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Biomedical subjects

R A Cooper

Publications and source records attributed to R A Cooper.

At least 145 records · Page 8Linked to original sources
PubMed1993

Purification, nucleotide sequence and some properties of a bifunctional isomerase/decarboxylase from the homoprotocatechuate degradative pathway of Escherichia coli C.

A 1.8-kbp region of DNA that appeared from deletion subcloning to code for 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase and 5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase was investigated further. By nucleotide sequencing, a single open reading frame was found encoding a polypeptide of M(r)44514. One of the deletion subclones expressed the decarboxylase and isomerase activities at elevated levels and was used to facilitate purification of the enzyme(s). Both activities copurified, indicating that they were distinct activities of the same protein. Some kinetic properties of the purified isomerase/decarboxylase protein were investigated and it was shown that there is a 49,000-fold preference for 2-hydroxyhepta-2,4-diene-1,7-dioate over the structurally related compound 5-carboxymethyl-2-hydroxymuconate, the substrate of a second isomerase in the same catabolic pathway. Comparison of the amino acid sequences of the two isomerases showed only a low level of similarity, suggesting that these two enzymes are not evolutionarily related. However, comparison of the N-terminal half of the isomerase/decarboxylase sequence (residues 1-202) with the second half (residues 203-406) showed significant similarity, suggesting that a duplication may have occurred to produce the bifunctional gene.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

The Escherichia coli C homoprotocatechuate degradative operon: hpc gene order, direction of transcription and control of expression.

Homoprotocatechuate (HPC; 3,4-dihydroxyphenylacetate) is catabolized to Krebs cycle intermediates via extradiol (meta-) cleavage and the necessary enzymes are chromosomally encoded in a variety of bacteria. Based on an analysis of the cloned pathway genes, the Escherichia coli C hpc gene cluster was thought to be arranged in two gene blocks transcribed from a central, divergent, operator/promoter region, which was negatively regulated by the Hpc repressor. By a variety of techniques including expression of cloned hpc genes in pUC18/19 vectors, unidirectional deletion subcloning, hybridization studies and nucleotide sequencing it has now been shown that the hpc pathway structural genes are transcribed in one direction. These experiments have also indicated that a decarboxylase and an isomerase of the pathway are encoded by a single gene (hpcE) and have established the exact structural gene order as hpcRphpcECBDGH. The position of the putative regulatory gene, hpcR, is upstream of the first structural gene (hpcE) for the Hpc pathway enzymes. The deduced open reading frame for the Hpc repressor specifies a protein of 148 amino acids with a subunit molecular weight of 17 kDa. The region between hpcR and the first gene for the pathway enzymes has a sequence similar to that for catabolite activator protein (CAP) binding. This region is immediately upstream of a promoter for the pathway structural genes, which has been identified by transcript mapping.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium.

Haemodynamic variables were measured following administration of rocuronium 0.6 mg.kg-1 or vecuronium 0.08 mg.kg-1 (approximately equivalent to 2 x ED95 doses) in patients anaesthetized with fentanyl 50 micrograms.kg-1 and scheduled to undergo elective coronary artery bypass grafting. There were increases in stroke volume index (+15%) and cardiac index (+11%), and a decrease in pulmonary capillary wedge pressure (-25%) following administration of rocuronium (P < 0.05). The changes in heart rate (+7%), mean arterial pressure (-5%), systemic vascular resistance (-12%) and other measured or derived indices were insignificant. In comparison the administration of vecuronium was associated with decreases in heart rate (-7%), mean pulmonary artery pressure (-17%), central venous pressure (-15%) and the rate-pressure product (-9%) (P < 0.05). The changes in mean arterial pressure (-7%), cardiac index (-6%) and systemic vascular resistance (-8%) following vecuronium were insignificant. There were no differences in any of the variables between rocuronium and vecuronium. The absolute values of all variables were, however, within acceptable clinical limits. There was no evidence of histamine release in any patient. The present study shows that rocuronium 0.6 mg.kg-1 is associated with changes of only small magnitude in haemodynamic variables.

Androstanols↗
PubMed1993

Prediction of pulmonary function in wheelchair users.

As a result of the improved medical treatment of infectious diseases, these formerly leading causes of mortality in the United States have been supplanted in rank by chronic events as the major causes of death. The major causes include coronary artery disease, respiratory disease, and cancer. Static and dynamic pulmonary functions in the apparently healthy wheelchair user population were measured and then modelled using stepwise regression. One hundred and nine wheelchair users (97 males, 12 females) with paraplegia (n = 77) or quadriplegia (n = 32) gave informed consent and participated in this study. Subjects ranged from being Olympic caliber wheelchair marathon racers to those who live sedentary life styles. Subjects performed three slow vital capacity (SVC) tests, three forced vital capacity (FVC) tests, and three maximal voluntary ventilation (MVV) tests while seated in their standard wheelchair. The order of the pulmonary function tests was randomized. Subjects also completed two functional residual capacity (FRC) measurements. Analysis of variance revealed significant differences in several pulmonary functions based on gender (FEVC, p = 0.0001, FEV1, p = 0.0001, FEVC 25-75%, p = 0.005, PEF, p = 0.002, FIVC, p = 0.002, RV, p = 0.0001, MVV, p = 0.0001, SVC, p = 0.001). The women's unforced prediction equations using age, height, weight did yield some significant correlations with predictions based upon ambulatory subjects. The men's unforced adapted prediction equations did reveal significant correlations with the validation group for FEVC (r = 0.66, p = 0.007), FEV1 (r = 0.62, p = 0.015), PIF (r = 0.95, p = 0.015), MVV (r = 0.57, p = 0.067), SVC (r = 0.69, p = 0.019), and RV (r = 0.67, p = 0.009). Pulmonary function in male wheelchair users should be predicted using equations which incorporate years with disability and level of impairment. Additional study is required to make any recommendations regarding women wheelchair users. However, study of pulmonary function in women should be made a priority. Pulmonary function is affected by the extent of physical impairment, and tends to decline as years with disability increase.

Adolescent↗
PubMed1993

Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure.

We have studied the onset and duration of action and pharmacokinetics of rocuronium bromide (Org 9426) during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium 0.6 mg kg-1 in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPLC. Onset time for maximum block, duration of clinical relaxation (T1(25)) and recovery index, were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and 28 (12.3) min and 19 (8.8) min, respectively, for patients with and without renal failure. The time for TOF ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) ml kg-1 min-1 and 3.7 (1.4) ml kg-1 min-1, respectively) and the mean residence times (97.1 (48.7) min and 58.3 (9.6) min) P < 0.05). The differences in other kinetic parameters were not significant. We conclude that the effects of rocuronium may be prolonged in patients with renal disease, because of a decreased clearance of the drug.

Adult↗
PubMed1993

Three views on faculty tenure in medical schools.

Three distinguished academicians share their thoughts on tenure and its future in academic medicine. Paul J. Friedman, from the University of California, San Diego, School of Medicine, explains and defends tenure as practiced in medical schools. He examines the question of giving tenure to clinical faculty, explains posttenure academic review, reports that the impending end of mandatory retirement will not have a significant effect on faculty turnover, and suggests that medical schools make the status of emeritus faculty more attractive. Next, Gail H. Cassell, from the University of Alabama School of Medicine, examines various beliefs about tenure and tenured faculty in the light of available studies, and concludes that many of the negative "myths" about the effect of tenure (e.g., promoting mediocrity and discouraging productivity) are not borne out by research findings. While she supports tenure, she maintains that better criteria are needed for awarding it; that the evaluation of faculty members' teaching needs much improvement; and that more research on tenure is needed. Finally, Richard A. Cooper, from the Medical College of Wisconsin, states that tenure should not continue, because the purposes of tenure (e.g., ensuring freedom of expression; providing long-term financial security and stability) should be and can be accomplished in other ways for all faculty, not just tenured faculty. A different system is needed, one that respects the value of all faculty, that responds to their diverse objectives, is fiscally responsible, and fosters the continuing culture and vitality of medical schools.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude↗
PubMed1993

SMARTWheels: development and testing of a system for measuring manual wheelchair propulsion dynamics.

The purpose of this project was to develop a system for dynamically sensing pushrim propulsion forces and torques and to collect kinetic data with the device. A system was developed to detect the forces and torques applied to the wheelchair pushrim, record, store, and process the measured data, and display the kinetic information for analysis. Ten adults, including four male wheelchair users, three ambulatory men, and three ambulatory women, pushed a wheelchair with the SMARTWheel on a dynamometer while their kinematics were videotaped. The kinetic data collected with our wheel were correlated with stick figure representations of digitized kinematic data obtained through video analysis. The close agreement between the kinetic results and the Kinematic results provided a temporal validation of the ability of the wheel to detect forces and torques applied to the wheelchair pushrim. The recorded forces and torques were in agreement with previously reported magnitudes.

Adult↗
PubMed1993

Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia.

The neuromuscular effects of intravenous rocuronium bromide, 0.6 mg.kg-1 or 0.9 mg.kg-1, were studied in four groups of 10 patients during anaesthesia with or without halothane (0.5-0.75% inspired concentration). Neuromuscular block was monitored using mechanomyography and train-of-four stimulation. The mean times to onset of complete neuromuscular block were 58 and 59 s using the 0.6 mg.kg-1 dose in patients anaesthetised with fentanyl and halothane respectively. The times of 34 min and 33 min for 25% recovery of T1 (first response in the train of four), 54 min and 52 min for 90% recovery of T1, 55 min and 60 min for a train of four ratio of 0.7, and 13 and 13 min respectively for the recovery index (25-75% recovery of T1) were not significantly different in these groups. Complete block with the 0.9 mg.kg-1 dose occurred in 47 s and 44 s respectively in the fentanyl and halothane groups. T1 recovered to 25% in 51 min and 58 min, and to 90% in 77 min and 86 min respectively in the two groups. The recovery indices and the times to spontaneous recovery of the train of four ratio to 0.7 were 17 min and 19 min, and 83 min and 93 min respectively. All the parameters were significantly different between the 0.6 mg.kg-1 and 0.9 mg.kg-1 doses. Halothane in the concentrations used did not influence the neuromuscular effects. It is concluded that rocuronium is a rapidly acting non-depolarising muscle relaxant with a duration of action similar to that of vecuronium and may be a useful alternative to suxamethonium for rapid tracheal intubation.

Adolescent↗
PubMed1993

The effect of phase separation on biphasic waveform defibrillation.

It has been hypothesized that the defibrillation efficacy of a biphasic shock is caused by the large change in voltage between the two phases. This study examined the effects of separating the two phases in time thus splitting in half the rapid voltage change at phase reversal. The study was performed in three parts each using six dogs. Part I determined defibrillation thresholds (DFTs) for two exponentially truncated biphasic waveforms (3.5/2 msec and 6/6 msec) with interphase time delays of 0, 1, 2, 3, 4, 6, 8, and 10 msec. In Part II, probability of success curves were generated using an up down method with 15 shocks for each delay for the 3.5/2 msec biphasic waveform with interphase delays of 0, 2, 3, 4, and 5 msec. In Part III, DFTs were determined using a 3.5/2 msec and 6/6 msec biphasic as well as a third waveform that consisted of two sequential 6-msec pulses of the same polarity with interphase delays of 0, 5, 10, 15, 20, 25, 50, and 100 msec. In all three parts the defibrillating cathode was a 6.17 cm2 transvenous spring electrode positioned in the RV apex and the anode was a 113 cm2 cutaneous left chest wall electrode patch. With all waveforms, the trailing edge voltage of the first phase was equal to the negative of the leading edge voltage of the second phase. There was no statistical difference in DFTs or in 50% successful defibrillation points for phase separations from 0 to 6 msec and 0 to 5 msec for Parts I and II, respectively. In Part I there was a significant increase in DFTs for phase separations of 8 and 10 msec compared to a phase separation of 0 msec. In Part III there was no significant difference for separations of 0 and 5 msec; however, there was a significant increase in DFT requirements for separations from 5 to 50 msec, which then decreased with a separation of 100 msec for all three waveforms tested. In conclusion, defibrillation efficacy was unchanged with phase separations up to 6 msec. With phase separation, the rapid voltage change during phase reversal is split in half and, thus, cannot explain the improved efficacy of biphasic waveforms.

Animals↗
PubMed1993

Internal cardioversion of atrial fibrillation in sheep.

BACKGROUND: The cardioversion efficacy of multiple defibrillation waveforms and electrode systems was compared in a sheep model of atrial fibrillation. METHODS AND RESULTS: Sustained atrial fibrillation could be induced with rapid atrial pacing in 23 (55%) of the animals. This study was performed in four parts. Six sheep with sustained atrial fibrillation were used for data analysis for each part, except in part 4 where five sheep without sustained atrial fibrillation were used. In part 1, four lead systems and four single capacitor truncated exponential defibrillation waveforms (two monophasic and two biphasic) were tested. In part 2, two transvenous lead systems were compared; one was a right-to-left system with one electrode located in the right side of the heart and the other electrode located in the left side of the heart, and the other was a totally right-sided system with both electrodes located in the right side of the heart. Eight (four monophasic and four biphasic) waveforms were tested with each lead system. In part 3, eight transvenous lead systems were compared, and two waveforms (one monophasic and one biphasic) were tested with each lead system. For parts 1-3, probability of success curves were determined for each waveform/lead system configuration using an up-down technique with 15 shocks per configuration. In part 4, shocks were synchronized to the QRS and given through two lead configurations during sinus rhythm in 20-V steps starting with 40 and ending with 500 V, and two waveforms were tested with each lead system (one monophasic and one biphasic). Ventricular fibrillation thresholds were determined by giving shocks during the T wave of sinus rhythm. For part 1, the three lead systems that used only intravenous catheter electrodes had significantly lower defibrillation requirements than the catheter-to-chest wall patch system. A 3/3-msec biphasic waveform had significantly lower defibrillation requirements than any of the other three waveforms in part 1. In part 2, the 3/3-msec biphasic waveform with a right-to-left lead system configuration had significantly lower defibrillation requirements than any other waveform lead system combination tested, and for each waveform tested, the right-to-left configuration had significantly lower requirements than the totally right-sided configuration. In part 3, for each waveform the right-to-left configuration had significantly lower voltage and energy requirements than the corresponding totally right-sided configuration. Furthermore, in part 3, waveform/lead configurations that probably generated high potential gradients near the sinoatrial node and near the atrioventricular node resulted in more postshock conduction disturbances. In part 4, there were no episodes of ventricular arrhythmias with shocks synchronized to the QRS. However, with synchronization to the T wave, ventricular fibrillation was induced in all five animals with the minimum tested voltage, which was 40 V. CONCLUSIONS: This acute model yielded sustained atrial fibrillation in approximately 55% of the animals. Cardioversion of atrial fibrillation in sheep is possible with very low energy requirements using transvenous electrode systems (50% successful energy of 1.3 +/- 0.4 J for the 3/3-msec biphasic waveform with a right-to-left lead system). The biphasic waveform had the lowest defibrillation requirements of any waveforms tested, and right-to-left lead systems resulted in lower defibrillation requirements than totally right-sided lead systems. Also, lead systems that probably generated high potential gradients near the sinoatrial and atrioventricular node areas resulted in more frequent episodes of postshock conduction disturbances. Furthermore, synchronization of the shock to the QRS was vital to avoid potentially lethal postshock ventricular arrhythmias...

Animals↗
PubMed1993

Design of a composite monocoque frame racing wheelchair.

Design of present-day racing wheelchairs developed out of necessity and common sense. The chairs first used in racing were everyday chairs; through years of trial and modification the racing chairs of today evolved. Very little advanced engineering has been applied to the design of racing chairs. The Finite Element Analysis model executed on a computer provided insight into structural problem areas in the design of unibody frame racing chairs. Slight modifications to the model can be used to investigate new shapes, loads, or materials without investing large amounts of time and money. Wind tunnel testing with scale models provided perspectives on different improvements to reduce drag. Shape improvements may play an important role in reducing the racer's time during competition. Shape may help to decrease drag for the user in either the upright or down position. Considering that the frontal area increases around 30% in the up position with current strut and chassis frames, monocoque shapes should excel. Finite element analysis and air drag analysis are important to the design of a composite racing wheelchair. Composite materials may promote more efficient and ergonomic racing wheelchairs.

Computer Simulation↗
PubMed1993

Epidural analgesia for labour using a continuous infusion of bupivacaine and alfentanil.

Seventy women who requested epidural pain relief in labour received a continuous epidural infusion at 8 ml h-1, which contained either 0.25% bupivacaine (n = 29), or a mixture of 0.125% bupivacaine and 0.005% alfentanil (n = 31), assigned randomly. Increments of 4 ml 0.25% bupivacaine were given on demand to prevent residual pain from uterine contractions. The two groups were compared for motor block of the lower limbs, number of increments required, type of delivery and neonatal Apgar scores. The group of women receiving the mixture of bupivacaine and alfentanil required between them seven increments; the group receiving bupivacaine alone required 15. One of the women receiving the mixture and eight of the women receiving bupivacaine alone had almost complete motor block. There were no differences in the mode of delivery or in the neonatal Apgar scores.

Adult↗
PubMed1992

Evidence for copper and 3,4,6-trihydroxyphenylalanine quinone cofactors in an amine oxidase from the gram-negative bacterium Escherichia coli K-12.

The cofactors present in a amine oxidase induced in Escherichia coli K-12 by growth on 2-phenylethylamine have been studied by spectroscopic methods. E.s.r. spectroscopy establishes the presence of cupric copper while resonance Raman spectroscopy on the phenylhydrazine derivative of the enzyme provides strong evidence for the oxidized form of 3,4,6-trihydroxyphenylalanine (TOPA) quinone. The amine oxidase should accordingly be classified as EC 1.4.3.6. This is the first report of such an amine oxidase in a Gram-negative bacterium.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Estimation of the potency of ORG 9426 using two different modes of nerve stimulation.

The potency of ORG 9426, a new nondepolarising muscle relaxant, has been estimated using two different modes of nerve stimulation in patients anaesthetised with thiopentone, nitrous oxide-oxygen and intravenous fentanyl. The force of contraction of adductor pollicis was measured following a single twitch (ST) at 0.1 Hz or a train-of-four (TOF) mode of stimulation at 2 Hz every ten seconds. Dose-response curves were constructed using a single-dose method. The ED50, ED90 and ED95 were 147,272 and 305 micrograms.kg-1 respectively using the ST mode and 125,230 and 257 micrograms.kg-1 using the TOF mode of stimulation. The ED50S were not significantly different but the differences between ED90S and ED95S were significant (P less than 0.05) indicating greater sensitivity of the neuromuscular junction using TOF stimulation. The results of this study suggest that the information obtained by single-twitch stimulation is not the same as that obtained from the first response of the TOF stimulation, suggesting apparently increased sensitivity (and apparently greater potency) with the TOF mode of stimulation. Org 9426 appears to be a drug with relatively low potency.

Adolescent↗
PubMed1992

Polyethylene debris-induced osteolysis and loosening in uncemented total hip arthroplasty. A cause of late failure.

Uncemented total hip arthroplasty has proven to be an acceptable alternative to cemented total hip arthroplasty with good short-term results. With the elimination of the use of polymethyl methacrylate for component fixation, failure at the bone-cement interface, with resultant osteolysis and progressive loosening, was thought to be preventable. Unfortunately the ultra-high-molecular-weight polyethylene acetabular insert can wear and produce particulate debris. This debris can stimulate an osteolytic reaction and lead to late aseptic loosening in a cementless total hip arthroplasty.

Acetabulum↗