Biomedical subjects
Publications and source records attributed to B M Buckley.
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The running cost and clinical application of a new, portable, direct-injection, high-performance, liquid chromatograph for the measurement of theophylline was compared with conventional laboratory-based analysis by studying the two methods in two parallel chest clinics. Thirty-six patients were managed with the portable method and 33 by the conventional system. They were already receiving theophylline preparations for treatment of their asthma or chronic airflow limitation. Over the 12-week period of study, the percentage of patients with levels in the therapeutic range rose from 33% to approximately 87% in both clinics, but this change was achieved in only 6 weeks using the portable system. Patients whose theophylline levels were increased into the therapeutic range had improved symptom scores as measured by visual analogue scales but we were unable to demonstrate any significant change in spirometry. The cost of the portable system compared favourably with laboratory analysis, and had the additional benefit of quicker detection of non-compliance and facility for discussion with the patients at the time of consultation.
There is controversy about whether protein interferes with ion measurements using ion-selective electrodes. We have investigated the effects of changes in the salt-bridge composition of five commercially available analysers with open, membrane-restricted or porous frit-restricted reference electrode junctions on measurements of an albumin solution prepared by gel filtration. When the manufacturers' salt bridges were used, instruments with open or membrane-restricted junctions showed apparent increases in the activity of ionized calcium, sodium and potassium in the presence of protein. When the hypertonic bridge solutions were replaced with 150 mmol/L potassium chloride this increase disappeared. The instrument with a porous frit-restricted junction showed no protein effect, but its response to changes in sample sodium chloride concentration in protein-free solution suggested that its junction was functionally equivalent to that formed with an isotonic sodium chloride bridge. Our results emphasize that liquid junction design and composition affect ion measurements in protein-containing solutions and suggest that the use of hypertonic bridge solutions for biological samples needs to be re-examined.
The substance concentration of ionized calcium (cCa2+) in blood, plasma or serum preanalytically may be affected by pH changes of the sample, calcium binding by heparin, and dilution by the anticoagulant solution. pH changes in whole blood can be minimized by anaerobic sampling to avoid loss of CO2, by measuring as soon as possible or by storing the sample in iced water to avoid lactic acid formation. cCa2+ and pH should be determined simultaneously. Plasma or serum: if centrifuged in a closed tube and measured immediately the pH of the sample will be close to the original value. If delay has occurred between centrifugation and the measurement, causing substantial loss of CO2, equilibration of the sample with a gas mixture corresponding to PCO2 = 5.3 kPa prior to the measurement is recommended. Conversion of the measured values to cCa2+ (7.4) is only valid if the pH is in the range 7.2-7.6 Ca2+ binding by heparin can be minimized by using either of the following: a final concentration of sodium or lithium heparinate of 15 IU/ml blood or less, by use of calcium titrated heparin with a final concentration less than 50 IU/ml blood. Dilution effect can be avoided by use of dry heparin in capillaries or syringes. When heparin solutions are used errors due to dilution or calcium binding can be reduced using syringes with a heparin solution containing free calcium ions corresponding to the mean concentration of ionized calcium in normal plasma. Conditions for blood collection, storage, and transport to avoid preanalytical errors are described.
The substance concentration of ionized calcium (cCa2+) in blood, plasma or serum preanalytically may be affected by pH changes of the sample, calcium binding by heparin, and dilution by the anticoagulant solution. pH changes in whole blood can be minimized by anaerobic sampling to avoid loss of CO2, by measuring as soon as possible or by storing the sample in iced water to avoid lactic acid formation. cCa2+ and pH should be determined simultaneously.
The pattern of enzyme changes in elderly fallers admitted to an acute geriatric unit was investigated. Creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were measured daily for 3 days after admission in all patients in whom a fall preceded admission. Of 270 patients, 52 (19%) had fallen prior to admission, of whom five (10%) had an acute myocardial infarction (AMI). In fallers without an AMI in whom a history was available, CK and AST activities were significantly higher (p less than 0.05) in patients who had spent more than 1 hour on the floor than in those who had spent less than 1 hour. No other clinical factor affected enzyme activities. CK and AST activities were raised in 66% and 40%, respectively, of fallers without an AMI. Elevation of CK and AST activities in elderly fallers is likely to be a result of the fall itself rather than of an AMI.
The diagnosis of acute myocardial infarction (AMI) in the elderly is difficult and often depends on the results of investigations. In a 3-month prospective study, 270 patients admitted to an acute geriatric unit were studied to determine the most effective diagnostic strategy for the diagnosis of AMI, and to assess the value of screening acute geriatric admissions for AMI. Patients were assessed clinically and investigated with serial electrocardiograms and measurements of serum creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase activities on three consecutive days after admission. Measurement of serum activity of CK and AST had a diagnostic sensitivity of 100% and specificity of 86.8% for AMI. This was the optimum combination of cardiac enzymes in the diagnosis of AMI. Although electrocardiograms on the first two days of admission had a low diagnostic sensitivity (33.3%) their usefulness was their high positive predictive value (100%) when characteristic of an AMI. AMI was considered in the differential diagnosis of 79 patients (29%). All 25 patients (9%) who had an AMI were in this group, and therefore screening all geriatric admissions for AMI is not clinically justified.
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The standard Bentiromide test and a new modified test using p-aminosalicylic acid (PAS) as a pharmacokinetic marker for p-aminobenzoic acid (PABA) have been evaluated in the detection of pancreatic exocrine insufficiency in children. The conventional two day test using a colorimetric assay for urinary PABA discriminated poorly between five children with pancreatic insufficiency and 13 others with normal pancreatic function. Two further groups of patients, comprising 28 with pancreatic exocrine insufficiency and 20 with normal pancreatic function underwent the modified test, and urine samples were analysed by high performance liquid chromatography. The results showed a complete separation between groups. The use of PAS eliminates a number of sources of error inherent in a two day Bentiromide test and provides a simplified and accurate diagnostic test for pancreatic insufficiency. The PABA-PAS modified test enables collection of the urine to be done during a single six hour period.
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Experience in clinical chemistry of direct reading ion-selective electrode analysers for the measurement of plasma Na+ and K+ concentrations has shown that the results obtained on any specimen may vary significantly from one make of instrument to another. To overcome these differences, the European Working Group on ISEs of the IFCC Expert Panel on pH, Blood Gases and Electrolytes have proposed that instruments should be standardised to report Na+ and K+ concentrations in undiluted plasma to agree with flame emission spectrometry in samples with normal plasma water bicarbonate concentrations and normal pH. In designing and setting the calibration of a new ISE analyser for Na+ and K+, the Corning 614, the manufacturer has attempted to satisfy this proposal using a large number of specimens obtained from patients. This paper presents details of the procedure used and the results of an independent evaluation of its validity in routine clinical practice.
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An epidemiologic screening survey was conducted in 325 male industrial workers to investigate the relation between serum total and ionized calcium concentrations and blood pressure. No relation was found. Previous reports of lower serum ionized calcium levels in hypertensive patients may be related to methodologic deficiencies both in the selection of subjects and in ionized calcium measurement. These data do not support the concept that increased blood pressure levels are related to calcium deficiency or to abnormal plasma calcium homeostasis.
Investigation of the uptake and metabolism of drugs by organs such as the liver may allow assessment of specific aspects of organ function. Rifampicin, when orally administered, is transported into the hepatocyte from portal blood and thence passes, with its deacetylated metabolite, into the systemic circulation and into bile. This paper reports an investigation of the pharmacokinetics of a sub-therapeutic oral dose of rifampicin in healthy subjects, in patients with cirrhosis and in subjects with Gilbert's syndrome. The areas under the plasma concentration curves (AUC) in patients with cirrhosis were significantly greater than in healthy subjects. Subjects with Gilbert's syndrome had decreased AUCs compared with healthy subjects and were clearly distinguished from patients with cirrhosis. Rifampicin concentration in serum was measured by HPLC using a novel direct injection technique.
Ethylene glycol in plasma, urine or dialysis fluid is analysed as the phenylboronate derivative by mixing with acetonitrile/acidified 2,2-dimethoxypropane containing phenylboronic acid. After centrifugation, a portion of the supernatant is analysed directly by gas-liquid chromatography using a 3% OV-101 column at 150 degrees C and flame-ionisation detection. Propane-1,3-diol is used as a reactive internal standard. The limit of accurate measurement is at least 0.1 g/L and the linear range extends up to 5.0 g/L. No sources of interference have been identified.
A manual column-switching technique is described for the measurement of phenytoin, phenobarbitone, carbamazepine, and carbamazepine 10,11-epoxide. The analytical system is designed to be portable for use at the out-patient clinic and comprises an isocratic pump, UV detector and injection valve, together with a preparation column. Diluted plasma or serum is injected, without pre-extraction, onto a preparation column which replaces the sample loop on the injection valve. After washing unwanted material to waste, the preparation column is switched in-line with the analytical column, where separation of analytes occurs. The precision, accuracy and carryover of this extra-laboratory system are comparable with those obtained with laboratory-based immunoassay systems. Operation of the system allows the reporting of results within 5 min of sample injection and requires no specialist skills. The technique should be of particular interest to district general hospital laboratories where workload does not justify the cost of an automated HPLC system as the total capital cost is comparable to that of a portable glucose analyser. In contrast to immunoassay systems consumable costs are minimal. The equipment is easy to transport and may be used in the out-patient department to provide an analytical service similar to that provided for the determination of prothrombin time at the anticoagulant clinic.