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Biomedical subjects

J W Walker

Publications and source records attributed to J W Walker.

At least 55 records · Page 3Linked to original sources

Abdominal and pelvic pain.

Complaints of abdominal and pelvic pain account for a large number of Emergency Department presentations. Unfortunately, the subjective, often ambiguous, complaint of pain may represent a broad spectrum of pathology ranging from relatively benign disorders to acute, life-threatening illness. It is the duty of the Emergency Department physician to separate the potentially lethal disorders from the less acute illnesses, a task that this article aims to make easier.

Abdomen, Acute↗

Reassessment of theophylline toxicity. Serum concentrations, clinical course, and treatment.

It has been reported in the medical literature that in cases of theophylline toxicity a relationship exists between the serum theophylline concentration and the severity of symptoms. We reviewed the records of 20 inpatients receiving long-term theophylline therapy who had serum theophylline concentrations of at least 20 mg/L (111 mumol/L) or who had symptoms of theophylline toxicity. No relationship between the serum concentrations and the severity of toxic effect was seen. Metabolic abnormalities similar to those previously reported in intentional acute intoxication were noted. Cardiac arrhythmias were seen in approximately half of the patients, hypotension in only one. No patient in whom a conservative form of therapy was initiated at diagnosis went on to develop additional toxic effects. It is our finding that severe toxic reactions to theophylline can occur over a wide range of serum concentrations. Conservative treatment measures, specifically drug discontinuation and interference with additional oral absorption by activated charcoal, should be instituted unless life-threatening symptoms are present, when more aggressive therapy (such as charcoal hemoperfusion) is warranted.

Aged↗

Photolabile protecting groups for an acetylcholine receptor ligand. Synthesis and photochemistry of a new class of o-nitrobenzyl derivatives and their effects on receptor function.

Two compounds have been synthesized that feature a photosensitive o-nitrobenzyl moiety attached directly to the carbamate nitrogen of carbamoylcholine. The well-characterized acetylcholine analogue, carbamoylcholine, was released from these derivatives in response to laser light pulses at wavelengths between 300 and 355 nm. Photolysis products were isolated by high-performance liquid chromatography and identified by chemical and spectroscopic analysis. The yield of carbamoylcholine molecules per photon absorbed was 0.25. A short-lived photochromic intermediate in the photolysis reaction was detected by laser flash photolysis. A single laser flash induced an instantaneous increase in absorbance at 406 nm, followed by a first-order decay to products, with a half-time of 0.07 ms for one of the compounds [N-[1-(2-nitrophenyl)ethyl]carbamoylcholine iodide] in aqueous buffers at pH 7 and 23 degrees C. Decay rates and quantum yields depended on the nature of the substituent on the protecting group. Evidence is presented in support of the conclusion that the transient species is an aci-nitro intermediate that decays directly to carbamoylcholine and therefore determines its rate of release. The photosensitive carbamoylcholine derivatives activated the nicotinic acetylcholine receptor only after photolysis, as determined by 86Rb+ flux measurements with membrane vesicles prepared from Torpedo californica and Electrophorus electricus. Before photolysis, the compounds interacted weakly with the acetylcholine-binding sites as shown by competitive inhibition of acetylcholine-stimulated flux at high concentrations. The compounds did not induce receptor desensitization at a significant rate. The new compounds afford several major advantages over other photoactivatable acetylcholine analogues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Methods for the detection of haemagglutinins in Aeromonas.

When grown in specified conditions and tested by a rocked-tile method, 40 of 41 isolates of two species of Aeromonas formed simultaneously at least two haemagglutinins among which were: (i) a mannose-sensitive haemagglutinins with strongest activity for guinea-pig or fowl red cells, formed by all of 31 isolates of A. hydrophila and 9 of 10 isolates of A. punctata ss. caviae; (ii) a haemagglutinin, sensitive to L-fucose or D-mannose, that reacted with human red cells and which was formed by all 41 isolates; and (iii) a mannose-resistant 'tanned red cell' haemagglutinin formed by 29 isolates of A. hydrophila and one isolate of A. punctata ss. caviae. Results emphasise that for the fullest possible identification of haemagglutinins produced by Aeromonas spp., strains should be cultured in a variety of conditions and tested with a wide range of red-cell species.

Aeromonas↗

Effects of thio-group modifications of Torpedo californica acetylcholine receptor on ion flux activation and inactivation kinetics.

The effects of thio-group modifications on the ion permeability control and ligand binding properties of the acetylcholine receptor were measured in reconstituted membranes prepared from purified Torpedo californica acetylcholine receptor and soybean lipids (asolectin). A quench flow device was used to obtain subsecond time resolution for agonist-stimulated cation influx using carbamylcholine chloride (Carb) as the ligand and 86Rb+ as the cation. The effects of disulfide reduction with dithiothreitol (DTT), affinity alkylation with [4-(N-maleimido)benzyl]trimethylammonium ion and bromoacetylcholine, and nonspecific alkylation with N-ethylmaleimide and N-benzylmaleimide were examined. Activation, fast inactivation, and slow inactivation rates were measured on the chemically modified membranes. The flux results were compared with similar measurements on native membranes, and the role of vesicle size, heterogeneity, and influx time on ion flux results was analyzed. Major conclusions are that the binding sites that react with affinity labels are the same sites that mediate ligand-activated ion flux and that blockade of one of the two ligand binding sites is sufficient to block about 95% of the ion flux response. The main effect of DTT reduction is to shift the EC50 values for activation and slow inactivation to higher Carb concentrations, consistent with a decrease in binding affinity for Carb. The EC50 value for fast inactivation was not affected by DTT. However, the maximum rate of ion flux activation and the maximum rate of fast inactivation were decreased 2-fold after DTT treatment.

Animals↗

Perfusion of the cerebral cortex by use of abdominal counterpulsation during cardiopulmonary resuscitation.

Perfusion of the cerebral cortex (rCCBF) during resuscitation from cardiac arrest was studied using 24 large dogs and three different resuscitation models. Conventional cardiopulmonary resuscitation (CPR) was compared with interposed abdominal compression CPR (IAC-CPR) and with IAC-CPR together with infusion of epinephrine. Conventional CPR produced a mean rCCBF of only 11% (0.057 +/- 0.07 ml/min/g) normal perfusion (0.54 +/- 0.14 ml/min/g). Even without epinephrine, IAC-CPR produced mean rCCBF equal to 51% (0.27 +/- 0.17 ml/min/g) of normal. With epinephrine, IAC-CPR produced rCCBF (0.93 +/- 0.49 ml/min/g) statistically indistinguishable from normal. Both models of IAC-CPR were significantly superior to conventional CPR in perfusion of the cerebral cortex.

Animals↗

A multicentre comparison of piroxicam and indomethacin in acute soft tissue sports injuries.

One hundred and five patients suffering from sport-associated soft tissue injuries were included in a randomized controlled trial comparing the efficacy and side-effects of piroxicam and indomethacin. Patients were treated for 7 days. Both groups showed a similar degree of improvement in joint tenderness, swelling and pain. Eighty-eight per cent of patients on piroxicam showed a marked or moderate improvement in their injury at the end of the trial and 79% of indomethacin-treated patients. Approximately 50% of patients in both groups resumed full activity within 7 days. One patient, in the indomethacin group, was withdrawn from treatment due to a side-effect.

Athletic Injuries↗

Differential efficacy of two non-steroidal anti-inflammatory drugs in the treatment of sports injuries.

Twenty-eight patients presenting with sports injuries were randomly allocated to receive either 200 mg sulindac twice daily or 400 mg ibuprofen 3-times daily. Pain symptoms (day and night ratings) and observer assessment of pain on movement, swelling and tenderness were recorded pre-treatment and after 3 and 7 days of therapy. One patient in the sulindac group was excluded from the study because initial symptoms were mild. Response, in terms of decrease in scores, was better in those receiving sulindac than in those given ibuprofen at both 3 and 7 days for the parameters of pain during the day (p less than 0.05 at 7 days) and pain on movement (p less than 0.05 at 3 days). Patient assessment of treatment at 3 and 7 days was significantly better in the sulindac group than in the ibuprofen group (p less than 0.025). The only reported side-effect was gastro-intestinal upset in a patient in the ibuprofen group. The results suggest that sulindac is an effective and well-tolerated treatment for the symptoms associated with sprain and strain injuries.

Adult↗

Activation and inactivation kinetics of Torpedo californica acetylcholine receptor in reconstituted membranes.

By use of a quench-flow technique to measure tracer ion flux rates in a physiologically significant time domain, the kinetics of activation and inactivation of purified reconstituted acetylcholine receptor (AChR) were investigated. After solubilization in sodium cholate, purification by affinity chromatography, and reconstitution into soybean lipids, the AChR from Torpedo californica displayed a characteristically fast rate of ion influx measured with 86Rb+. At 4 degrees C 1 mM carbamoylcholine (Carb) stimulated a fast (t1/2 = 7 ms) first-order filling of vesicle internal volume that presented a 10(4)-fold stimulation of ion flux rate by Carb. The concentration dependence of activation was sigmoidal with a half-maximal value at 3 X 10(-4) M Carb. In the presence of Carb, the purified AChR also underwent a two-step inactivation (desensitization) process. Inactivation was measured by preincubating AChR with Carb for various times (milliseconds to minutes) and then measuring the 86Rb+ influx rate. The two inactivation processes were each characterized by a distinct maximum rate (5.3 and 0.10 s-1) and by a different dependence on Carb concentration. The slow phase of inactivation gave a half-maximal rate at 2.5 X 10(-4) M Carb, and the fast inactivation was half-maximal at 1.3 X 10(-3) M Carb. The concentration dependence curves for both inactivation processes were approximately hyperbolic. The results are discussed in terms of models that describe the relationship between ligand binding and the processes of channel activation and desensitization.

Acetylcholine↗

Comparison of acetylcholine receptor-controlled cation flux in membrane vesicles from Torpedo californica and Electrophorus electricus: chemical kinetic measurements in the millisecond region.

In earlier studies with the acetylcholine receptor (AcChoR) of Electrophorus electricus the rate and equilibrium constants for a model that relates the ligand binding to ion translocation were determined, and the dependence of these constants on the concentrations of carbamoylcholine and acetylcholine, over a 200- and 5000-fold range, respectively, could be predicted. AcChoR-controlled cation flux has now been measured in Torpedo californica vesicles by using a pulsed-quench-flow technique with a 2-msec time resolution. Torpedo vesicles on a weight basis may contain several hundred times more receptor sites than do E. electricus vesicles. Techniques have been developed to (i) correct for the kinetic heterogeneity of the vesicle population; (ii) use the inactivation of the receptor by its natural ligand to reduce influx rates at high ligand concentrations to a measurable level (this permitted J(A), the influx rate coefficient before the onset of inactivation, to be measured); and (iii) determine the rate coefficients of two processes that lead to successive inactivations (desensitization) of the receptor and occur in different time regions. An extension of a model proposed for the E. electricus receptor accommodates the ion translocation in T. californica vesicles. The features in common are: (i) A rapid initial flux rate [J(A)(max) for T. californica is 310 sec(-1); for E. electricus it is 7.5 sec(-1)]. These differences in flux rates are consistent with a difference in AcChoR density. (ii) A rapid inactivation process [alpha(max) for T. californica is 2 sec(-1); for E. electricus it is 7 sec(-1)]. (iii) A slow AcChoR-controlled flux that continues after the rapid inactivation [J(I)(max) for T. californica is 1.3 sec(-1); for E. electricus it is 0.015 sec(-1)]. The main difference between the flux in the two types of vesicle is the existence of a second, slower, inactivation process in T. californica with a rate coefficient, beta, of 0.12 sec(-1). The second process leads to undetectable flux activity during the time of observation (30 sec in 10 mM carbamoylcholine). These studies are also significant because fundamental differences may exist between the mechanism of AcChoR-controlled ion flux in synaptic (Torpedo) and conducting (E. electricus) membranes.

Animals↗

Effects of thio-group modifications on the ion permeability control and ligand binding properties of Torpedo californica acetylcholine receptor.

Chemical modification of membrane-bound Torpedo californica acetylcholine receptor by the disulfide reducing agent dithiothreitol has two major effects on receptor function: (1) it shifts the dose-response curve for agonist-induced increases in 22Na+ permeability to 10-fold higher concentrations, and (2) it decreases the binding affinity of the receptor for the same agonist about 6-fold. In the experiments reported here, the agonist used was carbamoylcholine. Despite the quantitative changes in agonist binding and flux response, dithiothreitol-treated membranes display all other functional properties expected of a receptor. The flux response is blocked by preincubation of the membranes with carbamoylcholine, a phenomenon known as desensitization. In parallel, the receptor undergoes a carbamoylcholine-induced shift from a low-affinity to a high-affinity binding state for the same agonist. All of the effects of dithiothreitol are reversed by the oxidizing agent 5,5'-dithiobis(2-nitrobenzoic acid). Alkylation of the membranes with N-ethylmaleimide after dithiothreitol reduction results in complete inhibition of the flux response, and the effect is not reoxidation treatment. The N-ethylmaleimide also shifts the receptor into a very low-affinity binding state for carbamylcholine that is shifted to only a slightly higher affinity by preincubation with carbamoylcholine. Prior to reduction, N-ethylmaleimide has no effect on receptor binding or flux properties. Detailed binding studies on affinity-alkylated receptor membranes indicate that the alpha-neurotoxin binding site not occupied by the affinity label displays all the same properties as unlabeled membranes, including the dithiothreitol and N-ethylmaleimide effects. The results are discussed in the context of several hypotheses previously proposed to account for the diverse effects of thio-group modifications on the acetylcholine receptor.

Animals↗

Retirement style and retirement satisfaction: retirees aren't all alike.

Postretirement patterns of work--employment for pay, voluntary activities, or no work-like activities--were examined for 1511 recent retirees from major corporations. A related typology of retirement style--reorganizer, rocking chair, holding on, and dissatisfied patterns--was also used. These patterns were examined in terms of preretirement characteristics of the respondents, postretirement attitudes about retirement, and retirement satisfaction. Multivariate analyses comparing the salience of retirement style with health, income, occupation, and preretirement feelings about retiring for predicting retirement satisfaction indicated that retirement style was a significant predictor of overall retirement satisfaction, and the subscales of satisfaction with activities and satisfaction with finances. Implications of these findings for preretirement counseling and retirement policies are discussed.

Aged↗