17 research outputs found
Inverted left atrial appendage: An unrecognized cause of left atrial mass
AbstractJ Thorac Cardiovasc Surg 1997;114:278-8
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Concomitant weekly docetaxel, cisplatin and radiation therapy in locally advanced non-small cell lung cancer: a dose finding study
The optimal dose of weekly docetaxel in combination with cisplatin and concomitant thoracic radiation therapy (XRT) in patients with locally advanced non-small cell lung cancer (NSCLC) is not well defined. The purpose of this study was to define the maximal tolerated dose (MTD) of docetaxel in this combination. Eligible patients had unresectable stage IIIA or IIIB NSCLC without pleural effusion. Treatment consisted of cisplatin 25 mg/m
2 plus docetaxel weekly and concomitant standard XRT for a total of 60 Gy at 200 cGy/fraction/day 5 times weekly for 6 weeks. The starting dose of docetaxel in the first cohort was 15 mg/m
2/week. This dose was escalated by 5 mg/m
2 per cohort of 3 patients. No intrapatient dose escalation was allowed. The doses of cisplatin and XRT were not escalated. A total of 23 patients were enrolled, and 19 patients were evaluable for analysis. The first cohort (docetaxel 15 mg/m
2/week) completed treatment without any Grade 3 or 4 toxicities. The second cohort (docetaxel 20 mg/m
2/week) was expanded to 6 patients because of Grade 3 cough observed in 1 patient. One of 5 patients experienced Grade 3 esophagitis at the docetaxel 25 mg/m
2/week dose level. Dose limiting toxicity consisting of Grade 3 esophagitis was reached in 4 of 5 patients receiving docetaxel at 30 mg/m
2/week. This study determined the MTD of weekly docetaxel to be 25 mg/m
2 when combined with cisplatin 25 mg/m
2 and radiation therapy for locally advanced NSCLC. Further evaluation of this regimen in a phase II trial is underway
Behavioral treatment of spitting in a child with autism spectrum disorder: Functional analysis, intervention evaluation, and maintenance assessment
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APOE genotype-dependent pharmacogenetic responses to rapamycin for preventing Alzheimer's disease
The ε4 allele of Apolipoprotein (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD), the most common form of dementia. Cognitively normal APOE4 carriers have developed amyloid beta (Aβ) plaques and cerebrovascular, metabolic and structural deficits decades before showing the cognitive impairment. Interventions that can inhibit Aβ retention and restore the brain functions to normal would be critical to prevent AD for the asymptomatic APOE4 carriers. A major goal of the study was to identify the potential usefulness of rapamycin (Rapa), a pharmacological intervention for extending longevity, for preventing AD in the mice that express human APOE4 gene and overexpress Aβ (the E4FAD mice). Another goal of the study was to identify the potential pharmacogenetic differences in response to rapamycin between the E4FAD and E3FAD mice, the mice with human APOE ε3 allele. We used multi-modal MRI to measure in vivo cerebral blood flow (CBF), neurotransmitter levels, white matter integrity, water content, cerebrovascular reactivity (CVR) and somatosensory response; used behavioral assessments to determine cognitive function; used biochemistry assays to determine Aβ retention and blood-brain barrier (BBB) functions; and used metabolomics to identify brain metabolic changes. We found that in the E4FAD mice, rapamycin normalized bodyweight, restored CBF (especially in female), BBB activity for Aβ transport, neurotransmitter levels, neuronal integrity and free fatty acid level, and reduced Aβ retention, which were not observe in the E3FAD-Rapa mice. In contrast, E3FAD-Rapa mice had lower CVR responses, lower anxiety and reduced glycolysis in the brain, which were not seen in the E4FAD-Rapa mice. Further, rapamycin appeared to normalize lipid-associated metabolism in the E4FAD mice, while slowed overall glucose-associated metabolism in the E3FAD mice. Finally, rapamycin enhanced overall water content, water diffusion in white matter, and spatial memory in both E3FAD and E4FAD mice, but did not impact the somatosensory responses under hindpaw stimulation. Our findings indicated that rapamycin was able to restore brain functions and reduce AD risk for young, asymptomatic E4FAD mice, and there were pharmacogenetic differences between the E3FAD and E4FAD mice. As the multi-modal MRI methods used in the study are readily to be used in humans and rapamycin is FDA-approved, our results may pave a way for future clinical testing of the pharmacogenetic responses in humans with different APOE alleles, and potentially using rapamycin to prevent AD for asymptomatic APOE4 carriers