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S D Heys

Publications and source records attributed to S D Heys.

141 records · Page 8Linked to original sources
PubMed1990

Measurement of albumin synthesis in humans: a new approach employing stable isotopes.

A new method for measuring albumin synthesis in humans with stable isotopes is presented. This can readily be applied in most clinical conditions, even when albumin losses are occurring or when repeated assessment is required. After rapid intravenous injection of a large dose of [13C]leucine (57 mg/kg body wt, 19.4 atoms%), plasma samples were taken at intervals up to 90 min. The enrichment of free leucine in plasma measured by gas chromatography-mass spectrometry rose to a peak at 10 min and then fell slowly, whereas that in liver biopsies (from surgical patients) ranged from 101.5 to 80.5% of the plasma value between 10 and 90 min after injection. The fractional synthesis rate (FSR) was calculated by dividing the increase in enrichment of leucine in albumin, measured by gas isotope ratio mass spectrometry, by the area under the plasma free leucine enrichment vs. time curve after allowing for the period between synthesis of the protein and its secretion into the plasma. The FSR in healthy postabsorptive males was 7.2 +/- 1.3%/day, and the absolute synthesis rate was 157 +/- 39 mg.kg body wt-1.day-1. These rates are comparable to those obtained by other methods.

Adult↗
PubMed1989

Anaesthetic agents and their effect on tissue protein synthesis in the rat.

1. Rates of protein synthesis were measured, in vivo, in lung, liver, heart and skeletal muscle of young male rats. Groups of rats were exposed for 1 h duration to one of the following anaesthetic regimens: 1.4% halothane, 2.2% halothane, 1.4% halothane in 66% nitrous oxide, intravenous pentobarbitone (20 mg/kg) and intravenous midazolam (18 mg/kg) combined with fentanyl (2 micrograms/kg). Fractional rates of protein synthesis were determined by injecting [3H]phenylalanine (150 mumol/100 g body weight). 2. Liver protein synthesis was depressed significantly by all regimens, except midazolam/fentanyl, by up to 37.7% of control values. Lung protein synthesis was significantly reduced by all the anaesthetic agents by up to 30% of control rates. 3. The effects of the anaesthetic agents on skeletal muscle and heart were small and not statistically significant. 4. There was no evidence of ventilatory depression as manifested by changes in arterial blood gas partial pressures of CO2 and O2, except in the group treated with 2.2% halothane.

Anesthetics↗
PubMed1988

Influence of the hepatic drug-metabolizing enzyme-inducer phenobarbitone on cyclosporine nephrotoxicity and hepatotoxicity in renal-allografted rats.

We have investigated the influence of phenobarbitone ([PB]; 40 mg/kg/day), an inducer of hepatic drug metabolism, on high-dose cyclosporine ([CsA] 40 mg/kg/day) nephrotoxicity in normal Lewis (Lew) and renal allografted (DA X Lew F1----Lew) rats of both sexes. In untreated normal animals, CsA nephrotoxicity, assessed biochemically and histologically, in terms of acute and chronic renal structural damage, was consistently greater in male than in female rats. The capacity of PB to induce CsA metabolism was accompanied in normal rats by reductions in nephro- and hepatotoxicity and by prolonged survival of both female and male rats. Similar reductions in CsA-induced renal functional impairment and acute tubular cell injury were achieved in transplanted female (but not male) animals by concomitant PB administration. Continuous PB treatment in transplanted rats was, however, associated with the appearance of hepatic necrosis. While this effect of PB, and its failure to reduce CsA-induced chronic renal damage mitigate against its prospective value in reversing CsA toxicity, PB may nevertheless prove valuable in assessing further the role of drug metabolism in the pathogenesis of CsA nephrotoxicity.

Acetylglucosaminidase↗
PubMed1987

Pattern of injuries in survivors of a helicopter crash.

The pattern of injuries caused when a helicopter crashed after an uncontrolled descent of approximately 15 m is described. Eleven patients were admitted to hospital for further treatment and observation, and 7 were treated in the Accident and Emergency Department. One-third of the victims sustained injuries to the dorsolumbar spine. Some conditions which could improve flight safety are discussed.

Accidents, Aviation↗
PubMed1985

Renal function in rats treated with cyclosporin following unilateral nephrectomy.

The effects of oral cyclosporin A (25 mg/kg/day) on renal function and structure in groups of normal, laparotomized and unilaterally nephrectomized DA rats was assessed over a 4-week period. In each group, the drug caused impairment of function, although there was evidence of improvement during the course of the study. Cyclosporin A toxicity was most marked in the nephrectomized animals, where histological examination at 4 weeks revealed extensive damage to proximal straight tubular cells. Only minimal structural damage was observed in the two other groups. Cyclosporin A concentrations in whole blood and kidney were estimated by radioimmunoassay at 4 weeks. Similar drug levels were found in normal, laparotomized and nephrectomized animals, except for an unexplained fall in blood levels in the laparotomy group. The significance of these observations is discussed in the context of current knowledge concerning the physiological effects, toxicology and pharmacology of cyclosporin A.

Acetylglucosaminidase↗
PubMedDate not supplied

Alleviation of experimental cyclosporin A toxicity by substitution of fish muscle oil as drug vehicle.

The toxicity of cyclosporin A (CsA) formulated in either olive oil (OO) or fish muscle oil (FO) was investigated in groups of normal Sprague-Dawley rats or in animals which had undergone laparotomy or unilateral nephrectomy. CsA (25 mg/kg/day for 14 days) was administered by gavage from the time of operation, and indices of renal and hepatic function were determined at regular intervals. Urinary thromboxane B2 (TxB2) excretion and whole blood CsA concentrations were determined on day 14, when renal histology was also examined. Compared to CsA/OO treatment, and observed only in normal animals, body weight was significantly increased following administration of CsA/FO, to values similar to those observed following treatment with FO alone. Although there was evidence of renal dysfunction in all CsA-treated animals, irrespective of drug vehicle, elevations in plasma urea and urinary N-acetyl-beta-D-glucosaminidase activity were significantly more pronounced in rats given CsA/OO compared with CsA/FO. Indeed, compared with pretreatment values, no significant changes in these parameters were observed in CsA/FO-treated nephrectomized animals. Whilst there were no great differences in plasma creatinine or creatinine clearance rates between CsA/OO- and CsA/FO-treated groups, animals given CsA/FO showed less evidence of renal structural change as assessed by proximal tubular cell vacuolation, basophilia and microcalcification. The extent of hepatic impairment was also significantly less pronounced when FO was used as drug vehicle. Groups of CsA/FO-treated animals also demonstrated significantly lower whole blood CsA levels compared with CsA/OO groups; moreover, TxB2 excretion was significantly lower in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Cell signal mechanisms, conjugated linoleic acids (CLAs) and anti-tumorigenesis.

Fats have been adversely implicated in the aetiology of many forms of cancer yet evidence is accumulating that certain types of fatty acids have anticancer properties. This is well documented for fish-oil fatty acids of the n-3 family. Recently, fatty acids found to occur naturally in ruminant-derived food products were found to have anticancer properties. These fatty acids were identified as conjugated linoleic acids (CLAs) derived from the parent linoleic acid by its partial hydrogenation by rumen bacteria. Studies with tumour-bearing animals have shown that consumption of CLAs particularly with regard to breast and prostate cancer is beneficial. Studies with cancer cells have also shown that these fatty acids can inhibit cell proliferation and induce cell death. However, little is known regarding the mechanisms of action of these CLAs. In particular, which cellular signal mechanisms are regulated by CLAs which can explain their anticancer properties. We have shown that CLAs specifically up-regulate cell signal systems at the level of gene expression (mRNA, protein) in human breast and prostate cancer cells which are responsible for the induction of apoptosis or programmed cell death. These findings support the anticancer effects of CLA found in animal models and indicate similar effects could occur in man.

Animals↗
PubMedDate not supplied

NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer.

NM23 gene product is a putative metastases suppressor gene which has structural homology to a nucleoside diphosphate kinase. Previous studies examining the relationship between NM23 gene product expression and survival in patients with colorectal cancer have revealed conflicting results. However, no study has focused on young patients with colorectal cancer. This study was carried out to determine if expression of the NM23 gene product was correlated with metastatic potential and survival in young patients (45 years and under) with colorectal cancer. Eighty- one patients with colorectal cancer were studied and the presence of the NM23 gene product (H1) was detected using standard immunohistochemical techniques. NM23 gene product expression did not correlate with tumour stage, lymph node involvement by tumour, presence of distant metastases, extramural vascular invasion or degree of tumour differentiation. Independent risk factors for overall survival were: Dukes' stage (p=0.00001) and extramural vascular invasion (p=0.003). NM23 expression was not an independent prognostic indicator (p=0.55). Therefore, NM23 expression does not correlate with existing indicators of tumour aggressiveness and behaviour nor is it an independent predictor of survival in young patients with colorectal cancer.

Adolescent↗
PubMedDate not supplied

Evidence for Fas counter attack in vivo from a study of colorectal cancer.

Peritumoural cytotoxic lymphocytic infiltrates in colorectal carcinoma may attack tumour cells by expressing Fas ligand and inducing tumour cell apoptosis. However, tumours may mount a by down regulating their Fas pathway and expressing Fas ligand themselves to induce apoptosis of lymphocytes. This study used immunohistochemistry to demonstrate the presence of CD8+ lymphocytes and Fas ligand. The score of CD8+ peritumoural lymphocytes was negatively correlated with the Fas ligand score of the tumour. The results provide evidence for the Fas theory, but further work would be required to determine if this is a significant factor in the tumour-host interaction.

Aged↗
PubMedDate not supplied

Immunonutrition in clinical practice: what is the current evidence?

The clinical trials of immunonutrition that we have undertaken have often been small, single centre studies. They have often been of limited statistical power and have often included patients with a variety of underlying disease states and at different points in the disease process. Three meta-analysis and a consensus statement in conjunction with a systematic review, have been performed in an attempt to overcome many of these limitations and understand further the clinical place for immunonutrition. However, there are still many questions regarding the place of immunonutrition in clinical practice that we still do not understand or have definitive answers to. For example, do we really know what is the optimal combination of nutrients and in what quantities they should be provided? Do we understand any potential interactions that might occur between these nutrients? What is the effect of the patients nutritional state? When and for how long should immunonutrition provided? What is the impact of the patients' underlying disease process and how does this interact with the provision of immunonutrition? At the present time whilst there is some indication and evidence as to which patients might benefit most, and as to those who may not benefit or even suffer detrimental effects from immunonutrition, we still can not answer these questions with any definitive authority. It is essential now that we undertake large well designed, well controlled multicentre studies with adequate statistical power to answer these questions. The indications are that immunonutrition has the potential to help patients but its place must be more clearly defined before its widespread acceptance into clinical practice is based on sound scientific evidence.

Clinical Trials as Topic↗
PubMedDate not supplied

A pilot study with long term follow up of hyperbaric oxygen pretreatment in patients with locally advanced breast cancer undergoing neo-adjuvant chemotherapy.

Work in an animal cancer model suggests that pretreatment with hyperbaric oxygen can improve tumor vascularity rendering chemotherapy more effective. Accordingly 32 subjects with locally advanced breast carcinoma (>5cm diameter) entered into a randomized clinical trial where a course was administered of six intravenous pulses of cyclophosphamide 1000mg/m2 i.v., doxorubicin 50mg/m2 i.v. and vincristine 1.5mg/m2 i.v. In the case group this was preceded by ten, once daily, sessions of hyperbaric oxygen therapy (HBO2) administered either at 2.4 or 2.0 atmospheres absolute. Eleven out of 15 subjects tolerated a full course of HBO2 and chemotherapy. All 17 control subjects tolerated a full course of chemotherapy. Tumor extravascular extracellular or edema fluid was reduced after HBO2 but there was no reduction in tumor cell volume and no indication of increased vascularity on MRI. Clinical and pathological responses to chemotherapy were the same in both groups and there was no evidence of neovascularisation. Five year survival in those who tolerated the trial regime was 73% and did not differ between the groups. This mortality was cancer related.

Adult↗
PubMedDate not supplied

Arginine metabolism in benign and malignant disease of breast and colon: evidence for possible inhibition of tumor-infiltrating macrophages.

L-Arginine concentrations have been measured in benign and malignant breast and colonic neoplasms and compared with the macrophage content and arginase activity within these tumors. Our study confirmed previous findings of elevated plasma arginine concentrations in malignancy and demonstrated that tissue free-arginine concentrations are substantially higher in malignant (mean 9.8 mumol/g protein) than benign (2.8 mumol/g protein) breast disease. Similarly, malignant colonic neoplasms had a higher free-arginine concentration than benign colonic polyps (14.0 vs. 7.0 mumol/g protein). The macrophage content of the malignant tumors was also significantly higher than in the benign conditions (278 vs 29/high power field in breast disease), but despite this, there was no detectable difference in the arginase activity. These findings suggest that tumor-infiltrating macrophages are not able to produce this enzyme, and/or its activity is inhibited within the tumor cell milieu. The differences observed in the arginine concentrations within these lesions has potentially important implications for the pathway of arginine metabolism and local host antitumor responses.

Arginase↗