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Biomedical subjects

M J Ellis

Publications and source records attributed to M J Ellis.

At least 55 records · Page 3Linked to original sources
PubMed1993

The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy.

OBJECTIVES: We compared the responses of the stress hormones, cortisol, ACTH, vasopressin (AVP), corticotrophin releasing hormone (CRH) and catecholamines to elective conventional and laparoscopic cholecystectomy. DESIGN: A right upper quadrant transverse incision was used for conventional cholecystectomy, and four 1-2-cm incisions for the laparoscopic procedure (for insertion of surgical instruments, diathermy, fibreoptic telescope and light source, and carbon dioxide insufflation). Blood was sampled immediately prior to premedication (temazepam), after induction of anaesthesia (fentanyl and thiopentone) and at 10-minute intervals until the end of the procedure (N2O maintenance, vecuronium relaxation). A blood sample was taken after reversal, and then at 10-minute intervals for 50 minutes. Plasma sodium and blood pressure were measured at similar intervals. Results are expressed as mean +/- standard error. PATIENTS: Twelve patients were studied (six in each group). MEASUREMENTS: Peptide hormones were measured by radioimmunoassay, cortisol by ELISA and catecholamines by HPLC. RESULTS: The mean premedication hormone values for the conventional and laparoscopic procedures did not increase significantly after induction of anaesthesia. Within 10 minutes of the first incision, however, there was a marked concordant rise in mean plasma ACTH and AVP levels for both procedures (conventional: ACTH, from a premedication value of 10.2 +/- 1.7 to 80.1 +/- 14.3 pmol/l, AVP from 1.2 +/- 0.4 to 117 +/- 24 pmol/l, P < 0.01 for both hormones; laparoscopic: ACTH from 5.8 +/- 2.6 to 55.1 +/- 26.0 pmol/l, AVP from 1.6 +/- 0.11 to 49.2 +/- 27.09 pmol/l). At the end of both types of operation mean levels of ACTH and AVP were still elevated, although the ACTH: AVP ratio had increased. Greater variability in ACTH and AVP responses was seen in the laparoscopic than in the conventional procedure, three patients showing a relatively small response to surgery. Total secretion of ACTH during both types of surgery was not significantly less both during (P < 0.05), and after (P < 0.01) laparoscopic surgery. For both procedures, the timing of AVP and ACTH peaks was significantly related (P < 0.002). A small but significant rise in CRH was observed 30 minutes after the start of surgery for both procedures P < 0.05). The timing of CRH and ACTH peaks was unrelated. The maximum mean plasma cortisol level for the conventional procedure (1268 +/- 147 nmol/l) was reached 20 minutes after reversal of anaesthesia and remained at this level until the end of sampling. The cortisol response was comparable during the laparoscopic procedure but was beginning to fall at 60 minutes post-operatively. Plasma adrenaline responses to the two types of surgery were not significantly different, but the plasma total noradrenaline response to laparoscopic surgery as indicated by the response area during the first 20 minutes was significantly increased (P < 0.02). Plasma sodium, renin activity and initial systolic blood pressure fall were not significantly different during the two procedures. CONCLUSIONS: For both procedures, the peak of ACTH secretion after incision is likely to be AVP dependent, and the timing of peak levels of these two hormones was significantly related. Subsequent ACTH secretion may be the result of an interaction between AVP and CRH. Laparoscopic cholecystectomy results in a smaller AVP rise than does the conventional procedure, and plasma AVP falls more rapidly post-operatively. During the period of observation, ACTH, CRH, cortisol and adrenaline responses were not significantly lessened by the laparoscopic approach, but there was a significant increase in the noradrenaline response. Stress hormone monitoring may assist further improvements in surgical technique.

Adrenocorticotropic Hormone↗
PubMed1991

Plasma corticotrophin releasing factor and vasopressin responses to exercise in normal man.

OBJECTIVE: To evaluate the hypothalamo-pituitary-adrenal (HPA) response to both mild and intense exercise. DESIGN: Maximum oxygen consumption (VO2max.) was initially determined. Exercise to 20% (mild) and 90% (intense) VO2max. was undertaken in random order. Subjects were exercised over a 5-minute period to the required level of intensity, which was maintained for a further 10 minutes. SUBJECTS: Six trained male athletes. MEASUREMENTS: Brachial vein blood was sampled before and at 5-minute intervals during and after exercise and assayed for plasma cortisol, ACTH, arginine vasopressin (AVP), corticotrophin releasing factor (CRF), sodium and lactate levels. Haemoglobin and haematocrit were measured before and at the end of exercise. Heart rate was monitored continuously and blood pressure measured whenever blood was sampled before and after exercise. RESULTS: Maximum heart rate was 184 +/- 2 and 82 +/- 5 (mean +/- SEM) beats per minute at 90 and 20% VO2max. respectively. Plasma volume fell by 8.7 +/- 2.4% with intense exercise. Significant increases in plasma concentrations of AVP, ACTH and cortisol, but not CRF, occurred during intense exercise. Plasma sodium concentration, which increased during intense but not mild exercise, peaked at 10 minutes after the onset of exercise and preceded the rise in plasma AVP. The AVP peak clearly preceded the ACTH peak in two subjects and occurred synchronously with it in three subjects. CONCLUSION: These results indicate that although significant HPA activation occurs during intense exercise, CRF does not appear to play a major role in mediating the ACTH response to an acute episode of vigorous exercise in man. AVP may be more important in this regard.

Adrenocorticotropic Hormone↗
PubMed1991

The effect of acute exercise on the secretion of corticotropin-releasing factor, arginine vasopressin, and adrenocorticotropin as measured in pituitary venous blood from the horse.

We have used the technique which we have developed for collecting pituitary venous blood from conscious, undisturbed horses to study the effect of acute vigorous exercise on the secretion of CRF, arginine vasopressin (AVP) and ACTH. Pituitary venous (pit) blood was collected every 1-5 min from nine trained racehorses at rest in the stable. The horses then trotted quietly for 10 min, after which they galloped as fast as possible for 4-6 min, before returning to the stable where sampling continued. In Exp 1 (n = 5) no blood samples were taken during exercise, whereas in Exp 2 (n = 4), pit blood was collected every 30 sec during exercise. Immediately after exercise, significant elevations in heart rate (P less than 0.001), body temperature (P less than 0.01) and hematocrit (P less than 0.001) were observed as compared with preexercise values. Jugular cortisol levels were higher after exercise (301.9 +/- 35.2 nmol/liter; mean +/- SEM) than before (187.3 +/- 34.8; P less than 0.01; n = 9). Likewise, jugular AVP levels increased with exercise (before, 0.65 +/- 0.11 pmol/liter; after 3.2 +/- 0.6; P less than 0.01; n = 6), whereas jugular CRF was not altered by exercise (before, 0.38 +/- 0.08 pmol/liter; after, 0.93 +/- 0.31; n = 6; NS). In Exp 1, no significant changes in pit ACTH, AVP, or CRF were observed after exercise. However in Exp 2 when pit blood was sampled during exercise all horses showed an immediate and dramatic rise in ACTH (P less than 0.01) and AVP (P less than 0.005) secretion which peaked during galloping with mean fractional changes above resting levels of 23.6 +/- 9.9 for ACTH and 51.7 +/- 24.0 for AVP. After exercise pit AVP levels were not different from resting, whereas ACTH remained elevated (11.4 +/- 6.9-fold above resting levels). By contrast, pit CRF levels were not altered by exercise. In both experiments together, pit AVP and ACTH concentrations were correlated in eight of the nine horses, whereas pit CRF and ACTH concentrations were positively correlated in only one of seven horses. We conclude that acute exercise causes a transient increase in ACTH secretion which occurs synchronously with an increase in AVP secretion. CRF does not appear to play a major role in mediating the initial ACTH response to exercise.

Adrenocorticotropic Hormone↗
PubMed1990

Plasma corticotrophin-releasing factor and vasopressin responses to hypoglycaemia in normal man.

The plasma cortisol, ACTH, AVP and corticotrophin-releasing factor (CRF) responses to insulin-induced hypoglycaemia were investigated in six normal men using a controlled, randomized, cross-over design. Hormonal concentrations were determined following insulin or saline injection. The maximum cortisol response was seen at 90 min while plasma ACTH, AVP and CRF concentrations peaked at 45 min following insulin injection. The responses of the insulin-treated and control groups were compared by assessing the incremental response from baseline (pre-injection) to peak hormone levels. A significant increase was observed for each hormone following insulin injection. The mean of the incremental responses between 30 and 120 min in each subject was also statistically greater for each hormone in the insulin-treated group when compared with the control group. These results are consistent with the hypothesis that AVP and CRF are both physiological mediators of ACTH secretion induced by a hypoglycaemic stress.

Adrenocorticotropic Hormone↗
PubMed1989

Trace element levels in the blood of workers in two steel works and a non-ferrous plant handling lead and cadmium compared with a non-exposed population.

The concentrations of 14 elements in the blood of steelworkers and industrial workers exposed to lead- and cadmium-containing dusts were measured and compared with a control group drawn from University and hospital laboratory staff. Measurements were also made of the concentrations of 20 elements in the dusts. Significantly elevated levels were observed for cadmium and lead in whole blood, but no other significant variations were noted. The concentrations of these two elements in the dusts confirmed the exposure of those groups showing high levels of cadmium and lead. High levels of iron or chromium in some of the dusts were not correlated with any changes in the mean blood levels of the exposed groups.

Air Pollutants, Occupational↗
PubMed1989

Reversal of hepatic encephalopathy and alteration in amino acid profiles after blocking a surgical splenorenal shunt by interventional radiological techniques.

Portal-systemic shunts are effective in preventing haemorrhage from varices in portal hypertension, but at the price of hepatic encephalopathy. We describe the blockage of a splenorenal shunt using interventional radiology, in a patient with incapacitating chronic encephalopathy. The procedure successfully reversed encephalopathy, without haemodynamic disturbances or haemorrhage from recurrent varices and was associated with a return of the plasma amino acid profile towards normal, with a reduction in aromatic amino acids and an increase in branch chain amino acids. This observation supports the hypothesis that changes in plasma amino acid profiles in patients with portal-systemic shunting are due to the diversion of portal blood rather than the underlying chronic liver disease.

Amino Acids↗
PubMed1988

Circulating plasma corticotrophin-releasing factor-like immunoreactivity.

Normal human peripheral plasma, examined by direct radioimmunoassay (RIA) for human corticotrophin-releasing factor (CRF) using seven different antisera, showed marked inhibition of tracer binding to antiserum. This apparently high CRF-like immunoreactivity (CRF-LI) did not dilute in parallel with synthetic human CRF-41. In comparison, most equine and ovine plasma samples had low CRF-LI concentrations. Plasma fractionation of both normal and late pregnancy human plasma on Sephadex G-75 at neutral pH indicated the majority of the CRF-LI to be of large molecular size. The molecular weight was estimated to be approximately 29,000 following chromatography of normal human plasma on Sephacryl S-200. The high CRF-LI in normal plasma was reduced to barely detectable levels by methanol treatment despite the recovery of added human CRF-41 of greater than 80%. Methanol extracts of late pregnancy human plasma, however, retained high CRF-LI which exhibited the immunoreactive and Sephadex elution characteristics of synthetic human CRF-41. 125I-Labelled human CRF-41 added to human plasma showed a reversible, time-dependent alteration in molecular size and reduction in binding to excess antiserum. These findings indicate that direct RIA of human CRF in unextracted plasma leads to spurious results and suggest the presence in human plasma of an interfering factor and/or binding substance that is not generally apparent in equine or ovine plasma under the conditions described.

Animals↗
PubMed1980

Free insulin, C-peptide and glucagon profiles in insulin dependent diabetes mellitus.

Glucose and hormone profiles, including plasma levels of glucagon, GH, total insulin, free immunoreactive and biologically active insulin were determined by hourly sampling in two groups of insulin dependent diabetics. The five patients in Group I were recently diagnosed and still had residual beta-cell function. The other six in Group II had disease of longer duration, had developed insulin antibodies, and were non-secretors of C-peptide. All patients were studied while receiving their usual maintenance doses of Semilente monocomponent insulin (Novo). Daily insulin requirements were 25.6 +/- 4 U in Group I and 52.2 +/- 7 U in Group II. The glucose profiles were similar in the periprandial periods but over the whole 24-hour period control was more unstable in the patients of Group II and during the period 2400-0200 h plasma glucose fell to low levels (minimum plasma glucose 1.5-3.0 mmol/l). Free insulin levels rose to peak levels over a similar time course but then fell more slowly in the Group II subjects. These patients had higher free, biologically active insulin and lower glucagon levels which were coincident in time with the early morning hypoglycaemia. These observations suggest that raised free insulin levels in the setting of an impaired counter-regulatory glucagon response are one of the factors contributing to glucose instability in long-standing diabetics.

Adolescent↗
PubMed1978

In vitro bioactivity of insulin analogues: lipogenic and anti-lipolytic potency and their interaction with the effect of native insulin.

This paper presents a survey of the biological potencies of a variety of naturally-occurring and semi-synthetic insulin analogues and a study of the joint biological action of some of these materials with native insulin. Biological activity was tested on isolated rat fat cells using lipogenesis from glucose as the metabolic index. A brief comparison using inhibition of fat cell lipolysis was included. The results indicated: 1. Analogue potencies varied considerably (0.4-100% insulin activity). Values obtained were mainly confirmatory but included two further B1-modified materials and a tricarbamylated insulin. The results supported previous indications on the relative roles of the A1, B1, and B29 residues of insulin for hormone activity. 2. Analogue bioactivities, whether assessed by stimulation of lipogenesis or inhibition of lipolysis, were similar for the four materials tested in both systems. The response of fat cells with respect to both metabolic indices occurred over a comparable range of insulin concentrations, with half maximal effects at 30-35 pmol 1(-1) insulin. 3. The presence of modified insulins appeared to alter the biological action of native insulin in vitro. Small effects of both potentiation and antagonism were identified.

Adipose Tissue↗
PubMed1977

B1-3,5-diiodotyrosine insulin: a valid tracer for insulin.

Insulin, specifically substituted at the PheB1 position with 3,5-diiodotyrosine, has been tested in several biological and immunological systems. Immunoreactivity was assessed using antisera specific for different parts of the insulin molecule. Biological activity in vitro was estimated on isolated rat fat cells. In vivo bioactivity (hypoglycaemia) and metabolism (metabolic and urinary clearance rates, half-life, apparent distribution space) were measured by infusion of the material into greyhounds. The results indicated that this B1-labelled insulin preparation was biologically fully active and, unlike randomly labelled preparations of iodoinsulin, was metabolised with kinetics indistinguishable from those of the unlabelled hormone. We suggest that this material is a valid tracer for insulin, fulfilling the criteria of high specific activity and biological identity to the native hormone.

Adipose Tissue↗
PubMed1976

Biological properties of chemically modified insulins. I. Biological activity of proinsulin and insulin modified at A1-glycine and B29-lysine.

Beef insulin, pork proinsulin and four derivatives of beef insulin modified at the A1-B29 site on the molecular surface have been studied. Three derivatives had a synthetic crosslink between the A and B chains. Previous studies with these materials [2, 3 and 5] had demonstrated in vivo bioactivities which were much higher than those displayed in vitro. This paper reports experiments which explain this discrepancy. The analogues were administered at equimolar rates to anaesthetised greyhounds by a priming-dose constant infusion technique and the plasma concentrations achieved were estimated by radioimmunoassay. Proinsulin and the modified insulins were metabolised more slowly than insulin. Biopotency values, which related fall in plasma glucose concentration to the total administered dose of analogue, agreed broadly with published results of conventional in vivo bioassays. On the other hand, calculation of potency in relation to the serum concentration of analogue actually achieved, yielded results which agreed more closely with in vitro assay data. We conclude that for these analogues, reported discrepancies between in vitro and in vivo biopotencies can be largely explained by the different rates at which these materials are metabolised.

Adipose Tissue↗
PubMed1976

Studies with the autotransplanted ovine pancreas: glucagon and insulin secretion.

Basic studies on the secretion of glucagon and insulin by the ovine pancreatic autotransplant in the neck are described. Of the 17 transplants in the series none failed to secrete glucagon and only three failed to secrete insulin in detectable amounts. The longest surviving transplant actively secreted both hormones 3 years after transplantation and five other transplants were functional and the animals healthy after 16 months. Exocrine secretion disappears shortly after transplantation. Sodium butyrate and alanine each promoted the secretion of both hormones by the transplant. Glucagon failed to promote insulin secretion by the transplant, although it apparently stimulated the ovine in situ pancreas. The immediate (presumably direct) effect of insulin was to inhibit transplant glucagon secretion. Hypoglycaemia induced by peripheral insulin administration failed to stimulate glucagon secretion by the transplant, although it did promote glucagon secretion by the ovine in situ pancreas. Heparin did not markedly suppress basal transplant secretion of either glucagon or insulin. Phasic response patterns occurred with both hormones during long butyrate perfusions, although first-phase responsiveness was not a constant feature. In one trial, first-phase responses fell off with repeated short butyrate infusions. Glucagon and insulin secretory patterns in response to butyrate were remarkably alike, suggesting a common mechanism. Loss of specific functions by the ovine pancreas after transplantation is discussed.

Animals↗