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B Allolio

Publications and source records attributed to B Allolio.

At least 109 records · Page 6Linked to original sources
PubMed1995

Dual-energy X-ray absorptiometry at the lumbar spine in German men and women: a cross-sectional study.

A cross-sectional, population-based study of 238 randomly selected females and 224 males with German ethnic background (aged 20-80 years) was carried out to establish lumbar spine bone mineral density (BMD) values, using dual X-ray absorptiometry (DXA), for a German population. Comparison was made to the reference range provided by the manufacturer of the DXA equipment. No sex difference in peak spine BMD was found in our study (1.091 +/- 0.114 g/cm2 for males versus 1.070 +/- 0.113 g/cm2 for females, n.s.). Different patterns of bone loss could be detected in both sexes. In premenopausal women there was no significant correlation between age and BMD (y = 1.044 + 0.00047x, r = 0.03, P = 0.73) whereas reduction of female BMD at the spine was demonstrated in postmenopausal women (y = 1.189-0.0041x, r = -0.28, P = 0.01), underscoring the important role of the menopause for later manifestation of spinal osteoporosis in women. In contrast, in males we found no significant change of BMD with aging (y = 1.071-0.0007x, r = -0.08, P = 0.25). Employing commonly used exclusion criteria, BMD values of the study subjects were found mostly within the normal range of BMD. The major finding of our study was good concordance between female data of our study population and the reference data provided by the manufacturer. Clinically significant discrepancies between our data and the Hologic reference range for males could be detected. Our data on males (30-39 years of age) were up to 7% lower than those provided by the manufacturer, probably due to differences in sampling procedures.

Absorptiometry, Photon↗
PubMed1995

Complex effects of age and gender on hypothermic, adrenocorticotrophic hormone and cortisol responses to ipsapirone challenge in normal subjects.

The effects of a challenge dose of the 5-HT1A agonist, ipsapirone (0.3 mg per kg body weight), or placebo on body temperature and on adrenocorticotrophic hormone (ACTH) and cortisol release, were examined in 30 normal subjects (14 males, 19-74 years and 16 females, 22-69 years) using a randomized, double blind design. Irrespective of age or gender, ipsapirone induced a significant reduction in body temperature relative to placebo and a significant increase in ACTH and cortisol release. Maximal temperature reduction by ipsapirone was significantly blunted in older subjects and was inversely related to age. There was no gender difference in the hypothermic response to ipsapirone. ACTH and cortisol responses showed an opposite impact of aging in males and females. Whereas both responses diminished with age in male subjects, they increased with age in females. The cortisol response of older females was significantly larger than that of all the other subjects. Adverse effects of ipsapirone were also more marked in elderly females and were correlated with ACTH and cortisol responses. These findings should be taken into consideration in the use of ipsapirone and other 5-HT1A agonists as challenge procedures for studying central serotonergic function in depression and other disorders. Careful matching of control and experimental subjects is indicated so as to avoid spurious results which reflect the effects of age and gender rather than the pathophysiology of the disorders being investigated.

Adrenocorticotropic Hormone↗
PubMed1995

No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms.

The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis.

Adolescent↗
PubMed1995

High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone.

High concentrations of unbound cortisol in late pregnancy have been explained by the antiglucocorticoid activity of high progesterone levels. To further test this hypothesis we studied the effect of high-dose progesterone on baseline and corticotrophin-releasing hormone (CRH)-induced hormone secretion in humans. In a double-blind crossover study eight healthy male volunteers received either progesterone (0.714 mg.kg-1.h-1 for 60 min followed by a dose of 0.45 mg.kg-1.h-1 over a total infusion time of 315 min) or vehicle as a continuous intravenous infusion. At 210 min a CRH test (0.1 microgram/kg body weight as bolus iv) was performed. Within 30 min after the start of progesterone administration the serum progesterone level increased to 454 +/- 31 nmol/l and remained in the range of third trimester pregnancy concentrations throughout the infusion period. During vehicle infusion the progesterone level remained in the normal range for healthy males and demonstrated a small but significant increase after CRH (1.52 +/- 0.23 vs 0.74 +/- 0.14 mmol/l; p < 0.01). However, baseline and CRH-stimulated serum cortisol and plasma adrenocorticotrophic hormone remained unaffected by high-dose progesterone. Moreover, unbound salivary cortisol also was not affected by progesterone, suggesting that there is no significant competition for transcortin binding sites. In conclusion, no antiglucorticoid activity was found after short-term administration of progesterone in males. These findings cast doubts on the concept that the alterations of the pituitary-adrenal axis in late pregnancy are induced by the antiglucocorticoid activity of high progesterone concentrations.

Adrenocorticotropic Hormone↗
PubMed1995

Multicenter German reference data base for peripheral quantitative computer tomography.

The wide spread use of bone densitometers in Germany and other European countries has required the establishment of a validated reference population data base. A semianthropomorphic forearm cross-calibration phantom (EFP), developed during a concerted research action of the European Union's programme in Biomedical Engineering (COMAC-BME), was used to cross-calibrate the peripheral quantitative computer tomography (pQCT) devices at four German centers participating in the multicenter study. In total, 723 women and 208 men were included in the normal data base. No significant regional differences were found between the data of the different centers. In addition to the manufacturers calibration standard, proper calibration of the pQCT devices could be monitored during collection of the normal female and male data base. As a merit of the COMAC-BME study the measurements obtained with all pQCT devices thus ensured an uniform reference data base for distal radius measurements in Germany.

Adult↗
PubMed1994

[The Gitelman syndrome--a differential diagnosis of Bartter syndrome].

BACKGROUND: Hypokalemia due to renal potassium wasting in the absence of hypertension, moderate metabolic alkalosis, hyperreninism and hyperaldosteronism suggest the presence of Bartter's syndrome. The underlying cause is an inherited defect of sodium chloride reabsorption in the thick ascending limb of Henle. A differential diagnosis of Bartter's syndrome is Gitelman's syndrome, another hypokalemia-hypomagnesemia syndrome, which is thought to be caused by a transport defect in the distal tube. PATIENTS AND METHODS: We report 3 patients presenting with signs primarily suggestive of Bartter's syndrome, who turned out to have Gitelman's syndrome after determining the excretion of calcium in the urine. RESULTS: Two women, 36- and 55-year old, suffered from paresthesias in the hands and feet and from tetanic convulsions. The brother of the 36-year old woman presented in our hospital because of an accidentally discovered hypokalemia without any clinical symptoms. In all patients the outstanding biochemical features were hypokalemia, hypomagnesemia and moderate metabolic alcalosis. The renin and aldosterone values were inappropriately high. The most characteristic finding in the urine, besides the presence of hyperkaliuria was the diminution of calcium excretion, despite normocalcemia. CONCLUSION: The association between sodium and calcium reabsorption in the loop of Henle predicts hypercalciuria in patients with a defect in salt reabsorption in this segment, as in Bartter's syndrome. In Gitelman's syndrome the laboratory features resemble the findings in Bartter's syndrome, except for the presence of hypocalciuria. Since hypocalciuria follows also the administration of thiazide diuretics, which act in the early part of distal tube, a transport defect in this part of the tube is thought to be responsible for the electrolyte disturbances in Gitelman's syndrome. The measurement of the urinary calcium excretion in patients with an unclear hypokalemia-hypomagnesemia-syndrome allows easily the differentiation between Bartter's and Gitelman's syndrome.

Adult↗
PubMed1994

Clonal composition of human adrenocortical neoplasms.

The mechanisms of tumorigenesis of adrenocortical neoplasms are still not understood. Tumor formation may be the result of spontaneous transformation of adrenocortical cells by somatic mutations. Another factor stimulating adrenocortical cell growth and potentially associated with formation of adrenal adenomas and, less frequently, carcinomas is the chronic elevation of proopiomelanocortin-derived peptides in diseases like ACTH-dependent Cushing's syndrome and congenital adrenal hyperplasia. To further investigate the pathogenesis of adrenocortical neoplasms, we studied the clonal composition of such tumors using X-chromosome inactivation analysis of the highly polymorphic region Xcen-Xp11.4 with the hybridization probe M27 beta, which maps to a variable number of tandem repeats on the X-chromosome. In addition, polymerase chain reaction amplification of a phosphoglycerokinase gene polymorphism was performed. After DNA extraction from tumorous adrenal tissue and normal leukocytes in parallel, the active X-chromosome of each sample was digested with the methylation-sensitive restriction enzyme HpaII. A second digestion with an appropriate restriction enzyme revealed the polymorphism of the region Xcen-Xp11.4 and the phosphoglycerokinase locus. Whereas in normal polyclonal tissue both the paternal and maternal alleles are detected, a monoclonal tumor shows only one of the parental alleles. A total of 21 female patients with adrenal lesions were analyzed; 17 turned out to be heterozygous for at least one of the loci. Our results were as follows: diffuse (n = 4) and nodular (n = 1) adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome, polyclonal pattern; adrenocortical adenomas (n = 8), monoclonal (n = 7), as well as polyclonal (n = 1); adrenal carcinomas (n = 3), monoclonal pattern. One metastasis of an adrenocortical carcinoma showed a pattern most likely due to tumor-associated loss of methylation. In the special case of a patient with bilateral ACTH-independent macronodular hyperplasia, diffuse hyperplastic areas and a small nodule showed a polyclonal pattern, whereas a large nodule was monoclonal. We conclude that most adrenal adenomas and carcinomas are monoclonal, whereas diffuse and nodular adrenal hyperplasias are polyclonal. The clonal composition of ACTH-independent massive macronodular hyperplasia seems to be heterogeneous, consisting of polyclonal and monoclonal areas.

Adenoma↗
PubMed1994

[Bilateral massive macronodular adrenal gland hyperplasia. A rare cause of Cushing's syndrome].

A 46-year-old man with known arterial hypertension for 10 years had, over the last two years, developed increasing obesity, particularly of the trunk, with other symptoms typical of Cushing's syndrome. Hormone analysis demonstrated hypercortisolism and decreased plasma ACTH concentration. The dexamethasone inhibition test failed to show any significant suppression of serum cortisol. Plasma ACTH was not increased in the corticotrophin-releasing hormone and the metyrapone tests. In the short ACTH test there was an excessive cortisol increase. Abdominal computed tomography revealed both adrenals to be enlarged (6 x 4 cm) and coarsely nodular. Adrenolytic treatment with ketoconazole (400 mg daily) caused symptoms of adrenal insufficiency, but a reduced dosage of 200 mg daily lowered the cortisol level to between 5 and 11 micrograms/dl and normalized the blood pressure and clinical signs of Cushing's syndrome disappeared. Subsequent bilateral adrenalectomy confirmed the diagnosis of massive macronodular adrenal hyperplasia. Substitution treatment with twice daily 25 mg cortisone acetate and 0.05 mg fludrocortisone was started postoperatively.

Adrenal Gland Diseases↗
PubMed1994

Precision of dual X-ray absorptiometry and peripheral computed tomography using mobile densitometry units.

Irrespective of the method used for noninvasive bone mass determination, data comparison between different centers is a major problem as significant interunit variation may occur. We, therefore, have employed mobile densitometry units to reduce interunit variability in two large epidemiologic studies in Germany. Two cars were equipped with either two dual X-ray absorptiometry (DXA) instruments (QDR 1000 Hologic, USA) (car I) or a special purposed scanner for peripheral quantitative computed tomography (pQCT) (XCT 900, Stratec, FRG) (car II). The cars were moved across Germany 11,090 km and 1651 km during the studies over a period of 30 and 7 months, respectively. Precision in vitro was determined using hydroxyapatite phantoms. Forty-eight patients underwent duplicate measurements at the lumbar spine (n = 22) and hip (n = 26) for assessing reproducibility in vivo. Between the two series of scans, the car was moved 63 km. Long-term precision in vitro of the QDR 1000 instruments were 0.41% and 0.59% for BMD with no evidence of machine drift (rate of change per year 0.04% and 0.05%, respectively). Short-term reproducibility in vivo showed a coefficient of variation (cv) of 1.02% for spinal BMD (L2-L4) and 1.72% for femoral neck. Long-term precision in vitro of the pQCT scanner was 0.9%. Our study shows precision in vivo and in vitro and stability of the mobile densitometers similar to that achieved with stationary equipment. In conclusion, mobile densitometry may become a useful tool not only for epidemiologic surveys and clinical trials but also for routine evaluation in less densely populated areas.

Absorptiometry, Photon↗
PubMed1994

[Incidence of femoral neck fractures in the German Federal Republic in comparison to other countries].

Reported age-adjusted incidence rates vary markedly in Europe and the US, making the transposition of results from elsewhere questionable. The aim of this study is to fill this gap and to compare the hip fracture incidence between Germany and other countries. Population-based epidemiologic research was conducted in Düren (84251 residents), because its population is representative for West Germany as far as age and social structure are concerned, and because medical care is virtually self-contained within the community. Patient files and discharge statistics of the three local hospitals were thoroughly reviewed. Hip fractures after adequate trauma and pathological fractures were excluded. Between 1987 and 1989 276 inadequate hip fractures were identified among the resident population. There was a highly significant increase in the age-specific incidence of hip fractures in both sexes, but females were more frequently affected (crude average annual incidence rate per 100,000: females 291.3 males 110.2). The age-adjusted incidence rates for Germany in comparison to published international data follow on third position after the high rates reported for Norway and the US. The annual incidence of 70,000 hip fractures for the former Federal Republic of Germany is significantly higher than expected.

Adult↗
PubMed1994

The stress response to laparoscopic cholecystectomy: investigation of endocrine parameters.

Laparoscopic cholecystectomy, as a typical example of minimal invasive surgery, is associated with low complication rates and minimal patient discomfort, and provides the same safety as conventional cholecystectomy. In the present prospective observational study, endocrine parameters as indicators for stress response were measured. We investigated 53 patient with laparoscopy cholecystectomy and 12 patients with conventional cholecystectomy. Blood samples were taken pre-, peri-, and postoperatively for measurement of ACTH, cortisol, prolactin, and growth hormone. General anesthesia followed a standardized protocol. The increase in all stress hormones did not differ between patients in the two groups, and was comparable with that reported in the literature and the findings of our own previous studies in patients undergoing conventional cholecystectomy and elective colon resection. We conclude that laparoscopic cholecystectomy is associated with a pronounced endocrine stress response that does not account for the observed differences in the peri- and postoperative complication rate or patient comfort.

Adrenocorticotropic Hormone↗
PubMed1994

Reduced lymphocyte beta 2-adrenoceptor density and impaired diastolic left ventricular function in patients with glucocorticoid deficiency.

OBJECTIVE: Patients with adrenal crisis are at risk of severe hypotension not responding to administration of catecholamines. As glucocorticoids may be a prerequisite for intact beta-adrenoceptor function, impaired adrenoceptor activity may explain the hypotension and reduced cardiac performance in adrenal insufficiency. The aim of our study was, therefore, to further elucidate the permissive action of glucocorticoids on adrenergic function and cardiac performance. DESIGN: Prospective randomized controlled study. PATIENTS: Nine patients with adrenal insufficiency were investigated before and 48 hours after glucocorticoid withdrawal. Mineralocorticoid therapy remained unchanged during the study period. MEASUREMENTS: Lymphocyte beta 2-adrenoceptor density, intracellular c-AMP response to isoprenaline, platelet alpha 2-receptor density, plasma catecholamines, serum cortisol, plasma ACTH, echocardiography. RESULTS: Glucocorticoid depletion was demonstrated by a fall in serum cortisol from mean +/- SEM 441 +/- 62 to 45 +/- 18 nmol/l. Glucocorticoid withdrawal decreased lymphocyte beta 2-receptor density from 798 +/- 111 to 498 +/- 54 binding sites/cell (P < 0.05) and the intracellular c-AMP response to isoprenaline from 15.0 +/- 4.2 to 8.2 +/- 1.7 pmol/10(6) cells (P < 0.05). Echocardiography showed impaired diastolic relaxation after glucocorticoid withdrawal with prolongation of the rapid filling period (80.3 +/- 12.5 vs 138.3 +/- 11.8 ms, P < 0.05). Plasma catecholamines, platelet alpha 2-receptor density and systolic left ventricular function were not affected by glucocorticoid deficiency. CONCLUSIONS: This study demonstrates the importance of normal glucocorticoid levels for beta 2-adrenoceptor function and helps to explain the decreased responsiveness to catecholamines and the impaired cardiac performance in adrenal crisis.

Adolescent↗
PubMed1994

Suramin in adrenocortical cancer: limited efficacy and serious toxicity.

OBJECTIVE: No satisfactory treatment for adrenocortical carcinoma (ACC) is available. We investigated the efficacy and toxicity of suramin in the treatment of metastatic ACC since suramin has been recently reported to be active as a single agent therapy for patients with ACC and prostatic carcinoma. DESIGN: We collected data on 9 patients with metastatic ACC treated with suramin in four centres in Germany between 1987 and 1992. PATIENTS: Nine patients (5 women, 4 men; age range 32-67 years) were included. Biochemical evidence of steroid excess was found in 6/9, in three leading to clinical symptoms (hypertension, hyperglycaemia, hirsutism, gynaecomastia). MEASUREMENTS: Tumour responses were assessed by radiological and biochemical evaluation. Other investigations included regular measurements of blood cell counts, coagulation, hepatic and renal function parameters, and serum suramin concentrations. RESULTS: The patients received cumulative doses ranging from 8.2 to 30.2 g suramin over periods of 1-15 months. 3/9 achieved a partial response, 2/9 disease stabilization and 4/9 experienced progressive disease. Tumour responses were transient. Suramin treatment was without direct influence on steroid excess. Serious side-effects included coagulopathy (6/9), thrombocytopenia (6/9), polyneuropathy (2/9) and allergic skin reactions (4/9); the death of two patients was possibly related to suramin therapy. Both toxicity and tumour response were strongly associated with serum level or cumulative dose of suramin. CONCLUSIONS: (1) Suramin is of antineoplastic efficacy in the treatment of metastatic adrenocortical carcinoma. (2) The clinical use of suramin is limited by a narrow therapeutic window with the risk of serious and possibly lethal toxicity at one extreme, and loss of efficacy at the other. Strict monitoring of suramin serum levels is mandatory aiming at levels between 200 and 250 mg/l. Suramin should not be considered as first-line treatment for metastatic adrenocortical carcinoma. (3) To improve treatment options in adrenocortical carcinoma as well as for further investigation on the usefulness of suramin, controlled prospective trials are urgently needed.

Adrenal Cortex Neoplasms↗
PubMed1994

Impairment of adrenocortical function associated with increased plasma tumor necrosis factor-alpha and interleukin-6 concentrations in African trypanosomiasis.

African sleeping sickness (SS) is a severe, potentially lethal parasitic disease. The treatments of choice are the antiparasitic agents suramin, which is adrenotoxic, and/or melarsoprol. We evaluated the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis of patients with SS before, during, and after therapy with suramin and/or melarsoprol, in two sequential stages. First, we employed the standard adrenocorticotropic hormone (ACTH) 1-24 stimulation test (250 micrograms i.v.) to assess the maximal adrenocortical responsiveness of 69 patients with SS and 38 normal controls. We demonstrated paradoxically subnormal cortisol responses before suramin therapy [net cortisol response 60 min after stimulation: 10.5 +/- 2.9 (mean +/- SE) vs. 17.5 +/- 1.0 micrograms/dl for controls, p = 0.004], with 27% of the patients falling within the adrenal insufficiency range (stimulated cortisol concentration < 20 micrograms/dl). These responses subsequently and unexpectedly improved with suramin and/or melarsoprol therapy. Second, we performed a human corticotropin-releasing hormone (hCRH) test (100 micrograms i.v.) in 68 additional patients with SS and 14 control subjects to examine whether the glucocorticoid deficiency observed was primary and/or secondary. Compared to controls, the ACTH and cortisol responses to hCRH were blunted (ACTH after 60 min: 29 +/- 7 vs. 58 +/- 8 pg/ml in controls, p = 0.014; cortisol: 15.2 +/- 1.5 vs. 19.6 +/- 0.7 micrograms/dl, p = 0.018), suggesting the presence of secondary adrenal insufficiency. There was improvement of both ACTH and cortisol responsiveness to hCRH with therapy, with cortisol recovery occurring before ACTH, suggesting an additional primary component of adrenal dysfunction in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies.

The mechanisms of tumorigenesis of adrenocortical neoplasms have not been elucidated as yet. However, loss of heterozygosity at chromosomal locus 17p has been consistently observed in adrenocortical cancer. p53 is a recessive tumor suppressor gene located on chromosome 17p. Mutations in the p53 gene play an important role in the tumorigenesis of diverse types of human neoplasms including breast and colon cancers. More than 90% of all mutations discovered in such tumors have been detected in 4 hot spot areas that lie between exons 5 and 8. In contrast to wild-type p53, mutant p53 accumulates intracellularly and can be easily detected by immunohistochemistry. We therefore investigated the frequency of p53 mutations in human adrenocortical neoplasms using molecular biology and immunohistochemistry techniques. Five patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11 patients with adrenocortical carcinomas (8 female, 3 male; ages 15-50 yr), and two adrenocortical tumor cell lines were studied. After DNA extraction from frozen tumor tissue or paraffin-embedded material, exons 5 through 8 were amplified using the polymerase chain reaction and directly sequenced by the dideoxy termination method. Immunohistochemistry was performed on paraffin-embedded tumor specimens obtained during adrenalectomy using a monoclonal antibody reacting with both wild-type and mutant p53. Prevalence of mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical cell lines, 2/2. Single point mutations were detected in 3 cases (exons 5, 6, and 7, respectively), and rearrangements of exon 7/8 and 8 were found in 2 cases. Immunohistochemistry detected strong nuclear and/or cytoplasmic p53 immunoreactivity in all adrenocortical carcinomas with point mutations of the p53 gene but not in adenomas and carcinomas with the wild-type sequence or with deletion/rearrangement of the p53 gene. We conclude that p53 plays a role in the tumorigenesis of adrenocortical carcinomas but is of less importance to benign adenomas.

Adolescent↗