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Biomedical subjects

P R Pannall

Publications and source records attributed to P R Pannall.

At least 19 recordsLinked to original sources

Stability of the CK-MB isoenzyme on routine storage.

Unlike earlier studies on the stability of the CK-MB isoenzyme carried out on control sera and on semi-purified and purified CK isoenzymes, we have studied the stability of CK-MB measured electrophoretically in patient sera under different laboratory storage conditions. The values obtained if the test was done immediately were significantly higher than those done on stored samples. There was no difference between specimens stored at -20 degrees C overnight or kept at room temperature (RT) for a few hours, but values were significantly lower (p less than 0.005) in specimens left at RT for 6 h and then stored overnight at 4 degrees C. To determine the effects of longer storage, further specimens stored either at -20 degrees C or at 4 degrees C for up to 4 days were also tested for CK-MB stability by electrophoresis and by immunoinhibition and immunoenzymetric methods. The immunological methods were included in the study to assess method dependency of CK-MB stability. CK-MB was stable at -20 degrees C by all methods, but at 4 degrees C, CK-MB was stable only by immunological and not by electrophoretic (p less than 0.005) measurement. Specimens stored under adverse conditions (4-6 days at RT) showed 50% deterioration of CK-MB when measured electrophoretically but only about 20% when measured immunologically.

Creatine Kinase

Morphine responders with unexplained pain after cholecystectomy may have sympathetic overactivity.

In patients with unexplained pain after cholecystectomy, morphine often induces pain and may increase plasma aspartate aminotransferase activity because of exaggerated or prolonged rises in pressure within the biliary system. Previous studies have demonstrated that patients showing increases in aspartate aminotransferase have increases in plasma concentrations of noradrenaline and dopamine prior to and soon after induction of pain. The purpose of this study was to assess sympathetic activity under basal conditions in patients with (responders) and without (non-responders) increases in aspartate aminotransferase after challenge with morphine. When compared to non-responders, morphine responders had higher plasma concentrations of noradrenaline (p = 0.0001) and dopamine (p = 0.02) and higher urinary excretion of noradrenaline over 24 h (p = 0.03). Plasma and urinary levels of adrenaline were similar in the two groups. These observations indicate higher basal levels of sympathetic activity in the subgroup of patients showing increases in aspartate aminotransferase after challenge with morphine.

Aspartate Aminotransferases

Placebo-controlled trial of dexamethasone for chronic biliary pain after cholecystectomy.

Activation of the sympathetic nervous system appears to be relevant in some patients with unexplained pain after cholecystectomy, particularly those who show increases in plasma transaminase activity after challenge with morphine (morphine responders). In this study, the hypothesis that dexamethasone would improve chronic biliary pain, perhaps by suppressing activation of the sympathetic nervous system, was tested in a double-blind, placebo-controlled, cross-over trial in 20 patients, 10 morphine responders and 10 nonresponders. Before treatment with dexamethasone and placebo, urinary excretion of norepinephrine (NE) was significantly higher (p less than 0.05) in morphine responders than in nonresponders. During treatment with dexamethasone, 1 mg each night for 4 weeks, neither morphine responders nor nonresponders showed a significant improvement in pain or nausea or a significant reduction in sympathoadrenomedullary activity as assessed by urinary excretion of catecholamines. At the dose administered, dexamethasone was unhelpful for chronic pain after cholecystectomy and did not result in suppression of the sympathetic nervous system as assessed by urinary excretion of NE.

Biliary Tract Diseases

Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis.

Substantial amounts of phenols are produced in the human colon by bacterial fermentation of protein. In the colonic mucosa of animals, phenols are inactivated predominantly by conjugation with sulphate. The purpose of this study was to confirm sulphation of phenols by isolated colonocytes from man and to evaluate mucosal sulphation in inflammatory bowel disease using the phenol, paracetamol, in rectal dialysis bags. The incubation of paracetamol with colonocytes isolated from resected colon specimens (n = 7) yielded a mean (SE) value of 7.0 (0.9) mumols/g dry weight of paracetamol sulphate after 60 minutes but virtually undetectable values of paracetamol glucuronide. Paracetamol sulphate was detected in rectal dialysates from all control subjects, with a mean (SE) value of 4.2 (0.8) nmol/hour. Sulphation was significantly impaired (p less than 0.01) in 19 patients with active ulcerative colitis (0.6 (0.2) nmol/hour) and in 17 patients with ulcerative colitis in remission (1.1 (0.4) nmol/hour). Sulphation in eight patients with Crohn's colitis (4.3 (2.1) nmol/hour) was similar to that in control subjects. Impairment of the capacity of the mucosa to sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic burden on colonic epithelial cells, which are continuously exposed to endogenous phenols from the colonic lumen.

Acetaminophen

Choriogonadotropin-mediated thyrotoxicosis in a man.

A 38-year-old man with a metastatic gonadotropin-secreting tumor of unknown primary origin presented with both clinical and biochemical findings of hyperthyroidism in association with markedly increased concentrations of human choriogonadotropin (hCG) in plasma. After chemotherapy, the concentrations of both hCG and free thyroxin decreased and the patient became euthyroid. We discuss the rare occurrence of this presumably hCG-driven hyperthyroidism in men and compare it with the relatively more common eumetabolic hyperthyroidism associated with choriocarcinoma in women.

Adult

Reliability of the porphobilinogen screening assay.

A survey conducted by the Australian Association of Clinical Biochemists Porphyrin Working Party on urinary porphobilinogen screening showed good sensitivity (75-97.5%). This is contrary to reports in the literature and to our own observations. We therefore assessed a widely used screening method (Watson-Schwartz) and found poor sensitivity (40-69%), and even less sensitivity (28-53%) when the urine samples were normally coloured or concentrated. Thus the results obtained by the Working Party might mislead one to infer that the Watson-Schwartz method is reliable.

Clinical Laboratory Techniques

Evaluation of evoked potentials and cerebrospinal fluid analysis in the differential diagnosis of multiple sclerosis.

During the 6 years to December 1988, 191 patients underwent evoked potential (EP) studies and cerebrospinal fluid (CSF) analysis for oligoclonal bands at the Queen Elizabeth Hospital, for the differential diagnosis of multiple sclerosis (MS). Clinical data at the time of study separated patients into 3 groups, as follows: (i) multiple sclerosis (n = 90) - McDonald and Halliday Classification, 1977, (ii) other neurological disease (n = 82) and (iii) no neurological disease (n = 19). In cases of clinically definite MS, visual evoked potentials (VEPs) were abnormal and oligoclonal bands were detected in 64% and 59% of cases, respectively. However, only 15% of patients with suspected MS had abnormal VEPs, and only 23% had oligoclonal bands. Other studies have shown figures differing from these, though not necessarily significantly. We found a substantial number of EP (20%) but few CSF (4%) abnormalities in disorders other than MS, and no abnormalities in cases without neurological disease. The various figures for abnormal results in cases assessed for the differential diagnosis of MS are influenced not only by laboratory methods, but by the degree of clinical suspicion in relation to the cases selected, as well as by differences in populations from which cases are derived. Long-term prospective studies of diagnostically indeterminate cases are still required to determine the diagnostic weighting that can be applied on the basis of abnormal investigational results. Magnetic resonance imaging will not resolve these questions since it has limitations of its own, particularly with regard to specificity.

Adult

Do nonesterified fatty acids displace thyroxin from its plasma binding sites in severe nonthyroidal illnesses?

Severe nonthyroidal illnesses have been associated with increases in nonesterified fatty acids (NEFA) and the dialyzable fraction of thyroxin (T4) in plasma. We have further investigated their possible relationship in severe nonthyroidal illnesses as well as in induced in vivo and in vitro situations involving increased NEFA. We demonstrate that there is no relationship between NEFA and the dialyzable fraction of T4, either in severe nonthyroidal illnesses or in the other situations, unless plasma NEFA concentrations exceed 5 mmol/L in normal persons or 1.7 mmol/L in nonthyroidal illnesses, and that this concentration was not reached in the patients we studied, with one exception. We conclude that NEFA are unlikely to contribute to an inhibition of the binding of T4 to the binding proteins that might be present in plasma of patients with severe nonthyroidal illnesses unless their NEFA concentrations are very high.

Binding Sites

Circadian rhythms in patients with abdominal pain syndromes.

Circadian rhythms for cortisol, 6-sulphatoxy melatonin and core body temperature were compared in control subjects and patients with functional abdominal pain. There were 20 patients with biliary pain after cholecystectomy, ten with biliary pain without cholecystectomy and 14 with irritable bowel syndrome. Rhythms were determined by urine collections at intervals of 4 h for 48 h and by overnight monitoring of core body temperature using the Vitalog system. Data were fitted to a sine curve to yield the time of maximal urinary excretion/lowest temperature and the amplitude of each rhythm. Urinary excretion of free cortisol was similar in patients and control subjects. For urinary 6-sulphatoxy melatonin, the timing (phase) of rhythms was similar in patients and controls but those with pain had a lower urinary excretion of 6-sulphatoxy melatonin (p less than 0.05) and a rhythm of lower amplitude (p less than 0.02). The amplitude of the temperature rhythm was also lower in patients with biliary pain with and without prior cholecystectomy (p less than 0.05). Functional abdominal pain is associated with 6-sulphatoxy melatonin and temperature rhythms of low amplitude, presumably because of suppression of circadian oscillators.

Abdomen

Atypical LD isoenzymes with five diffuse bands and evidence for two types of binding.

We describe a plasma LD isoenzyme pattern in which all five bands are unusually diffuse and of retarded mobility, an appearance not previously reported. This was shown to be due to binding to immunoglobulin G from which the enzyme could be displaced by an antiserum to gamma chains. Protein A-Sepharose removed most of the LD activity from plasma but did not dissociate the complex, indicating that the Fab end of the Ig molecule was involved in binding. Antiserum to kappa chains displaced LD5 from the complex but had no effect on the anodal bands. By contrast NAD displaced the anodal isoenzymes but not LD5. We suggest that two types of binding are involved. The LD5 complex appears to represent a true antigen-antibody reaction whereas the binding to the faster isoenzymes does not. We also suggest that immunoprecipitation is more reliable than immunoelectrophoresis or immunodiffusion for demonstrating IgG in such complexes and may be of value in defining the nature of binding.

Aged

Colorimetric measurement of D(-)lactate in plasma.

We describe a method for the direct assay of D(-)lactate in plasma using D(-)lactate dehydrogenase and a color reagent to produce a formazan color measured at 510 nm. This method agrees well with a modified lactate UV end-point method r = 0.998 and the regression equation y = 0.974x + 0.13. The precision for low and high concentrations of D(-)lactate is 4.8% and 3.6% within-batch and 8.9% and 1.7% between-batch. Recoveries average 105% and 98% for D(-)lactate at concentrations of 1 and 5 mmol/L, respectively. The proposed method is inexpensive and suitable for routine and emergency use, and shares reagents used for the assay of L(+)lactate and 3-hydroxybutyrate.

3-Hydroxybutyric Acid

Importance of postmortem changes in measurements of thyroid function in studies of sudden infant death syndrome.

Various measurements of thyroid function were made from serum sampled at necropsy by cardiac puncture in adults and compared with the equivalent values before death. There were significant increases in serum total T3 (0.66 before death, 1.14 nmol/l after death), free T3 (0.82 to 1.52 pmol/l), and reverse T3 (1.12 to 1.75 nmol/l); and significant decreases in total T4 (73.7 to 56.6 nmol/l), free thyroxine index (FTI) (83.2 to 56.6), and free T4 (14.2 to 11.9 pmol/l). The increase in serum T3, presumably from T4 deiodination after death, observed in this study may explain the increased T3 concentration reported in serum sampled from cases of sudden infant death syndrome (SIDS).

Humans