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D M Murphy

Publications and source records attributed to D M Murphy.

At least 55 records · Page 3Linked to original sources
PubMed1996

The SAM framework: modeling the effects of management factors on human behavior in risk analysis.

Complex engineered systems, such as nuclear reactors and chemical plants, have the potential for catastrophic failure with disastrous consequences. In recent years, human and management factors have been recognized as frequent root causes of major failures in such systems. However, classical probabilistic risk analysis (PRA) techniques do not account for the underlying causes of these errors because they focus on the physical system and do not explicitly address the link between components' performance and organizational factors. This paper describes a general approach for addressing the human and management causes of system failure, called the SAM (System-Action-Management) framework. Beginning with a quantitative risk model of the physical system, SAM expands the scope of analysis to incorporate first the decisions and actions of individuals that affect the physical system. SAM then links management factors (incentives, training, policies and procedures, selection criteria, etc.) to those decisions and actions. The focus of this paper is on four quantitative models of action that describe this last relationship. These models address the formation of intentions for action and their execution as a function of the organizational environment. Intention formation is described by three alternative models: a rational model, a bounded rationality model, and a rule-based model. The execution of intentions is then modeled separately. These four models are designed to assess the probabilities of individual actions from the perspective of management, thus reflecting the uncertainties inherent to human behavior. The SAM framework is illustrated for a hypothetical case of hazardous materials transportation. This framework can be used as a tool to increase the safety and reliability of complex technical systems by modifying the organization, rather than, or in addition to, re-designing the physical system.

Accidents, Traffic↗
PubMed1996

Effect of a tobacco-related nitrosamine on intercellular communication in human urothelial cells: a possible factor in smoking-related bladder carcinogenesis.

Bladder cancer is associated with smoking. Among the tobacco-derived carcinogens suspected of being involved in initiating the disease are nitrosamines found in urine. In this study a nitrosamine found in the urine of smokers was tested using a tissue culture model of normal human urothelium. Explant cultures were established from ureters and exposed to 5 ng/ml of the derivative. This level had been demonstrated previously to induce a variety of changes associated with initiation of carcinogenesis. Proliferation of the cultures was increased following exposure to the carcinogen, and the gap junction intercellular communication was reversibly inhibited. Examination of the connexin 43 protein and message status showed that the mRNA was unaffected, but the protein was not detectable using anti-connexin 43 antibody. The expression of the protein recovered within 24 h of removal of the carcinogen, indicating that the continued presence of the agent was necessary. Given the roles of cell proliferation and cell communication in carcinogenesis, the results may suggest a mechanism involving pre- or post-initiation deregulation of cell communication systems. Whether the enhanced growth is a separate effect or a consequence of reduced communication is an intriguing question.

Carcinogens↗
PubMed1995

Mechanical ventilation with or without 7-day circuit changes. A randomized controlled trial.

OBJECTIVE: To determine whether a practice of not routinely changing ventilator circuits in patients who require prolonged mechanical ventilation is associated with an increased incidence of nosocomial pneumonia. DESIGN: Randomized controlled trial. SETTING: Intensive care units in two university-affiliated teaching hospitals. PATIENTS: 300 patients admitted to an intensive care unit who required mechanical ventilation for more than 5 days. INTERVENTION: Patients were randomly assigned to receive either no routine ventilator circuit changes or circuit changes every 7 days. MEASUREMENTS: The primary outcome measure was the incidence of ventilator-associated pneumonia. Other outcome measures included duration of mechanical ventilation, length of hospital stay, and hospital mortality. RESULTS: 147 patients were randomly assigned to receive no routine ventilator circuit changes, and 153 patients were randomly assigned to receive circuit changes every 7 days. The two groups were similar at the time of randomization with regard to demographic characteristics, intensive care unit admission diagnoses, and severity of illness. Ventilator-associated pneumonia was seen in 36 patients (24.5%) receiving no routine changes and in 44 patients (28.8%) receiving changes every 7 days (relative risk, 0.85 [95% CI, 0.55 to 1.17]). No statistically significant differences for hospital mortality, intensive care unit mortality, death during mechanical ventilation, death in patients with ventilator-associated pneumonia, or mortality directly attributed to ventilator-associated pneumonia were found between the two treatment groups (P > or = 0.11). Patients receiving changes every 7 days had 247 circuit changes costing a total of $7410; patients receiving no routine changes had a total of 11 circuit changes costing $330. CONCLUSION: The elimination of routine ventilator circuit changes can reduce medical care costs without increasing the incidence of nosocomial pneumonia in patients who require prolonged mechanical ventilation.

Adult↗
PubMed1995

Control of group C meningococcal disease in Australian aboriginal children by mass rifampicin chemoprophylaxis and vaccination.

An outbreak of 12 cases of meningitis, 11 caused by Neisseria meningitidis serogroup C, occurred at Doomadgee from September, 1990, to April, 1991. The incidence of meningitis was 17.55/10(3) person-years. Only children aged 1-10 years were affected. In October, 1990, or shortly thereafter, 473/509 children aged between 1 and 15 years inclusive had one dose of Mencevax AC. From the time of vaccination until April, 1991, a further eight cases occurred, six in vaccinated children. Vaccine efficacy in 1-15 year olds was calculated as 77%. Despite this, in April, 1991, the prevalence of antibody to group C polysaccharide in vaccinated children (78%) was not significantly different from that in unvaccinated children and adults. 46 nonresponders were revaccinated, and, in February, 1992, 78% had antibodies to group C polysaccharide. In April, 1991, an estimated 3.0% of the population had group C organisms, carriage being directly related to household crowding. In June, 1991, 2 months after mass prophylaxis with rifampicin, none of these individuals were carriers. In October, 1991, the carriage rate of group C organisms was 0.64%. There have been no further cases caused by the epidemic strain. Although uncrowded housing is a basic need, mass chemoprophylaxis and two doses of vaccine for children should be used in similar outbreaks.

Adolescent↗
PubMed1995

Expression of p53 in urothelial cell cultures from tumour-bearing and tumour-free patients.

An explant culture technique was used to culture normal urothelium from patients with muscle-invasive bladder cancer (transitional cell carcinoma, TCC) (n = 11) and from non-tumour-bearing patients (n = 60). Cell cultures were examined for expression of p53 using the monoclonal antibody p53-240. There was a statistically significant increase in p53 expression in normal urothelial cell cultures from patients with TCC (P < 0.0005). Normal urothelial cultures from patients with TCC also showed more rapid proliferation in vitro when compared with non-tumour-bearing patients (P < 0.0005). A subgroup of non-tumour-bearing patients (n = 14) showed > 5% of cells expressing p53. p53 expression in this subgroup was found to correlate with cell proliferation in vitro (r2 = 0.766). None of these urothelial specimens was observed to express p53 when paraffin-embedded preparations were stained with p53-D07 antibody prior to culture. The rate of cellular proliferation in this subgroup did not differ from that of normal urothelium from TCC patients. Twenty-two paraffin-embedded, muscle-invasive TCC specimens were also evaluated for p53 expression using p53-D07. The expression of p53 in these tumours did not differ from that observed in normal urothelial cell cultures from patients with TCC (P = 0.26). This study identifies an overexpression of p53 in normal urothelial cells from patients with TCC and in proliferating cultures from a significant subgroup of patients without malignant disease. Increased p53 expression in normal cultured urothelial cells from patients with bladder cancer implies a global change in the mechanisms controlling urothelial cell division. This may represent an early step in the pathway to carcinogenesis.

Carcinoma, Transitional Cell↗
PubMed1995

The effect of late-onset ventilator-associated pneumonia in determining patient mortality.

STUDY OBJECTIVE: To determine whether the development of late-onset ventilator-associated pneumonia (VAP) is associated with an increased risk of hospital mortality. DESIGN: Prospective cohort study. SETTING: ICUs of two university-affiliated teaching hospitals. PATIENTS: Three hundred fourteen patients admitted to an ICU who required mechanical ventilation for greater than 5 days. INTERVENTIONS: Prospective patient surveillance and data collection. MEASUREMENTS: The primary outcome measures were the development of late-onset VAP (ie, occurring > 96 h after intubation) and hospital mortality. RESULTS: Late-onset VAP was observed in 87 patients (27.7%). Thirty-four (39.1%) patients with late-onset VAP died during hospitalization compared with 85 patients (37.4%) without late-onset VAP (relative risk, 1.04; 95% confidence interval [CI], 0.76 to 1.43). Twenty patients (6.4%) developed late-onset VAP due to a "high-risk" pathogen (ie, Pseudomonas aeruginosa, Acinetobacter sp, Xanthomonas maltophilia) with an associated mortality rate of 65%. Stepwise logistic regression analysis identified five variables as independent risk factors for hospital mortality (p < 0.05): an organ system failure index of 3 or greater (adjusted odds ratio [AOR], 3.4; 95% CI, 2.0 to 5.8; p < 0.001), having a nonsurgical diagnosis (AOR, 2.1; 95% CI, 1.3 to 3.6; p = 0.002), a premorbid lifestyle score of 2 or greater (AOR, 1.8; 95% CI, 1.1 to 2.9; p = 0.015), acquiring late-onset VAP due to a "high-risk" pathogen (AOR, 3.4; 95% CI, 1.2 to 10.0; p = 0.025), and having received antacids or histamine type-2 receptor antagonists (AOR, 1.7; 95% CI, 1.0 to 2.9; p = 0.034). Additionally, we found the occurrence of late-onset VAP due to high-risk pathogens to be the most important predictor of hospital mortality among patients developing VAP (AOR, 5.4; 95% CI, 2.8 to 10.3; p = 0.009). CONCLUSIONS: Nosocomial pneumonia due to certain high-risk microorganisms is an independent risk factor for hospital mortality among patients requiring prolonged mechanical ventilation. We suggest that future investigations of late-onset VAP stratify patient outcomes according to the distribution of high-risk pathogens when reporting their results.

APACHE↗
PubMed1995

Primary explants of human uroepithelium show an unusual response to low-dose irradiation with cobalt-60 gamma rays.

Recent results using very low doses of radiation have suggested that there is a hypersensitive region where cultures show an enhanced level of cell killing leading to a non-monotonic survival curve. This effect has been observed at doses below 2 Gy in mammalian systems and at much higher doses in insect cells. In this paper we report observation of the effect in primary human uroepithelial cell cultures. The effect was measured using a postirradiation proliferation assay where irradiated explants of standard size were allowed to proliferate for 14 days after exposure to 60Co gamma irradiation. By 14 days the majority of cultures derived from explants irradiated with 2-5 Gy showed little evidence of growth inhibition and cell numbers approached or even exceeded those obtained in the controls. There was, however, a significant reduction in cell number and growth rate in all cultures exposed to doses lower than 1 Gy. Oncoprotein (p53, c-myc, bcl-2, p21 ras) and EGFR expression were also measured in these cultures and were significantly increased. Morphological evidence of apoptosis was present in all irradiated cultures at 4 h after exposure, but this persisted for longer periods in cultures exposed to low doses.

Cell Survival↗
PubMed1995

Variation in the expression of p53, c-myc, and bcl-2 oncoproteins in individual patient cultures of normal urothelium exposed to cobalt 60 gamma-rays and N-nitrosodiethanolamine.

The controls determining the initial response of cells to DNA damage probably determine whether a cancer will ultimately occur. Efficient repair or apoptosis represents extremes of control mechanisms. Misrepair can lead to fixation of damage. The changes in oncoprotein expression of three genes involved in the regulation of repair of DNA damage and postdamage proliferation of cells were measured in cultures of normal urothelium from 55 patients without any malignancy. The aim was to obtain information on interperson variation in response to carcinogens in the human population. The group included 10 pediatric patients < 2 years old. Two different carcinogenic agents, ionizing radiation and N-nitrosodiethanolamine, which represent widely different DNA-damaging pathways, were used. Both of these cause bladder cancer in humans. Cells from explanted tissue were examined after carcinogen exposure for levels of p53, c-myc, and bcl-2 proteins. Both carcinogens led to increased levels of cytoplasmic p53 protein expression, although there was significant interpatient variation. bcl-2 showed a very significant increase in expression after radiation exposure. c-myc was high and variable pre- and postexposure. Individual patient culture changes in the expression of the three oncoproteins did not correlate significantly with each other or with cell growth, suggesting that the controls are complex. Pediatric samples had lower mean control values of p53 and bcl-2 than did adult samples. This was due to the absence in this group of high controls seen in some adult cultures. The result suggest that an early breakdown in control mechanisms of growth arrest and apoptosis may occur in urothelium after carcinogen exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Transplant nephrectomy over 20 years: factors involved in associated morbidity and mortality.

Of 1,048 renal transplants performed between 1971 and 1990, transplant nephrectomy was performed in 86 (8.2%). Mean patient age was 33 years (range 3.8 to 66.5). Postoperative complications occurred in 60% of the patients, including wound infection in 20% and major hemorrhage in 4 patients. The external iliac artery was ligated in 4 patients. The incidence and severity of the complications were greater in patients with acute rejection. Four patients died: 1 of ischemic bowel and metastatic carcinoma, 1 of pulmonary embolism, and 2 of sepsis and disseminated intravascular coagulation. The nephrectomy rate increased significantly (p < 0.005) when cyclosporine A was initially introduced. Added care is necessary when new immunosuppressants are used. The majority of our failed transplants were left in situ without compromising overall patient well-being.

Adolescent↗
PubMed1994

Renal transplantation in patients with spina bifida.

OBJECTIVES: Renal transplantation in patients with spina bifida is not commonly performed, although these patients have a high incidence of end-stage renal disease. METHODS: Between February 1989 and December 1991, we performed 5 cadaveric renal transplants in 4 patients with spina bifida. There were 3 male patients and 1 female patient with a mean age of 22.5 years (range, 10 to 36 years). All patients had lumbar myelomeningoceles repaired shortly after birth. Three patients were wheelchair-bound due to their neurologic deficit. Prior to renal transplantation, management of neuropathic bladder dysfunction consisted of ileal conduit (1 patient), "clam" cystoplasty with clean intermittent self-catheterization (CISC; 1 patient), and CISC alone (2 patients). RESULTS: In this series, 1 patient died of fungal septicemia 6 weeks postoperatively. One patient underwent transplantation again following primary nonfunction of his original allograft. Serum creatinine levels were 56, 91, and 120 mmol/L, respectively, after 18 months' follow-up. CONCLUSIONS: This article demonstrates the feasibility of cadaveric renal transplantation in selected patients with end-stage renal failure and spina bifida. We currently recommend that these patients not be excluded from gaining the benefits of renal transplantation.

Adolescent↗
PubMed1994

Pathogenicity of the hookworm, Ancylostoma pluridentatum, in a Florida panther (Felis concolor coryi) kitten.

We evaluated clinical signs and administered anthelmintic treatment to a wild-caught, captive Florida panther (Felis concolor coryi) kitten from Big Cypress National Preserve, Florida (USA) infected with the hookworm, Ancylostoma pluridentatum. Clinical signs observed included poor body condition, lethargy, and below normal red blood cell numbers, hemoglobin concentration, and packed cell volume, and elevated eosinophil numbers. In addition, a maximum of 936 Ancylostoma sp. eggs/g of feces were found on Day 11 of captivity. Following oral administration of 20 mg/kg pyrantel pamoate on Day 11, 26 A. pluridentatum were collected from the feces. Based on the resolution of clinical signs, cessation of egg shedding, and a return to normal hematologic values following anthelmintic treatment, we believe that infection with A. pluridentatum was the primary cause of the stressed conditions in the panther kitten.

Administration, Oral↗
PubMed1993

Older donors and kidney transplantation.

Reluctance to use kidneys from older donors (> 50 years of age) is based on reports of inferior results. We reviewed our experience with 45 kidneys transplanted from older donors. Primary nonfunction, immediate graft function, and 1-, 2- and 3-year graft survival rates were similar to those obtained with kidneys transplanted from donors aged between 20 and 40 years. Renal function at 1 year (as measured by serum creatinine) was poorer in kidneys from older donors. No beneficial effect with respect to graft survival was noted with cyclosporin therapy compared to conventional immunosuppression; however, the numbers are small. We conclude that kidneys from older donors are a valuable source for transplantation.

Adult↗
PubMed1993

c-myc expression in renal carcinoma: correlation with clinical parameters.

There is evidence that c-myc is expressed in renal carcinomas and that it is associated with histological grade. This study reports on the clinical correlations of oncogene expression and clinical features of the disease. Tissue sections from 97 patients (95 primary and 12 secondary cancers) were immunostained with a c-myc oncoprotein antibody. The tumours were scored for extent and intensity of nuclear and cytoplasmic staining. Ninety patients were suitable for follow-up study. High levels of expression correlated significantly with increasing T category and nuclear grade, as well as with venous invasion. No correlation with nodal involvement, the presence of metastases, tumour architecture or cell type was found. The extent of nuclear staining was related to survival (although not to recurrence), but in a multivariate analysis did not provide independent prognostic information. It was concluded that semiquantitative assessment of levels of c-myc oncoprotein does not provide clinically useful prognostic information.

Adult↗
PubMed1993

Ploidy and prognosis in renal carcinoma.

The value of tumour ploidy status as a prognostic indicator in renal carcinoma is disputed. In this retrospective study the DNA content of 90 primary and 10 secondary renal cell carcinomas was measured using flow cytometry. Data on recurrence and survival were available in all cases. Tumours were staged according to the TNM system and histological grade was based on nuclear morphology. Formalin-fixed, paraffin-embedded material was processed using standard techniques. Multiple samples were examined in 19 cases. Of the primary tumours, 52 were diploid, 24 were aneuploid and 6 were tetraploid; 8 patients had uninterpretable histograms. Ploidy of the secondary tumours was similar to that of their respective primaries. Aneuploidy correlated with higher grade but not with TNM category and, although associated with an increased risk of death, did not provide independent prognostic information. Heterogeneity of ploidy was found in 6 of the 19 cases where more than 1 sample was assessed. It was concluded that tumour DNA content in renal carcinoma is weakly linked to outcome, is subject to sample error and does not provide accurate prognostic information as a single independent variable.

Adult↗
PubMed1993

Seasonal affective disorder: response to light as measured by electroencephalogram, melatonin suppression, and cerebral blood flow.

This study was designed to test the hypothesis that patients with SAD have significantly different physiological responses to light than healthy age- and sex-matched controls. We studied retinal contrast sensitivity, visual evoked EEG responses, and melatonin suppression by, and cerebral blood flow response to, full-spectrum artificial daylight. There was no significant difference between 10 patients and 11 controls in retinal contrast sensitivity, or amplitude or latency of N2, P2, P100 or P300 on EEG. We compared melatonin suppression in 12 SAD patients and 12 controls. During exposure to 500 lux and 1500 lux artificial daylight both the SAD patients and controls had a significant melatonin percentage suppression; however, the percentage suppression did not differ significantly between the SAD patients and the controls. In addition, we carried out a small pilot study into the effect of light on cerebral blood flow in four SAD patients and four controls. Before exposure to 1500 lux artificial daylight there was no significant difference between patients and controls in global, regional or cerebral hemispheric blood flow. After light exposure the SAD patients and controls had a significantly different percentage change in cerebral blood flow. We suggest that patients with SAD do not have significantly physiological responses to light than controls, except perhaps in cerebral blood flow. Furthermore, mechanisms other than supersensitivity of melatonin suppression must explain both the pathophysiology of the disorder and its response to treatment with light.

Bipolar Disorder↗