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Biomedical subjects

Michael O'Reilly

Publications and source records attributed to Michael O'Reilly.

18 recordsLinked to original sources

Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer.

PURPOSE: To study the safety of bevacizumab with capecitabine-based chemoradiotherapy. PATIENTS AND METHODS: Patients with inoperable pancreatic adenocarcinoma received bevacizumab 2 weeks before radiotherapy (50.4 Gy treating the primary tumor and gross adenopathy), every 2 weeks during radiotherapy (12 patients each at 2.5, 5.0, 7.5, and 10 mg/kg), and after radiotherapy until disease progression. Capecitabine was administered on days 14 through 52 (650 mg/m2 orally twice daily for the first six patients; 825 mg/m2 for the remaining patients). RESULTS: Significant acute gastrointestinal (43% grade 2; 4% grade 3), hand and foot syndrome (21% grade 2), and transient hematologic (8% grade 3 or greater) events were uncommon with protocol mandated dose reductions of capecitabine grade 2 toxicity (43% of patients). Among the first 30 patients treated, three patients had tumor-associated bleeding duodenal ulcers, and one had a contained duodenal perforation. No additional bleeding events occurred among the final 18 patients after patients with duodenal involvement by tumor were excluded. Nine (20%) of 46 assessable patients had confirmed partial responses until distant progression for a median of 6.2 months. Four patients have undergone pancreaticoduodenectomy without perioperative complication. The median survival was 11.6 months (95% CI, 9.6 to 13.6), from the start of protocol therapy. CONCLUSION: Concurrent bevacizumab did not significantly increase the acute toxicity of a relatively well-tolerated chemoradiotherapy regimen. However, ulceration and bleeding in the radiation field possibly related to bevacizumab occurred when tumor involved the duodenal mucosa. The encouraging efficacy end points suggest that the further study of bevacizumab with chemoradiotherapy is warranted.

Adult↗

Incidence and predictors of difficult and impossible mask ventilation.

BACKGROUND: Mask ventilation is an essential element of airway management that has rarely been studied as the primary outcome. The authors sought to determine the incidence and predictors of difficult and impossible mask ventilation. METHODS: A four-point scale to grade difficulty in performing mask ventilation (MV) is used at the authors' institution. They used a prospective, observational study to identify cases of grade 3 MV (inadequate, unstable, or requiring two providers), grade 4 MV (impossible to ventilate), and difficult intubation. Univariate and multivariate analyses of a variety of patient history and physical examination characteristics were used to establish risk factors for grade 3 and 4 MV. RESULTS: During a 24-month period, 22,660 attempts at MV were recorded. 313 cases (1.4%) of grade 3 MV, 37 cases (0.16%) of grade 4 MV, and 84 cases (0.37%) of grade 3 or 4 MV and difficult intubation were observed. Body mass index of 30 kg/m or greater, a beard, Mallampati classification III or IV, age of 57 yr or older, severely limited jaw protrusion, and snoring were identified as independent predictors for grade 3 MV. Snoring and thyromental distance of less than 6 cm were independent predictors for grade 4 MV. Limited or severely limited mandibular protrusion, abnormal neck anatomy, sleep apnea, snoring, and body mass index of 30 kg/m or greater were independent predictors of grade 3 or 4 MV and difficult intubation. CONCLUSIONS: The authors observed the incidence of grade 3 MV to be 1.4%, similar to studies with the same definition of difficult MV. Presence of a beard is the only easily modifiable independent risk factor for difficult MV. The mandibular protrusion test may be an essential element of the airway examination.

Adult↗

Low tyrosine content of growth media yields aflagellate Salmonella enterica serovar Typhimurium.

Identification of Salmonella serotypes is based on flagellar and somatic antigens. The absence of flagella may consequently affect complete identification of the serotype; here it is shown that Salmonella enterica serovar Typhimurium exhibits morphological differences dependent on the peptone constituents of the culture medium. Aflagellate salmonella were produced in certain media where the nutritional ingredient was casein-based peptone or gelatin-based peptone; in gelatin-based peptone, aggregates of salmonella were observed. However, in media containing soy-based peptone as the primary nutrient, salmonella displayed a normal flagellated morphology. Transfer of aflagellate salmonella from nutritionally poor media, with casein- or gelatin-based peptone, into rich nutrient broth allowed flagella synthesis, indicating that the aflagellate form is still able to produce flagella. Amino acid sequencing of the peptones producing aflagellate organisms showed a relatively low tyrosine concentration: only 0.03+/-0.01 g l(-1) for gelatin-based buffered peptone water, compared to 0.21+/-0.01 for soy-based buffered peptone water. Tyrosine is essential for flagellin, which is the subunit of the salmonella flagellar filament. The addition of 200 muM tyrosine to casein-based peptone media produced flagellate salmonella; 2 mM glucose was needed in addition to tyrosine to achieve a similar morphology in gelatin-based media. Therefore, culture media containing less than 1.20 g tyrosine l(-1), and of limited carbohydrate source, when used for serological testing of clinical isolates, may result in an incomplete serological identification.

Carbohydrates↗

An anesthesia information system designed to provide physician-specific feedback improves timely administration of prophylactic antibiotics.

Surgical site infections are a frequent cause of morbidity and mortality and add significantly to the cost of care. One component of the national Surgical Infection Prevention (SIP) program is to ensure timely administration of prophylactic antibiotics, a key factor to reduce postoperative infection. Our anesthesia department decided to assume the responsibility for timing and administration of antibiotic prophylaxis and we initiated a multitiered approach to remind the anesthesiologist to administer the prophylactic antibiotics. We used our anesthesia clinical information system to implement practice guidelines for timely antibiotic administration and to generate reports from the database to provide specific feedback to individual care providers with the goal of ensuring that patients receive antibiotic prophylaxis within 1 h of incision. Before the initiation of this project, 69% of eligible patients received antibiotics within 60 min of the incision. After the program began, there was a steady increase in compliance to 92% 1 yr later. Provider-specific feedback increases compliance with practice guidelines related to timely administration of prophylactic antibiotics. Anesthesia information systems hold promise for implementing and monitoring new practice guidelines and the anesthesiologist may play a key role in influencing surgical outcomes by ensuring appropriate therapy that may not be directly related to anesthesia care.

Anesthesiology↗

Autofluorescence in eleocytes of some earthworm species.

Immunocompetent cells of earthworms, coelomocytes, comprise adherent amoebocytes and granular eleocytes (chloragocytes). Both cell populations can be expelled via dorsal pores of adult earthworms by exposure to an electric current (4.5 V) for 1 min. Analysis by phase contrast/fluorescence microscopy and flow cytometry demonstrated that eleocyte population of several species exhibits a strong autofluorescence. A high percentage (11-35%) of autofluorescent eleocytes was recorded in Allolobophora chlorotica, Dendrodrilus rubidus, Eisenia fetida, and Octolasion sp. (O. cyaneum, O. tyrtaeum tyrtaeum and O. tyrtaeum lacteum). In contrast, autofluorescent coelomocytes were exceptionally scarce (less than 1%) in representative Aporrectodea sp. (A. caliginosa and A. longa) and Lumbricus sp. (L. castaneus, L. festivus, L. rubellus, L. terrestris). Thus, this paper for the first time describes profound intrinsic fluorescence of eleocytes in some--but not all--earthworm species. The function (if any) and inter-species differences of the autofluorescent coelomocytes still remain elusive.

Animals↗

Epidemiology of cat-scratch disease hospitalizations among children in the United States.

BACKGROUND: Cat-scratch disease (CSD), caused by infection with Bartonella henselae, affects both children and adults but is principally a pediatric disease. Typical CSD is generally benign and self-limited and is characterized by regional lymphadenopathy with fever. Infections can, however, be accompanied by focal or diffuse inflammatory responses (atypical CSD) involving neurologic, organ (liver/spleen), lymphatic or skeletal systems. METHODS: Pediatric hospitalizations with CSD listed as a diagnosis were examined using the Kids' Inpatient Database for the year 2000. National estimates of CSD-associated hospitalizations, hospitalization rates and various hospitalization statistics were examined for patients younger than 18 years of age. RESULTS: During 2000, an estimated 437 (SE 43) pediatric hospitalizations associated with CSD occurred among children younger than 18 years of age in the United States. The national CSD-associated hospitalization rate was 0.60/100,000 children younger than 18 years of age (95% confidence interval, 0.49-0.72) and 0.86/100,000 children younger than 5 years of age (95% CI 0.64-1.07). Accompanying diagnoses included neurologic complications (12%), organ (liver/spleen) involvement (7%) and "other" (5%). Atypical CSD accounted for approximately 24% of the CSD-associated hospitalizations. The median charge for a CSD-associated hospitalization was 6140 dollars with total annual hospital charges of approximately 3.5 million dollars among children in the United States. CONCLUSIONS: The CSD-associated hospitalization rate among children during 2000 appeared similar to those estimated for the 1980s in the United States, despite significant increases in cat ownership in the intervening time. Early serologic and molecular testing for CSD in children is suggested to minimize unnecessary interventions and promote optimally effective care when supportive measures are required.

Adolescent↗

The quality of randomized controlled trials in major anesthesiology journals.

Increased attention has been directed at the quality of randomized controlled trials (RCTs) and how they are being reported. We examined leading anesthesiology journals to identify if there were specific areas for improvement in the design and analysis of published clinical studies. All RCTs that appeared between January 2000 and December 2000 in leading anesthesiology journals (Anesthesiology,Anesthesia & Analgesia,Anaesthesia, and Canadian Journal of Anaesthesia) were retrieved by a MEDLINE search. We used a previously validated assessment tool, including 14 items associated with study quality, to determine a quality score for each article. The overall mean weighted quality score was 44% +/- 16%. Overall average scores were relatively high for appropriate controls (77% +/- 7%) and discussions of side effects (67% +/- 6%). Scores were very low for randomization blinding (5% +/- 2%), blinding observers to results (1% +/- 1%), and post-beta estimates (16% +/- 13%). Important pretreatment clinical predictors were absent in 32% of all studies. Significant improvement in the reporting and conduct of RCTs is required and should focus on randomization methodology, the blinding of investigators, and sample size estimates. Repeat assessments of the literature may improve the adoption of guidelines for the improvement of the quality of randomized controlled trials.

Anesthesiology↗

Guidelines for the provision of echocardiography in Canada: recommendations of a joint Canadian Cardiovascular Society/Canadian Society of Echocardiography Consensus Panel.

Recognizing the central role of echocardiographic examinations in the assessment of most cardiac disorders and the need to ensure the provision of these services in a highly reliable, timely, economical and safe manner, the Canadian Cardiovascular Society and Canadian Society of Echocardiography undertook a comprehensive review of all aspects influencing the provision of echocardiographic services in Canada. Five regional panels were established to develop preliminary recommendations in the five component areas, which included the echocardiographic examination, the echocardiographic laboratory and report, the physician, the sonographer and indications for examinations. Membership in the panels was structured to recognize the regional professional diversity of individuals involved in the provision of echocardiography. In addition, a focus group of cardiac sonograhers was recruited to review aspects of the document impacting on sonographer responsibilities and qualification. The document is intended to be used as a comprehensive and practical reference for all of those involved in the provision of echocardiography in Canada.

Canada↗

Quantitative analysis of biomarkers defines an optimal biological dose for recombinant human endostatin in primary human tumors.

PURPOSE: In a recent study, we presented preliminary evidence for biological activity in a Phase I dose-finding study (15-600 mg/m(2)) of recombinant human endostatin in patients with refractory solid tumors. Here, we conducted additional biomarker analyses to correlate changes in tumor biology with dose. EXPERIMENTAL DESIGN: Excisional tumor biopsies were obtained at baseline and after 56 days of endostatin therapy. Laser scanning cytometry (LSC) was used to quantify biomarker levels in whole tissue sections. Apoptosis in tumor cells (TCs) and tumor-associated endothelial cells (ECs) was quantified by fluorescent three-color anti-CD31/terminal deoxynucleotidyl transferase-mediated nick end labeling staining. Microvessel densities were measured by LSC-guided vessel contouring. Levels of tumor-associated EC BCL-2 and hypoxia-inducible factor 1alpha were determined by immunofluorescence and LSC quantification. The results, including tumor blood flow measured by positron emission tomography, were analyzed using a quadratic polynomial model. RESULTS: Significant increases in EC death and decreases in tumor microvessel density were observed, with maximal effects of endostatin at a dose of 249 mg/m(2) (95% confidence interval, 159-338) and 257 mg/m(2) (95% confidence interval, 183-331), respectively. In contrast, levels of TC death were uniformly low and did not correlate with endostatin dose. Maximal nuclear hypoxia-inducible factor 1alpha and minimal EC Bcl-2 levels were observed at approximately 250 mg/m(2), although the changes did not reach statistical significance. CONCLUSIONS: The data suggest that endostatin had optimal biological activity at doses approximately 250 mg/m(2) in our cohort of patients. Endostatin's failure to induce high levels of TC death may explain its lack of significant clinical activity in this Phase I trial.

Angiogenesis Inhibitors↗

Comparison of spinal vs general anesthesia via laryngeal mask airway in inguinal hernia repair.

HYPOTHESIS: The use of laryngeal mask airway and propofol in inguinal hernia repair results in shorter operative and recovery room times. DESIGN: Randomized control trial. SETTING: University hospital. PATIENTS: From May 2000 to March 2002, a convenience sample of 79 patients was invited to participate; 34 entered the study. Fifteen patients were randomized to subarachnoid block, and 18 patients were randomized to laryngeal mask airway. No patients withdrew from the study because of adverse effects. All study subjects were followed up for 6 months. INTERVENTION: General anesthesia via laryngeal mask airway or lidocaine subarachnoid block anesthesia for inguinal hernia repair. MAIN OUTCOME MEASURES: Operative and recovery room times; surgeon evaluation of the adequacy of the anesthetic technique; 36-Item Short-Form Health Survey scores before and after operation. RESULTS: Total time from entry into the operating room to discharge home was slightly longer in the subarachnoid block group (285 vs 262 minutes; 95% confidence interval, 251-317 minutes) but this difference was not statistically or clinically significant. Patient satisfaction was high with both techniques; patient-reported outcomes were the same. Surgeons rated muscle relaxation and exposure better with the subarachnoid block. CONCLUSIONS: We found no differences between short-acting spinal anesthesia and general anesthesia via laryngeal mask airway with intravenous propofol in efficiency or in early or late outcomes after elective inguinal hernia repair. Surgeon and patient preferences appear to be the most important reasons for selecting an anesthetic technique for individual patients undergoing inguinal hernia repair.

Adult↗

Improving Door-to-Drug time and ST segment resolution in AMI by moving thrombolysis administration to the Emergency Department.

BACKGROUND: We describe a combination of measures to reduce Door-to-Drug (DTD) time and improve the Emergency Department (ED) management of ST elevation MI (STEMI): appointment of a Cardiology Nurse Specialist, application of the American College of Cardiology and the American Heart Association (ACC/AHA) guidelines, changing the site of thrombolysis from the CCU to the ED, the introduction of a single bolus thrombolytic agent. METHODS: The 12-month period before and after the introduction of the measures were retrospectively reviewed. One hundred and sixty patients were discharged from the CCU with the diagnosis of myocardial infarction confirmed by ECG and enzyme criteria. Eighty patients had STEMI and fulfilled criteria for thrombolytic therapy at the time of presentation to hospital. A full data set was available on 35/38 of patients in the 12 months prior to the measures (Year 1), and 39/42 in the 12 months subsequent (Year 2). RESULTS: Median DTD time fell from 80 to 22 min after institution of the measures. Median Pain-to-Drug time also fell from 270 to 140 min. Thrombolytic agent given in the ED rose from 3% in Year 1, to 72% in Year 2. IV beta-blocker administered in the ED rose from 12% to 79%, resulting in median time to receiving IV beta-blocker falling from 63 to 19 min. Elevated ST segments resolved by >/=70% in <2 h in 53% of Year 2 patients, compared with 23% of Year 1 patients. Combined major in-hospital adverse clinical events were reduced from 49% to 15%. CONCLUSION: This combination of measures reduces DTD time, improves speed to delivery of important concomitant medications, and significantly improves the time to ST segment resolution and outcome in STEMI.

Adult↗

Identifying opportunities to address the congestive heart failure burden: the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) study.

BACKGROUND: Medical, social and economic costs of congestive heart failure (CHF) continue to rise. There exists a 'care gap' between what the optimal care populations with CHF should receive and actually do receive. Central to the goal to develop effective strategies against the 'care gap' is accurate measurement of the CHF burden. Administrative data are limited in detail and accuracy and clinical databases suffer from limited size. Improving Cardiovascular Outcomes in Nova Scotia (ICONS) is a province-wide population-based disease management study with access to all patient health data including outcomes. METHODS: Medical records of all patients admitted to any Nova Scotia health care institution with a cardiovascular disorder were prospectively examined by trained abstractors. Patients were followed up and health outcomes measured through assignment of unique identifier numbers and linkage with Vital Statistics Nova Scotia. This report summarizes baseline data for the population admitted to hospital with a diagnosis of CHF between October 15, 1997 and October 14, 1998. RESULTS: There were 2637 unique patients enrolled with 3547 hospitalizations. The median length of stay was eight days, with in-hospital mortality of 18.2%; 10.8% were discharged to long term care. The mortality rate was 38.7% at 12 months and the rehospitalization rate was 39.9%. Average age was 75 +/- 10 years (median 76) and 52% were female. There were 4.5 comorbidities per patient. Left ventricular ejection fraction (LVEF) was measured in fewer than 40%; of these, fewer than 39% had a documented ejection fraction less than 40%. At discharge, 61.3% of survivors were prescribed angiotensin-converting enzyme (ACE) inhibitors, 6.0% angiotensin blockers, 42.1% beta-blockers, 75.6% diuretics, 26.1% calcium channel blockers and 19.3% warfarin. Females were older and had lower rate of LVEF testing and ACE and warfarin usage. CONCLUSION: The burden of disease for CHF in Nova Scotia is large and affects an elderly population with multiple comorbidities. Adverse outcomes such as death, rehospitalization and admission to a chronic care facility are common. Measurement of the 'care gap' requires consideration of these factors and of elderly and female patients regardless of left ventricular function. Successful strategies will likely be multidisciplinary in scope with a focus toward improving access to care.

Aged↗

An analysis of reintubations from a quality assurance database of 152,000 cases.

STUDY OBJECTIVE: To determine if the majority of reintubations, a potentially preventable adverse event, were predominantly due to residual muscle relaxant effects, we analyzed our quality assurance database to identify the causes of reintubation. DESIGN: Retrospective study. SETTING: University of Michigan Department of Anesthesiology Quality Assurance (QA) database. MEASUREMENTS: We analyzed QA records from 152,939 anesthetic cases performed from 1994 to 1999 at our institution. Of these cases, 107,317 were performed with a general anesthetic. The medical record of each patient requiring reintubation was obtained and reviewed to determine the cause of the reintubation. RESULTS: A total of 191 reintubation events were identified. One hundred twelve of the 191 (59%) reintubations were due to respiratory problems; 11 of the 191 (6%) reintubations were due to complications of neuromuscular blocking drug use. Other causes were unintentional extubation, surgical complication, endotracheal tube problems, and cardiac problems. One hundred five reintubations (105/191, 55%) occurred in the operating room and 86 (86/191, 45%) occurred in the postanesthesia care unit. CONCLUSION: Respiratory complications were the most common cause of reintubation in the perioperative period. Complications related to the neuromuscular blocking drugs were the fourth most common cause of reintubation. More reintubations occurred in the operating room than the postanesthesia care unit. Muscle relaxant effect and opioid effect are rare causes of respiratory failure in the anesthetized patient in the immediate postoperative period.

Aged↗

Reducing unnecessary cross-matching: a patient-specific blood ordering system is more accurate in predicting who will receive a blood transfusion than the maximum blood ordering system.

UNLABELLED: Most blood transfusions are given in the operating room. Adoption of the Maximum Surgical Blood Ordering Schedule in the 1970s reduced the amount of blood unnecessarily cross-matched, but the national cross-match-to-transfusion ratio remains at approximately two-to-one. We tested the ability of a patient-specific blood ordering system (PSBOS) to more accurately predict potential operative transfusion. All adult patients who had blood cross-matched before surgery (February through June 1999) for elective operative procedures at the University of Michigan Hospital were identified. Complex surgeries were excluded. Surgeons estimated the expected blood loss for their surgeries, and the expected postoperative hematocrit was calculated using the patient's blood volume, the surgeon-defined expected blood loss, and preoperative hematocrit. Lowest tolerated hematocrit was set at 21% except in patients with coronary artery disease or who were ASA physical status III or more (28%). Sensitivity, specificity, positive predictive value, and negative predictive value of the PSBOS were calculated. Our analysis included 178 cases in which blood was cross-matched before surgery, representing 69 different surgeries and 42 surgeons. Only 16% of patients received an intraoperative transfusion. Of the 156 patients that PSBOS predicted would not require an operating room transfusion, 139 were not transfused. Of the 21 patients PSBOS predicted would be transfused, 11 were. The sensitivity of the algorithm as tested was 41%, the specificity 93%, the positive predictive value was 55%, and the negative predictive value was 89%. We conclude that PSBOS, which includes patient and surgeon variables in transfusion prediction, is more accurate than the Maximum Surgical Blood Ordering Schedule, which uses only surgical procedure. IMPLICATIONS: Currently, many units of blood set aside for surgery are never required, resulting in extra work and expense for blood banks. A formula that included patient weight and hematocrit and typical surgery blood loss was used to predict who would require transfusions. We reduced the predicted number of patients who had blood set aside from 178 to 21.

Adolescent↗

Management of rabies in humans.

Rabies is a fatal disease in humans, and, to date, the only survivors of the disease have received rabies vaccine before the onset of illness. The approach to management of the rabies normally should be palliative. In unusual circumstances, a decision may be made to use an aggressive approach to therapy for patients who present at an early stage of clinical disease. No single therapeutic agent is likely to be effective, but a combination of specific therapies could be considered, including rabies vaccine, rabies immunoglobulin, monoclonal antibodies, ribavirin, interferon-alpha, and ketamine. Corticosteroids should not be used. As research advances, new agents may become available in the future for the treatment of human rabies.

Adrenal Cortex Hormones↗

Report from the society for biological therapy and vascular biology faculty of the NCI workshop on angiogenesis monitoring.

The field of tumor angiogenesis has seen explosive growth over the last 5 years. Preclinical as well as early clinical evaluation of novel compounds is progressing at a rapid pace. To gain a perspective on the field and to take stock of advances in the understanding of molecular mechanisms underlying the process of tumor angiogenesis as well as ways of monitoring the activity of agents, the Society for Biologic Therapy and the National Cancer Institute's Vascular Biology Faculty convened a Workshop on Angiogenesis Monitoring in November 2002. The Workshop was composed of invited speakers and participants from academia, industry, and government. It was divided into 3 sessions, each chaired by leaders in the field. The first focused on advances in the understanding of the cellular and molecular mechanisms of angiogenesis in tumors. The second examined preclinical assay systems that are useful in vascular biology. The third addressed the translation to the clinic and monitoring of antiangiogenic activity of agents in patients and novel trial designs. What follows is a summary of the discussions and findings of each session.

Animals↗