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Biomedical subjects

D Murphy

Publications and source records attributed to D Murphy.

At least 109 records · Page 6Linked to original sources

Measuring outcomes in the treatment of alcohol dependency.

The selective promotion of clinical services which have proven effectiveness is a movement that is gaining momentum within healthcare. Outcome evaluation in treatment services for alcohol dependency is given as an example of the methodological issues associated with the establishment of clinical efficacy. It is argued that the adoption of clear protocols for assessment, treatment and outcome are a prerequisite of the process. There are costs associated with in-house follow-up studies but the benefits of feedback are evident for patients and for staff providing their care. Although exposing service providers (and commissioners) to the possibility of negative feedback, outcome evaluation in the treatment of alcohol dependency should be an integral part of provision. The principle of systematic assessment of efficacy applies to healthcare provision generally and should include management, teaching, purchasing and policymaking.

Alcoholism↗

Fifteen-year experience of testicular neoplasm in a regional centre.

BACKGROUND: During a 15-year period from 1980 to 1995, 63 patients from the Geelong region of Victoria presented with germ cell neoplasm. METHODS: In this retrospective review performed by studying hospital records, treating specialists' notes and by telephone interviews, 61 of 63 patients were identified. RESULTS: A tumour incidence of four cases per 100,000 male population per year with an overall cancer-specific survival of 95% is demonstrated. Follow-up ranged from 18 months to 15 years. The incidence of seminoma was 30%; patients with seminoma presented at a later stage than those with non-seminoma. CONCLUSIONS: The present study demonstrates the increasing incidence of testicular tumour in the Geelong region, and the excellent prognosis of this disease with management outside of the tertiary referral centre.

Adolescent↗

The effect of age and diet on the oral glucose tolerance test in ponies.

To evaluate the effects of age and diet on the oral glucose tolerance test (OGTT) in healthy ponies, OGTTs were performed on 2 groups of British native breed ponies (Group A: 7 foals [6-9 months], Group B: 7 mature individuals [6-13 years]) when maintained on either a high fibre pelleted ration only (Groups A and B) or a hay only diet (Group B). Plasma glucose response, following oral glucose administration, for Group A (basal plasma glucose concentration [Glu0] 4.6 +/- 0.4 mmol/l (mean +/- s.d.) increasing to 11.5 +/- 1.3 mmol/l at 90 min) was significantly different (P < 0.05) from that observed for Group B (Glu0 of 4.3 +/- 0.2 mmol/l increasing to 6.8 +/- 1.3 mmol/l at 90 min), when fed the same diet. For Group B ponies, the plasma glucose response, following oral glucose administration, was significantly different (P < 0.05) when fed hay only (Glu0 4.6 +/- 0.4 mmol/l increasing to 9.6 +/- 2.1 mmol/l at 150 min) compared to when fed the high fibre pelleted ration. These results indicate that both age and diet have a significant effect on plasma glucose concentrations measured during an OGTT.

Aging↗

Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia.

The purpose of this study was to determine the impact of a scheduled change of antibiotic classes, used for the empiric treatment of suspected gram-negative bacterial infections, on the incidence of ventilator-associated pneumonia and nosocomial bacteremia. Six hundred eighty patients undergoing cardiac surgery were evaluated. During a 6-mo period (i.e., the before-period), our traditional practice of prescribing a third generation cephalosporin (ceftazidime) for the empiric treatment of suspected gram-negative bacterial infections was continued. This was followed by a 6-mo period (i.e., the after-period) during which a quinolone (ciprofloxacin) was used in place of the third-generation cephalosporin. The incidence of ventilator-associated pneumonia was significantly decreased in the after-period (n = 327) compared with the before-period (n = 353) (6.7 versus 11.6%; p = 0.028). This was primarily due to a significant reduction in the incidence of ventilator-associated pneumonia attributed to antibiotic-resistant gram-negative bacteria (0.9 versus 4.0%; p = 0.013). Similarly, we observed a lower incidence of bacteremia attributed to antibiotic-resistant gram-negative bacteria in the after-period compared with the before-period (0.3 versus 1.7%; p = 0.125). These data suggest that a scheduled change of antibiotic classes can reduce the incidence of ventilator-associated pneumonia attributed to antibiotic-resistant gram-negative bacteria.

Adolescent↗

The impact of nosocomial infections on patient outcomes following cardiac surgery.

STUDY OBJECTIVE: To evaluate the relationship between nosocomial infections and clinical outcomes following cardiac surgery, and to identify risk factors for the development of nosocomial infections in this patient population. DESIGN: Prospective cohort study. SETTING: Barnes-Jewish Hospital, St. Louis, a university-affiliated teaching hospital. PATIENTS: Six hundred five consecutive patients undergoing cardiac surgery. INTERVENTIONS: Prospective patient surveillance and data collection. MAIN OUTCOME MEASURES: Occurrence of nosocomial infections, multiorgan dysfunction, hospital mortality, and risk factors for the acquisition of nosocomial infections. RESULTS: One hundred thirty-one (21.7%) patients acquired at least one nosocomial infection following cardiac surgery. Four independent risk factors for the development of a nosocomial infection were identified: the duration of mechanical ventilation, postoperative empiric antibiotic administration, the duration of urinary tract catheterization, and female gender. Thirty (5.0%) patients died during their hospitalization. The mortality rate of patients acquiring a nosocomial infection (11.5%) was significantly greater than the mortality rate of patients without a nosocomial infection (3.2%) (odds ratio [OR]=4.0; 95% confidence interval [CI]=2.7 to 5.8; p<0.001). Multiorgan dysfunction was found to be the most important independent determinant of hospital mortality (adjusted OR=23.8; 95% CI=13.5 to 42.1; p<0.001) along with the aortic cross-clamp time (adjusted OR=2.3; 95% CI=1.7 to 3.0; p=0.002) and severity of illness as measured by APACHE II (acute physiology and chronic health evaluation) (adjusted OR=1.1; 95% CI=1.1 to 1.2; p=0.019). Ventilator-associated pneumonia, clinical sepsis, female gender, the cardiopulmonary bypass time, and severity of illness were identified as independent risk factors for the development of multiorgan dysfunction. Among hospital survivors, patients acquiring a nosocomial infection had longer hospital lengths of stay compared to patients without a nosocomial infection (20.1+/-13.0 days vs 9.7+/-4.5 days; p<0.001). CONCLUSIONS: Nosocomial infections, which are common following cardiac surgery, are associated with prolonged lengths of hospitalization, the development of multiorgan dysfunction, and increased hospital mortality. These data suggest potential interventions for the prevention of nosocomial infections following cardiac surgery that could substantially improve patient outcomes and decrease medical care costs.

APACHE↗

Midterm results with the Sorin Monostrut heart valve prosthesis.

OBJECTIVE: To monitor the hematological and clinical sequelae of a single tilting disc cardiac valve prosthesis. DESIGN: Prospective nonrandomized trial. SETTING: University teaching hospital. PARTICIPANTS: All patients receiving a single mechanical cardiac valve prosthesis were offered the Sorin Monostrut valve if they met the criteria for valve use. Seventy-five per cent of the patients entered were in New York Heart Association (NYHA) functional class III or IV. One hundred and forty-seven patients were subsequently followed at three months and then yearly after valve implantation for seven years. MAIN OUTCOME MEASURES: At one year, preoperative indexes of hemolysis were compared with three-month and one-year postoperative values. Actuarial curves for survival, freedom from cerebrovascular events and explantation were constructed for the seven-year follow-up period. RESULTS: Hemolysis, as measured by lactate dehydrogenase values, commonly occurs preoperatively, remaining significantly elevated three months and one year following valve implantation. Serum haptoglobin was normal preoperatively but was significantly low at one year. Anemia was uncommon and most patients had normal reticulocyte counts at one year. At three years, 81% of patients were in NYHA functional class I. CONCLUSIONS: Midterm results show that this valve is structurally reliable and meets all current requirements for a safe mechanical valve.

Adult↗

Chronic debilitating fatigue in Irish general practice: a survey of general practitioners' experience.

BACKGROUND: Doctors are called upon to treat chronic debilitating fatigue without the help of a protocol of care. AIMS: To estimate the incidence of chronic debilitating fatigue in Irish general practice, to obtain information on management strategy and outcome, to explore the attitudes of practitioners (GPs) towards the concept of a chronic fatigue syndrome (CFS), and to recruit practitioners to a prospective study of chronic fatigue in primary care. METHOD: A total of 200 names were selected from the database of the Irish College of General Practitioners (ICGP); 164 of these were eligible for the study. RESULTS: Altogether, 118 questionnaires were returned (72%). Ninety-two (78%) responders identified cases of chronic fatigue, giving an estimated 2.1 cases per practice and an incidence of 1 per 1000 population. All social classes were represented, with a male to female ratio of 1:2. Eleven disparate approaches to treatment were advocated. Many (38%) were dissatisfied with the quality of care delivered, and 45% seldom or hardly ever referred cases for specialist opinion. The majority (58%) accepted CFS as a distinct entity, 34% were undecided, and 8% rejected it. Forty-two (35%) GPs volunteered for a prospective study. CONCLUSION: Chronic fatigue is found in Irish general practice among patients of both sexes and all social classes. Doctors differ considerably in their management of patients and are dissatisfied with the quality of care they deliver. Many cases are not referred for specialist opinion. A prospective database is required to accurately assess the scale of this public health problem and to develop a protocol of care.

Adult↗

A new fibre optic sensor for respiratory monitoring.

A new fibre optic plethysmograph has been designed to monitor respiration non invasively. The device incorporates the idea of using thoracic and abdominal belts similar to conventional inductance plethysmography but uses an optical fibre woven into the belts rather than the usual coiled wire. The fibre optic belts incorporate a loop design in the fibre and rely on "macrobending" losses from laser light transmitted down the fibre when the bend radius of the loop changes during respiration. Changes in lung volume are monitored by analysing the relatively large resultant changes in light transmitted through the fibre. The output from the light detector has been interfaced to a computer containing a data acquisition card and the resultant intensity trace is monitored in real time using a virtual instrument created using LabVIEW graphical programming. Preliminary results suggest a highly sensitive system capable of detecting small changes in lung volume using a technique which is not susceptible to electrical noise and which is electrically safe.

Adult↗

Circadian rhythms and autoregulatory transcription loops--going round in circles?

Recent advances in the molecular analysis of biological timing have appeared to bring us closer to an answer to the 'big question', namely, 'What is the timing mechanism that enables an organism to measure the circadian (around 24 h) period?'. In this minireview, we consider the validity of the fashionable concept that autoregulatory feedback loops, centered on transcription, form the basis of the clock, and we offer a fresh view of recent progress as it relates to mammalian systems.

Animals↗

Kinesin movement on glutaraldehyde-fixed microtubules.

Glutaraldehyde-cross-linked microtubules were investigated as substrates for kinesin motility. Microtubules, formed in vitro from chicken brain tubulin, were stabilized with Taxol and chemically fixed with glutaraldehyde. The degree of tubulin monomer cross-linking as a function of time and glutaraldehyde concentration was characterized using polyacrylamide gel electrophoresis. Atomic force microscopy of fixed microtubules indicated that the cross-linking is sufficient to stabilize the gross structure of the microtubules against air drying or a distilled water challenge. Kinesin movement on immobilized, fixed microtubules was determined using a kinesin-coated bead motility assay observed with differential interference contrast microscopy. Within measurement error, kinesin bead movement velocities were independent of the degree of microtubule cross-linking. Binding affinity, however, decreased with increased cross-linking. Although air- and water-challenged microtubules did not support kinesin motility, a dilute suspension of glutaraldehyde-fixed microtubules in buffer supported kinesin motility for at least 2 days without any substantial degradation of activity. Fixed microtubules may be useful for several applications, including affinity purification of microtubule-associated proteins and motility measurements under extreme conditions of temperature and other variables.

Animals↗

A systematic survey of the intergenic region between the murine oxytocin- and vasopressin-encoding genes.

The genomic region between the oxytocin (OT) and vasopressin (VP) genes in the two strains of mice was independently sequenced by our two groups. In this report, we present our collated sequence data and analyses. The mouse intergenic region (MUIGR) was aligned to that of the rat, which has been reported to contain 6.4-kb long interspersed nuclear element (LINE). The MUIGR sequences in the two mice strains did not contain any LINE sequences. This suggests that the approximately 3.5-kb sequence that is conserved between the rat and mouse intergenic regions is likely to be involved in the regulation of OT and VP expression. We also observed several conserved putative transcription factor recognition sequences. Analysis of the MUIGR revealed the lack of any significant ORFs, but the presence of several repetitive elements.

Animals↗

Isolation, expression, and chromosomal localization of the human mitochondrial capsule selenoprotein gene (MCSP).

The mitochondrial capsule selenoprotein (MCS) (HGMW-approved symbol MCSP) is one of three proteins that are important for the maintenance and stabilization of the crescent structure of the sperm mitochondria. We describe here the isolation of a cDNA, the exon-intron organization, the expression, and the chromosomal localization of the human MCS gene. Nucleotide sequence analysis of the human and mouse MCS cDNAs reveals that the 5'- and 3 '-untranslated sequences are more conserved (71%) than the coding sequences (59%). The open reading frame encodes a 116-amino-acid protein and lacks the UGA codons, which have been reported to encode the selenocysteines in the N-terminal of the deduced mouse protein. The deduced human protein shows a low degree of amino acid sequence identity to the mouse protein (39%). The most striking homology lies in the dicysteine motifs. Northern and Southern zooblot analyses reveal that the MCS gene in human, baboon, and bovine is more conserved than its counterparts in mouse and rat. The single intron in the human MCS gene is approximately 6 kb and interrupts the 5'-untranslated region at a position equivalent to that in the mouse and rat genes. Northern blot and in situ hybridization experiments demonstrate that the expression of the human MCS gene is restricted to haploid spermatids. The human gene was assigned to q21 of chromosome 1.

Amino Acid Sequence↗

Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease.

A randomized, double-blind placebo-controlled clinical trial was designed to assess the safety, efficacy, and duration of the bronchodilation resulting from the addition of 500 micrograms of ipratropium bromide (Atrovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution. A total of 195 patients (63% men, average age 64 years) with > 10 pack-year smoking histories and stable, moderate-to- severe chronic obstructive pulmonary disease (COPD; forced expiratory volume in 1 second [FEV1] 1.02 liter, 38.8% predicted) from eight university-affiliated chest clinics in seven U.S. cities were enrolled into the study. Asthma, rhinitis, and eosinophilia were exclusions, as was daily use of > 10 mg of prednisone (or 20 mg on alternate days). There was a 2-week stabilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rates, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having been off theophylline for 24 hours and beta 2-agonists for 12 hours and performed a baseline spirometry. They then received their morning small volume nebulizer treatment of albuterol to which was added either 500 micrograms if ipratropium bromide or a saline placebo. Spirometry was repeated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 2-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pulmonary symptoms and adverse effects every 14 days. The 8-hour spirometry was repeated on test day 43 and finally on test day 85. Primary data evaluated were the peak increase in FEV1 and the area between the FEV1 baseline value and the 8-hour FEV1 curve. Similar calculations were made for forced vital capacity (FVC) and 25-75% forced expiratory flow (FEF25-75%). On test day 1 the peak increase in FEV1 for the ipratropium bromide + albuterol subjects was 26% greater than those on placebo + albuterol (p < 0.003). The area under the 8-hour FEV1 curve was 64% greater in those given ipratropium bromide on test day 1 (p < 0.0002). Similar increases were seen in FVC and FEF25-75%. The peak improvements in FEV1 and FVC with the addition of ipratropium bromide to albuterol were maintained on test days 43 and 85. Considering the safety and efficacy profiles of this combination, the data would suggest that ipratropium bromide inhalation solution should be considered first-line therapy for those patients with COPD requiring small volume nebulizer treatments.

Administration, Intranasal↗