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ABSTRACT: OBJECTIVE:: There is continuing controversy regarding the effect of glucocorticoids on a systemic inflammatory process. Based on a model of glucocorticoid action that includes both pro- and anti-inflammatory effects, we used the human experimental endotoxemia model to test the hypothesis that a transient elevation of plasma cortisol to stress-associated levels would enhance a subsequent (delayed) systemic inflammatory response to bacterial endotoxin. DESIGN:: Prospective, randomized, double-blind, placebo-controlled clinical investigation. SETTING:: Academic medical center. SUBJECTS:: Thirty-six healthy human volunteers. INTERVENTIONS:: Participants were randomized to receive a 6-hr intravenous infusion of saline (Control), an intermediate dose of cortisol (Cort80; 6.3 mg/hr/70 kg), or a high dose of cortisol (Cort160; 12.6 mg/hr/70 kg) on day 1. On day 2, participants received an intravenous injection of 2 ng/kg Escherichia coli endotoxin followed by serial measurements of plasma cytokine concentrations. MEASUREMENTS AND MAIN RESULTS:: Baseline participant characteristics and cortisol and cytokine concentrations were similar in all three groups. The plasma cortisol response to endotoxemia on day 2 was similar in all three groups. The interleukin-6 response to endotoxemia was significantly increased in the Cort80 Group compared with the Control Group (p = 0.004), whereas the interleukin-10 response was significantly suppressed (p = 0.034). Corresponding results for the Cort160 Group were not significantly different from Control Group values. CONCLUSIONS:: In this study, transient elevation of in vivo cortisol concentrations to levels that are observed during major systemic stress enhanced a subsequent, delayed in vivo inflammatory response to endotoxin. This appeared to be a dose-dependent effect that was more prominent at intermediate concentrations of cortisol than at higher concentrations of cortisol.
Critical care medicine 09/2009; · 6.37 Impact Factor
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ABSTRACT: The aim of most population-based studies of media is to relate a specific exposure to an outcome of interest. A research program has been developed that evaluates exposure to different components of movies in an attempt of assess the association of such exposure with the adoption of substance use during adolescence. To assess exposure to movie substance use, one must measure both viewing time and content. In developing the exposure measure, the study team was interested in circumventing a common problem in exposure measurement, where measures often conflate exposure to media with attention to media. Our aim in this paper is to present a validated measure of exposure to entertainment media, the Beach method, which combines recognition of a movie title with content analysis of the movie for substance use, to generate population based measures of exposure to substance use in this form of entertainment.
Communication Methods and Measures 02/2008; 2(1-2):134-151.
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Douglas J Robertson,
E Robert Greenberg, Michael Beach,
Robert S Sandler,
Dennis Ahnen,
Robert W Haile,
Carol A Burke,
Dale C Snover,
Robert S Bresalier,
Gail McKeown-Eyssen,
Jack S Mandel,
John H Bond,
Rosalind U Van Stolk,
Robert W Summers,
Richard Rothstein,
Timothy R Church,
Bernard F Cole,
Tim Byers,
Leila Mott,
John A Baron
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ABSTRACT: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia.
Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored.
CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia.
CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.
Gastroenterology 08/2005; 129(1):34-41. · 11.68 Impact Factor
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ABSTRACT: In some studies, high calcium intake has been associated with an increased risk of prostate cancer, but no randomized studies have investigated this issue.
We randomly assigned 672 men to receive either 3 g of calcium carbonate (1,200 mg of calcium), or placebo, daily for 4 years in a colorectal adenoma chemoprevention trial. Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses. Subject reports were verified by medical record review. Serum samples, collected at randomization and after 4 years, were analyzed for 1,25-(OH)2 vitamin D, 25-(OH) vitamin D, and prostate-specific antigen (PSA). We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels.
After a mean follow-up of 10.3 years, there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [unadjusted rate ratio, 0.83; 95% confidence interval (95% CI), 0.52-1.32]. Most cases were not advanced; the mean Gleason's score was 6.2. During the first 6 years (until 2 years post-treatment), there were significantly fewer cases in the calcium group (unadjusted rate ratio, 0.52; 95% CI, 0.28-0.98). The calcium risk ratio for conversion to PSA >4.0 ng/mL was 0.63 (95% CI, 0.33-1.21). Baseline dietary calcium intake, plasma 1,25-(OH)2 vitamin D and 25-(OH) vitamin D levels were not materially associated with risk.
In this randomized controlled clinical trial, there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect.
Cancer Epidemiology Biomarkers & Prevention 03/2005; 14(3):586-9. · 4.12 Impact Factor
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ABSTRACT: Postoperative pain after total knee arthroplasty (TKA) is severe, and achieving adequate analgesia remains a clinical challenge. We tested the hypothesis that, in patients having unilateral TKA under intrathecal (IT) anesthesia, the addition of a femoral nerve block would provide superior analgesia when compared with IT morphine and demonstrate fewer adverse side effects. In a single-blinded and controlled trial, 41 ASA I-III patients undergoing unilateral TKA were randomized into 2 groups. Both groups received 15 mg of IT hyperbaric bupivacaine for the surgical anesthetic. Group ITM received 250 microg of IT morphine and group FNB received an ultrasound-assisted femoral nerve block with 40 mL of 0.5% ropivacaine, 5 microg/mL of epinephrine, and 75 microg of clonidine. At 1, 2, 4, 6, 12, and 24 h postoperatively, we measured visual analog scales for pain, cumulative IV morphine consumption, hemodynamics, and side effects. There were no statistically significant differences in morphine consumption, pain at rest, or pain with movement. However, group FNB had fewer perioperative side effects including nausea, vomiting, and pruritus (P < 0.05 for each event). This corresponded to a decrease in patient satisfaction in group ITM, in which 20% of the patients rated their experience as "unsatisfactory" (P < 0.05). We conclude that, in comparison with IT morphine, a single injection femoral nerve block provides equivalent analgesia but with a significant reduction in side effects for patients having TKA under bupivacaine intrathecal anesthesia.
Anesthesia & Analgesia 12/2004; 99(5):1539-43; table of contents. · 3.29 Impact Factor
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ABSTRACT: Postoperative pain after total knee arthroplasty (TKA) is severe and can complicate early physical therapy. We tested the hypothesis that intrathecal clonidine would improve postoperative analgesia for TKA using a hyperbaric bupivacaine spinal anesthetic. In a double-blinded, placebo-controlled protocol, 81 ASA physical status I-III patients undergoing either a single or bilateral TKA were randomized into 4 groups with the following 2-mL solutions added to 15 mg of hyperbaric bupivacaine: 1) sterile saline, 2) morphine (250 microg), 3) morphine (250 microg) with clonidine (25 microg), and 4) morphine (250 microg) with clonidine (75 microg). At 1, 2, 4, 6, 12, and 24 h postoperatively, we measured visual analog scales (VAS), cumulative IV morphine consumption, hemodynamics, nausea, ancillary drugs, and side effects. Our primary comparison was between the clonidine with morphine groups versus the morphine group. We found that the combined administration of intrathecal clonidine and morphine decreased 24 h IV morphine consumption by 13 mg (P = 0.028) when compared with intrathecal morphine alone. This corresponded to a decrease in the VAS score of 1.3 cm at 24 h postoperatively (P = 0.047). Adverse side effects were similar among all groups with the exception of more relative hypotension in the clonidine groups through postoperative hour 6. We conclude that the coadministration of intrathecal clonidine and morphine decreases the 24-h IV morphine consumption and improves the 24-h VAS score when compared with intrathecal morphine alone. IMPLICATIONS: In this prospective, randomized, double-blinded, and placebo-controlled trial, we identify an effective postoperative analgesic approach in total knee replacement surgery. Intrathecal morphine (250 microg) combined with clonidine (25 or 75 microg) provided superior analgesia compared with intrathecal morphine alone.
Anesthesia & Analgesia 05/2003; 96(4):1083-8, table of contents. · 3.29 Impact Factor
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John A Baron,
Bernard F Cole,
Robert S Sandler,
Robert W Haile,
Dennis Ahnen,
Robert Bresalier,
Gail McKeown-Eyssen,
Robert W Summers,
Richard Rothstein,
Carol A Burke, [......],
Gerald J Beck,
John H Bond,
Tim Byers,
E Robert Greenberg,
Jack S Mandel,
Norman Marcon,
Leila A Mott,
Loretta Pearson,
Fred Saibil,
Rosalind U van Stolk
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ABSTRACT: Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel.
We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals.
Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 percent). The incidence of one or more adenomas was 47 percent in the placebo group, 38 percent in the group given 81 mg of aspirin per day, and 45 percent in the group given 325 mg of aspirin per day (global P=0.04). Unadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg group (95 percent confidence interval, 0.69 to 0.96) and 0.96 in the 325-mg group (95 percent confidence interval, 0.81 to 1.13). For advanced neoplasms (adenomas measuring at least 1 cm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the respective relative risks were 0.59 (95 percent confidence interval, 0.38 to 0.92) and 0.83 (95 percent confidence interval, 0.55 to 1.23).
Low-dose aspirin has a moderate chemopreventive effect on adenomas in the large bowel.
New England Journal of Medicine 04/2003; 348(10):891-9. · 53.30 Impact Factor
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ABSTRACT: We present a case report of two infants given a bupivacaine caudal anaesthetic as a means of achieving sedation for a diagnostic brain magnetic resonance imaging (MRI). Patient 1 was born at 27 weeks of gestation and presented to our hospital at 39 weeks postconception with a history of bronchopulmonary dysplasia and apnoea/bradycardia spells. He was undergoing a brain MRI for the work up of persistent apnoea and craniofacial abnormalities. Patient 2 was a term infant at 42 weeks postconception undergoing a MRI for the work up of a seizure disorder. Both infants fell asleep shortly after placement of the caudal blocks and the studies were completed successfully without complications. Utilizing this technique, we avoided dealing with a potentially difficult airway (patient 1), exacerbating postoperative apnoea and the negative implications of intravenous sedation during a study where there is limited access to the patient's airway.
Pediatric Anesthesia 03/2003; 13(2):171-4. · 2.10 Impact Factor
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ABSTRACT: Controversy exists regarding the need for nerve stimulation when performing an ultrasound (US)-guided peripheral nerve block. We tested the hypothesis that the quality of a femoral nerve block (FNB) performed with US is equivalent to an FNB performed with US and nerve stimulation.
One hundred seven patients undergoing unilateral total knee arthroplasty were randomized to receive either a US-guided FNB (group US) or a US-guided FNB with nerve stimulation (group USNS). Thirty milliliters of bupivacaine 0.5% was injected in both groups. At 10, 20, 30, and 40 mins after block placement, blinded motor and sensory examinations were conducted. Secondary outcomes included time to perform the block, the number of needle redirections, and 24-hrs intravenously administered morphine equivalent consumption.
There were no significant differences in the proportion of patients with either a partial or complete block. At 40 mins, 95.7% of the USNS subjects had a partial or complete sensory block of the femoral nerve (complete in 71.7% and partial in 24%) compared with 88.1% of US subjects (complete in 69% and partial in 19.1%; odds ratio, 2.97; P = 0.19). There were more needle redirections in group USNS (4.1 vs 1.1, P < 0.001), with a higher percentage of patients requiring 2 or more needle attempts (44.2% vs 18.9%, P < 0.01). The time to perform the block in group USNS was longer (188 vs 148 secs, P = 0.01).
The addition of nerve stimulation to a US-guided FNB did not change preoperative block efficacy.
Regional anesthesia and pain medicine 34(5):508-13. · 4.16 Impact Factor
