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Biomedical subjects

C J Roberts

Publications and source records attributed to C J Roberts.

At least 163 records · Page 9Linked to original sources
PubMed1984

Active site mapping of the serine proteases human leukocyte elastase, cathepsin G, porcine pancreatic elastase, rat mast cell proteases I and II. Bovine chymotrypsin A alpha, and Staphylococcus aureus protease V-8 using tripeptide thiobenzyl ester substrates.

The primary subsite specificities of human leukocyte elastase, cathepsin G, porcine pancreatic elastase, rat mast cell proteases I and II, bovine chymotrypsin A alpha, and the protease from strain V-8 of Staphylococcus aureus have been mapped with a series of tripeptide thiobenzyl ester substrates of the general formula Boc-Ala-Ala-AA-SBzl, where AA represents one of 13 amino acids. In addition, the effects of a P2 Pro and P4 methoxysuccinyl and succinyl groups were investigated. In an attempt to introduce specificity and/or reactivity into the substrate Boc-Ala-Ala-Leu-SBzl(X), the 4-chloro-, 4-nitro-, and 4-methoxythiobenzyl ester derivatives were studied. Enzymatic hydrolyses of the substrates were measured in the presence of 4,4'-dithiobis(pyridine) or 5,5'-dithiobis(2-nitrobenzoic acid), which provided a highly sensitive assay method for free thiol. The thio esters were excellent substrates for the enzymes tested, and in many cases, the best substrates reported here have kcat/KM values higher than those reported previously. The best substrate for human leukocyte elastase was Boc-Ala-Pro-Nva-SBzl(Cl), which has a kcat/KM of 130 X 10(6) M-1 s-1. A very reactive rat mast cell protease substrate, Boc-Ala-Ala-Leu-SBzl(NO2), was also found. The S. aureus V-8 protease was the most specific enzyme tested since it hydrolyzed only Boc-Ala-Ala-Glu-SBzl. Substituents on the thiobenzyl ester moiety of Boc-Ala-Ala-Leu-SBzl resulted in decreased KM values with human leukocyte elastase and rat mast cell protease I when compared to the unsubstituted derivative.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Application of an automated enzymatic technique for the determination of non-esterified fatty acids in bovine blood.

An enzymatic method for the measurement of non-esterified fatty acid (NEFA) concentrations in blood was applied to samples from dairy cows. The method was carried out on a discrete analyser and showed considerable savings over other methods, particularly in time. The precision of the method was very high and the accuracy was good within normal concentration ranges when compared with an extraction reference method. Using this enzymatic method, it is possible to measure NEFA concentrations in bovine serum or plasma on a routine basis. The results will be of particular value in assessing the metabolic and nutritional status of cows in the post parturient period.

Animals↗
PubMed1984

Size and lipolytic capacity of bovine adipocytes from subcutaneous and internal adipose tissue.

Adipose tissue samples were taken from five dairy cows in early lactation. Various external and internal sites were chosen, and after isolation of the adipocytes, their size and lipolytic capacity were measured. It was found that cells from all the sites showed high lipolytic activity, although there was a four-fold difference between cells from perirenal fat and those from omental fat, which showed the highest activity. It was not possible to detect any relationship between diameter and lipolytic capacity of the adipocytes.

Abdomen↗
PubMed1984

Coccidioidomycosis in acquired immune deficiency syndrome. Depressed humoral as well as cellular immunity.

Progressive pulmonary coccidioidomycosis has not been previously reported in the setting of acquired immune deficiency syndrome (AIDS). A patient with AIDS, progressive pulmonary coccidioidomycosis, Pneumocystis carinii pneumonia, and disseminated cytomegalovirus is described. Diagnosis of these opportunistic pathogens was made by bronchoalveolar lavage and transbronchial lung biopsy. Results of traditional complement fixation serologic testing for cytomegalovirus were negative; however, the more sensitive enzyme-linked immunosorbent assay did indicate infection. Coccidioidal complement fixation tests, precipitin tests, counter-immunoelectrophoresis, and immunodiffusion tests demonstrated negative findings. These results provide additional evidence that some patients with AIDS have defects in humoral as well as cellular immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1984

The action of gamma-aminobutyric acid (GABA) and ethylenediamine (EDA) on Limulus and Helix central neurones and rat cerebellar and sympathetic ganglion neurones.

Intracellular recordings were made from central Limulus and Helix neurones and extracellular recordings from rat cerebellar Purkinje cells and sympathetic ganglia. The actions of gamma-aminobutyric acid (GABA) and ethylenediamine (EDA) and related analogues on these preparations were investigated. On Limulus neurones inhibited by GABA, EDA and piperazine were 81 and 186 times respectively less potent than GABA. Both the GABA and EDA events were chloride mediated, having similar reversal potentials and were reversibly antagonised by picrotoxinin. The EDA response persisted in high magnesium Ringer. On Helix neurones inhibited by GABA, EDA was 92 times less potent while on neurones excited by GABA, EDA was 9.25 times less potent. The other analogues tested had little or no GABA-like effect on either preparation. On rat cerebellar Purkinje cells, EDA was equipotent with GABA and both compounds were antagonised by bicuculline. Flurazepam only potentiated the action of EDA on 3 out of 23 cells tested while the GABA response of all 23 cells was potentiated by the benzodiazepine. Diaminopropionic acid was a weak inhibitor of cerebellar Purkinje cell firing but flurazepam potentiated this response in 6 out of 10 cells tested. On rat cervical ganglion neurones, EDA was half the potency of GABA and likewise the other analogues were less potent than GABA as depolarising agents. Incubation with glutamic acid decarboxylase inhibitors had no effect on the EDA response. Cross desensitisation between GABA and EDA was demonstrated using the ganglion preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Neuropharmacological studies on the receptors mediating responses to carbachol, amino acids and octopamine on Limulus and Hirudo central neurons.

Intracellular recordings were made from central neurons of Limulus polyphemus and from Retizu cells of the leech, Hirudo medicinalis. The effects of carbachol, amino acids and octopamine were examined on these neurons. Octopamine was found to have a mainly inhibitory effect on a few Limulus neurons. The effects of octopamine were mimicked by clonidine and napthazoline but not by xylazine. Both compounds were slightly more potent than octopamine. Yohimbine, metoclopramide, chlorpromazine and chlordimeform failed to antagonize this octopamine response. The excitatory effect of carbachol was blocked by alpha-bungarotoxin, 10(-7)M. Neither this concentration nor higher concentrations of alpha-bungarotoxin had any effect on L-glutamate excitation. m-Carboxyphenyl derivatives of alanine and glycine acted differentially on Limulus neurons responding to L-glutamate. m- Carboxyphenylglycine only inhibited neurones which showed a biphasic response to L-glutamate while m- carboxyphenylalanine only excited these neurons. Both compounds excited leech Retzius cells, with m- carboxyphenylalanine being about 20 times more potent than m- carboxyphenylglycine . The actions of alpha- ketokainate and allo-alpha- ketokainate were compared to kainate, dihydrokainate and L-glutamate on leech Retzius cells. The equipotent molar ratios for kainate, dihydrokainate , alpha- ketokainate and allo-alpha- ketokainate were 0.0029 +/- 0.0004, 0.021 +/- 0.047, 0.029 +/- 0.005 and 0.14 +/- 0.0093 respectively with L-glutamate as one. All the analogues were more potent than L-glutamate. Quinolinic acid had no glutamate-like activity on either Limulus or Hirudo neurons. Methyltetrahydrofolate was inactive on Limulus neurons but excited leech Retzius cells, being slightly less potent than L-glutamate. Dibutyl cAMP terminated the excitatory actions of kainate on both Limulus and Hirudo neurons. Anisatin , a putative GABA antagonist, was a potent antagonist of GABA inhibition on Limulus neurons.

Amino Acids↗
PubMed1984

A pilot evaluation of radiography of the acute abdomen.

A pilot study to assess the value of abdominal films in acute surgical admissions was undertaken. The effect of chest and abdominal radiographs on the initial management of 100 consecutive patients was assessed. A management change of 10% was found and the implications are discussed. Patients with non-specific abdominal pain and women under 40 years of age had normal radiography. Pregnancy should first be excluded in the latter group.

Abdomen, Acute↗
PubMed1984

Drug induction of hepatic enzymes in the elderly.

Previous workers have suggested that hepatic enzyme induction by drugs does not occur in the elderly. We have studied the effect of a potent enzyme inducer--glutethimide--on a group of nine patients over the age of 70 years, using antipyrine clearance as a measure of hepatic drug metabolism. After six days treatment with glutethimide, antipyrine clearance rose from 22.8 +/- 4.5 ml/min to 38.3 +/- 7.6 ml/min (P less than 0.001). The results suggest that the elderly are at risk for the full range of drug interactions due to hepatic microsomal enzyme induction.

Aged↗
PubMed1984

Epidemiology for medical students: a course relevant to clinical practice.

A new course was designed to make epidemiology clinically relevant to medical undergraduates. The objectives were that students should (1) know the epidemiology of common diseases, (2) understand epidemiological concepts useful in diagnosis and treatment, and (3) be able to critically assess published medical evidence. Results of a written examination showed that objectives 1 and 2 had been 'easily' achieved by 80% and 68% of students respectively. Student opinion of the course, assessed by an anonymous questionnaire, showed that the majority of students considered the course to be an important part of medical education. Before the course 19% felt 'reasonably able' or 'very able' to achieve nine specific objectives related to epidemiological concepts in diagnosis and treatment. By the end of the course this had risen to 78%.

Education, Medical, Undergraduate↗
PubMed1984

Antipyrine absorption after delayed oesophageal capsule transit.

Twenty fasted patients were given hard gelatin capsules containing antipyrine and barium, and in ten patients the capsule arrested and disintegrated in the oesophagus. Plasma antipyrine was assayed at 10 min intervals for 1 h, then 30 min intervals for a further 3 h. The plasma concentration-time curves for the patients in whom the capsule entered the stomach rapidly, and for those in whom the capsule lodged in the oesophagus, were compared. The absorption in the first hour was calculated from the area under the plasma concentration-time curve and found to be significantly lower if the capsule disintegrated in the oesophagus (P less than 0.0005). The time to peak plasma concentration was delayed by an average of 46 min (P less than 0.01) and the peak plasma concentration was significantly lower (P less than 0.05) if delayed capsule transit occurred. Delayed capsule transit through the oesophagus significantly changed the pharmacokinetic profile of antipyrine.

Absorption↗
PubMed1984

The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

The oral and intravenous pharmacokinetics of labetalol were determined in five subjects before and after a 3 week course of glutethimide 500 mg/day. After glutethimide there was a significant reduction in the AUC after the oral dose of labetalol, from 40,596 +/- 11,534 (mean +/- s.e. mean) to 22,057 +/- 6,276 ng ml-1 min (2P less than 0.05), and systemic bioavailability was reduced from 30.3 +/- 2.8 to 17.0 +/- 3.5% (2P less than 0.001). There was no significant change in labetalol plasma concentration-time curve (AUC) following an intravenous dose, half-life, volume of distribution, and plasma clearance. The oral and intravenous pharmacokinetics of labetalol were determined in six subjects before and after a 3 day course of cimetidine 1.6 g/day. After cimetidine there was a significant reduction in the volume of distribution of labetalol, from 520 +/- 51 to 445 +/- 24 1 (2P less than 0.05). The AUC of labetalol after the oral dose increased by 66%, from 51,029 +/- 7,950 to 84,772 +/- 19,444 ng ml-1 min (2P = 0.06). The systemic bioavailability of labetalol increased from 25.1 +/- 2.4 to 39.0 +/- 7.6% (2P = 0.06). There was no significant change in labetalol AUC after the intravenous dose, half life, and plasma clearance. There were no significant changes in resting heart rate and supine systolic and diastolic blood pressure following labetalol plus glutethimide, or labetalol plus cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

A study of the potential interactions between azapropazone and frusemide in man.

Ten healthy individuals received frusemide 40 mg orally for 7 days. Following a drug free period of 7 days they received azapropazone 600 mg twice daily for 7 days and then both treatments for a further 7 days. Sodium excretion fell from 141 +/- 16.8 mmol/day to 84.3 +/- 6.8 mmol/day (P less than 0.01) on initiation of azapropazone treatment. The natriuretic response to frusemide was unchanged by premedication with azapropazone. Urate excretion rose from 3.35 +/- 0.249 mmol/day to 4.98 +/- 0.365 mmol/day on initiation of azapropazone therapy but subsequently returned to baseline values. Plasma uric acid fell from 0.289 +/- 0.024 mmol/l to 0.167 +/- 0.0125 mmol/l (P less than 0.001) on azapropazone but rose to 0.186 +/- 0.0116 mmol/l (P less than 0.001) with the addition of frusemide. Azapropazone may cause sodium retention but after repeated administration frusemide still has a marked diuretic action. The hypouricaemic effect of azapropazone is only slightly antagonised by frusemide at the doses studied.

Adult↗
PubMed1984

Prophylaxis against ventricular arrhythmias in suspected acute myocardial infarction: a comparison of tocainide and disopyramide.

Five hundred and seventy one patients admitted to a coronary care unit with suspected acute myocardial infarction were considered for entry into a double-blind study. Two hundred and eighty-three patients were excluded, mainly because of recent treatment with beta-adrenoceptor blocking agents, life threatening arrhythmias requiring specific treatment and left ventricular failure presenting with hypotension or pulmonary oedema. Two hundred and eighty-eight entered the trial of whom 202 were subsequently confirmed to have had myocardial infarction. The effects of tocainide and disopyramide on ventricular arrhythmias were compared with placebo over the first 48 h period. The three treatments were given by a combination of intravenous infusion and oral administration. The doses used were tocainide 500 mg intravenously over 30 min plus 2800 mg orally over 48 h and disopyramide 150 mg intravenously over 30 min plus 1050 mg orally over 48 h. As judged by counts of ventricular premature beats, tocainide and disopyramide exerted a similar and significant antiarrhythmic effect. The median number of ventricular premature beats over the first 24 h of treatment was 58 on placebo compared with 30 on tocainide (P less than 0.05) and 19 on disopyramide (P less than 0.05). The corresponding figures for the second 24 h were 9, 6 and 2, respectively. There were eight deaths and three episodes of ventricular fibrillation with no significant differences between the three treatment groups. Sustained ventricular tachycardia was observed in one patient in the tocainide group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1984

The effect of posture at the time of administration on the central depressant effects of the new hypnotic zopiclone.

Nine healthy volunteers swallowed 7.5 mg zopiclone in the standing and lying positions on different occasions. Plasma concentrations of zopiclone and psychometric tests, including simple and complex reaction time, and critical flicker fusion threshold, were performed at regular intervals after drug administration. The results show that when the drug was swallowed in the supine position, there was a significant delay in the onset of the impairment of psychomotor function, with prolongation in time to peak impairment by 30-40 min (P less than 0.02). The overall impairment in psychomotor performance was found to be significantly less after administration of the drug in the supine position (P less than 0.005). Pharmacokinetic analysis revealed a prolongation in lag time of greater than 20 min before absorption began (P less than 0.002) after supine drug administration, with a significantly lower rate constant of absorption (P less than 0.02). Area under the plasma concentration-time curve extrapolated to infinity and rate constant of elimination were not significantly different between the two modes of administration. We conclude that to obtain a rapid and complete effect from the hypnotic zopiclone, the tablet should be swallowed in the standing position.

Adult↗
PubMed1984

Effects of chronic oral cimetidine on apparent liver blood flow and hepatic microsomal enzyme activity in man.

Cimetidine 200 mg three times daily and 400 mg at night was given to 10 subjects for four weeks. Apparent liver blood flow was measured by indocyanine green clearance and microsomal enzyme activity by antipyrine clearance, before and after cimetidine. There was no reduction in indocyanine green clearance but antipyrine clearance, as expected, was significantly reduced by 15% at four weeks. Chronic cimetidine treatment does not reduce apparent liver blood flow and is therefore unlikely to be of use in the treatment of portal hypertension. The cimetidine associated hepatic enzyme inhibition appears to persist with prolonged treatment. Therefore patients on chronic cimetidine remain vulnerable to certain drug interactions.

Adult↗
PubMed1984

Introducing guidelines into clinical practice.

The impetus for guidelines of practice has been accelerated by a worldwide trend towards insurance based systems of health care. In the past it has been the tradition for the clinician to order all the diagnostic procedures that conceivably might help to clarify what is wrong with a patient, or what course of treatment should be followed. This traditional view ignores the stubborn economic reality that resources are finite and that it is no longer possible to be both endlessly generous and continually fair. Making judgements about the need for, and value of, services now forms an important part of coping with this problem. Clinical practice has to strive to be as safe as possible and to produce a given benefit at a socially acceptable cost. Guidelines are recommendations, preferably developed by clinicians themselves, which describe how and when individual clinical activities should be offered in order to achieve these objectives. Utilisation review of current practice is a valuable source of information for the development of guidelines. In the United Kingdom the Royal College of Radiologists attempted to do this in connection with the use of pre-operative chest X-rays. In 1979 they published the findings of a multicentre review of 10,619 consecutive cases of elective non-cardiopulmonary surgery undertaken in 8 centres throughout the United Kingdom. Substantial variations were found in national practice. Use of pre-operative chest X-rays varied from 11.5% of patients in one centre to 54.2% of patients in another centre. The study also found that the chest X-ray report did not seem to have much influence on the decision to operate nor on the decision to use inhalation anaesthesia. The College study failed to find "any evidence at all for the effectiveness of pre-operative chest X-ray when used routinely" and it was estimated that even if the procedure was 10% effective the costs of avoiding one death would be approximately 1 million pounds. These findings provided the impetus for the College to develop guidelines for the use of pre-operative chest X-rays in hospitals in the United Kingdom. Creating a change in clinical practice through the introduction of guidelines is a three stage process: Stage I: introducing the idea of a change in practice. Stage II: introduction of guidelines into clinical practice. Stage III: sustained implementation of guidelines in clinical practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnostic Tests, Routine↗