Legal interest in mental health practice.
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Humans↗
Biomedical subjects
R D Miller
Publications and source records attributed to R D Miller.
The impact of the right to refuse treatment in a forensic patient population: six-month review.
In December of 1987, the Wisconsin supreme court held that all involuntarily committed mental patients in the state had the right to refuse psychotropic medication unless a court held that they were incompetent to make treatment decisions. The authors studied the effects of this decision in a 165-bed forensic hospital over the first six months after implementation of the decision. They found that 29 percent of patients already on psychotropic medication initially refused further treatment as opposed to 75 percent of newly admitted patients. Of refusers, 32 percent eventually resumed taking medication voluntarily; courts overturned the refusals of all the 51 percent who maintained their refusals, after an average delay of over a month. The length of procedural delays actually increased over the six months of the study as the courts learned of the decision. The authors compare their findings with other reported studies of implementation of right to refuse treatment decisions and discuss differences between the right to refuse treatment for civilly and criminally committed patients.
Commitment of Persons with Psychiatric Disorders↗
Teaching forensic psychiatry to medical students.
Are separate courses on forensic psychiatry available for medical students? During the 1985 to 1986 academic year, the authors surveyed all U.S. medical schools to identify courses on forensic/legal psychiatry. A minority of schools included separate courses or practicums on forensic psychiatry or mental health law. In a follow-up telephone survey, instructors of each of these courses were interviewed. Information was obtained on format of course, duration, discipline of instructor or instructors, topics covered, reading materials, institutional settings, and the number of students who took the course. The results are discussed and compared with earlier surveys.
Curriculum↗
Child abuse reporting law needs changes.
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Child↗
Development of self-tolerance in normal mice. Appearance of suppressor cells that maintain adult self-tolerance follows the neonatal autoantibody response.
T cell populations from BALB/c mice at different ages were analyzed to determine when in development Ts cells specific for the anti-mouse RBC (MRBC) autoantibody response become activated. Previous studies have shown that adult CD8+ T cells actively suppress this autoimmune response and adult spleen cells depleted of CD8+ cells can generate an anti-MRBC response in culture with MRBC. The present results demonstrate that T cells from mice less than 1 wk of age do not suppress the in vitro anti-MRBC response of adult spleen cell populations depleted of CD8+ Ts cells. By 2 wk of age Ts cells are detectable in this anti-self response and reach adult levels by 3 wk of age. Non-specific "natural suppressor" cells normally present in neonatal spleen cell populations are unable to suppress this autoantibody response, although they are active in suppressing anti-SRBC responses in the same cultures. Before the appearance of Ts cells active in the anti-MRBC response, neonatal spleen cell populations can generate anti-MRBC antibody-forming cells, both spontaneously in vivo and in vitro. The in vitro anti-MRBC response of neonatal spleen cells was shown to be Ag driven and Ag specific. The ability of unfractionated spleen cells to generate this response in vitro declines with age and is relatively low by 3 wk. This decline in responsiveness occurs simultaneously with the appearance of suppression specific for the anti-MRBC response, suggesting that the two events may be causally related.
Aging↗
Suppressor T cells and self-tolerance. Active suppression required for normal regulation of anti-erythrocyte autoantibody responses in spleen cells from nonautoimmune mice.
Spleen cells from young, nonautoimmune strains of mice cultured with syngeneic E do not develop a significant anti-mouse E response in vitro, consistent with a state of self-tolerance to this Ag. In order to study the role of active suppression in regulating mouse RBC-(MRBC) specific cells in nonautoimmune cell populations, the effect of depleting T cell subsets on the generation of anti-MRBC autoantibodies by nonautoimmune spleen cells was determined. Spleen cells from young BALB/c and C57BL/6 mice were found to generate significant numbers of IgM and IgG anti-MRBC autoantibody-forming cells in culture with MRBC after depletion of Ly-2+ cells by anti-Ly-2 and C treatment. The response which develops is Ag dependent, Ag specific, and dependent upon L3T4+ Th. The magnitude and isotype of this response is similar to the anti-MRBC response generated by spleen cells from 12-mo-old, autoimmune NZB mice and young NZB mice also treated to remove Ly-2+ cells. Addition of isolated Ly-2+ T cells, but not L3T4+ or Ly-2- T cells, to spleen cells depleted of Ly-2+ cells restores apparently normal regulation of the anti-MRBC response in vitro. These data demonstrate that control of a specific autoantibody response to MRBC by nonautoimmune spleen cell populations requires active regulation by an Ly-2+ T cell subset.
Animals↗
Multicenter clinical trials comparing cefotetan with moxalactam or cefoxitin as therapy for obstetric and gynecologic infections.
The clinical efficacy and safety of cefotetan was assessed in two multicenter clinical trials involving 335 evaluable patients hospitalized with obstetric and gynecologic infections. In Study I, cefotetan was compared with moxalactam and in Study II, cefotetan was compared with cefoxitin. The clinical response rate in Study I was 67 of 70 patients for cefotetan (96 percent) and 33 of 34 patients (97 percent) for moxalactam. In Study II, the clinical response rate was 138 of 147 patients in the cefotetan group (94 percent) and 76 of 84 patients in the cefoxitin group (91 percent). For the patients with bacteriologic response data, 196 of 205 cefotetan patients (96 percent), 23 of 24 moxalactam patients (96 percent), and 70 of 75 cefoxitin patients (93 percent) had a satisfactory bacteriologic response. Cefotetan was well tolerated and produced no major adverse reactions. The mean amount of cefotetan given was lower than that of moxalactam or cefoxitin.
Adult↗
Quantitation of pancuronium, 3-desacetylpancuronium, vecuronium, 3-desacetylvecuronium, pipecuronium and 3-desacetylpipecuronium in biological fluids by capillary gas chromatography using nitrogen-sensitive detection.
A sensitive and specific capillary gas chromatographic (GC) assay was developed for the quantitation of the quaternary ammonium steroidal neuromuscular blocking drugs pancuronium (PANC), vecuronium (VEC) and pipecuronium (PIP), as well as the metabolites 3-desacetylpancuronium (3-desPANC) and 3-desacetylvecuronium (3-des VEC) in plasma, bile and urine; the putative metabolite 3-desacetylpipecuronium (3-des PIP) was extracted and quantitated only in urine. The procedure employed a single dichloromethane extraction of the iodide ion-pairs of the monoquaternary or bisquaternary ammonium compounds (including internal and external standards) from acidified, ether-washed biological fluid followed by the formation of stable O-tert.-butyldimethylsilyl derivatives at the 3-hydroxy steroidal position of the metabolites. An automated capillary GC system fitted with a nitrogen-sensitive detector and an integrator was then used to analyze and quantitate both parent compounds and their derivatized metabolites. Optimal extraction, derivatization and GC conditions, as well as short-term stability and recoveries of these drugs and metabolites in plasma, are reported. Electron ionization mass spectrometry combined with GC was used to confirm the identities of compounds eluted from the column. The assay demonstrated a 10(3)-fold linear range up to 5000 ng/ml for PANC, VEC, 3-des VEC and PIP, and lower limits of detection with adequate precision of 2 ng/ml for PANC, VEC and PIP, and 4 ng/ml for 3-des VEC; 3-des PANC was linear from 8 to 500 ng/ml while 3-des PIP was linear from 25 to 1000 ng/ml. The precision (coefficient of variation) of the calibration curves for underivatized drugs and their derivatized metabolites over the linear ranges was 2-20% and the reproducibility of the assay over a range of clinical concentrations of these drugs found in human plasma was 5-16% for PANC, 2-4% for VEC and 6-11% for PIP. No interferences were detected in the assay of plasma samples from 106 surgical patients.
Androstane-3,17-diol↗
Rat liver beta-glucuronidase. cDNA cloning, sequence comparisons and expression of a chimeric protein in COS cells.
A cDNA for rat liver beta-glucuronidase was isolated, its sequence determined and its expression after transfection into COS cells studied. The deduced amino acid sequence of the rat liver clone showed 77% homology with that from the cDNA for human placental beta-glucuronidase and 47% homology with that deduced from the cDNA for Escherichia coli beta-glucuronidase. Several differences were found between the cDNA from rat liver and that previously reported from rat preputial gland. Only one change leads to an amino acid difference in the mature enzyme. A chimeric clone was constructed by using a fragment encoding the first 18 amino acid residues of the signal sequence from the human placental cDNA clone and a fragment from the rat clone encoding four amino acid residues of the signal sequence, all 626 amino acid residues of the mature rat enzyme, and all of the 3' untranslated region. After transfection into COS cells the chimeric clone expressed beta-glucuronidase activity that was specifically immunoprecipitated by antibody to rat beta-glucuronidase. The Mr value of 76,000 of the expressed gene product was characteristic of the glycosylated rat enzyme. It was proteolytically processed in COS cells to Mr 75,000 6 h after metabolic labelling. At least 50% of the expressed enzyme was secreted at 60 h post-transfection, but the secreted enzyme did not undergo proteolytic processing. These results provide evidence that the partial cDNA isolated from a rat liver library contains the complete coding sequence for the mature rat liver enzyme and that the chimeric signal sequence allows normal biosynthesis and processing of the transfected rat liver enzyme in COS cells.
Amino Acid Sequence↗
Large doses of vecuronium and plasma histamine concentrations.
The authors studied 20 surgical patients to determine the effect of large doses of vecuronium on plasma histamine concentrations. Patients were unpremedicated and anaesthetized with nitrous oxide and halothane via a mask. Tracheal intubation was performed without the use of muscle relaxants. Fifteen min later and before surgery had begun, vecuronium, in doses of 0.1 and 0.2 mg.kg-1 (n = 10 for each dose), was administered as an IV bolus. Arterial blood samples were obtained prior to and 2, 5, and 10 min after vecuronium administration and analyzed for plasma histamine by a radioenzymatic method. Arterial blood pressure and heart rate were measured continuously. In one patient who received 0.1 mg.kg-1 of vecuronium, plasma histamine concentrations at 2 min were 275 per cent of the control histamine value but fell below control at 10 min. This increase in plasma histamine was not associated with clinically important changes in blood pressure or heart rate. As a group, study patients had no significant changes in plasma histamine concentrations with either dose of vecuronium. In addition, mean plasma histamine values for each sampling interval did not differ between the two patient groups. Mean arterial blood pressure (MAP) decreased significantly at 10 min in patients receiving vecuronium 0.1 mg.kg-1, and at 2 and 10 min in patients receiving 0.2 mg.kg-1 of vecuronium. However, these decreases in MAP were not clinically important. Changes in plasma histamine concentrations did not correlate with corresponding changes in MAP. Heart rate did not change significantly in any patient during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The retrospective evaluation of competency to stand trial.
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Criminal Psychology↗
Interactions of virulent and avirulent Legionella pneumophila with human polymorphonuclear leukocytes.
Isogenic virulent/avirulent variants of Legionella pneumophila (Lp) were examined in vitro for their effect on PMN function as determined by measurement of peak chemiluminescence and superoxide anion production. When exposed to virulent/avirulent strains of Lp, PMN function was less than that seen following exposure to E. coli, the reduction of the oxidative burst being more pronounced with virulent Lp strains in both assays. To determine whether differences in reduced PMN function correlate with differences in complement component C3 binding by virulent and avirulent Lp, four pairs of organisms were incubated in normal human serum and examined by quantitative immunofluorescence. All strains of Lp bound less C3 than E. coli, although each to different degrees. Avirulent isogenic strains bound more C3 than their virulent counterparts with one exception. Depressed PMN function following exposure to Lp may be due to reduced C3 binding, although other virulence-associated factors may be involved.
Complement C3↗
Pipecuronium and pancuronium: comparison of pharmacokinetics and duration of action.
The pharmacokinetics of pipecuronium 0.07 mg kg-1 and pancuronium 0.1 mg kg-1 were compared in 39 ASA class I or II patients. Plasma concentrations of these agents were measured for 6 h following administration, using a sensitive and specific capillary gas chromatographic assay. Concentration v. time data were analysed by non-linear regression and fitted to a two- or three-compartment model as appropriate. Neuromuscular blockade was assessed by measuring the mechanical evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. Pipecuronium had a larger steady-state volume of distribution (Vss) (309 (SD 103) ml kg-1) and greater plasma clearance (Cl) (2.4 (0.6) ml kg-1 min-1) than pancuronium (199 (54) ml kg-1 and 1.5 (0.4) ml kg-1 min-1, respectively). The volumes of the central compartment, distribution and elimination half-lives and mean residence times were similar for both agents and within the range expected for drugs of this type. The durations of action (injection to 25% recovery of twitch tension) of pipecuronium and pancuronium were similar: 98.0 (36.1) min and 117.2 (35.8) min, respectively. We conclude that the time courses of neuromuscular blockade following pipecuronium and pancuronium are similar, despite the differences in Vss and Cl.
Adult↗
Fitness effects of a deletion mutation increasing transcription of the 6-phosphogluconate dehydrogenase gene in Escherichia coli.
Directed evolution in microbial organisms provides an experimental approach to molecular evolution in which selective forces can be controlled and favorable mutations analyzed at the molecular level. Here we present an analysis of a mutation selected in Escherichia coli in response to growth in a chemostat in which the limiting nutrient was gluconate. The selectively favored mutation, designated gnd+ (862), occurred in the gene gnd coding for 6-phosphogluconate dehydrogenase, used in gluconate metabolism. Although the allele is strongly favored in chemostats in which the limiting nutrient is gluconate, the selective effects of gnd+ (862) are highly dependent on growth conditions. In chemostats in which growth is limited by a mixture of gluconate and either ribose, glucose, or succinate, the gnd+ (862) allele is favored, disfavored, or neutral according to the relative concentrations of the substrates. The gnd+ (862) allele results from a deletion of 385 nucleotide pairs in the region 5' to the promoter of gnd, and one endpoint of the deletion is contiguous with the terminus of an IS5 insertion sequence located near gnd in E. coli K12. The gnd+ (862) allele shows a marked increase in transcription that accounts for most or all of the increased enzyme activity.
Alleles↗
Vecuronium in alcoholic liver disease: a pharmacokinetic and pharmacodynamic analysis.
To determine the effect of alcoholic liver disease on the pharmacokinetics and pharmacodynamics of vecuronium, the authors administered vecuronium 0.1 mg.kg-1 iv to ten surgical patients with alcoholic liver disease and ten healthy surgical patients. All patients were anesthetized with nitrous oxide and isoflurane. We recorded and quantitated the force of thumb adduction in response to supramaximal ulnar nerve stimulation. Plasma concentrations of vecuronium and its 3-desacetyl metabolite were determined by a capillary gas chromatography assay. Only the time to attain 100% twitch depression (onset time) was prolonged in liver disease patients (2.8 +/- 0.7 min; mean +/- SD) as compared to control patients (1.9 +/- 0.4 min). The time from vecuronium administration to recovery of twitch tension was unaffected by alcoholic liver disease. The time to the reappearance of twitch response was 32.7 +/- 9.7 min in patients with liver disease and 36.8 +/- 15.5 min in controls. Plasma concentration-time data were fit to a two-compartment model. Vecuronium clearance, steady-state volume of distribution, and elimination half-time were unchanged by alcoholic liver disease. The authors conclude that alcoholic liver disease does not affect the pharmacokinetics or duration of action of vecuronium when an intravenous bolus dose of 0.1 mg.kg-1 is administered.
Adult↗
Vecuronium inhibits histamine N-methyltransferase.
Although there have been clinical reports of significant hypotension and flushing associated with the use of vecuronium, it produces minimal cardiovascular effects in the vast majority of patients. In addition, there is no evidence that vecuronium stimulates the release of histamine. The authors performed in vitro kinetic studies to determine the effect of vecuronium on histamine N-methyltransferase (HNMT), the primary catabolic enzyme for histamine in humans. They also examined plasma from patients who had received vecuronium (0.1 or 0.2 mg/kg) to determine whether clinically used concentrations of the drug could inhibit HNMT. It was determined that vecuronium is a strong inhibitor of HNMT; apparent Ki = 1 microM. The inhibition is competitive with respect to methyl-donor and noncompetitive with respect to histamine. Vecuronium, in doses greater than or equal to 0.1 mg/kg, may delay the metabolism of histamine by HNMT in vitro.
Histamine N-Methyltransferase↗
The pharmacodynamics and pharmacokinetics of vecuronium in patients anesthetized with isoflurane with normal renal function or with renal failure.
The duration of action and the pharmacokinetics of vecuronium were compared in patients with and without renal function. Twenty patients were studied: 12 with renal failure who were to receive kidney transplants from cadaveric donors, and eight with normal renal function. After oral premedication with diazepam, 10 mg, anesthesia was induced with thiopental, 4 mg/kg iv, and maintained with the inhalation of 60% nitrous oxide and 0.9-1.1% isoflurane, end-tidal concentration, in 40% oxygen. The force of thumb adduction in response to supramaximal ulnar nerve stimulation was monitored and recorded. An intravenous bolus of vecuronium, 0.1 mg/kg, was administered after 15 min of a stable end-tidal isoflurane concentration, as measured by mass spectrometry. Venous blood was then sampled at frequent intervals for 4 h following the bolus. Vecuronium concentrations in plasma were quantified by a sensitive and specific gas chromatographic assay. Data were analyzed by nonlinear least squares regression and described by a two-compartment model. The duration of neuromuscular blockade was longer in patients with renal failure than in those with normal renal function. This increased duration may be related to both a decreased plasma clearance and a prolonged elimination half-life of vecuronium in the renal failure group.
Anesthesia, Inhalation↗
The insanity defense for sex offenders: jury decisions after repeal of Wisconsin's Sex Crimes Law.
After repeal of a Wisconsin statute permitting hospitalization of defendants convicted of sexual crimes, the authors noted an increase in the percentage of sex offenders among persons hospitalized after being found not guilty by reason of insanity. They also found that a greater proportion of hospitalized sex offenders than of other kinds of offenders were diagnosed as nonpsychotic. Illustrating with three case studies, the authors argue that despite trends away from the therapeutic model of corrections, juries continue to make decisions that provide treatment for defendants perceived to need it, even if the legal criteria for those decisions do not appear to be met.
Adult↗