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Biomedical subjects

D E Roberts

Publications and source records attributed to D E Roberts.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of different treatment regimens for the emergence of new resistance under therapy.

OBJECTIVE: To compare the effects of different therapy regimens on the probability of emergence of new resistant mutants during therapy. METHODS: We developed a stochastic model of infection and treatment to calculate the probability of de novo resistance during therapy. We simulated diverse treatment regimens, with different efficacy in controlling HIV replication. We studied the use of genotypic testing to choose treatment protocols specifically tailored against the wild type. RESULTS: The probability of emergence of a previously nonexisting drug-resistant mutant during therapy depends crucially on the drug regimen used. In particular, therapy protocols targeting the wild-type strain may lead to a higher probability of treatment failure due to resistance. Conversely, targeting the minority strains in the population, which readily mutate into the resistant variety, significantly lowers the probability of a new resistant emerging under therapy. CONCLUSIONS: Use of genotypic testing may lead to wrong decisions in the choice of therapy if the population dynamics of production of new resistant mutants is not taken into account.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Use of superficial femoropopliteal vein for suprainguinal arterial reconstruction in the presence of infection.

BACKGROUND: Conventional treatment of mycotic aneurysms or graft infections of the aortoiliac segment by in situ or extra-anatomic prosthetic reconstruction has a high mortality and morbidity rate, with a substantial risk of persistent graft infection. The use of autologous vein may reduce this. METHODS: Eleven patients with suprainguinal arterial infections including two with mycotic aortic aneurysms, four with aortic graft infections, four infected femorofemoral grafts and an infected axillofemoral graft were treated by debridement and in situ reconstruction with autologous superficial femoropopliteal vein. All patients received appropriate antibiotic therapy and were followed by regular postoperative duplex imaging. Preoperative femoral vein duplex imaging was performed in eight of the 11 patients. RESULTS: Ten of the 11 patients survived with a functioning graft and without limb loss or evidence of infection at 4-33 months. One patient died from myocardial infarction after operation. Three patients had minor swelling of one leg. Four patients required subsequent angioplasty of anastomotic stenoses detected by duplex surveillance. CONCLUSION: Superficial femoropopliteal vein is an excellent conduit for suprainguinal reconstruction in the presence of infection. Duplex imaging is useful for confirming the suitability of deep veins for use as a graft and for postoperative surveillance.

Aged↗
PubMed2000

Clinically significant gastrointestinal bleeding in critically ill patients in an era of prophylaxis.

OBJECTIVE: Clinical studies examining stress-related gastrointestinal bleeding in critically ill patients vary in their clinical definitions and assessment of clinical significance. Although there is evidence that routine prophylaxis decreases stress-related gastrointestinal bleeding, recent studies indicate a decreasing incidence, independent of the use of prophylactic medications. The purpose of this study was to determine the incidence of and risk factors for clinically significant, endoscopically proven gastrointestinal bleeding in critically ill patients. METHODS: A database (prospectively collected data) of 8338 patients admitted to the surgical and medical intensive care units at major tertiary care center from July 1988 to April 1995 was examined. All patients with significant upper gastrointestinal bleeding as defined by a drop in hemoglobin of >20 g/L and endoscopic evidence of an upper GI tract source were identified. Risk factors for GI bleeding from stress ulceration were compared in bleeding and nonbleeding patients. A case-control study analyzing risk factors for bleeding in the abdominal aortic aneurysm subgroup was performed. RESULTS: After exclusion criteria, 12/7231 (0.17%) patients had clinically significant, endoscopically proven bleeding. Significant risk factors included age, septic shock, abdominal aortic aneurysm repair, and nutritional support. Intensive care unit stay was prolonged in patients with stress-related bleeding. There was no difference in incidence of hypotension, clamp time, APACHE score, or operating room time in patients with abdominal aortic aneurysm repair as compared with controls. CONCLUSIONS: In an intensive care unit where stress prophylaxis is widely used, clinically important gastrointestinal bleeding is uncommon. Further study is needed to define the optimal prophylaxis regimen and the role for its selective use in high-risk patients.

Aged↗
PubMed1999

Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa.

The identification of mucosal immune responses required for protection against sexual transmission of HIV is essential for the development of an efficacious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) of 11 rhesus monkeys following colonic exposure to two molecular clones of SIV. Two monkeys had no signs of infection. Three monkeys became persistently infected. Transient infections, characterized by the sporadic detection of virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the monkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP. Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP. Three or six months postexposure, these animals and four naive controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670. All four monkeys with strong SIV env-specific MHC-restricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protected. These experiments provide the first direct evidence that transient mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. Furthermore, a strong correlation between SIV env-specific MHC-restricted CTL in the LP and protection against colonic mucosal challenge was observed.

Animals↗
PubMed1999

Oxidative stress in humans during work at moderate altitude.

Increased oxidative stress has been associated with work at high altitude; however, it is not known whether oxidative stress is a significant problem at moderate altitudes. The oxidative stress indicators, breath pentane (BP), 8-hydroxydeoxyguanosine (8-OHdG), oxygen radical absorption capacity (ORAC), 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and lipid peroxides (LPO) were measured in breath, blood and urine samples of U.S. Marines engaged in moderate altitude ( approximately 3000 m) cold weather field training. The test subjects were divided into a placebo and four antioxidant supplement groups (n = 15/group) and received the following supplements for 28 d: 1) vitamin E, 440 alpha-tocopherol equivalents (alpha-TE); 2) vitamin A, 2000 retinol equivalents (RE) of beta-carotene; 3) vitamin C, 500 mg ascorbic acid; 4) a mixture of 440 alpha-TE, 2000 RE of beta-carotene, 500 mg ascorbic acid, 100 microg selenium and 30 mg zinc daily. Strenuous work ( approximately 23 MJ/d) in cold weather at moderate altitude was accompanied by increases in several indicators of oxidative stress that were not effectively controlled by conventional antioxidant supplements. The group receiving the antioxidant mixture exhibited lower BP (P < 0. 05) compared with those receiving single antioxidant supplements; however, not all markers of oxidative stress responded like BP. Because these markers did not respond in the same manner, it is important to include markers from more than one source to assess the effect of supplemental dietary antioxidants.

Adult↗
PubMed1999

Effect of antioxidant supplementation on urine and blood markers of oxidative stress during extended moderate-altitude training.

OBJECTIVE: To investigate the increase in oxidative stress during work at moderate altitudes due to additional energy expenditure, tissue anoxia, and UV light exposure. METHODS: Thirty US Marine Corps volunteers were divided into placebo (P) and antioxidant supplement (S) groups and tested for markers of oxidative stress before (t0), at the midpoint of (t1), and after (t2) 14 days of winter training at a moderate altitude (approximately 2700 m). The antioxidant supplement consisted of a daily dose of 20,000 IU beta-carotene, 400 IU vitamin E, 500 mg vitamin C, 100 micrograms selenium, and 30 mg zinc. The following markers of oxidative stress were measured: urine thiobarbituric acid reactive substances (TBARSs), urine hydroxynonenal (HNE), urine 8-hydrodeoxyguanosine (8-OHdG), plasma total peroxyl radical trapping potential (TRAP), and plasma lipid hydroperoxides (LPOs). Urine was collected on a 24-hr basis at t0, t1, and t2; blood samples were collected at t0 and t2. RESULTS: P group LPOs increased 30% (p < 0.05) between t0 and t2, whereas S group LPOs did not increase. Both groups exhibited significant increases in urine TBARSs, HNE, and 8-OHdG by t2. Urine TBARSs, HNE, and 8-OHdG increased between t0 and t1 in both groups, with the greater increase in the S group. The conflicting results between the plasma and urine markers of oxidative stress may be due to a time-phase relationship. CONCLUSIONS: The results of this study suggest that work in a moderate-altitude cold-weather environment is accompanied by increased oxidative stress, despite relatively high intakes of dietary and supplemental antioxidants.

Adult↗
PubMed1998

Postoperative laboratory and imaging investigations in intensive care units following coronary artery bypass grafting: a comparison of two Canadian hospitals.

OBJECTIVES: To compare the utilization and cost of common laboratory and imaging tests following admission to the intensive care unit (ICU) after coronary artery bypass surgery in two hospitals. The hospitals use different strategies to order tests postoperatively: one hospital uses a mandated protocol while the other does not. DESIGN: Demographic and testing data were prospectively collected in both hospitals as part of an ongoing ICU management program. Thirteen commonly performed laboratory tests or imaging procedures were compared. Average costs for each test were calculated, and utilization and cost of testing were compared per admission and per day in ICU. SETTING: Two tertiary care ICUs in different Canadian cities. PATIENTS: Consecutive patients admitted to ICU following coronary artery bypass graft surgery over a two-year period. MAIN RESULTS: There were 415 admissions to the Health Sciences Centre in Winnipeg, Manitoba and 504 to the Jewish General Hospital (JGH) in Montreal, Quebec. There were no demographic, length of stay or ICU mortality differences. A postoperative protocol for ordering investigations is used at JGH. Striking differences in test utilization were noted, with more investigations performed per admission and per unit day at JGH (P < 0.001). The average cost of the investigations was greater at JGH ($160 more per admission; $75 more per intensive care day). CONCLUSIONS: There are marked differences in the investigation pattern and costs for coronary artery bypass patients admitted to ICU in these hospitals. It is suggested that the benefits of frequent routine determinations of bloodwork, electrocardiograms and chest radiographs should be reevaluated in this patient population.

Canada↗
PubMed1998

Femoral osteomyelitis after tooth extraction.

Up to 35% of normal individuals may harbor Hemophilus aphrophilus in their oropharynx. Generally, this organism is well tolerated and rarely causes systemic infections; however, osteomyelitis may occur and it has previously been described involving the spine. Because of an intrinsic ability to inhibit leukocytes, osseous infections from this organism characteristically present in an insidious fashion. A case of severe femoral osteomyelitis after dental extraction is described.

Femur↗
PubMed1997

A citywide analysis of the utilization of common laboratory tests and imaging procedures in ICUs.

OBJECTIVE: To identify and discriminate between patient and institutional determinants of investigation costs in the ICU. DESIGN: Retrospective survey. SETTING: All seven hospitals in the city of Winnipeg, Manitoba, Canada. PARTICIPANTS: One hundred consecutive admissions to each of 11 ICUs. Two teaching hospitals (TH1 and TH2) each have three units (medical, surgical, and coronary care), the five community hospitals (CHs) have single combined units. TH1 operates an information-based management system. MEASUREMENTS: Each admission was categorized as MEDICAL, SURGICAL, or CARDIAC. The frequency and cost of 17 laboratory or imaging procedures were collected for each admission. Demographic data included age, length of ICU stay, APACHE II (acute physiology and chronic health evaluation) score, therapeutic intervention scoring system (TISS) data, and ICU survival. The primary diagnosis on admission and acquisition of significant problems or complications after admission were collected. RESULTS: Multivariate models revealed that length of stay, TISS score, and acquisition of a problem after ICU admission were strongly associated with increased costs in all categories (p=0.0001). Admission to TH2 was associated with greater costs in all categories (p=0.0001 MEDICAL and CARDIAC; p=0.0016 SURGICAL). Admission to a CH was associated with lower cost for SURGICAL admissions (p=0.0014), but costs at CHs were not significantly lower than at TH1 for MEDICAL (p=0.18) or CARDIAC (p=0.22) admissions. CONCLUSIONS: ICU investigation costs vary significantly between institutions and are not always linked to patient-dependent factors. Acquisition of nosocomial and iatrogenic events during ICU admission increases costs dramatically. Costs are not necessarily greater in teaching hospitals.

APACHE↗
PubMed1996

Intensive care unit admission following successful cardiopulmonary resuscitation: resource utilization, functional status and long-term survival.

A retrospective review of consecutive admissions (n = 285) to a university hospital intensive care unit (ICU) following cardiopulmonary resuscitation was conducted to determine long-term outcome, length of stay (LOS), and ICU resource consumption. Ninety-four patients (33%) survived to hospital discharge. Hospital survivors had longer ICU LOS than non-survivors (5.1 +/- 0.8 vs. 2.8 +/- 0.4 days, P < 0.001) and longer hospital stays (22.5 +/- 3.7 vs. 2.9 +/- 1.2 days, P < 0.001). Average laboratory and pharmacy costs per admission were greater in hospital survivors than non-survivors. Most patients returned to their pre-arrest homes functionally independent and 58% of hospital survivors were alive 2 years after discharge. It is possible that attempts to appropriately limit therapy in patients with poor prognosis may help direct resources towards patients who will benefit.

Activities of Daily Living↗
PubMed1996

A comparison of opioid solutions for patient-controlled epidural analgesia.

Sixty patients took part in a randomised, double-blind study to compare the analgesic and side effects of three opioid-containing solutions for patient-controlled epidural analgesia following abdominal surgery. Patients in group 1 received a solution containing bupivacaine 0.125% with fentanyl 10 micrograms.ml-1, group 2 bupivacaine 0.125% with diamorphine 125 micrograms.ml-1, group 3 pethidine 2.5 mg.ml-1. All groups received 4 ml.h-1 background infusion and 3 ml boluses every 20 min if necessary. There were no significant differences between the groups in visual analogue scale pain scores (p = 0.537) or volumes of solution used at 24 h (p = 0.351) or 48 h (p = 0.105). Motor block was significantly higher in group 2 (p < 0.004) and pruritus occurred significantly less in group 3 (p < 0.05). We conclude that these three solutions produce equivalent analgesia but that pethidine 2.5 mg.ml-1 may be associated with fewer side effects.

Aged↗
PubMed1994

Antineutrophil cytoplasmic autoantibodies in the immunodiagnosis of systemic necrotizing vasculitis.

If testing of ethanol-fixed neutrophils remains the most commonly used method to screen for ANCA. C-ANCA is highly sensitive and specific for Wegener's granulomatosis if strict criteria in defining this IF pattern are followed. P-ANCA is not specific for MPO-ANCA, when used as a screening test. Because of the increasing recognition of atypical cytoplasmic staining patterns and the lack of specificity of nuclear staining of neutrophils for MPO-ANCA, confirmatory testing by ELISA is advisable in all cases of atypical neutrophil cytoplasmic staining and in all cases of neutrophil nuclear or perinuclear staining.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Pyridostigmine bromide does not alter thermoregulation during exercise in cold air.

This study examined the effects of acute and chronic pyridostigmine bromide (PB) administration on thermoregulatory and metabolic responses to exercise in cold air (5 degrees C). Seven healthy men completed two 7-day trials in a double-blind, crossover experimental design: during one trial they received PB (30 mg three times daily) and during the other trial they received placebo. For each trial, subjects attempted four (3 h) exercise tests: low-intensity exercise (approximately 25% VO2max) and moderate-intensity exercise (approximately 50% VO2max), on days 2 and 3 and again on days 6 and 7. Metabolic rate, body temperatures, and venous blood samples were obtained before and during exercise. Red blood cell acetylcholinesterase inhibition induced by PB increased (p < 0.05) from 34% on day 1 to 43% on days 3-7. Metabolic rate, body temperatures, and regional heat conductance responses were not different between trials. Plasma glucose, glycerol, free fatty acid, lactate, sodium, and potassium concentrations were not different between trials. In addition, differences were not found between acute and chronic experiments for any thermoregulatory or metabolic responses. These findings demonstrate that the PB dosage used by military personnel, as a pharmacological defense against nerve-agent poisoning, should not cause any adverse thermoregulatory or metabolic effects during moderate activity in cold climates.

Adult↗