The future for clinical scientists in laboratory medicine.

Clinical science in the UK has been presented with a range of opportunities and new initiatives in recent years. This review summarizes the contribution of clinical scientists to the changing face of laboratory medicine, and describes some recent UK Government initiatives to modernize the scientific service and develop the people who work in it. Recent changes in the regulation of professional practice and the need for maintenance of professional competence are also discussed.

A comparison of 1.5% glycine and 2.7% sorbitol-0.5% mannitol irrigants during transurethral prostate resection.

PURPOSE: We performed a prospective randomized trial comparing glycine 1.5% with 2.7% sorbitol-0.5% mannitol irrigating solution. We evaluated blood loss, fluid absorption, temperature change, cardiac effects and postoperative symptoms. MATERIALS AND METHODS: Between April 1998 and July 1999, 205 treated patients were included in the statistical analysis. Intraoperative irrigating fluid absorption was measured with the patient on the operating table. Serum cardiac troponin I was used as a marker of perioperative myocardial damage. Operative details were recorded, including the type of anesthesia, resection time and the weight of resected tissue. Postoperative symptoms were documented prospectively. RESULTS: Mean patient age was not significantly different in the glycine and sorbitol-mannitol groups. (72.1 versus 73.7 years). American Society of Anesthesiologists grade was also comparable. Median resection time was 27 minutes and resected tissue weighed a mean of 21 gm. The median resection rate was 0.8 gm. per minute. Blood loss and temperature changes during resection were similar in the 2 groups. Overall median blood loss was 216 ml. and irrigant absorption was 140 ml. In the sorbitol-mannitol group significantly less fluid was apparently absorbed during resection (median 88.2 versus 184.4 ml.). Analysis of the incidence of symptoms of the transurethral prostate resection syndrome did not show any differences in the irrigant groups. Cardiac damage measured using troponin I also showed no significant difference in the 2 groups, although there was a high overall incidence of 7.5%. CONCLUSIONS: We noted no significant differences in 1.5% glycine and 2.7% sorbitol-0.5% mannitol as an irrigating solution for transurethral prostate resection.

Postmortem prolactin as a marker of antemortem stress.

AIM: To determine whether raised prolactin concentrations could be identified using postmortem venous blood and whether the level of prolactin correlated with antemortem stress. METHODS: Blood was obtained from the right femoral vein of 100 random adult necropsy cases, all of whom had been dead less than four days. Prolactin was determined in the samples by microparticle immunoassay. The levels of prolactin obtained were then analysed in relation to sex and cause of death, with particular emphasis on a history of antemortem stress and drug use. RESULTS: Prolactin in all cases of trauma was in the normal range (up to 500 mU/l). In cases of sudden unexpected deaths the mean concentration was 533 mU/l (95% confidence interval (CI), 372 to 694 mU/l). Postoperative deaths or cases with chronic disease had a mean value of 1027 mU/l (95% CI, 735 to 1319 mU/l). Cases of suicide had a mean value of 1398 mU/l. Analysis of the suicides by sex showed a significant difference, the mean in female cases being 2072 mU/l compared with 692 mU/l in male cases. In three of the four female suicides with the highest prolactin, the hyperprolactinaemia might have been attributable to a drug effect, but one case still had unexplained hyperprolactinaemia. CONCLUSIONS: It is possible to detect prolactin reliably in postmortem venous blood samples. Prolactin values at necropsy differ according to the cause of death, with markedly higher values in postoperative deaths and in the chronically ill. Hyperprolactinaemia in cases of suicide is likely to result from the effects of the drugs used, but the levels were higher than previously reported.

Acute renal failure due to McArdle's disease.

A 37-year-old previously fit man developed acute renal failure associated with rhabdomyolysis following a brief period of strenuous exercise. Subsequent muscle biopsy and ischaemic arm exercise confirmed the diagnosis of McArdle's disease. This case illustrates that McArdle's disease can present with acute renal failure in the absence of a past history of exercise-induced muscle pain and stiffness.

Nontraumatic rhabdomyolysis and acute renal failure.

Four cases of acute renal failure occurring in association with unusual causes of nontraumatic rhabdomyolysis are reported. Three of the four were associated with drug overdoses.

Therapeutic drug monitoring--the need for audit?

The experience of therapeutic drug monitoring (TDM) of seven drugs as part of the normal biochemistry services over the period April 1982-83 is reported. Reagent costs alone for these assays exceeded pounds 15,000. Of 1,841 digoxin estimations, 56 per cent fell within the therapeutic range whereas 25 per cent were potentially toxic. Fifty per cent of 968 lithium measurements were lower than 4 mg L-1, placing many of these patients at risk of treatment failure. Only 29 per cent and 32 per cent of 369 theophylline and 440 phenytoin concentrations respectively were within their well-established ranges. In only around 20 per cent of requests for theophylline and phenytoin assay was sufficient clinical information supplied to the laboratory. In the majority of patients with theophylline or phenytoin concentrations outwith the therapeutic range, further analysis was not requested and so optimisation of dosage cannot be assumed to have occurred. The wide therapeutic ranges of carbamazepine and phenobarbitone ensured that most patients attained acceptable concentrations. Sodium valproate analysis was requested on 160 occasions despite the poor correlation between the concentration of this drug and its therapeutic and toxic effects. TDM can be an expensive exercise which must be subjected to rigorous cost-benefit analysis. Requests should be made on a customised drug assay form and interpretative advice on individual patient problems made available. Recommendations for the organisation, daily running and clinical supervision of TDM are made.

Determination of retinol-binding protein in serum by kinetic immunonephelometry with polyethylene glycol pretreatment.

This work describes the use of polyethylene glycol as a pretreatment reagent to remove endogenous light scattering material from serum samples prior to automated immunonephelometric analysis on a centrifugal analyser. An assay system for retinol-binding protein is described, which allows rapid (10 minutes) quantitation of retinol-binding protein in serum samples with a detection limit of 5 mg/L and between-assay coefficients of variation ranging from 2.9% to 4.0%. The assay range is 5-80 mg/L and accuracy comparisons with a Mancini single radial immunodiffusion method yield a regression line y = 0.89 x + 0.52 (r = 0.98, n = 22). The problem of analyte precipitation associated with use of pretreatment regimes is discussed.

Effect of starvation and elective surgery on hand dynamometry and circulating concentration of various proteins.

The effect of 4 days total starvation (water only) in five normal subjects on the circulating concentrations of various proteins was studied. Changes in plasma albumin and total protein concentrations were compared with those of six patients undergoing elective abdominal surgery with partial starvation and six patients undergoing orthopaedic surgery with adequate feeding - (0.126-0.146 MJ/kg/day and 1.2-1.4 g protein/kg/day). In a companion study hand grip strength was measured daily in ten normal subjects during starvation and in 18 patients undergoing surgery for hernia repair (n = 6), cholecystectomy (n = 6) and major abdominal surgery (n = 6). Starvation produced marked reductions (approximately 30%) in the circulating concentrations of retinol binding protein and prealbumin but did not significantly affect the plasma concentration of immunoglobulins (IgG, IgA, IgM) acute phase reactants (orosomucoid, haptoglobin, alpha(1) antitrypsin), albumin and total protein. On the other hand both types of elective surgery produced significant reductions in plasma albumin and total protein concentrations irrespective of feeding. Grip strength was not significantly altered by four days of starvation but surgery produced a temporary reduction in grip strength, the extent and duration of which was related to the severity of operation. This study helps to separate the effect of surgery and starvation on hand dynamometry and circulating protein concentrations and indicates their limitations as indicators of nutritional state.