Patents for intellectual property.
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Humans↗
Biomedical subjects
R E Meyer
Publications and source records attributed to R E Meyer.
Temperature-dependent changes in physiologic parameters of spontaneous canine soft tissue sarcomas after combined radiotherapy and hyperthermia treatment.
PURPOSE: The objectives of this study were to evaluate effects of hyperthermia on tumor oxygenation, extracellular pH (pHe), and blood flow in 13 dogs with spontaneous soft tissue sarcomas prior to and after local hyperthermia. METHODS AND MATERIALS: Tumor pO2 was measured using an Eppendorf polarographic device, pHe using interstitial electrodes, and blood flow using contrast-enhanced magnetic resonance imaging (MRI). RESULTS: There was an overall improvement in tumor oxygenation observed as an increase in median pO2 and decrease in hypoxic fraction (% of pO2 measurements <5 mm Hg) at 24-h post hyperthermia. These changes were most pronounced when the median temperature (T50) during hyperthermia treatment was less than 44 degrees C. Tumors with T50 > 44 degrees C were characterized by a decrease in median PO2 and an increase in hypoxic fraction. Similar thermal dose-related changes were observed in tumor perfusion. Perfusion was significantly higher after hyperthermia. Increases in perfusion were most evident in tumors with T50 < 44 degrees C. With T50 > 44 degrees C, there was no change in perfusion after hyperthermia. On average, pHe values declined in all animals after hyperthermia, with the greatest reduction seen for larger T50 values. CONCLUSION: This study suggests that hyperthermia has biphasic effects on tumor physiologic parameters. Lower temperatures tend to favor improved perfusion and oxygenation, whereas higher temperatures are more likely to cause vascular damage, thus leading to greater hypoxia. While it has long been recognized that such effects occur in rodent tumors, this is the first report to tie such changes to temperatures achieved during hyperthermia in the clinical setting. Furthermore, it suggests that the thermal threshold for vascular damage is higher in spontaneous tumors than in more rapidly growing rodent tumors.
Animals↗
Craving: what can be done to bring the insights of neuroscience, behavioral science and clinical science into synchrony.
Alcohol self-administration behavior is the common thread that is necessary to bring the insights of neuroscience, behavioral science and clinical science into synchrony around the concept of craving. Animal models should address the molecular and cellular changes that take place in behaviorally relevant brain regions of rats consequent to chronic self-administration of ethanol. Animal models can focus on the biology of the anticipatory state in alcohol preferring/consuming rats, as well as studies of the effects of possible medications on this state in the animal model, on actual alcohol consuming behavior, and on the residual effects of chronic alcohol on the non-human mammalian brain. In human studies of craving, cue-reactivity in the absence of the opportunity to drink alcohol does not have the same salience as cue-reactivity in which drinking is possible. Moreover, actual drinking behavior serves to validate self-reports of craving. Studies of limited alcohol self-administration in the laboratory are an essential element in screening new medications for the treatment of alcoholism. Studies to date suggest no adverse reaction to the participation of alcoholic subjects in limited alcohol self-administration studies, but the research community should continue to monitor carefully the outcomes of alcohol-dependent subjects who participate in this type of research, and efforts should always be made to encourage these subjects to enter active treatment. In outpatient clinical trials of new treatments for alcoholism, the assessment of craving should include queries regarding symptoms and signs of protracted abstinence such as sleep disturbances, as well as questions regarding situational craving. Field observations of alcoholics in their favorite drinking environments would contribute greatly to our understanding of the real-world phenomenology of craving.
Alcohol Drinking↗
Local 42 degrees C hyperthermia improves vascular conductance of the R3230Ac rat mammary adenocarcinoma during sodium nitroprusside infusion.
The effect of sodium nitroprusside-induced hypotension on the perfusion of the R3230 adenocarcinoma during local 42 degrees C hyperthermia was studied using a combination of intravital microscopy and laser Doppler flowmetry. Fischer 344 rats were implanted with dorsal skin flap window chambers containing the R3230Ac tumor and allocated to three treatment groups (34 degrees C with nitroprusside, 42 degrees C with nitroprusside, and 42 degrees C with 0.9% saline). After baseline observation at 34 degrees C, tumors were locally heated to 42 degrees C using a water bath and either 0.9% saline or nitroprusside sufficient to reduce blood pressure 20% below pretreatment baseline was infused. Nitroprusside at 34 degrees C decreased tumor vascular conductance 40% with no effect on the diameter of arterioles entering the tumor. The diameter of arterioles entering 42 degrees C heated tumors increased 35% independent of blood pressure change. Saline at 42 degrees C had no effect on tumor vascular conductance; however, nitroprusside at 42 degrees C increased tumor vascular conductance 55%. Local 42 degrees C tumor heating, combined with a moderate reduction in blood pressure with nitroprusside, overrides the vascular steal effect associated with reduced perfusion pressure alone and results in improved tumor perfusion. Observations of the effect of vasodilator substances on normothermic tumor perfusion cannot be extrapolated to situations where moderate hyperthermia is used.
Adenocarcinoma↗
The crisis in clinical research.
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Humans↗
Multiple deliveries in North Carolina: effects on birth outcomes.
OBJECTIVES: The purpose of this study is to examine the trends in multiple deliveries in North Carolina and assess their effect on the rates of low birth weight, fetal mortality, and infant mortality. METHODS: Using North Carolina vital statistics files, trends in multiple births, categorized by race, maternal age, and birth weight, were examined for the period 1980-1997. A partitioning method was used to estimate the contribution of maternal age distribution and age-specific multiple birth rates to the overall increase in multiple births, and the contribution of the changing multiple birth rate to observed trends in low birth weight and fetal and infant mortality. RESULTS: Between 1980 and 1997, the state's multiple birth rate increased by 40%. Most of the increase was due to a rise in the age-specific multiple birth rates, rather than a shift in the maternal age distribution. The increase in the multiple birth rate accounted for a substantial proportion of the increase in low birth weight among Whites and Blacks. The rise in multiple births also hindered further declines in fetal and infant mortality during this time. CONCLUSIONS: Multiple births are an increasingly important contributor to perinatal outcomes, and warrant greater consideration in research aimed at evaluating trends in low birth weight and infant mortality.
Adult↗
The changing landscape for clinical research.
The authors review the history of U.S. clinical research and identify the profound changes stemming from advancements in the biomedical sciences, the recent transformation in the organization and financing of health care delivery, and the increasing application of information technologies. They observe that the enterprise must reorganize to account for the changed landscape, but there is a lack of the data necessary to monitor change and determine the extent to which clinical research is successfully realigning and sustaining itself. The authors discuss the evolving definition, scope, and venues for clinical research, and review previous analyses of clinical research's difficulties and remedies proposed: shared responsibility in the financing of academic medicine, support by federal and private health insurers for routine costs of patient care in clinical trials, and strengthened collaboration between and among industry, academia, insurers, and government. The authors conclude by describing two major initiatives to foster clinical investigation in the new landscape. The first is the Clinical Research Summit Project, a convocation of representative stakeholders from the health care system with an interest in clinical research, whose charge will be to formulate a national agenda for clinical research that has the broad-based support of the stakeholders. Among the challenges of this undertaking are the needs to identify new and stable sources of support for clinical research infrastructure, assess the future workforce needs for clinical investigation, and devise new methods to ensure the continued vitality and account-ability of clinical research. The second is the Clinical Research Task Force, an initiative of the Association of American Medical Colleges (AAMC), which is already exploring and advising on how AAMC member organizations can best strengthen their capacity to support clinical research programs in the current scientific, health care delivery, and financial environment.
Academic Medical Centers↗
Field immobilization and euthanasia of American opossum.
Seventeen recently trapped opossum, Didelphis virginiana, (median weight 2.45 kg; range = 1.6-5.0 kg; quartiles = 1.8-3.3 kg) were immobilized with either telazol (15 or 30 mg/kg) or a mixture of medetomidine (100 micrograms/kg), butorphanol (0.2 mg/kg), and ketamine HCl (10 mg/kg) based on estimated weights. Anesthetized animals were subjected to cardiac puncture for blood withdrawal and toe pinch. Euthanasia was accomplished by intracardiac administration of 1 ml of concentrated pentobarbital sodium/phenytoin solution. Weights were underestimated for 14 of 17 animals, but were within 0.5 kg of the actual weight. Both drug combinations provided rapid and calm immobilization. Median time to recumbency for the medetomidine-butorphanol-ketamine group (n = 5) was 6 min (range = 4-10 min; quartiles = 6 and 8 min). The median time to recumbency was not statistically different for the low (n = 6) and high dose (n = 6) telazol groups, 3 and 3.5 min respectively (quartiles 3; 3.5 and 4; 5.5 min). The stronger heart beat with telazol immobilization facilitated cardiac puncture. All five animals administered the medetomidine-butorphanol-ketamine mixture and three of six animals given the low telazol dose reacted to cardiac puncture. Only one of six animals given the estimated 30 mg/kg dose of telazol reacted slightly to cardiac puncture. We conclude that 30 mg/kg telazol provides sufficient immobilization and analgesia to allow accurate cardiac puncture of the opossum if the procedure is performed within 5 to 10 min of recumbency. Intracardiac administration of concentrated pentobarbital sodium/phenytoin solution followed by bilateral thoracotomy provides appropriate euthanasia suitable for field situations.
Analgesics↗
Chronic alcohol abuse and the acute sedative and neurophysiologic effects of midazolam.
The aim of the present investigation was to examine benzodiazepine sensitivity in abstinent alcoholics. For this purpose, two escalating doses of the benzodiazepine midazolam were i.v. administered to nine alcohol-dependent patients after 2-3 weeks of abstinence and 12 healthy, non-alcoholic volunteers. A variety of dependent measures were examined, including the power spectrum of the resting electroencephalogram (EEG) and evoked EEG responses, saccadic eye movements, self-reported sedation, and vigilance task performance. Analyses revealed a significant association between plasma midazolam levels and changes in EEG beta power, pattern shift visual evoked potential amplitude, heart rate, and saccade amplitude and velocity. The patient and control groups differed significantly in the onset latencies of their saccadic eye movements, and marginally in EEG beta power, both before and after midazolam. However, no differences were detected between the groups in the dose of midazolam required to produce sedation or in midazolam's neurophysiological effects.
Adult↗
Persistent delirium following cessation of heavy alcohol consumption: diagnostic and treatment implications.
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Age Factors↗
Is incarceration during pregnancy associated with infant birthweight?
OBJECTIVES: This study examined whether incarceration during pregnancy is associated with infant birthweight. METHODS: Multivariable analyses compared infant birthweight outcomes among three groups of women: 168 women incarcerated during pregnancy, 630 women incarcerated at a time other than during pregnancy, and 3910 women never incarcerated. RESULTS: After confounders were controlled for, infant birthweights among women incarcerated during pregnancy were not significantly different from women never incarcerated; however, infant birthweights were significantly worse among women incarcerated at a time other than during pregnancy than among never-incarcerated women and women incarcerated during pregnancy. CONCLUSIONS: Certain aspects of the prison environment (shelter, food, etc.) may be health-promoting for high-risk pregnant women.
Adult↗
Stroma-free human hemoglobin A decreases R3230Ac rat mammary adenocarcinoma blood flow and oxygen partial pressure.
We examined the effect of a nitric oxide (NO) quencher, stroma-free human hemoglobin A (HbA0; 0.01, 0.05, 0.1, 0.2 g/kg), on the blood flow measured using the Doppler flow technique, tumor oxygen pressure (pO2) and the diameter of the arterioles using R3230Ac mammary adenocarcinoma as the tumor model. In female Fischer 344 rats with 1-cm-diameter tumors implanted in the lateral aspect of the left quadriceps, intravenous infusion of 0.1 and 0.2 g/kg HbA0 decreased both central tumor and peripheral tumor blood flow by 20-30% (P < 0.05). Tumor pO2 decreased 28% with 0.2 g/kg HbA0, from 15 mm Hg (baseline) to 11 mm Hg at 10 min (P = 0.02). Although 0.2 g/kg HbA0 increased blood flow 55% in the left quadriceps muscle proximal to the implanted tumor (P < 0.05), HbA0 had little effect on blood flow in right quadriceps muscle with no tumor implanted, and increased right quadriceps pO2, from 21 mm Hg (baseline) to 23 mm Hg at 10 min (P = 0.03). HbA0 increased mean arterial pressure 5-10% in a manner that was dependent on dose while heart rate concurrently decreased 9-19%. The diameter of the arterioles supplying the tumor was rapidly reduced 10% by 0.2 g/kg HbA0 (P = 0.037) and remained stable through 60 min of observation (P = 0.005). HbA0 selectively reduces tumor blood flow and tumor pO2 through vasoconstriction of the arterioles supplying the tumor. Vascular NO quenching provides an alternative to NO synthase inhibition as a means to achieve the goal of selective tumor hypoxia.
Adenocarcinoma↗
Questions methods used to validate tympanic thermometry.
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Animals↗
The disease called addiction: emerging evidence in a 200-year debate.
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Alcoholism↗
Six-month follow-up of naltrexone and psychotherapy for alcohol dependence.
BACKGROUND: The goal of this study was to examine the persistence of naltrexone's effects on drinking outcomes among alcoholics following discontinuation of treatment and to determine whether coping skills therapy improves long-term outcomes compared with supportive therapy. METHODS: Eighty of 97 alcohol-dependent subjects randomized to receive naltrexone or placebo and either coping skills therapy or supportive therapy for 12 weeks were assessed at a 6-month off-treatment follow-up. RESULTS: Subjects who received naltrexone were less likely to drink heavily or to meet criteria for alcohol abuse or dependence than subjects who received placebo. The effect of naltrexone therapy on abstinence rates persisted only through the first month of follow-up. Coping skills therapy was associated with decreased levels of drinking among subjects who received placebo. Psychotherapy condition, however, did not predict alcohol diagnosis at follow-up. CONCLUSIONS: Some but not all of the benefits resulting from short-term naltrexone treatment persist after discontinuation of treatment. The findings suggest that continued treatment with naltrexone may be beneficial for some patients.
Adaptation, Psychological↗
Neuropsychopharmacology: are we ready for a paradigm shift?
The "paradigm shift" in the title of this article refers to molecular biology. The real challenge to molecular biologists interested in applying their methods to an understanding of psychiatric disorders involves the development of models that account for gene/environment/development interaction. Because of the existence of homologous animal models of addictive disorders, as well as a rich body of clinical observations and clinical and behavioral research, and recent data suggesting that chronic exposure to addictive drugs results in changes in gene expression in neurons from behaviorally relevant brain regions, addictive disorders offer a serendipitous model (to molecular biologists) that may have relevance to subsequent application in other areas of psychiatry and psychology.
Humans↗
Naltrexone, relapse prevention, and supportive therapy with alcoholics: an analysis of patient treatment matching.
Alcohol-dependent patients (N = 97) were randomly assigned to receive either naltrexone or placebo and either relapse prevention therapy or supportive therapy. The present report explored the hypothesis that patients could be matched to the above treatments on the basis of specific pretreatment characteristics. Treatment matching variables explored included craving, alcohol dependence severity, and cognitive measures of learning and memory. Results of linear regression analyses tentatively suggest that patients experiencing higher levels of craving and poorer cognitive functioning may derive the greatest benefit from naltrexone versus placebo. For psychotherapy, lower levels of verbal learning were associated with poorer drinking outcomes for relapse prevention therapy but not for supportive therapy. Conversely, higher levels of verbal learning were associated with better outcomes for relapse prevention therapy but not for supportive therapy.
Adolescent↗