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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 199 records · Page 11Linked to original sources

Active role of T cells in promoting an in vitro autoantibody response to self erythrocytes in NZB mice.

The in vitro anti-self erythrocyte antibody response of NZB spleen cells appears to be influenced directly by T cells. Thy-1+, L3T4+ helper T cells are required for: (i) the generation in vitro of MRBC-specific IgM and IgG AFC by spleen cells from 'autoimmune' (9-12-month old) NZB mice and (ii) the generation in vitro of MRBC-specific IgM and IgG AFC by spleen cells depleted of suppressor cells from pre-autoimmune (2-3-months-old) NZB mice which show no clinical signs of an anti-MRBC response. It is evident from the present and previous studies that the anti-MRBC autoantibody response is regulated in pre-autoimmune spleen cell populations by Ly2+ T cells. Ly2-T cells from both pre-autoimmune and autoimmune mice in sufficient numbers can overcome this normal regulation and promote the anti-MRBC response in cultures of unfractionated pre-autoimmune spleen cells. Ly2- T cells isolated from autoimmune NZB mice were consistently more active in this than the Ly2- T cells isolated from pre-autoimmune mice, suggesting an enrichment of MRBC-reactive Ly2- T cells in autoimmune NZB mice. The Ly2- T cells from autoimmune NZB mice greatly enhance the autoimmune anti-MRBC response relative to a modest enhancement of the response to a foreign antigen, SRBC, produced by the same cells. These data indicate that T cells play an important role both in supporting the autoantibody response to MRBC and in disrupting tolerance, leading to autoimmunity in NZB mice.

Animals↗

Emerging problems for staff associated with the release of potentially dangerous forensic patients.

Mental health professionals have been concerned recently about their liability for the actions of patients in their outpatient practices. The history of suits against clinicians for negligent release of inpatients extends back several decades since before the Tarasoff decision. The authors suggest that the same consumerism/victims' rights trends that resulted in Tarasoff and its progeny are likely to rebound again on forensic clinicians and that such pressures are likely to add to other political and social pressures that already complicate the treatment of forensic inpatients. They present three cases to illustrate the dilemmas involved in the release of forensic patients and argue that clinicians must bear significant responsibility for their current plight because of overstated claims of capacities to predict and treat aggressive behavior.

Adult↗

The response of depressed inpatients to isocarboxazid.

Fifty-six inpatients with unipolar depression completed treatment with isocarboxazid. In comparing the differences between responders and nonresponders, it was found that psychomotor retardation, pathological guilt, daily persistence of unremitting symptoms, phobic anxiety, dexamethasone suppression test nonsuppression, and neuroticism were significantly more common among nonresponders. Reactivity of mood, blaming others, and extraversion were more common in responders. Total endogenous depression scores on the Newcastle 1, Newcastle 2, and Michigan scales were also significantly higher in nonresponders. Attained platelet monoamine oxidase inhibition was similar in both groups.

Adult↗

Cloning, sequencing, and expression of cDNA for human beta-glucuronidase.

We report here the cDNA sequence for human placental beta-glucuronidase (beta-D-glucuronoside glucuronosohydrolase, EC 3.2.1.31) and demonstrate expression of the human enzyme in transfected COS cells. We also sequenced a partial cDNA clone from human fibroblasts that contained a 153-base-pair deletion within the coding sequence and found a second type of cDNA clone from placenta that contained the same deletion. Nuclease S1 mapping studies demonstrated two types of mRNAs in human placenta that corresponded to the two types of cDNA clones isolated. The NH2-terminal amino acid sequence determined for human spleen beta-glucuronidase agreed with that inferred from the DNA sequence of the two placental clones, beginning at amino acid 23, suggesting a cleaved signal sequence of 22 amino acids. When transfected into COS cells, plasmids containing either placental clone expressed an immunoprecipitable protein that contained N-linked oligosaccharides as evidenced by sensitivity to endoglycosidase F. However, only transfection with the clone containing the 153-base-pair segment led to expression of human beta-glucuronidase activity. These studies provide the sequence for the full-length cDNA for human beta-glucuronidase, demonstrate the existence of two populations of mRNA for beta-glucuronidase in human placenta, only one of which specifies a catalytically active enzyme, and illustrate the importance of expression studies in verifying that a cDNA is functionally full-length.

Amino Acid Sequence↗

Pancuronium and vecuronium pharmacokinetics and pharmacodynamics in younger and elderly adults.

To evaluate the effect of aging on the distribution, metabolism, and neuromuscular junction sensitivity to pancuronium and vecuronium, the authors determined the pharmacokinetics and pharmacodynamics of these drugs in 12 healthy elderly subjects (70-84 yr) and 12 young adults (30-57 yr) during halothane-nitrous oxide anesthesia. Plasma concentrations of the muscle relaxants were determined using a selective ion-monitoring mass spectrometric technique specific for the parent compound. For vecuronium, plasma clearance (3.7 +/- 1.0 and 5.2 +/- 0.8 ml X kg-1 X min-1, respectively), and volume of distribution at steady-state (179 +/- 31 and 244 +/- 38 ml X kg-1, respectively) were lower in the elderly than in young adults; values for distribution half-lives, elimination half-life, and sensitivity of the neuromuscular junction were similar for the two groups. For pancuronium, there were no statistically significant differences between groups for these pharmacokinetic or pharmacodynamic parameters. However, there was a trend toward reduced clearance (20%) and prolonged elimination half-life (16%) in the elderly as compared to the younger patients. The authors conclude that healthy elective surgical patients between the ages of 70 and 84 yr of age do not differ markedly from younger adults in their pharmacokinetic/pharmacodynamic response to vecuronium and pancuronium.

Adult↗

Continuous infusion of vecuronium: the effect of anesthetic agents.

The authors studied the effects of enflurane, isoflurane, and fentanyl, each in combination with 60% nitrous oxide, on the vecuronium infusion rate necessary to maintain constant 90% depression of control muscle twitch tension. Thirty healthy surgical patients were given an initial 0.1 mg/kg bolus of vecuronium, followed by an infusion of vecuronium at an initial rate of 1.0 microgram . kg-1 . min-1. After 1 h of steady-state 90% twitch depression, plasma vecuronium concentrations (Css90) were measured by capillary column gas chromatography. Total plasma clearance of vecuronium was estimated using Css90 values. Vecuronium infusion rates (mean +/- SD) were similar for patients given enflurane (0.28 +/- 0.13 microgram . kg-1 . min-1) and isoflurane (0.30 +/- 0.13 microgram . kg-1 . min-1), but significantly higher in patients given fentanyl (0.92 +/- 0.37 microgram . kg-1 . min-1). Values for Css90 in the patients receiving enflurane and isoflurane were similar (71 +/- 34 and 72 +/- 44 ng/ml, respectively), but significantly higher in those receiving fentanyl (165 +/- 48 ng/ml). Total plasma clearance was similar during enflurane, isoflurane, and fentanyl anesthesia (4.4 +/- 2.6, 4.6 +/- 1.2, and 5.6 +/- 1.9 ml X kg-1 min-1, respectively). The authors conclude that patients receiving isoflurane and enflurane require markedly lower vecuronium infusion rates to achieve 90% neuromuscular blockade than those receiving fentanyl. The enhancement of neuromuscular blockade by isoflurane and enflurane represents a change in the pharmacodynamics of vecuronium-induced neuromuscular blockade, rather than a change in pharmacokinetics.

Anesthetics↗

Factors affecting the decision to prosecute mental patients for criminal behavior.

Several authors have argued that under certain circumstances it is both necessary and therapeutic to bring criminal charges against psychiatric patients who have committed assaults or manifested other criminal behavior. Others have argued that prosecution may impair therapeutic alliances and may lead to increased litigation by patients. In this paper the authors present four cases in which patients in the public mental health system were prosecuted, and they discuss factors that affect the decision to pursue prosecution. They argue that both clinicians and legal professionals need specific training to help them recognize the differences between behavior that a patient's illness prevents him from controlling and impulsive behavior, stemming from character pathology, that can appropriately be addressed by criminal sanctions.

Adult↗

Patient access to medical records in a forensic center: a controlled study.

Several psychiatric facilities have opened their records partially or completely to patients. The authors report the results of a two-part study in which 20 patients on a minimum-security unit of a forensic center were allowed to read their records and later to write in them. Staff and patient attitudes toward granting patients access to their records were measured before and during the study and were compared with staff and patient attitudes on two units where patients were not granted access. Only eight study patients actually read their charts and none wrote in them, but the majority of both study and control patients felt that access had been helpful. No significant differences in patient behaviors were found on any of the units as a result of access. Staff attitudes toward access did not differ significantly before or after the study, and few differences were found in staff charting practices.

Attitude of Health Personnel↗

Health law and mental health law courses in US medical schools.

Results of a recent survey of all 127 medical schools in the United States indicate that about two fifths of medical schools offer a separate course that focuses on topics in medicine and law and a number of medical schools integrate health law topics into other courses. Presumably reflecting concern over temporary medical malpractice litigation, most health law courses include informed consent, medical malpractice, privileged/confidential information, and patients' rights. In contrast, schools that offer a course on psychiatry and law are clearly in a minority. It is elective at all but two of the 13 schools with such a course. Although the hours allotted and the format of these courses vary greatly, courses typically cover most of the topics listed on the questionnaire. Most of the courses are led or co-led by a member of the American Academy of Psychiatry and the Law. Information from two additional surveys suggests two related factors that may influence a medical school to present a separate course on health law. Medical licensing boards were surveyed to determine which states require physicians to be examined on health law. In two states that require physicians to pass a separate medical jurisprudence examination for licensure, all four-year medical schools offer a course on health law for medical students. Medical malpractice companies providing coverage in all 50 states and the District of Columbia were surveyed to determine which states have the highest claim rates. The claim rate per 1,000 physicians insured per year was significantly greater in states with health law courses than was the rate in states without such courses.

Curriculum↗

Evaluation of competency to stand trial in defendants who do not want to be defended against the crimes charged.

Implicit but significant assumptions made in the criminal justice system include beliefs that criminals do not commit crimes to be tried and convicted and that, once arrested, defendants' primary motives are to avoid or minimize the legal consequences of the charges they face. When those assumptions are not correct, clinicians and legal decision makers are faced with difficult tasks. The authors present three cases of defendants who were not primarily concerned with defending themselves against the charges they faced, but rather with using the criminal justice procedures to further personal goals, and discuss the problems involved for forensic evaluators and courts.

Adult↗

The treating psychiatrist as forensic evaluator in release decisions.

In a previous paper, the author argued that clinicians who perform initial forensic evaluations might be better able to assume subsequent treating relationships with those they have evaluated than independent evaluators. In this paper, the author discusses the problems involved when clinicians who have established treatment relations with patients are then called upon to testify in release hearings. He concludes that the conflicts potentially are more significant in this situation, and that treating clinicians should not evaluate their patients for release.

Adult↗

Models of mental health service delivery to correctional institutions.

The mentally disordered offender falls into the "no man's land" between prison and mental health systems. A number of reasons are given to explain why mental health service to this special group is in crisis again, and to lay the base for understanding the advantages and disadvantages of five different models of service delivery. The authors conclude by favoring small psychiatric units attached to major prisons.

Commitment of Persons with Psychiatric Disorders↗

Quantitative estimation of quaternary ammonium neuromuscular blocking agents in serum by direct insertion probe chemical ionization mass spectrometry.

A new method based on selected ion monitoring chemical ionization mass spectrometry was developed to measure the quaternary ammonium neuromuscular blocking agents, pancuronium and vecuronium, in serum. An ion-pair extraction procedure is utilized to separate the compounds of interest from biological fluids. The intensities of the ion currents produced by the bisamines formed from the drugs and the corresponding deuterated internal standards through thermolytic dequaternization are monitored. The assay shows good linearity over the range of 1-500 ng/ml. This assay has been utilized in a variety of clinical pharmacokinetic studies involving surgical pediatric, geriatric and obstetric patients requiring anesthesia.

Chemical Phenomena↗