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Biomedical subjects

W D Fraser

Publications and source records attributed to W D Fraser.

At least 145 records · Page 8Linked to original sources
PubMed1991

Intact parathyroid hormone concentration and cyclic AMP metabolism in thyroid disease.

In 35 thyrotoxic patients and 35 patients receiving thyroxine replacement therapy mean serum intact parathyroid hormone concentrations were lower than in euthyroid normal volunteer controls. In 20 hypothyroid patients intact PTH was increased relative to euthyroid controls. Mean serum adjusted calcium was increased in thyrotoxic patients relative to euthyroid controls and in 8 toxic patients with elevated serum adjusted calcium (greater than 2.60 mmol/l) intact PTH was below the assay detection limit (less than 0.5 pmol/l). Indices of PTH activity were consistent with intact PTH measurements in thyrotoxic patients with nephrogenous cyclic adenosine monophosphate lower, tubular maximum reabsorption of phosphate higher, and urinary calcium creatinine ratio higher than controls. In hypothyroid patients these indices of PTH activity suggest relative end organ resistance to PTH with nephrogenous cyclic adenosine monophosphate similar, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio lower than in controls. In treated hypothyroid patients nephrogenous cyclic adenosine monophosphate was higher, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio higher than in controls. These results are compatible with the hypothesis that thyroid status modifies the renal responses to PTH (1-84).

Adolescent↗
PubMed1990

The effects of intraoperative hypothermia and cardiopulmonary bypass on trace metals and their protein binding ratios.

The ability of intraoperative hypothermia to modify the metabolic response to cardiopulmonary bypass (CPB) was assessed by serial alterations in iron, zinc and copper, and in their molar binding ratios to their respective transport proteins, in 20 male patients under-going elective coronary artery surgery and randomised to an operative blood temperature of 28 degrees C or 20 degrees C. Decreases in serum iron and zinc concentrations, typical of the acute phase response, were preceded by early rises. Significant alterations in the metal: protein molar binding ratios preceded significant changes in the serum concentrations of the metals and occurred earliest in the zinc: albumin binding ratio, which was apparent by the time of skin incision. An intraoperative temperature of 20 degrees C modified iron and zinc concentrations and their protein binding ratios during surgery but not in the post-operative period. These early changes in trace metals and their protein binding ratios are a simple and inexpensive method of quantitating the response to surgical injury and may be useful in assessing new interventions in cardiopulmonary bypass. An awareness of the trace element response to surgical injury is essential to avoid misdiagnoses of iron deficiency anaemia or zinc deficiency.

Adult↗
PubMed1990

Response of serum interleukin-6 in patients undergoing elective surgery of varying severity.

1. Recent studies have suggested that interleukin-6 is a major mediator of the acute-phase protein response in man. The aim of the present study was to investigate the relationships between the response of serum interleukin-6 to surgery, the type of surgical procedure performed and the response of serum C-reactive protein. 2. Timed venous blood samples were taken from 26 patients in five broad surgical categories (minor surgery, cholecystectomy, hip replacement, colorectal surgery and major vascular surgery). C-reactive protein and interleukin-6 were measured in each sample. 3. Serum interleukin-6 rose within 2-4 h of incision in all patients and the magnitude of the response differed among the various surgical groups. The response of interleukin-6 correlated (r = 0.80, P less than 0.001) with the duration of surgery. In contrast, serum C-reactive protein was not detectable after minor surgery (less than 10 mg/l) and the response of C-reactive protein did not differ among the more major surgical groups. The response of interleukin-6 showed a weak, but significant, correlation with the response of C-reactive protein (r = 0.67, P less than 0.001). 4. We conclude that serum interleukin-6 is a sensitive, early marker of tissue damage. In general, the greater the surgical trauma, the greater the response of serum interleukin-6 and the greater the peak serum concentration of interleukin-6. Our results are consistent with a role for interleukin-6 in the induction of C-reactive protein synthesis.

C-Reactive Protein↗
PubMed1990

The loss of circadian rhythm for intact parathyroid hormone and nephrogenous cyclic AMP in patients with primary hyperparathyroidism.

The measurement of serum intact parathyroid hormone (PTH) (1-84) over a 24-h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N-cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1-84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1-84) secretion.

Adult↗
PubMed1990

Hypercalcaemia in rheumatoid arthritis revisited.

The prevalence and mechanisms of hypercalcaemia were studied in a series of patients attending a regional referral centre for rheumatic diseases. In a prospective study one case of hypercalcaemia due to primary hyperparathyroidism was found in 251 consecutive patients who were screened over a three month period. In a retrospective study of 39 patients who had been discovered to be hypercalcaemic during the preceding 12 months known cases of hypercalcaemia were found in 38 (97%) cases. Primary hyperparathyroidism was the most common cause (n = 24; 62%), followed by thiazide treatment in five (13%), cancer in three (8%), immobility in three (8%), vitamin D toxicity in two (5%), and chronic liver disease in one (3%). In one case the diagnosis remained unclear after full investigation. This study shows that the causes of hypercalcaemia in rheumatological patients are similar to those in the general population. These observations contrast with previous reports, which suggested that hypercalcaemia may be a complication of rheumatoid arthritis itself.

Adult↗
PubMed1990

Breast cancer-associated hypercalcaemia: a reassessment of renal calcium and phosphate handling.

The mechanisms of hypercalcaemia were assessed in 20 hypercalcaemic patients with breast cancer. Abnormalities suggestive of a PTH-related peptide (PTHrP) mechanism were observed in up to 60% of cases; urinary cyclic adenosine monophosphate (UcAMP) was elevated in nine patients (45%), renal tubular reabsorption of calcium (RTRCa) was elevated in nine (45%) and the renal tubular threshold for phosphate reabsorption (TmPO4) depressed in 12 (60%). While TmPO4 was lower in patients with high UcAMP, there was no consistent relationship between RTRCa and UcAMP or UcAMP and the extent of bone metastases. In a control group of nine normocalcaemic breast cancer patients, bone resorption as assessed by urinary calcium/creatinine ratio was slightly increased but UcAMP, RTRCa and TmPO4 were generally normal. These observations indicate that a PTHrP-mediated mechanism of hypercalcaemia may be operative in up to 60% of patients with breast cancer, irrespective of the presence or extent of bone metastases.

Biomarkers↗
PubMed1990

Thyrotropin receptor antibodies associated with post-operative relapse of thyrotoxicosis in a pregnancy complicated by neonatal thyrotoxicosis.

This case describes the clinical, biochemical and immunological features associated with relapse of thyrotoxicosis during pregnancy in a patient who had recently undergone a subtotal thyroidectomy for Graves' disease. The baby, shortly after birth, showed clinical and biochemical features of thyrotoxicosis which responded to carbimazole therapy. Thyrotropin receptor antibodies and thyroid stimulating antibodies were present in the blood of the mother and baby. The clinical course of the neonatal thyrotoxicosis correlated with the TSH receptor antibody levels.

Adult↗
PubMed1990

The circadian rhythm of intact parathyroid hormone-(1-84): temporal correlation with prolactin secretion in normal men.

Serum PTH-(1-84), PRL, and adjusted calcium concentrations were determined at 30-min intervals for a 24-h period in six normal adult men. PTH-(1-84) and PRL both exhibited two peaks of increased secretion [1600-1900 and 0200-0600 h for PTH-(1-84); 2000-2200 and 0400-0800 h for PRL]. For each subject there was a striking similarity in the magnitude of secretion of the two hormones and a consistent temporal relationship. Thus, the maximum correlation coefficients of 0.62-0.83 were obtained for the six subjects when the PRL surge lagged that of PTH-(1-84) by 0.5-3.5 h. In contrast, the correlation between PTH-(1-84) and adjusted calcium was weaker (r = -0.36 to -0.66) and showed no consistent temporal relationship (0.0-10.5 h). These data support the concept of higher center control of PTH-(1-84) secretion with the possible involvement of factors common to the control of PRL secretion.

Adult↗
PubMed1990

Measuring free thyroxin by using magnetic antibody-containing microcapsules.

We describe a novel magnetic-separation microencapsulated antibody displacement assay for free thyroxin. The method is rapid (results available in just over an hour), with a detection limit of 3 pmol/L, and an interassay precision of less than 10% over the range 8-75 pmol/L. Results are not influenced by changes in the concentration of thyroxin-binding globulin or albumin, nor by the presence of circulating anti-thyroxin antibodies or physiological concentrations of nonesterified (free) fatty acids. A reference interval of 8.4-18.4 pmol/L was established for a large euthyroid adult population. Patients with various nonthyroidal illnesses exhibited a similar reference interval (6.2-17.4 pmol/L). Results from pregnant women, at all stages of gestation, were within the nonpregnant euthyroid reference interval. Complete discrimination was obtained between the euthyroid reference interval and values from patients with untreated thyrotoxicosis (24-75 pmol/L). Excellent, though incomplete, discrimination was obtained for patients with untreated hypothyroidism (less than 3.0-9.0 pmol/L). Results for a group of patients defined as having compensated euthyroidism (5.0-15 pmol/L) showed considerable overlap with the euthyroid reference interval. Patients taking thyroxin, who were clinically euthyroid and whose serum concentration of thyrotropin was within its euthyroid reference interval, had free thyroxin concentrations in the range 13.4-24.2 pmol/L. We discuss the validity of this assay in clinical practice.

Analysis of Variance↗
PubMed1990

Umbilical cord hematoma following diagnostic funipuncture.

Major complications associated with funipuncture have been reported but are rare. This is a report of a diagnostic funipuncture performed on a 29-week fetus with a single umbilical artery and multiple malformations. Immediately after the procedure, a voluminous hematoma developed at the site of needle insertion in association with a severe fetal bradycardia. Fetal death was confirmed within 5 minutes of needle insertion. It is hypothesized that the risk of complications of funipuncture may vary according to the clinical indication for the procedure and may be increased in the presence of certain fetal malformations. The rapid evolution of complications, as occurred in the present case, underlines the importance of having a clear plan of management in the event of mishap and discussing this plan with the parents before undertaking diagnostic funipuncture.

Adult↗
PubMed1990

Complement activation involvement in decompression sickness of rabbits.

A hypothesis has been proposed that claims much of the phenomena of decompression sickness (DCS) are mediated by the complement system of blood plasma. This "complement hypothesis" can be used to explain the variation in susceptibility of individuals to DCS, including the phenomena of acclimatization and de-acclimatization. In this study, certain predictions of the complement hypothesis were examined by exposing rabbits to a particular pressure profile; some were observed to have symptoms of DCS and some showed none. Those that were observed to have symptoms were also found to have native complement systems that were activated by air bubbles, and those that did not show symptoms of DCS when exposed to the same pressure profile had native complement systems that were not activated by air bubbles. Rabbits that had shown symptoms of DCS the first 2 times that they were exposed to the pressure profile could be acclimatized to the pressure profile by pharmacologically decomplementing them in vivo. After being decomplemented, they showed no symptoms of DCS when they were exposed to the same pressure profile for a third time. When the decomplemented rabbits were allowed to remain inactive for a period of time that was sufficient to allow their complement systems to return to normal, after having been decomplemented, and were then subjected to the pressure profile for the fourth time, they were each again observed to have symptoms of DCS, i.e., they became de-acclimatized when their complement systems had returned to their native sensitivity. These results provide further experimental support for the complement hypothesis.

Animals↗
PubMed1989

Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia.

Three intravenous bisphosphonates were compared in the treatment of cancer-associated hypercalcaemia. 48 patients were randomly allocated to one of three treatment groups (each with 16 subjects)--30 mg pamidronate or 600 mg clodronate, both as single intravenous infusions; or etidronate as three infusions of 7.5 mg/kg per day for three consecutive days. Patients were rehydrated with normal saline before bisphosphonate treatment. All three bisphosphonates lowered serum calcium by inhibiting bone resorption; pamidronate was the most potent in this respect. By comparison with the other groups, more patients in the pamidronate group became normocalcaemic, and the effect on serum calcium was apparent sooner and lasted longer.

Administration, Oral↗
PubMed1989

Contrasting mechanisms of hypercalcemia in patients with early and advanced humoral hypercalcemia of malignancy.

The mechanisms of hypercalcemia were assessed in 15 patients with humoral hypercalcemia of malignancy (HHM) who had tumors at various stages of progression. In patients with early tumors, bone biopsies were generally normal and the hypercalcemia was due to an elevation in renal tubular resorption of calcium. Conversely, osteoclastic resorption was markedly increased in patients with advanced tumors, particularly those in whom the biopsies were obtained postmortem. Osteoclast surface (Oc.S) correlated positively with the stage of tumor progression (r = 0.80, p less than 0.002), degree of immobility (r = 0.87, p less than 0.002), and level of urinary cyclic AMP excretion (r = 0.60, p less than 0.02). When compared with a group of ambulant patients with primary hyperparathyroidism (HPT), osteoblast surface (Ob.S%) in HHM was depressed (median and range): 1.2% (0-11.6%) versus 5.3% (1.1-32.0%) (p less than 0.001). However, a relatively low Ob.S (4%) and raised Oc.S (43.5%) were also seen in an immobilized patient with severe HPT. These data suggest that the PTH-related peptides currently invoked in the pathogenesis of HHM may initially cause hypercalcemia by enhancing renal tubular calcium resorption. The increase in osteoclastic activity and depression of osteoblastic activity that subsequently occurs is probably due to the combined effects of immobilization and higher circulating levels of PTHrP on the skeleton. However, the release of other bone-resorbing factors by the tumor, which have a depressant effect on osteoblastic activity, remains possible.

Adult↗
PubMed1989

Hypothermia and the stress response to cardiopulmonary bypass.

There is no consensus on the optimal level of intraoperative hypothermia during cardiopulmonary bypass (CPB). To assess the effect of systemic cooling on the stress response to CPB, the acute phase and endocrine responses were measured in 20 male patients undergoing elective coronary artery surgery and randomised to an intraoperative blood temperature of 28 degrees C or 20 degrees C. The acute phase response was assessed by changes in the plasma concentration of C-reactive protein (CRP) and the endocrine response by the urinary excretion of the counter-regulatory hormones adrenaline, noradrenaline and cortisol. The groups were comparable with respect to age, anthropometric indices, cross clamp and bypass times. There was no significant difference in the groups in the acute phase response but the endocrine response was attenuated in the 20 degrees C group. These findings may have implications for the severely stressed preoperative patient.

Acute-Phase Proteins↗
PubMed1989

Application of a fiber-matrix model to transport in renal tubules.

The effects of tight junction structure on water and solute fluxes across proximal tubular epithelium were examined with fiber-matrix equations previously derived by Curry and Michel (1980. Microvascular Research. 20:96-99). Using plausible estimates of tight junction fiber length and width the model predicts solute (Ps) and water permeability (Lp) coefficients that agree with the measured values. When fiber-matrix and pore models were compared for physiologically relevant ranges of matrix void fraction (80-98%) and pore radii (0-20 A), the fiber-matrix model predicted a 10-fold higher Lp/Ps ratio. Lp/Ps was most sensitive to small changes in tight junction structure when void fractions exceeded 90%. Void fractions of 96.5% and 97.1% predicted previously measured values for Lp and solute permeabilities in rat and rabbit proximal tubules. These values are consistent with void fractions and permeabilities of artificial membranes. The fiber-matrix tight junction model was incorporated into a model of reabsorption from the rat proximal tubule developed by Weinstein (1984). American Journal of Physiology. 247:F848-F862.) A void fraction of 98% predicted the experimental results for isosmotic reabsorption driven by active transport. Changing void fraction over the range of 97-99% produced a 50-75% change in predicted volume reabsorption with active transport. According to the fiber-matrix model: (a) solute permeabilities alone cannot be used to predict Lp, (b) previously measured solute permeabilities in the proximal tubule are compatible with significant water reabsorption through a water-permeable tight junction, and (c) hydraulic and solute permeabilities may be sensitive to small changes in tight junction fiber length and diameter or ionic strength within the tight junction.

Absorption↗
PubMed1989

Plasma albumin and haemodilution: the problem of interpretation in sequential studies.

The ability of four formulae (3 based on packed cell volume and one on alpha-2 macroglobulin) to correct for postoperative dilutional changes in plasma albumin was assessed in 4 patients undergoing coronary artery surgery. Cardiopulmonary bypass is a stringent test of the efficacy of the formulae to correct for haemodilution as a large volume of fluid is added to the circulation in a relatively short period of time. Plasma albumin was measured 8 times in the perioperative period in the 4 patients and the clinical situation was mimicked in vitro by adding various volumes of diluent to whole blood. None of the formulae consistently corrected for predicted changes in plasma albumin concentration in vivo; two of the formulae corrected for in vitro changes in plasma albumin but the same formulae produced considerable over-correction when applied in vivo. The problem of correcting for perioperative dilutional changes in plasma albumin is discussed.

Coronary Artery Bypass↗