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Biomedical subjects

C C Miller

Publications and source records attributed to C C Miller.

151 records · Page 9Linked to original sources
PubMedDate not supplied

Neurodegenerative changes including altered tau phosphorylation and neurofilament immunoreactivity in mice transgenic for the serine/threonine kinase Mos.

Transgenic mice expressing the oncogenic protein-serine/threonine kinase Mos at high levels in the brain display progressive neuronal degeneration and gliosis. Gliosis developed in parallel with the onset of postnatal transgene expression and led to a dramatic increase in the number of astrocytes positive for GFAP, vimentin, and possibly tau. Interestingly, vimentin is normally expressed only in immature or neoplastic astrocytes, but appears to be induced to high levels in Mos-transgenic, mature astrocytes. Mos can activate mitogen activated protein kinase (MAPK) and MAPK has been implicated in Alzheimer-type tau phosphorylation. In the Mos-transgenic brain we found increased levels of phosphorylation at one epitope on tau containing serines 199 and 202 (numbering according to human tau), a pattern similar but not identical to that found in Alzheimer's disease. In addition, Mos-transgenic mice express a novel neurofilament-related protein that might be a proteolytic neurofilament heavy chain degradation product. These results suggest that activation of protein phosphorylation in neurons can result in changes in cytoskeletal proteins that might contribute to neuronal degeneration.

Animals↗
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Thoracic aortic aneurysms.

Remarkable progress has been made in the surgical treatment of thoracoabdominal aortic aneurysms. The decline in mortality and complication rates can be attributed to improvements in perioperative care and in surgical technique, particularly the adoption of adjunct distal aortic perfusion and cerebrospinal fluid drainage. Neurologic deficit is no longer a major threat to patients, as the use of adjuncts has brought the incidence down to 2.4% for all thoracoabdominal aortic aneurysms. However, we continue to pursue research to improve organ preservation, particularly for the most troublesome extent II thoracoabdominal aortic aneurysm.

Aortic Aneurysm, Thoracic↗
PubMedDate not supplied

Echocardiographic assessment of patients receiving long-term treatment with anorexiant medications.

OBJECTIVE: To describe the prevalence and evaluate the risk of echocardiogram-determined valvulopathy in patients who received fenfluramine and phentermine in an effort to lose weight, in comparison with normal control subjects. METHODS: A historical cohort study was conducted in a clinical obesity-management practice. A total of 164 patients (88% women) who were treated with fenfluramine-phentermine for weight loss had echocardiographic evaluations. A subsample was cross-validated. RESULTS: The prevalence of mild or greater aortic regurgitation was 18.3%, and the prevalence of moderate or greater mitral regurgitation was 3.7%. The prevalences of mild or greater tricuspid and pulmonary valve regurgitation, valve thickening, and pulmonary hypertension were 23.2%, 5.5%, 10.4%, and 6.7%, respectively. No significant increases in risk were found for moderate or greater regurgitation of any valve. Patients had at least a 3-fold risk for mild or greater aortic regurgitation (standardized morbidity ratio [SMR] = 3.03; 95% confidence interval [CI] = 2.05 to 4.33) and a 2-fold risk for tricuspid regurgitation (SMR = 2.24; 95% CI = 1.58 to 3.06) in comparison with normal healthy adults. Age and duration of drug therapy predicted increased risk for aortic regurgitation. Four patients who had moderate or greater aortic regurgitation had taken the fenfluramine-phentermine combination continuously for 454, 615, 645, and 984 days. CONCLUSION: Use of serotonergic anorexiant medications may increase risk for mild or greater aortic and tricuspid regurgitation, although selection bias and obesity as causes of the association cannot be ruled out. Age and duration of drug therapy were predictors of aortic valvulopathy. Population-based studies are needed to confirm these preliminary findings.

Journal Article↗
PubMedDate not supplied

Stratified multivariate analysis of prognostic markers in breast cancer: a preliminary report.

Published results using prognostic markers in breast cancer have been very confusing to oncologists, surgeons, and pathologists alike. As a result, there is a wide variation in opinion among oncologists about the utility of these markers in clinical practice. This study was undertaken to determine the utility of stratified multivariate survival analysis in integrating the commonly used prognostic factors into a user-friendly prognostic scheme, and its implication for treatment decision making. 300 women with invasive ductal carcinoma of the breast who were followed-up for 28-112 months (median 72 months) were entered in the study. Patients with distant metastases, those with bilateral or multifocal tumors, and special types of carcinoma were excluded. Variables included in the stratified multivariate survival analysis were estrogen receptor (ER) status, tumor size, nodal status, histological grade, number of mitotic figures per ten high power fields (MF/10HPF), and type of initial therapy. Data was subjected to Kaplan-Meier survival analysis and the log rank test for statistical significance at different steps of the analysis. Cut-off values for ER that produced a significant difference in survival varied from 9 fmol/mg protein to as high as 76 fmol/mg protein in different patient groups, and MF/10HPF varied from 6 to 21. Patients were stratified into different groups that enabled better evaluation of treatment outcome. Patients could also be combined into three groups with significantly different survival rates (p < 0.0001). Stratified multivariate survival analysis show that prognostic markers a) are interdependent, and their cut-off values vary depending on other tumor characteristics, and b) if used in a systematic way, they can be used to guide treatment decisions.

Adult↗