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Biomedical subjects

R A Cooper

Publications and source records attributed to R A Cooper.

At least 127 records · Page 7Linked to original sources

Perspectives on the physician workforce to the year 2020.

Physician supply and demand for the period extending to 2020 were assessed from three perspectives: physician utilization in group- and staff-model health maintenance organizations, physician distribution, and the future supply of nonphysician clinicians. The national norm for physician demand in 1993 was estimated to be 205 per 100,000 population. Demand is projected to increase 18% by 2020, because of both an expansion in beneficial services and a reduction in physician work effort. Supply initially will increase more rapidly, resulting in a surplus of 31,000 physicians (5% of patient care physicians) in the year 2000 and increasing to 62,000 physicians (8%) in 2010, after which the gap will narrow. Similar results were obtained when previous studies that had projected surpluses of 73,000 to 165,000 physicians (15% to 30%) in the year 2000 were reevaluated. However, physician distribution is not homogeneous, and the number of physicians per capita currently varies by more than twofold among states. Relative to the national norm, surpluses already exist in some states and shortages in others. In addition, the supply of nonphysician clinicians with independent practice authority is increasing. Their numbers are projected to double by 2010, equaling 60% of the number of patient care physicians. Measured as physician equivalents, their growth will equal the growth in physician supply. Thus, in terms of physicians alone, there is no evidence of a major impending national surplus. Local surpluses will be influenced principally by how physicians distribute themselves geographically. The major determinant of overall physician surpluses in the future will be the extent to which patients continue to seek physicians for services that also will be offered by an expanded workforce of nonphysician clinicians. Policy is needed that encompasses the universe of clinicians who will be providing care to patients in the next century.

Demography↗

The Oligocene bottleneck and New Zealand biota: genetic record of a past environmental crisis.

Mitochondrial DNA (mtDNA) 12S sequences from the two New Zealand ratite orders, the kiwi and moa, indicate that each group represents a separate colonization event. However, the amount of mtDNA genetic diversity observed within each of the New Zealand groups is similar, and limited, which is not consistent with the ratite phylogenetic tree. We examine the Cenozoic (65-0 million years ago) geological history of New Zealand for possible causes and summarize evidence for land area and climatic changes. A genetic bottleneck is hypothesized and tested, by using molecular data from a second mitochondrial locus (ND6) and a further taxon, the New Zealand acanthisittid wrens. The data support the existence of a widespread genetic bottleneck during the mid-Cenozoic in New Zealand and demonstrate the benefits of synthesizing traditional research with new molecular techniques.

Animals↗

Sequence of the hpcC and hpcG genes of the meta-fission homoprotocatechuic acid pathway of Escherichia coli C: nearly 40% amino-acid identity with the analogous enzymes of the catechol pathway.

The meta-fission pathway for homoprotocatechuic acid (HPC) catabolism is chemically analogous to the oxidative meta-fission pathway for catechol degradation and so provides an opportunity to investigate how the enzymes of chemically similar, but specific, pathways might have arisen. Two more genes of the HPC pathway from Escherichia coli C, hpcC, encoding 5-carboxymethyl-2-hydroxymuconic acid semialdehyde (CHMS) dehydrogenase, and hpcG, encoding 2-oxohept-3-ene-1,7-dioic acid (OHED) hydratase, have now been sequenced to aid this analysis. The CHMS dehydrogenase showed 40% amino acid (aa) sequence identity with the corresponding enzyme of the catechol pathway, and the OHED hydratase showed 36% aa sequence identity with the catechol pathway hydratase. The CHMS dehydrogenase is a member of the aldehyde dehydrogenase superfamily that includes enzymes from animal, plant and microbial sources. Since it appears that the dioxygenase, isomerase and decarboxylase enzymes of the two pathways are not closely related, it is proposed that the two sets of enzymes have arisen separately, but with the muconic acid semialdehyde dehydrogenases and the hydratases being recruited, respectively, from the same ancestral sources.

3,4-Dihydroxyphenylacetic Acid↗

Formation in vitro of the 3,4,6-trihydroxyphenylalanine quinone cofactor.

An Escherichia coli K-12 2-phenylethylamine oxidase gene with a mutated leader sequence region produced a largely inactive form of the enzyme in the cytoplasm. This form of the enzyme was activated 30-50-fold on incubation at 30 degrees C in the absence of any added cofactors. After activation the enzyme contained a quinone which was not detected in the non-activated form. This is the first report of the formation in vitro of any quinoenzyme cofactor.

Amine Oxidase (Copper-Containing)↗

The comparative metabolism of the four pyrrolizidine alkaloids, seneciphylline, retrorsine, monocrotaline, and trichodesmine in the isolated, perfused rat liver.

Despite their similarity in structure, pyrrolizidine alkaloids (PAs) vary in their LD50s and in the organs in which toxicity is expressed. We have examined whether there are differences in the metabolism of certain PAs that are associated with these quantitative and qualitative differences in toxicity. Isolated rat livers were perfused with one of four PAs (seneciphylline, retrorsine, monocrotaline, and trichodesmine) at 0.5 mM for 1 hr, and the pyrrolic metabolites determined that were released into perfusate and bile or bound in the liver. The proportion of the PA removed by the liver varied from 93% for retrorsine to 55% for trichodesmine. However, trichodesmine-perfused livers released the greatest amount of the dehydroalkaloid into the perfusate. These reactive pyrrolic metabolites appear to be largely responsible for the toxicity of PAs. Over the course of a 1-hr perfusion, dehydroalkaloid release varied fourfold among the PAs examined. Seneciphylline and retrorsine significantly increased bile flow. Highest concentrations of PAs in bile were achieved at 30-40 min perfusion. Conversion of dehydroalkaloid to the conjugate 7-glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (GSDHP) is a detoxification reaction. GSDHP release into bile varied from 80 nmol/g liver for trichodesmine to 880 nmol/g for retrorsine. Release of the less toxic hydrolytic product of dehydroalkaloids, 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine, was also determined. Bound pyrroles in liver are probably an indication of heptatoxicity. At the end of perfusion these varied from 55 nmol/g for monocrotaline to 195 nmol/g for retrorsine. The chemical form of the bound pyrroles is a 7-thioether conjugate of 6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine. No 7,9-dithio conjugate was detected, indicating that only monoalkylation has been found. These differences in metabolic pattern reflect differences in reactivity of the initially formed dehydroalkaloid and can account for the toxicological differences between the parent PAs.

Alkaloids↗

A physician workforce for the 21st century.

Medicine is entering an unprecedented era of provider abundance, including both physician and nonphysician providers. Over the next several decades, the projected number of primary care physicians will be more than adequate to meet national needs, although there is no assurance that any number of physicians will create an equitable distribution. At the same time, a growing surplus of specialists is projected. A balanced abundance in both primary care and specialty medicine will continue if approximately 33% of first-year residents ultimately practice primary care and 67% become specialists. In contrast, a shift to 50:50, as has been proposed by the Committee on Graduate Medical Education and others, will lead to a superabundance in primary care and a potential deficiency in specialty medicine later in the 21st century. Under either scenario, maintaining balance will be aided by those physicians with sufficient generalist skills to enable them to practice at the interface of primary care and specialty medicine, the domain of "middle care." The nation will be well served by educational policy that imparts such generalist expertise to medical students and that creates a workforce of highly skilled physicians capable of caring for patients in the technologically advanced clinical environment of the future.

Clinical Competence↗

The sea anemone purine, caissarone: adenosine receptor antagonism.

Caissarone, a sea anemone iminopurine, produced an increase in the twitch response of the electrically stimulated guinea-pig ileum-myenteric plexus. In the same assay, caissarone reduced the inhibitory response to the endogenous neuromodulator, adenosine, the A1 adenosine receptor agonist, R-phenylisopropyladenosine (R-PIA), and the A2 agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA) in a dose-dependent manner. Schild plot analysis of antagonism by caissarone yielded slopes of near unity, indicating that caissarone acts as a simple competitive antagonist at the adenosine receptor. The dissociation constants (KB) for caissarone ranged from 0.53 mM to 0.78 mM. In functional nicotinic receptor assays in two human cell lines, caissarone failed either to potentiate or to reduce carbamylcholine-mediated 86Rb+ efflux. Thus, the enhancing activity of caissarone on the gut could not be attributed to activity at the ganglionic nicotinic receptor. Based on structure and pharmacological activity, caissarone appears to be the first marine product described as an adenosine receptor antagonist.

Animals↗

Using the split Latram for better breast projection in breast reconstruction.

Over the years, although methods of breast reconstruction have improved, the ability to build a symmetrical projecting breast has not. When stacked Meme implants were used, better projection was obtained. Folding the transverse rectus abdominis musculocutaneous flaps allows for good projection; however, the breast is then quite wide and large. For smaller breast women with projection and some larger breasted women as well, splitting and stacked flaps give a much better result. We now do this procedure with simultaneous Latram and mastectomy surgery in fewer than 3 hours.

Breast Neoplasms↗

Breast abscess as a late complication of plombage.

The authors describe a patient who had undergone plombage as a treatment for tuberculosis approximately 40 years previously and who presented with a breast abscess secondary to migration of the plombage material. This complication of plombage, which has not previously been reported, was demonstrated by computed tomography.

Abscess↗

Pharmacokinetics of rocuronium bromide in patients with and without renal failure.

We studied the onset and duration of action and pharmacokinetics of rocuronium bromide 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 and duration of clinical relaxation (DUR25) were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min, respectively, for patients with and without renal failure. The time for train-of-four 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.

Androstanols↗

Power wheelchair range testing and energy consumption during fatigue testing.

The range of a power wheelchair depends on many factors including: battery type, battery state, wheelchair/rider weight, terrain, the efficiency of the drive train, and driving behavior. The purpose of this study was to evaluate the feasibility of three methods of estimating power wheelchair range. Another significant purpose was to compare the current draw on pavement to current draw on an International Standards Organization (ISO) Double Drum tester at one m/sec. Tests were performed on seven different power wheelchairs unloaded, and loaded with an ISO 100 kg test dummy. Each chair was configured according to the manufacturer's specifications, and tires were properly inflated. Experienced test technicians were used for the tennis court tests, and treadmill tests. An ISO 100 kg test dummy was used for the ISO Double Drum test. Energy consumption was measured over a distance of 1500 m for each of the three test conditions. The rolling surface was level in all cases. Repeated measure analysis of variance (ANOVA) revealed a significant difference (p = 0.0001) between the predicted range at maximum speed for the three tests. Post hoc analysis demonstrated a significant difference (p < 0.01) in estimated range at maximum speed between the Double Drum test and the treadmill test, as well as between the Double Drum test and the tennis court test. Our results indicate no significant difference (p > 0.05) between the predicted range at maximal speed between the treadmill and tennis court tests. A simple relationship does not exist between the results of range testing with the Double Drum tester and the tennis court. An alternative would be to permit the use of a treadmill for range testing as simple relationships between all pertinent treadmill and tennis court range data were found. For the Double Drum tester used, the current demand is higher than under normal usage. This presents a problem as current is related to load torque in a power wheelchair. Hence, the Double Drum tester friction must be reduced. The predicted range for the tennis court test at maximum speed ranges from a low of 23.6 km to a high of 57.7 km. The range of the power wheelchair can be improved by the use of wet lead acid batteries in place of gel lead acid batteries.

Electric Power Supplies↗

Lead systems for atrial defibrillation.

In summary, these five studies show that electrode locations that include both left and right atrium result in lower thresholds. Thresholds from right atrium to chest wall patch are higher than thresholds from right atrium to cardiac vein, suggesting that confinement of the electric field by a transvenous electrode system is advantageous. Of the transvenous locations tested, the right atrial appendage to left atrial appendage defibrillation vector consistently had the lowest defibrillation energy threshold. The proximal coronary sinus to right atrial vector may be inappropriate due to the high thresholds observed. The large variability of the mean threshold for the obtuse marginal location in the cardiac vein vasculature suggests that this vector may result in higher thresholds in some instances. Electrode locations that have high defibrillation thresholds and are in close proximity to the sinoatrial or atrioventricular node increase the likelihood of sinus arrhythmias or conduction block following the defibrillation shocks. No difference was detected between the thresholds between the single catheter, two electrode system and the two catheter system, despite the variability of location of the electrode in the right atrium, suggesting that such a catheter may provide a simpler implantation procedure and equivalent thresholds in some patients. These findings suggest that coronary sinus/great cardiac vein catheter designs should strive for implantation in the distal portion of the great cardiac vein so that the shocking electrode underlies the left atrium with the other shocking electrode located in the right atrium.

Animals↗

Mammography in men.

PURPOSE: To evaluate mammographic findings in men with abnormality of the breast. MATERIALS AND METHODS: The most common indications for mammography, performed in 263 men (mean age, 62 years; range, 19-93 years), were breast tenderness in 88 men (33%) and palpable mass in 79 men (30%). All chief symptoms and all mammographic findings were categorized. Biopsy results were correlated with mammographic findings in 24 patients. Follow-up ranged from 6 months to 8 years 4 months (mean, 3 years 4 months). RESULTS: The most common mammographic finding was gynecomastia in 213 men (81%). Gynecomastia was unilateral or asymmetric in 168 men (72%). Biopsy results in 14 patients with gynecomastia were negative for cancer; the 199 other patients did not have cancer at follow-up. Six patients had breast cancer: Four had primary breast cancer, and two had metastases to the breast from extramammary malignancies. No cancer had the mammographic appearance of gynecomastia. None of the 43 patients younger than age 50 years had cancer. CONCLUSION: A man with breast enlargement or a palpable mass who has the mammographic diagnosis of gynecomastia need not undergo biopsy unless there are other strong clinical indications [corrected]. A man younger than age 50 years with diffuse breast enlargement or a palpable, nonindurated, central, subareolar mass need not undergo mammography unless there are other strong clinical indications.

Adult↗

Evaluation of methods for determining rearward static stability of manual wheelchairs.

Wheelchair standards have been under development for several years. A set of tests has been approved by the American National Standards Institute (ANSI) and by the International Standards Organization (ISO) but continue to be refined. Static stability is one of the indicators used to evaluate manual wheelchairs and is measured by placing a loaded wheelchair on a platform that is tilted until the wheelchair's front wheels lift off of the platform. Currently, if the wheelchair parking brakes slip, a block is placed behind the rear wheels and the tip angle is measured. The results for eight different wheelchairs with three load cases showed that the rearward tip angle for the block is significantly different (p < 0.05) from that with the brakes alone.

Biomechanical Phenomena↗