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Biomedical subjects

Michael Murphy

Publications and source records attributed to Michael Murphy.

At least 55 records · Page 3Linked to original sources
PubMed2003

Modulation of plasma thiols and mixed disulfides by BNP7787 in patients receiving paclitaxel/cisplatin therapy.

BACKGROUND: BNP7787 (disodium 2,2'-dithio-bis-ethane sulfonate) was evaluated in a phase I clinical trial with paclitaxel and cisplatin to assess the safety and potential efficacy for preventing or reducing cisplatin- and paclitaxel-induced toxicities. During this trial the effects of BNP7787 administration on the total concentrations (oxidized plus free) of cysteine, homocysteine and GSH in plasma, free and total GSH in WBC and rate of urinary excretion of cysteine were studied. The pharmacokinetics of ultrafilterable (free, non-protein bound) platinum were also determined after cisplatin (75 mg/m(2)) treatment which followed paclitaxel (175 mg/m(2)) and BNP7787 (8.2 to 27.6 g/m(2)). METHODS: Plasma thiols were measured by HPLC with fluorescence detection and platinum was measured by atomic absorption spectrophotometry. RESULTS: BNP7787 administration produced a significant depletion of all plasma thiols in all the patients studied. Differences were noted in the kinetics of BNP7787-induced depletion of cysteine and other thiols. A significant depletion of cysteine occurred with a time lag of about 2 h after the end of BNP7787 infusion, while a reversible depletion of GSH and homocysteine occurred immediately following the start of BNP7787 infusion, with the plasma thiol/disulfide nadir corresponding to the end of infusion. The mean half-life of cysteine depletion following BNP7787 administration was 2.2 h, significantly longer than for homocysteine (0.23 h), or GSH (0.18 h; P<0.05 for both). A several-fold increase in the urinary excretion of cysteine occurred following BNP7787 administration in all patients. The BNP7787-induced thiol/disulfide depletion in plasma was not affected by cisplatin administration ( P>0.05). BNP7787 administration had no effect on the ultrafilterable platinum pharmacokinetics. The 2-h lag in the depletion of cysteine, the most abundant thiol in plasma, suggests that the process may be related to the formation of free mesna from BNP7787 and that increased levels of mesna are not in circulation until after 2 h after BNP7787 administration. No effect of BNP7787 was seen on the GSH concentration in WBC, possibly reflecting the inability of these cells to take up BNP7787. CONCLUSION: The results suggest that BNP7787 has the potential to enhance cisplatin antitumor activity by depleting the reactive thiols in plasma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis.

Vascular access site thrombosis is a major cause of morbidity in patients receiving hemodialysis. The role of hypercoagulable states in recurrent vascular access site thrombosis remains poorly understood. Data are limited regarding systemic anticoagulation to improve access graft patency, because of concern about hemorrhagic complications. We determined the prevalence of hypercoagulable states and clinical outcome (thrombotic and hemorrhagic) after initiation of antithrombotic therapy in a series of patients with recurrent vascular access site thrombosis. We evaluated 31 patients who had sustained 119 thrombotic events that resulted in vascular access graft failure during the year before evaluation. Sixty-eight percent of patients tested had elevated concentrations of antibody to anticardiolipin or topical bovine thrombin, and 18% of patients tested had heparin-induced antibodies. More than 90% of patients had elevated factor VIII concentration, 62% had elevated fibrinogen concentrations, and 42% had elevated C-reactive protein concentrations. Twenty-nine patients were given antithrombotic therapy: 13 with warfarin sodium, 12 with unfractionated heparin (UFH), and 11 with low molecular weight heparin (LMWH). Seven patients received more than one antithrombotic agent, sequentially. Nineteen patients have had no thrombotic events since beginning antithrombotic therapy (10 with warfarin, 3 with UFH, 6 with LMWH). Mean follow-up was 8.6 months (median, 7 months). Eight patients sustained 10 bleeding complications (5 with warfarin, 3 with UFH, and 2 with LMWH). In conclusion, hypercoagulable states are common in patients with recurrent vascular access site thrombosis. Antithrombotic therapy may increase vascular access graft patency, but is associated with significant risk for hemorrhage. Prospective studies are needed to evaluate the role and safety of antithrombotic agents in improving vascular access graft patency.

Adult↗
PubMed2003

Patient safety and blood transfusion: new solutions.

Current risk from transfusion is largely because of noninfectious hazards and defects in the overall process of delivering safe transfusion therapy. Safe transfusion therapy depends on a complex process that requires integration and coordination among multiple hospital services including laboratory medicine, nursing, anesthesia, surgery, clerical support, and transportation. The multidisciplinary hospital transfusion committee has been traditionally charged with oversight of transfusion safety. However, in recent years, this committee may have been neglected in many institutions. Resurgence in hospital oversight of patient safety and transfusion efficacy is an important strategy for change. A new position, the transfusion safety officer (TSO), has been developed in some nations to specifically identify, resolve, and monitor organizational weakness leading to unsafe transfusion practice. New technology is becoming increasingly available to improve the performance of sample labeling and the bedside clerical check. Several technology solutions are in various stages of development and include wireless handheld portable digital assistants, advanced bar coding, radiofrequency identification, and imbedded chip technology. Technology-based solutions for transfusion safety will depend on the larger issue of the technology for patient identification. Devices for transfusion safety hold exciting promise but need to undergo clinical trials to show effectiveness and ease of use. Technology solutions will likely require integration with delivery of pharmaceuticals to be financially acceptable to hospitals.

Blood Transfusion↗
PubMed2003

Emotional and social dysfunction in patients following surgical treatment for brain tumour.

Patients following brain surgery for tumour were assessed using the Emotional and Social Dysfunction questionnaire on a self-rating and partner version of the questionnaire. Analyses were performed on those patients who had self-ratings following surgery for astrocytoma (n=13), meningioma (n=26), neuroma (n=13) and pituitary adenoma (n=17). Patients with astrocytoma were rated highest when compared to the other tumour groups, although all groups of patients performed more poorly on some of the individual scales compared to a matched control group of extra-cerebral neurosurgery patients and terminally ill cancer patients. A malignant (n=48) and benign (n=33) classification similarly showed a higher partner and self-rating of malignant tumour patients. Both diagnosis and location of lesion determined outcome independently. Some differences in profile and severity between patient self-ratings and partner ratings indicate the need to survey both perspectives. This study shows a broader based emotional dysfunction in these patients which includes such prominent features such as anger, helplessness, fatigue, emotional dyscontrol, indifference, and maladaptive behaviour. These results are discussed in terms of follow-up therapeutic care and the need to further explore the relationship between lesion location and emotional profile.

Adenoma↗
PubMed2003

The ESDQ: a new method of assessing emotional and social dysfunction in patients following brain surgery.

The Emotional and Social Dysfunction Questionnaire (ESDQ) has been designed to overcome some of the difficulties of inappropriately applying psychiatric based questionnaires to brain-damaged populations. Two-hundred and twenty-five patients were assessed following brain surgery (BS) using a self-rating patient version of the ESDQ and 211 of these patients were rated by their partner. A factor analysis using a varimax rotation and principal components analysis found the partner results to show eight factors including, Anger, Helplessness, Emotional Dyscontrol, Indifference, Inappropriateness, Fatigue, Maladaptive behaviour, and Insight. The analysis of the Self-rating questions revealed a similar profile, Anger, Emotional Dyscontrol, Helplessness, Inertia, Fatigue, Indifference, Inappropriate, and Euphoria. The scales based on the factors were subjected to discriminant analysis in which the BS patients were compared with a combination control group of neurosurgical outpatients and terminally-ill cancer patients, all of which were without cerebral complaints. The brain surgery results for the partner-rated and the Self-rated version of the ESDQ were compared with control ratings of 42 partners and 54 self-ratings, respectively. The analysis showed a significant discrimination for the Partner-rated version on each of the eight scales individually with an overall significant overall separation (Wilks Lambda=.903, chi=21.1, df=8, p=<.005). The Self-rated version showed less separation on an individual scale basis the Emotional Dyscontrol scale failing to show a significant separation. The overall difference on the Self-rating version was significant [Wilks Lambda=.908, chi=26.2, df=8, p=<.001). The levels of internal consistency of the questionnaire scales were found to be satisfactory (Alpha,.78 -.94). Also the relationship between ESDQ scales and standardised measures of aggression, anxiety, depression, and vigour (STAXI, HADS, and POMS) gave an indication of acceptable levels of concurrent validity.

Adult↗
PubMed2003

Does the DRD2-Taq1 A polymorphism influence treatment response to bupropion hydrochloride for reduction of the nicotine withdrawal syndrome?

Bupropion hydrochloride is effective in promoting long-term abstinence from smoking and may reduce risk for relapse through attenuation of withdrawal symptoms and craving. Bupropion is a weak dopamine reuptake inhibitor, and individual genetic variation in the dopamine D2 receptor has been associated with nicotine dependence in case-control studies. Thirty smokers were randomly assigned to bupropion or placebo and interviewed using the Minnesota Nicotine Withdrawal Scale on two occasions: prior to starting medication and after 14 days on bupropion or placebo. The individual symptoms of craving, irritability, and anxiety were significantly reduced in the bupropion group, whereas no withdrawal symptoms were diminished in the placebo group. Within the bupropion group, subgroup analyses with stratification by genotype demonstrated that craving, irritability, and anxiety were significantly attenuated only among subjects with DRD2-Taq1 A2/A2 genotypes. In the DRD2-Taq1 A1/A1 and A1/A2 groups, no significant reduction was seen in any individual symptom of the nicotine withdrawal syndrome. These data suggest that bupropion attenuates specific symptoms of the nicotine withdrawal syndrome and that this effect may be modified by genotype for the dopamine D2 receptor.

Adult↗
PubMed2003

Reciprocal Cdc25A and p27 expression in B-cell non-Hodgkin lymphomas.

Cell cycle regulation is often altered in cancer and deregulation of the cell cycle checkpoints is common in human neoplasia. The dual-specificity phosphatase Cdc25A and the cell cycle inhibitor p27 both play an important role in the regulation of the G1-S transition. We evaluated Cdc25A mRNA expression by in situ hybridization and p27 protein expression by immunohistochemistry in 42 histologically indolent B-cell non-Hodgkin lymphoma (NHL and 51 histologically aggressive B-cell NHL. Overexpression of Cdc25A (>50% tumor cells positive) was detected in 5 of 42 cases (12%) of histologically indolent B-cell NHL and in 29 of 51 (57%) of histologically aggressive B-cell NHL (P < 0.001). In contrast, high p27 protein expression (>50% tumor cells positive) was observed in 29 (69%) cases of indolent but in only one case (2%) of aggressive B-cell NHL (P < 0.0001). Thus, overexpression of Cdc25A and concomitant loss of p27 expression are associated with high grade B-cell NHL and may contribute to their aggressive biologic behavior.

Cell Count↗
PubMed2003

Determinants of adult mortality in Russia: estimates from sibling data.

OBJECTIVES: It would be useful to have a quick and cost-effective method to study individual-level determinants of mortality in countries where reliable data are not available. We have modified indirect demographic methods and applied them to a population sample to investigate predictors of mortality in Russia. METHODS: A national sample of the Russian population was interviewed in a cross-sectional survey. The participants were asked about characteristics of their eldest siblings, including their vital status, year of birth, and year of death (if deceased). The association between personal characteristics and mortality risk was estimated for 682 male and 698 female siblings (of whom 122 and 81, respectively, had died). RESULTS: In both sexes, mortality was strongly associated with smoking and low education. After adjustment for smoking and education, mortality was elevated in men and women who drank alcohol at least once a month. Mortality was also higher among in men who had been binge drinking (more than half a bottle of vodka per drinking session) at least once a week (adjusted risk ratio [RR] = 2.5; 95% confidence interval [CI] = 1.2-4.9) and in women who were binging at least once a month (RR = 3.9; CI = 1.1-14.5) compared with nonbinging. SUBJECTS: Similar associations with drinking were seen for cardiovascular deaths in men. Childhood social circumstances were not associated with mortality. CONCLUSIONS: The study of siblings appears to be a cost-effective alternative for estimating risk factors for mortality in literate populations. This study identified smoking, low education, and alcohol consumption (especially binge drinking) as risk factors for mortality in Russia.

Adult↗
PubMed2003

How clonal is Staphylococcus aureus?

Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable "core" genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.

Alleles↗
PubMed2003

Selective processing of smoking-related cues in current smokers, ex-smokers and never-smokers on the modified Stroop task.

The aim of this study was to investigate selective processing biases towards smoking-related stimuli in relation to acute abstinence and smoking history. Differences in the processing of smoking-related and control cues in current smokers, ex-smokers and never-smokers on the modified Stroop task were investigated, with smokers randomized to either abstain or smoke normally for a period of 24 h. The results indicated no significant effect of deprivation (abstinent versus non-abstinent smokers), or of smoking history (ex- versus never-smokers) on colour-naming times for smoking-related versus control words. However, there was a significant effect of smoking status (current versus non-smokers) on colour-naming times for smoking words compared to control words (i.e. slower colour-naming of smoking-related words in smokers). This effect approached significance when stimuli were presented in a masked exposure condition. Among smokers, colour-naming interference was associated with the personality trait of Sensitivity to Reward. These results indicate a processing bias for smoking-related cues in current smokers. However, this bias does not appear to be a permanent feature of nicotine addiction, given the lack of difference between ex-smokers and never-smokers.

Adult↗
PubMed2003

Screening for handicapping hearing loss in the elderly.

OBJECTIVE: To compare 2 screening methods for unrecognized handicapping hearing loss in the elderly. STUDY DESIGN: Cross-sectional study. POPULATION: Five hundred forty-six older individuals who underwent audiometry at biennial examination 22 of the Framingham Heart Study and who took the Hearing Handicap Inventory for the Elderly-Screening (HHIE-S) questionnaire. OUTCOMES MEASURED: The 2 screening methods were the 10-item HHIE-S and 1 global question: "Do you have a hearing problem now?" The gold standard was an audiogram showing a pure tone threshold of 40 dB HL or higher at 1 and 2 kHz in one ear or at 1 or 2 kHz in both ears. Both screening methods were compared with the gold standard in terms of sensitivity, specificity, and predictive values. The 10-item screening version of the HHIE-S (cutoff score between 8 and 10) had a sensitivity of 35% and a specificity of 94% for detecting the criterion hearing loss. The global subjective measure had greater sensitivity (71%) but lower specificity (71%) than the HHIE-S. Combining the global question and the HHIE-S items failed to improve the specificity of the global question or the sensitivity of the HHIE-S. CONCLUSIONS: The global measure of hearing loss was more effective than the detailed questionnaire in identifying older individuals with unrecognized handicapping hearing loss. Primary care physicians are encouraged to ask their patients whether they have a hearing problem and refer patients who do for formal hearing testing.

Activities of Daily Living↗
PubMed2003

Mothers with living children and children with living mothers: the role of fertility and mortality in the period 1911-2050.

Whether an individual has one or more surviving children at a given age and/or a surviving parent depends both on fertility (not only number of children, but also timing of childbearing) and mortality. We consider the contribution of changes in mortality and fertility to past and likely future trends on availability of such kin. The proportion of people aged 60 with a mother alive will more than double between those born in 1911 and 1970, and the figure will increase for at least the next 30 years. While there are increasing concerns about the availability of informal care for elderly people from children in the next quarter century or so, in fact we conclude that a higher proportion of elderly people are likely to have a surviving child than for any generation ever born in Britain, and will have more than any foreseeable future cohort.

Adult↗
PubMed2002

Mortality patterns in the Russian Federation: indirect technique using widowhood data.

OBJECTIVE: The Russian mortality crisis of the early 1990s attracted considerable attention, but information on possible covariates of mortality is lacking, and concerns have been raised about the validity of official mortality data. To help elucidate the determinants of mortality, we examined whether indirect demographic techniques could be used to study mortality in countries such as the Russian Federation, where mortality data are inadequate, using input data independent from official vital statistics. METHODS: A national sample of the population was interviewed (n = 1600, response rate = 67%). Participants who had ever been married (82% of the sample) were asked about the date of birth and vital status of their first spouse. Spousal mortality was then estimated indirectly for the 531 men and 710 women for whom valid data were available. FINDINGS: The estimated risk of death between the ages of 35-69 years was 57% for male spouses and 17% for female spouses. Corresponding figures derived from national data for 1990 were 52% and 25% for the Russian Federation, and 31% and 20% for the United Kingdom. According to spouses' reports, 38% of their husbands died from cardiovascular disease, 22% from cancer, and 14% from injuries and accidents. Mortality of male spouses was inversely related to the education level of their wives, and the age-adjusted hazard ratios for death from all causes, compared to primary education, were 0.77 for secondary education and 0.57 for university education (trend P = 0.03). Mortality was also inversely related to ownership of household items, but not to size of settlement, pride in Russia, membership in the Soviet Communist Party, nationality or self-assessed social status. CONCLUSIONS: Although the indirect estimates were imprecise (partly owing to the small population size of the study), and mortality in women was probably underestimated (owing to many factors, including poorer reporting by males and high male mortality), our results are nevertheless consistent with the mortality pattern observed in official mortality data. The indirect technique thus appears to be a useful tool to study the determinants of mortality in the Russian Federation and other populations, where reliable or sufficiently extensive data are not available.

Adult↗