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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 649 records · Page 36Linked to original sources
PubMedDate not supplied

Hepatic biotransformation of parathion: role of cytochrome P450 in NADPH- and NADH-mediated microsomal oxidation in vitro.

In vitro studies have established that cytochrome P450 (P450) is deactivated by the electrophilic sulfur atom released during the enzymic oxidation of parathion to paraoxon. However, in vivo studies in rats have been unable to demonstrate significant P450 loss. This study evaluated the possibility that there may be alternate pathways of parathion biotransformation in liver, other than those mediated by P450 and supported by NADPH. Initial experiments confirmed that parathion administration did not decrease microsomal P450 or testosterone hydroxylation activities. Subsequent in vitro experiments identified an NADH-dependent pathway of parathion biotransformation, and MS was used to confirm that paraoxon and 4-nitrophenol were the products of both the NADH- and NADPH-dependent reactions. The Michaelis constants of the NADH-dependent formation of paraoxon and 4-nitrophenol (26 +/- 6 microM and 53 +/- 10 microM, respectively) were approximately 3-fold greater than those for the NADPH-supported reactions (9 +/- 1 microM and 18 +/- 3 microM, respectively). Induction of male rats with phenobarbital and dexamethasone, but not beta-naphthoflavone, produced similar increases in the rates of NADH- and NADPH-mediated parathion metabolism. Rates of NADH- and NADPH-dependent metabolism were highly correlated in linear relationships. An anti-NADPH-cytochrome P450 reductase (NADPH-P450 reductase) antibody partially inhibited microsomal parathion oxidation mediated by either cofactor, and the P450 inhibitor clotrimazole was similarly effective against the NADH- and NADPH-supported oxidation of parathion. Finally, a reconstituted system containing P450 2B1, NADPH-P450 reductase, and phospholipid supported parathion oxidation mediated by NADH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Rat hepatic microsomal aldehyde dehydrogenase. Identification of 3- and 4-substituted aromatic aldehydes as substrates of the enzyme.

The rat hepatic microsomal aldehyde dehydrogenase (mALDH) metabolizes aliphatic and aromatic aldehydes to the corresponding acids with NAD as the optimal cofactor. However, dehydrogenation of the aliphatic compounds is substantially more efficient. In the present study, a series of aromatic aldehydes was evaluated as substrates of the purified mALDH so that the physicochemical factors that contribute to substrate affinity could be evaluated. Substitution of the aromatic system in the 3- and 4-positions produced relatively good substrates, but 2-substituted congeners did not undergo dehydrogenation. However, aldehydes with hydrophilic substituents in the 3- or 4-positions and those with extremely bulky substituents at both positions (e.g., 3,4-dibenzyloxy) were also poor substrates for the enzyme and dehydrogenation was undetectable. A quantitative structure-activity relationship was determined that related the logarithm of the Michaelis constants for 27 substituted aromatic aldehydes with the zero-order connectivity function of the molecule (0 chi), the shapes of the 3- and 4-substituents (kappa), and the electronic nature of the 4-substituent (sigma). In this equation, 81% of the data variance was explained. From a consideration of the dimensions of 3-phenoxybenzaldehyde, which was a relatively good substrate, the mALDH possesses a narrow cleft within the active site that is at least 7.5 angstroms wide and extends at least 12 angstroms from the catalytic residue (probably cysteine). Previously established relationships between connectivity functions and molecular polarizability suggest that dipolar interactions within the active site, as well as dispersion forces, may play a role in substrate specificity. Although optimal shapes for carbocyclic substituents were not provided by the analysis, the unfavorable effect on dehydrogenation from hydrophilic and large substituents suggests that the active site of the mALDH is relatively rigid and that the orientation of the substrate in relation to the catalytic cysteine and the cofactor binding site is critical.

Acetaldehyde↗
PubMedDate not supplied

Tape injury in the patient with total hip replacement.

Patients undergoing total hip replacement surgery may experience edema around the incision related to intraoperative positioning and manipulation of the extremity, as well as general soft tissue damage. The edema may contribute to the impairment of skin integrity when tape is applied to secure postoperative dressings. This article describes how the problem of impaired skin integrity was identified and the process used to determine the contributing factors. The interventions used by three nursing specialty areas to correct the problem are also described.

Adhesives↗
PubMedDate not supplied

Cefotetan therapy for gonococcal urethritis and cervicitis.

The authors compared the safety and efficacy of 0.5 and 1.0 g of cefotetan with that of 0.25 g of ceftriaxone in a 3:3:2 randomized distribution. Of 172 patients (96 men, 76 women) aged 18-43 years who were being treated at the Delgado Venereal Disease Clinic, New Orleans Health Department, for acute gonococcal urethritis or cervicitis, 123 were evaluable (81 men, 42 women). All men and 16 women were initially symptomatic. All were culture positive for Neisseria gonorrhoeae. At the 4-8 day follow-up, cultures were negative for N. gonorrhoeae in all except one man and one woman, each of whom received cefotetan 0.5 g. Symptoms were eliminated 12-72 hr after therapy in all groups. Cefotetan was well tolerated, and there were few adverse experiences reported. Thus, the authors consider cefotetan safe and effective for the treatment of uncomplicated gonorrhea.

Adolescent↗
PubMedDate not supplied

Effect of genetic obesity and experimental diabetes on hepatic microsomal mixed function oxidase activities.

In male rats, genetic obesity and experimental diabetes are associated with altered activities of several of the hepatic microsomal P-450 isozymes concerned with steroid and xenobiotic oxidation. The present study examined the roles of insulin and ketonaemia in effecting these changes. In obese male Zucker rats, androstenedione 6 beta-, 16 alpha- and 16 beta-hydroxylase activities (mediated by P450PCN-E, P-450UT-A and P450PB-B, respectively) were significantly decreased to 21%, 20% and 43% of lean control. Obesity was also associated with a significant decrease in the activities of N-nitrosodimethylamine demethylase (P-450j) and aniline p-hydroxylase to about 70%. A similar decrease in total microsomal P-450 was also observed. Androstenedione 7 alpha-hydroxylase activity (mediated by P-450UT-F) was unchanged in these animals. In streptozotocin-induced diabetic male Wistar rats, androstenedione 7 alpha- and 16 beta-hydroxylase activities were significantly elevated to 230% and 270% of control, respectively. Significant increases in the rates of N-nitrosodimethylamine demethylase and aniline p-hydroxylase were also noted in diabetic rat liver. In contrast, the activity of P-450UT-A was reduced to 30% of control and P-450PCN-E-specific 6 beta-hydroxylation was unchanged. Control of the diabetic state with insulin treatment reversed all the changes in P-450-mediated activities. Significant correlations were found between serum concentrations of insulin and catalytic activities of P-450PB-B (rho = -0.46), P-450UT-F (rho = -0.65) and P-450j (rho = -0.71). Positive correlations of the same magnitude were also found between these mixed function oxidase activities and beta-hydroxybutyrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aniline Hydroxylase↗
PubMedDate not supplied

Cost of illness of epilepsy in the US: comparison of patient-based and population-based estimates.

PURPOSE: To analyze the direct medical costs associated with epilepsy in the US using a cost-of-illness analysis that incorporates both a patient-based approach and a population-based approach. METHODS: Patient-based or 'bottom-up' analysis relied on information provided by a panel of experienced epilepsy clinicians to determine the number and type of medical resources used by individuals with epilepsy. Population-based or 'top-down' analysis relied on cost estimates from a nationally representative sample in the 1987 National Medical Expenditure Survey. RESULTS: The average annual cost per individual in the patient-based analysis was $1,490. The average annual cost per individual in the population-based analysis was $1,510 with average yearly costs per adult of $1,480 and $1,740 per child. New cases of epilepsy are associated with costs of $362 million for the first year of treatment; existing cases of epilepsy are estimated to cost the US nearly $2 billion. CONCLUSIONS: The results of this study indicate incident cases are more than twice as expensive as prevalent cases, and the need to properly care for epilepsy patients is increasingly important in today's health care environment, where the emphasis is on providing effective treatments while simultaneously lowering the costs.

Adolescent↗
PubMedDate not supplied

Nutrition support in clinical practice: review of published data and recommendations for future research directions. National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition.

In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family.

Humans↗
PubMedDate not supplied

Right atrial thrombi complicating use of central venous catheters in hemodialysis.

BACKGROUND: There has been an increase in the use of central venous catheters for temporary hemodialysis access. In this report, we describe a case series of 12 patients on hemodialysis who developed intracardiac clots associated with the use of central venous catheters, their outcomes and review the literature on this syndrome. METHODS: Retrospective, single-center case series of 12 patients with right atrial thrombi associated with central venous catheter use for dialysis vascular access. These patients were treated between June 1, 2001 and June 30th 2002 at the three University of Rochester affiliated dialysis clinics. The medical records of these patients were reviewed to obtain information concerning demographics, dialysis history, dates of catheter insertion, catheter complications, identification and dimensions of intracardiac thrombi, echocardiographic data, and outcome of anticoagulant therapy. RESULTS: Right heart thrombi were identified in 12 patients in our hemodialysis population over the study interval. Anticoagulation for 6 months led to clot resolution in more than 50% of our patients. Bacteremia recurred in 6 patients (50%), in spite of catheter replacement. There was zero mortality related to presence of clots in the short term. One patient with non-bacteremic right atrial thrombus suffered sudden cardiac arrest, but was successfully resuscitated. CONCLUSION: Right atrial thrombi may occur in hemodialysis patients who use central venous catheters for dialysis access. These clots are frequently found in the right atrium or right atrial-superior vena caval junction. Ten of 12 patients (83%), had catheter-associated bacteremia, but the precise relationship between bacteremia and intracardiac clots is unclear. Chronic anticoagulation for 6 months lead to resolution of these clots in more than 50% of patients in our series.

Journal Article↗
PubMedDate not supplied

Building and growing a hospital intranet: a case study.

BACKGROUND: The Intranet is a rapidly evolving technology in large hospitals. In this paper, we describe the first phase of an Intranet project in a multi-hospital system in New York City. OBJECTIVES: (1) To encourage the use of the Intranet among physicians, nurses, managers, and other associates in a multi-hospital system; and (2) to build the Intranet in a cost-effective manner using existing resources. METHODS: A WebTrends Log Analyzer assessed the Intranet use in terms of the number of accesses from each department. RESULTS: A broad range of features, including medical knowledge resources, clinical practice guidelines, directions, patient education, online forms, phone directory, and discussion forums were developed. Analysis of more than 890,000 hits revealed the departments with hits greater than 1,000 were the Library (6,130), Physicians Gateway (2,539), Marketing (1,321), Information Systems (1,241), and Nutrition (1,221). Of 819 unique visitors, 74 per cent visited more than once. CONCLUSIONS: It is possible to create and diffuse an Intranet in a multi-hospital system in a cost-effective manner. However, the key challenges were selling the potential of this new technology to opinion leaders and other stakeholders, and converting pre-existing printed content by obtaining word processed and image files from other departments or contracted print publishers.

Computer Communication Networks↗
PubMedDate not supplied

Continuous quality improvement in Canadian health care organizations.

A survey of Canadian health care organizations indicates growing interest in the philosophy and methods of continuous quality improvement (CQI). Most organizations are still in the early stages of learning and applying CQI. Although CEOs have been learning about CQI and have been participating in quality councils, they are less involved in using and teaching CQI techniques. Major obstacles reported in developing quality improvement are lack of time, limited resources, lack of training, and pressures to deal with other changes. Only a few organizations question the value of developing quality improvement, and many who have not yet adopted CQI say they intend to do so.

Canada↗
PubMedDate not supplied

Improving access to clinical offices.

Optimal access to office care requires a detailed understanding of a practice's capacity to provide care and demand for services. Once capacity and demand are known, they can be effectively managed to provide care today for those needs that arise today. Such a system of "open access" benefits clinicians and patients alike. This article describes specific steps a practice can take to achieve open access.

Ambulatory Care↗