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Biomedical subjects

P Merriam

Publications and source records attributed to P Merriam.

11 recordsLinked to original sources
PubMed2004

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.

Adult↗
PubMed2001

Galanin receptor 1 gene expression is regulated by cyclic AMP through a CREB-dependent mechanism.

The galanin receptor-1 (GalR1) protein belongs to a family of G protein-coupled receptors for the neuropeptide galanin (GalR1, GalR2 and GalR3) distributed throughout the central and peripheral nervous system. Activation of galanin receptors by their ligands results in increased feeding, impaired learning, enhanced opiate analgesia and decreased opiate place preference. We have shown that opiate withdrawal, which is known to increase levels of cAMP in the locus coeruleus (LC), results in an increase in the number of galanin binding sites and the level of GalR1 mRNA in the LC. We have isolated a 3.6-kb fragment 5' of the inititiation codon of the mouse GalR1 gene and generated a series of deletion mutations of this fragment driving expression of luciferase for use in transient transfection assays in PC12 and Cath.a cell lines. Treatment with forskolin, but not dideoxyforskolin, up-regulates GalR1 transcription, likely through elevation of cAMP levels. The region between - 1050 and - 700 base pairs upstream of exon one is necessary both for basal activity of the GalR1 promoter and for forskolin-mediated increases in transcription. The forskolin effect can be blocked by simultaneous mutation of a CRE-like site and a CRE/DRE-like site, but not mutation of either site alone. Gel shift and super-shift experiments demonstrate that the transcription factor CREB can bind to both sites and is likely to be responsible for the cAMP-mediated increase in GalR1 promoter activity. This study provides a molecular mechanism for the increased GalR1 expression in the LC seen following opiate withdrawal.

Animals↗
PubMed1998

Coronary Artery Smoking Intervention Study (CASIS): 5-year follow-up.

The authors compared the effect of a behavioral multicomponent smoking cessation special intervention (SI) to an advice-only intervention (AO) on smoking status at 5 years for smokers with coronary disease (n = 160). Regression analyses revealed an interaction between intervention type and disease severity such that patients in the SI group with greater degrees of coronary artery disease showed significantly higher cessation rates (odds ratio = 344 for 3-vessel disease in the SI vs. AO, p = .01). Factors predicting maintained abstinence included having 12 or more years of education, contemplating quitting smoking or being ready to begin action to quit at baseline, and having a higher self-efficacy score.

Cohort Studies↗
PubMed1997

Smoking cessation benefits in HMOs.

A survey was undertaken in the Spring of 1994 to understand the types of smoking cessation services offered by HMOs to one state's employees. Responses documented that the vast majority of HMOs offered nicotine replacement therapy, as well as behavioral classes and courses, with no difference in availability of programs by HMO model type. Considerable variance was found among plans with respect to the structure of the services, and the conditions for accessing benefits. This variation in part may reflect the lack of empirical evidence concerning which approach is most effective. HMOs have provided leadership within the health services and insurance industry with respect to inclusion of cessation benefits. A challenge for HMOs is to design coordinated systems for their smoking cessation services including development of appropriate monitoring systems. Such monitoring will allow plans to better assess participation and effectiveness, and to make benefit and operational decisions on the basis of performance.

Administration, Cutaneous↗
PubMed1993

Physicians' attitudes and reported practices toward smoking intervention.

The objective of this study was to examine differences in the attitudes and reported practices toward smoking intervention of 224 internal medicine, family practice, and surgical physicians from one medical school faculty. Most internists and family practice physicians reported intervening with their patients who smoke, whereas only 50% of surgeons reported intervening with their patients who smoke. Each of the physician groups attached a high degree of importance to smoking cessation in patients with various chronic diseases. Physicians reported that they were most likely to intervene in the smoking habits of young patients, those with reversible disease, those who were receptive to intervention, and with those who had made previous quit attempts. The three obstacles identified by the various physician groups most related to the delivery of quit smoking intervention included the amount of time involved, patient receptivity, and associated lifestyle problems. The results of this study suggest differences among physician specialties in their intervention efforts with smokers and those factors related to the delivery of stop smoking advice. Further reinforcement of specific physician specialty groups for the important role of physicians in assisting their patients to stop smoking remains.

Adult↗
PubMed1992

Smoking cessation and severity of disease: the Coronary Artery Smoking Intervention Study.

We tested the effectiveness of an individually delivered behavioral multicomponent smoking intervention (SI) against offering advice only (AO) to 267 patients after coronary arteriography. After 6 months, 51% of AO patients and 62% of SI patients reported abstinence. Validated rates were 34% and 45% for AO and SI patients, respectively. Logistic regression analyses, controlling for severity of illness, stage of change, and self-efficacy, among other variables, showed that, at 6 months, the SI had the most effect for patients with more severe coronary artery disease (CAD) who had been admitted with a myocardial infarction (95% confidence interval = 2.05, 124.85). At 12 months, only severity of disease mediated SI effects (95% confidence interval = 3.10, 58.00). Similar results were seen for cotinine-validated cessation. This study confirms the effectiveness of individually administered SI for more seriously ill patients with CAD and raises questions as to how to better intervene with those individuals with less severe disease.

Attitude to Health↗
PubMedDate not supplied

Ketamine-fentanyl-midazolam infusion for the control of symptoms in terminal life care.

In this report, we describe nine terminally ill patients with metastatic cancer who were treated with an intravenous infusion consisting of ketamine (2 mg/ml)/fentanyl (5 micrograms/ml)/midazolam (0.1 mg/ml) (K/F/M) to control pain after traditional analgesic therapies were unsuccessful. In addition to pain, all patients exhibited some symptoms of cognitive compromise and agitation. After initiation of the K/F/M infusion, all patients exhibited some degree of qualitative improvement in these symptoms as well as in overall pain control. We feel that these observations warrant reporting of the efficacy of this infusion for the treatment of uncontrolled pain and agitation in terminally ill patients when the traditional methods of pain control are inadequate.

Aged↗
PubMedDate not supplied

Severity of angiographically proven coronary artery disease predicts smoking cessation.

We investigated the relationship between the extent of coronary artery disease (CAD) and the likelihood of cigarette smoking cessation in a population of 84 smokers between 21 and 75 years of age undergoing elective or urgent coronary angiography at the University of Massachusetts Medical Center. The smokers were enrolled in a pilot study investigating the relationship of hospitalization and coronary arteriography for coronary artery disease to subsequent smoking cessation and were scored at baseline as having none, one-, two-, or three-vessel disease. Smoking status at a mean follow-up time of 11 months was obtained by telephone interview, at which point 50% reported not smoking. Logistic regression showed a significant relationship between smoking cessation and two factors: the anatomic extent of CAD and the experience of having had coronary artery bypass surgery or percutaneous transluminal coronary angioplasty following the initial catheterization. We discuss the relative roles of patient knowledge and motivation and physician intervention, and their implications for smoking cessation interventions.

Adult↗
PubMedDate not supplied

Cis-dichlorodiammineplatinum (II) (NSC-119875): hearing loss and other toxic effects in rhesus monkeys.

Ototoxicity and general toxicity of cis-dichlorodiammineplatinum (ii), a compound with antitumor activity, were evaluated in four rhesus monkeys. Audiometry was performed with shock avoidance to donditioned stimuli of pure tones at frequencies from 0.25 to 18 kHz. Histopathologic lesions of the inner ear were identified with phase-contrast microscopy of surface preparations from the organ of Corti. The monkeys were also submitted to physical examinations, hematologic and blood chemical determinations, necropsies, and histopathologic evaluations. Cis-dichlorodiammineplatinum (II) was injected intravenously in one monkey in five daily doses of 1.25 mg/kg (LD50) and in three monkeys in ten to 26 doses of 0.625 mg/kg five times per week. Transient hearing loss occurred in the monkey treated with the largest dose and in one of the three animals treated at the lower dose. In both monkeys apparently normal hearing reappeared after 120 and 200 days. No hearing loss was detectable in the other two animals. All four monkeys, however, had loss of hair cells in the organ of Corti and lesions were most severe among the outer hair cells of the lower turns. Other effects in all four monkeys included severe chronic glomerulonephritis with intermittent azotemia. Two monkeys (positive controls) injected intramuscularly with ten or 25 daily doses of neomycin sulfate (50 mg/kg) responded with delayed permanent hearing loss that appeared 3 months after the start of treatment. Deafness was substantiated by a total loss of inner hair cells in the upper turns, by a severe loss in the lower turns, and by a moderate or severe loss of outer hair cells in the lower turns. The above observations indicated that cis-dichlorodiammineplatinum (II), at a treatment regimen which caused more severe organ toxicity, caused less severe ototoxicity than neomycin sulfate and destroyed hair cells at different sites than neomycin sulfate.

Animals↗