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Biomedical subjects

D Willgoss

Publications and source records attributed to D Willgoss.

10 recordsLinked to original sources
PubMed2000

Tenoxicam i.v. for major gynaecological surgery--effects on renal function.

Thirty women presenting for major gynaecological oncology surgery under a standardized, combined epidural/general anaesthetic technique received either placebo or tenoxicam 20 mg intravenously, in a randomized double-blinded manner prior to surgery. Plasma and urinary electrolytes, creatinine, prostaglandins PgE2 and PgF1 alpha, and thromboxane (TxB2) were collected 12 hours preoperatively and then for four days postoperatively. There were no significant differences in any of the measured parameters between the groups, at any of the measurement times. Mean (SD) creatinine clearance at baseline, 24 h and 48 h was 100.4 (29.7) and 86.9 (27.5), 128.1 (45.9) and 115.0 (40.3), 137.5 (50.7) and 121.6 (38.6) in the placebo and tenoxicam groups respectively (P = 0.28). Both groups required similar amounts of intraoperative ephedrine and intravenous fluids to maintain blood pressure. The minimal changes in plasma and renal parameters reflect predictable responses to major surgery and rehydration rather than any response to cyclooxygenase inhibition. This may underscore the importance of maintenance of blood pressure during the course of surgery and postoperative care, and perhaps the usefulness of a fluid loading regimen to preserve renal function during surgery. The predicted attenuation of renal prostaglandin-mediated protective mechanisms and enhancement of the catecholamine-mediated renal vasoconstriction by the use of a single 20 mg dose of tenoxicam in this study were not seen. Modulation of renal concentrating mechanisms or excretion of sodium and potassium by tenoxicam was not apparent and a large increase in study size would be required to detect a significant difference in these parameters as a consequence of the drug, over and above any changes in response to surgery and epidural anaesthesia.

Aged↗
PubMed1999

Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure.

For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.

Acute Kidney Injury↗
PubMed1999

Cell survival or death in renal tubular epithelium after ischemia-reperfusion injury.

A major contributor to the development and progression of ischemia-reperfusion (IR)-induced acute renal failure (ARF) is the loss of functioning tubular epithelial cells by means of various cell deletion or death processes. Although the term "acute tubular necrosis" is still used to describe the pathology of ARF, this is a misnomer because apoptotic cell death, as well as necrosis, occurs [1, 2] along with desquamation and loss of viable epithelial cells [3]. Apoptosis was first described in renal disease in 1987 in an animal model of hydronephrosis [4]. In ARF, with reference to only the death processes, the relative contribution of necrosis or apoptosis possibly depends on the extent of the initiating events. For example, after prolonged total renal ischemia, necrosis or "accidental cell death" occurs from the resultant negation of the cell's energy and protein levels. In apoptosis, the cells use their own energy processes and proteins to die, and often the initiating ischemia is more mild [5]. Finally, despite prolonged ischemia, within the heterogeneous renal cell populations there are those that are more sensitive to ischemia, such as the proximal straight tubule and to some extent the thick ascending limb (TAL) of the loop of Henle. It may be hypothesized that these cells tend to undergo necrosis in comparison with the less sensitive segments that undergo apoptosis. Because apoptosis is gene driven, its identification is important because of the possibility of its modulation via molecular controls. However, despite these new concepts of ARF, patient death remains high, at approximately 30 to 50% of ARF cases. Recovery from ARF depends not only on the replacement or regeneration of cells deleted by death, the theme of many recent studies, but also on protection of cells from death. Both processes are dependent on many of the cellular and molecular controls that have evolved in multicellular organisms to manage normal development, differentiation and growth processes, but that then become involved in the pathogenesis and progression of many renal diseases, including ARF.

Acute Kidney Injury↗
PubMed1991

Cell kinetics in parathyroid adenomas: evidence for decline in rates of cell birth and tumour growth, assuming clonal origin.

OBJECTIVE: We aimed to provide a cell kinetic explanation for the demonstrated lack of disease progression in most patients with mild, asymptomatic primary hyperparathyroidism. DESIGN: We compared cell birth rates, estimated at the time of adenoma excision, with the lowest birth rates needed to grow tumours of the observed size. PATIENTS: Sixty-three patients with primary hyperparathyroidism due to a single chief cell adenoma who had normal renal function were followed up for long enough to demonstrate cure after surgical excision. MEASUREMENTS: Fresh adenoma tissue was incubated with tritiated thymidine. The proportion of cells synthesizing DNA was determined directly by radioautography in 18 cases, and indirectly from the regression of label index on rate of DNA synthesis in 45 cases. The birth rate of new cells was calculated assuming the duration of S phase to be 12 hours. The number of cells in each adenoma was estimated both from parenchymal weight and from total DNA content, and the minimum birth rate needed to produce this number of cells from a single cell, beginning in utero, was calculated on an exponential model. RESULTS: The mean observed birth rate of new cells (mean (SD)) was 17.3 (11.1)%/year, and the minimum needed birth rate was 42.8 (21.6)%/year, significantly, (P less than 0.001) higher than the observed birth rate. CONCLUSIONS: The rate of mitosis had fallen substantially during the life span of most parathyroid adenomas. To account for this, we propose that the mutation implied by a clonal origin increases the secretory setpoint. Because proliferation, as well as hormone secretion, is influenced by calcium in parathyroid cells, the expected result would be rapid initial growth, slowing down as tumour size reached an asymptotic value corresponding to the total rate of hormone secretion needed to raise the plasma calcium to the new setpoint.

Adenoma↗
PubMed1981

DNA synthesis and secretory activity in parathyroid adenomas.

DNA synthesis was measured in vitro by incorporation of [3H]thymidine into DNA in 42 parathyroid chief cell adenomas immediately after surgical removal. The results ranged from 18 to 185 DPM/microgram DNA and showed a positive correlation with pre-operative values for serum immunoreactive parathyroid hormone (r = + 0.47; P < 0.001) and plasma calcium (r = + 0.35; P < 0.05). There was no correlation between DNA synthesis and tumour weight or mean diameter of tumour cell nuclei. The results suggest that DNA synthesis and cell division in parathyroid adenomas are determined in part by the secretory activity of the tumour. DNA synthesis measured on one occasion is not necessarily an overall index of tumour growth.

Adenoma↗
PubMed1975

Urinary cyclic AMP in diagnosis and management of hypercalcaemia: studies of patients without primary hyperparathyroidism.

Urinary adenosine -3' ,5' - cyclic monophosphate was measured in 14 patients with hypercalcaemia not caused by primary hyperparathyroidism. Increased levels were found in patients with malignant disease without bone metastases and believed to be examples of paraendocrine syndrome. Decreased levels were found in patients with metastatic carcinoma involving bone, and in patients with multiple myeloma, lymphoma and immobilisation after fracture. Results obtained during treatment for hypercalaemia are described in three patients. In two hypercalcaemic patients (one with hyperthyroidism and one with breast cancer with bone metastases) normal levels were found. This measurement is a useful substitute for assay of serum parathyroid hormone and is of value in the diagnosis of hypercalcaemia, in monitoring effects of treatment and in revealing underlying mechanisms.

Aged↗
PubMed1975

Urinary excretion of cyclic AMP in primary hyperparathyroidism.

Urinary adenosine 3' 5' - cyclic monophosphate (cyclic AMP) was assessed by a competitive protein binding method in 19 patients with primary hyperparathyroidism (PHPT) and in 15 control subjects. The mean value of 6.6 +/- S.E. 0-64 muM per 24 hours for the patients with PHPT was higher (P less than 0-001) than the mean control value of 3-2 +/- 0-24 muM per 24 hours. In all hypercalcaemic patients without renal insufficiency, urinary cyclic AMP excretion was more than 4 muM per 24 hours and decreased in the 15 patients investigated after parathyroidectomy. In a normocalcaemic hyperparathyroid patient and in three hyperparathyroid patients with renal insufficiency, urinary cyclic AMP was less than 4 muM per 24 hours.

Creatinine↗