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Biomedical subjects

A Shenkin

Publications and source records attributed to A Shenkin.

At least 73 records · Page 4Linked to original sources
PubMed1992

The effects of systemic intraoperative hypothermia on the acute-phase and endocrine response to cardiac surgery.

To determine the ability of intraoperative hypothermia to modify changes in the plasma protein component of the acute-phase response (APR) and the plasma hormone component of the endocrine response (ER) to surgical injury, 20 patients undergoing coronary artery surgery were randomised to an intraoperative blood temperature of 28 degrees C or 20 degrees C during cardiopulmonary bypass (CPB). Serial measurements of pack-cell-volume corrected concentrations (PCVCC) of five plasma proteins (albumin, prealbumin, transferrin, caeruloplasmin, ferritin) and six plasma hormones (adrenaline, noradrenaline, cortisol, triiodothyronine, thyroxine, and thyroid-stimulating hormone) were obtained twice preoperatively, seven times during surgery, six times in the 24 hours following surgery, and a further four times until the seventh postoperative day. A more profound level of intraoperative hypothermia significantly reduced the plasma adrenaline response to CPB but not the other components of the ER or APR.

Acute-Phase Reaction↗
PubMed1992

Increased interleukin 6 concentrations in the absence and presence of HIV-1 infection in haemophilia.

AIMS: To measure IL-6 concentrations in asymptomatic HIV-1 antibody positive and negative haemophilic patients and to correlate these with IgG concentrations and CD4 positive cell numbers. METHODS: IL-6 concentrations were measured by bioassay in stored serum from a prospective cohort of haemophilic patients in whom immunoglobulins and T cell subsets had been determined. Values of IL-6 and immunoglobulins were also correlated with severity of liver disease. RESULTS: IL-6 concentrations were raised in haemophilic patients independent of HIV-1 antibody status. In HIV-1 antibody positive patients there was no correlation between IL-6 concentrations and CD4 positive cell numbers, but there was a correlation with IgG (r = 0.4; p = 0.05). In HIV-1 antibody negative patients there were no significant correlations. CONCLUSIONS: Haemophilic patients have increased IL-6 concentrations; in HIV-1 positive patients this is independent of the decline in CD4 cell count. The raised concentrations do not correlate with the clinical severity of liver disease.

Adult↗
PubMed1991

Role of the protease-antiprotease balance in peritoneal exudate during acute pancreatitis.

The peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals. Overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study. Human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation. The trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases. Of 21 exudates examined, three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases. All three patients were shocked at the time of sampling, two dying of fulminant pancreatitis within 24 h. Overwhelming of the peritoneal antiproteases was not confirmed, but may occur in a few instances where proteolytic enzyme release or zymogen activation continues. Intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man. The current data suggests that few patients are likely to benefit from such an approach.

Acute Disease↗
PubMed1991

Serum interleukin 6 (IL-6) - effect of surgery and under-nutrition.

We aimed to investigate the role of IL-6 as a mediator of the acute phase response (APR) in man; to assess the effect of under-nutrition on serum/plasma IL-6 levels; and to assess the value of IL-6 as a prognostic indicator by measuring IL-6 in timed venous samples taken from surgical patients and from protein deficient and control rats post-turpentine injections. Serum IL-6 rose in all surgical patients within 2-4h of incision. Peak levels differed among the groups and correlated significanlly with duration of surgery (r = 0.75, p<0.001). CRP did not rise in some patients and discriminated poorly among the groups. Patients who developed complications had higher IL-6 values at 24h post-incision than those making uneventful recoveries. Protein depleted rats had a significantly slower IL-6 response than controls. Serum IL-6 is a sensitive, early marker of tissue damage which might help to predict the development of surgical complications. Under-nutrition affects the IL-6 response in rats and may do so in man.

Editorial↗
PubMed1991

Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer.

It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation.

Acute-Phase Reaction↗
PubMed1991

Effect of surgical injury and intraoperative hypothermia on whole body protein metabolism.

Whole body protein turnover and urinary nitrogen and 3-methyl-L-histidine (3-MH) excretion were measured before and after cardiac surgery using cardiopulmonary bypass in 20 male patients randomized to an intraoperative blood temperature of 28 or 20 degrees C. Rates of whole body protein synthesis (WBPS) and breakdown (WBPB) were determined from the 15N isotopic enrichment of urinary urea, ammonium, and from a calculated end-product average (EPA) after a primed 24-h infusion of [15N]glycine. In the postoperative period, there was a 40% increase in median nitrogen excretion in the 28 degrees C group (P less than 0.03) and a 22% increase in the 20 degrees C group (P = 0.10). There was a 79% increase in the median postoperative 3-MH excretion in the 28 degrees C group (P = 0.01) and a 66% increase in the median postoperative 3-MH excretion in the 20 degrees C group (P less than 0.01). Postoperatively, there was a 23% fall in the median value of WBPS in the 28 degrees C group (P less than 0.01) and an 11% fall in the 20 degrees C group [not significant (NS)] measured by 15N enrichment of urinary urea. In contrast, when WBPS was measured from isotopic enrichment of urinary ammonium, there was an increase in the median value of the postoperative rates of WBPS in both groups, by 20% in the 28 degrees C group (P = NS) and 29% in the 20 degrees C group (P = 0.03). There was no significant change in the rate of WBPS and WBPB, judged by the postoperative EPA in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Trypsinogen activation peptides assay in the early prediction of severity of acute pancreatitis.

Trypsinogen activation can be quantified by measurement of released activation peptides (TAP assay). TAP assay in urine was performed on admission for 55 patients with acute pancreatitis. TAP concentration correlated with subsequent disease severity in 87%, whereas C-reactive protein concentration, and multifactorial scoring at 48 h, were correct in 55% and 84%. Sensitivity and specificity for TAP assay were 80% and 90%, for C-reactive protein 53% and 55%, and for multifactorial scoring at 48 h, 60% and 93%. Urine TAP assay distinguishes acute pancreatitis without trypsinogen activation from acute pancreatitis with trypsinogen activation, and helps to identify patients who will progress to the severe acute disease. Use of the assay should allow early intensive treatment of those who need it.

Acute Disease↗
PubMed1990

Magnesium deficiency in patients on home enteral nutrition.

Home enteral nutrition (HEN) is an established method of long term nutritional support. Many patients receiving HEN have Crohn's disease complicated by intestinal failure and malnutrition, including magnesium deficiency. It is unknown if HEN can correct magnesium deficiency or if patients on HEN can become magnesium deficient. We measured total magnesium intake in nine patients receiving HEN, and assessed their magnesium status. Two patients had magnesium intakes below the recommended dietary allowance of 15 mmol/day. Four patients (44%) had biochemical evidence of magnesium deficiency, although no patient had clinical signs of magnesium deficiency. Several magnesium deficient patients used a liquid feed which had a low magnesium content. Patients on HEN should have their magnesium status checked regularly and may require magnesium supplements.

Journal Article↗
PubMed1990

Palmitate turnover and its response to glucose infusion in weight-losing cancer patients.

Palmitate turnover in weight-stable control subjects (n = 4) and weight-losing patients with progressive malignant disease (n = 4) has been determined. Measurements were made after an overnight fast and during glucose infusion (3.5 mg/kg/min). Turnover rates were calculated from plateau isotopic enrichment of palmitate in plasma during a continuous infusion of 1-13C palmitate. Palmitate turnover was higher in the cancer group before (180%) and during glucose loading (170%) compared with the control group. Palmitate turnover was reduced during glucose administration by approximately 34% in both groups. Plasma concentration of insulin was decreased and of cortisol was increased in the cancer group compared with the control group before and during glucose infusion. We conclude that cancer patients with weight loss have increased rates of fatty acid turnover indicative of enhanced mobilisation of body fat stores. Altered plasma concentrations of insulin and cortisol may mediate this effect. Nonetheless, even at more advanced stages of cachexia cancer patients have normal control mechanisms for inhibiting fatty acid turnover following administration of carbohydrate.

Journal Article↗
PubMed1990

Parenteral nutrition in bone marrow transplantation.

Twenty-nine patients undergoing bone marrow transplantation (BMT) were randomised prospectively to evaluate the effect of parenteral nutrition (TPN) on morbidity and mortality. Fourteen patients received a standard regimen of TPN for 10 +/- 4 days (mean +/- SD). All patients had free access to oral diet, which was significantly reduced compared to pre-transplant intake. In the TPN group, serum bilirubin by day 14 and serum bilirubin and gamma glutamyl transferase by day 21 were significantly higher than in the controls (p < 0.05). These differences probably reflect the higher incidence of serious pyrexia (T > 38.5' C) and blood culture positive rates in the TPN group. Weight loss in the control group was significantly greater than that of the TPN group (p < 0.05). TPN did not affect time to grafting or incidence of graft-versus-host disease. The use of TPN in the nutritional support of patients in small BMT units requires careful consideration.

Journal Article↗
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

Estimation of paraproteins by immunoturbidimetry and electrophoresis followed by scanning densitometry.

A comparison of paraprotein estimation by immunoturbidimetry (IT) and electrophoresis followed by scanning densitometry (EFD) showed significant differences in concentration for IgG, IgA, and IgM paraproteins. Overestimation of IgM paraproteins by IT was particularly marked. Our data suggest that both techniques should be used for IgG and IgA paraproteins but for IgM paraproteins IT was found to be unsuitable and EFD is the method of choice.

Blood Protein Electrophoresis↗
PubMed1989

A two-site immunoradiometric assay for C-reactive protein in serum.

An immunoradiometric assay was developed for C-reactive protein in serum. The assay had a sensitivity of 5 micrograms/l and good precision. Correlation with radial immunodiffusion (r = 0.916) and EMIT (r = 0.935) was close. A reference range for healthy adults of 0.05-4.0 mg/l was derived.

C-Reactive Protein↗
PubMed1989

Effect of nutritional status on acute phase protein response to elective surgery.

The aim of this study was to assess the effect of nutritional status on the acute phase protein response to elective surgery. Matched pairs of patients with gastric or colorectal cancer were studied. Undernourished patients (body-weight less than 80 per cent of ideal and triceps skinfold thickness less than 65 per cent of standard) were matched with controls (body-weight greater than 95 per cent of ideal and triceps skinfold thickness greater than 80 per cent of standard) for age, sex, type of pathology and surgery. Blood samples taken preoperatively and on days 1-5 after operation were analysed for C-reactive protein, alpha 1-antitrypsin, alpha 1-acid glycoprotein, albumin, prealbumin and transferrin. There was no significant difference in any of the preoperative protein concentrations between the two groups although undernourished patients tended to have lower transferrin concentrations (mean +/- s.e.m., 2.2 +/- 0.3 g/l) than the control group (2.9 +/- 0.1 g/l). C-reactive protein response was significantly smaller in the undernourished group than in the control group (P = 0.05, Mann-Whitney U test). The responses of the other acute phase proteins did not differ between the two groups. There was no difference in the length of hospital stay after operation when undernourished patients (mean +/- s.e.m., 17.7 +/- 3.0 days) were compared with controls (14.3 +/- 3.6 days). Undernourished patients therefore have an attenuated C-reactive protein response to elective surgery. The significance of this in relation to morbidity and mortality in severely ill patients requires further investigation.

Acute-Phase Proteins↗
PubMed1989

C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis.

In a series of patients with acute pancreatitis we have studied complement factors, antiproteases (alpha 2-macroglobulin and alpha 1-antiprotease) and C-reactive protein to determine the value of their sequential measurement in the prediction of outcome relative to clinical assessment and current multiple factor scoring systems. Complement factors were unhelpful in predicting the severity of an attack. alpha 2-Macroglobulin levels were significantly lower in complicated attacks during days 3-8 and alpha 1-antiprotease levels were significantly higher during days 4-8. C-reactive protein concentrations showed the best discrimination between mild and complicated attacks, levels rising higher and persisting for longer in complicated attacks; these differences were highly significant from day 2 (the morning after admission) to day 8. The concentrations providing the best discrimination were found to be greater than or equal to 210 mg/l for the peak C-reactive protein (on the second, third or fourth day) and greater than or equal to 120 mg/l for the C-reactive protein at the end of the first week. Analysis demonstrated both the peak or seventh-day C-reactive protein concentration to be of similar accuracy to either the Ranson or Glasgow multiple factor scoring systems and slightly better for attacks associated with gallstones. The C-reactive protein assay is simple, quick to perform, provides useful clinical information and is more likely to be of value and to be adopted into routine clinical practice than multiple factor scoring systems.

Acute Disease↗