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Biomedical subjects

C Collier

Publications and source records attributed to C Collier.

At least 19 recordsLinked to original sources

Age-adjustment in experimental animal data and its application to lung cancer in radon-exposed rats.

Procedures for age-adjustment of cancer fractions are proposed which do not require fixed age intervals. The full available information on survival times can then be used, which is especially important in small treatment groups. For incidental cancers a non-decreasing prevalence function and for fatal cancers the Kaplan-Meier estimator is used. In the latter case, the estimated competing risk of the control population is standardized, not its true survival. This makes the technique also applicable to treatment groups with high incidence, which otherwise may give adjusted rates above 100%. In the application part these age-adjustment techniques are used here to study lung cancer in radon-exposed Wistar and Sprague-Dawley rats. The data include a classification in fatal and incidental lung cancers. For fatal lung cancer, the lifetime excess absolute risk (LEAR) at 1 WLM averaged over all exposed groups is 0.67x10(-4) for the Wistar rats, while for the Sprague-Dawley rats it is 0.40x10(-4). For the Sprague-Dawley rats, there are several groups exposed later in life. When the averaging is restricted to animals with start of exposure prior to 150 days of age, the weighted average risk among the Sprague-Dawley rats is 0.79x10(-4). Compared to groups with similar exposures as young adults (up to about 150 days), animals exposed later in life have substantially lower lifetime risks. The Wistar rats include groups with roughly equal exposure rates and ages at start of exposure, but with increasing exposure duration. Within these groupings the LEAR at 1 WLM does not decrease with additional exposure at higher age, as would be expected if the risk from exposures at different ages would be additive.

Administration, Inhalation↗

Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction.

BACKGROUND: Cardiac troponin I and T (cTnI and cTnT) are specific biochemical serum markers for acute myocardial infarction (AMI). However, cTnI diagnostic assays are plagued by difficulties, resulting in >/=20-fold differences in measured values. These discrepancies may result from the release of the numerous cTnI modification products that are present in ischemic myocardium. The resolution of these discrepancies requires an investigation of the exact forms of cTnI present in the bloodstream of patients after myocardial injury. METHODS AND RESULTS: A western blot-direct serum analysis protocol was developed that allowed us to detect intact cTnI and a spectrum of up to 11 modified products in the serum from patients with AMI. For the first time, we document both a cTnI degradation pattern and the existence of phosphorylated cTnI in serum. The number and extent of these modifications reflect patterns similar to the time profiles of the routine clinical serum markers of total creatine kinase, creatine kinase-MB, and cTnI (determined by ELISA). Data from in vitro experiments, which were undertaken to study the degradation of human recombinant cTnI and cTnT when spiked in serum, indicate that some modification products present in patient serum existed in the myocardium and that recombinant cTnI alteration dramatically reduces the detectability of cTnI by the Immuno1 assay over time (our assay was unaffected). CONCLUSIONS: This pilot study defines, for the first time, what forms of cTnI and cTnT appear in the bloodstream of AMI patients, and it clarifies the lack of standardization between different cTnI diagnostic assays.

Biomarkers↗

Chest pain with nondiagnostic electrocardiogram in the emergency department: a randomized controlled trial of two cardiac marker regimens.

BACKGROUND: Early detection of acute myocardial infarction (AMI) may save lives. In the emergency setting, it is unclear whether the early use of certain cardiac markers (myoglobin and cardiac troponin I [cTnI]) assists in making appropriate decisions whether to admit or discharge patients with chest pain of possible ischemic cause who have nondiagnostic electrocardiograms (ECGs). We performed a study to determine whether the addition of new cardiac markers in the emergency department results in improved clinical decisions. METHODS: A single-blind randomized controlled trial was conducted between June 1997 and June 1998 in a tertiary care emergency department in Kingston, Ont. Of 296 patients aged 30 years or more who presented to the emergency department with chest pain and nondiagnostic ECGs, 146 were randomly assigned to the intervention group (determination of baseline creatine kinase [CK] level, CK MB fraction and cTnI level, and myoglobin level at baseline and at 2 hours) and 150 to the control group (determination of baseline CK level and CK MB fraction). Outcome measures included the rate of admission to the inpatient cardiology service and length of stay in the emergency department. RESULTS: Of the 296 patients, 34 (11.5%) received a diagnosis of AMI in the emergency department, and 92 (31.1%) had chest pain of noncardiac cause. Patients in the intervention group were less likely than those in the control group to be admitted to the cardiology service (67 [45.9%] v. 81 [54.0%]). The absolute difference in the proportion (8.1% [95% confidence interval -3.3 to 19.5]), although potentially important clinically, was not statistically significant. The length of stay in the emergency department was essentially the same in the 2 study groups. At 30 days, the proportions of patients with a diagnosis of recurrent angina (58.2% in the intervention group and 58.0% in the control group) and AMI (12.3% and 14.7%) were also similar. INTERPRETATION: The optimal cardiac marker panel to be used in the emergency department remains unknown. The addition of serial testing of myoglobin with cTnI confirmation to the standard panel did not substantially change the clinical management or outcomes of patients presenting with chest pain and nondiagnostic ECGs.

Adult↗

Epidural catheter breakage: a possible mechanism.

The breakage of an epidural catheter within a patient is an uncommon but troublesome complication of continuous epidural block, and its cause is rarely discovered. Several possible mechanisms for catheter breakage have been proposed, but few can be reproduced experimentally. Review of two recent medicolegal cases concerning catheters that were severed at the time of insertion led to laboratory studies in an attempt to find an explanation. The results of this work demonstrated that it was possible to break or severely damage an epidural catheter by heavy contact between the tip of the epidural needle and a bony surface, if a length of the catheter was protruding from the tip.

Journal Article↗

Screening for acute myocardial injury: creatine kinase is comparable to myoglobin.

During the last decade, there have been many studies comparing myoglobin and the troponins to creatine kinase MB. Myoglobin was introduced as an early marker, but most studies have not directly compared it to total creatine kinase in any detail. We retrospectively (9/98-5/99) examined 1772 paired samples from 1572 patients drawn in the emergency department to assess the optimum decision limits, sensitivity, specificity, positive predictive values (PPV), and negative predicitve value (NPV) for creatine kinase and myoglobin in predicting acute myocardial injury. Of the admitted patients, 114 had acute myocardial injury, 166 had angina and 89 had non-cardiac chest pain; 1203 patients were discharged. Initially low creatine kinase (<100 IU/l; minimum 19 IU/l) and myoglobin (<100 microg/l; minimum 9.5 microg/l) results were identified in 63.5% and 88.3% of patients, respectively, emphasizing the importance of serial sampling. Receiver operator characteristic analysis demonstrated optimum decision limits at 100 IU/l and 70 microg/l, respectively. These levels were associated with sensitivity/specificity/PPV/NPV of 66/66/13/96 for creatine kinase and 54/85/22/96 for myoglobin. We conclude that both tests are comparable for initial screening of patients with chest pain in the emergency department. Since creatine kinase is faster, cheaper, and more widely available, it is the test of choice for our institution.

Creatine Kinase↗

Linking community-based blood pressure measurement to clinical care: a randomized controlled trial of outreach and tracking by community health workers.

OBJECTIVES: This study assessed the effectiveness of enhanced tracking and follow-up services provided by community health workers in promoting medical follow-up of persons whose elevated blood pressures were detected during blood pressure measurement at urban community sites. METHODS: In a randomized controlled trial, 421 participants received either enhanced or usual referrals to care. Participants were 18 years or older, were either Black or White, and had blood pressure greater than or equal to 140/90 mm Hg and income equal to or less than 200% of poverty. The primary outcome measure was completion of a medical follow-up visit within 90 days of referral. RESULTS: The enhanced intervention increased follow-up by 39.4% (95% confidence interval [CI] = 14%, 71%; P = .001) relative to usual care. Follow-up visits were completed by 65.1% of participants in the intervention group, compared with 46.7% of those in the usual-care group. The number needed to treat was 5 clients (95% CI = 3, 13) per additional follow-up visit realized. CONCLUSIONS: Enhanced tracking and outreach increased the proportion of persons with elevated blood pressure detected during community measurement who followed up with medical care.

Adolescent↗

Acute asthma epidemics, weather and pollen in England, 1987-1994.

Recent epidemics of acute asthma have caused speculation that, if their causes were known, early warnings might be feasible. In particular, some epidemics seemed to be associated with thunderstorms. We wondered what risk factors predicting epidemics could be identified. Daily asthma admissions counts during 1987-1994, for two age groups (0-14 yrs and > or = 15 yrs), were measured using the Hospital Episodes System (HES). Epidemics were defined as combinations of date, age group and English Regional Health Authority (RHA) with exceptionally high asthma admission counts compared to the predictions of a log-linear autoregression model. They were compared with control days 1 week before and afterwards, regarding seven meteorological variables and 5 day average pollen counts for four species. Fifty six asthma epidemics were identified. The mean density of sferics (lightning flashes), temperature and rainfall on epidemic days were greater than those on control days. High sferics densities were overrepresented in epidemics. Simultaneously high sferics and grass pollen further increased the probability of an epidemic, but only to 15% (95% confidence interval 2-45%). Two thirds of epidemics were not preceded by thunderstorms. Thunderstorms and high grass pollen levels precede asthma epidemics more often than expected by chance. However, most epidemics are not associated with thunderstorms or unusual weather conditions, and most thunderstorms, even following high grass pollen levels, do not precede epidemics. An early warning system based on the indicators examined here would, therefore, detect few epidemics and generate an unacceptably high rate of false alarms.

Adolescent↗

Application of AN69 hydrogel to islet encapsulation. Evaluation in streptozotocin-induced diabetic rat model.

The polymer AN69 (polyacrylonitrile-sodium methallylsulfonate) is a reference in biocompatibility in the field of hemodialysis. Its use for the encapsulation of living cells has been already described, but this study is the first description of AN69 hydrogel-encapsulated islet isograft in streptozotocin (STZ) diabetic rats. The aim of this work is to evaluate the biocompatibility of the AN69 hydrogel by comparison of the efficacy of free versus encapsulated islets transplanted to balance diabetes. Pancreatic islets are isolated from adult male Lewis rats by a standard collagenase digestion and purified on Ficoll density gradients. The AN69 hollow fiber is obtained by coextrusion of an 8% AN69 collodion. The hollow fiber is filled with islets suspended in agarose at the final concentration of 10,000 islets/ml, closed with surgical clips and implanted. The recipients are rendered diabetic by intravenous injection of STZ. The experimental design includes 4 groups of 8 rats: group 1: control, group 2: diabetic rats intraperitoneally implanted with 6000 free islets, group 3: diabetic rats intraperitoneally implanted with 9000 encapsulated islets, group 4: diabetic control. Weight and fasting glycemia are evaluated twice a week, diuresis once a week. After free islet implantation, rat survival is improved with glycemia below 250 mg/dl during 22 days. Compared to group 2, the status of group 3 is better, with a glycemia below 250 mg/dl during at least 70 days. This tends to demonstrate the biocompatibility of AN69 and is the first step of the validation of the use of AN69 for living cell encapsulation.

Acrylic Resins↗

Transdermal fentanyl as treatment for chronic low back pain.

Management of chronic low back pain often includes oral opioid use. The effectiveness of therapy is dependent upon compliance, which in turn is dependent upon response, side effects, access, and convenience. Our hypothesis was that a transdermal fentanyl system would provide more effective pain management than oral opioids. Fifty patients with chronic low back pain were examined. After litration to levels corresponding to current oral opioid use, each patient was maintained on transdermal fentanyl for one month. Oral opioid therapy was then resumed. Their experience was assessed with the a visual analogue scale for pain intensity, a numerical pain score, the Oswestry disability questionnaire, the pain disability index, and the Verran Snyder-Halpern sleep scale. Significant improvement in pain relief and disability was found with transdermal fentanyl compared with oral opioids. Mild opioid side effects were common, but easily controlled. Use of transdermal fentanyl is an effective alternative to oral opioids for managing chronic low back pain.

Administration, Cutaneous↗

Effect of thunderstorms and airborne grass pollen on the incidence of acute asthma in England, 1990-94.

BACKGROUND: Thunderstorms and prior grass pollen counts were investigated as predictors of daily hospital admissions for asthma in England. This study was motivated by reports in the literature of spectacular asthma epidemics associated with thunderstorms, particularly in the grass pollen season. METHODS: Asthma admissions for two age groups (0-14 years and 15 and over) were measured using the Hospital Episodes System (HES) in the 14 regional health authorities (RHAs) in England. Thunderstorms were measured daily in each RHA using densities of sferics (lightning flashes). Relative asthma excesses for moderate positive and exceptionally high sferic densities, with or without previous high grass pollen counts, were measured using log linear autoregression--allowing for weekly, seasonal, and longer term background variation--and pooled over RHAs by calculating geometric means. RESULTS: Relative risks from all RHAs were pooled to form geometric means. Exceptional sferic densities were associated with a relative excess risk of around 25% in both age groups. Moderate sferic densities were associated with a smaller excess, statistically significant in the two age groups taken together. In five RHAs in which grass pollen counts were available, high pollen counts for the previous five days were associated with an amplification of the excess associated with thunderstorms. CONCLUSION: Very large sferic densities are associated with moderate rises in hospital admissions for acute asthma. However, typical thunderstorm days are not associated with spectacular asthma epidemics of the scale previously reported in the literature. Thunderstorm-associated excesses are amplified after a run of high pollen counts.

Acute Disease↗

A community waterborne outbreak of salmonellosis and the effectiveness of a boil water order.

OBJECTIVES: A 1993 large water-borne outbreak of Salmonella typhimurium infections in Gideon, Mo, a city of 1100 with an unchlorinated community water supply, was investigated to determine the source of contamination and the effectiveness of an order to boil water. METHODS: A survey of household members in Gideon and the surrounding township produced information on diarrheal illness, water consumption, and compliance with the boil water order. RESULTS: More than 650 persons were ill; 15 were hospitalized, and 7 died. Persons consuming city water were more likely to be ill (relative risk [RR] = 9.1, 95% confidence interval [CI] = 2.9, 28.4), and the attack rate increased with increased water consumption. S. typhimurium was recovered from samples taken from a city fire hydrant and a water storage tower. Persons in 31% (30/ 98) of city households had drunk unboiled water after being informed about the boil water order, including 14 individuals who subsequently became ill. Reasons for noncompliance included "not remembering" (44%) and "disbelieving" (25%) the order. CONCLUSIONS: Communities with deteriorating water systems risk widespread illness unless water supplies are properly operated and maintained. Effective education to improve compliance during boil water orders is needed.

Data Collection↗

Factors associated with client-reported HIV infection among clients entering methadone treatment.

To determine demographic and behavioral factors associated with client-reported HIV infection among new enrollees in methadone maintenance treatment programs (MMTPs) in Massachusetts and Connecticut, we examined ethnographic data and interview data from MMTP clients (N = 674). Clients responded to questions about behaviors in the 30 days before drug treatment. ETHNOGRAPH was used to analyze qualitative data, and logistic regression analysis was used to identify variables associated with client-reported HIV infection. Statistical significance was set at p < .05. The client-reported HIV infection rate was 20% (132/674). Odds ratios for factors associated with client-reported HIV infection were being white (0.53), increase in age (1.07), use of non-injected heroin (0.12), use of injected heroin (6.24), cocaine injection (1.78), sharing of "works" with strangers (2.15), and "safer sex" behavior (4.04). Additionally, 35% of those who did not use illicit drugs reported being seropositive. The qualitative data suggested HIV positive clients were concerned about protecting sex partners, and learning of HIV infection motivated some to stop using drugs. Although some clients engaged in low-risk behaviors, others did not, therefore the potential for HIV transmission among injection drug users (IDUs) in Connecticut and Massachusetts exists. HIV prevention and drug treatment program personnel should reinforce and build on the low-risk behaviors that are acceptable and adopted by some in this population.

Adult↗

Preoperative chemoradiation for adenocarcinoma of the pancreas: excessive toxicity of prophylactic hepatic irradiation.

PURPOSE: In an effort to reduce relapse in the liver and improve survival in patients with potentially resectable adenocarcinoma of the pancreatic head, we combined whole-liver irradiation with our standard preoperative chemoradiation regimen. METHODS AND MATERIALS: Eleven patients with biopsy-proven, potentially resectable adenocarcinoma of the pancreatic head were treated with 50.4 Gy of external beam irradiation to the pancreas (1.8 Gy/day, 5 days/week) and concurrent continuous infusion 5-fluorouracil (300 mg/m2 per day). The liver was treated with 23.4 Gy on Days 8 through 21 (13 fractions; 1.8 Gy/fraction). Patients, who upon restaging with radiography and computed tomography were considered to have resectable tumors, were subsequently taken to surgery. If, at surgery, tumors were resectable, pancreaticoduodenectomy was performed, and 10 Gy of intraoperative electron-beam radiation therapy was delivered to the bed of the resected pancreas. RESULTS: All 11 patients completed chemoradiation. Two treatment-related deaths occurred following chemoradiation, prompting premature termination of the study. Of seven patients taken to surgery, four underwent resection. Seven patients have died of disease, five with liver metastases. CONCLUSIONS: Prophylactic hepatic chemoradiation, as given in this study, was associated with two treatment-related deaths and a higher than expected incidence of subsequent liver metastases. Our data do not support the use of this treatment program in patients with adenocarcinoma of the pancreas.

Adenocarcinoma↗