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Biomedical subjects

R D Miller

Publications and source records attributed to R D Miller.

At least 307 records · Page 17Linked to original sources

Pharmacokinetics of Org NC45 (norcuron) in patients with and without renal failure.

To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal renal function group, n = 4) and 0.14 mg kg-1 (renal failure group, n = 5). Four additional patients with normal renal function were given Org NC 45 0.14 mg kg-1 to determine the onset, duration and recovery rate of neuromuscular blockade. The serum concentration of Org NC 45 was determined by normal-phase high performance liquid chromatography (sensitivity 50 ng ml-1), and a two-compartment open pharmacokinetic model was fitted to resulting data. Estimates of distribution half-life (T 1/2 alpha), elimination half-life (T 1/2 beta), volume of distribution at steady state (Vss) and clearance of Org NC 45 did not differ significantly between patients with normal renal function and those with renal failure. The onset, duration and recovery rate times of the neuromuscular blockade by Org NC 45 0.14 mg kg-1 in patients with normal renal function and those with renal failure did not differ significantly.

Adult↗

Pharmacokinetics of edrophonium in anephric and renal transplant patients.

The pharmacokinetics of edrophonium were determined in patients anaesthetized with nitrous oxide and halothane undergoing kidney transplant nephrectomy (n=6) or transplantation of a live related donor kidney (n = 6). Serum concentrations of edrophonium were assayed by high pressure liquid chromatography and pharmacokinetic variables computed using non-compartmental analysis. Patients undergoing transplant nephrectomy had a significant increase in elimination half-life and a significant decrease (67%) in serum clearance when compared with kidney transplant recipients or patients with normal renal function. Pharmacokinetic indices for edrophonium in patients receiving a kidney transplant did not differ from those in patients with normal renal function. We conclude that absence of renal function decrease excretion of edrophonium to an extent similar to that of other acetylcholinesterase inhibitors, neostigmine and pyridostigmine.

Adult↗

Pharmacokinetics of edrophonium and neostigmine when antagonizing d-tubocurarine neuromuscular blockade in man.

The pharmacokinetics and effectiveness of edrophonium antagonism of d-tubocurarine neuromuscular blockade were compared with that of neostigmine in surgical patients anesthetized with halothane and nitrous oxide. After an intravenous (iv) injection of d-tubocurarine (0.3 mg/kg), the single twitch tension was allowed to return to five per cent of the control level. Edrophonium, 0.5 or 1.0 mg/kg (n = 12), or neostigmine, 0.07 mg/kg (n = 6), was then given iv in combination with atropine, 1.0 mg, as a 2-min controlled infusion. Train-of-four and single twitch tension were followed for 60 min in all patients. Twelve patients were monitored for 90 min, six patients for 120 min, four patients for 150 min, and two patients for 240 min. Blood was sampled intermittently for four hours and assayed for edrophonium or neostigmine using high-pressure liquid chromatography. Edrophonium was found to promptly antagonize the d-tubocurarine blockade. Twitch tension rapidly increased to a plateau (a rate of increase in twitch tension of less than 2 per cent of control per min) which was sustained in all cases. The mean time to plateau for edrophonium was 2.9 +/- 0.21 (+/-SE) min as compared to 6.1 +/- 0.75 min for neostigmine. Neuromuscular blockade did not reappear in any patient. The degree of antagonism of the neuromuscular blockade by neostigmine and edrophonium was not significantly different. Except for a longer distribution half-life, the pharmacokinetic variables for edrophonium did not differ significantly from those for neostigmine. The elimination half-lives of edrophonium and neostigmine were 110 +/- 34 min (mean +/- SD) and 77 +/- 47 min, respectively. The authors therefore conclude that edrophonium, 0.5-1.0 mg/kg, has pharmacokinetic variables comparable to neostigmine and produces prompt, sustained, and effective antagonism of d-tubocurarine neuromuscular blockade.

Adult↗

Clinical pharmacology of ORG NC45 (NorcuronTM): a new nondepolarizing muscle relaxant.

To determine the neuromuscular effects of a new muscle relaxant, ORG NC45 (Norcuron), a monoquaternary homologue of pancuronium, 84 ASA Class I or II patients were studied under halothane and nitrous oxide anesthesia. The ED50 (dose of muscle relaxant causing a 50% depression of twitch tension) of pancuronium and ORG NC45 was 0.022 mg/kg (r = 0.90) and 0.015 mg/kg (r =0.80), respectively, for a potency ratio of 1.5 (0.022/0.015). The duration of action (time from injection to 90% recovery of control twitch tension) was 27 +/- 5 min with ORG NC45, 0.02 mg/kg, and 65 +/- 16 min with pancuronium in an equivalent dose of 0.03 mg/kg. The increase in duration of neuromuscular blockade from repetitive doses was greater with pancuronium than with ORG NC45. Reversal of an ORG NC45 neuromuscular blockade was accomplished with doses of neostigmine slightly less than those required for pancuronium. Under thiopental-nitrous oxide anesthesia, endotracheal intubation was easily performed using ORG NC45, 0.07-0.14 mg/kg. The duration of action of ORG NC45, 0.07 mg/kg, was about one-third that of pancuronium (0.1 mg/kg). It was concluded that ORG NC45 is more potent and has a shorter duration of action with both initial and repetitive doses than does pancuronium. With these characteristics and the reported lack of cardiovascular effects, the authors believe further clinical trials are warranted.

Adult↗

Role of outer envelope contamination in protection elicited by ribosomal preparations against Neisseria gonorrhoeae infection.

A recent report (Cooper et al., Infect. Immun. 28:92-100, 1980) demonstrated that immunization of guinea pigs with ribosomal preparations was protective (approximately 90%) against chamber infections with Neisseria gonorrhoeae. Similar protection has been demonstrated with other cellular immunogens such as outer membranes (OM) (92%) or purified lipopolysaccharide (LPS) (83%). Protection of LPS (5 to 100 micrograms) was dose dependent (83% with 100 micrograms). Treatment of LPS with pronase reduced the protection by 50%. Ribosomal preparations contained LPS contamination (3.9%) based on dry weight determinations by 2-keto-3-deoxyoctonate analysis. Analysis of ribosomal preparations isolated from cells after lactoperoxidase-mediated 125I labeling indicated a major OM contamination (Protein I). The ribosomal preparation also contained low levels of succinic and lactic dehydrogenase. Passive hemagglutination tests revealed that sera from guinea pigs immunized with ribosomal preparations also demonstrated antibody to OM proteins and LPS. LPS was able to absorb one line of precipitation seen in immunodiffusion reactions as well as the bactericidal activity of such sera. OM preparations were unable to absorb the remaining precipitin line or remove the bactericidal activity. It appears that LPS is the major antigen responsible for the bactericidal activity seen in ribosome-immune sera.

Absorption↗

Extracellular enzymes of Legionella pneumophila.

All strains of Legionella pneumophila tested produced detectable levels of extracellular protease, phosphatase, lipase, deoxyribonuclease, ribonuclease, and beta-lactamase activity. Weak starch hydrolysis was also demonstrated for all strains. Elastase, collagenase, phospholipase C, hyaluronidase, chondroitinase, neuraminidase, or coagulase were not detected in any of these laboratory-maintained strains.

Deoxyribonucleases↗

Amino acid requirements for Legionella pneumophila growth.

The amino acids L-arginine, L-isoleucine, L-leucine, L-methionine, L-serine, L-threonine, and L-valine were essential for the growth of Legionella pneumophila in a chemically defined medium. A partial requirement for L-cysteine (or L-cystine) was also observed. A minimal medium containing only the eight required amino acids supported the growth of this bacterium only if the medium was supplemented with L-glutamic acid. This latter compound was the only amino acid capable of stimulating growth in the eight-amino acid medium.

Amino Acids↗

Beyond the old state hospital: new opportunities ahead.

Despite criticism from many quarters, the state hospitals continue to perform important roles in patient care, evidenced by increasing admissions in recent years. The hospitals serve as back-up facilities for patients who cannot be treated in community settings, and, because of their size, they are able to offer specialized services that community-based programs cannot provide. In addition, smaller patient populations and stricter rules about adequacy of staff and treatment programs have opened up new opportunities for hospitals to move into other important areas involving affiliation with academic centers, such as professional training and clinical research. Because of the state hospital's central role in a growing number of legal and public policy issues, professionals in such facilities must become active participants in the decision-making processes that shape mental health policy and determine the quality of patient care.

Commitment of Persons with Psychiatric Disorders↗

High performance liquid chromatography (HPLC) of natural products. IV. The use of HPLC in biosynthetic studies of cephalosporin C in the cell-free system.

A new cepham metabolite has been isolated from the filtered broth of Cephalosporium acremonium by high performance liquid chromatography (HPLC) and identified as 7 beta-(5-D-amino-adipamido)-3 beta-hydroxy-3 alpha-methyl-cepham-4 alpha-carboxylic acid (I). Pure penicillin N was prepared using HPLC in the analytical mode. When I was added in place of penicillin N as substrate for the cell-free biosynthetic of cephalosporin, no formation of deacetoxycephalosporin C (II) was observed. A synthetic cepham derivative, 7 beta-(5-D-aminoadipamido)-3-exomethylene-cepham-4 alpha-carboxylic acid (III) was also tested in the cell-free system as a possible intermediate. The compound III was shown to be an inhibitor of the ring expansion enzyme that converts penicillin N to deacetoxycephalosporin C.

Acremonium↗

A comparison of phenelzine and imipramine in depressed inpatients.

Phenelzine and imipramine were compared double-blind, in 43 depressed inpatients. A placebo week preceded drug treatment; this allowed early identification of placebo responders who did not therefore enter the study. After three weeks treatment, the two drugs were equally effective on Hamilton, Beck and SCL-90 measures of depression and anxiety. On the the SCL-90 scales of hostility and paranoia imipramine was more effective; in some patients phenelzine was associated with increased hostility. Measurement of MAO inhibition and plasma tricyclic levels indicated that adequate doses were generally used - (mean 81 mg/day phenelzine and 144 mg/day imipramine).

Adult↗

Cyclodialysis with air injection in black patients.

Thirty-two cases are presented in which cyclodialysis with air injections was used to treat glaucoma in black patients. Nineteen of the 32 cases were of aphakic glaucoma and most represented failures of other glaucoma surgery. The success rate was found at 12 months postoperative follow-up to be 75%. Three of 13 eyes with phakic glaucoma developed cataracts. Cyclodialysis may be superior to trabeculectomy for surgical treatment of glaucoma in black patients.

Adult↗

Trabeculectomy in black patients.

A series of 122 trabeculectomies in black patients is presented, with a minimum postoperative follow-up of 12 months. Glaucoma was controlled in 57% of the cases (39% without medication and 18% with medication) and 43% were uncontrolled at 12 months. Several characteristics were observed in these patients that seem to influence success. A high correlation was found between the presence of a bleb and successful control of pressure without medication. The rate of success was found to decrease little after 12 months postoperative follow-up.

Adolescent↗