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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 127 records · Page 7Linked to original sources

Interaction of ORG 9426 and some of the clinically used intravenous anaesthetic agents in the cat.

The interaction of ORG 9426, a new non-depolarizing neuromuscular blocking agent, with intravenous anaesthetic drugs (fentanyl, thiopental, midazolam, droperidol and etomidate) has been investigated in cats. During an infusion of one of the above anaesthetics, the ED95 dose was determined by titration, and thereafter muscle relaxation was maintained with four subsequent doses of ORG 9426. Neither the potency nor the duration of action of the first dose nor that of the maintenance doses of ORG 9426 differed from those observed in a control group of cats anaesthetized with intraperitoneally administered pentobarbital. The recovery rates were similar in all groups. The authors conclude that, under the conditions of this study, commonly used intravenous anaesthetic drugs are not likely to influence the neuromuscular blocking potency and time course of action of ORG 9426 to any appreciable degree.

Androstanols↗

Need-for-treatment criteria for involuntary civil commitment: impact in practice.

There has been considerable discussion in the literature on the differences between criteria for involuntary commitment that are based on dangerousness and criteria based on need for treatment. A number of states have adopted clinical criteria, and other state legislatures are actively considering them. Some libertarians argue that dangerousness is constitutionally required if a person is to undergo the loss of liberty involved in commitment. Citing widely publicized data from the state of Washington, they predict that a return to clinical criteria would result in a deluge of inappropriate commitments. Some clinicians counter that use of clinical criteria would result in selection of a much more appropriate clinical population and point to research indicating that strict observation of the need-for-treatment provisions of the APA model commitment statute would actually decrease the number of commitments. The author examines state hospital admission and census data from eight states that added need-for-treatment criteria to their commitment codes between 1975 and 1990 and argues that the data indicate that there is little reason to believe that such changes would result in the deluge of admissions predicted by the critics.

Ambulatory Care↗

Bactericidal activity of imipenem compared to erythromycin against intracellular Legionella pneumophila.

Pneumonia is the leading cause of death due to nosocomial infections with mortality ranging from 30 to 70%. Because imipenem has potent in vitro activity against virtually all major causes of nosocomial pneumonia, including P. aeruginosa, S. aureus, members of the family Enterobacteriaceae, and anaerobic organisms, it is used by many physicians as the empirical therapy of choice in severe nosocomial pneumonias. Recognition of Legionella species as nosocomial pathogens has been increasing. The incidence of Legionnaires' disease among patients with nosocomial pneumonia is reported to be as high as 30% (1), but the real prevalence is unknown. Imipenem has bactericidal activity against Legionella in vitro but has not previously been tested for efficacy against intracellular Legionellae.

Cells, Cultured↗

Grievances and law suits against public mental health professionals: cost of doing business?

Although there has been an increase in risk of malpractice for all physicians, general psychiatrists continue to have a relatively low risk of being sued. With the change in the nature of involuntary patient populations as a result of dangerousness criteria for commitment, and the advent of an activist mental health bar, however, psychiatrists who work in the public sector are significantly more likely than private psychiatrists to face grievances and law suits. While specific data providing direct comparisons of numbers of lawsuits between private and public psychiatrists are not available, a review of the existing literature supports this hypothesis, particularly with respect to grievances. The author suggests reasons for the increased risk of legal challenges faced by psychiatrists working with committed patients, and discusses various strategies for preparing ward staff as well as professional staff to reduce the risk of being challenged as well as the chance of losing grievances and law suits. While the article focuses on psychiatrists, most of its arguments are equally applicable to other mental health professionals, whose risk of being legally challenged is escalating rapidly.

Hospitals, Psychiatric↗

Professional versus personal ethics: methods for system reform?

It has been suggested that changes in, and more vigorous enforcement of, professional ethical codes might lead to significant improvements in the quality of expert testimony by mental health professionals. The author examines the arguments for and against this thesis, and concludes that lack of consensus on controversial issues is likely to impede implementation and enforcement of meaningful ethical codes. He argues that attempts to educate the courts and legislatures through writings, testimony, and interdisciplinary teaching are more likely to be effective for the foreseeable future.

Dangerous Behavior↗

Superficial nasal mucosal blood flow and nasal patency following topical oxymetazoline hydrochloride.

The objective of this study was to evaluate the effect of 60 micrograms oxymetazoline on nasal mucosal blood flow (NMBF) measured by laser Doppler velocimetry. Nasal airflow (measured by anterior rhinomanometry) and subjectively perceived airflow (measured by visual analog scales) were also evaluated. A reduction of NMBF (mL/100 g tissue/min) was observed following local application of 60 micrograms oxymetazoline that was not observed after the vehicle was applied. For example, NMBF at baseline was measured at 78.8 +/- 10.3 mL/100 g tissue/min (mean +/- SEM). During the five minutes following vehicle application, mean values remained at 81.8 +/- 8.8 mL/100 g tissue/min. Five minutes after topical oxymetazoline treatment, NMBF was reduced 49% to 38.3 +/- 10.2 mL/100 g tissue/min. Nasal airflow (mL/sec), which was measured before and after LDV probe placement, was not significantly increased in either the ipsilateral (281.4 +/- 33.1 to 314.3 +/- 31.6) or contralateral nostril (335.7 +/- 26.9 to 262.1 +/- 36.4), probably due to the limited surface application of drug. Subjective assessments of congestion by both the investigator and the subject showed significant improvements in the ipsilateral nostril. We conclude that, under the conditions of our study, localized application of 60 micrograms oxymetazoline significantly reduces superficial nasal blood flow and provides subjectively perceived improvements in nasal stuffiness.

Administration, Topical↗

Reversal of neuromuscular blockade in humans by neostigmine and edrophonium: a mathematical model.

Generalizations of the integrated model describing the interaction of nondepolarizing neuromuscular blocking drugs with reversible anticholinesterase drugs described in Unadkat et al. (1) are reported. The models can deal with possible incomplete reversal (irreversible block) and/or noninstantaneous anticholinesterase kinetics. Experimental data were obtained from 22 human volunteers. Different levels of steady-state vecuronium block were induced in each volunteer (in the range of 50% to 95%), and reversed by short infusions of edrophonium (10 volunteers) or neostigmine (12 volunteers). Edrophonium or neostigmine concentrations and twitch tension (measured as the force of thumb adduction) were measured. The generalized integrated models fit the data well. In the case of neostigmine we find a nondistributional delay in its action. We relate this delay to the slow decarbamylation rate of the (neostigmine-induced) carbamylated anticholinesterase observed in vitro, and are able to model such noninstantaneous anticholinesterase kinetic processes. For both edrophonium and neostigmine we detect an inverse relationship between the (induced) level of initial block and maximal percentage recovery.

Adult↗

Psychosocial aspects of palliative care in advanced cancer.

One hundred patients with advanced cancer referred to a palliative care service were evaluated for psychosocial distress using a standard questionnaire. A high incidence of emotional upset, financial distress, and home-care problems was found. Psychosocial distress is common among patients (and their families) with advanced cancer and may have a significant impact on provision of optimal care. Community services are often inadequate. A dedicated palliative care service employing a multidisciplinary approach can best provide care. We make specific recommendations about how to combat psychosocial distress using specific administrative and management techniques.

Adult↗

Analysis of the 5' flanking region of the human beta-glucuronidase gene.

We have sequenced 4.2 kb of the 5' flanking region of the human beta-glucuronidase gene, compared this sequence to the 5' upstream sequence reported for the murine gene, determined the transcription start sites of the human gene, and studied expression of human minigene deletion constructs in COS cells. The 200 bp immediately 5' to the translation initiation codon have a high G + C content (72%) and contain no TATA box, two properties commonly associated with "housekeeping genes." The sequence 5' to -200 bp contains seven Alu repetitive elements which account for more than 50% of this flanking sequence. From deletion analysis of minigene constructs, 200 bp of 5' sequence appeared sufficient for maximal expression in transfected COS cells. S1 nuclease protection analysis showed that transcription initiates from a cluster of sites around -30 bp in all tissues examined. In some cases, a low but detectable level of transcription also initiates 126 bp upstream of the ATG. Inspection of the sequence surrounding both start sites revealed some similarity to the recently described "initiator" transcriptional control element (S.T. Smale and D. Baltimore (1989), Cell 57: 103-113). Comparison of the 5'flanking sequence with that available from the murine beta-glucuronidase gene reveals only one 28-bp highly conserved region, which surrounds the -126 start site.

Amino Acid Sequence↗

Mild intraoperative hypothermia increases duration of action and spontaneous recovery of vecuronium blockade during nitrous oxide-isoflurane anesthesia in humans.

We compared the duration of action and recovery times for vecuronium in normothermic and mildly hypothermic patients. Ten patients were actively cooled to a central body temperature near 34.5 degrees C, and ten were maintained at a normothermic central temperature (greater than 36.5 degrees C); temperature was measured in the distal esophagus. Vecuronium 0.1 mg/kg was administered as an intravenous (iv) bolus to all patients, and the evoked mechanical response to train-of-four stimulation was recorded. Five hypothermic and five normothermic patients were allowed to recover spontaneously. In the remaining five in each group, neostigmine (40 micrograms/kg) and atropine (20 micrograms/kg) was administered when the first twitch (T1) height spontaneously recovered to 10% of control (T1 = 10% of the pre-vecuronium twitch tension). Vecuronium's duration of action (from injection of drug until T1 = 10%) was 28 +/- 4 and 62 +/- 8 min during normothermia and hypothermia, respectively (P less than 0.05). The corresponding values for spontaneous recovery from T1 = 10% to TOF ratio greater than 75% were 37 +/- 15 and 80 +/- 24 min (P less than 0.05), and for neostigmine-induced recovery were 10 +/- 3 and 16 +/- 11 min (difference not significant). We conclude that mild hypothermia increases the duration of action of and time for spontaneous recovery from vecuronium-induced neuromuscular blockade.

Adult↗

Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats.

The pharmacokinetics, biodisposition, and neuromuscular blocking properties of 3-desacetylvecuronium were studied in 17 adult cats. Animals were divided into three groups: five cats with kidney failure induced by bilateral ligation of the renal pedicles, six cats with galactosamine-induced fulminant hepatitis, and six control cats. An intravenous bolus of 300 micrograms.kg-1 of 3-desacetylvecuronium was rapidly injected into the jugular vein. Arterial blood, urine, and bile samples were collected at regular intervals for 6 h in control cats and for 8 h in cats with kidney or liver failure. The liver was excised for analysis at the end of the experiment. In cats with renal failure, 3-desacetylvecuronium pharmacokinetic and pharmacodynamic variables did not differ from those in control cats. In cats with liver failure, plasma clearance was significantly less and mean residence time greater than in control cats (2.8 +/- 0.6 vs. 14.1 +/- 6.5 ml.kg-1.min-1 and 334 +/- 225 vs. 49 +/- 29 min, mean +/- SD, respectively). Volume of distribution at steady state in cats with liver failure and in control cats was not different. Also, in cats with liver failure, the duration of action and recovery index of 3-desacetylvecuronium was significantly greater than in control cats (168 +/- 62 vs. 82 +/- 32 min, and 39 +/- 19 vs. 10 +/- 4 min, respectively). Onset time of neuromuscular blockade was similar in all three groups. Total recovery of 3-desacetylvecuronium, for all three groups, in urine, bile, and liver was 90 +/- 11% (mean +/- SD). In control cats, 70 +/- 18% of 3-desacetylvecuronium was recovered in bile and liver and 19 +/- 14% in urine. No 3,17-bidesacetylvecuronium (a putative 3-desacetylvecuronium metabolite) was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Detection of bacterial mRNA using polymerase chain reaction.

A method was developed for the detection of bacterial mRNAs using reverse transcriptase followed by the polymerase chain reaction (PCR) and Southern blot analysis. The method involves brief inhibition of protein synthesis with chloramphenicol, followed by reverse transcription, PCR amplification of cDNA and Southern blot hybridization. Detection of mRNAs by reverse transcription-PCR-Southern blot analysis is orders of magnitude more sensitive than Northern blot hybridization.

Blotting, Southern↗

Law, psychiatry and rights.

This article deals with the effect of the shift in emphasis from the moral rights to the legal rights concept in psychiatry with reference to matters such as involuntary civil commitment, the right to treatment, the right to refuse treatment, the duty to warn or to protect, the duty to protect future patients from abusive colleagues and the duty to become politically active.

Commitment of Persons with Psychiatric Disorders↗