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Biomedical subjects

R Temple

Publications and source records attributed to R Temple.

At least 19 recordsLinked to original sources
PubMed2001

Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes.

The increase in eosinophils at the site of antigen challenge has been used as evidence to suggest that this cell type plays a role in the pathophysiology of asthma. Aberrant production of several different cytokines, particularly interleukin (IL)-5, has been shown to result in eosinophilia. IL-5 influences the development and maturation of eosinophils in a number of different ways. Of note is the ability of IL-5 to act as a survival factor for eosinophils specifically inhibiting apoptosis. The precise mechanism by which IL-5 exerts its effect remains obscure. We used microarray technologies to investigate the changes in the messenger RNA expression profile of eosinophils after treatment with IL-5. Using the Affymetrix Hu6800 chip, a total of 80 genes were observed to be regulated by 2-fold or greater. Many of the genes previously identified as regulated by IL-5 were regulated in our microarray experiments. Of the 73 genes found to be upregulated, many were shown to play a role in adhesion, migration, activation, or survival of eosinophils or hematopoietic cells, whereas the function of others was unknown. To facilitate the identification of genes that govern the apoptosis and survivability of eosinophils, we used an alternative cellular model, TF1.8 cells, whose survival was also dependent on IL-5. Comparison of these models identified four genes, Pim-1, DSP-5 (hVH3, B23), CD24, and SLP-76, whose regulation was similarly coordinated in both systems. Identification of Pim-1 and SLP-76 as regulated by IL-5 led us to suggest a direct role for these proteins in the IL-5 signaling pathway in eosinophils. The tissue distribution of these genes demonstrated that Pim-1 and SLP-76 were relatively restricted to the eosinophil compared with their expression in brain, bone marrow, kidney, liver, and lung. By contrast, DSP-5 and CD24 were confirmed as ubiquitous in their expression by microarray.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: ethical and scientific issues.

In recent years, several authors have argued that placebo-controlled trials are invariably unethical when known effective therapy is available for the condition being studied, regardless of the condition or the consequences of deferring treatment. Some have also disputed the value of placebo-controlled trials in such a setting, asserting that the comparison of new treatment with old treatment is sufficient to establish efficacy and is all that should be of interest. This article considers the ethical concerns about use of placebo controls and describes the limited ability of active-control equivalence (also known as noninferiority) trials to establish efficacy of new therapies in many medical contexts. The authors conclude that placebo-controlled trials are not uniformly unethical when known effective therapies are available; rather, their acceptability is determined by whether the patient will be harmed by deferral of therapy. If patients are not harmed, such trials can ethically be carried out. Furthermore, active-control trials, although valuable, informative, and appropriate in many circumstances, often cannot provide reliable evidence of the effectiveness of a new therapy.

Controlled Clinical Trials as Topic↗
PubMed2000

Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 2: practical issues and specific cases.

Placebo controls are commonly used in clinical trials of investigational treatments because they have important advantages. In recent years, some have criticized the use of placebo-controlled trials when effective alternative therapy exists, regardless of the expected effect of the therapy. In part 1 of this paper, ethical arguments are addressed and the interpretive problems inherent in the use of active-control equivalence trials to establish efficacy of a new treatment are clarified. However, uncertainties may complicate decisions about appropriate use of placebo controls in some situations. Part 2 discusses more fully the ethical considerations for using placebo controls in particular medical settings. The value and relevance of placebo-controlled trials of new agents in situations in which proven effective therapy is available are also explored.

Controlled Clinical Trials as Topic↗
PubMed1997

Temporal decline in filling prescriptions for terfenadine closely in time with those for either ketoconazole or erythromycin.

Temporal changes in the rates of filling terfenadine prescriptions within 2 days of those for either oral erythromycin or oral ketoconazole were described with use of paid pharmacy claims data from 1988 through 1994 in state Medicaid programs from Michigan and Ohio and in a large health maintenance organization. There were rapid and significant declines in the rates of filling prescriptions for either erythromycin or ketoconazole within 2 days of prescriptions for terfenadine in all three databases that coincided with 1992 publicity about the cardiovascular risk of terfenadine. These findings suggest that the use of terfenadine with contraindicated medications has declined in response to relabeling and publicity concerning the safe use of terfenadine. Further study is necessary to estimate the absolute level of concurrent use of terfenadine with contraindicated medications.

Adolescent↗
PubMed1997

Long-term follow-up of bowel management after spinal cord injury.

Although neurogenic bowel is a major sequelae of spinal cord injury (SCI), little is known about long-term outcomes of bowel management. The major purposes of this study were to: 1) describe bowel management programs, 2) determine the prevalence of gastrointestinal (GI) complaints, including evacuation problems and GI symptoms, 3) describe the impact of neurogenic bowel on life activities, 4) describe satisfaction with bowel management and, 5) identify the relationship between outcomes and selected injury characteristics. A telephone survey questionnaire was administered to 171 adults with a mean SCI duration of 8.9 years (SD = 8.9) and mean age of 39.5 years (SD = 14.5). The most common bowel program reported was chemical rectal stimulant (39%). The average dietary fiber intake was 6.8 grams (SD = 4.6). The prevalence of total GI complaints was 90% and 76% during the past year and the past month, respectively. Despite the high prevalence of complaints, overall satisfaction was high. Persons with long-term SCI can benefit from continuing assessment by the rehabilitation team, dietary instruction on fiber needs, and dissemination of information on new methods or treatments. Future research needs include prospective studies to assess change over time and to test interventions to improve outcomes.

Adolescent↗
PubMed1996

Approval of new drugs in the United States. Comparison with the United Kingdom, Germany, and Japan.

In a study reported herein, the marketing approval dates of 214 drugs newly introduced into the world market from January 1990 through December 1994 were compared in 4 countries. The analysis reveals that the United States and the United Kingdom have similar patterns of drug availability, although the United States has a number of therapies with significant public health benefits that are not yet available in the United Kingdom. The findings also show that the United States outpaces both Germany and Japan in approving important new drugs. Various strategies adopted by the Food and Drug Administration to expedite its pharmaceutical review process, including the use of industry user fees, are described.

Drug Approval↗
PubMed1993

The results of efforts to improve compliance with supportive periodontal treatment in a private practice.

Patients who receive routine supportive periodontal treatment (SPT) tend to keep their teeth longer and enjoy greater periodontal health than those individual who do not receive this therapy. Previous studies have found less than optimal compliance to suggested SPT. The study reported in this paper covered 5 years of patient data and measured the effects of efforts to improve compliance in a private periodontal practice. These efforts included attempts at simplifying compliance, maintaining records of compliance, informing patients of the consequences of noncompliance, and attempting to identify noncompliers before active periodontal therapy was initiated. The results were measured against a similar group studied in previous work within the same office published in 1984. The main finding of the present study was an increase in complete compliance from 16% in 1984 to 32% in 1991. This increase came largely at the expense of the noncompliant group. The reason for the increase in compliance is likely due to efforts to increase compliance carried out in the office. However, other factors such as change in the hygiene practice law, increased public awareness of dental needs, and economic depression may also have affected compliance. This information suggests that noncompliance can be reduced if the problem is recognized and efforts are made to increase compliance.

Adolescent↗