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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 109 records · Page 6Linked to original sources
PubMed1993

Comparative study of the bactericidal activity of ampicillin/sulbactam and erythromycin against intracellular Legionella pneumophila.

Intracellular bactericidal activity of ampicillin/sulbactam and erythromycin was determined with a human macrophage-like (U-937) cell line infected with Legionella pneumophila. Cell monolayers inoculated with L. pneumophila were treated with erythromycin, ampicillin, sulbactam, or ampicillin/sulbactam during the logarithmic phase of bacterial growth. Intracellular bacterial counts were determined at 2-h intervals for 8 h from the time that antibiotics were added. The number of viable intracellular bacteria increased during this time by 0.9 x log10 cfu/mL (P < 0.05) in the control culture, did not change significantly in the cultures treated with ampicillin or sulbactam, decreased by 0.8 x log10 cfu/mL (P < 0.05) with erythromycin, and decreased by 1.8 x log10 cfu/mL with ampicillin/sulbactam (P < 0.05). The number of cfu/mL was significantly less after incubation with ampicillin/sulbactam than with erythromycin (P < 0.05). Ampicillin/sulbactam appeared to have greater bactericidal activity against intracellular L. pneumophila than erythromycin in this in-vitro model. The bactericidal action of ampicillin/sulbactam was significantly greater than would be expected from the additive effects of ampicillin plus sulbactam, suggesting synergic bactericidal activity.

Ampicillin↗
PubMed1993

Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients.

BACKGROUND: Succinylcholine has been the agent of choice when clinical conditions require emergency airway protection during a rapid-sequence induction of anesthesia. Rocuronium, a new nondepolarizing muscle relaxant with a brief onset of action, but devoid of the adverse reactions associated with succinylcholine, may be an alternative to succinylcholine. To test this hypothesis, the authors compared rocuronium with succinylcholine and vecuronium for rapid-sequence induction of anesthesia. METHODS: Fifty patients, ASA 1-3, were randomly designated to receive one of three intravenous doses of rocuronium (0.6, 0.9, and 1.2 mg/kg), vecuronium (0.1 mg/kg), or succinylcholine (1.0 mg/kg). Patients were premedicated with midazolam and fentanyl, and received 2-7 mg/kg thiopental for induction of anesthesia. Sixty seconds after receiving a muscle relaxant, intubation of the trachea was attempted by a clinician who was blinded to the muscle relaxant administered. Neuromuscular monitoring was established before administration of the muscle relaxant. The time from injection of muscle relaxant until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded. Tracheal intubating conditions were evaluated, and the presence or absence of fasciculations was noted. RESULTS: Onset times for patients receiving 0.9 mg/kg (75 +/- 28 s) and 1.2 mg/kg rocuronium (55 +/- 14 s), and succinylcholine (50 +/- 17 s) were similar. Onset times for the groups given 0.6 mg/kg rocuronium (89 +/- 33 s) and vecuronium (144 +/- 39 s) were significantly longer. Clinical duration of action was longest with 1.2 mg/kg rocuronium, similar with 0.6 and 0.9 mg/kg rocuronium, and vecuronium, and least with succinylcholine. CONCLUSIONS: There is a dose-dependent decrease in onset time with rocuronium. The onset times for the two larger doses of rocuronium were similar to that for succinylcholine, but clinical duration of action with rocuronium was significantly longer. The brief onset time achieved with rocuronium indicates that administration of 0.9-1.2 mg/kg is an acceptable alternative to succinylcholine for rapid-sequence induction of anesthesia.

Adolescent↗
PubMed1993

Legionella pneumophila protease inactivates interleukin-2 and cleaves CD4 on human T cells.

The role of the Legionella pneumophila protease in the pathogenesis of Legionnaires' disease is unclear. In this study, we assessed the effect of purified protease preparations on human recombinant interleukin-2 (IL-2), the IL-2 receptor, and several additional human T-cell surface proteins to determine whether protease contributes to the virulence of L. pneumophila by interfering with human T-cell activation and function. IL-2-induced proliferation of CTLL-2 cells was inhibited by coincubation with protease (10 to 100 U/ml). Protease at concentrations of > or = 10 U/ml cleaved human recombinant IL-2 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reaction mixtures containing 125I-labeled IL-2 and protease. Protease treatment of activated human T cells did not inhibit binding of a monoclonal antibody directed against the alpha subunit of the IL-2 receptor and did not interfere with binding of IL-2 to IL-2 receptors on the lymphocytes. Treatment of blood mononuclear cells or activated T cells with protease (50 U/ml) inhibited the binding of a monoclonal antibody directed against CD4. In contrast, protease treatment did not inhibit the binding of antibodies against CD3, CD8, class II major histocompatibility complex, and the transferrin receptor. Heat inactivation (65 degrees C for 20 min) of the protease or treatment with the metal chelator EDTA ablated the inhibitory effect of the protease. The ability of the protease to degrade IL-2 and cleave CD4 on human T cells suggests that protease may contribute to the pathogenesis of Legionnaires' disease by impeding T-cell activation and immune function.

Bacterial Proteins↗
PubMed1993

Central nervous system effects of intrathecal muscle relaxants in rats.

When given for a sufficient time and dose intravenously, neuromuscular blocking drugs eventually can enter the cerebrospinal fluid (CSF). To study the potential pharmacologic consequences of neuromuscular blocking drugs in the CSF, a model was developed in the rat by using an intrathecal infusion of these drugs. A cannula was stereotaxically implanted in a lateral cerebral ventricle of anesthetized male Sprague-Dawley rats (250-300 g). Several days later, the effects of an intraventricular infusion (5 microL/min) of atracurium (0.804 mumol/mL), pancuronium (0.172 mumol/mL), and vecuronium (21.978 mumol/mL) were studied in unanesthetized rats. These rats (n = 6 in each group) exhibited dose-dependent hyperexcitability, during drug infusion, with seizures occurring at threshold doses of (mean), 0.12, 0.26, and 0.065 +/- 0.010 and 3.32 mumol/kg of atracurium, pancuronium, and vecuronium, respectively. The neuromuscular ED50 (intravenous dose required to produce a 50% depression of twitch tension) in rats determined by other investigators are 0.408, 0.115, and 0.352 mumol/kg for atracurium, pancuronium, and vecuronium, respectively. Therefore, seizure threshold doses were not related to the potencies of these drugs as neuromuscular blocking drugs. Based on these data, central nervous system effects were studied over the subseizure dose range approximating 1/100, 1/10, and 1/5 of the cumulative dose causing seizures for each drug (n = 5 for each dose). At 1/100 of seizure dose, decreased locomotor activity and piloerection occurred. At 1/10 to 1/5 of seizure dose, agitation, shivering, splayed limbs, and whole body shaking resulted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Chronic Obstructive Pulmonary Disease Early Intervention Trial (Lung Health Study). Baseline characteristics of randomized participants.

The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The hypothesis being tested is that over a 5-year period, a comprehensive intervention program can reduce both the rate of decline in pulmonary function and the rates of respiratory morbidity and mortality in middle-aged smokers with mild to moderate airflow obstruction. The primary outcome variable of the trial is the annual rate of decline of maximum postbronchodilator FEV1. Secondary outcomes are the development of respiratory and nonrespiratory morbidity and mortality. After screening 73,694 cigarette smokers, aged 35 to 60 years, 5,887 participants were randomized into three equal groups: usual care, smoking intervention with daily use of a metered-dose inhaler with ipratropium bromide, and smoking intervention with inhalation of placebo. Eligible participants had a ratio of FEV1 to forced vital capacity (FVC) of 70 percent or less, were free of known life-limiting conditions, expressed willingness to enter the intervention program if so randomized, and gave written informed consent prior to entry into the trial. Spirometry, methacholine challenge, and questionnaires were strictly standardized within and across centers. The purpose of this report is to describe the characteristics of randomized participants at the time of entry into the study. For both sexes, three measures of lung function--average cross-sectional FEV1/FVC ratio, FEV1, and FEV1 percentage of predicted normal--showed slight downward trends for each successively older 5-year age cohort. The increase in FEV1 after isoproterenol was 15 percent or more in only 2.4 percent of men and 2.8 percent of women. A positive response to methacholine (defined as a fall in FEV1 of > 20 percent from baseline at concentrations up to 25 mg/ml) occurred in 63 percent of men and 87 percent of women. The cross-sectional prevalences of cough, phlegm, wheeze on most days or nights, and shortness of breath were 49 percent, 43 percent, 32 percent, and 43 percent, respectively. Respiratory symptoms were reported by a higher proportion of participants in the younger age groups than in the older age groups. Participants who reported cough, phlegm, and/or wheeze averaged lower FEV1 percent predicted and higher probability of positive response to methacholine than participants who did not. Shortness of breath appeared to be significantly associated with lower lung function and higher reactivity in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Toward the therapeutic use of obscene language: a legal and clinical review.

Obscenity has been the subject of a series of court cases centered around the First Amendment, and its interpersonal effects have been studied by psychotherapists and communications theorists. But little has been written about the impact of the use of obscenity by patients in group settings to discharge their feelings and to dominate and harass staff and other patients. The authors argue that if staff are to be able to work effectively with patient populations who utilize obscenity routinely for these purposes, they must become more comfortable with its use, and to treat it as another symptom of the patients' interpersonal difficulties. Guidelines for the therapeutic use/management of obscenity on the ward are offered.

Erotica↗
PubMed1992

Restriction fragment length polymorphism of the murine C4 and Slp genes: two C4 groups.

We have examined the related H-2 genes coding for the fourth component of complement (C4) and the sex-limited protein (Slp) from 30 inbred mouse strains by Southern blot analysis. With four restriction enzymes, 11 RFLP patterns distributed among 26 different H-2 haplotypes have been identified. Strains of the same serologic H-2 haplotype were found to have identical RFLP patterns. It was confirmed that the number of C4-related genes in most haplotypes is two, Slp and C4; but H-2SWI6 (SWI6) and SWI9, which have the same RFLP pattern, have four and Sw7 has five. Although C4 and Slp have many similarities, they also were found to contain distinctive features: relative to Slp, each C4 allele examined has two insertions totaling 1.1 kb located in introns 14 and 15; and each Slp allele examined, excluding hybrids, has a provirus insertion upstream. No other large deletions or insertions were detected. The RFLP patterns are also due to 10 polymorphic restriction sites, which have been placed on standard maps; two are associated with Slp and eight are associated with C4.Sk strains, the only strains that express low serum levels of C4, have the same RFLP phenotype as Sw14, Sw18, and Swx; Sk may have arisen from a recent common ancestor of these strains. Homologous recombination has been important in the formation of existing C4 alleles. However, based on complete linkage disequilibrium between three RFLP internal to C4, the haplotypes have been divided into two groups that may have functional significance.

Animals↗
PubMed1992

Persistent paralysis in critically ill patients after long-term administration of vecuronium.

BACKGROUND: The muscle relaxant vecuronium is sometimes administered to facilitate mechanical ventilation. Neuromuscular paralysis lasting up to seven days may occur after the termination of long-term administration (i.e., more than two days) of vecuronium in critically ill patients. We investigated the role of clinical factors and plasma concentrations of vecuronium and its metabolite in causing this prolonged neuromuscular blockade. METHODS: We studied 16 critically ill adult patients (8 women and 8 men) who had received vecuronium to facilitate mechanical ventilation for at least two consecutive days. Clinical factors and plasma concentrations of vecuronium and 3-desacetylvecuronium, the active metabolite of vecuronium, were compared in patients with and without prolonged neuromuscular blockade. In addition, we performed detailed pharmacokinetic studies in the patients without prolonged neuromuscular blockade. RESULTS: Seven of the 16 patients had prolonged neuromuscular blockade, lasting from six hours to more than seven days, after the termination of vecuronium therapy. These seven patients, six of whom were women, had higher plasma magnesium concentrations and lower arterial blood pH values than the nine patients without prolonged neuromuscular blockade. They also had higher plasma concentrations of 3-desacetylvecuronium and a higher frequency of renal failure (seven of seven patients vs. four of nine patients, P less than 0.03). In the patients without prolonged neuromuscular blockade, the mean (+/- SD) plasma clearance, elimination half-life, and volume of distribution of vecuronium were 2.5 +/- 1.0 ml per kilogram of body weight per minute, 299 +/- 154 minutes, and 1.1 +/- 0.6 liters per kilogram, respectively. CONCLUSIONS: Prolonged neuromuscular blockade after the termination of long-term treatment with vecuronium is associated with metabolic acidosis, elevated plasma magnesium concentrations, female sex, and probably more important, the presence of renal failure and high plasma concentrations of 3-desacetylvecuronium.

Critical Illness↗
PubMed1992

Expression and regulation of a recurrent anti-erythrocyte autoantibody idiotype in spleen cells from neonatal and adult BALB/c mice.

BALB/c spleen cells depleted of CD8+ T cells generate an autoantibody response to mouse RBC (MRBC) when cultured 5 days in the presence of syngeneic RBC. More than 80% of the cells secreting anti-MRBC antibody are blocked by an antiidiotypic mAb that recognizes the G8 Id. This G8 Id was originally identified in an autoimmune NZB mouse derived anti-MRBC mAb and later characterized as a dominant Id in NZB anti-MRBC autoantibodies. Furthermore, the CD8+ regulatory T cells that control this autoimmune response in BALB/c mice are specifically eliminated by cytotoxic treatment with the G8 mAb + C, suggesting that the regulatory cells recognize the G8 Id. Spleen cells from neonatal BALB/c mice, which lack those regulatory cells can generate an in vitro antibody response to MRBC without depletion of CD8+ cells. More than 80% of these AFC were also found to express the G8 Id. We propose that Id determinants on autoantibodies that are produced neonatally induce Id-specific regulatory cells that maintain peripheral tolerance to self-RBC throughout the life of normal animals.

Animals↗
PubMed1992

Killing of Legionella pneumophila by nitric oxide in gamma-interferon-activated macrophages.

The role of nitric oxide (NO) radicals in killing the intracellular bacterial pathogen Legionella pneumophila (Lp) was examined in infected macrophages. Murine (RAW 264.7) and human (HL-60) cell monolayers were treated with 100 U/ml gamma-interferon (IFN) and cocultured with Lp in the presence and absence of NGMMA, a specific inhibitor of NO production. Viable Lp in IFN-treated RAW 264.7 cells decreased from 3.8 to 0.7 +/- 0.12 log CFU/ml after 24 h incubation, whereas in IFN+NGMMA-treated RAW 264.7 cells, viable Lp persisted at 2.2 +/- 0.2 log CFU/ml after 24 h. This increased survival corresponded with an inhibition of NO production (5.65 +/- 2.99 microM with NGMMA vs. 58.6 +/- 5.36 microM without NGMMA). Viable Lp were susceptible to killing, in a dose-dependent fashion, by 0, 2.5, and 5.0 mM sodium nitroprusside, a source of NO radicals. IFN-treated RAW 264.7 cells also had significantly decreased levels of intracellular iron (below assay limit) when compared to IFN+NGMMA-treated cells (72.0 +/- 0.78% of control). Normally permissive HL-60 cells treated with IFN were bacteriostatic rather than bactericidal, and NO production was not detected above background. Thus, NO radicals play a critical role in the bactericidal activity against Lp by IFN-treated RAW 264.7 cells, but the absence of NO production limits IFN-treated HL-60 cells to bacteriostasis.

Animals↗
PubMed1992

The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat.

Sevoflurane was compared to isoflurane anesthesia alone and in combination with atracurium or vecuronium in 84 rats using the sciatic nerve-anterior tibialis muscle preparation. Both bolus injection and infusion rate techniques were used to evaluate these drug interactions. The ED(50) (dose which produced a 50% depression of twitch tension) of atracurium was 311 +/- 31 and 360 +/- 32 microg.kg(-1) during 1.25 MAC sevoflurane and isoflurane anesthesia respectively. The ED(50) of vecuronium was 190 +/- 27 and 149 +/- 14 microg.kg(-1) during 1.25 MAC sevoflurane and isoflurane anesthesia respectively. The mean infusion rates of atracurium and vecuronium required to maintain a 50% depression of twitch tension were 5.04 +/- 0.7 and 2.02 +/- 0.3 mg.kg(-1).hr(-1). These infusion rates were 5.04 +/- 0.7 and 2.02 +/- 0.3 mg.kg(-1).hr(-1) during 1.25 MAC sevoflurane and 3.73 +/- 0.3 and 1.81 +/- 0.4 mg.kg(-1).hr(-1) during 1.25 MAC isoflurane anesthesia respectively. With both atracurium and vecuronium, the infusion rate required to maintain a 50% depression twitch of tension was inversely related to the concentrations of isoflurane and sevoflurane. The authors conclude that sevoflurane is similar in potency to that of isoflurane in augmenting a vecuronium or atracurium induced neuromuscular blockade in a dose-dependent manner.

Journal Article↗
PubMed1992

Clinical management of abutments with intracoronal attachments.

A method of preparing teeth to accommodate intracoronal attachments is presented. The resulting prosthesis incorporates a fixed partial denture with physiologically contoured crowns and a removable partial denture with a precisely determined path of insertion. These techniques stress the importance of surveyed diagnostic casts and coordinated tooth preparations for artificial crowns to facilitate treating complex cases.

Crowns↗
PubMed1992

The effects of phenindamine tartrate on sleepiness and psychomotor performance.

Phenindamine, an H1-receptor antagonist that was developed almost 50 years ago, has been associated with both drowsiness and insomnia. Since its central nervous system profile has not been well characterized, we used a series of psychomotor tests to conduct two studies. In the first, 12 subjects received single oral doses of phenindamine (25 mg), diphenhydramine (50 mg), terfenadine (60 mg), or placebo in a four-way crossover study. Psychomotor tests included choice reaction time (CRT), tracking, and hand steadiness (HS). In the second trial, 15 subjects received single oral doses of phenindamine (25 mg), pseudoephedrine (60 mg), phenindamine and pseudoephedrine, diphenhydramine (50 mg), or placebo in a five-way crossover study. Psychomotor tests included CRT, HS, and a task that divided attention between tracking and reaction time. Introspective drowsiness was measured in both trials with use of a visual analog scale (VAS) and the Stanford Sleepiness Scale (SSS). All assessments were made before and 1, 3, and 5 hours after drug administration. In the first trial, diphenhydramine produced significant impairment relative to placebo (p < 0.05) in CRT, tracking, and HS tasks and higher SSS and VAS scores, with peak effect noted at 3 hours. Phenindamine did not significantly differ from placebo or terfenadine. In the second trial, diphenhydramine produced significant impairment relative to placebo (p < 0.05) in CRT, divided attention, HS, and VAS, and SSS, also peaking at 3 hours. Stanford Sleepiness Scale scores after phenindamine were greater than placebo at 3 hours (p < 0.05) but significantly less than diphenhydramine (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Inefficient bacteriolysis of Escherichia coli by serum from human neonates.

To assess bacteriolysis in human neonates, Escherichia coli O7w:K1:NM were incubated with sera from eight healthy neonates, serum pooled from the eight neonates, and serum pooled from healthy adults. The adult serum killed E. coli. In contrast, the bacteria were not killed during incubation with sera from the eight neonates, the pooled neonatal serum, or with heat-inactivated adult serum. However, the combination of pooled neonatal serum and heat-inactivated adult serum killed the bacteria. Supplemental IgG-containing antibodies that bound to E. coli did not enhance the bactericidal activity of the neonatal serum. Ten of 12 blood isolates of E. coli from septic neonates but only 8 of 15 isolates from septic adults were serum-sensitive (killed during incubation with adult serum) (P less than .05). Therefore, neonatal serum killed E. coli inefficiently and was deficient in non-IgG heat-stabile component(s) required for bacterial killing. Compared with adults, neonates were more frequently septic with serum-sensitive strains of E. coli.

Adult↗
PubMed1992

Pharmacokinetics of rocuronium bromide (ORG 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation.

To determine the effect of end-stage renal disease on the pharmacokinetics of reocuronium bromide (ORG 9426), a new nondepolarizing monoquaternary steroidal neuromuscular blocking drug, the authors administered 600 micrograms/kg rocuronium (2 x ED95) intravenously to ten patients undergoing cadaver renal transplantation and ten healthy patients undergoing elective minor surgery (controls). All patients were anesthetized with nitrous oxide (50-70% in oxygen) and isoflurane (end-tidal concentrations of 1.2 +/- 0.5% and 0.8 +/- 0.2%, mean +/- SD, for control and transplant groups, respectively). Plasma concentrations of rocuronium were determined by capillary gas chromatography. A population-based pharmacokinetic analysis (NONMEM) was used to determine typical values, standard errors, and interindividual variability for the pharmacokinetic parameters and to determine whether these values differed between control and renal transplant patients. Total plasma clearance (2.89 +/- 0.25 ml.kg-1.min-1, mean +/- SE) and volume of the central compartment (76.9 +/- 10.6 ml/kg) did not differ between control and renal transplant patients, whereas volume of distribution at steady state was greater in renal transplant patients (264 +/- 19 ml/kg) than in control patients (207 +/- 14 ml/kg). This resulted in a longer elimination half life in renal transplant patients (97.2 +/- 17.3 min) compared to controls (70.9 +/- 4.7 min). The authors conclude that renal failure and renal transplantation alter the distribution but not the clearance of rocuronium.

Adult↗