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Biomedical subjects

K O'Rourke

Publications and source records attributed to K O'Rourke.

At least 37 records · Page 2Linked to original sources
PubMed2000

Job satisfaction among nursing staff in a military health care facility.

Job satisfaction in the workplace affects absenteeism, turnover, and performance. We conducted a cross-sectional study of 201 nursing personnel to assess satisfaction among nursing staff at a military hospital in the southwestern United States. Participants completed a self-administered survey in which they rated professional status, autonomy, pay, organizational policies, task requirements, and interaction by importance and satisfaction. Autonomy, professional status, and pay were the most important factors and organizational policies was the least important factor. Military staff were slightly more satisfied with staff interactions than civilian staff. Nursing personnel working in specialty care units were significantly more satisfied with interactions and professional status, but they valued organizational policies less than those working in general units. Professionals were significantly more satisfied with pay and autonomy, whereas nonprofessionals were more satisfied with task requirements and professional status.

Cross-Sectional Studies↗
PubMed2000

Increased prevalence and analysis of risk factors for indinavir nephrolithiasis.

PURPOSE: Indinavir is a protease inhibitor used for treating HIV-1. The drug is lithogenic and was thought to cause a 3% incidence of kidney stones. We evaluated a cohort of patients positive for HIV on indinavir to determine the incidence of indinavir nephrolithiasis and identify risk factors for indinavir stone formation. MATERIALS AND METHODS: Our cohort study of the prevalence of indinavir nephrolithiasis included 155 patients with HIV for 5,732 patient-weeks. The same cohort was then used for a retrospective chart review to assess patient age, weight, duration of drug use, time to stone formation, CD4 count, creatinine, alanine transaminase, and urinary pH and specific gravity as risk factors for stone formation. RESULTS: We estimated the cumulative incidence of indinavir stone formation by the Kaplan-Meier product limit estimator method. At 78 weeks 43.2% of patients had stones (95% confidence interval [CI] 0.292 to 0.543). Increasing age was the only variable that was a statistically significant predictor of indinavair urolithiasis (relative risk 0.955, 95% CI 0.918 to 0.993, p = 0.0159). The mean duration plus or minus standard deviation of indinavir use was statistically the same in each group (42.5 +/- 27. 2 and 40.3 +/- 27.1 weeks in those without and with stones, respectively) despite the observed mean time to stone formation of 23.0 +/- 19.8 weeks. CONCLUSIONS: The clinical prevalence of indinavir nephrolithiasis is much greater than initially reported. Nephrolithiasis during indinavir use does not appear to induce patients to withdraw from the drug.

Adult↗
PubMed1999

Age distribution of Helicobacter pylori seroprevalence among young children in a United States/Mexico border community: evidence for transitory infection.

Helicobacter pylori infection has been linked to a spectrum of gastroduodenal diseases of broad public health impact, yet the natural history of this frequently asymptomatic infection remains poorly understood. Evidence suggests that initial acquisition occurs primarily during childhood and may persist throughout life. The seroprevalence of H. pylori antibodies was examined in 365 primary schoolchildren aged 4-7 years in a low-income United States/Mexico border community from January to May 1996. Overall, 21% of the 365 children tested positive, with a significant monotonic decrease in seroprevalence by 1-year age intervals (36% in children aged 4 years, 24% in those aged 5 years, 20% in those aged 6 years, and 14% in those aged 7 years). The odds ratio for each 1-year age increase was 0.76 (95% confidence interval: 0.6, 1.0) after adjustment for relevant covariates. Given that H. pylori antibodies diminish after infection clears, this trend suggests that transient infection may be common in young children. In contrast, hepatitis A virus seroprevalence increased with age. There was a moderate association (odds ratio = 1.47, 95% confidence interval: 0.8, 2.9) of H. pylori with hepatitis A virus seroprevalence that weakened after adjustment for age and socioeconomic status (odds ratio = 1.26, 95% confidence interval: 0.6, 2.5). Follow-up studies are needed to clarify the natural history of Helicobacter pylori infection and identify predictors of initial acquisition, persistence, and recurrence.

Age Distribution↗
PubMed1999

Direct costs of coronary artery bypass grafting in patients aged 65 years or more and those under age 65.

BACKGROUND: Over the past 20 years, there have been marked increases in rates of coronary artery bypass grafting (CABG) among older people in Canada. The objectives of this study were to accurately estimate the direct medical costs of CABG in older patients (age 65 years or more) and to compare CABG costs for this age group with those for patients less than 65 years of age. METHODS: Direct medical costs were estimated from a sample of 205 older and 202 younger patients with triple-vessel or left main coronary artery disease who underwent isolated CABG at The Toronto Hospital, a tertiary care university-affiliated hospital, between Apr. 1, 1991, and Mar. 31, 1992. Costs are expressed in 1992 Canadian dollars from a third-party payer perspective. RESULTS: The mean costs of CABG in older and younger patients respectively were $16,500 and $15,600 for elective, uncomplicated cases, $23,200 and $19,200 for nonelective, uncomplicated cases, $29,200 and $20,300 for elective, complicated cases, and $33,600 and $23,700 for nonelective, complicated cases. Age remained a significant determinant of costs after adjustment for severity of heart disease and for comorbidity. Between 59% and 91% of the cost difference between older and younger patients was accounted for by higher intensive care unit and ward costs. INTERPRETATION: CABG was more costly in older people, especially in complicated cases, even after an attempt to adjust for severity of disease and comorbidity. Future studies should attempt to identify modifiable factors that contribute to longer intensive care and ward stays for older patients.

Age Factors↗
PubMed1999

Long-term follow-up of a randomized trial of interferon therapy for chronic hepatitis B in a predominantly homosexual male population.

BACKGROUND/AIMS: Extended follow-up of a previously published therapeutic trial with interferon alfa is now available to further clarify the long-term outcome of HIV-negative and HIV-positive subjects with chronic hepatitis B virus infection after interferon alfa therapy. METHODS: Forty-five subjects with compensated liver disease and chronic hepatitis B infection with evidence of active hepatitis B replication were studied. These subjects were enrolled between 1986 and 1991 and had been randomized, stratified by HIV status, to either receive interferon therapy (10 MU/m2 of lymphoblastoid interferon alfa 3 times per week for 12 weeks) or no treatment. Hepatitis B serology, serum hepatitis B viral DNA and alanine aminotransferase were measured on an annual to biannual basis. CD4-positive T lymphocyte counts and HIV RNA concentration were also obtained. RESULTS: From 9 months post-interferon alfa treatment to the end of the extended follow-up (4 to 9 years), the relative risk of seroconverting to anti-HBe positive for subjects who had received interferon alfa therapy compared to those who did not was not significant in either HIV-negative (p = 0.80) or HIV-positive (p = 0.62) subjects. CONCLUSIONS: Unlike the first 9 months following interferon alfa therapy, the rate of elimination of markers of hepatitis B virus replication, regardless of HIV status, was not increased above the natural rate beyond 9 months following interferon alfa therapy.

Adult↗
PubMed1999

The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.

At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy.

Adolescent↗
PubMed1999

Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome--a comparative observational study. The Canadian Streptococcal Study Group.

Twenty-one consecutive patients with streptococcal toxic shock syndrome (TSS) between December 1994 and April 1995 were treated with a median dose of 2 g of intravenous immunoglobulin (IVIG)/kg (cases) and were compared with 32 patients with streptococcal TSS between 1992 and 1995 who did not receive IVIG therapy (controls). The outcome measure was 30-day survival. Patient plasma was tested for its ability to inhibit T cell activation induced by the infecting strain. The proportion of cases with 30-day survival was higher than that of the controls with 30-day survival (67% vs. 34%, respectively; P = .02). Multivariate analysis revealed that IVIG administration and a lower Acute Physiology and Chronic Health Evaluation II score were associated with survival; the odds ratio for survival associated with IVIG therapy was 8.1 (95% confidence interval, 1.6-45; P = .009). IVIG therapy enhanced the ability of patient plasma to neutralize bacterial mitogenicity and reduced T cell production of interleukin-6 and tumor necrosis factor alpha. IVIG may be an effective adjunctive therapy for streptococcal TSS, possibly because of its ability to neutralize bacterial exotoxins.

APACHE↗
PubMed1999

Asymptomatic primary biliary cirrhosis: a study of its natural history and prognosis.

OBJECTIVE: To document the natural history of asymptomatic primary biliary cirrhosis and identify prognostic features that would predict the development of symptomatic disease. METHODS: A retrospective chart review of all patients with abnormal liver biochemical tests and antimitochondrial antibody-positive, liver biopsy-compatible primary biliary cirrhosis who were seen in a single tertiary care center between 1983 and 1994 was performed. Statistical analysis using Cox regression was employed to compare survival of the study population with an age- and gender-matched control population and to identify potential prognostic variables. RESULTS: Ninety-one patients were included. Median age at presentation was 53.2 yr. Ninety percent were female. Median follow up was 61.2 months (range 7-206 months). Thirty-six percent (33 patients) became symptomatic with 11% (10 patients) progressing to death or liver transplant. Median predicted length of survival from onset of disease for the entire cohort was 14 yr. Patient survival was less than that predicted for an age- and gender-matched control population (p < 0.05). Univariate and multivariate analysis on a broad spectrum of clinical, biochemical, and histological features at the time of initial presentation failed to reveal any prognostic variables that would distinguish those who would become symptomatic from those who would remain symptom-free. Specifically, three primary variables of interest (associated autoimmune disorders, hepatomegaly, and histological stage) were not found to predict prognosis. CONCLUSION: Patients who present with asymptomatic primary biliary cirrhosis have a shorter life span than the general population. Presently, there are no prognostic features that identify the patients who will develop progressive disease from those who will remain symptom-free. Therefore, treatment should be offered to all patients.

Adult↗
PubMed1998

The death inhibitory molecules CED-9 and CED-4L use a common mechanism to inhibit the CED-3 death protease.

The apoptotic machinery of Caenorhabditis elegans includes three core interacting components: CED-3, CED-4, and CED-9. CED-3 is a death protease composed of a prodomain and a protease domain. CED-4 is a P-loop-containing, nucleotide-binding molecule that complexes with the single polypeptide zymogen form of CED-3, promoting its activation by autoprocessing. CED-9 blocks death by complexing with CED-4 and suppressing its ability to promote CED-3 activation. A naturally occurring alternatively spliced form of CED-4 that contains an insertion within the nucleotide-binding region (CED-4L) functions as a dominant negative inhibitor of CED-3 processing and attenuates cell death. Domain mapping studies revealed that distinct regions within CED-4 bind to the CED-3 prodomain and protease domain. Importantly, the CED-4 P-loop was involved in prodomain binding. Disruption of P-loop geometry because of mutation of a critical lysine (K165R) or insertional inactivation (CED-4L) abolished prodomain binding. Regardless, K165R and CED-4L still retained CED-3 binding through the protease domain but were unable to initiate CED-3 processing. Therefore, the P-loop-prodomain interaction is critical for triggering CED-4-mediated CED-3 processing. Underscoring the importance of this interaction was the finding that CED-9 contacted the P-loop and selectively inhibited its interaction with the CED-3 prodomain. These results provide a simple mechanism for how CED-9 functions to block CED-4-mediated CED-3 processing and cell death.

Apoptosis↗
PubMed1998

Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex.

Genetic analysis of apoptosis in the nematode Caenorhabditis elegans has revealed the cell death machine to be composed of three core interacting components. CED-4 (equivalent to mammalian Apaf-1) is a nucleotide binding molecule that complexes with the zymogen form of the death protease CED-3, leading to its autoactivation and cell death. CED-9 blocks death by complexing with CED-4 and attenuating its ability to promote CED-3 activation. An equivalent ternary complex was found to be present in mammalian cells involving Apaf-1, the mammalian death protease caspase-9, and Bcl-XL, an anti-apoptotic member of the Bcl-2 family. Consistent with a central role for caspase-9, a dominant negative form effectively inhibited cell death initiated by a wide variety of inducers.

Antibodies↗
PubMed1998

Conflict of interest in the debate over calcium-channel antagonists.

BACKGROUND: Physicians' financial relationships with the pharmaceutical industry are controversial because such relationships may pose a conflict of interest. It is unknown to what extent industry support of medical education and research influences the opinions and behavior of clinicians and researchers. The recent debate over the safety of calcium-channel antagonists provided an opportunity to examine the effect of financial conflicts of interest. METHODS: We searched the English-language medical literature published from March 1995 through September 1996 for articles examining the controversy about the safety of calcium-channel antagonists. Articles were reviewed and classified as being supportive, neutral, or critical with respect to the use of calcium-channel antagonists. The authors of the articles were asked about their financial relationships with both manufacturers of calcium-channel antagonists and manufacturers of competing products (i.e., beta-blockers, angiotensin-converting-enzyme inhibitors, diuretics, and nitrates). We examined the authors' published positions on the safety of calcium-channel antagonists according to their financial relationships with pharmaceutical companies. RESULTS: Authors who supported the use of calcium-channel antagonists were significantly more likely than neutral or critical authors to have financial relationships with manufacturers of calcium-channel antagonists (96 percent, vs. 60 percent and 37 percent, respectively; P<0.001). Supportive authors were also more likely than neutral or critical authors to have financial relationships with any pharmaceutical manufacturer, irrespective of the product (100 percent, vs. 67 percent and 43 percent, respectively; P< 0.001). CONCLUSIONS: Our results demonstrate a strong association between authors' published positions on the safety of calcium-channel antagonists and their financial relationships with pharmaceutical manufacturers. The medical profession needs to develop a more effective policy on conflict of interest. We support complete disclosure of relationships with pharmaceutical manufacturers for clinicians and researchers who write articles examining pharmaceutical products.

Biomedical Research↗
PubMed1998

A role for FADD in T cell activation and development.

FADD is a cytoplasmic adapter molecule that links the family of death receptors to the activation of caspases during apoptosis. We have produced transgenic mice expressing a dominantly interfering mutant of FADD, lacking the caspase-dimerizing death effector domain, as well as mice overexpressing the poxvirus serpin, CrmA, an inhibitor of caspases downstream of FADD. While thymocytes from either line of mice were completely protected from CD95-dependent cytotoxicity, neither transgene afforded protection from apoptosis induced during thymocyte selection and neither led to the lymphoproliferative disorders associated with deficiencies in CD95. However, in FADD dominant negative (FADDdd) mice, early thymocyte development was retarded and peripheral lymphocyte pools were devoid of normal populations of T cells. We show that thymocytes and peripheral T cells from FADDdd display signaling anomalies, implying that FADD plays a previously uncharacterized role in T cell development and activation.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Predictive value of cytomegalovirus (CMV) antigenemia and digene hybrid capture DNA assays for CMV disease in human immunodeficiency virus-infected patients.

Oral ganciclovir prophylaxis decreases the incidence of cytomegalovirus (CMV) disease among persons infected with the human immunodeficiency virus (HIV), but universal prophylaxis is not cost-effective. We evaluated urine and peripheral blood mononuclear cell cultures, a qualitative and quantitative antigenemia assay, and a commercially available CMV DNA hybridization assay for their ability to predict CMV disease in 138 HIV-infected patients. During a median follow-up of 10 months, 23 patients (17%) developed CMV disease. The sensitivity, specificity, positive predictive value, negative predictive value, and mean lead times for the antigenemia assay (with use of a threshold of 8 positive cells per 10(5) peripheral blood mononuclear cells as a positive) were 74%, 91%, 63%, 95%, and 95 days, respectively. Corresponding figures for the DNA hybridization assay were 91%, 64%, 34%, 97%, and 152 days. These assays can identify patients at increased risk of CMV disease and should allow a strategy of preemptive therapy to be tested.

AIDS-Related Opportunistic Infections↗
PubMed1998

Impact of community organization of women on perinatal outcomes in rural Bolivia.

An intervention to improve maternal and child health was conducted in a remote Bolivian province with limited access to modern medical facilities. The intervention focused on initiating and strengthening women's organizations, developing women's skills in problem identification and prioritization, and training community members in safe birthing techniques. Its impact was evaluated by comparing perinatal mortality rates and obstetric behavior among 409 women before and after the intervention. Perinatal mortality decreased from 117 deaths per 1,000 births before the intervention to 43.8 deaths per 1,000 births after. There was a significant increase in the number of women participating in women's organizations following the intervention, as well as in the number of organizations. The proportion of women receiving prenatal care and initiating breast-feeding on the first day after birth was also significantly larger. The number of infants attended to immediately after delivery likewise increased, but the change was not statistically significant. This study demonstrates that community organization can improve maternal and child health in remote areas.

Adolescent↗