The significance of subclinical hypothyroidism in regard to ensuing hyperlipidemia remains unclear. Because an unfavorable lipid profile would provide a possible explanation for the reported association of coronary-heart disease with this syndrome, we have evaluated the relationship of thyrotropin (TSH) with total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides in patients with normal thyroid function (n = 4886) as well as subclinical (n = 1055) and manifest (n = 92) hypothyroidism. Serum concentrations of LDL cholesterol were similar in euthyroid persons (134+/-39 mg/dL) and in patients with subclinical hypothyroidism (137+/-40 mg/dL) but were higher (178+/-70 mg/dL, p < 0.01) in overt hypothyroidism. Within the group of subjects with subclinical hypothyroidism there was no apparent relationship between serum concentrations of TSH ranging from 4.0 to 49.0 microU/mL and concentrations of LDL cholesterol. Thus, there is no "threshold value" of TSH in these patients per se necessitating substitution therapy with thyroxine.
The identification of individuals who 'died far too early' or 'lived far too long' as compared to their survival probabilities from a Cox regression can lead to the detection of new prognostic factors. Methods to identify outliers are generally based on residuals. For Cox regression, only deviance residuals have been considered for this purpose, but we show that these residuals are not very suitable. Instead, we develop and propose two new types of residuals: the suggested log-odds and normal deviate residuals are simple and intuitively appealing and their theoretical properties and empirical performance make them very suitable for outlier identification. Finally, various practical aspects of screening for individuals with outlying survival times are discussed by means of a cancer study example.
Parametric models are only occasionally used in the analysis of clinical studies of survival although they may offer advantages over Cox's model. In this paper, we report experiences that we have made fitting parametric models to data sets from different clinical trials mainly performed at the Vienna University Medical School. We emphasize the role of residuals for discriminating among candidate models and judging their goodness of fit. The effect of misspecification of the baseline distribution on parameter estimates and testing has been explored. The results from parametric analyses have always been contrasted with those from Cox's model.
Recombinant vaccinia virus has been widely employed as a cancer vaccine in several clinical trials. In this study we explored, employing BALB/c mice transgenic for the rat neu oncogene, the ability of the recombinant vaccinia virus neu (rV-neuT) vaccine to inhibit growth of neu+ mammary carcinomas and whether the efficacy of vaccination was dependent on: a) carcinogenesis stage at which the vaccination was initiated; b) number of vaccinations and c) route of delivery (systemic vs local). BALB-neuT mice were vaccinated one, two and three times by subcutaneous (s.c) and intramammary gland (im.g) injection with rV-neuT or V-wt (wild type vaccinia virus) starting at the stage in which mouse mammary gland displays atypical hyperplasia, carcinoma in situ or invasive carcinoma. We demonstrated that vaccination using rV-neuT was more effective when started at an earlier stage of mammary carcinogenesis and after three vaccinations. im.g vaccination was more effective than s.c vaccination in inhibiting mammary carcinogenesis, eliciting anti-Neu antibodies, increasing anti-Neu IgG2a/G3 isotypes and inducing antibodies able to trigger mammary tumor cell apoptosis and antibody dependent cellular cytotoxicity. The better protective ability of rV-neuT im.g vaccination was associated with its capacity to induce a superior degree of in vivo mammary cancer cell apoptosis. Our research suggests that intratumoral vaccination using recombinant vaccinia virus could be employed to increase the activity of a genetic cancer vaccine. This study may have important implications for the design of cancer vaccine protocols for the treatment of breast cancer and of accessible tumors using recombinant vaccinia virus.
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