Prostaglandins as mediators of stress reaction.
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Prostaglandins↗
Biomedical subjects
H Kehlet
Publications and source records attributed to H Kehlet.
Postoperative depression of lymphocyte transformation response to microbial antigens.
Cell mediated immunofunction, as expressed by total lymphocyte count, B and T cell count, in vitro blastogenic response to unspecific mitogens (phytohaemagglutinin and poke weed mitogen) and microbial antigens (Candida albicans, purified protein derivative, Staphylococcus aureus and Escherichia coli), was assessed in 8 otherwise normal patients undergoing elective, uncomplicated gastric surgery. The results showed a significant depression in all parameters on the first and/or third postoperative day, except for the blastogenic response to unspecific mitogens, which was unchanged throughout the study. Compared with the preoperative value, the total lymphocyte count decreased by 48% with a similar fall in both T and B cells. The blastogenic response to C. Albicans, purified protein derivative, Staph. aureus and E. coli decreased by 45, 42, 75 and 76% respectively. When measured on the seventh and ninth postoperatively days all parameters had returned to preoperative levels. Thus, even during clinically uncomplicated surgery, significant cell mediated immunodepression can be demonstrated by the blastogenic response of peripheral lymphocytes to common microbial antigens. The results suggest that this phenomenon may be secondary to the disappearance of specific reactive lymphocytes from the peripheral blood following surgical trauma.
Adult↗
The effect of short-term glucagon infusion on kidney function in normal man.
Kidney function was studied in six normal males before and during a 2 h glucagon (10 ng/kg/min) infusion. The following variables were determined during each 20 min clearance period; glomerular filtration rate (GFR), renal plasma-flow (RPF) , filtration fraction (FF), urinary albumin and beta2-microglobulin-excretion rates. Glucagon infusion resulted in a fourfold increase in plasma glucagon concentration. The infusion induced a significant increase in GFR (+9%), FF (+9%) and urinary beta2-microglobulin excretion rate (+32%), (p less than 0.01). RPF and urinary albumin excretion rates were not significantly changed. We suggest that glucagon may contribute to the reversible kidney function alterations typically found in poorly regulated juvenile diabetes, a state with relative or absolute hyperglucagonaemia.
Adult↗
Diurnal variations in plasma prolactin, growth hormone, cortisol and blood glucose in labile diabetes mellitus.
In labile diabetes mellitus wihout ketoacidosis we have studied plasma prolactin levels and a possible causal connection between fluctuation in blood glucose concentration and plasma prolactin, growth hormone and cortisol levels. The hormone concentrations in plasma and blood glucose concentration were determined at 20 min intervals for a 24 h period in six male patients with insulin treated diabetes mellitus. Prolactin varied within the normal range but without any significant rise in relation to sleep in five out of the six patients. Growth hormone levels were low with superimposed secretory peaks. Plasma cortisol showed a normal diurnal rhythm. Blood glucose fluctuated as expected, but the variations and especially the falls in blood glucose to non-hypoglycaemic levels were not followed by increases in plasma hormone concentrations. No relationship could be demonstrated between the changes in the plasma concentration of prolactin, growth hormone and cortisol.
Adolescent↗
C-peptide and insulin during blockade of the hyperglycaemic response to surgery by epidural analgesia.
UNLABELLED: Insulin secretion, as expressed by peripheral plasma insulin and C-peptide levels, was studied during and after abdominal hysterectomy in six patients having general anaesthesia and in six patients having epidural analgesia. The hyperglycaemic response to surgery was abolished during epidural analgesia. Insulin as well as C-peptide levels in plasma were low and unchanged during general anaesthesia and low and slightly decreasing during epidural analgesia. CONCLUSIONS: (1) Insulin secretion to the hyperglycaemic stimulus is blocked during surgery: (2) abolition of the hyperglycaemic response to surgery by epidural analegesia is not caused by an increased insulin secretion.
Adult↗
The blocking effect of epidural analgesia on the adrenocortical and hyperglycemic responses to surgery.
The adrenocortical and hyperglycemic responses to hysterectomy were studied in five groups of patients receiving: general anesthesia (group I), general anesthesia + epidural analgesia extending from Th10-S5 (group II), general anesthesia + epidural analgesia extending from Th8-S4--5 (group III), general anesthesia + epidural analgesia extending from Th4--6-S5 (group IV) and epidural analgesia extending from Th4-S5 without general anesthesia (group V). The results showed that the cortisol response was abolished in group V, inhibited in group IV and normal in groups II and III. The hyperglycemic response to surgery was inhibited in groups II, III and IV, and abolished in group V. Epidural analgesia from Th4 to S5, preventing the adrenocortical and hyperglycemic responses to hysterectomy, and possibly also inhibiting other components of the endocrine-metabolic response to surgery, may have important applications in further studies of the physiologic significance of the endocrine-metabolic response to surgery.
Adrenal Cortex↗
Rapid decrease in plasma-triiodothyronine during surgery and epidural analgesia independent of afferent neurogenic stimuli and of cortisol.
Changes in circulating triiodothyronine (T3), thyroxine (T4), binding of thyroid hormones to plasma proteins (resin-T3 test), cortisol, and glucose were evaluated in sixteen patients undergoing abdominal hysterectomy. In eight of the patients afferent neurogenic impulses from the surgical area were blocked during and after operation by epidural analgesia. These patients were pain-free, and the normal stress-induced increase in cortisol and glucose was abolished. During epidural analgesia and general anesthesia plasma-T3 fell rapidly and values in the hypothyroid range were found 6 hours after skin incision. Similarly, an increase in the resin-T3 test reflected decreased binding of T3 to plasma proteins. Plasma-T4 decreased slightly during surgery and epidural analgesia (as it does when other anaesthetics are given), but increased during general anaesthesia. These results indicated that the alterations in thyroid hormones and their binding to plasma proteins after surgery are not caused by a stress-induced increase in plasma-cortisol or by neurogenic afferent stimuli from the surgical area, factors which are both known to affect concentrations of other hormones.
Adult↗
Comparative study of ultrasound, 131I-19-iodocholesterol scintigraphy, and aortography in localising adrenal lesions.
Twenty-seven consecutive patients with endocrinological disease necessitating adrenal surgery underwent blind preoperative investigation with ultrasound, renal aortography, and adrenocortical scintigraphy for an adrenal lesion. Nine patients had pituitary-dependent Cushing's syndrome, five had pituitary-independent Cushing's syndrome, four had an adrenocortical androgenic excess, and nine had a preoperative diagnosis of phaeochromocytoma. The predictive value of preoperative ultrasound was 100% for a positive finding and 79% for a negative result. Preoperative aortography had a predictive value of 83% for a positive finding and 64% for a negative result; and the predictive value of adrenocortical scintigraphy was 100% for a positive finding and 85% for a negative finding. In localising biochemically suspected adrenal lesions ultrasound should be the first choice, since it is rapid, noninvasive, cheap, and reasonably accurate. Adrenocortical scintigraphy has a similar diagnostic value, especially in Cushing's syndrome, but it is time consuming. Nevertheless, it may be preferable for diagnosing small glucocorticoid-secreting adenomas. Aortography should be reserved for cases with inconclusive diagnoses and suspected extra-adrenal phaeochromocytomas.
Adolescent↗
Short ACTH test in assessing hypothalamic-pituitary-adrenocortical function.
The adrenocortical response to the simple 30-minute ACTH stimulation test was compared with the hypothalamic-pituitary-adrenocortical (HPA) response to insulin-induced hypoglycaemia in 25 patients with various degrees of hypothalamic-pituitary malfunction. The correlations between the increase in plasma cortisol during insulin hypoglycaemia and that during ACTH stimulation (r = 0-66) and between peak plasma cortisol levels during the two tests (r = 0-90) were highly significant. Peak plasma cortisol levels in individual patients were similar on both tests, no patient showing any major discrepancy between the two test results. Thus the simple 30-minute ACTH stimulation test seems to be reliable in detecting imparied HPA function.
Adolescent↗
Cyclic AMP, glucose and cortisol in plasma during surgery.
Cyclic AMP, glucose and cortisol in plasma were measured before, during and after major surgery (hysterectomy, six patients) and minor surgery (tympanoplasty, 10 patients). During major surgery cyclic AMP as well as glucose and cortisol showed a pronounced increase. During minor surgery cyclic AMP, glucose and cortisol levels were significantly lower than in the group undergoing major surgery. It is concluded that the increase of plasma cyclic AMP during operative procedures is related to the severity of the trauma.
Adult↗
Quantitation of the accelerating effect of metyrapone on cortisol metabolism.
Quantitation of the accelerating effect of metyrapone on cortisol metabolism has been made by determination of the metabolic clearance rate (MCR) of exogenous cortisol during a metyrapone load. Six adrenalectomized patients were studied. The slope of cortisol concentrations in plasma was determined after intravenous administration of 0-3 mg cortisol/kg b.w. with or without metyrapone 17-5 mg/kg b.w./h. In all six patients studied, the MCR of cortisol increased during metyrapone load from an average of 12-3 +/- 5-0 (SD) l/h to 29-6 +/- 15-7 (SD) l/h or corrected for body weight 3-0 +/- 1-1 (SD) ml/kg b.w./min to 7-1 +/- 2-5 (SD) ml/kg b.w./min. The discrepancy discovered in clinical practice between the relatively small rise in plasma total corticosteroid concentration and the greater increase in urinary excretion of corticosteroid metabolites during the metyrapone test may be explained by the findings in this study.
Adrenalectomy↗
Effect of epidural analgesia on the glycoregulatory endocrine response to surgery.
Plasma concentrations of glucose, insulin, glucagon, cortisol, growth hormone and prolactin were measured repeatedly in ten females undergoing abdominal hysterectomy during general anaesthesia. In addition to general anaesthesia five of the patients had continuous epidural analgesia effective for the first 26 postoperative hours. Plasma glucose was elevated during surgery and postoperatively, but not in patients having epidural analgesia. Insulin was low and unchanged in both groups. Glucagon was unchanged and similar in both groups. Cortisol was lower during surgery in the epidural group, but not postoperatively. Growth hormone increased during surgery in four of five patients receiving general anaesthesia alone, but no changes were observed in the epidural group. Prolactin was greatly elevated in all patients immediately after induction of anaesthesia and then fell rapidly during surgery, similarly in both groups. It is concluded that epidural analgesia can inhibit the hyperglycaemic response to surgical stress, but this effect cannot be uniformly correlated to changes in peripheral plasma levels of insulin, glucagon, cortisol, growth hormone or prolactin.
Adult↗
Effect of metyrapone on cortisol binding capacity in plasma.
Metyrapone was added in vivo to six different samples of normal plasma (0.1 mg/ml plasma) and administered orally (30 mg/kg) to 5 adrenalectomized patients. An increased ratio free, non protein-bound cortisol: total cortisol in plasma was demonstrated after metyrapone in all six in vitro studies and in 4 of the 5 adrenalectomized patients. These findings may explain the accelerating effect of metyrapone on cortisol metabolism.
Adrenalectomy↗
Effects of androgens on oxygen affinity in vivo and 2,3-diphosphoglycerate content of red cells in peripheral arterial insufficiency.
The effect of testosterone on the red cell concentration of 2,3-diphosphoglycerate (2,3-DPG) and on the in vivo oxygen affinity of venous blood was investigated. Six male patients with peripheral arteriosclerosis received 500 mg testosterone enantas intramuscularly for 15 weeks. Six matched controls received 2 ml NaCl weekly for the same period of time. The hemoglobin concentration, the hematocrit, and the 2,3-DPG concentration increased significantly during testosterone treatment, while no significant changes in the oxygen affinity could be detected. It is concluded that testosterone in the doses applied here does not improve oxygen unloading from the blood.
Aged↗
Glucocorticoid maintenance therapy following adrenalectomy: assessment of dosage and preparation.
Plasma cortisol was monitored repeatedly after oral administration of cortisol and cortisone (cortisone acetate) to seven adrenalectomized patients with pituitary-dependent Cushing's syndrome. The amount of glucocorticoid administered was 25 mg cortisol or 33 mg cortisone/g urine creatinine/24 h. Peak plasma cortisol levels were within recommended values in all patients after cortisone and in three of the patients after cortisol. The remaining four patients had elevated peak plasma cortisol levels after cortisol. Transcortin binding capacity in plasma was normal. It is concluded that cortisol as well as cortisone is suitable for oral glucocorticoid substitution therapy in patients with normal liver function, but that cortisone apparently gives a marginally smoother plasma cortisol curve. However, it is essential to monitor plasma cortisol after institution of glucocorticoid maintenance therapy, since different and unpredictable plasma cortisol levels may exist after a given amount of glucocorticoid, although the dose required correlates reasonably well with creatinine excretion in urine.
Administration, Oral↗
[Diurnal variations in blood glucose and plasma cortisol in juvenile diabetes mellitus without ketoacidosis].
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Adolescent↗
A rational approach to dosage and preparation of parenteral glucocorticoid substitution therapy during surgical procedures. A short review.
A rational physiological schedule for parenteral glucocorticoid substitution therapy during surgical procedures is proposed based on the principle of imitating the normal hypothalamic-pituitary-adrenocortical response to surgery. The schedule includes the injection of 25 mg cortisol intravenously in all patients together with induction of anaesthesia. Following major surgery, 100 mg cortisol dissolved in saline or glucose is continuously infused intravenously every 24 hours until gastrointestinal function permits oral intake of usual glucocorticoid substitution therapy. In case continuous cortisol infusion is undesirable, 25 mg cortisol is injected intravenously every four hours. Following minor surgery, usual oral glucocorticoid therapy is started immediately after the operation. It is recommended to use water-soluble cortisol preparations and not cortisone acetate, which results in limited plasma cortisol levels.
Administration, Oral↗
Urinary excretion of free cortisol in impaired renal function.
Total cortisol and free, non protein-bound coritsol in plasma and urinary excretion of unconjugated free cortisol were measured during iv infusion of cortisol at varying dose rates in eight patients with impaired renal function. The results showed that free urinary cortisol decreased with decreased glomerular filtration rate (GFR), also compared to free cortisol level in plasma. An increase in free cortisol in plasma had no influence on GFR. It is concluded that determination of free urinary cortisol, otherwise useful in diagnosing Cushing's syndrome, may be of less value in patients with impaired renal function.
Aged↗