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Biomedical subjects

B Murphy

Publications and source records attributed to B Murphy.

At least 19 recordsLinked to original sources
PubMed2000

Identification of receptors for neuromedin U and its role in feeding.

Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species. It is widely distributed in the gut and central nervous system. Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.

Amino Acid Sequence↗
PubMed2000

Loxapine for schizophrenia.

BACKGROUND: Loxapine is a drug with D2/D3 receptor antagonist activity and a higher affinity for D3 than D2. Some authors have suggested that loxapine is more effective than typical antipsychotics in reducing the negative symptoms of schizophrenia, that extrapyramidal side-effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as atypical. OBJECTIVES: To determine the effects of loxapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1995) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. SELECTION CRITERIA: All randomised controlled clinical trials relevant to the care of schizophrenia that compared loxapine to other treatments. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted but excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. MAIN RESULTS: Compared to placebo, loxapine is antipsychotic (Global effect - not improved at 6 weeks, n=66, RR 0.6 CI 0.4-0.9 NNT 4 CI 2-62) with similar adverse effect profile to typical drugs. Is as effective as typical drugs in the short term (4-12 weeks) (Global effect - not improved, n=411, RR 0.89 CI 0.7-1.2). Very limited heterogeneous data suggest that, given intramuscularly (IM), loxapine may be at least as sedating as IM haloperidol and thiothixene. REVIEWER'S CONCLUSIONS: Loxapine is antipsychotic but its effects are under researched. It is not clearly different from typical drugs in either its positive or adverse effects.

Antipsychotic Agents↗
PubMed2000

The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys.

Stress exposure impairs the cognitive functioning of the prefrontal cortex (PFC). Previous research has examined the dopamine (DA) D1 receptor mechanisms underlying this response. The current study performed a preliminary examination of the role of D4 receptor mechanisms by determining whether the selective D4 receptor antagonist, PNU-101387G, could prevent stress-induced working memory deficits in monkeys. Animals were tested on the delayed response task following treatment with PNU-101387G (0 or 0.1-0.8 mg/kg, 60-min pretreatment), and the pharmacological stressor, FG7142 (0 or 0.2 mg/kg, 30-min pretreatment). FG7142 significantly impaired delayed response performance relative to vehicle; PNU-101387G pretreatment produced a dose-related reversal of the FG7142 response. PNU-101387G had no significant effects on its own, but there were trends toward improvement at low doses and impairment at higher doses. Further studies in a larger number of animals appear warranted. These preliminary findings suggest that D4 receptor mechanisms contribute to stress-induced cognitive dysfunction.

Animals↗
PubMed2000

Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy.

BACKGROUND: Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown. METHODS: One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation. RESULTS: In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004). CONCLUSIONS: Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.

Adult↗
PubMed2000

Prophylactic nitroglycerin did not reduce myocardial ischemia during accelerated recovery management of coronary artery bypass graft surgery patients.

OBJECTIVE: To evaluate the use of a high dose of nitroglycerin (NTG) for prophylaxis against myocardial ischemia and infarction in patients undergoing coronary artery bypass graft (CABG) surgery with accelerated recovery. DESIGN: Prospective, double-blind, placebo-controlled randomized study. SETTING: A university-based medical center. PARTICIPANTS: Forty adult patients presenting for elective CABG surgery. INTERVENTIONS: Forty patients were divided into 2 blinded study groups. Twenty patients received 2 microg/kg/min of NTG starting before induction of anesthesia and continuing for 6 hours after extubation in the intensive care unit. The placebo group (n = 20) received normal saline during this same interval. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, incidence and severity of myocardial ischemia, and myocardial infarction rates were determined. There were no differences in hemodynamic parameters between groups. The incidence of ischemia was approximately 35% in each group. Myocardial infarction (as determined by elevated creatine kinase-MB fraction, troponin I, and electrocardiogram criteria) was 10% in the placebo group and 5% in the NTG group (p = 0.234). CONCLUSIONS: This study shows a high incidence of myocardial ischemia and infarction in patients presenting for CABG surgery with an accelerated recovery management scheme. NTG was well tolerated clinically; however, it was not found to be protective against myocardial ischemia or infarction in this setting.

Adult↗
PubMed2000

Centrally administered MTII affects feeding, drinking, temperature, and activity in the Sprague-Dawley rat.

MTII, an agonist of melanocortinergic receptors, is a well-documented anorexigenic agent in rats. Many investigators have reported its effects on feeding without considering concurrent alterations in other behaviors. Accordingly, we performed studies to simultaneously measure nocturnal feeding, drinking, activity, and temperature of rats after intracerebroventricular (third ventricle) administration of a wide dose range of MTII (0.05-500 ng). We observed that MTII modulates these physiological parameters in a dose-dependent manner. Low doses of MTII (0.05 ng) caused reductions in feeding without alterations in body temperature, drinking, or activity. In contrast, hyperthermia and disrupted drinking patterns, along with food intake reductions, were evident at doses exceeding 50 ng. The fact that low doses altered only feeding, whereas higher doses affected a range of parameters, suggests that certain melanocortin-induced behavioral changes may be mediated by distinct populations of melanocortin receptors with varying affinities or that those changes seen at higher doses may be nonspecific in nature.

Animals↗
PubMed2000

Clinical features of schizophrenia and linkage to chromosomes 5q, 6p, 8p, and 10p in the Irish Study of High-Density Schizophrenia Families.

OBJECTIVE: Schizophrenia is clinically heterogeneous. Recent linkage studies suggest that multiple genes are important in the etiology of schizophrenia. The authors examined the hypothesis of whether the clinical variability in schizophrenia is due to genetic heterogeneity. METHOD: Using data from the Irish Study of High-Density Schizophrenia Families (N=265 pedigrees; N=1,408 individuals), the authors attempted to predict, from major symptoms and signs of psychosis, evidence for linkage within families for schizophrenia-related disorders to chromosomal regions 5q21-5q31, 6p24-6p22, 8p22-8p21, and 10p15-10p11. RESULTS: No substantial evidence was found for associations between clinical features of schizophrenia and linkage to chromosomes 5q, 6p, or 10p. However, affected individuals from families with evidence for linkage to 8p had significantly more affective deterioration, poorer outcome, more thought disorder, and fewer depressive symptoms than affected individuals from the other families in the study. CONCLUSIONS: These results raise the possibility that the putative susceptibility gene for schizophrenia localized in the 8p22-8p21 region may predispose individuals to the core dementia-praecox syndrome described by Kraepelin more than 100 years ago.

Chromosomes, Human, Pair 10↗
PubMed2000

Sibling correlation of deficit syndrome in the Irish study of high-density schizophrenia families.

OBJECTIVE: The deficit syndrome is a subtype of schizophrenia characterized by primary and enduring negative features of psychopathology. It appears to reflect a distinct subtype within the syndrome of schizophrenia. Little is known about the familial or genetic aspects of the deficit syndrome. The purpose of this study was to determine whether deficit versus nondeficit subtypes are correlated in sibling pairs affected with schizophrenia. METHOD: The present study was based on the Irish Study of High-Density Schizophrenia Families. From the earlier study the authors selected a subset of patients who were members of sibling pairs in which both siblings had been diagnosed with "core" schizophrenia, which included schizophrenia, simple schizophrenia, and schizoaffective disorder with poor outcome. The Schedule for the Deficit Syndrome was used to make deficit versus nondeficit diagnoses, which were based on chart examinations by reviewers blind to sibling status. This method resulted in 65 patients being diagnosed with the deficit syndrome and 401 patients diagnosed as nondeficit (prevalence=13.9%). This group included 347 full sibling pairs, which were analyzed for resemblance with respect to deficit versus nondeficit subtype by means of logistic regression. RESULTS: Deficit versus nondeficit subtypes were significantly correlated in sibling pairs concordant for core schizophrenia. CONCLUSIONS: Familial factors contribute significantly to whether a person has the deficit subtype of schizophrenia. This familial contribution could be genetic or environmental.

Adult↗
PubMed2000

Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer.

PURPOSE: To assess the activity and toxicity of the combination of gemcitabine and cisplatin in the treatment of chemotherapy-naive patients with metastatic urothelial cancer. PATIENTS AND METHODS: Forty-six patients with measurable stage IV carcinoma of the urothelium were enrolled onto this trial. Gemcitabine 1,000 mg/m(2) was administered intravenously for 30 to 60 minutes on days 1, 8, and 15 of each 28-day cycle. Cisplatin was administered after gemcitabine on day 1 of each cycle. The first 11 patients received an initial cisplatin dose of 100 mg/m(2). Due to the hematologic toxicity observed in several of these patients, the dose was reduced to 75 mg/m(2) in the remaining 35 patients. Patients were treated with six cycles, unless disease progression or severe toxicity necessitated earlier discontinuation. RESULTS: Ten of the 46 patients achieved a complete response and nine showed a partial response. The overall response rate was 41%. The median time to treatment failure was 5.5 months. The median survival was 14.3 months, and the 1-year survival probability was 54%. Most of the toxicities were hematologic and, in general, easily manageable. CONCLUSION: Gemcitabine plus cisplatin is active in the treatment of metastatic urothelial cancer in chemotherapy-naive patients and has an acceptable clinical safety profile. Studies are under way to further define the place of gemcitabine in combination with other chemotherapeutic agents in the treatment of metastatic urothelial cancer.

Adult↗
PubMed2000

Dose reduction in gastrointestinal and genitourinary fluoroscopy: use of grid-controlled pulsed fluoroscopy.

OBJECTIVE: We evaluated the diagnostic accuracy of a grid-controlled fluoroscopy unit compared with a conventional continuous fluoroscopy unit for a variety of abdominal and pelvic fluoroscopic examinations. SUBJECTS AND METHODS: Seventy patients (29 men and 41 women; age range, 24-78 years) were enrolled in one of seven abdominal and pelvic fluoroscopic examinations, including upper gastrointestinal series (n = 20), barium enema (n = 10), voiding cystourethrogram (n = 10), percutaneous abdominal catheter tube injection (n = 10), hysterosalpingogram (n = 10), and percutaneous needle insertion and catheter placement (nephrostomy, percutaneous biliary drainage) (n = 10). Each patient underwent at least 10 sec of continuous fluoroscopy that was randomly and blindly compared with 10-sec periods of pulsed fluoroscopy at 15, 7.5, and 3.75 frames per second. A radiologist outside the examination room, unaware of the frame rate per second, evaluated the procedure in real time on a television monitor. The radiologist assessed image quality and diagnostic acceptability using a scoring system. Statistical analysis was performed using the paired Student's t test. RESULTS: For all procedures at all frame rates, we found no statistically significant superiority of one frame rate over another. For most procedures, the slower frame rates were considered equivalent to continuous fluoroscopy when the images were assessed for image quality and diagnostic confidence. CONCLUSION: Our findings suggest that most abdominal and pelvic fluoroscopic procedures can be performed at substantially lower frame rates than those used for continuous fluoroscopy; adopting this procedure may lead to substantial dose savings for the patient and the fluoroscopy operator.

Adult↗
PubMed2000

Role of corticotropin-releasing factor (CRF) receptors in the anorexic syndrome induced by CRF.

Genetic manipulations of corticotropin-releasing factor (CRF)(1) and CRF(2) receptors have resulted in data suggesting that the CRF(2) receptor could mediate the effects of CRF on appetite or satiety. We have attempted to obtain pharmacological evidence for this hypothesis by comparing the ability of a high-affinity peptide, mixed CRF antagonist [cyclo 30-33,f12,L18,21E30, A32,K33]sucker fish urotensin (12-41)NH(2) [cUTSN (12-41)] with a small-molecule CRF(1)-selective antagonist, NBI-27914, and a CRF(2)-selective peptide antagonist, antisauvagine-30, to attenuate the anorexic effects of CRF. We also monitored other behaviors that accompanied CRF-induced anorexia. CRF-induced anorexia was significantly correlated with a reduction in locomotor activity and an increase in freezing behavior and piloerection. cUTSN (12-41) and antisauvagine-30 significantly attenuated the effects of CRF (0.04 nmol) on food intake along with the behavioral syndrome that accompanied anorexia. In contrast, NBI-27914 did not attenuate either of the above-mentioned CRF-induced phenomena when given centrally at doses ranging from 0.13 to 10 nmol/2.5 microl or when given orally at 20 to 40 mg/kg. Although these data support the hypothesis that the CRF(2) receptor mediates the appetite suppression induced by CRF, they also suggest that the CRF(2) receptor could mediate the stress-like behaviors that accompany CRF-induced appetite suppression.

Animals↗
PubMed1999

Comparison of intestinal function in human immunodeficiency virus-seropositive patients in Kampala and London.

BACKGROUND: White homosexual men with human immunodeficiency virus (HIV) show progressive impairment of intestinal function assessed in terms of intestinal permeability and absorptive capacity. In this study we aimed to determine the effects of heterosexually acquired HIV on small-intestinal function in native Africans, among whom there is a high prevalence of tropical enteropathy. METHODS: Intestinal absorptive capacity (using 3-O-methyl-D-glucose, D-xylose, and L-rhamnose) and permeability (differential 5-h urinary excretion of lactulose/L-rhamnose) were assessed in healthy white (n = 57) and black (n = 14) controls in London, apparently healthy black Africans in Kampala, Uganda (n = 26), HIV-infected patients with (n = 9) and without (n = 30) diarrhoea in Kampala, and 39 white homosexual men with HIV in London who were stratified to resemble the African patient group. RESULTS: Intestinal integrity and absorptive capacity were significantly (P < 0.01) impaired in both black controls in London and apparently healthy black Africans, compared with white controls. HIV-infected white and black patients without diarrhoea did not differ significantly from white and black African controls, respectively, with the exception of increased intestinal permeability among the white patients. White and black African patients with HIV/acquired immunodeficiency syndrome (AIDS) and diarrhoea were found to have marked malabsorption and increased intestinal permeability. Although the relative increase in intestinal permeability was similar in the two groups, by far the largest values for intestinal permeability were found among black Africans with HIV/AIDS and diarrhoea. CONCLUSIONS: Whites and blacks differ with regard to intestinal barrier function. HIV-positive black Africans without gastrointestinal symptoms differ insignificantly from white Londoners with homosexually acquired disease, whereas those with gastrointestinal symptoms have markedly abnormal indices of small-intestinal function with severely comprised intestinal integrity.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Physical performance and associated electrolyte changes after haemoglobin normalization: a comparative study in haemodialysis patients.

BACKGROUND: To determine the effects of different haemoglobin (Hb) levels on exercise performance and associated electrolyte changes, a prospective, randomized, double-blinded crossover study was completed in 14 haemodialysis patients. METHODS: Performance and changes in arterial [K+] and lactate were compared at rest and during a maximal incremental cycling exercise at a Hb concentration ([Hb]) of 10 g/dl ([Hb]10) and 14 g/dl ([Hb]14) following an initial baseline test (Hb: 8.3 +/- 0.2 g/dl, mean +/- SEM). Ages ranged from 23 to 65 years and patients were divided into younger (age 23-45 years, n = 9) and older (aged 55-65 years, n = 5) groups. RESULTS: Peak work rate and VO2 peak were higher at [Hb]14 than at [Hb]10. 145 +/- 9 vs 134 +/- 9 W, mu +/- SEM, P < 0.01, and 1.90 +/- 0.11 vs 1.61 +/- 0.11 l/min, P < 0.01, respectively. Improvements were demonstrated in both younger and older groups at the higher target [Hb], with an improved aerobic performance evident particularly in younger patients. However, performance remained below that predicted for comparable sedentary controls. Resting plasma [K+] was raised at both [Hb]10 and [Hb]14 compared with baseline (P < 0.01) although the change in [K+] from rest to peak exercise (delta[K+]) was similar at each level. The delta[K+] per unit work performed (used as a marker of K+ regulation) was, however, inversely related to the [Hb] (baseline: 80 +/- 12 micromol/l/kJ vs [Hb]10, 61 +/- 8, P < 0.01, vs [Hb]14. 49 +/- 7, P < 0.05). Exercise induced a significant but similar rise in lactate concentration at both target [Hb] (P < 0.001), which remained markedly elevated for at least 10 min after exercise in both younger and older groups. CONCLUSIONS: These data demonstrate that a physiological [Hb] improves, but does not normalize, exercise performance in end-stage renal failure. Both younger and older patients appear to benefit similarly from the enhanced oxygen transport. Impaired K+ regulation is apparently related to [Hb] and could well contribute to the observed limitations in performance.

Adult↗
PubMed1999

Impaired wound contraction in stromelysin-1-deficient mice.

OBJECTIVE: To determine whether the deletion of stromelysin-1, a single metalloproteinase gene product, will alter the time course and quality of dermal wound repair in mice. SUMMARY BACKGROUND DATA: After dermal injury, a highly coordinated program of events is initiated by formation of a fibrin clot, followed by migration of keratinocytes, contraction of the dermis, recruitment of inflammatory macrophages, formation of granulation tissue with angiogenesis, and finally tissue remodeling. Matrix metalloproteinases are rapidly induced in the dermis and granulation tissue and at the leading edge of the epidermis in the healing wounds. METHODS: Incisional and circular full-thickness wounds 2 to 10 mm were made in the dermis of stromelysin-1-deficient and wild-type mice. The wounds were analyzed for rate of cellular migration and epithelialization. The wound contraction was examined by immunohistochemical staining for alpha-smooth muscle actin and fluorescent staining for fibrillar actin. RESULTS: Independent of the age of the animal, excisional wounds in stromelysin-1-deficient mice failed to contract and healed more slowly than those in wild-type mice. Cellular migration and epithelialization were unaffected in the stromelysin-1-deficient animals. The functional defect in these mice is failure of contraction during the first phase of healing because of inadequate organization of actin-rich stromal fibroblasts. CONCLUSIONS: Excisional dermal wound healing is impaired in mice with a targeted deletion in the stromelysin-1 gene. Incisional wound healing is not affected. These data implicate stromelysin-1 proteolysis during early wound contraction and indicate that stromelysin-1 is crucial for the organization of a multicellular actin network.

Animals↗
PubMed1999

Health and well-being of women family carers: a comparative study with a generic focus.

OBJECTIVE: To examine differences between women family carers of people with chronic illnesses or disabilities and a group of women 'non-carers' in self-reported physical health, psychological well-being, life satisfaction, social support and feelings of overload. METHOD: Using a computer-assisted telephone interviewing system, a random survey of more than 26,000 households was conducted in Victoria to identify and then interview a representative sample of family carers of people with disabilities or chronic illnesses. The women in the sample (n = 857) were then compared with a sample of women with 'usual family responsibilities' (n = 219) in terms of physical and emotional states. RESULTS: We found higher rates of self-reported ill-health and use of medication, more negative effect, and less life satisfaction and perceived social support, among carers than among women in the comparison group. Even though the latter were more likely to be caring for one or more children, compared with the carers they reported less overload. Irrespective of carers status, women without partners expressed less life satisfaction, and more social isolation and negative effect. CONCLUSIONS AND IMPLICATIONS: The poorer health status and emotional well-being of carers compared with non-carers among women, and associations between overload, social isolation, negative effect and health problems within carers, point to a number of practical interventions such as promoting an awareness in GPs and other health professionals of the impact of caregiving on the health of their patients; informing them about relevant community services; and encouraging appropriate referrals.

Adaptation, Psychological↗