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Biomedical subjects

B Allolio

Publications and source records attributed to B Allolio.

At least 145 records · Page 8Linked to original sources
PubMed1990

Infusion of low dose etomidate: correction of hypercortisolemia in patients with Cushing's syndrome and dose-response relationship in normal subjects.

To investigate the adrenostatic potential of a nonhypnotic low dose etomidate infusion, we administered 0.03 mg/kg etomidate in a bolus injection, followed by constant infusion of 0.3 mg/kg.h for 24 h to 6 patients with severe Cushing's syndrome. The dose-response relationship also was determined in 15 normal subjects. Three groups of 5 received, respectively, doses of 0.03, 0.1, and 0.3 mg/kg.h etomidate for 5 h after an initial bolus dose of 0.03 mg/kg. The response to exogenously administered ACTH [0.25 mg ACTH-(1-24)], injected after the etomidate or control infusion, was determined in all normal subjects. In the six hypercortisolemic patients, serum cortisol concentrations decreased from 1374 +/- 436 nmol/L (mean +/- SEM) to 188 +/- 91 nmol/L after 11 h of etomidate infusion and remained low until the end of the infusion. Cortisol levels returned to pretreatment concentrations by 24 h. Excretion of urinary free cortisol decreased from 1180 +/- 196 to 185 +/- 66 nmol/day. In the normal subjects, administration of etomidate led to a dose-dependent decrease in serum cortisol from about 550 to 83 nmol/L, while 11-deoxycortisol rose from low or undetectable levels up to 346 nmol/L. In response to ACTH, cortisol levels rose in inverse proportion to the etomidate dose. It was, however, significantly reduced compared to normal saline infusion even after the lowest dose. Changes in aldosterone and corticosterone concentrations were similar to those in cortisol, and 11-deoxycorticosterone changed in a pattern similar to that of 11-deoxycortisol. Two of five normal subjects reported tiredness during the highest etomidate infusion. No other side-effects were noted. We conclude that iv administered etomidate in a low nonhypnotic dose reduces serum cortisol concentrations in a dose-dependent manner in both hyper- and eucortisolemic subjects. This study suggests that etomidate at a dose of 0.1 mg/kg.h or lower may be an effective strategy for the control of severe hypercortisolemia.

Adolescent↗
PubMed1990

A multihormonal response to corticotropin-releasing hormone in inferior petrosal sinus blood of patients with Cushing's disease.

Bilateral, selective, and simultaneous catheterization of the inferior petrosal sinus is not only a valuable tool in the differential diagnosis of Cushing's syndrome, but may also provide new insights into paracrine interactions at the pituitary level. We have investigated whether CRH (1 microgram/kg BW) has any effect on the release of PRL, GH, TSH, or the alpha-subunit of hCG during this procedure. Sixteen patients under evaluation for Cushing's syndrome (Cushing's disease, n = 12; ectopic ACTH syndrome, n = 2; glucocorticoid resistance, n = 1; hormonally inactive adenoma, n = 1) were catheterized. Two of the patients with Cushing's disease received 4.0 mg naloxone iv 15 min before stimulation with CRH. Patients with Cushing's disease demonstrated a central/peripheral gradient and an intersinus gradient not only for ACTH, but also for PRL, alpha-subunit, GH, and TSH, provided that the latter two hormones were not completely suppressed by the glucocorticoid excess. Moreover, all hormones increased in response to CRH on the side with the highest ACTH concentration; PRL rose from 31.2 +/- 6.4 to 61.6 +/- 12.4 micrograms/L (P less than 0.01), and alpha-subunit from 2.6 +/- 0.6 to 6.4 +/- 1.7 micrograms/L, (P less than 0.01). Naloxone was unable to abolish the PRL or alpha-subunit increase in response to CRH. A multihormonal response to CRH in inferior petrosal sinus blood was also observed in the patient with glucocorticoid resistance and in the patient with the hormonally inactive tumor, but not in the patients with ectopic ACTH secretion. The multihormonal response to CRH could be explained by cosecretion of other hormones together with ACTH from corticotroph adenoma, by an effect of CRH on pituitary blood flow, or by a paracrine action of pituitary corticotrophs on adjacent normal pituitary cells. Our results do not support the concept that such a paracrine action is mediated by beta-endorphin. However, a higher dose of naloxone may be required to antagonize the action of pituitary beta-endorphin.

Adrenocorticotropic Hormone↗
PubMed1990

Infusion of beta-endorphin has no suppressive effect on the releasing hormone-stimulated pituitary-adrenal-axis of normal human subjects.

The existence of a short-loop feedback inhibition of pituitary ACTH release by administration of beta-endorphin was postulated. However, data on the effect of peripherally administered beta-endorphin in humans are highly controversial. We infused human synthetic beta-endorphin at a constant rate of 1 microgram.kg-1.min-1 or normal saline to 7 normal volunteers for 90 min. Thirty min after starting the beta-endorphin or placebo infusion, releasing hormones were injected as a bolus iv (oCRH and GHRH 1 microgram/kg, GnRH 100 micrograms, TRH 200 micrograms) and blood was drawn for measurements of beta-endorphin immunoreactivity, all other pituitary hormones, and cortisol. Infusion of beta-endorphin resulted in high beta-endorphin plasma levels with a rapid decrease after the infusion was stopped. During the control infusion, beta-endorphin plasma levels rose in response to CRH. Plasma ACTH and serum cortisol levels in response to the releasing hormone were not different in subjects infused with beta-endorphin or placebo. The PRL response to TRH was significantly higher after beta-endorphin than after placebo (area under the stimulation curve 1209 +/- 183 vs 834 +/- 104 micrograms.l-1.h). There was no difference in the response of all other hormones measured. Our data on ACTH and cortisol secretion do not support the concept of a short-loop negative feedback of beta-endorphin acting at the site of the pituitary.

Adrenocorticotropic Hormone↗
PubMed1990

Intracellular free amino acid patterns in duodenal and colonic mucosa.

We report for the first time the concentrations of free amino acids in human intestinal biopsies obtained by routinely performed endoscopy. We studied 15 medical patients with no changes of the mucosa and six HIV-infected persons with duodenitis. The mean (and SD) sum of all amino acids, taurine excepted, was 61.9 (5.4) mmol/kg dry weight in duodenal biopsies of HIV-negative subjects (n = 11) and 82.9 (0.6) mmol/kg in colonic specimens: 50% (44%) of the total (minus taurine) consisted of aspartate and glutamate and 14% (12%), of the essential amino acids. The relative amino acid pattern in duodenum and colon differed completely from that for muscle: aspartate was fourfold higher; glutamate, phenylalanine, glycine, valine, leucine, and isoleucine were about twofold higher. In contrast, glutamine amounted only to 4% (duodenum) to 14% (colon) of muscle glutamine. In duodenal biopsies of the HIV-infected persons, we found significantly (P less than 0.01, except glutamine: P less than 0.025) increased concentrations of glutamate (24.1 vs 17 mmol/kg dry weight), ornithine (1.4 vs 0.4), valine (2.2 vs 1.7), and glutamine.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cardiac function in endocrine diseases: I. Acromegaly.

The aim of our echocardiographic study was to characterize cardiac function and anatomy of 14 acromegalics (A: 9 women, 5 men; mean age: 42.4 yrs) more closely. The duration of acromegaly in 4 of these patients was between 3 and 12 years; the disease was diagnosed for the first time in the other patients. Double M-mode echocardiography was performed in all patients and the results compared with data obtained from a control group of 24 healthy volunteers (N: 22 men, 2 women; mean age: 23 yrs). The mean left ventricular diameter at end-diastole was greater in the acromegalics than in the controls (A: 55 +/- 6 mm, N: 50 +/- 4 mm; p less than 0.005, means +/- SD). After correction for age and body surface area, it, however, was outside the 95% confidence interval in 5 patients. Left ventricular hypertrophy was present in 3 patients, one of whom had coexistent arterial hypertension. A total of 3 patients were hypertensive. Significantly higher values for the maximal velocity of systolic wall thickening (A: 6.1 +/- 0.6 cm/s, N: 4.2 +/- 0.6 cm/s, p less than 0.001) and diameter change (A: 12.4 +/- 2.0 cm/s, N: 10.6 +/- 1.0 cm/s, p less than 0.005) indicate increased contractility with concurrently increased relaxation; fractional shortening did not differ significantly (A: 38 +/- 5%, N: 37 +/- 5%, ns). The isovolumetric relaxation period at diastole was slightly longer in the acromegalics (A: 70 +/- 17 ms, N: 61 +/- 13 ms, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1989

[Principles of glucocorticoid therapy from the viewpoint of the internist].

40 years after the first clinical application of cortisone, glucocorticoids have become an indispensable part of the treatment of various internal disorders. The many side effects of glucocorticoids, however, clearly diminish their utility and stand in the way of their full acceptance by the patient. All principles of glucocorticoid therapy, therefore, aim at the improvement of the ratio between benefits and unwanted effects. There are 3 ways to achieve this goal: 1. Topical application (e.g. beclomethasone-17, 21-dipropionate for the local therapy of bronchial asthma); 2. special timing of glucocorticoid administration (e.g. alternating therapy); 3. active fight against unwanted effects by means of additional therapeutic measures (e.g. prophylactic therapy of osteoporosis induced by steroids). New perspectives may offer themselves as soon as macrocortin--a mediator of glucocorticoid action--will become available.

Administration, Topical↗
PubMed1989

Gel chromatographic characterization of immunoreactive adrenocorticotropin in patients with ACTH hypersecretion.

We investigated the molecular size of circulating immunoreactive ACTH by gel chromatography in patients with ACTH hypersecretion due to various disorders of the hypothalamic-pituitary-adrenal axis. 4 patients with Addison's disease, 2 with Nelson's syndrome, 4 with Cushing's disease, 6 with the ectopic ACTH syndrome (2 bronchial carcinoma, 1 medullary carcinoma, 1 metastatic islett cell carcinoma, 1 benign bronchial carcinoid and 1 patient with occult ectopic Cushing's syndrome) and 1 patient with hypersecretion of ACTH from a clinically nonfunctioning pituitary adenoma were studied. Analysis of the molecular size of immunoreactive ACTH was performed by gel chromatography on a Sephadex G-75 column (superfine, 100 x 1.5 cm) equilibrated with 1% formic acid. 2 ml fractions were collected and evaporated to dryness. The ACTH content of the recovered samples was determined by RIA. In Addison's disease, Nelson's syndrome and Cushing's disease the plasma showed a single peak of ACTH immunoreactivity at the expected position of 1-39 ACTH. In the ectopic ACTH syndrome the plasma of 4 patients revealed at chromatography at least one other peak eluting between the void volume and 1-39 ACTH suggestive of a high molecular weight form of ACTH whereas plasma of 2 patients showed only a single ACTH peak at the position of labeled 1-39 ACTH. The patient with a clinically non-functioning pituitary adenoma revealed a gel filtration pattern similar to the patients with ectopic ACTH syndrome and secretion of high molecular weight ACTH. We conclude that secretion of high molecular weight forms of ACTH is not a unique feature of the ectopic ACTH syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

ACTH Syndrome, Ectopic↗
PubMed1989

[Assessment of nutritional status--a part of routine clinical diagnosis: cholinesterase activity as a nutritional indicator].

Nutritional assessment has not yet been established as integral part of basic clinical diagnostic procedures everywhere, eventhough the prognostic relevance of malnutrition is well known. One of the reasons is the lack of nutritional indicators, which are specific of and sensitive for changes of the nutritional status on the one hand, and routinely analyzed on the other. We report on the utility of serum cholinesterase, which has the shortest half-life of all plasma proteins, to identify malnourished patients. 54 internal inpatients with malignant diseases or in septic state were followed up prospectively with respect to courses of cholinesterase (CHE), albumin (ALB), transferrin (TRA), and body weight over periods of 4 weeks. A correct correlation to malnutrition was defined as plasma concentrations less than reference ranges or continuous concentr. fall greater than 10%. Based on 132 observations (65 with continuous weight loss, mean: -5.5% of original w.; 54 w. gain, mean +4.6%, 13 constant w.), changes of CHE had the highest correlation to weight changes (r = 0.79, p less than 0.001), compared to the courses of TRA- or ALB-levels (r = 0.65/0.68). Incorrect positive results (conc. fall or conc. less than ref. range without weight loss): absolute levels - CHE 4%, ALB 4%, TRA 22%; conc. courses - CHE 0%, ALB 0%, TRA 6%. Incorrect negative: absolute c. - CHE 63%, ALB 30%, TRA 28%; courses - CHE 15%, ALB 19%, TRA 17%. The common determination of CHE and ALB-courses allowed a correct identification of malnutrition in 96% of all observations, with the same result as the courses of ALB + TRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗
PubMed1989

[Diagnosis and therapy of asymptomatic adrenal tumors].

Adrenal tumours had been discovered incidentally (since 1981) in 32 patients (23 females and nine males; mean age 54 [25-73] years) who had had computed tomography (CT) or ultrasonography for other reasons: none had a history or symptoms of such tumour. Tumours were bilateral in eight, right or left-sided in 12 each: all had been confirmed by CT. Average tumour size was 3 cm (1-9 cm). Three patients had cortisol-producing adrenal tumours, and there was one benign phaeochromocytoma (abnormally high adrenaline and noradrenaline excretion). Fine-needle biopsies in two patients revealed a benign histology. An adrenalectomy was performed in eight patients (the one phaeochromocytoma, six adenomas and one ganglioneuroma). Follow-up CT in 11 of the non-operated patients 6-48 months later (mean of 14 months) did not demonstrate any increase in tumour size so that a waiting attitude seems justified: benign tumours are clearly much more frequent than malignant ones. However, if the tumour diameter is greater than 6 cm, an adrenalectomy is indicated because of the danger of malignancy.

Adenoma↗
PubMed1989

[Treatment of metastatic adrenal carcinoma with suramin].

A right adrenocortical carcinoma (weighing 978 g) was removed from a 45-year-old man in April 1986, the tumour bed then being irradiated with 40 Gy. Subsequently discovered multiple lung metastases were treated with cisplatin, etoposide and bleomycin, without improvement. Treatment with mitotane (Lysodren) was also without effect and had to be discontinued because of severe side effects. Treatment with suramin (Germanin) was begun in August 1987. After a loading dose of 10.7 g for six weeks the lung metastases regressed almost completely. But lung metastases were again demonstrated in January 1988 during a low-dose maintenance regimen of suramin. Increased dosage arrested further growth, but achieved no regression of the metastases. The patient died unexpectedly in April 1988 of acute circulatory failure. Suramin administration had been discontinued six weeks earlier because of bronchopneumonia and general deterioration. Thrombocytopenia, coagulation disorders and moderate proteinuria were the side effects of suramin treatment.

Adrenal Cortex Neoplasms↗
PubMed1989

[Coccidioidomycosis--differential diagnosis of lung infiltrates with peripheral eosinophilia].

A 20-year-old man developed pulmonary coccidioidomycosis after travelling in Mexico and California. Cardinal clinical symptoms were fever, pulmonary infiltrate with ipsilateral hilar adenopathy on the chest X-ray, and a 14% eosinophilia in the peripheral blood. In addition he experienced erythema nodosum, arthralgias and night sweats. After a five-week febrile course the symptoms disappeared spontaneously without specific treatment. Coccidioidomycosis was diagnosed by serology, and Coccidioides immitis grew in the sputum culture. With ever more travellers to other parts of the globe coccidioidomycosis must be considered in the differential diagnosis of pulmonary infiltrates with peripheral eosinophilia.

Abdomen↗
PubMed1989

Management and efficacy of intensified insulin therapy--starting in outpatients.

Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here on the logistics, efficacy, and safety of IIT, started in outpatients. Over 8 months, 52 type I and type II diabetics were followed up whose insulin regimens consecutively had been changed from conventional therapy to IIT. Two different IIT strategies were compared: free mixtures of regular and intermediate (12 hrs)-acting insulin versus the basal and prandial insulin treatment with preprandial injections of regular insulin, and ultralente (24 hrs-acting) or intermediate insulin for the basal demand. After 8 months HbA1 levels had decreased from 10.6% +/- 2.4% to 8.0% +/- 1.3% (mean +/- SD). There was no difference between the two regimens with respect to metabolic control; but type II patients maintained the lowered HbA1 levels better than type I patients. Only two patients were hospitalized during the follow-up time because of severe hypoglycemia. An increase of body weight due to the diet liberalization during IIT became a problem in one-third of the patients. Our results suggest that outpatient initiation of IIT is safe and efficacious with respect to near-normoglycemic control. Weight control may become a problem in IIT patients.

Blood Glucose↗