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Biomedical subjects

W D Fraser

Publications and source records attributed to W D Fraser.

At least 163 records · Page 9Linked to original sources

The prognostic value of TSH receptor binding and thyroid stimulating antibodies following antithyroid drug treatment of Graves' disease.

Following a course of medical therapy for Graves' disease approximately 50% of patients relapse. Previous studies have tried to identify these patients by measuring antibodies to the TSH receptor using a range of assay methods. Such studies have produced widely discrepant results. The aim of the present study was to compare the accuracy with which TSH receptor binding antibodies and thyroid-stimulating antibodies could identify cases of relapse and remission. Fifty-six newly diagnosed and previously untreated Graves' disease patients were recruited into the study. At presentation 4 were negative for TSH receptor antibody and 5 negative for TS-ab. The remaining 47 were positive for TSH receptor antibody and TS-ab although correlation of the degree of abnormality between methods was poor (r = 0.13 NS). After 12 months carbimazole treatment 28 patients relapsed during the following year and 19 remained in remission. TSH receptor antibody levels obtained at the end of a 12-month course of treatment correctly identified 93% who relapsed and 95% who remained in remission. TS-ab levels could only correctly identify 68% who relapsed and 53% who remained in remission. These results have shown that the accuracy with which patients likely to relapse can be identified depends on the assay method chosen which may account for some of the discrepancies found in previously published studies.

Adult↗

The circadian rhythm of intact parathyroid hormone (1-84) and nephrogenous cyclic adenosine monophosphate in normal men.

A pronounced circadian rhythm has been demonstrated for intact parathyroid hormone (1-84) in the serum of normal male adults. The broad nocturnal rise of parathyroid hormone (1-84) secretion appears to be of physiological significance, for it is accompanied by a significant rise in nephrogenous cyclic adenosine monophosphate. The rate of return of parathyroid hormone (1-84) to baseline concentrations varies between individuals, an observation which has implications for the optimal time of sampling for the investigation of possible mild hyperparathyroidism.

Adult↗

The "in vitro" effects of lithium on the immune system.

This study has examined the "in vitro" effects of Lithium Carbonate on the immune system at low (10(-3), 10(-2)mM) and therapeutic (0.5-1.5 mM) concentrations. Lithium, in the presence of a range of mitogens, was found to increase the incorporation of 3H-thymidine into peripheral blood mononuclear (PBM) cells. At concentrations greater than 1 mM IL2 production was also enhanced. Lithium was also found to increase IgG and IgM production--an estimate of B cell function, the effects being greatest at concentrations within the therapeutic range. However at these levels Lithium inhibited cAMP production. Whether Lithium acts individually on these processes or whether one reaction is merely the result of another is unclear at present.

B-Lymphocytes↗

Changes in iron, zinc, and copper concentrations in serum and in their binding to transport proteins after cholecystectomy and cardiac surgery.

Concentrations of iron, zinc, and copper and of their respective transport proteins transferrin, albumin, and ceruloplasmin were measured in serum after elective cholecystectomy and cardiac surgery. The pattern of changes in the concentrations of iron, zinc, and copper was reproducible, with an early increase in serum iron and zinc, then a decrease in the concentrations as these metals are dissociated from their serum transport proteins. Zinc and iron concentrations change before the increase in C-reactive protein, which begins 8 h after incision, whereas the copper concentration in the serum remains constant in the early postoperative period. Quantitative and kinetic differences were observed in both the trace metal and protein changes after cardiac surgery and cholecystectomy. These studies indicate the complexity of interpreting changes in trace elements in serum after surgery.

Adult↗

The serum interleukin 6 response to elective surgery.

We have investigated changes in serum interleukin 6 (IL-6) in patients undergoing elective cholecystectomy. Serum IL-6 increased in all patients within 1.5 hour of incision, reaching a maximum between 1.5-4 hours after incision (median 50 U/ml; range 22-79 U/ml). The maximum serum IL-6 correlated with the length of the operation (r = 0.95). Serum C-reactive protein was not detectable until 8-12 hours post-incision, but maximum serum C-reactive protein did not correlate with maximum serum IL-6 concentration or length of operation. There was no consistent increase in plasma interleukin 1 or tumour necrosis factor following surgery. Serum IL-6 is an early marker of tissue damage and may be of value in the study of the metabolic response to injury.

C-Reactive Protein↗

Diurnal variation in admission to hospital of women in labour.

In women having spontaneous labour or premature rupture of the membranes there is a marked diurnal variation in times of admission to hospital. Analysis of 4755 nulliparous women with single pregnancies in cephalic presentation at term, indicated that they presented in labour or with premature rupture of the membranes nearly twice as frequently during the night as during the evening. The peak hours for delivery were late morning and afternoon. The authors discuss previously published reports of similar findings and of a diurnal variation in maternal hormone levels in humans and experimental animals. The potential clinical importance of this phenomenon is considered.

Circadian Rhythm↗

Renal oncocytoma in pregnancy: a case report.

Oncocytoma is an uncommon renal tumour and this is the first report of such a tumour occurring in a pregnant woman. Optimal treatment is nephrectomy and the prognosis is usually good, though metastasis has been reported. It is unknown whether pregnancy alters tumour behaviour or the prognosis.

Adenoma↗

Rapid, sensitive detection of plasma IL-1 by extraction and bioassay.

A method for separating IL-1 from plasma inhibitors by silica extraction has been developed and coupled to a highly sensitive bioassay using the LBRM TG6 cell line and the I1-2 dependent HT2A cell line. Using this assay we have detected IL-1 activity in plasma from patients undergoing elective surgery.

Animals↗

Comparison of intestinal calcium absorption and circulating 1,25-dihydroxyvitamin D levels in malignancy-associated hypercalcaemia and primary hyperparathyroidism.

The relation between circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) levels and intestinal calcium absorption--as determined by an oral calcium load test--was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid-like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid-like features. It is postulated that in the former, the 'inappropriately' detectable or raised 1,25(OH)2D levels may have been due to enhanced renal 1 alpha-hydroxylase activity stimulated by the parathyroid hormone (PTH)-like effect of a non-PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non-humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is 'end organ' resistance to the effects of 1,25(OH)2D due to a generalized malabsorptive process.

Calcium↗

'Apathetic' thyrotoxicosis presenting with hypercalcaemia and spurious normalization of serum thyroid hormone levels.

A patient with thyrotoxicosis presented with weight loss and hypercalcaemia, leading to an erroneous diagnosis of occult malignant disease. Intercurrent illness and drug treatment of hypercalcaemia in this patient caused a depression of circulating thyroid hormone levels, leading to a delay in diagnosis. Radionuclide studies of thyroid function, in contrast, consistently suggested a thyrotoxic state. It is suggested that in this situation, radionuclide studies may give a more accurate assessment of thyroid status than biochemical tests, which may be difficult to interpret in the presence of non-thyroidal illness.

Antithyroid Agents↗

Relation between complement activation and susceptibility to decompression sickness.

The consequences of complement activation and the symptoms of decompression sickness are similar. Consequently, the relation between the sensitivity of individuals to complement activation by air bubbles and their susceptibility to decompression sickness has been examined. Plasma samples from 34 individuals were incubated with air bubbles, and the concentration of the fluid phase metabolites of complement activation C3a, C4a, and C5a were measured with radioimmunoassays. It was found that both the anaphylatoxins C3a and C5a were produced by the presence of air bubbles but that the anaphylatoxin C4a was not. This finding indicates that air bubbles activate the complement system by the alternate pathway. One group of individuals was found to be particularly sensitive to complement activation by this pathway. They produced 3.3 times more C3a and 5.3 times more C5a in their plasma samples incubated with air bubbles as did the other group. Sixteen individuals were subjected to a series of pressure profiles that were severe enough to produce bubbles in their circulatory system that could be detected by Doppler ultrasonic monitoring. The group of individuals that had been identified as being more sensitive to complement activation by the alternate pathway was also found to be more susceptible to decompression sickness.

Adult↗

Decrement in postural control during mild hypobaric hypoxia.

The effects of mild hypoxia on the postural control system of 39 naive subjects were examined by measuring the postural sway with a Kistler force platform, at ground level and at one of four simulated altitudes: 1,521 m (5,000 ft), 2,438 m (8,000 ft), 3,048 m (10,000 ft), or 3,658 m (12,000 ft). The total sway increased above the ground level controls for the 1,521 m, 2,438 m, and 3,048 m exposures (p less than or equal to 0.005) as did the sway at the lowest measurable frequency (p less than or equal to 0.002), but no change in sway was seen in those subjects exposed to 3,658 m as compared to ground level values. Significant interaction between altitude and exposure was observed at p less than or equal to 0.04, reflecting the definite effect at the lower altitudes and the lack of an effect at the higher altitude. The multiple comparison test indicated no difference between the responses at 1,524 m, 2,438 m, and 3,048 m. Both arterial oxygen saturation, SaO2, and the end-tidal oxygen partial pressure, PetO2, decreased in relation to the test altitudes with a statistically significant interaction between altitude and PetO2 (p less than or equal to 0.02), and SaO2 (p less than or equal to 0.005). There was no significant interaction between altitude and end-tidal carbon dioxide partial pressure (p = 0.4853). The postural control mechanisms, as an intergrative functional unit, are very sensitive to acute mild hypoxia. Arguments are advanced to indicate that intervention of compensatory mechanisms at higher altitudes may explain the recovery of postural stability at 3,658 m.

Adult↗

Effect of fenoprofen on thyroid function tests.

We observed that a few patients taking the anti-inflammatory drug fenoprofen showed increases in total and free T3 serum levels without convincing evidence of an associated thyrotoxicosis. To confirm these findings, two volunteers were given fenoprofen for two weeks. Within this time total T3 levels almost doubled and free T3 levels increased threefold. Administration of fenoprofen did not have any measurable effect on T4 or TSH estimations. Cross-reactivities of fenoprofen and 4'-hydroxyfenoprofen were studied with antisera from various total and free T3 assays. Results show that the metabolite cross-reacts with the antisera from Amerlex total and free T3 assay kits. A lesser degree of interference was observed with the Corning total and free T3 assays. 4'-hydroxyfenoprofen had no effect on an 'in house' total T3 assay. Laboratories should therefore be aware of the possibility that their assay may be subject to interference by fenoprofen or its metabolites while clinicians should be aware of this interference in order that they may avoid unnecessary and harmful treatment.

Adult↗

Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement?

To establish their role in monitoring patients receiving thyroxine replacement biochemical tests of thyroid function were performed in 148 hypothyroid patients studied prospectively. Measurements of serum concentrations of total thyroxine, analogue free thyroxine, total triiodothyronine, analogue free triiodothyronine, and thyroid stimulating hormone, made with a sensitive immunoradiometric assay, did not, except in patients with gross abnormalities, distinguish euthyroid patients from those who were receiving inadequate or excessive replacement. These measurements are therefore of little, if any, value in monitoring patients receiving thyroxine replacement. To stop doing thyroid function tests in these cases would result in considerable savings nationally in the cost of reagents in laboratories using commercial kits.

Adolescent↗