Automation of toxicological screenings on a Hewlett Packard Chemstation GC-MS system.

OBJECTIVES: To optimize the interpretation of GC-MS toxicological screenings (i.e., to facilitate ion specific queries, create custom reports specifically adapted to each confirmation procedure, and eliminate redundant and/or inaccurate data on library search reports). DESIGN AND METHODS: The MS Chemstation software of the Hewlett Packard 5972 is constructed in a modular way. We made extensive modifications to two modules, the data analysis and the report modules, using the built-in MS Chemstation macro language. RESULTS: Ion specific queries were automated for over 60 commonly encountered analytes. Custom reports were created for the confirmation of positive drugs-of-abuse immunoassay results. With the incorporation of decision support rules into the data processing and the reporting phases, we obtained sensitive, accurate, and concise reports. CONCLUSIONS: The MS Chemstation software can be tailored to the needs of each individual application. The incorporation of a rule-based decision support system enhances the quality of the GC-MS toxicological screenings and results in faster, easier, and more reliable processing.

Effects of non-pharmacological sympathetic sudomotor denervation on sweating in humans with essential palmar hyperhidrosis.

OBJECTIVE: Quantitative sweat production and -ionic composition in Essential Hyperhidrosis (EH), and the effects of T2-T3 thoracoscopic sympathicolysis (TS) hereon, are unknown. Standardised pilocarpine iontophoresis sweat tests were performed before and after TS in order to study these issues. DESIGN AND METHODS: Pilocarpine iontophoretic sweat tests measuring maximal sweat production (mg) and sweat Na+, K+ and Cl- concentrations (mMol/L) were performed on both forearms of 10 EH patients, before and six weeks after TS, and in normal volunteers. RESULTS: As compared to normals, preoperative maximal sweat production was 30% higher (199.4 +/- 68.8 (SD) vs. 150.6 +/- 45.6 mg) in EH patients; due to type II error, however, statistical significance was not reached. Na+ and Cl- concentrations were similar, and K+ concentration was slightly lower in EH patients. After TS, sweat production had decreased to equal levels as in normals (149.1 +/- 52.1 mg), whereas the Na+ (from 33.6 +/- 6.9 to 51.0 +/- 6.4 mMol/L), Cl- (from 21.5 +/- 6.6 to 37.2 +/- 7.1 mMol/L) and K+ (from 7.5 +/- 1.3 to 8.6 +/- 2.2 mMol/L) concentrations had increased. CONCLUSIONS: EH patients present 30% higher maximal sweat production at their forearms. This increase may be due to an increased activity of the adrenergic component of sweat gland innervation. The post-TS increase in Na+, Cl- and K+ concentrations suggests that the adrenergic component of sweat gland innervation in itself decreases sweat ion concentrations.

Electrophoresis of serum protein to detect alpha 1-antitrypsin deficiency: five illustrative cases.

We describe five cases of severe alpha 1-antitrypsin (AAT) deficiency to illustrate the importance of visual inspection of electrophoretic patterns of serum proteins. In four patients the diagnosis of AAT deficiency was clinically unsuspected; in the other patient, the electrophoretic pattern was the first clue to confirm the diagnosis. Densitometric scanning of these patterns invariably overestimated the concentration of alpha 1-globulin. By visually inspecting electrophoretic strips instead of relying on densitometry, clinical chemists can help detect AAT deficiency earlier.

Urinary and plasma catecholamines and urinary catecholamine metabolites in pheochromocytoma: diagnostic value in 19 cases.

We review our data on the measurement of catecholamines and their metabolites in 19 patients with pheochromocytoma. All the assays were specific high-performance liquid chromatographic procedures with electrochemical detection. The assay of fractionated metanephrines was 100% sensitive. Normal values for both urinary norepinephrine and epinephrine were found in two asymptomatic patients with pheochromocytoma. Normal values for 3-methoxy-4-hydroxymandelic acid (VMA) were found in two patients with pure epinephrine-secreting tumors and in one patient with multiple endocrine neoplasia type II. Plasma catecholamines were usually less increased than their urinary counterparts. We recommend the specific measurement of norepinephrine and epinephrine as the initial test for patients with suggestive symptoms, and specific measurement of normetanephrine and metanephrine for patients in whom an adrenal mass is incidentally found. We argue against the use of total metanephrines, total catecholamines, and VMA because of their lack of diagnostic sensitivity.

Acute and chronic intoxication with carbromal preparations.

An important number of acute intoxications can be ascribed to the abuse of, until now, non-prescription carbromal preparations. Prolonged use of these drugs also leads to chronic intoxication with bromide accumulation. The clinical features and treatment of three suicidal Obral overdoses and of two patients presenting with bromism are presented. Laboratory findings, from admission to recovery, consist of qualitative TLC and quantitative HPLC drug assays in body fluids and the determination in plasma of the two competing ions chloride and bromide. The high frequency of acute intoxications and carbromal induced bromism stresses the need to bring these preparations under prescription.

Agarose electrophoresis and inhibitor tests for isoamylase determination can give complementary clinical information.

We report the presence of an extremely high proportion of "aged" amylase in the serum and cyst fluid of a patient with a pancreatic pseudocyst. A salivary amylase inhibitor test helped us to differentiate these "aged" pancreatic amylases from salivary fractions having a similar electrophoretic mobility.

Plasma catecholamine concentrations in essential hyperhidrosis and effects of thoracoscopic D2-D3 sympathicolysis.

Essential hyperhidrosis (EH) is caused by a poorly understood overactivity of the sympathetic fibres passing through the upper dorsal sympathetic ganglia D2 and D3. These ganglia are also in the pathway of the sympathetic innervation of the heart and lungs. Therefore, although the predominant sympathetic neurotransmitter at the eccrine sweat glands is acetylcholine, the plasma concentration of noradrenaline (NA) (which is the main sympathetic neurotransmitter at the end organs including the heart and the lungs) may be elevated. Furthermore, as there are some indications for generalized sympathetic overactivity in EH, the plasma concentration of adrenaline (A) may also be elevated. Plasma levels of NA and A were therefore determined in 13 EH patients before and after thoracoscopic D2-D3 sympathicolysis (TS). Preoperative NA and A plasma levels were all within the normal limits used in our laboratory. After TS, mean NA plasma levels are significantly decreased, whereas mean A are unchanged. We conclude that sympathetic overactivity in EH is limited to the upper dorsal sympathetic ganglia and that some of the cardiovascular and pulmonary effects that are observed after TS may be associated with the decrease in NA.

Lorazepam fast-dissolving drug formulation (FDDF) and intravenous administrations as anaesthetic premedicants: a pharmacokinetic analysis.

The pharmacokinetics of lorazepam premedication were studied in 16 patients using two different formulations (intravenous and FDDF oral administrations). Arterial blood samples were taken at intervals for up to 600 min after administration of 4 mg of each formulation, and plasma lorazepam concentrations were determined by gas-chromatography with electron capture detection. Concentration-time data for individual subjects were analysed by model-independent methods. The derived pharmacokinetic parameters indicated a rapid distribution (median T1/2 lambda 1 i.v. = 15.2 min, median T1/2 lambda 1 oral = 31.6 min) into a steady-state volume of distribution approximating total body water, with a long elimination half-life and a low clearance. Vdss and clearance were similar with both treatments. The absorption of FDDF lorazepam was rapid in half of the patients and provided a high plasma concentration of lorazepam (Cmax = 61.8 ng ml-1) in a short time interval (Tmax = 58 min), but there were considerable inter-individual differences. This variability in absorption might explain why premedication with FDDF lorazepam is sometimes less effective than expected.

A survey of medical informatics in Belgium.

The Belgian Society for Medical Informatics (MIM) organized a survey in 1986 in order to assess the present state of development of medical informatics in Belgium. Questionnaires were sent to hospitals, laboratories, private practitioners and pharmacists, as well as to social security organizations and software industries. The response rate was higher in hospitals (93%) than in any other category. Results showed a large number of computerized hospitals (93% of general acute care hospitals and 91% of psychiatric hospitals). There has been a sharp increase (+ 15%) in computerization of the admission, accounting and billing procedures since 1985, most likely in relation with administrative rules issued by the Belgian Government. The same trend (+ 20%) has been observed for computer applications in clinical laboratories, between 1984 and 1985. There is almost one computer terminal for ten beds in the hospitals with more than 200 beds in 1986. This figure exemplifies the present trend to on-line access to data. Computerized instrumental aids to medicine such as text processing, imaging or computerized interpretation of signals have known a rapid extension during recent years, although less comprehensive than administrative applications in hospitals and in social security organizations. The present state of other applications in medicine (general practice, pharmacy, etc.) was more difficult to assess as those information systems remain more pinpointed. In all medical fields, there appears to be a new rise in computer programs offered by software companies.

The respective effects of serum thyroxine and triiodothyronine on serum thyrotropin and lipid parameters in endemic juvenile hypothyroidism.

The respective effects of serum total T4 concentration and of serum total T3 concentration on serum TSH concentration and on lipid parameters were compared in 84 7- to 16-year-old children of the Northern Zaire goitre endemia classified in group A (T4 greater than 77 nmol/l and T3 greater than 1.69 nmol/l), B (low T4, normal T3) and C (low T4, low T3). Mean serum TSH level was normal in group A (2.3 mU/l), it raised to 39.4 mU/l in group B (p less than 0.001) and to 166.3 mU/l in group C (p less than 0.001 vs A and B). Low density lipoprotein cholesterol and apoprotein B were increased in group B vs A (p less than 0.05) and in group C vs A (p less than 0.001) and B (p less than 0.001 for apoprotein B; not significant for cholesterol). High density lipoprotein cholesterol and apoprotein A1 were similar in the three groups. Mean serum triglyceride level, not different in groups A and B, was doubled in group C (p less than 0.001). Multiple regression analysis showed that serum TSH, apoprotein B, and triglyceride levels were influenced by both thyroid hormones concentrations with a predominant effect of serum T4 on the first two parameters and of serum T3 on the last one. In conclusion, low serum T4 with normal T3 concentrations resulted in an increase in serum TSH and in an altered lipid metabolism; it clearly represented an hypothyroid state.

Iron and total iron-binding capacity in serum of patients receiving iron-dextran: Kodak Ektachem methodologies, spectrophotometry, and atomic-absorption spectrometry compared.

We compared the analytical performance of the Kodak Ektachem XR700 assays of iron (Fe) and total iron-binding capacity (TIBC) with that of a conventional ferrozine assay (performed with a Cobas-Bio) and occasionally with that of atomic-absorption spectrometry (AAS). The correlation was modest between Kodak and Cobas-Bio concentrations of Fe in serum (r = 0.79). Multiple outliers were noticed in samples from hemodialysis patients, with Cobas values exceeding those of Kodak by as much as 26 mumol/L. These intermethod differences were not dissipated by dialysis, but were invariably accompanied by an even higher total Fe content of the serum as judged by AAS (20 to 80 mumol/L higher). TIBC values by Kodak and Cobas-Bio were highly correlated (r = 0.99); again, the Cobas-Bio results exceeded those by Kodak in some hemodialysis patients, but always for samples with higher Fe concentrations by the Cobas-Bio. By AAS, the TIBC values of these patients also exceeded those by Kodak, to about the same extent as observed for serum Fe. These intermethod differences in Fe and TIBC were seen only in patients who had received an intravenous Fe-dextran (Imferon) injection two to three days before blood sampling but could be generated in vitro by adding Imferon to serum from normal controls. Less than 6% of dextran-bound Fe is measured as Fe by Kodak, as opposed to 20-30% by Cobas-Bio and 89-120% by AAS. We conclude that the Kodak Fe slides are superior to liquid reagents, by exclusively measuring protein-bound circulating Fe pools.

Spuriously low concentrations of serum iron measured with generation 14 Kodak Ektachem slides: prevalence, possible causes, and partial improvement with generation 16 slides.

For sera with iron (Fe) concentrations < 4 mumol/L, Kodak Ektachem slides Generation (GEN) 14 (without ascorbic acid) yielded systematically lower results for Fe than did liquid Ferrozine-based reagents from Baker containing ascorbic acid (10 g/L, final concentration) and adapted to Cobas-Bio. During an 8-month comparison period, outliers (defined as [Fe]Cobas - [Fe]Kodak > 4 mumol/L) were seen in 21 of the 8731 sera (0.24%) tested, corresponding to < 5% of the sera with [Fe]Kodak < 4 mumol/L. In vitro addition of ascorbic acid and (or) Fe identified at least two types of outliers: type 1 (approximately 70%), characterized by [Fe]Kodak > 0.4 mumol/L, by (supra)normal Fe recovery in Kodak slides in the presence or absence of ascorbic acid (10 g/L), and by between-method differences in serum Fe (Cobas - Kodak) that were significantly correlated with serum Zn content (P < 0.0004); and type 2 (approximately 30%), tentatively ascribed to contamination by EDTA, with serum Fe by Kodak < 0.4 mumol/L and Fe recovery near 0%, both of which could be significantly and dose-dependently increased by addition of ascorbic acid (5-20 g/L). For both types of outliers, flameless atomic absorption spectrometry (AAS) yielded results that were significantly higher than concentrations by Kodak with GEN 14. Use of GEN 16 slides (containing ascorbic acid) improved concordance of Kodak results with Cobas, and hence with flameless AAS, for both types of outliers; abolished Zn dependency of results; and increased Fe results in sera with type 2 outliers, although these remained substantially lower than by Cobas. However, like other ascorbic acid-containing reagents, GEN 16 slides were more sensitive to interference by dextran-bound Fe, as assessed during in vitro addition experiments and comparisons involving samples from Fe-dextran-treated patients. GEN 16 slides are hence expected to more frequently overestimate the physiologically available protein-bound Fe in hemodialysis patients. In hospital laboratories, this new interference will probably arise more frequently than the spuriously low results with GEN 14, hence warranting further efforts in optimizing Fe slides.