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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 19 recordsLinked to original sources
PubMed1996

Localization of the mouse gene releasing sex-limited expression of Slp.

To probe genetic variation in the regulation of sexual dimorphism, we have characterized the mouse protein Slp, coded by the gene sex-limited protein (Slp). Slp expression in many strains is limited to males and is androgen-dependent. However, female expression is also observed in rare strains, due to nonlinked gene(s) termed regulator of sex-limitation (rsl). In this report we demonstrate that female expression of Slp results from homozygous recessive allele(s) at a single autosomal locus that maps to a 2.2-centimorgan interval on chromosome 13. This conclusion was supported by extensive genetic analyses including the use of polymorphic microsatellites to type numerous backcross progeny and a recombinant inbred series and to identify the congenic interval in three independently derived congenic strains. Four attractive candidate genes were identified by the localization of rsl. Interestingly, rsl was found not only to enable expression in females but to also increase expression in males. The findings suggest that the expression of Slp and perhaps other sexually dimorphic proteins is regulated by two pathways, one that is dependent upon rsl but not androgens and another that is rsl-independent but requires androgens.

Animals↗
PubMed1995

Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus.

The gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) has been proposed recently as a candidate gene for the mouse severe combined immune deficiency (scid) locus. We have used a partial cDNA clone for human DNA-PKcs to map the mouse homologue using a large interspecific backcross panel. We found that the mouse gene for DNA-PKcs does not recombine with scid, consistent with the hypothesis that scid is a mutation in the mouse gene for DNA-PKcs.

Animals↗
PubMed1995

Mouse H2 congenic intervals: analysis and use for mapping.

In this study we exploit the unique genetic resource of inbred mouse major histocompatibility complex (H2) congenic and recombinant strains to construct a high-resolution map of microsatellite loci in and around the H2 region, as well as an independent genetic map of other loci on mouse Chromosome (Chr) 17. Microsatellite loci were analyzed in 11 C57BL/10 (B10) strains to determine the size of the congenic interval in each. The length of the congenic interval found in each strain varied widely. Interestingly, the intervals were generally smaller than statistical expectations. However, the observed congenic intervals were still sufficiently long that these strains and probably wild-derived H2 congenics are an important source of genetic variability. The staggered ends of the various congenic intervals and the recombinants were used to construct the map. This map will be useful for physical cloning and to help localize novel genes. As evidence of the mapping application of congenic strains, locational information was derived about Trp53-ps and Stl.

Animals↗
PubMed1995

Edrophonium increases mivacurium concentrations during constant mivacurium infusion, and large doses minimally antagonize paralysis.

BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is metabolized by plasma cholinesterase. Although edrophonium does not alter plasma cholinesterase activity, we have observed that doses of edrophonium that antagonize paralysis from other nondepolarizing muscle relaxants are less effective with mivacurium. We speculated that edrophonium might after metabolism of mivacurium, thereby hindering antagonism of paralysis. Accordingly, we determined the effect of edrophonium on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion. METHODS: We infused mivacurium to maintain 90% depression of adductor pollicis twitch tension and then gave edrophonium in doses ranging from 125-2,000 micrograms/kg without altering the mivacurium infusion. Peak twitch tension after edrophonium was determined to estimate the dose of edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium; plasma cholinesterase activity and mivacurium concentrations before and after edrophonium were measured. Additional subjects were given 500 micrograms/kg edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium. RESULTS: With mivacurium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg) produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized mivacurium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereoisomers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity was unchanged. CONCLUSIONS: Edrophonium doses that antagonize d-tubocurarine and vecuronium are less effective in antagonizing the neuromuscular effects of mivacurium during constant infusion. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edrophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is impaired, and therefore we question whether edrophonium should be used to antagonize mivacurium.

Adolescent↗
PubMed1995

Public evaluations of unrepresented defendants.

Previous articles have addressed the ethical and legal issues involved when private psychiatrists perform forensic evaluations on criminal defendants before the defendants have access to counsel; but there have been few studies addressing evaluations requested through public facilities and by clinicians other than psychiatrists. The authors present the results of a detailed study of defendants admitted for evaluations of competency to proceed to a forensic inpatient unit in one state, as well as data from a national survey of state forensic facilities. The studies were designed to measure the incidence of unrepresented defendants in a population referred for competency evaluation, as well as to examine the reasons for such occurrences. The data reveal that court-ordered evaluations of unrepresented defendants are rare, but continue to exist.

Commitment of Persons with Psychiatric Disorders↗
PubMed1995

Characterization of daytime sleepiness and psychomotor performance following H1 receptor antagonists.

BACKGROUND: While first generation H1-receptor antagonists are widely used, there are relatively few data describing their comparative effects on subjective daytime sleepiness and psychomotor performance. OBJECTIVE: To compare the effects of first generation H1 receptor antagonists on subjective daytime sleepiness and psychomotor performance. METHODS: We conducted two single-dose, cross-over studies. In the first, we validated our methodology in 18 healthy subjects by examining the response to diphenhydramine (50 mg), terfenadine (60 mg), and placebo. In the second trial, we evaluated the relative effects following diphenhydramine (50 mg), diphenhydramine (25 mg), chlorpheniramine (4 mg), and placebo. Psychomotor tests included choice reaction time, hand steadiness, and a test that divided attention between tracking and reaction time. Introspective drowsiness was measured using a visual analog scale and the Stanford Sleepiness Scale. Assessments were made prior to dosing and at one, three, and five hours after dosing; a 7-hour post-drug assessment was included in the second trial. RESULTS: In the first trial, 50 mg diphenhydramine produced significant impairment relative to placebo in both subjective and objective assessments (P < .05). Responses following terfenadine did not differ from placebo. In the second study, all three regimens produced subjective and objective soporific effects to a significantly greater degree than placebo. For example, significant introspective sleepiness was noted three hours following all three regimens (P < .05) and slower choice reaction times were noted one and three hours after dosing (P < .05). The general rank order of effects was diphenhydramine (50 mg), followed by diphenhydramine (25 mg), followed by chlorpheniramine (4 mg). Significant differences among the three regimens were, for the most part, confined to greater soporific effects from diphenhydramine relative to chlorpheniramine (P < .05). CONCLUSIONS: Taken together, our observations confirm that subjective and objective measures of sleepiness and psychomotor performance occur following single doses of diphenhydramine and chlorpheniramine, but not terfenadine. Differences in soporific effects do exist among regimens of first-generation compounds.

Adolescent↗
PubMed1994

Computed tomographic study of the common cold.

BACKGROUND: Colds are common, but the abnormalities they produce in the nasal passages and sinus cavities have not been well defined. METHODS: We studied healthy adult volunteers with self-diagnosed colds of 48 to 96 hours' duration and obtained the following data: information on symptoms, computed tomographic (CT) studies of the nasal passages and sinuses, mucosal-transport times, measures of nasal-airway resistance, and viral-culture studies. Thirty-one subjects (mean age, 24 years) had complete evaluations, including CT scans, which were read without knowledge of the clinical data. An additional 79 subjects underwent the same evaluations, except the CT scans. RESULTS: Of the 31 subjects with CT scans, 24 (77 percent) had occlusion of the ethmoid infundibulum; 27 (87 percent) had abnormalities of one or both maxillary-sinus cavities; 20 (65 percent) had abnormalities of the ethmoid sinuses; 10 (32 percent) had abnormalities of the frontal sinuses; and 12 (39 percent) had abnormalities of the sphenoid sinuses. Infraorbital air cells were present in 14 subjects (45 percent), and pneumatization of the middle turbinate (concha bullosa) was noted in 11 subjects (35 percent). Also common were engorged turbinates (in 7 subjects) and thickening of the walls of the nasal passages (in 13). After two weeks, the CT studies were repeated in 14 subjects, none of whom received antibiotics. In 11 of these subjects (79 percent) the abnormalities of the infundibula and sinuses had cleared or markedly improved. Nasal-airway resistance was abnormal in 29 (94 percent) and mucosal transport in 19 (61 percent) of the 31 subjects who had CT scans. Rhinovirus was detected in nasal secretions from 24 (27 percent) of 90 subjects. CONCLUSIONS: The common cold is associated with frequent and variable anatomical involvement of the upper airways, including occlusion and abnormalities in the sinus cavities.

Adult↗
PubMed1994

Onset and duration of rocuronium and succinylcholine at the adductor pollicis and laryngeal adductor muscles in anesthetized humans.

BACKGROUND: Rocuronium, a new nondepolarizing muscle relaxant, has a rapid onset of activity and may be suitable as a component of a rapid-sequence induction of anesthesia. We evaluated a range of doses on onset and duration of effect at the larynx and the adductor pollicis and compared these characteristics with those of succinylcholine. METHODS: Forty-eight patients aged 18-70 yr, of ASA physical status 1-3, were randomly allocated to receive succinylcholine (1 mg/kg) or one of three doses of rocuronium (0.4, 0.8, or 1.2 mg/kg) during surgery. Anesthesia was induced and maintained with propofol and fentanyl. The trachea was intubated without the use of muscle relaxants, and the cuff of the endotracheal tube placed between the vocal cords. Neuromuscular transmission was monitored by mechanomyography at the laryngeal adductor and adductor pollicis muscles. Muscular activity was evoked with supramaximal stimuli in a train-of-four sequence every 12 s to the anterior branch of the recurrent laryngeal nerve and the ulner nerve. RESULTS: At the laryngeal adductors, peak effect exceeded 99% in all patients given succinylcholine and in none (0%), five (42%), and ten (83%) of those given rocuronium 0.4, 0.8, and 1.2 mg/kg, respectively. At the adductor pollicis, peak effect exceeded 99% in all study patients except two who received rocuronium 0.4 mg/kg (peak effects 91% and 97%). Onset of effect with succinylcholine was significantly more rapid at the laryngeal adductors (34 +/- 12 s, mean +/- SD) than at the adductor pollicis (56 +/- 15 s); this was true also for rocuronium 0.4 mg/kg (92 +/- 29 s and 155 +/- 40 s for the laryngeal adductors and adductor pollicis, respectively). Onset times were similar at the two muscle groups with rocuronium 0.8 and 1.2 mg.kg-1: 96 +/- 29 and 74 +/- 36 s with 0.8 mg/kg and 54 +/- 30 and 65 +/- 21 s with 1.2 mg/kg at the laryngeal adductors and the adductor pollicis, respectively. CONCLUSIONS: The laryngeal adductors are more resistant to the action of rocuronium than is the adductor pollicis. Consequently, the onset of effect of rocuronium, in doses greater than 0.8 mg/kg, is similar to that of succinylcholine at the adductor pollicis but is significantly delayed compared with that of succinylcholine at the laryngeal adductors.

Adolescent↗
PubMed1994

The effect of hypothermia on adductor pollicis twitch tension during continuous infusion of vecuronium in isoflurane-anesthetized humans.

The effect of total body cooling on force of contraction of the adductor pollicis was determined during a constant rate infusion of vecuronium. Anesthesia was induced with thiopental and maintained with isoflurane/nitrous oxide in eight volunteers (study group) and seven surgical patients (control group). After train-of-four (TOF) stimulation of the ulnar nerve, we measured the amplitude of the first response (T1) in the train and the ratio of the fourth-to-first response (TOF ratio). Vecuronium was then administered as an intravenous (i.v.) bolus, 25 micrograms/kg, followed by continuous i.v. infusion, 25 micrograms.kg-1 x h-1; central body (core) temperature was maintained stable for 60 min, at the end of which T1 and TOF responses were constant. In the study group, core temperature was then reduced (using circulating-water blankets) by a mean of 2.6 degrees C, decreasing the T1 and TOF ratio, respectively, by 19% and 18% per degrees C reduction in adductor pollicis temperature. Normothermia was maintained in the control group for a mean of 111 min, with no significant change in T1 and TOF responses. We conclude that, during a constant-rate infusion of vecuronium, the magnitude of neuromuscular block increases significantly when adductor pollicis temperature decreases secondary to core cooling.

Adult↗