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Biomedical subjects

K O'Rourke

Publications and source records attributed to K O'Rourke.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effectiveness of emergency medical services for victims of out-of-hospital cardiac arrest: a metaanalysis.

STUDY OBJECTIVE: To determine the relative effectiveness of differences in response time interval, proportion of bystander CPR, and type and tier of emergency medical services (EMS) system on survival after out of hospital cardiac arrest. METHODS: We performed a comprehensive literature search, excluding EMS systems other than those of interest (systems of interest were those comprising one tier with providers of basic life support [BLS] or advanced life support [ALS] and those comprising two tiers with providers of BLS or BLS-defibrillation followed by ALS), patient population of fewer than 100 cardiac arrests, studies in which we could not determine the total number of arrests of presumed cardiac origin, and studies lacking data on survival to hospital discharge. Metaanalysis using generalized linear model with dispersion estimation for random effects was then performed. RESULTS: Increased survival to hospital discharge was significantly associated with tier (P < .01), response time interval (P < .01), and bystander CPR (P = .04). A significant interaction was detected between response time interval and bystander CPR (P = .02). For the studies analyzed, survival was 5.2% in a one-tier EMS system or 10.5% in a two-tier EMS system. A 1-minute decrease in mean response time interval was associated with absolute increases in survival rates of .4% and .7% in a one-tier and two-tier EMS systems, respectively. CONCLUSION: Increased survival to hospital discharge may be associated with decreased response time interval and with the use of a two-tier EMS system as opposed to a one-tier system. The data available for this analysis were suboptimal. Policymakers need more methodologically rigorous research to have more reliable and valid estimates of the effectiveness of different EMS systems.

Cardiopulmonary Resuscitation↗
PubMed1996

Cost-effectiveness analysis of potential improvements to emergency medical services for victims of out-of-hospital cardiac arrest.

STUDY OBJECTIVE: To measure the incremental cost-effectiveness of various improvements to emergency medical services (EMS) systems aimed at increasing survival after out-of-hospital cardiac arrest. METHODS: We performed cost-effectiveness analysis based on (1) metaanalysis of effectiveness of the various EMS systems, (2) costing of each component of EMS systems, (3) modeling of the relationship between the proportion of cardiac arrest victims who receive CPR and the proportion of individuals trained, (4) modeling of the relationship between response time interval and the characteristics of the EMS system, (5) measurement of quality of life, and (6) decision analysis to combine the results of the first five components. RESULTS: The incremental cost-effectiveness ratio for a 48-second improvement in mean response time in a one-tier EMS system yielded by the addition of more EMS providers was $368,000 per quality-adjusted life year (QALY). For improved response time in a two-tier EMS system by the addition of more basic life support (BLS)/BLS-defibrillator (BLS-D) providers to the first tier, the ratio was $53,000 per QALY with pump vehicles or $159,000 per QALY with ambulances. Change from a one-tier EMS to a two-tier EMS system by the addition of initial BLS/BLS-D providers in pump vehicles as the first tier was associated with a cost per QALY of $40,000. Change from one-tier EMS to two-tier EMS by the addition of initial BLS/BLS-D providers in ambulances as the first tier was associated with a cost per QALY of $94,000. CONCLUSION: The most attractive options in terms of incremental cost-effectiveness were improved response time in a two-tier EMS system or change from a one-tier to a two-tier EMS system. Future research should be directed toward identification of the costs of instituting the first tier of a two-tier EMS system and identification of cost-effective methods of improving response time.

Cardiopulmonary Resuscitation↗
PubMed1996

The interaction of human immunodeficiency virus infection and hepatitis B virus infection in infected homosexual men.

A retrospective analysis of 99 hepatitis B-positive homosexual men with known human immunodeficiency virus (HIV) status was conducted to study the interaction of concurrent HIV infection on the course of their chronic hepatitis B virus (HBV) infection. All 99 subjects had chronic hepatitis B, 43 of whom were HIV antibody negative and 56 of whom were HIV antibody positive at the time of their initial presentation. Serial serum aminotransferase levels were used as an indirect estimate of the severity of hepatic inflammation. Factors that may influence the course of hepatitis B, HIV status, hepatitis B e antigen (HBeAg)/hepatitis B e antibody (HBeAb) status, alcohol intake, and zidovudine (AZT) therapy were correlated with aminotransferase values. Overall, there was no difference in mean serum alanine aminotransferase (ALT) levels between HIV antibody-negative and HIV antibody-positive patients. There is a higher prevalence rate of HBeAg in HIV antibody-positive patients (p < 0.05), and the seroconversion rate from HBeAg to HBeAb was lower in HIV antibody-positive patients compared with HIV antibody-negative patients (p < 0.05). However, reactivation rates from HBeAb to HBeAg were no different in the HIV antibody-positive and negative hepatitis B carriers. With mild, moderate, or heavy alcohol intake, we observed no statistically significant difference in mean serum alanine aminotransferase levels and no mean serum aspartate aminotransferase levels between HIV antibody-negative patients versus HIV antibody-positive patients. Similarly, there was no significant difference in the pattern of serum aminotransferase in those subjects treated with or without AZT. The mortality rates were higher in HIV antibody-positive patients (n = 8) compared with in HIV antibody-negative patients (n = 2). Seventy-five percent (n = 6) of the HIV antibody-positive patients died from acquired immunodeficiency syndrome (AIDS), and overall only two patients died of liver disease, one in each group. We conclude that there is no overt influence by HIV or the treatment thereof on the course of chronic HBV infection in a population of homosexual men. In HIV-infected patients, death from AIDS predominated; hence, the main target for therapy should be HIV rather than HBV.

Anti-HIV Agents↗
PubMed1996

Mechanisms of changes in renal handling of sodium following transjugular intrahepatic portal systemic stent-shunt (TIPSS).

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic stent-shunt (TIPSS) reduces the portal pressure gradient and leads to better control of ascites. The aim of this study was to evaluate (1) changes in renal handling of sodium following TIPSS and (2) the mechanism of these changes. DESIGN: Prospective study. SETTING: Tertiary referral centre for liver diseases. METHODS: Eighteen patients with ascites undergoing TIPSS for recurrent variceal haemorrhage (16) (3 or more hospital admissions because of variceal haemorrhage whilst being treated endoscopically) or refractory ascites (2) were studied. Urinary sodium (UNa), creatinine clearance (CrCl), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), Angiotensin II (AII) and lithium clearance (LiCl) were measured before and 3 months after TIPSS when portography was performed and the portal pressure gradient (PPG) also measured. All patients were haemodynamically stable and had received no diuretics for at least 1 week before blood sampling. RESULTS: Improvement in ascites was achieved in all patients in whom TIPSS was inserted successfully (reduction in PPG to < 12 mmHg). PPG was reduced from a mean of 19 (+/-6) to 8.8 (+/-3.4) mmHg (P < 0.001). Urinary sodium and creatinine clearance improved significantly following TIPSS (P < 0.001, P < 0.001, respectively). PRA, All, cGMP and LiCl were abnormal before TIPSS and improved significantly following TIPSS (P < 0.007, P < 0.001, P < 0.001 and P < 0.01, respectively). ANP was not significantly different from normal controls and did not change significantly following TIPSS. Changes in UNa did not correlate with the Pugh score or the change in PPG. CONCLUSION: The results of this study show that TIPSS is associated with significant improvement in UNa, CrCl, PRA, AII, cGMP and LiCl. The change in UNa following TIPSS was independent of the severity of underlying liver disease or the change in PPG.

Adult↗
PubMed1996

The association of hepatitis C viral infection with porphyria cutanea tarda in the Lothian region of Scotland.

Porphyria cutanea tarda (PCT) is believed to be associated with reduced hepatic uroporphyrinogen decarboxylase activity and risk factors such as alcohol abuse and medication with oral contraceptives and certain other drugs. Recently it has been suggested that hepatitis C virus (HCV) infection may also be associated with PCT. We have therefore reviewed the prevalence of HCV infection in a series of patients with PCT in the Lothian region of Scotland. We identified 12 patients with PCT, all of whom had abnormal liver function tests. Liver histology revealed chronic active hepatitis in six patients, micronodular cirrhosis in four patients, hepatocellular carcinoma in one patient and normal findings in one HIV positive patient. Out of 12 patients tested, 11 were positive for anti-HCV antibodies by second generation enzyme linked immunosorbent assay (ELISA 2), and by recombinant immunoblot assay (RIBA 2); positive serology was confirmed by polymerase chain reaction (PCR). In a second group of 14 patients with chronic HCV infection matched for age and sex with the PCT patients, all had normal urinary uroporphyrin excretion. We have thus confirmed in Scotland early reports from Spain and Italy that PCT is strongly associated with HCV infection. This could explain the development of inflammatory changes in the liver and progression of liver disease in patients with PCT. Porphyrin metabolism, however, appears normal in patients with chronic HCV infection without PCT.

Adult↗
PubMed1995

Elevated levels of syndecan-1 expression confer potent serum-dependent growth in human 293T cells.

Syndecan-1 is the best studied integral membrane proteoglycan and functions to modulate epithelial cell attachment and physiology. Extracellularly, syndecan-1 binds both growth factors and extracellular matrix components, and intracellularly, its cytoplasmic portion interacts with cytoskeletal components. To investigate the possible role of syndecan-1 in epithelial cell transformation that is characterized by alteration in extracellular matrix interactions and cytoskeleton architecture, we established stable transfectants of syndecan-1 in a highly transformed human renal epithelial line expressing two viral oncogenes, adenovirus E1a and SV40 large T antigen (293T cell line). Expression of syndecan-1 core protein and appropriate posttranslational attachment of glycosaminoglycan chains was confirmed by enzymatic digestion and Western blot analysis. Overexpresser cells grew at a significantly faster rate than the vector-transfected control cells in serum-rich media but showed a proliferative disadvantage in serum-reduced media. In addition to this serum dependency, syndecan-1 overexpression caused a partial reversal of the transformed phenotype with the expressing clones becoming more anchorage dependent and less motile than the vector-transfected counterparts. Surprisingly, the overexpressers were more tumorigenic when injected s.c. into nude mice. These results indicate that syndecan-1 expression plays a role in the control of cell proliferation and suggest that serum-dependent growth may be the more reflective of tumorigenicity in nude mice.

Animals↗
PubMed1995

Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase.

Although the mechanism of mammalian apoptosis has not been elucidated, a protease of the CED-3/ICE family is anticipated to be a component of the death machinery. Several lines of evidence predict that this protease cleaves the death substrate poly(ADP-ribose) polymerase (PARP) to a specific 85 kDa form observed during apoptosis, is inhibitable by the CrmA protein, and is distinct from ICE. We cloned a ced-3/ICE-related gene, designated Yama, that encodes a protein identical to CPP32 beta. Purified Yama was a zymogen that, when activated, cleaved PARP to generate the 85 kDa apoptotic fragment. Cleavage of PARP by Yama was inhibited by CrmA but not by an inactive point mutant of CrmA. Furthermore, CrmA blocked cleavage of PARP in cells undergoing apoptosis. We propose that Yama may represent an effector component of the mammalian cell death pathway and suggest that CrmA blocks apoptosis by inhibiting Yama.

Apoptosis↗
PubMed1995

FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.

Using the cytoplasmic domain of Fas in the yeast two-hybrid system, we have identified a novel interacting protein, FADD, which binds Fas and Fas-FD5, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8. FADD contains a death domain homologous to the death domains of Fas and TNFR-1. A point mutation in FADD, analogous to the lpr mutation of Fas, abolishes its ability to bind Fas, suggesting a death domain to death domain interaction. Overexpression of FADD in MCF7 and BJAB cells induces apoptosis, which, like Fas-induced apoptosis, is blocked by CrmA, a specific inhibitor of the interleukin-1 beta-converting enzyme. These findings suggest that FADD may play an important role in the proximal signal transduction of Fas.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease.

BACKGROUND & AIMS: Recurrence of Crohn's disease frequently occurs after surgery. A randomized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohn's disease after surgical resection is performed. METHODS: One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were randomized to a treatment group (1.5 g mesalamine twice a day) or a placebo control group within 8 weeks of surgery. The follow-up period was a maximum of 72 months. RESULTS: The symptomatic recurrence rate (symptoms plus endoscopic and/or radiological confirmation of disease) in the treatment group was 31% (27 of 87) compared with 41% (31 of 76) in the control group (P = 0.031). The relative risk of developing recurrent disease was 0.628 (90% confidence interval, 0.40-0.97) for those in the treatment group (P = 0.039; one-tail test) using an intention-to-treat analysis and 0.532 (90% confidence interval, 0.32-0.87) using an efficacy analysis. The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 (90% confidence interval, 0.47-0.91) in the effectiveness analysis and 0.635 (90% confidence interval, 0.44-0.91) in the efficacy analysis. There was only one serious side effect (pancreatitis) in subjects in the treatment group. CONCLUSIONS: Mesalamine (3.0 g/day) is effective in decreasing the risk of recurrence of Crohn's disease after surgical resection is performed.

Adult↗
PubMed1995

The effect of hospital staff training on management of obstetrical patients referred by traditional birth attendants.

A hospital staff training program was conducted in Guatemala to improve outcomes for patients with obstetrical and neonatal complications. This study examines the effect of the training program on the subset of women referred to the hospital by traditional birth attendants (TBAs). The program's goals were to institute standards of care for obstetrical and neonatal patients as well as to improve relations between hospital staff and TBAs. The training program was evaluated by comparing changes in the number of referrals, patient satisfaction, patient management, as well as Apgar scores and perinatal mortality. Evaluations were based on 756 questionnaires administered to TBA referred mothers. There was a significant increase in the overall numbers of referred women as well as improvement in patient satisfaction and decreased waiting time between admission and treatment. Apgar scores and perinatal mortality also improved, but changes were not statistically significant.

Adolescent↗
PubMed1995

Müller and retinal pigment epithelial (RPE) cell expression of NGFI-A and c-fos mRNA in response to medium conditioned by the RPE.

Retinal pigment epithelial (RPE) cells secrete a factor(s) which promotes Müller and RPE cell survival and proliferation in vitro. These influences may play developmental and functional roles as well as contribute to ocular pathologies such as proliferative vitreoretinopathy (PVR). In the past few years, a number of immediate early genes (IEGs) have been identified. Many IBGs encode transcription factors, the expression of which is altered by stimuli such as growth factors. Since an RPE-derived factor(s) elicits proliferation of Müller and RPE cells, we investigated the expression of two IEGs, NGFI-A and c-fos, in both cell types after treatment with medium conditioned by the RPE (RPE-CM). We found that Müller and RPE cells had increased levels of NGFI-A mRNA following treatment with RPE-CM; in contrast, only a slight increase in c-fos mRNA was induced in RPE, but not Müller cells. Immunolabeling for NGFI-A protein revealed nuclear staining in both cell types which corresponded with the increased mRNA levels in RPE-CM-treated cultures. This in vitro study demonstrates a potential mechanism by which RPE-secreted factors may exert autocrine or paracrine effects on retinal cells in vivo. Specifically, NGFI-A may be the primary target of a second messenger system that is regulated by an RPE-derived factor(s).

Animals↗
PubMed1995

Evaluation of short-course therapy with cefixime or rifampin for eradication of pharyngeally carried group A streptococci. The Ontario GAS Study Group.

Therapy to eradicate pharyngeally carried group A streptococci (GAS) has increasingly been used in the management of institutional outbreaks and is now recommended for household contacts of patients with streptococcal toxic shock syndrome. In this randomized, controlled trial, contacts of patients with GAS infections were screened for pharyngeal GAS colonization. Those whose cultures were positive were randomized to receive either cefixime (8 mg/[kg.d]; maximum 400 mg) or rifampin (20 mg/kg; maximum, 600 mg) once a day for 4 days. Two to five days following completion of therapy, repeated cultures were negative for 13 (38%) of 34 rifampin recipients and 71 (77%; 95% CI, 69%-85%) of 97 cefixime recipients. At 10-14 days after treatment, only 53% of cefixime recipients remained culture-negative. Rates of successful clearance improved with increasing age (P < .01); among 17 adults who received cefixime, the success rate was 94%. Four days of therapy with rifampin is not effective for eradication of pharyngeally carried GAS. Four days of therapy with cefixime may be effective for adults, but further studies are needed.

Adolescent↗
PubMed1995

Postoperative analgesia after lumbar laminectomy: epidural fentanyl infusion versus patient-controlled intravenous morphine.

We compared the efficacy and safety of continuous epidural fentanyl infusion with intravenous morphine via a patient-controlled analgesia system (IV-PCA) in the management of postoperative pain after lumbar laminectomy. Twenty patients undergoing elective lumbar laminectomy were randomly allocated to one of two groups. The epidural group (n = 10) received an epidural fentanyl infusion (2 micrograms/mL at 4-10 mL/h) while the IV-PCA group (n = 10) received IV morphine through a PCA system. The general anesthetic technique was standardized. Visual analog pain scores were recorded at 12, 24, and 48 h after the operation. The amount of morphine (or its equivalent in fentanyl) used over the 48-h postoperative period was documented. The postoperative pain scores were significantly lower in the epidural group than in the IV-PCA group throughout the study period. The total consumption of morphine (or its fentanyl equivalent) over the 48-h period was significantly lower (P < 0.001) in the epidural group compared to the IV-PCA group. Although more patients in the IV-PCA group required urinary catheterization and had somnolence than the epidural group, there was no difference in the incidence of vomiting or pruritus. No patient developed respiratory depression or wound infection. We conclude that continuous epidural infusion of fentanyl is superior to IV-PCA morphine in the management of pain after lumbar laminectomy.

Analgesia, Patient-Controlled↗
PubMed1995

Do geriatric programs decrease long-term use of acute care beds?

OBJECTIVE: To determine whether the introduction of coordinated geriatric and discharge planning services at teaching and community hospitals in Toronto has changed the number of beds occupied by patients awaiting transfer to long-term care institutions. DESIGN: Retrospective review of social work records for the period 1985-1992. SETTING: Two tertiary and four primary acute care hospitals in Metropolitan Toronto. PARTICIPANTS: Hospitals were matched for location, acuity, and teaching affiliation. MAIN OUTCOME MEASURES: The numbers of beds occupied by patients awaiting transfer to nursing homes or chronic care hospitals were noted. RESULTS: In those teaching and community hospitals that had introduced coordinated geriatric and discharge planning services, there was a reduction in the percentage of beds occupied by patients awaiting long-term care placement (average-51%), whereas in hospitals without geriatric services, the percentage of beds occupied by patients awaiting long-term care placement increased (average + 25%) (P = .05 by Fisher's exact method, 95% confidence limit odds ratio 0, .9999). CONCLUSION: The introduction of coordinated geriatric and discharge planning services was associated with a decrease in the percentage of beds occupied by patients awaiting long-term care in both teaching and community hospitals.

Aged↗
PubMed1995

Age as a determinant of cardiopulmonary resuscitation outcome in the coronary care unit.

OBJECTIVE: To determine whether age is associated with the outcome of cardiopulmonary resuscitation (CPR) in the coronary care unit (CCU). DESIGN: Retrospective chart review. SETTING: The coronary care units of two Canadian tertiary care teaching hospitals. PATIENTS: Two hundred sixty-four coronary care unit patients undergoing cardiopulmonary resuscitation between January 1, 1985 and June 30, 1992. RESULTS: There was no significant difference in survival to discharge after CPR between patients less than 70 years of age (17.0%) and patients 70 years of age and older (17.2%) (odds ratio = 0.99; 95% confidence interval = 0.46, 1.80). Patients 70 years of age and older who survived to discharge after CPR had significantly greater lengths of stay (28.1 vs 19.3 days, P = .008). CONCLUSIONS: Age was not associated with a difference in survival to discharge after CPR in the CCU, although a clinically significant difference could not be excluded because of limited power.

Adult↗
PubMed1995

Expression and chromosomal localization of cDNA clones from an enriched human retinal pigment epithelial (RPE) cell line library: identification of two RPE-specific genes.

We have previously constructed an enriched cDNA library from a human retinal pigment epithelium (RPE) cell line and generated expressed sequence tags (ESTs) from novel clones. Here, we report the analysis of expression of 14 cDNAs and identify two clones, AA1 and AA28, that appear to be specifically expressed in RPE but not in any other tissue tested. We have also localized 15 novel cDNAs (including the two RPE-specific cDNAs) to human chromosomes using in situ hybridization or in conjunction with somatic cell hybrid analysis. The cDNAs were mapped to the following chromosomal regions: 1p35-->p33, 1q41-->q42 (two clones), 3q11.2-->q13.1, 3q24-->q25, 4q13-->q21, 6q22-->q23, 7q34-->q36, 10q23-->q24, 11q23-->q24, 15q25-->q26, 19p13.3, 20p13, 21q11.2-->q21, and 21q22.2-->q22.3. The genetic and functional analysis of the two RPE-specific genes should contribute to a better understanding of RPE function. Chromosomal localization of RPE cDNAs will be valuable in identifying candidate genes for inherited diseases involving RPE dysfunction and aid in establishing the expression map of the human genome.

Blotting, Northern↗