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Biomedical subjects

M G Scott

Publications and source records attributed to M G Scott.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hemoglobin Raleigh as the cause of a falsely increased hemoglobin A1C in an automated ion-exchange HPLC method.

Irreversible glycation of the hemoglobin A0 (HbA0) beta chain leads to the production of HbA1C, which can be used to monitor long-term blood glucose control in patients with diabetes mellitus. HbA1C is less positively charged than nonglycated HbA0, and this decrease in charge is the basis of ion-exchange and electrophoretic methods that measure HbA1C. We recently identified a sample that appeared to contain 46% HbA1C by an automated ion-exchange HPLC method (Bio-Rad Variant) but only 3.8% by an immunoinhibition latex agglutination method. A combination of traditional and mass spectrometric protein analysis and genomic DNA analysis of the Hb beta chain and genes revealed that the patient was heterozygotic for Hb-Raleigh, a variant containing a valine-->alanine substitution at position 1 of the beta chain. The amino-terminal alanine in this variant Hb is posttranslationally modified by acetylation, leading to a charge difference similar to glycation and making the behavior of HbA1C and Hb Raleigh virtually identical in the ion-exchange HPLC method. This observation suggests that it is important to confirm HbA1C values in excess of 15%, especially if they are not consistent with the clinical picture, by an independent HbA1C method such as immunoassay or boronic acid affinity chromatography. However, for this particular variant Hb, even these latter methods might be misleading, because the acetylated N-terminal amino acid of the Hb-Raleigh beta chain cannot be glycated.

Aged↗
PubMed1998

Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population.

Measurement of blood concentrations of cystatin C (cysC), a cysteine protease inhibitor present in human plasma, has been suggested for use as an indicator of glomerular filtration rate (GFR) in a manner analogous to the use of plasma creatinine (SCR). In this study, cysC and SCR were measured in plasma from pediatric patients (4-19 years) with renal disease for whom a "gold standard" measurement of GFR via inulin clearance (C(IN)) was available. The data analyses were divided into two age groups: group A (4-12 years, n = 26) and group B (12-19 years, n = 34). For both age groups, the linear correlation coefficient of [cysC](-1) vs C(IN) (mL/min/1.73 m2) (r = 0.765 for group A and r = 0.869 for group B) was less than that of the linear correlation coefficient of [SCR](-1) vs C(IN) (r = 0.841 for group A and r = 0.892 for group B). As a single measurement for detection of abnormal GFR, however, the optimum receiver-operator characteristic point for cysC measurement (for group A at cysC >1.2 mg/L, sensitivity = 80%, specificity = 91%; and for group B at cysC >1.4 mg/L, sensitivity = 87%, specificity = 100%) was numerically superior to that for SCR measurement (for group A at SCR >8.0 mg/L, sensitivity = 67%, specificity = 100%; and for group B at SCR >9.0 mg/L, sensitivity = 91%, specificity = 91%), using a reference value for normal GFR of C(IN) > 90 mL/min/1.73 m2. However, these differences were not statistically significant. CysC measurement appears to be broadly equivalent to SCR measurement for estimation of GFR in pediatric patients.

Adolescent↗
PubMed1997

HPLC method for monitoring SDZ PSC 833 in whole blood.

P-glycoprotein (Pgp) is a 170-kDa membrane transporter that mediates drug efflux and is an effector of multidrug resistance. SDZ PSC 833 (PSC), a nonimmunosuppressive cyclosporine that potently modulates Pgp, is currently under clinical evaluation in patients with cancer. We have developed a reversed-phase HPLC assay for determining PSC blood concentrations that utilizes a step gradient with linear segments to resolve PSC into two distinct peaks (likely to be keto and enol isomers). To clinically validate the assay, PSC concentrations were obtained by HPLC from nine patients receiving oral doses of 5 mg/kg every 6 h. Values ranged from 0.91 to 5.4 mg/L during the dosing period, comparable with concentrations of PSC that modulate Pgp in vitro. In addition, we investigated the immunoreactivity of the Abbott TDx cyclosporin A (CsA) monoclonal whole-blood assay for PSC. The TDx CsA assay cross-reacts approximately 17% with PSC as determined by adding known amounts of PSC to whole blood. When PSC concentrations obtained by the TDx CsA assay were divided by 0.17, we found agreement between the TDx CsA assay and the HPLC PSC assay for samples from nine patients.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Blood substitutes: evolution and future applications.

The development of oxygen-carrying blood substitutes has progressed significantly in the last decade with phase I and phase II clinical trials of both hemoglobin-based and perfluorocarbon-based oxygen carriers nearing completion. As these products approach clinical use it is important for the laboratory medicine community to be aware of their effects on routine laboratory testing and the settings in which they might be used. Here we review the forces driving the development of oxygen-carrying blood substitutes, the clinical settings in which they might be used, the major categories of oxygen carriers in clinical trials, and the challenges faced by these products as they approach clinical use.

Animals↗
PubMed1997

Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests.

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.

Animals↗
PubMed1996

Using bar-code technology to capture clinical intervention data in a hospital with a stand-alone pharmacy computer system.

The use of bar-code technology to capture data on pharmacists' clinical interventions is described. At a hospital in Northern Ireland, patient-specific information could not be accessed through the pharmacy computer system. A system comprising six hand-held bar-code readers and software for downloading data was purchased. The pharmacy staff selected a range of fields for recording a wide array of data on clinical interventions, including the outcomes. Patient details that could not easily be bar-coded had to be recorded manually. The process was evaluated over three four-week cycles, with the data fields being revised after each cycle and the interventions being judged for their clinical appropriateness and their conformance to inhouse standards. After the third cycle, the need for manual recording of information was eliminated. A total of 857 interventions were made during the three cycles. Performance met or exceeded the standard for 7 (50%) of 14 indicators for the first cycle, 8 (53%) of 15 for the second cycle, and 13 (81%) of 16 for the final cycle. For all three cycles, the majority of the interventions were important and resulted in an improvement in the standard of care. A bar-code-driven data collection system successfully replaced a manual system for documenting pharmacists' clinical interventions.

Clinical Pharmacy Information Systems↗
PubMed1996

A pharmacokinetic and pharmacodynamic evaluation of buffered sublingual captopril in patients with congestive heart failure.

OBJECTIVE: The pharmacokinetics and pharmacodynamics of buffered sublingual captopril were assessed in patients with congestive heart failure (CHF). METHODS: The study was carried out in a randomised single-blind cross-over fashion (n = 6, 4 males and 2 females) and involved two study days, at least 7 days apart. Baseline measurements were carried out for plasma renin activity (PRA), blood pressure (B.P.) and heart rate (H.R.). Captopril (12.5 mg) was administered sublingually with dibasic potassium phosphate which maintained salivary pH at 7, or perorally with 100 ml of water. Further B.P., H.R. measurements and venous blood samples were taken over a 3 hour period post-drug administration. Blood samples were analysed for captopril and PRA levels. RESULTS: tmax after buffered sublingual administration of captopril, which ranged from 40-60 min (median = 40 min), was significantly shorter than after peroral administration (range 60-120 min, median = 90 min). Cmax was slightly greater after buffered sublingual than after peroral administration with mean values of 108.2 vs. 94.0 ng.ml-1. AUC values were similar after both routes of administration. Systolic and diastolic B.P. vs. time profiles for each administration method were significantly different i.e. sublingual administration produced an earlier reduction in B.P., however, HR did not differ significantly between the two routes. CONCLUSION: The data indicate that this novel administration method of captopril leads to an increased rate, but an unchanged extent of captopril absorption, suggesting a modest therapeutic advantage with the use of buffered sublingual captopril if a rapid reduction in blood pressure is required.

Administration, Sublingual↗
PubMed1996

Impact of point-of-care testing on patients' length of stay in a large emergency department.

We prospectively investigated whether routine use of a point-of-care testing (POCT) device by nonlaboratory operators in the emergency department (ED) for all patients requiring the available tests could shorten patient length of stay (LOS) in the ED. ED patient LOS, defined as the length of time between triage (initial patient interview) and discharge (released to home or admitted to hospital), was examined during a 5-week experimental period in which ED personnel used a hand-held POCT device to perform Na, K, Cl, glucose (Gluc), and blood urea nitrogen (BUN) testing. Preliminary data demonstrated acceptable accuracy of the hand-held device. Patient LOS distribution during the experimental period was compared with the LOS distribution during a 5-week control period before institution of the POCT device and with a 3-week control period after its use. Among nearly 15 000 ED patient visits during the study period, 4985 patients (2067 during the experimental period and 2918 during the two control periods) had at least one Na, K, Cl, BUN, or Gluc test ordered from the ED. However, no decrease in ED LOS was observed in the tested patients during the experimental period. Median LOS during the experimental period was 209 min vs 201 min for the combined control periods. Stratifying patients by presenting condition (chest pain, trauma, etc.), discharge/admit status, or presence/absence of other central laboratory tests did not reveal a decrease in patient LOS for any patient subgroup during the experimental period. From these observations, we consider it unlikely that routine use of a hand-held POCT device in a large ED such as ours is sufficient by itself to impact ED patient LOS.

Blood Chemical Analysis↗
PubMed1995

Audit of antibiotic usage in medium-sized general hospital over an 11-year period. The impact of antibiotic policies.

The objective of the present study was to evaluate trends in antibiotic expenditure over an 11-year period (1982-1992) in a 370-bed district general hospital in Northern Ireland and to examine the impact of two separate antibiotic policies on antibiotic usage. A further objective was to examine the attitudes of prescribers to the second policy. Drug utilization review was used to collect information on antibiotic expenditure and usage before and after introduction of separate antibiotic policies in 1985 (not intensively monitored) and 1989 (intensively monitored). A main questionnaire was used to determine the attitudes of prescribers. The first policy (1985) showed no benefits with regard to the number of antibiotic entities stocked (45 before, 45 after), number of dosage units issued (9.3% increase) or expenditure (33.3% increase). The 1989 policy led to significant reductions in the number of antibiotic entities stocked (28.9%), number of antibiotics issued (11.9%) and expenditure (6.1%). Expenditure began to spiral upwards when active monitoring of the second policy was suspended. The majority of prescribers (87.2%) who responded to the questionnaire (56.5% response rate) felt that the 1989 policy made a positive contribution to antibiotic usage in the hospital.

Anti-Bacterial Agents↗
PubMed1995

The effect of pH on the buccal and sublingual absorption of captopril.

The effect of pH on the buccal and sublingual absorption of captopril was evaluated using in vitro techniques and human studies. Partitioning of captopril into n-octanol was lowest over the pH range 5 to 8 and highest at pH values 3, 4 and 9. Using the buccal absorption technique, the partitioning of captopril (2 mg) was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8, and 9). Lowest buccal partitioning occurred at pH 3 while maximal buccal partitioning occurred at pH 7. These data clearly indicated that the buccal absorption of captopril pharmacokinetic and pharmacodynamic parameters were determined after administration of buffered sublingual captopril (pH 7, optimal hP for absorption as determined from the buccal partitioning data) and unbuffered sublingual captopril. The study was performed in eight healthy volunteers in a randomised single-blind cross-over fashion. The tmax for captopril was found to be approximately 11 minutes earlier after buffered versus unbuffered sublingual administration and AUC0-30 min increased by approximately 30% in the case of buffered captopril. Cpmas, AUC0-180 min and relative bioavailability did not differ between the buffered and unbuffered administration. Pharmacodynamic parameters (BP, heart rate and plasma renin activity) did not differ significantly between buffered and unbuffered sublingual administration. The increased rate of captopril absorption after buffered sublingual administration was small and is likely to offer little therapeutic advantage over conventional sublingual formulation.

1-Octanol↗
PubMed1995

Current status of US programs for training clinical laboratory scientists and anticipated impact of healthcare reform.

We surveyed directors of medical technology (MT) and postdoctoral clinical chemistry (CC) training programs and of clinical pathology (CP) and combined anatomic/clinical pathology (AP/CP) residency programs regarding the number, quality, training emphasis, and job-placement experience of trainees for 1985-95 as well as the directors' opinions on the impact of "healthcare reform." Responses were received from directors of 94 of 249 (38%) MT programs, 14 of 15 (93%) CC programs, and 63 of 138 (46%) pathology residency programs. In all four categories the numbers of trainees have increased steadily over the last 5 to 7 years but are expected to remain stable or decrease slightly. Directors of MT and CC programs expect increasing difficulty placing their graduates; directors of AP/CP and CP residency programs do not. Although > 60% of MT graduates have entered private hospitals, this is anticipated to decrease, with a concomitant increase in university hospital placements. Of the AP/CP residents, > 60% and < 5% accepted service- and research-oriented positions, respectively. In contrast, 83% of CP residents entered university hospitals, with half of these taking research-oriented positions. Among CC graduates, 41% joined university hospitals and 10-15% accepted positions in each of either private hospitals or industry or reference laboratories. The emphasis of training varies, with clinical service and pathophysiology the major focus in AP/CP programs. CP and CC programs take two distinct approaches--some accentuating management, and others emphasizing research. Finally, MT program directors appear the most optimistic regarding the opportunities that healthcare reform may present.

Chemistry, Clinical↗
PubMed1995

Clinical utility of biochemical analysis of cerebrospinal fluid.

In addition to microbial culture, cytology, and immunological studies, physicians rely on the clinical chemistry laboratory for biochemical analysis of patients' cerebrospinal fluid (CSF). However, apart from routine glucose and protein determinations, the clinical value of other CSF analytes is often unclear. Here, we review the literature pertaining to the use of CSF biochemical measurements in managing patients with infectious disease, neoplasia, stroke and trauma, and dementia. Although a small number of studies demonstrate potential usefulness of some markers, we conclude that, without further study, the data are insufficient to support the routine clinical use of most of the analytes examined.

Central Nervous System Neoplasms↗
PubMed1994

Evaluation of a new colorimetric assay for serum lithium.

Using patient samples (n = 175) collected in our clinical chemistry laboratory, we have undertaken an analysis of a new colorimetric dry slide-based serum lithium (Li+) assay from Eastman Kodak for its Ektachem instrumentation series. Analyzer imprecision was acceptable, and good correlation was seen between the Ektachem assay and an ion-selective electrode (ISE)-based assay currently in use in our laboratory (r = 0.99). At all concentrations tested, potassium (K+), triglycerides, or bilirubin did not detectably interfere with the Ektachem determination of Li+. At concentrations within the reference range (135-145 mmol/L), sodium (Na+) did not affect the Ektachem Li+ determination. A slight Na(+)-dependent positive bias in the Li+ determination was evident at 157 mmol/L, but became clinically significant (> or = 0.2 mmol/L) only at physiologically extreme concentrations (> 188 mmol/L) of Na+. Very high concentrations (> 325 mg/dl) of hemoglobin also were found to cause a clinically significant positive bias. We conclude that the determination of Li+ by the Kodak Ektachem is precise, accurate, and adequately free from bias due to common interferents or other monovalent cations, and, therefore, is an acceptable alternative to currently available methods for the monitoring of serum LI+.

Bilirubin↗
PubMed1994

Pulmonary aspiration in mechanically ventilated patients with tracheostomies.

The purpose of this descriptive study was to evaluate feeding aspirations in adult patients receiving long-term mechanical ventilatory support, including the incidence of aspirations, the frequency of silent (clinically inapparent) aspirations, and differences between aspirators and nonaspirators. Aspiration data were determined by review of videofluoroscopic (VF) tapes of modified barium swallow procedures performed on 83 medically stable patients admitted to a chronic ventilator unit. Demographic and clinical variables were obtained from review of subjects' medical records. Forty-two subjects (50 percent) aspirated during VF testing and 37 of 48 (77 percent) aspirations were silent. Subjects who aspirated were significantly older than those who did not aspirate (p = 0.007). Swallowing disorders were common, particularly disturbances of the pharyngeal phase. We conclude that feeding aspiration is seen frequently in patients with tracheostomies receiving prolonged positive pressure mechanical ventilation. Advanced age increases the risk of aspiration in this population. Episodes of aspiration are not consistently accompanied by clinical symptoms of distress to alert the bedside observer to their occurrence.

Adult↗