University of Texas Health Science Center at Houston

About: University of Texas Health Science Center at Houston is a education organization based out in Houston, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 27309 authors who have published 42520 publications receiving 2151596 citations. The organization is also known as: UTHealth & The UT Health Science Center at Houston.

Recombinant human anti-transforming growth factor β1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I/II trial of CAT-192

Abstract: Objective. To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta 1 (TGF beta 1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). Methods. Patients with SSc duration of < 18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mglkg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGF beta 1 and TGF beta 2. Results. Forty-five patients were enrolled. There was significant morbidity and mortality, including I death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). Conclusion. We report the first evaluation of a systemically administered and repeatedly dosed anti-TGF beta 1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed. (Less)

The frequency of diagnostic errors in outpatient care: estimations from three large observational studies involving US adult populations

Abstract: Background The frequency of outpatient diagnostic errors is challenging to determine due to varying error definitions and the need to review data across multiple providers and care settings over time. We estimated the frequency of diagnostic errors in the US adult population by synthesising data from three previous studies of clinic-based populations that used conceptually similar definitions of diagnostic error. Methods Data sources included two previous studies that used electronic triggers, or algorithms, to detect unusual patterns of return visits after an initial primary care visit or lack of follow-up of abnormal clinical findings related to colorectal cancer, both suggestive of diagnostic errors. A third study examined consecutive cases of lung cancer. In all three studies, diagnostic errors were confirmed through chart review and defined as missed opportunities to make a timely or correct diagnosis based on available evidence. We extrapolated the frequency of diagnostic error obtained from our studies to the US adult population, using the primary care study to estimate rates of diagnostic error for acute conditions (and exacerbations of existing conditions) and the two cancer studies to conservatively estimate rates of missed diagnosis

Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression.

Abstract: The epidermal growth factor receptor (EGFR) and its ligand transforming growth factor (TGF) alpha are hypothesized to form an autocrine growth loop in non-small cell lung cancer (NSCLC) and to play an important role in tumor formation and progression We studied the association between overexpression of EGFR, TGF-alpha, or both, and overall survival of patients with resectable NSCLC Overexpression, defined as >20% of tumor cells staining on immunohistochemistry, was examined in 96 tumor samples from consecutive patients having resection of previously untreated, well-staged NSCLC who were then followed prospectively (median follow-up, 207 months) The expression of three other ligands for EGFR (epidermal growth factor, cripto, and amphiregulin) was examined by Northern analysis to determine whether they might also contribute to a potential growth stimulatory loop Overall, survival was calculated by the method of Kaplan and Meier, and prognostic factors were compared using the log-rank test Overexpression of EGFR only was found in 32% (31 of 96), of TGF-alpha only in 10% (10 of 96), of both EGFR and TGF-alpha in 38% (37 of 96), and of neither in 19% (19 of 96) of tumors EGFR and TGF-alpha overexpression was observed in all tumor stages and histological types but was most frequent in squamous cell carcinoma By univariate and multivariate analyses, only tumor stage, not histology or overexpression of EGFR, TGF-alpha, or both, had a significant impact on overall survival No expression of epidermal growth factor or cripto was observed at the total cellular RNA level of Northern analysis in tumor or benign lung, suggesting that in NSCLC these ligands may not participate in an autocrine growth stimulatory loop with EGFR Differential overexpression of amphiregulin in malignant versus normal lung was observed, but this expression pattern did not have a prognostic impact Thus, EGFR and TGF-alpha overexpression is frequent in early-stage NSCLC but is not associated with a survival difference These findings suggest that this growth factor/receptor loop is more important for lung tumor formation than for tumor progression

A Tale of Two Diseases Atherosclerosis and Rheumatoid Arthritis

Abstract: Acute coronary syndromes are responsible for most of the morbidity and mortality caused by coronary atherosclerosis. Both unstable angina and acute myocardial infarction are characterized by coronary thrombosis, usually caused by rupture or fissuring of a coronary plaque. Yet the occurrence of plaque rupture and coronary thrombosis is not related to severity of coronary plaques, and functional factors other than the mere presence of atherosclerotic lesions play an important role.1 2 Recent studies have focused on the inflammatory component of atherosclerosis, trying to highlight the differences between stable and unstable coronary plaques. An increasing body of evidence supports the hypothesis that atherosclerosis shares many similarities with other inflammatory/autoimmune diseases. Indeed, there are surprising similarities in the inflammatory/immunologic response observed in atherosclerosis, in unstable angina, and in rheumatoid arthritis, the prototype of autoimmune disease (Table⇓). However, although our understanding of the molecular and immunological mechanisms of rheumatoid arthritis has greatly progressed, due to the relatively easy access to the diseased tissue (synovium) and to the availability of animal models, the study of the inflammatory and immunological components of atherosclerosis is still in its initial stages. Unfortunately, it is more difficult for cardiologists to follow the evolution of inflammatory response in plaques or make correlations with the clinical course. Furthermore, although mice models of atherosclerosis have been developed in the last few years, there are still no animal models able to reproduce the events occurring in acute coronary syndromes. Thus, the study of the molecular mechanisms of rheumatoid arthritis may give valuable hints for research on the inflammatory/immunological mechanisms of atherosclerosis and acute coronary syndromes. Activation of inflammatory cells (in particular macrophages and mast cells), releasing many collagen-breaking enzymes within atherosclerotic plaques is likely to play an important role in destabilization of plaques.3 Collagen degradation is also an essential …