Cerebrospinal fluid spectrophotometry of bilirubin, not the Xanthochromic Index, for the detection of CT-negative sub-arachnoid haemorrhage.
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Biomedical subjects
Publications and source records attributed to A M Cruickshank.
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Alcoholic ketoacidosis (AKA) is a common reason for investigation and admission of alcohol dependent patients in UK emergency departments. Although well described in international emergency medicine literature, UK emergency physicians rarely make the diagnosis of AKA. There is increasing evidence that rather than being benign and self limiting, AKA may be a significant cause of mortality in patients with alcohol dependence. This literature review discusses the history, characterisation, pathophysiology, diagnosis, and management of AKA.
After subarachnoid haemorrhage (SAH), cerebral angiography is usually performed to establish a site of bleeding, which may then be treated surgically to prevent a potentially catastrophic re-bleed. The investigation of choice in the diagnosis of SAH is computerised tomography (CT). However, because CT can miss some patients with SAH, cerebrospinal fluid (CSF) spectrophotometry should be performed in those patients with negative or equivocal CT scans or those who have presented several days after the suspected bleed. Spectrophotometry should aim to detect the presence of both oxyhaemoglobin and bilirubin because either one or both of these pigments may contribute to xanthochromia following SAH. CSF supernatant is scanned using a double beam spectrophotometer at wavelengths between 350 nm and 650 nm. Oxyhaemoglobin alone produces an absorption peak at 413-415 nm, bilirubin alone produces a broad peak at 450-460 nm, and bilirubin together with oxyhaemoglobin produce a shoulder at 450-460 nm on the downslope of the oxyhaemoglobin peak. To minimise the frequency of false positive and false negative results, a protocol has been developed, which is described.
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[3H]AMPA and [3H]kainate binding to rat spinal cord was localised most densely in the substantia gelatinosa of the dorsal horn. Phospholipase A2 elicited a dose-dependent increase in specific [3H]AMPA binding but not in [3H]kainate binding. The enhancement of [3H]AMPA binding was blocked by bromophenacyl bromide and at 0 degree C and was not mimicked by arachidonic acid. Since GluR-B is the only AMPA receptor subunit detectable in the rat spinal cord, and recombinant homomeric GluR-B assemblies do not bind [3H]kainate, these results suggest phospholipase A2 may modulate [3H]AMPA binding to putative homomeric GluR-B receptors.
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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.
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)
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.
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.
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.
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.
The biochemical status of 152 patients in the Intensive Therapy Unit (ITU) was examined in relation to their clinical outcome. Patients who died in ITU or within one week of discharge were found to have significantly poorer riboflavin status than those who survived, but the majority of these measurements were within the normal range. Normal ranges established on a healthy population may therefore not be appropriate in investigation of vitamin nutritional status in seriously ill patients. These results do however suggest that riboflavin status is a risk factor in critically ill patients, and that subclinical riboflavin depletion may affect outcome.
There have been recent reports of hospitalised patients developing clinical thiamine deficiency, combined with much debate on the optimal supplementation of thiamine for the parenterally fed patient, particularly in the intensive therapy environment. We performed a retrospective study on 158 patients admitted to the Intensive Care Unit who required nutritional support. Patients who survived had significantly higher body thiamine status than those who died (p less than 0.01). There was no difference between serum albumin concentrations of the two groups. Twenty percent of the patients had biochemical evidence of thiamine deficiency and the mortality rate in these patients was 72% as compared with 50% mortality overall. Follow-up results suggest that current levels of thiamine supplementation are insufficient for critically ill intravenously fed patients. We suggest that patients be given a loading dose of 50-250 mg thiamine on admission to the Intensive Care Unit.
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