TPA: is it worth the price?

What, then, are the relative merits of TPA and streptokinase? Existing evidence supports the concept that reperfusion rates are somewhat higher with TPA, particularly after 4 hours when streptokinase is relatively ineffective but the degree of myocardial salvage is likely to be small. Streptokinase has the major advantage of a proven track record, both in terms of improved survival and a low incidence of complications. TPA has the theoretical advantages of less activation of the systemic thrombolytic system and a shorter half-life, but the clinical relevance of these factors has not been shown and may be difficult to prove. Also, whereas a reasonable treatment protocol has been established by consensus for streptokinase, the optimal dosage and infusion time for TPA have not been defined and may be subject to individual variation. Finally, the cost of TPA is substantially higher than for streptokinase. In light of these considerations, the FDA advisory panel's recommendation to withhold approval of TPA becomes easier to understand. Clearly, additional evidence verifying the safety and efficacy of TPA is needed. If and when TPA is released, the clinician will be faced with a choice of thrombolytic agents. Assuming equal safety and efficacy, streptokinase may remain the drug of choice for most patients because of its lower cost. Finally, it is likely that the next few years will see additional refinements in TPA that may further enhance efficacy while decreasing the incidence of complications, and that a competitive market for TPA will reduce the cost. Reports of these developments are anxiously awaited.     

Pharmaceutical representatives in academic medical centers

OBJECTIVE: To determine the nature, frequency and effects of internal medicine housestaff and faculty contacts with pharmaceutical representatives (PRs). DESIGN AND SETTING: The authors surveyed internal medicine faculty at seven midwest teaching hospitals and housestaff from two of the teaching programs. The survey asked about type and frequency of contacts with PRs and behavior that might be related to these contacts. T-tests and logistic regression were used to estimate the relationship between reported physician contacts and behavioral changes. PARTICIPANTS: Two hundred forty faculty (78%) and 131 house officers (75%) responded to the survey. RESULTS: Faculty and housestaff averaged 1.5 brief contacts per month with PRs. Housestaff averaged more than one meal/month at pharmaceutical company expense. Twenty-five percent of faculty and 32% of residents reported changing their practices at least once based on PR contact. Independent predictors of faculty change in practice were brief or extended conversations and free meals. Predictors of faculty requests for formulary addition were brief conversations and receipt of honoraria or research support. Only brief conversations independently predicted housestaff changes in practice. CONCLUSION: Academic housestaff and faculty have frequent PR contact; such contact is related to changes in behavior. The potential for influence of PRs in academic medical centers should be recognized, and their activities should be evaluated accordingly.     

Analysis of Decreasing Adverse Events with Endoscopic Ultrasound in a New Advanced Endoscopy Program Over Time

Digestive Diseases and Sciences - New innovations and increasing utility of endoscopic ultrasound (EUS) are associated with rare but serious risks. We investigate the rates and risk factors for...     

Strategies to address participant misrepresentation for eligibility in Web‐based research

Emerging methodological research suggests that the World Wide Web (“Web”) is an appropriate venue for survey data collection, and a promising area for delivering behavioral intervention. However, the use of the Web for research raises concerns regarding sample validity, particularly when the Web is used for recruitment and enrollment. The purpose of this paper is to describe the challenges experienced in two different Web‐based studies in which participant misrepresentation threatened sample validity: a survey study and an online intervention study. The lessons learned from these experiences generated three types of strategies researchers can use to reduce the likelihood of participant misrepresentation for eligibility in Web‐based research. Examples of procedural/design strategies, technical/software strategies and data analytic strategies are provided along with the methodological strengths and limitations of specific strategies. The discussion includes a series of considerations to guide researchers in the selection of strategies that may be most appropriate given the aims, resources and target population of their studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Regulatory mechanisms in cell-mediated immune responses. IV. Expression of a receptor for mixed lymphocyte reaction suppressor factor on activated T lymphocytes

Suppression of the mixed lymphocyte reaction (MLR) by a soluble factor produced by alloantigen-activated spleen cells requires genetic homology between the factor-producing cells and responder cells in MLR. The ability of lymphocytes used as MLR responder cells to adsorb MLR suppressor factor was tested to investigate the expression of a receptor structure for suppressor molecules. Normal spleen or thymus cells had no effect on suppressor activity. Concanavalin A (Con A)-activated thymocytes, however, effectively removed suppressor activity, suggesting that the receptor is expressed only after activation and is not present or not functional on resting cells. Significantly neither phytohemagglutinin- nor lipopolysaccharide-activated lymphoid cells absorbed the factor. Furthermore, only Con A-activated thymocytes demonstrating genetic homology with the cell producing suppressor factor for H-2 regions to the right of I-E were effective absorbants. Alloantigen-stimulated spleen cells syngeneic to the suppressor cell also removed suppressor activity. These data support an hypothesis that subsequent to stimulation in MLR, T lymphocytes express a receptor, either through synthesis or alteration of an existing molecular structure, which then provides the appropriate site for interaction with suppressor molecules.     

Persistence of colonization of intestinal mucosa by a probiotic strain,Lactobacillus casei subsp. rhamnosus Lcr35, after oral consumption

The colonization by the probiotic Lactobacillus casei subsp. rhamnosus Lcr35 of the gastrointestinal tracts of mice and humans was studied. The mice were orally given 10(9) CFU of Lcr35 either once or three times at 24-h intervals. A 16S ribosomal nucleic probe used in hybridization assays detected Lcr35 in the feces of mice for up to 3 days after the feeding, at a level of 10(8) to 10(9) CFU/g of feces. In the human assay, 12 healthy volunteers were enrolled in a randomized trial and ingested Lcr35 at a dosage of 10(8) or 10(10) or 10(12) CFU every day for 7 days. Then, after a 3-week posttreatment period, there was a second intake period similar to the first one. Analysis of fecal samples showed significant increases in the number of lactobacilli during the first intake period, whatever the dose given. The greatest increases were observed in subjects harboring the lowest indigenous population of Lcr35-like bacteria. During the 3-week posttreatment period, the number of CFU slightly decreased over time, and an increase, although not a statistically significant one, was observed during the second test period. These findings suggest that Lcr35 is able to survive within the gastrointestinal tract.     

Spontaneous in vivo retrovirus-infected T and B cells, but not dendritic cells, mediate antigen-specific Fas ligand/Fas-dependent apoptosis of anti-retroviral CTL

C57BL/6 (H-2b), but not spontaneous virus-expressing AKR.H-2b congenic, mice generate retrovirus-specific CD8+ CTL responses to the immunodominant Kb-restricted epitope, KSPWFTTL. AKR.H-2b non-responsiveness is mediated by a peripheral tolerance mechanism. When co-cultured with primed B6 antiviral pCTL, AKR.H-2b splenocytes are recognized by the antiviral TcR as "veto" cells, which inhibit by an exquisitely virus-specific, MHC-restricted, veto cell FasL/responder T cell Fas, mediated apoptotic mechanism. Here, AKR.H-2b thymus, lymph node, and bone marrow cells are also shown to inhibit antiviral CTL generation. Purified AKR.H-2b CD4+ and CD8+ T cells, and B cells, served effectively as FasL-dependent veto cells. In contrast, AKR.H-2b dendritic cells (DC) did not efficiently veto antiviral CTL responses, despite expressing sufficient MHC class I/viral peptide complexes for TcR recognition. AKR.H-2b DC also expressed FasL mRNA and cell surface protein, albeit at a lower level than AKR.H-2b T and B cells. These findings suggest a fail-safe escape mechanism by virus-infected cells for escape from CTL-mediated immunity.     

Heritability and Expression of C-Reactive Protein in Type 2 Diabetes in the Diabetes Heart Study

Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS). Heritability estimates of CRP levels were obtained using variance component models. Genetic influence on serum CRP levels by single nucleotide polymorphisms (SNPs) in the CRP and APOE genes was evaluated by association analysis using mixed models. Subjects were Caucasian American (84%) and African-American (16%), 53% female, and had an average age of 62.2 ± 9.2 years. The median CRP level was 3.3 mg/L (range 0 to 59.3 mg/L), and estimated heritability for CRP was approximately 40%. Estimates of heritability were significantly greater than zero (P < 0.0001) and relatively constant, despite adjustments for important modifiers (age, sex, ethnicity, diabetes duration, statin-use and anti-inflammatory use) of CRP. There was no significant evidence for association of CRP levels with CRP gene SNPs; however, consistent with previous reports, there was significant evidence of association of CRP levels with polymorphisms within the APOE gene. These data indicate CRP levels are significantly influenced by genetic (and/or environmental) factors that are shared within DHS families. While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed.