Search PubMed⌕ Search

Biomedical subjects

A Shenkin

Publications and source records attributed to A Shenkin.

At least 55 records · Page 3Linked to original sources
PubMed1995

The effect of nutritional status on the cytokine and acute phase protein responses to elective surgery.

Weight loss and impaired nutritional status are associated with increased complications following surgery. This study aimed to assess the effect of nutritional status on the magnitude of the acute phase protein response, and determine if this is associated with changes in the magnitude of the related cytokine responses. Nineteen patients (10 wellnourished, 9 malnourished on the basis of body composition) undergoing major abdominal surgery were studied by frequent blood sampling in the early postoperative period. There was a significant reduction in the plasma C-reactive protein response in the malnourished group, but no difference between the groups in the responses of alpha 1-antitrypsin, alpha 1-acid glycoprotein, or in the trace elements iron or zinc, which reflect induction of ferritin and metallothionein. There was an early increase in IL-6, soluble receptors of TNF, and in IL-1 receptor antagonist in both groups, but no detectable increase in plasma IL-1 or TNF. There was no difference between the wellnourished and malnourished group for any of these markers of activation of the cytokine network. Weight loss is therefore associated with a reduction in aspects of the acute phase response, but this is due to impaired effectiveness rather than reduced magnitude of the cytokine response.

Acute-Phase Proteins↗
PubMed1995

The relationship between pancreatic enzyme release and activation and the acute-phase protein response in patients with acute pancreatitis.

It has been suggested that the severity of an attack of acute pancreatitis is related to the presence of intraglandular trypsinogen activation and that disease severity is also reflected by the degree of the acute-phase protein response. In this study we examine the relationships among amylase release, the degree of trypsinogen and prophospholipase A2 activation [as measured by urinary trypsinogen activation peptide (TAP) and prophospholipase A2 activation peptide (PLAP) concentrations], and the serum concentrations of the acute phase-protein C-reactive protein (CRP) and the principal mediator of the acute-phase protein response, interleukin-6 (IL-6). Twenty-four patients (14 mild and 10 severe attacks) were studied. Peak serum amylase concentrations were seen within 12 h and peak urinary TAP/creatinine (Cr) and PLAP/Cr ratios between 12 and 24 h after the onset of symptoms, preceding those of IL-6 and CRP. The integrated TAP/Cr and PLAP/Cr responses were significantly greater in those with severe disease [95% confidence internal (CI) = 106-259.6 pmol/mmol/h, p < 0.0008; and 95.1% CI = 462.2-3887 pmol/mmol/h, p < 0.003, respectively]. The integrated amylase response was not significantly greater in those with severe disease (95.6% CI = -415 to 832 IU/L/h, p < 0.14). There was a strong correlation among the integrated IL-6, TAP/Cr (r = 0.63, p < 0.01), and PLAP/Cr (r = 0.64, p < 0.01) responses but a poor correlation with the integrated amylase response (r = 0.19, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Cerebrospinal fluid interleukin-6 and its diagnostic value in the investigation of meningitis.

We examined the measurement and the diagnostic value of cerebrospinal fluid interleukin-6 (CSF IL-6) in meningitis. The cytokine was measured by bioassay (B9 hybridoma cell line) and by immunoassay (in-house radioimmunoassay). We compared the diagnostic value of CSF IL-6 determination with that of other biochemical markers of meningitis. Although there was significant correlation between bioactive and immunoactive IL-6 (r = 0.724, P < 0.001), results were frequently different with biological/immunological ratios ranging from 0.2 to 24.3 (mean 4.6). Gel permeation chromatography suggested that the discrepancy in biological and immunological activities was not due to molecular heterogeneity, but may be explained by the presence of a synergistic factor. Interleukin-6 concentration was markedly elevated in CSF from most patients with bacterial meningitis compared to patients with viral meningitis and those without evidence of infection. However, low IL-6 levels by radioimmunoassay did not exclude bacterial meningitis (sensitivity 86%). CSF total protein and CSF glucose were significantly different between all three groups, but there was no significant difference in lactate concentration between virally infected and normal CSF, both of which had lower lactate concentrations than those in bacterial infection. CSF IL-6 measurement had greater sensitivity, specificity and predictive value than these other biochemical markers, and hence a rapid assay for IL-6 in CSF may contribute to the early diagnosis of bacterial infection.

Biomarkers↗
PubMed1995

Effect of glycoprotein and protein hormones on human meningioma cell proliferation in vitro.

Speculation that meningiomas are subject to female hormone influence is supported by their higher incidence in women and reports of exacerbation of symptoms during pregnancy and the luteal phase of the menstrual cycle. Previous reports have concentrated on the effects of the steroid hormones oestradiol and progesterone on meningioma proliferation. In this study we have investigated the roles of the glycoproteins LH, FSH and human chorionic gonadotrophin (hCG), and the protein hormones prolactin (PRL) and human placental lactogen (hPL) on the proliferation of human meningiomas in vitro. The three glycoproteins had an inhibitory effect on meningioma proliferation ranging from 5.0-50.0%, 10.0-63.0% and 2.4-34.0% at the highest concentrations of LH (25 mIU/ml), FSH (15 mIU/ml) and hCG (30 IU/ml) respectively. Cultures were also treated with PRL (100 and 200 ng/ml) and hPL (5 and 10 ng/ml) and the protein hormones had a stimulatory effect on cell proliferation of 12.0-55.5% and 11.4-73.6% when treated with 200 ng/ml PRL and 10 micrograms/ml hPL respectively. Our data suggest that increasing levels of the protein hormones PRL and hPL, falling levels of hCG and the absence of LH and FSH in the second and third trimesters of pregnancy may play a role in the acceleration of meningioma growth in these stages of pregnancy.

Adult↗
PubMed1995

Nutritional assessment in the critically ill.

Although many of the measurements and techniques outlined in this article may be epidemiologically useful and correlate with morbidity and mortality, no single indicator is of consistent value in the nutritional assessment of critically ill patients. Measurements such as anthropometrics, total body fat estimation, or delayed hypersensitivity skin testing either are liable to non-nutritional influences or lack accuracy and precision in individual patients. Plasma concentrations of hepatic proteins are affected significantly by the patient's underlying disease state and therapeutic interventions and therefore lack specificity. Although the measurement of these proteins is of little value in the initial nutritional assessment of the critically ill, serial measurement, particularly of plasma pre-albumin, may be useful in monitoring the response to nutritional support. Nitrogen balance is a widely used and valuable nutritional indicator in the critically ill. Direct measurement of urine nitrogen is the preferred test, although nitrogen excretion often is derived from 24-hour urine urea measurement, an inexpensive and easy procedure, but one that is less accurate. More accurate techniques of assessing change in nutritional status, such as IVNAA of total body nitrogen or isotopic measurement of exchangeable potassium or sodium, are more expensive, less available, unsuitable for repeated analyses, and less feasible in severely ill patients. Total body nitrogen measured using IVNAA and total-body potassium, however, are the most accurate ways of measuring body composition in the presence of large amounts of edema fluid. The application of body composition measurements to patient care remains poorly defined because of the many problems encountered with the various techniques, including cost, availability, and radiation exposure. Improved, more sensitive and, preferably, bedside methods for the measurement of body composition are needed. It is of paramount importance that these methods are validated extensively in the critically ill as well as in more stable patients, not only in terms of analytical accuracy, but also to define the point at which altered body composition influences clinical outcome. The biochemical measurement of levels of vitamins, minerals, and trace elements is invaluable in demonstrating specific deficiencies associated with disease and assessing whether long-term nutritional support is adequate. Such measurements rarely are necessary to make the initial clinical decision to give nutritional support, however. The most widely used measures of nutritional state are nitrogen balance and secretory protein concentrations, and these indices improve when sick patients recover.(ABSTRACT TRUNCATED AT 400 WORDS)

Critical Illness↗
PubMed1994

Metabolic and inflammatory responses after open or laparoscopic cholecystectomy.

Metabolic and inflammatory responses and changes in fatigue were studied in groups of patients undergoing either laparoscopic (n = 14) or open (n = 10) elective cholecystectomy. The mean(s.e.m.) cortisol concentration was significantly (P < 0.001) increased from 342(80) and 424(91) nmol l-1 before operation to 895(46) and 966(53) nmol l-1 after surgery in patients undergoing laparoscopic and open cholecystectomy respectively. There was no difference in cortisol response between the groups. Glucose concentration was increased (P < 0.02) at the end of surgery from mean(s.e.m.) preoperative levels of 5.54(0.15) and 6.16(0.15) mmol l-1 to postoperative values of 7.46(0.29) and 8.46(0.86) mmol l-1 for the laparoscopic and open procedures respectively. The mean glucose concentration during the initial 12 h after surgery was significantly greater (P < 0.02) following open than laparoscopic cholecystectomy. The mean(s.e.m.) albumin concentration fell significantly (P < 0.01) during surgery by an equivalent extent from 38.9(0.77) and 38.5(1.10)g l-1 to 35.2(0.79) and 34.6(0.97) g l-1. The mean (95 per cent confidence interval) interleukin (IL)6 concentration peaked 4 h after surgery at 57.2 (44.6-73.4) pg ml-1 following laparoscopic and 99.3 (72.8-135.4) pg ml-1 after open cholecystectomy. Mean (95 per cent confidence interval) C-reactive protein (CRP) levels at 24 h were 17.0 (12.7-21.2) and 49.0 (25.3-93.6) mg l-1 and at 48 h 28.0 (21.4-35.4) and 70.0 (36.4-133.6) mg l-1 following laparoscopic and open operations. The differences in IL-6 and CRP level between the groups were significant (P < 0.01). Mean(s.e.m.) fatigue scores were significantly (P < 0.05) increased from preoperative values of 2.4(0.24) and 2.6(0.44) to 5.5(0.56) and 6.8(0.51) at 24 h after laparoscopic and open operations. At 48 h the mean(s.e.m.) fatigue score (5.6(0.57)) remained significantly (P < 0.05) raised only after open cholecystectomy. Hand grip strength was significantly (P < 0.05) reduced only after the open procedure, to a mean(s.e.m.) of 88(6) per cent of the preoperative value. These results demonstrate that aspects of the metabolic and acute-phase responses are attenuated following laparoscopic cholecystectomy, consistent with a reduction in tissue trauma.

Blood Glucose↗
PubMed1994

Postoperative changes in resting energy expenditure and interleukin 6 level in infants.

The relationship was determined between resting energy expenditure (REE) and interleukin (IL)6 level following surgery in infants. Sixteen infants of mean(s.e.m.) weight 3.2(0.2) kg undergoing uncomplicated surgery were studied. The operative stress score was recorded and plasma IL-6 levels were measured before and 4, 8, 12 and 24 h after surgery. Respiratory gas exchange was measured by indirect calorimetry before and at 2, 4, 6, 8, 10, 12, 24 and 48 h. Urinary nitrogen excretion was measured and calculated. IL-6 levels increased significantly after surgery (P = 0.006) and were maximal at 12 h. There was a linear correlation between the increase in IL-6 level and operative severity score (r = 0.61, P = 0.012). REE increased significantly after operation (P < 0.001), peaking at 2-4 h, and returned to baseline levels by 12 h. The changes in REE preceded those in IL-6. IL-6 is a marker of the stress response in infants and may play a role in the subsequent modulation of this response.

C-Reactive Protein↗
PubMed1994

Relationship between weight loss, reduction of body cell mass and inflammatory response in patients with cancer.

Reduced food intake is a major cause of continuing weight loss in patients with cancer. Previous work has suggested that an ongoing inflammatory response may also contribute to weight loss and alter the nature of body tissue loss. To examine this, body cell mass was estimated using measurements of total body potassium (TBK) in 31 patients with gastrointestinal cancer and weight loss with or without an inflammatory response (C-reactive protein level above 5 mg/l). Albumin levels, total body water and 24-h urinary creatinine clearance were also measured. When measured TBK was expressed as a percentage of predicted normal values there was a significant reduction in TBK for patients with an inflammatory response compared with that of those without (P = 0.04). However, when a different prediction equation for TBK was used this difference was not significant (P = 0.29). Therefore, it remains uncertain whether an ongoing inflammatory response in patients with cancer and weight loss contributes to loss of body cell mass.

Aged↗
PubMed1994

Effect of megestrol acetate on weight loss, body composition and blood screen of gastrointestinal cancer patients.

Reduced food intake is probably the major cause of continuing weight loss in cancer patients. Therefore, agents which stimulate food intake may be of significant benefit to such patients. To examine this, a randomized double-blind placebo controlled study of megestrol acetate was carried out. 38 gastrointestinal cancer patients with weight loss (8-43% of pre-illness stable weight) were entered into the study. 26 were evaluable at 6 weeks and 21 at 12 weeks. Clinical details, serum biochemistry and haematology were examined at 6 and 12 weeks and total body water, total body potassium at 12 weeks after the baseline assessment. There was no significant weight change in either group over the 6 or 12 weeks. Furthermore, there was no significant difference in total body water, total body potassium, blood biochemistry or haematology between the groups over the study period. It does not appear that megestrol acetate at a dose of 480 mg/day results in weight gain in advanced gastrointestinal cancer patients with weight loss.

Journal Article↗
PubMed1994

Cytokine changes in the postoperative period.

The trauma of elective surgery leads to the release of cytokines, many of which act primarily at local level having been released from tissue macrophages, circulating monocytes or other activated tissues. There is also a reproducible response in plasma IL-6, the magnitude of which relates to the magnitude of operative trauma. It seems likely that cytokines have an important role in mediating the anorexia associated with the postoperative period, and this may be associated with increased release of CRF from the hypothalamus. Further studies on the interrelationship between cytokine and neuroendocrine systems will lead to a greater understanding of the control of food intake following injury, and will permit the development of new strategies to improve the effectiveness of nutrition at this time.

Cytokines↗
PubMed1994

Selenium and glutathione peroxidase status in paediatric health and gastrointestinal disease.

To examine the effect of paediatric GI disease on selenium concentration in plasma and glutathione peroxidase activity in plasma and red cells, results in children with Crohn's disease (n = 39), cystic fibrosis (n = 14), intractable diarrhoea (n = 13), and biliary atresia (n = 10) were compared with those from 86 healthy children undergoing routine operations. In Crohn's disease, plasma selenium concentrations were rarely low, but glutathione peroxidase activity was increased in the plasma and reduced in the red cells. Selenium concentration and glutathione peroxidase activity increased with steroid treatment but decreased with a selenium-deficient elemental diet. Plasma selenium concentration was normal in children with cystic fibrosis but very low in severely malnourished children with biliary atresia and intractable diarrhoea. Selenium concentration and glutathione peroxidase activity should be monitored in children with severe malnutrition or requiring prolonged nutritional support. Supplementation is recommended in cases of severe selenium depletion.

Adolescent↗
PubMed1994

Trypsinogen activation peptides (TAP) concentrations in the peritoneal fluid of patients with acute pancreatitis and their relation to the presence of histologically confirmed pancreatic necrosis.

This study measured the volume and colour, as well as concentrations of trypsinogen activation peptides (TAP) in the peritoneal fluid of 22 patients with acute pancreatitis and related these findings to the presence of pancreatic necrosis. Nine patients had a severe attack with histologically confirmed pancreatic necrosis, seven a severe attack without confirmed necrosis, and six a mild attack, also without confirmed necrosis. A free fluid volume > 20 ml or free fluid colour > grade 5 on the Leeds chart, or both detected histologically confirmed pancreatic necrosis with a sensitivity of 100% and specificity of 31%. A total peritoneal fluid TAP concentration of > or = nmol detected histologically confirmed pancreatic necrosis with a sensitivity of 89% and specificity of 85%, figures comparable with contrast enhanced computed tomography. These findings suggest that the measurement of peritoneal fluid TAP concentrations can detect effectively histologically confirmed pancreatic necrosis and that such measurements may prove useful in the selection of patients for surgery.

Acute Disease↗
PubMed1993

Role of interleukin-6 in mediating the acute phase protein response and potential as an early means of severity assessment in acute pancreatitis.

A number of laboratory and clinical studies have shown that interleukin-6 is the principal mediator of the acute phase protein response. In this study the relationship between serum concentrations of interleukin-6 and C-reactive protein in acute pancreatitis are examined and the ability of interleukin-6 to discriminate between severe and mild attacks is assessed. We have studied 24 patients (10 severe and 14 mild). Serum samples were collected on admission, six hourly for 48 hours and then 12 hourly for a further three days. When the areas under the curves of individual patients were compared there was a strong correlation between the total production of interleukin-6 and C-reactive protein (r = 0.73) (Spearman rank correlation) and peak interleukin-6 and C-reactive protein concentrations (r = 0.75), suggesting a close relationship between interleukin-6 and C-reactive protein production. Both on admission and peak interleukin-6 concentrations were significantly higher in patients with severe than mild disease. There was no significant difference in on admission C-reactive protein concentrations, although significant differences were seen when peak concentrations were considered. Utilising a peak interleukin-6 concentration of > 130 u/ml, we were able to distinguish between severe and mild attacks of acute pancreatitis with a sensitivity of 100% and specificity of 71%. These figures were comparable with those for peak C-reactive protein, a C-reactive protein of > 150 mg/l detecting severe attacks of acute pancreatitis with a sensitivity of 90% and specificity of 79%. In view of the fact that interleukin-6 concentrations peaked earlier than those of C-reactive protein, interleukin-6 is capable of providing comparable, but earlier severity prediction than C-reactive protein.

Acute Disease↗
PubMed1992

Effect of combined prednisolone, epidural analgesia, and indomethacin on the systemic response after colonic surgery.

Twenty patients undergoing colonic resection were randomized to either conventional postoperative pain treatment with morphine chloride and acetaminophen (group 1, n = 9) or methylprednisolone sodium succinate 90 minutes before surgery plus intraoperative neural blockade, with a postoperative analgesic regimen with combined bupivacaine hydrochloride-morphine and indomethacin sodium for systemic effect (group 2, n = 11). Assessments of pain, pulmonary function, convalescence, and various injury factors were done several times until 8 days after surgery. Postoperative pain and hyperthermic response were eliminated in group 2. Conventional reduction in pulmonary function measures was improved in group 2, and fatigue and mobility were less pronounced. Prostaglandin E2, interleukin 6, and C-reactive protein levels increased in both groups, but significantly less in group 2. These results suggest that a combined neural and humoral blockade may more effectively inhibit the global stress response to elective surgery than previously observed with neural blockade with or without indomethacin.

Acetaminophen↗
PubMed1992

Bioelectrical impedance analysis in the measurement of the body composition of surgical patients.

The evaluation of nutritional status in surgical patients remains a difficult problem. Bioelectrical impedance analysis (BIA) is a new method of body composition analysis which is easily performed at the bedside. This study determined the accuracy of BIA in the measurement of total body water (TBW) and potassium (TBK) in a heterogeneous group of surgical patients. The resistance and reactance components of impedance were measured with a whole body impedance analyser. Tritiated water dilution and whole body monitoring were the reference methods for TBW and TBK analysis. With the BIA technique the coefficient of variation for the estimation of TBW was 8.1 per cent and for TBK was 6.4 per cent. Allowing for the errors of the reference methods these results show that BIA is of limited value in the estimation of TBW but may provide a useful index of TBK.

Adult↗
PubMed1992

Effect of aseptic abscesses in protein-deficient rats on the relationship between interleukin-6 and the acute-phase protein, alpha 2-macroglobulin.

1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0-14 days) after the injection for determination of albumin, total protein, alpha 2-macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response. 2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main alpha 2-macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 +/- 0.5 versus 5.33 +/- 0.75 g/l, P < 0.01, and area under the concentration-time curve 18.43 +/- 2.13 versus 7.96 +/- 1.48 g/l-1 days, P < 0.01, in the normal group and protein-deficient group, respectively). 3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6-48 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗