes in I-PSS versus baseline at end-point were -6.3 and -6.1, respectively, compared with -5.2 with finasteride alone (SR alfuzosin vs. finasteride, p = 0.01; combination vs. finasteride, p = 0.03). The percentages of patients with a decrease in I-PSS of at least 50% were 43, 42 and 33% for SR alfuzosin, the combination and finasteride, respectively (SR alfuzosin vs. finasteride, p = 0.008; combination vs. finasteride, p = 0.009). In the overall population, increases in Qmax were greater with SR alfuzosin and the combination, compared with finasteride alone after 1 month of therapy, but changes at end-point were similar in the three treatment groups. In those 47% of patients likely to be obstructed (baseline Qmax <10 ml/s), however, mean increases in Qmax were significantly higher with SR alfuzosin, alone or in combination, whatever the visit. Finasteride, alone or in combination, significantly impaired sexual function. The incidence of postural symptoms was low and similar in the three treatment groups. CONCLUSION: In this 6-month trial, SR alfuzosin was more effective than finasteride, with no additional benefit in combining both drugs.

5-alpha Reductase Inhibitors↗
PubMed1998

Clinical uroselectivity: a 3-year follow-up in general practice. BPH Group in General Practice.

The objectives of this open-labeled study were to assess the clinical uroselectivity of alfuzosin in a long-term follow-up study in general practice. A total of 3,228 patients with clinical benign prostatic hyperplasia (BPH) from 812 centers were included in a prospective 3-year open-labeled study and treated with alfuzosin (immediate-release formulation) at the recommended dosage. Symptom score (Boyarsky, modified) and a 20-item BPH-specific health related quality of life (HRQL) score (Urolife BPH QoL 20), which included three questions on sexuality, were self-administered at baseline, 3, 6, 12, 18, 24, 30 and 36 months. Symptom score was significantly reduced by 54% at 3 months and this reduction was maintained up to 36 months; the HRQL score was significantly improved by 45.4% at 12 months and this improvement was also maintained up to 36 months. Alfuzosin was well tolerated: the quantitative and qualitative distribution of adverse events (AEs) was similar to that previously observed in placebo-controlled studies. 4.2% of the patients dropped out due to AEs. This study confirms the long-term safety profile of alfuzosin in general practice and highlights the need to measure HRQL in the context of clinical uroselectivity.

Adrenergic alpha-Antagonists↗
PubMed1998

The buffering effect of a computer support network on caregiver strain.

ComputerLink was a computer support network for family caregivers of people with Alzheimer's disease. In a 12-month experiment, 102 caregivers were randomly assigned to an experimental group that had access to ComputerLink or to a control group that did not. This investigation examined whether caregivers in the experimental group had greater reductions in four types of care-related strain by the end of the 1-year study. ComputerLink reduced certain types of strain if caregivers also had larger informal support networks, were spouses, or did not live alone with their care receivers. More frequent use of the communication function was related to significantly reduced strain for caregivers who were initially more stressed and for non-spouse caregivers. Greater use of the information function was related to significantly lower strain among caregivers who lived alone with care receivers. Overall, ComputerLink appeared to be an effective tool for reducing strain for some caregivers.

Alzheimer Disease↗
PubMed1998

Cystic fibrosis newborn screening: impact on reproductive behavior and implications for genetic counseling.

OBJECTIVE: To evaluate the impact of newborn screening for cystic fibrosis (CF) on the reproductive knowledge and behavior of CF families and to determine if heterozygote detection with the immunoreactive trypsinogen (IRT) method in conjunction with DNA analysis (IRT/DNA) influences knowledge and attitudes about reproduction in false-positive families. METHODS: The Wisconsin CF Neonatal Screening Project investigated 650 340 infants from 1985 to 1994 in a comprehensive randomized controlled trial to study both benefits and risks of newborn screening and to determine if early diagnosis would improve the prognosis of children with CF. Assessments of reproductive knowledge, attitudes, and behaviors of 135 families of children diagnosed as having CF in both the early treatment group and control groups were made 3 months after diagnosis using a questionnaire which was completed by 100 families. The same questionnaire was administered 1 year later to evaluate retention of information. It was completed by 71 families. A follow-up assessment tool was also administered in 1994 and responses obtained from 73 families. Knowledge, attitudes, and behavior among false-positive families were also assessed at the time of the sweat test in 206 families who experienced IRT screening and 109 families tested with the IRT/DNA method. Follow-up assessments were completed 1 year later in 106 IRT families and 63 IRT/DNA families. RESULTS: In families with a CF child, 95% initially understood that there was a 1 in 4 risk in subsequent pregnancies, and there was good retention of this information 1 year later. At the 1994 assessment, 52% of families had not yet conceived more children, but 74% of these already had children. In the couples in whom CF was diagnosed in the first child, 70% (95% confidence interval = 54% to 85%) conceived more children. There were 43 subsequent pregnancies in 31 families. Prenatal diagnosis was used by 26% of the families (8/31) for 21% of the pregnancies (9/43). There were 3 pregnancies with CF detected, all of which were carried to term. In the false-positive groups, >95% of families initially understood that their child definitely did not have CF. There was no difference between false-positive IRT and IRT/DNA groups, and the information was retained at 1 year. Follow-up assessment 1 year after negative sweat tests revealed that 7% of the IRT and 10% of the IRT/DNA families still thought about the results often or constantly. When asked whether the experience of screening affected feelings about having more children, an affirmative response was obtained in 4% of IRT families but in 17% of IRT/DNA families. One year later, more than half of the false-positive IRT/DNA families did not understand that they were at increased risk of having a child with CF. CONCLUSIONS: We conclude that CF neonatal screening does not have a significant impact on the reproductive behavior of most families and that prenatal diagnosis is not used by the majority of CF families. IRT/DNA testing experiences seem to affect attitudes about having more children, and some parents are confused about the implications of the results, even with genetic counseling. However, persistent concerns about the sweat test result are limited. Questions raised by this study confirm the need for more research regarding the process of genetic counseling and its impact on reproductive attitudes and behavior in the newborn screening setting.

Cystic Fibrosis↗
PubMed1998

Sporadic chromosome abnormalities in human lymphocytes and previous exposure to chemicals.

Sporadic abnormalities in lymphocyte cultures are often attributed to in vitro culture variations of no clinical significance. The data presented here compare the findings from 11,873 cells of 230 patients referred with histories of previous chemical exposure (usually to mixtures of solvents and/or pesticides) with 27,050 cells from 855 patients referred for other reasons. Detection of 0.38% or more, structural abnormalities (approximately 1 in 30 cells) was 27.2 times more likely in exposed persons than in controls and the finding of a single autosomal trisomic cell was 14.4 times more likely in exposed persons. These highly statistically significant findings were similar to the frequencies of abnormalities reported in other studies of persons exposed to benzene, pesticides, herbicides and irradiation. It is recommended that findings of sporadic abnormalities in lymphocytes be routinely recorded, and patients with positive findings followed up to discover whether there are past histories of significant exposures.

Adolescent↗
PubMed1997

Dobutamine stress echocardiography in the detection of coronary artery disease in a clinical practice setting.

UNLABELLED: In this prospective study, patients referred for coronary angiography for detection of disease underwent dobutamine stress echocardiography to define its value in a clinical practice setting. RESULTS: Of 219 patients studied, 170 (78%) had significant coronary artery disease. The overall sensitivity and specificity of dobutamine stress echocardiography for coronary artery disease were 82 and 65%, respectively. The sensitivity was 88% for detection of triple-vessel disease, 83% for double-vessel disease, and 74% for single-vessel disease. Positive and negative predictive values for coronary artery disease were 89 and 51%, respectively. Dobutamine stress echocardiography correctly identified only 72 of 138 patients with significant stenosis of the left anterior descending coronary artery. In 219 patients, 345 of 657 major epicardial vessels had significant disease. Dobutamine stress echocardiography could only correctly identify the vessel involved in 188. Triple-vessel disease was present in 65 patients. Dobutamine stress echocardiography correctly categorised 18% (n = 12) of these. The remainder were incorrectly classified as having double-vessel disease or single-vessel disease (n = 45), or no disease at all (n = 8). CONCLUSION: Dobutamine stress echocardiography performs well. However, lower specificity may lead to unwarranted referrals for coronary angiography, and the low NPV give false reassurance as to the absence of disease.

Aged↗
PubMed1997

Dobutamine stress echocardiography in the detection of coronary artery disease: importance of the pretest likelihood of disease.

Although the accuracy of dobutamine stress echocardiography for the detection of coronary artery disease in a high-risk population is known, it has not been well defined for lower risk groups. Two probability groups, high (>75%; n = 199) and intermediate (>10% but < or =75%; n = 118), were studied. Dobutamine stress echocardiography was performed in a standard fashion. Significant coronary artery disease was defined as a >50% luminal diameter stenosis on coronary angiography. The positive predictive accuracy of dobutamine stress echocardiography for the detection of coronary artery disease was greater in the high-probability group (96% vs 86%), as was the sensitivity (89% vs 78%), whereas the negative predictive value was greater in the intermediate-probability group (50% vs 23%), as was the specificity (63% vs 50%). Dobutamine stress echocardiography does have a diagnostic role in the evaluation of patients with an intermediate probability of coronary artery disease.

Aged↗
PubMed1997

Regulation of hepatic glutaminase in the streptozotocin-induced diabetic rat.

The liver of diabetic animals removes increased quantities of glutamine. We therefore examined factors that affect hepatic glutaminase activity in hepatocytes and mitochondria. Glutamine use, through glutaminase, was measured in isolated rat hepatocytes by monitoring the production of 14CO2 from [1-(14)C]glutamine. Hepatocytes from streptozotocin-induced diabetic rats use glutamine more rapidly than do hepatocytes from normal or insulin-maintained diabetic rats. Glutamine use in all of these hepatocytes was stimulated by glucagon and epinephrine. Glutaminase activity, assayed in broken mitochondrial membranes, was increased approximately 2.5-fold in diabetic rats. The sensitivity of glutaminase, measured in intact liver mitochondria, to phosphate was markedly left-shifted in mitochondria from diabetic rats compared with those from controls. In fact, glutaminase was increased 10-fold at 2.5 mmol/l phosphate compared with controls. This increased sensitivity of glutaminase to physiological concentrations of phosphate is characteristic of its hormonal activation. Therefore, activation of glutaminase plays a major role in diabetes and is as important as increases in its total enzyme amount in determining the increased glutamine uptake in diabetes.

Animals↗