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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 91 records · Page 5Linked to original sources
PubMed1996

Dermatology teleconsultations to Central Prison: experience at East Carolina University.

OBJECTIVE: To review our experience with dermatology teleconsultations between East Carolina University School of Medicine in Greenville and Central Prison in Raleigh, NC. MATERIALS AND METHODS: Consultation forms kept on file in the Department of Internal Medicine served as the source of data. One physician reviewed the forms from the initial 22 months of our dermatology teleconsultation service to Central Prison. Patient demographics and the diagnoses made by the consulting physician were recorded. Recommendations were tabulated as either diagnostic or therapeutic. Diagnoses and recommendations for known HIV-positive individuals were separately recorded. RESULTS: One hundred thirty-eight dermatology teleconsultations were performed over the 22-month period. Seventy two per cent of the patients seen were African-American. The average age was 32 years. One hundred fifty-nine diagnoses were made. The most common problems were eczema and acneiform eruptions. Fifty-nine diagnostic and 252 therapeutic recommendations were made. CONCLUSION: Consultants generally were confident of their diagnoses and management decisions. Dermatologists can assist primary care physicians through telemedicine consultation.

Adult↗
PubMed1996

GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function.

To identify and characterize novel factors required for nuclear transport, a genetic screen was conducted in the yeast Saccharomyces cerevisiae. Mutations that were lethal in combination with a null allele of the gene encoding the nucleoporin Nup100p were isolated using a colony-sectoring assay. Three complementation groups of gle (for GLFG lethal) mutants were identified. In this report, the characterization of GLE2 is detailed. GLE2 encodes a 40.5-kDa polypeptide with striking similarity to that of Schizosaccharomyces pombe RAE1. In indirect immunofluorescence and nuclear pore complex fractionation experiments, Gle2p was associated with nuclear pore complexes. Mutated alleles of GLE2 displayed blockage of polyadenylated RNA export; however, nuclear protein import was not apparently diminished. Immunofluorescence and thin-section electron microscopic analysis revealed that the nuclear pore complex and nuclear envelope structure was grossly perturbed in gle2 mutants. Because the clusters of herniated pore complexes appeared subsequent to the export block, the structural perturbations were likely indirect consequences of the export phenotype. Interestingly, a two-hybrid interaction was detected between Gle2p and Srp1p, the nuclear localization signal receptor, as well as Rip1p, a nuclear export signal-interacting protein. We propose that Gle2p has a novel role in mediating nuclear transport.

Amino Acid Sequence↗
PubMed1996

A molecular and evolutionary study of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata.

Beta-globin gene families in eutherians (placental mammals) consist of a set of four or more developmentally regulated genes which are closely linked and, in general, arranged in the order 5'-embryonic/fetal genes-adult genes-3'. This cluster of genes is proposed to have arisen by tandem duplication of ancestral beta-globin genes, with the first duplication occurring 200 to 155 MYBP just prior to a period in mammalian evolution when eutherians and marsupials diverged from a common ancestor. In this paper we trace the evolutionary history of the beta-globin gene family back to the origins of these mammals by molecular characterization of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata. Using Southern and restriction analysis of total genomic DNA and bacteriophage clones of beta-like globin genes, we provide evidence that just two functional beta-like globin genes exist in this marsupial, including one embryonic-expressed gene (S.c-epsilon) and one adult-expressed gene (S.c-beta), linked in the order 5'-epsilon-beta-3'. The entire DNA sequence of the adult beta-globin gene is reported and shown to be orthologous to the adult beta-globin genes of the North American marsupial Didelphis virginiana and eutherian mammals. These results, together with results from a phylogenetic analysis of mammalian beta-like globin genes, confirm the hypothesis that a two-gene cluster, containing an embryonic- and an adult-expressed beta-like globin gene, existed in the most recent common ancester of marsupials and eutherians. Northern analysis of total RNA isolated from embryos and neonatals indicates that a switch from embryonic to adult gene expression occurs at the time of birth, coinciding with the transfer of the marsupial from a uterus to a pouch environment.

Age Factors↗
PubMed1996

Synthesis and characterization of a selective peptide antagonist of neuropeptide Y vascular postsynaptic receptors.

1. A cyclic dimeric nonapeptide neuropeptide Y (NPY) receptor antagonist, 1229U91, was synthesized by Fmoc chemistry and dimerised in solution. Its effects were assayed in mesenteric arteries from rats and mice, and in rat vas deferens. 2. Mesenteric arteries were cannulated and pressurised to 55 mmHg and the external diameters continuously measured. NPY, PYY, Leu31Pro34NPY and NPY(13-36) each caused concentration-related contractions with the order of potency PYY > or = Leu31Pro34NPY = NPY > NPY (13-36), consistent with the Y1 receptor subtype. 3. 1229U91 had no agonist activity in the arteries but caused a concentration-related rightward shift of NPY (mouse arteries) or Leu31Pro34NPY (rat) concentration-response curves. The antagonism was competitive with pKBS of 7.69 +/- 0.15 and 7.47 +/- 0.13 in the mouse and rat arteries, respectively. 4. Sympathetic nerves in the vas deferens were stimulated with a single electrical field pulse every 20 s and the twitch responses recorded. NPY, PYY, Leu31Pro34NPY and NPY(13-36) inhibited the twitches with the order of potency PYY > NPY > NPY(13-36) >> Leu31Pro34NPY, consistent with the Y2 receptor subtype. 5. 1229U91 inhibited the vas deferens twitch with a shallow concentration-response curve and a time-course of inhibition distinct from that of NPY. 1229U91 (30 microM) did not cause a rightward shift of the NPY concentration-response curve. 1229U91 is at least 5 orders of magnitude less potent in the vas deferens than in rat brain Y2 binding assays reported by others, suggesting that the brain and vas deferens Y2 receptors are different. 6. It is concluded that 1229U91 is a competitive antagonist of NPY Y1 vascular receptors and has additional properties that inhibit the electrically evoked twitch of the rat vas deferens.

Analysis of Variance↗
PubMed1995

An epidemiologic analysis of Mycobacterium avium complex disease in homosexual men infected with human immunodeficiency virus type 1.

Cofactors associated with the Mycobacterium avium complex (MAC) disease and its prognosis in incident cases of AIDS in homosexuals were studied. We compared 51 men in whom MAC disease developed as the initial AIDS-defining illness (termed AIDS illness hereafter); 157 men who had MAC disease subsequent to another AIDS illness; and 884 men who had only non-MAC AIDS illnesses. MAC disease was the initially diagnosed AIDS illness more often in Baltimore (6.9%) and Los Angeles (5.6%) than in Chicago (2.6%) and Pittsburgh (0) (P < .01). MAC disease also was a more common subsequent AIDS illness in Baltimore (14.3%) and Los Angeles (22.4%) than in Chicago (8.5%) and Pittsburgh (6.5%) (P < .0001). Prophylaxis for Pneumocystis carinii infection increased the occurrence of MAC disease as the initial AIDS illness (from 2.3% to 12.5%; P < .0001). A low white blood cell (WBC) count was slightly more predictive of MAC disease than was a low CD4+ cell count. At 0-6, 7-12, and 13-18 months before diagnosis, the WBC cell counts of 75.0%, 61.1%, and 50.0%, respectively, of those with MAC disease as the initial AIDS illness were < or = 3,400/microL. Men in whom cytomegalovirus disease developed were at higher risk for subsequent MAC disease (relative hazard = 2.65; P < .0001). MAC disease also increased the risk for subsequent cytomegalovirus disease (relative hazard = 3.96; P < .0001).

AIDS-Related Opportunistic Infections↗
PubMed1995

Factors associated with changes in the use of antiretroviral therapy by a cohort of homosexual men infected with human immunodeficiency virus type 1.

Changes in the use of antiretroviral drugs and factors associated with changes from monotherapy with zidovudine (ZDV) to other regimens were quantified in the Multicenter AIDS Cohort Study. Participants who had been receiving monotherapy with ZDV were categorized as (1) discontinuing ZDV monotherapy; (2) switching to disanosine (ddI), zalcitabine (ddC), or stavudine (d4T) monotherapy; (3) switching to combination therapy (ZDV with ddI, ddC, or d4T); or (4) continuing ZDV monotherapy. From 1990 to 1994, the percentage of participants using ZDV monotherapy decreased from 27% to 17% (among participants without AIDS) and from 60% to 17% (among those with AIDS). At the same time, the proportion of participants using combination therapy increased from zero to 8% (no AIDS) and from 8% to 26% (AIDS). Polychotomous logistic regression methods were used to identify the factors predicting changes from ZDV monotherapy. Among participants without AIDS, indicators of drug failure (such as a lower CD4 lymphocyte count or symptoms of human immunodeficiency virus type 1 infection) were predictive of the initiation of combination therapy, while among patients with AIDS they were predictive of a switch to an alternative monotherapy. A decrease in hemoglobin levels, a marker of ZDV toxicity, was predictive for all patients of a switch to other monotherapy. These data show that clinicians and patients are opting for more aggressive antiretroviral regiments and that changes in CD4 lymphocyte count and in the status of symptoms remain the primary guides for changes in therapy.

Antiviral Agents↗
PubMed1995

High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection.

Nevirapine, a potent nonnucleoside reverse transcriptase inhibitor, produces a transient antiviral effect at < or = 200 mg/day due to the selection of resistant virus. To examine if higher levels of nevirapine could produce sustained antiviral activity, its safety, pharmacokinetics, and antiviral activity at 400 mg/day were studied in 21 patients. There was a rapid reduction in immune complex-dissociated p24 antigen and serum human immunodeficiency virus RNA concentration in all patients, and 8 of 10 patients had > 50% reduction at 8 weeks. Nevirapine-resistant virus was isolated from all subjects tested at 12 weeks: The mean plasma trough level (4.0 micrograms/mL [15.8 microM]) exceeded the mean IC50 of resistant virus. Rash developed in 48% of patients and was a dose-limiting toxicity factor in 6. These data suggest that clinical testing of potent antiviral compounds that select for drug-resistant virus is justified to determine if serum levels of drug sufficient to overcome resistant virus can be attained.

Adult↗
PubMed1995

Clinical aspects of human immunodeficiency virus disease: clinical rationale for treatment.

Guidelines regarding the use of antiretroviral therapy in adult patients infected with human immunodeficiency virus have been based primarily on the results of 15 major clinical trials in which patients have been categorized according to CD4 cell counts, symptoms, prior therapy, and conditions. In patients with limited treatment experience and advanced disease, zidovudine monotherapy is associated with improved survival, whereas only a transient delay in progression of disease is observed in patients with > 200 CD4 cells/mm3. Adding zalcitabine to the treatment regimen of zidovudine-experienced patients with advanced disease has not been demonstrated to be of clinical benefit, whereas switching these patients to didanosine may delay disease progression. The effect of any antiretroviral therapy in zidovudine-experienced patients with < 50 CD4 cells/mm3 remains indeterminate. The perinatal transmission rate can be reduced by as much as two-thirds when zidovudine is administered to women after the first trimester.

CD4 Lymphocyte Count↗
PubMed1995

Synthesis and biological characterisation of a series of iberiotoxin analogues.

We report here the synthesis of iberiotoxin (IbTX), a 37-amino acid peptide containing three disulfide bridges, and a series of mono-looped analogues. All syntheses were conducted using Fmoc chemistry. Synthesis of IbTX gave a product which was indistinguishable from a reference sample in both its physico-chemical properties and its biological activity. A series of three mono-looped analogues, in which four of the six cysteines were replaced by alanine, were synthesised to give [Ala7,13,28,33]-IbTX, [Ala13,17,33,35]-IbTX and [Ala7,17,28,35]-IbTX. Oxidation of the linear form of [Ala7,17,28,35]-IbTX to form the Cys13 to Cys33 disulfide bridge proceeded more slowly than that of the other two analogues. None of these analogues was biologically active, indicating that no single loop is the mediator of channel blocking activity.

Amino Acid Sequence↗
PubMed1995

Effect of body position on ventricular CSF methotrexate concentration following intralumbar administration.

PURPOSE: Intralumbar methotrexate is one of the primary therapeutic modalities for the prevention and treatment of meningeal leukemia. However, methotrexate distribution to the ventricles is limited and highly variable following intralumbar dosing, and cytotoxic concentrations of methotrexate are not always achieved or sustained in the ventricular CSF. We used a nonhuman primate model to determine the effect of body position on the caudal distribution of an intralumbar dose of methotrexate. METHODS: Methotrexate (1.0 mg) was administered by intralumbar injection to four animals, which were then immediately placed either in an upright sitting position or in a prone position for 1 hour, then upright. Each animal served as its own control and was studied in each position on at least one occasion. RESULTS: The mean peak ventricular methotrexate concentration was 0.12 mumol/L (range, 0.091 to 0.20) in animals that were immediately placed upright, compared with 2.81 mumol/L (range, 0.21 to 8.9) in animals that remained prone for 1 hour. The mean area under the concentration-versus-time curves (AUC) was 0.51 mumol/L.h (range, 0.26 to 1.1) in the upright animals and 12.0 mumol/L.h (range, 0.9 to 35.4) in the prone animals. CONCLUSION: Maintaining a prone position for 1 hour after an intralumbar dose increased the peak methotrexate concentration and drug exposure in ventricular CSF. CSF drug distribution following intralumbar therapy can be influenced by body position after the injection.

Animals↗
PubMed1995

Work reengineering: the benefits and the barriers, an analytical review.

Hospital executives who are considering patient centered care (PCC) delivery models are undertaking a fascinating and sometimes frightening journey. Although the benefits are many, several barriers are often encountered on the way to achieving successful results. Many hospitals begin this initiative with enthusiasm and optimism because it makes so much sense. However, fear of change can set in when barriers overcome the motivation to proceed. This paper explores both the benefits and strategies for successfully overcoming the barriers. In the final analysis, each hospital's executive team must answer the call to this challenge. Their decisions hold the future of their hospital in the balance.

Attitude of Health Personnel↗
PubMed1994

Combined daily therapy with intravenous ganciclovir and foscarnet for patients with recurrent cytomegalovirus retinitis.

We treated seven patients (nine eyes) who had cytomegalovirus retinitis with daily intravenous ganciclovir plus foscarnet. All patients had demonstrated multiple progressions of retinitis on single-drug therapy, and some were intolerant to induction doses of one or both medications. Before combination therapy, the median number of progressions was five per patient. The mean interval between progressions was 11 weeks, and the mean interval before the final progression was four weeks. While taking combination therapy, two patients showed progression after 14 and 34 weeks. Two patients showed no progression after 17 and 36 weeks of follow-up. Three patients died after five, 14, and 23 weeks, respectively, without progression of retinitis. In every patient, the progression-free interval was longer during combination therapy than the previous progression-free interval during single-drug therapy. In no case was combination therapy stopped because of toxicity. Combination therapy was fairly well tolerated and appeared to prolong the interval to progression and to preserve vision in our patients.

AIDS-Related Opportunistic Infections↗
PubMed1994

The triangle model of responsibility.

Responsibility acts as a psychological adhesive that connects an actor to an event and to relevant prescriptions that should govern conduct. People are held responsible to the extent that (a) a clear, well-defined set of prescriptions is applicable to an event (prescription-event link); (b) the actor is perceived to be bound by the prescriptions by virtue of his or her identity (prescription-identity link); and (c) the actor is connected to the event, especially by virtue of appearing to have personal control over it (identity-event link). Studies supported the model, showing that attributions of responsibility are a direct function of the combined strengths of the 3 linkages (Study 1) and that, when judging responsibility, people seek out information that is relevant to the linkages (Study 2). The model clarifies prior multiple meanings of responsibility and provides a coherent framework for understanding social judgment.

Analysis of Variance↗
PubMed1994

Work redesign: a return to the basics.

Through a work redesign project, one hospital focuses on the root of the nursing care delivery system. The premise was simple--a return to the basics to redefine barriers, needed system changes, and role responsibilities. Successful outcomes include improved recruitment and retention as well as increased patient, staff and community satisfaction.

Delivery of Health Care↗
PubMed1993

A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma.

BACKGROUND: Prolonged infusional 5-fluorouracil (5-FU) and bolus 5-FU modulated by leucovorin are associated with higher response rates than bolus 5-FU alone. Cisplatin enhances 5-FU cytotoxicity in some preclinical models. METHODS: The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5-FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer. RESULTS: Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5-FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar-plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA-directed toxicity of 5-FU. The median tolerated dose level of 5-FU was 113 mg/m2/d (range, 64-150 mg/m2/d). Mean steady-state plasma concentrations (Cpss) of 5-FU appeared to increase linearly from 0.19 microM to 0.39 microM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5-FU Cpss than patients with grade 0 or 1 toxicity. CONCLUSIONS: The early onset of toxicity with this regimen of protracted infusional 5-FU/high-dose leucovorin and weekly cisplatin required marked attenuation of the 5-FU dose intensity, and the results were no better than that expected with infusional 5-FU alone.

Adult↗
PubMed1993

Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. SETTING: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). PATIENTS: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. INTERVENTIONS: Itraconazole, 200 mg given orally twice daily. MAIN OUTCOME MEASURES: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. RESULTS: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). CONCLUSIONS: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.

AIDS-Related Opportunistic Infections↗