The effective use of diagnostic radiology.
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Anesthesia, Inhalation↗
Biomedical subjects
C J Roberts
Publications and source records attributed to C J Roberts.
Diagnostic effectiveness of ultrasound in detection of neural tube defect. The South Wales experience of 2509 scans (1977-1982) in high-risk mothers.
2509 pregnant women were investigated between April 1, 1977, and March 31, 1980 (study 1), and April 1, 1980, and March 31, 1983 (study 2), to assess the effectiveness of diagnostic ultrasound in the diagnosis of neural tube defect (NTD) in women judged to be at high risk of NTD on the basis of raised serum alpha-fetoprotein or family history, or of other congenital malformation. The detection rate (sensitivity) for anencephaly was 100% in both studies. The detection rate for open spina bifida (OSB) improved from 33% in study 1 to 80% in study 2, specificity rose from 96% to 99%, the false-positive rate dropped from 57% to 9%, and the false-negative rate fell from 1% to 0.3%. Diagnostic ultrasound is likely to be conducted with greater vigilance and subjected to greater scrutiny than routine ultrasound because the patients have already been selected as being at high risk, the operators are more experienced, and their apparatus is likely to be more refined than that used for routine ultrasound. It is unlikely that the effectiveness levels for detection of OSB of 80% observed in this study could be sustained if diagnostic ultrasound were to be offered to all pregnant women. Consideration will need to be given to the question of whether an improved OSB detection rate will be worth the additional cost incurred in providing diagnostic ultrasound for every pregnant woman.
Anencephaly↗
Possible impact of audit on chest X-ray requests from surgical wards.
Use of chest X-rays in the surgical wards of two district general hospitals was monitored from 1976 to 1980. Utilisation fell by 42% in one hospital and by 26% in the other. There was no evidence that substantial reduction in the use of chest X-rays was associated with increased postoperative morbidity (as reflected in postoperative length of stay) or mortality. Indeed in one hospital there was a significant fall in postoperative length of stay and postoperative mortality during the study period. It is likely that publicity given to the overuse of preoperative chest X-rays and to the guidelines for more effective use which subsequently emerged has played an important part in bringing about the observed reduction in use of this investigation.
Costs and Cost Analysis↗
Blood composition and liver fat in post parturient dairy cows.
Cows from three different herds were used to investigate the relationship between plasma D(-)-3-hydroxybutyrate, serum free fatty acid and blood glucose concentrations and the amount of fat present in the liver in the week after calving. The study was particularly concerned with the diagnostic value of D(-)-3-hydroxybutyrate estimations. These estimations did not make a significant contribution to diagnosis of fatty liver nor did they reflect accurately the nutritional status of the cows.
3-Hydroxybutyric Acid↗
The efficacy of a serum screening service for neural-tube defects: the South Wales experience.
Serum-alpha-fetoprotein (AFP) levels were measured in more than 15 000 pregnant women in an investigation designed to examine the operational issues entailed in a large-scale population screening programme for antenatal detection of neural-tube defects. The proportion of open neural-tube defects (ONTD) terminated as a result of serum screening was 56.1% (66.6% for anencephaly and 40.7% for open spina bifida). The principle causes of poor efficacy were: failure of pregnant women to undergo screening (18.2% of ONTD were not screened); failure of the screening test to detect ONTD (20.4% of those screened were below the 90th centile); decisions against termination of detected ONTD (14% of ONTD detected by serum AFP were not terminated). Given present practices and knowledge it is doubtful whether overall efficacy levels above 65% for open spina bifida can be achieved under normal service conditions. The establishment of a regional or national screening programme on grounds of clinical efficacy alone may be premature. The decision would seem to hinge principally around a careful consideration of the economic issues.
Anencephaly↗
Skull X-ray guidelines.
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Costs and Cost Analysis↗
An investigation into the interaction between ethanol at low doses and the benzodiazepines nitrazepam and temazepam on psychomotor performance in normal subjects.
Ten healthy male volunteers received, in randomized order, temazepam 20 mg, nitrazepam 5 mg or placebo in combination with ethanol 0.1, 0.2 or 0.4 g/kg. Psychomotor tests were performed at regular intervals over 8 h. Ethanol alone at 0.4 g/kg significantly showed simple reaction time for between 30 and 60 min, whereas nitrazepam (5 mg) or temazepam (20 mg) plus the placebo alcohol dose (0.1 g/g) had no significant effect. The benzodiazepines and ethanol (0.2 and 0.4 g/kg) in combination showed no potentiation or prolongation of action. Both ethanol and the two benzodiazepines significantly reduced critical flicker detection in themselves and, in combination, had additive effects. Only nitrazepam and temazepam produced decreases in performance in the code substitution (DSST) test, and the time course of action of nitrazepam was markedly longer than that of temazepam. Ethanol alone had no detectable effect on immediate recall, prompted recall, learning, or word recognition tests. Both benzodiazepines reduced immediate and prompted recall and nitrazepam, in addition, reduced word recognition ability. It is concluded that the spectrum of CNS depressant actions of ethanol and the benzodiazepines are different and that there is no evidence of a potentiation or prolongation of their effects by concomitant administration of the doses used in the present study.
Adolescent↗
Multiple dose pharmacokinetics of ketoconazole and their effects on antipyrine kinetics in man.
Ketoconazole 200 mg was given twice daily for five days to eight subjects. The serum pharmacokinetics were examined with the first dose on day 1 and with the ninth dose on day 5. The serum half life of ketoconazole was 74.8 +/- 13.9 min (mean +/- S.D.) on day 1, and 155.9 +/- 32.7 min on day 5. On day 1 the area under the serum concentration time curve was 626.9 +/- 230.1 mg/l.min, and 1441 +/- 897.3 mg/l.min on day 5. Antipyrine kinetics were determined before and after the course of ketoconazole. There was no significant change in the clearance and half life of antipyrine. Ketoconazole in the doses used in this study does not appear to alter hepatic microsomal enzyme activity in man. The increased ketoconazole half life and area under the serum concentration time curve on day 5 were in part caused by food. Other mechanisms for these changes such as saturation of a tissue compartment or a change in the elimination of ketoconazole during chronic dosing, may also be responsible.
Adult↗
Plasma concentrations and central nervous system effects of the new hypnotic agent zopiclone in patients with chronic liver disease.
Eight healthy individuals and seven cirrhotic patients received 7.5 mg zopiclone orally. Two further cirrhotics received 3.75 mg. Plasma concentrations of zopiclone and psychometric tests including reaction time and critical flicker fusion threshold and electroencephalographic tracings were performed at regular intervals after drug administration. Peak plasma levels of zopiclone were similar in the two groups but the time to peak was delayed in the cirrhotics. Plasma zopiclone half-life was 8.53 +/- 0.83 h in the cirrhotics and 3.50 +/- 0.33 h in the healthy individuals. In the group of cirrhotics there was a negative correlation between zopiclone half-life and serum albumin concentration (r = -0.87). Zopiclone caused sedation in both groups. Reaction time was prolonged and critical flicker fusion threshold reduced in both groups. Recovery was delayed in the cirrhotics compared to the healthy subjects but was complete by 8 h. The size of the changes was somewhat greater in the cirrhotics but baseline observations differed between the groups. The mean dominant frequency was lower in the cirrhotics and fell slightly in that group after zopiclone administration. The response to zopiclone is delayed and exaggerated in cirrhosis. Precautions are therefore required when using this drug in patients with chronic liver disease.
Adult↗
Towards the effective use of diagnostic radiology in surgical practice: discussion paper.
This paper takes as an example of the cycle of evaluation the work of the Royal College of Radiologists in connection with the more effective use of preoperative chest X-ray. The work covers a six year period beginning with an observation of practice on a national sample in 1976, progressing to the comparison of existing practice with expectations in 1978. This was followed by the development of guidelines of practice which were disseminated informally, and formally through scientific papers and meetings from 1979. In 1981, practice was again observed in a pilot area to ascertain if the proposed guidelines had produced the desired affect. The results of this second review showed that the intentions of the guidelines had been achieved successfully, i.e. substantial reduction in utilization with considerable potential financial saving without any decrease in the original effectiveness or safety of the intervention. Thus this example shows the closing of the evaluation loop and the successful implementation of change.
Adult↗
Lipid deposition in different fiber types of skeletal muscle of periparturient dairy cows.
The intracellular deposition of neutral lipid in skeletal muscle of dairy cows before and after calving has been studied in biopsy samples taken from 72 cows in three herds. The amounts of neutral lipid in individual fibers were estimated using Oil red O-stained sections and an average value was calculated for each fiber type within a sample. Intracellular lipid deposition occurred mainly in type 1 fibers and reached its highest level one week after calving. The amount of lipid in muscle at this time showed a high correlation with the amount of lipid in liver and with the rate of lipid mobilization from tissue reserves.
Animals↗
Comparison of biochemical and histological methods of estimating fat content of liver of dairy cows.
The degree of fatty infiltration of the liver was estimated in two herds of dairy cows using biochemical and stereological methods. Estimation of hepatic triglyceride content biochemically or of fractional volume of fat in hepatocytes stereologically are both reliable methods of assessing fatty infiltration of the liver in the dairy cow. Estimation of hepatic total lipid content is not considered an acceptable alternative because the high basal level of non-triglyceride lipid masks the increase in hepatic triglyceride content which is characteristic of fatty liver.
Animals↗
Medical care as a risk-avoidance procedure: underwriting the cost of care in the UK.
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Adolescent↗
gamma-D-glutamylglycine as an antagonist of kainic acid on leech Retzius neurones.
Intracellular recordings were made from Retzius cells from the segmental ganglia of the leech, Hirudo medicinalis, gamma-D-Glutamylglycine, (50 microM), reversibly and preferentially antagonised the excitatory action of kainate, having no effect on actions of quisqualate or carbachol but at this concentration the antagonism was of short duration, reversing prior to washing off the gamma-D-glutamylglycine. However, higher concentrations of gamma-D-glutamylglycine (250-500 microM) reversibly antagonised both quisqualate and carbachol-induced excitatory responses, indicating a lack of specificity. The value of gamma-D-glutamylglycine in determining the possible site of action of kainate on leech Retzius cells is discussed.
Animals↗
The activity of cis and trans -2- (aminomethyl) cyclopropane carboxylic acids on GABA - related mechanisms in the central nervous system of Limulus and Periplanata and of mammals.
Some pharmacological actions of (+/-) - cis - and (+/-) - trans -2-(aminomethyl) cyclopropane carboxylic acids, conformationally restricted analogues of GABA, are described. The trans isomer (TAMP) was 17 and 4.5 times less active than GABA in hyperpolarising central neurones of Limulus and Periplanata and 10.8 times less active in displacing [3H]-muscimol from rat brain membranes. The cis isomer (CAMP) was ineffective on Limulus neurones at 35 mumoles, 650 times less active on Periplanata neurones and only weakly displaced [3H]-muscimol at 100 microM. Neither isomer inhibited synaptosomal uptake of [3H]-GABA at 100 microM. These data suggest that the invertebrate receptors studied respond to GABA in an extended conformation.
Animals↗
The pharmacology of Limulus central neurons.
1. Intracellular recordings have been made from neurons in the central nervous system of the horse-shoe crab, Limulus polyphemus. Neurons possess resting potentials between -40 and -60 mV, with action potentials ranging from 2-3 mV up to 60 mV in amplitude. Neurons also have excitatory and inhibitory postsynaptic potentials. 2. All the neurons studied are inhibited by GABA and excited by cholinomimetics. The GABA response is chloride mediated and reversibly antagonised by picrotoxinin but not by bicuculline or bicuculline methochloride or methoiodide. The cholinergic response is nicotinic and blocked by pentolinium, hexamethonium, chlorisondamine and dihydro-beta-erythroidine. 3. L-Glutamate can excite some cells, inhibit others and have a biphasic action, inhibition followed by excitation, on other cells. The inhibitory effect is chloride mediated and blocked by picrotoxinin. Ibotenate mimics the action of glutamate both in terms of inhibition and excitation but kainate and quisqualate only mimic the excitatory action of L-glutamate. 4. Dopamine, octopamine, 5-hydroxytryptamine and histamine excite some neurons while inhibiting others or have a biphasic action. Dopamine and octopamine normally have different effects on the same cell, suggesting they act via different receptors. Octopamine shows stereospecificity for the (-) isomer which is more than 100 times more active than the (+) isomer and octopamine is reversibly antagonised by phentolamine and cyproheptadine. 5. Proctolin has an excitatory action on these neurons and this effect is long lasting and can be potentiated by dibutyl cyclic AMP. 6. The pharmacology of Limulus central neurons is compared to the pharmacology of insect and crustacean central neurons. It is concluded that GABA and acetylcholine are central transmitters throughout the arthropods. It is also probable that L-glutamate and octopamine have a physiological role in the arthropod central nervous system. Proctolin appears to modify neuronal and muscle activity in the arthropods and has a modulatory or transmitter function.
Acetylcholine↗
The excitatory actions of a series of piperidine dicarboxylates on central neurons of the rat, snail, leech and horseshoe crab and on crab neuromuscular junction.
1. Intracellular recordings were made from Helix, Hirudo and Limulus central neurons and from Eupagurus leg muscle and extracellular recordings from rat lateral geniculate neurons. The actions of 2,3-, 2,4-, 2,5- and 2,6-piperidine dicarboxylates were tested on those preparations for both direct effects and interactions with the response to L-glutamate. 2. All four piperidine analogues were devoid of either reproducible direct or indirect effects on Helix and Limulus neurons save that the 2,5-analogue did mimic the action of L-glutamate on Limulus neurons which were inhibited by glutamate. 3. On Hirudo and rat neurons and on Eupagurus muscle, all four piperidines mimicked the action of L-glutamate, all were weak agonists on rat neurones while on Hirudo neurons the 2,5-analogue was the most potent but on Eupagurus muscle, the 2,3- and 2,6-analogues were the most potent. 4. All four piperidines potentiated the action of L-glutamate on rat and Hirudo neurons and on Eupagurus leg muscle and of muscle ejps. 5. The piperidine analogues indicate that there are differences between the glutamate receptors used in the present study and provide some supportive evidence that the preferred conformation for glutamate on crab leg muscle is partially folded while for Hirudo neurons it is more extended.
Animals↗