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PubMed2003

Mortality control charts for comparing performance of surgical units: validation study using hospital mortality data.

OBJECTIVE: To design and validate a statistical method for evaluating the performance of surgical units that adjusts for case volume and case mix. DESIGN: Validation study using routinely collected data on in-hospital mortality. DATA SOURCES: Two UK databases, the ASCOT prospective database and the risk scoring collaborative (RISC) database, covering 1042 patients undergoing surgery in 29 hospitals for gastro-oesophageal cancer between 1995 and 2000. STATISTICAL ANALYSIS: A two level hierarchical logistic regression model was used to adjust each unit's operative mortality for case mix. Crude or adjusted operative mortality was plotted on mortality control charts (a graphical representation of surgical performance) as a function of number of operations. Control limits defined as 90%, 95%, and 99% confidence intervals identified units whose performance diverged significantly from the mean. RESULTS: The mean in-hospital mortality was 12% (range 0% to 50%). The case volume of the units ranged from one to 55 cases a year. When crude figures were plotted on the mortality control chart, four units lay outside the 90% control limit, including two outside the 95% limit. When operative mortality was adjusted for risk, three units lay outside the 90% limit and one outside the 95% limit. The model fitted the data well and had adequate discrimination (area under the receiver operating characteristics curve 0.78). CONCLUSIONS: The mortality control chart is an accurate, risk adjusted means of identifying units whose surgical performance, in terms of operative mortality, diverges significantly from the population mean. It gives an early warning of divergent performance. It could be adapted to monitor performance across various specialties.

Hospital Mortality↗
PubMed2005

Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: roles of angiotensin II type 1 receptors and NAD(P)H oxidase.

BACKGROUND: In a previous study, we showed that simvastatin (SIM) therapy normalized sympathetic outflow and cardiovascular reflex regulation in chronic heart failure (CHF). However, the precise neural and cellular pathways for these effects are unknown. We hypothesized that SIM exerts its beneficial effect on autonomic function in CHF by downregulating central angiotensin II (Ang II) and superoxide mechanisms. METHODS AND RESULTS: Experiments were carried out on 36 male New Zealand White rabbits, 13 normal and 23 CHF. All rabbits were identically instrumented to record mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA). Echocardiography was used to monitor cardiac function. Reverse transcription-polymerase chain reaction, Western blotting, and lucigenin-enhanced chemiluminescence were used to measure gene expression of Ang II type 1 receptor and NAD(P)H oxidase subunits and NAD(P)H oxidase activity in the rostral ventrolateral medulla. Compared with the CHF control group, SIM significantly reduced the central Ang II-induced pressor and sympathoexcitatory responses, decreased baseline RSNA (57.3+/-3.2% to 22.4+/-2.1% of maximum, P<0.05), increased baroreflex control of heart rate (gain(max), 1.6+/-0.3 to 4.5+/-0.2 bpm/mm Hg, P<0.05), and increased RSNA (gain(max), 1.7+/-0.2% to 4.9+/-0.6% of maximum/mm Hg, P<0.01). Importantly, SIM improved left ventricular function (EF, 32.4+/-4.1% to 51.7+/-3.2%, P<0.05). SIM also downregulated mRNA and protein expression of Ang II type 1 receptor and NAD(P)H oxidase subunits and inhibited NAD(P)H oxidase activity in the rostral ventrolateral medulla of CHF rabbits. Chronic intracerebroventricular infusion of Ang II completely abolished the aforementioned effects of SIM in CHF rabbits. CONCLUSIONS: These data strongly suggest that SIM normalizes autonomic function in CHF by inhibiting central Ang II mechanisms and therefore the superoxide pathway. These data also demonstrate that SIM improves left ventricular function in pacing-induced CHF rabbits.

Animals↗
PubMed2006

In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery.

BACKGROUND: Recent studies have shown that stem cell therapy can promote tissue regeneration; however, monitoring stem cells in vivo remains problematic owing to limitations of conventional histological assays and imaging modalities. METHODS AND RESULTS: Murine embryonic stem (ES) cells were stably transduced with a lentiviral vector carrying a novel triple-fusion (TF) reporter gene that consists of firefly luciferase, monomeric red fluorescence protein, and truncated thymidine kinase (fluc-mrfp-ttk). ES cell viability, proliferation, and differentiation ability were not adversely affected by either reporter genes or reporter probes compared with nontransduced control cells (P=NS). Afterward, 1x10(7) of ES cells carrying the TF reporter gene (ES-TF) were injected into the myocardium of adult nude rats (n=20). Control animals received nontransduced ES cells (n=6). At day 4, the bioluminescence and positron emission tomography signals in study animals were 3.7x10(7)+/-5.8x10(6) photons.s(-1).cm(-2) per steradian (sr) and 0.08+/-0.03% injected dose/g, respectively (P<0.05 versus control). Both signals increased progressively from week 1 to week 4, which indicated ES cell survival and proliferation in the host. Histological analysis demonstrated the formation of intracardiac and extracardiac teratomas. Finally, animals (n=4) that were treated with intraperitoneal injection of ganciclovir (50 mg/kg) did not develop teratomas when compared with control animals (n=4) treated with saline (1 mL/kg). CONCLUSIONS: This is the first study to characterize ES cells that stably express fluorescence, bioluminescence, and positron emission tomography reporter genes and monitor the kinetics of ES cell survival, proliferation, and migration. This versatile imaging platform should have broad applications for basic research and clinical studies on stem cell therapy.

Animals↗
PubMed1995

Characteristics of trophoblast cells migrating from first trimester chorionic villus explants and propagated in culture.

We developed a method of propagating pure first trimester human trophoblast cells growing out of primary explants of mechanically derived chorionic villus fragments (Yagel et al, 1989; Graham et al, 1992). We have now extensively characterized these cells during their initial outgrowth and in long-term culture, employing a variety of markers and techniques as outlined below. By double label immunofluorescence using epithelial (cytokeratin) and mesenchymal (vimentin) cell markers, we identified the chorionic villus migrant cell populations as pure trophoblast (39 per cent of outgrowths) or a mixture of trophoblast and fibroblast (61 per cent). Further phenotyping of the pure trophoblast outgrowths by double label immunostaining using anti-cytokeratin antibody and a panel of other primary antisera revealed that these cells exhibit a variety of markers characteristic of extravillous invasive trophoblast cells in situ: insulin-like growth factor (IGF)-II, NDOG-5, proliferating cell nuclear antigen (PCNA), human leucocyte antigen framework antigen (W6/32) and a distinct set of integrins including alpha 1, alpha 3, alpha 5, alpha v and beta 1 subunits and alpha v beta 3/beta 5 vitonectin receptor. They were negative for alpha 6 and beta 4 integrin subunits. Immunogold electron microscopy of explants grown on type IV collagen gel revealed the production of conventional and oncofetal types of fibronectin by mononucleate trophoblast cells and human placental lactogen by multinucleate cells. Immunolabelling, flow cytometry and immunoprecipitation revealed that this phenotypic profile was retained with complete fidelity in the long-term culture; thus, trophoblasts migrating out of first trimester chorionic villus explants and their propagated progeny belong to the invasive extravillous trophoblast of the placenta.

Cell Movement↗
PubMedDate not supplied

Hospital bed surge capacity in the event of a mass-casualty incident.

INTRODUCTION: Traditional strategies to determine hospital bed surge capacity have relied on cross-sectional hospital census data, which underestimate the true surge capacity in the event of a mass-casualty incident. OBJECTIVE: To determine hospital bed surge capacity for the County more accurately using physician and nurse manager assessments for the disposition of all in-patients at multiple facilities. METHODS: Overnight- and day-shift nurse managers from each in-patient unit at four different hospitals were approached to make assessments for each patient as to their predicted disposition at 2, 24, and 72 hours post-event in the case of a mass-casualty incident, including transfer to a hypothetical, onsite nursing facility. Physicians at the two academic institutions also were approached for comparison. Age, gender, and admission diagnosis also were recorded for each patient. RESULTS: A total of 1,741 assessments of 788 patients by 82 nurse managers and 25 physicians from the four institutions were included. Nurse managers assessed approximately one-third of all patients as dischargeable at 24 hours and approximately one-half at 72 hours; one-quarter of the patients were assessed as being transferable to a hypothetical, on-site nursing facility at both time points. Physicians were more likely than were nurse managers to send patients to such a facility or discharge them, but less likely to transfer patients out of the intensive care unit (ICU). Inter-facility variability was explained by differences in the distribution of patient diagnoses. CONCLUSIONS: A large proportion of in-patients can be discharged within 24 and 72 hours in the event of a mass-casualty incident (MCI). Additional beds can be made available if an on-site nursing facility is made available. Both physicians and nurse managers should be included on the team that makes patient dispositions in the event of a MCI.

Bed Occupancy↗
PubMed2004

A comparison of the precision of seeds deposited as loose seeds versus suture embedded seeds: a randomized trial.

PURPOSE: Brachytherapy for prostate cancer with permanent low-dose-rate seeds has been shown to be an effective treatment for early stage prostate cancer. Due to the rapid falloff of dose, accurate seed placement is critical for optimal dosimetry. One approach to achieve optimal dosimetry is the use of seeds embedded in suture material. Seeds embedded in suture may not move after implantation as much as loose seeds. This would improve implant dosimetry. To evaluate this hypothesis a formal study was conducted in which half the gland was implanted with seeds embedded in suture and half with loose seeds. Final dosimetry is compared between both halves of the prostate. METHODS AND MATERIALS: Patients entered this Investigational Review Board approved prospective trial after completion of informed consent. At time of implant, the side of the gland to be implanted with loose as opposed to suture embedded seeds was randomly assigned. The patients then underwent intraoperative preplanned implantation. None of the preplans directed seed locations outside the prostate. Both the seeds embedded in suture and the loose seeds were implanted using needles with stylettes. At 4-6 weeks post implant, seed location was determined with CT. Both sides of the gland on CT were contoured and used for final dosimetric calculations. A cost function analysis was used to determine individual seed position deviation from intended to actual seed location. RESULTS: Eight patients were enrolled in the study. A total of 549 seeds were implanted; 240 seeds embedded in suture and 309 loose seeds. Prostate volumes ranged from 24.0-45.5 cc with a mean of 38.6 cc. The average radial deviation of the loose seeds from planned position was determined to be 3.1 mm compared with the average radial deviation of the suture embedded seeds of 3.7 mm. There was no improvement in the final dosimetry when suture embedded seeds where used. The D90 and V100 values for the half of the prostate implanted with suture embedded seeds were 71-140 (mean, 92.1) and 80.2-99.5 (mean, 89.6), respectively, for the half of the prostate implanted with loose seeds. (All D90, V100 values are % of prescription dose.) CONCLUSION: Seeds embedded in suture material do not lead to superior precision in seed deposition when compared with loose seeds, when implanted inside the prostate.

Brachytherapy↗
PubMed2002

Contrasting natures of lung growth after transplantation and lobectomy.

OBJECTIVE: We hypothesized that posttransplantation lung growth in an immature recipient and postlobectomy compensatory lung growth are two distinct processes. METHODS: Mature swine underwent left upper lobectomy, and growth of the left lower lobe was studied after 2 weeks and after 3 months. Left lower lobes from another set of mature pigs were transplanted into immature animals, and growth of the transplanted lobe was then studied after 2 weeks and after 3 months. Left lower lobes from mature animals that did not undergo operation were used as normal control lobes. The lobes were weighed on removal and fixed intrabronchially. Sections stained with hematoxylin and eosin were used to determine alveolar surface density and percentage volume of respiratory region. Immunostaining for 5-bromo-2'-deoxyuridine was used to determine alveolar cell proliferation index, and epidermal growth factor receptor expression was detected by Western blot. RESULTS: Postlobectomy lung growth (increase in lobe weight) reached statistical significance at 2 weeks, with a concomitant rise in cell proliferation index. The transplanted lobe, in contrast, exhibited a gradual growth response, with a statistically significant increase in cell proliferation index at 3 months. Volume of respiratory region was noted to increase only in the transplanted lobe at 3 months. Epidermal growth factor receptor expression was upwardly regulated relative to that in normal control lobes in the 2-week postlobectomy and 3-month posttransplantation lobes. CONCLUSIONS: Postlobectomy lung growth appears to be regulated by a different mechanism than is posttransplantation lung growth and is a more rapid and restorative process. The growth peaks in both processes correlate with upward regulation of cell proliferation index and epidermal growth factor receptor expression.

Animals↗
PubMed1996

Phenotypic heterogeneity of retinal pigment epithelial cells in vitro and in situ.

We have previously developed methods based upon differential cell adhesion to select for cells of two different phenotypes, epithelioid and fusiform, from cultures of human RPE. Here we considered whether the differences in cell shape correlated with differences in protein tyrosine phosphorylation since it is known that elevated phosphorylation perturbs the stability of the adherens junction, a major determinant of epithelial phenotype. In cultures of both phenotypes we found low tyrosine phosphorylation levels in postconfluent cultures, and the same complement of tyrosine phosphoproteins after treatment with a phosphatase inhibitor. However, in contrast to epithelioid cells, fusiform RPE failed to localize the phosphoproteins to junctional sites on the cell periphery. We also re-evaluated primary and passaged RPE cultures for additional cell shape variants. Several discrete phenotypes were identified within the same cultures. They required several weeks at confluency to develop in primary as well as in passaged cultures, but after developing they remained stable for months. Since explanted RPE cells manifest several shape variants in an identical culture environment we examined bovine RPE cells in situ to determine whether the cells were heterogenous with regards to some cell surface and cytoskeletal proteins that might contribute to cell shape. Circumferential actin microfilament bundles and the occluding junction protein ZO-1 had fairly uniform distributions among cells in the monolayer, but the intermediate filament protein vimentin and the pericellular expression of phosphotyrosine varied among individual cells. Therefore, despite its grossly homogeneous appearance, the RPE monolayer in situ might be considered a mosaic of structurally heterogeneous cells which can give rise to phenotypically-distinct subpopulations when propagated in vitro.

Adult↗
PubMed2004

Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML.

BACKGROUND: The progression of chronic myelogenous leukemia (CML) to blast crisis is supported by self-renewing leukemic stem cells. In normal mouse hematopoietic stem cells, the process of self-renewal involves the beta-catenin-signaling pathway. We investigated whether leukemic stem cells in CML also use the beta-catenin pathway for self-renewal. METHODS: We used fluorescence-activated cell sorting to isolate hematopoietic stem cells, common myeloid progenitors, granulocyte-macrophage progenitors, and megakaryocyte-erythroid progenitors from marrow during several phases of CML and from normal marrow. BCR-ABL, beta-catenin, and LEF-1 transcripts were compared by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay in normal and CML hematopoietic stem cells and granulocyte-macrophage progenitors. Confocal fluorescence microscopy and a lymphoid enhancer factor/T-cell factor reporter assay were used to detect nuclear beta-catenin in these cells. In vitro replating assays were used to identify self-renewing cells as candidate leukemic stem cells, and the dependence of self-renewal on beta-catenin activation was tested by lentiviral transduction of hematopoietic progenitors with axin, an inhibitor of the beta-catenin pathway. RESULTS: The granulocyte-macrophage progenitor pool from patients with CML in blast crisis and imatinib-resistant CML was expanded, expressed BCR-ABL, and had elevated levels of nuclear beta-catenin as compared with the levels in progenitors from normal marrow. Unlike normal granulocyte-macrophage progenitors, CML granulocyte-macrophage progenitors formed self-renewing, replatable myeloid colonies, and in vitro self-renewal capacity was reduced by enforced expression of axin. CONCLUSIONS: Activation of beta-catenin in CML granulocyte-macrophage progenitors appears to enhance the self-renewal activity and leukemic potential of these cells.

Adult↗
PubMed2006

Limiting the emergence of extended-spectrum Beta-lactamase-producing enterobacteriaceae: influence of patient population characteristics on the response to antimicrobial formulary interventions.

BACKGROUND: Effective methods to control the emergence of extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions. METHODS: To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included. RESULTS: After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P < .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]). CONCLUSIONS: The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

Adolescent↗
PubMed2005

Role of socioeconomic markers and state prohibition policy in predicting alcohol consumption among men and women in India: a multilevel statistical analysis.

OBJECTIVE: To investigate the independent contribution of individual socioeconomic markers and state prohibition policy on alcohol consumption among men and women in India. METHODS: The study used a multilevel cross-sectional analysis of alcohol consumption from the 1998-1999 Indian national family health survey of 301 984 adult individuals in 92 447 households in 3215 villages in 440 districts in 26 states, stratified by sex. FINDINGS: Men with no education were more likely to consume alcohol that those with a post graduate education (OR, 2.28; 95% CI, 2.08-2.50). Unlike men, women showed a U-shaped association between education and alcohol consumption. Men and women living in households at the lowest standard-of-living quintile were more likely to consume alcohol (OR, 1.92; 95% CI, 1.81-2.03, and OR, 2.72, 95% CI, 2.18-3.39), respectively, than those classified as living in the top quintile. Members of scheduled tribes and castes and other backward classes were more likely to consume alcohol than members of other caste groups. There was no difference in alcohol consumption between men from states that were not under prohibition (OR, 1.36; 95% CI 0.69-2.03) and those that were. By contrast, states not under prohibition has higher alcohol use by women (OR, 3.04, 95% CI, 1.59-4.48) than those under partial or complete prohibition. CONCLUSION: Caste, education and standard of living independently influence alcohol use in India. Prohibition policies appear to have little effect on alcohol use by men, but may reduce the proportion of women who consume alcohol. The socioeconomic patterning of health behaviours is likely to feed substantially into inequalities in health outcomes. Further investigation is required to understand how social and cultural factors in more localized contexts (e.g. districts) influence alcohol consumption.

Alcohol Drinking↗
PubMed2005

Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen.

OBJECTIVE: We examined the clinical performance of contraceptive vaginal rings (rings) delivering Nestorone (NES) progestin and ethinyl estradiol (EE). Ring removal times were signaled by menstrual events. Bleeding patterns, adverse events, patterns of use and continuation rates were the principal parameters evaluated. METHODS: In a two-stage 6-month trial, subjects were randomized to use rings releasing 50 microg/day of NES and either 10 (50/10) or 20 (50/20) microg/day of EE. Subjects were to keep rings continuously in situ until menstrual bleeding or prolonged spotting-signaled removal. Reinsertion was to occur 96 h later. After the randomized stage, an open-label 6-month trial of rings releasing 150 microg/day of NES and 15 microg/day of EE (150/15) began with the same menstrually signaled regimen. RESULTS: Two-hundred forty-six subjects participated in the trial. Six-month pregnancy rates ranged by ring dose from 1.3 to 3.9 per 100. For each ring dose combination, 6-month continuation rates were above 80 per 100. Bleeding and spotting (B+S) days in women with the 50 microg/day NES rings were similar in number to those experienced by cycling women not using contraception. Nevertheless, in the initial 90 days, fewer B+S days were reported by subjects with the 50/20 ring than by subjects with the 50/10 ring (p < .05). Throughout the trial, subjects using the 150/15 ring reported significantly fewer B+S episodes than did subjects with either 50 microg/day NES ring. CONCLUSION: Combined contraceptive rings used with a bleeding-signaled regimen led to few terminations attributed to bleeding problems and to acceptable continuation rates. The 150/15 ring appeared to induce fewer bleeding problems than did the lower-dose NES combination rings, but no important difference in 6-month continuation rates among the three doses was noted.

Adult↗
PubMed2006

Endoscopic versus open saphenous vein harvest for femoral to below the knee arterial bypass using saphenous vein graft.

BACKGROUND: Although the use of endoscopic vein harvest (EVH) in coronary artery bypass grafting is accepted, few studies have documented the implementation of EVH in peripheral vascular disease surgery. We hypothesized that EVH improves outcomes compared with open vein harvest (OVH) in patients undergoing femoral to below the knee arterial bypass surgery. METHODS: The charts of 144 consecutive patients undergoing infrainguinal bypass surgery over the course of 27 months were reviewed. A femoral to below the knee arterial bypass with saphenous vein was done in 88 patients (29 had EVH, 59 had OVH). The preoperative characteristics evaluated were age, gender, renal function, history of diabetes, hypertension, tobacco use, and previous infrainguinal bypass surgery on the affected side. End points included wound complications, length of hospital stay, operative time, angiographic and operative interventions for graft occlusion, patency rates, limb salvage, acute renal failure, myocardial infarction, and death. RESULTS: Patient characteristics and demographics were similar in the EVH and OVH groups. No operative intervention for occlusion was required in the EVH group (0/29) compared with 13.4% in the OVH group (8/59) (P = .03). At the mean follow-up time of 21 months, primary patency rate was 92.8% in the EVH group and 80.6% in the OVH group (P = .12). No significant differences were found between the EVH and OVH groups in postoperative complications, length of hospital stay, operative time, patency rates, limb salvage, and death. CONCLUSION: Despite our initial concerns of damaging the venous conduit with a minimally invasive approach to saphenous vein harvest, EVH in our experience has resulted in a trend toward improved patency rates and decreased infectious wound complications while affording the benefit of improved cosmesis. An endoscopic approach results in smaller incisions, decreased interventions for occlusion, and improved outcomes compared with OVH. EVH is the procedure of choice for harvesting saphenous vein for femoral to below the knee arterial bypass surgery.

Endoscopy↗
PubMed2006

Thoracic aortic endografting is the treatment of choice for elderly patients with thoracic aortic disease.

OBJECTIVE: To assess the effect of age on outcomes following thoracic aortic endografting. SUMMARY BACKGROUND DATA: Endograft therapy for thoracic aortic disease is rapidly evolving. This therapy is less invasive, and elderly patients with significant medical comorbidities are more frequently referred for endografting. We hypothesized that elderly patients over the age of 75 have worse outcomes after thoracic endografting than patients under the age of 75. METHODS: We retrospectively reviewed the charts of the first 42 patients who underwent endografting for thoracic aortic pathology. Charts were reviewed for demographics, comorbid conditions, perioperative complications and death, endoleaks, and results at 3, 6, and 12 months. Preexisting medical conditions were also evaluated to determine if any patient characteristics were associated with adverse outcomes. Perioperative morbidity included cardiac, pulmonary, renal, hemorrhagic, and neurologic (stroke and spinal cord injury) complications. RESULTS: Twenty-four patients were under the age of 75, and 18 patients were 75 or older. Baseline demographics and comorbidities were similar between the 2 groups. There were no differences in operative time, length of stay, perioperative mortality, or the incidence of significant complications between the 2 age groups. Gender, however, was associated with a statistically significant difference between the occurrence of complications, with more women experiencing complications than men (P = 0.026, relative risk = 2.36). One patient (age >75 years) in the entire cohort of 42 (2.4%) suffered a spinal cord injury. At 3 months, endoleaks were more common in the older age group (P = 0.059). CONCLUSION: Endograft therapy for thoracic aortic disease can be performed safely in elderly patients with no significant increase in perioperative morbidity or mortality compared with younger patients. Female gender is associated with a higher likelihood of perioperative complications, regardless of age. The overall incidence of spinal cord injury is very low. Endograft therapy, when anatomically possible, is the treatment of choice for thoracic aortic disease in elderly patients.

Adult↗
PubMed2000

Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study.

OBJECTIVE: To determine whether maternal influenza virus infection in the second and third trimesters of pregnancy results in transplacental transmission of infection, maternal auto-antibody production or an increase in complications of pregnancy. DESIGN: Case-control cohort study. POPULATION: Study and control cohorts were derived from 3,975 women who were consecutively delivered at two Nottingham teaching hospitals between May 1993 and July 1994. A complete set of three sera was available for 1,659 women. METHODS: Paired maternal ante- and postnatal sera were screened for a rise in anti-influenza virus antibody titre by single radial haemolysis and haemagglutination inhibition. Routine obstetric data collected during and after pregnancy were retrieved from the Nottingham obstetric database. Cord samples were tested for the presence of IgM anti-influenza antibodies, and postnatal infant sera were tested for the persistence of influenza-virus specific IgG. Paired antenatal and postnatal sera were tested against a standard range of auto-antigens by immunofluorescence. MAIN OUTCOME MEASURES: Classification of women as having definite serological evidence of an influenza virus infection in pregnancy (cases) or as controls. RESULTS: Intercurrent influenza virus infections were identified in 182/1,659 (11.0%) pregnancies. None of 138 cord sera from maternal influenza cases was positive for influenza A virus specific IgM. IgG anti-influenza antibodies did not persist in any of 12 infant sera taken at age 6-12 months. Six of 172 postnatal maternal sera from cases of influenza were positive for auto-antibodies. In all cases the corresponding antenatal serum was also positive for the same auto-antibody. There were no significant differences in pregnancy outcome measures between cases and controls. Overall, there were significantly more complications of pregnancy in the cases versus the controls, but no single type of complication achieved statistical significance. CONCLUSIONS: Influenza infection in the second and third trimesters of pregnancy is a relatively common event. We found no evidence for transplacental transmission of influenza virus or auto-antibody production in pregnancies complicated by influenza infections. There was an increase in the complications of pregnancy in our influenza cohort.

Adolescent↗
PubMed2004

Screening for lung cancer.

BACKGROUND: While population based screening for lung cancer has not been adopted by most countries, it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography are effective in reducing mortality from lung cancer. OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality. SEARCH STRATEGY: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE and EMBASE; 1966 to July 2000) ), bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effects model, but for other outcomes the fixed effect model was used. MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Adult↗
PubMed2003

Preoperative shock determines outcome for acute type A aortic dissection.

BACKGROUND: Acute type A aortic dissection is a life-threatening catastrophe. Surgical results have not improved. METHODS: The charts of all 70 patients surgically treated for acute type A primary aortic dissection during the period of January 1988 through April 2001 were reviewed. RESULTS: Average age was 59 +/- 2 years. Comorbidities included hypertension (66%), coronary artery disease (17%), and Marfan's syndrome (11%). At presentation, 23% were in shock, 17% had neurologic dysfunction, and 36% had coronary ischemia. The aortic valve was preserved in 55. Distal aortic anastomosis was performed under aortic cross-clamp ("closed") in 32 and "open" under circulatory arrest in 38 patients. Operative mortality was 18.6% (13 of 70 patients). Patients in shock had an operative mortality of 50% compared with stable patients of 9% (p = 0.0002). Mortality was similar regardless of technique. Univariate analysis revealed preoperative shock (p = 0.0002), tamponade (p = 0.003), and neurologic deficit (p = 0.02) to be associated with mortality. Multivariate analysis revealed hemodynamic stability (odds ratio = 0.10, p = 0.04) and outside transfer (odds ratio = 0.12, p = 0.03) to be negative predictors of mortality. Of 57 survivors, follow-up was 93% complete for an average of 46 +/- 6 months. The overall late reoperation rate was 24.6% (14 of 57 patients) at 50.3 +/- 12.3 months. Twelve patients (21%) underwent future aortic aneurysmal repair. No difference in reoperation rate was seen comparing "closed" (26%) with "open" (18%; p = 0.46). Of 42 preserved native valves, only 3 (7.1%) needed future valve replacement. CONCLUSIONS: In our experience, operative mortality was determined by preoperative hemodynamic instability. Technique did not impact survival or late reoperation. Early diagnosis and repair is critical to improving survival.

Adolescent↗
PubMed2005

Cyclo-oxygenase-2, endothelium and aortic reactivity during deoxycorticosterone acetate salt-induced hypertension.

OBJECTIVE: To test the hypothesis that the enhanced vascular responsiveness to norepinephrine that occurs during deoxycorticosterone acetate (DOCA)-salt induced hypertension is causally related to increased expression of cyclo-oxygenase (COX)-2 and oxidative stress, which diminishes the vasomodulatory influence of endothelium-derived nitric oxide. METHODS: Four groups of age-matched, male Sprague-Dawley rats were studied: Sham (normotensive); DOCA-salt (hypertensive); DOCA-salt treated with manganese(III) tetra(4-benzoic acid) porphyrin chloride [MnTBAP, an antioxidant; 15 mg/kg intraperitoneally (i.p.) for 21 days]; DOCA-salt treated with {N-[2-(cyclohexyloxy)-4-nitrophenyl]-methane sulfonamide} (NS-398, a COX-2 selective blocker; 5 mg/kg i.p. for 7 days). Contraction and relaxation were measured with FT03 force transducers coupled to a Grass polygraph in aortic rings bathed with physiologic salt solution (37 degrees C) and bubbled with a 5%CO2/95%O2 gas mixture. Aortic sensitivities (pD2 values) to norepinephrine and serum isoprostanes (8-iso-prostaglandin F2alpha, a marker of oxidative stress) were measured for each experimental paradigm. RESULTS: NS-398 significantly reduced maximal contractions in response to norepinephrine in aortic rings from Sham (44 +/- 3%) and DOCA-salt (96 +/- 2%) group rats. Expression of COX-2 protein increased significantly in vessels from DOCA-salt rats compared with those from Sham group rats. Treatment of DOCA-salt rats with either MnTBAP or NS-398 alleviated hypertension, normalized aortic pD2 values for norepinephrine and restored serum 8-isoprostane concentrations towards those observed in Sham group rats. CONCLUSIONS: COX-2 expression increases during DOCA-salt hypertension, and mediates production of factors that enhance rat aortic contractility in response to norepinephrine. Our data also suggest a role for increased oxidative stress, which is at least in part dependent on enhanced COX-2 expression, in the mechanism(s) of enhanced aortic contractility in response to norepinephrine during DOCA-salt hypertension.

Animals↗