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C Hagen

Publications and source records attributed to C Hagen.

At least 55 records · Page 3Linked to original sources

[Neuroendocrine disorders in anorexia nervosa--primary or secondary?].

Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic neuropeptides and monoamines are involved in the regulation of human appetite, and they are changed in several ways in anorexia nervosa. But it remains to be clarified whether these alterations are secondary or etiologic. Feeding behaviour in anorexia nervosa is characterised by a strong ambivalence and not by loss of appetite. Hypothalamic amenorrhea is a diagnostic criterion, and is not only secondary as it often precedes the weight loss and persists for a long time after weight and motor activity have returned to normal. Hypersecretion of corticotropin releasing hormone seems to be secondary to starvation, but at the same time it may keep up and intensify the anorexia, physical hyperactivity and amenorrhea. Low production of insulinlike growth factor-I and high growth hormone secretion reflects the nutritional deprivation. In conclusion most of the neuroendocrine abnormalities are secondary to weight loss, but some of them seem to participate in a circulus vitiosus and maintain the emaciated state.

Anorexia Nervosa↗

Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition.

OBJECTIVE: Studies with GH substitution in GH-deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End-points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day) versus placebo treatment for 12 months. DESIGN: Twenty-nine patients (mean age 45.5 +/- 2.0 years) with adult-onset GHD were studied in a double-blind, parallel design. Measurements of body composition by means of conventional anthropometry, bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and isometric muscle strength were performed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex-matched subjects was included. RESULTS: Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment. Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantly higher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral and subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P < 0.01) to levels no longer different from the control group. CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle: fat ratio (%) (placebo: 58:42 (baseline) vs 58:42 (12 months); GH: 66:34 (baseline) vs 72:28 (12 months) (P = 0.002); normal subjects: 67:33 (P < 0.05 when compared to 12 months placebo data)). Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over-hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7 +/- 9.8 (baseline) vs 51.6 +/- 8.2 (12 months); GH: 64.9 +/- 13.3 (baseline) vs 73.5 +/- 13.6 (12 months) (P < 0.05)). Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF-I levels (microgram/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270 +/- 31 (12 months GH) vs 156 +/- 8 (normal subjects (P < 0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months. CONCLUSIONS: (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained; (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo-controlled conditions; (3) uncontrolled data on muscle strength must be interpreted with caution; (4) a daily GH substitution dose of 2 IU/m2 seems too high in many adult patients.

Abdomen↗

Loss of antibody reactivity directed against the V3 domain of certain human immunodeficiency virus type 1 variants during disease progression.

We have previously shown that in AIDS patients a predominant species of infectious virus can be found which is not neutralized by homologous serum. The presence of the infectious virus was associated with the lack of type-specific antibody directed against the V3 domains of these virions. In contrast to this lack of V3-specific antibody, the other V3 domains of non-infectious virions were well recognized by antibody. To determine whether the lack of a V3-specific antibody response is due to a progressive loss of antibody during human immunodeficiency virus type 1 (HIV-1) infection, we monitored the anti-V3 antibody response in 90 patients over time. Anti-V3 antibodies were monitored by a V3-specific ELISA using 21 different V3 domains as a fusion with glutathione S-transferase (GST-V3) based upon sequences from 11 HIV-1 patient isolates and 10 sequences from an HIV-1 B subtype consensus-like GST-V3 expression library. This strictly heterologous screening showed a loss of V3-specific antibodies in 20 out of the 90 patients tested. To study the in vivo relevance of these findings we analysed V3 antibody loss in two patients. This strictly autologous antibody screening was performed based upon V3 sequences of the patients' cell-free virions. In both patients the loss of a V3-specific antibody could be detected in parallel to a decline of CD4+ T cells. Moreover, the escape of a distinct V3 variant was shown to correlate closely with the loss of the V3-specific antibody.

Amino Acid Sequence↗

Influence of growth hormone and androgens on body composition in adults.

The secretion of both growth hormone (GH) and androgens declines with age which may play a role in the senescent changes in body composition and organ function. Among healthy adults abdominal adiposity is an important negative determinant of GH secretion. Surprisingly, abdominal or android obesity seems inversely correlated with testosterone levels in males but not in females. The ability of GH to promote lipolysis and preserve or increase lean body mass has been reappraised in substitution studies in GH-deficient adults. By comparison, adequately controlled studies of androgen replacement in hypogonadal and/or elderly males are few. In view of the physiological and clinical relevance of obtaining information about the aging process, there is a need for controlled experiments addressing similarities and differences between the action of GH and sex steroids in adults.

Adult↗

Pulsatile thyrotropin secretion in patients with Addison's disease during variable glucocorticoid therapy.

The inhibitory action of physiological to pathophysiological serum cortisol levels on TSH secretion were investigated in 12 patients with Addison's disease on 3 occasions. 1) In continuation of the conventional hydrocortisone (HC) substitution, a medium dose of HC (0.5 mg/kg) was infused over 23 h. 2) After 24-h withdrawal of HC, the patients had placebo infusion over 23 h. 3) After 5 days of dexamethasone (1.5 mg/day), a high dose of HC (2.0 mg/kg) was infused over 23 h. Blood sampling was performed every 10 min during the last 10 h of the study period, followed by a TRH test (10 micrograms, iv), To mimic the normal diurnal rhythm for serum cortisol, HC was infused in graduated doses, and during medium dose infusion, the serum cortisol level and the TSH pulsatility pattern were similar to those seen in normal controls. The TSH mean level was 1.0 +/- 0.5 mU/L during medium doses of HC, increasing significantly (P < 0.05) to 2.0 +/- 1.6 mU/L during the low cortisol state and was significantly (P < 0.05) suppressed to 0.4 +/- 0.2 mU/L during high doses of glucocorticoids, when the pulse frequency was also significantly reduced (P < 0.01). Together with a dose-dependent inhibitory action of glucocorticoids on the TSH response to TRH, our data indicate that even physiological serum levels of cortisol have an influence on endogenous TSH secretion, probably caused by regulation of the pituitary sensitivity to TRH.

Addison Disease↗

Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study.

The effects of GH substitution on skeletal mass, bone turnover, and calcium metabolism were investigated in 29 patients with GH deficiency who were randomized to sc injections with GH (2 IU/m2 day) or placebo for 12 months. During GH treatment, serum insulin-like growth factor I increased 263 +/- 98% (P < 0.001). Serum osteocalcin, bone a alkaline phosphatase, and procollagen type I C-terminal propeptide increased by 376 +/- 78% (P < 0.005), 128 +/- 17% (P < 0.005), and 100 +/- 17% (P < 0.005), respectively. Serum type I collagen telopeptide and urinary levels of pyridinoline, deoxypyridinoline, and hydroxyproline rose by 158 +/- 39% (P < 0.005), 170 +/- 48% (P < 0.005), 156 +/- 78% (P < 0.005), and 161 +/- 50% (P < 0.005), respectively. Serum ionized calcium rose by 1.7 +/- 0.6% (P < 0.05), whereas serum PTH decreased insignificantly. Vitamin D metabolites remained unaltered. Urinary calcium/creatinine increased and phosphate/creatinine decreased transiently, returning to baseline values at 9 months. When measured by dual energy x-ray absorptiometry, whole body bone mineral density (BMD) and (BMD) of the radius decreased 2.4 +/- 0.6% (P < 0.05) and 3.5 +/- 1.0% (P < 0.005), respectively, whereas no significant changes were observed in BMD of the femur or spine. Our results indicate that long term GH treatment activates bone remodeling in patients with GH deficiency. The observed slight decrease in BMD may be explained by expansion of the remodeling space and reduced mean age of bone tissue. IT remains unclear whether long term treatment with GH will lead to an increase in bone mass and improved skeletal biomechanical competence.

Adult↗

Computer-aided morphometrical analysis of macroconidia in Fusarium sambucinum Fuckel sensu lato strains.

Forty-one strains of Fusarium sambucinum Fuckel sensu lato were classified on the basis of morphological data of the macroconidia obtained by automated microscopic image analysis. The classification factors were determined in six Fusarium strains of the section Discolor. The results show the relative homogeneity within the groups proposed by Nirenberg. A remarkable difference could be detected especially between the groups F. sambucinum, F. torulosum and F. sambucinum sensu lato on the one hand and F. spec nov. on the other.

Evaluation Studies as Topic↗

Effect of 4 weeks of octreotide treatment on prolactin, thyroid stimulating hormone and thyroid hormones in acromegalic patients. A double blind placebo-controlled cross-over study.

We aimed to test the hypothesis, that octreotide has a suppressive effect on unstimulated and TRH-stimulated PRL levels in both normo- and hyperprolactinaemic acromegalic patients, and besides to evaluate the effect of octreotide on unstimulated TSH and thyroid hormones. The present study is a doubleblind placebo-controlled cross-over trial; the 12 acromegalic patients were treated with octreotide or placebo (300 micrograms/d) for 4 weeks separated by a 12 weeks washout period. Before and after each 4 weeks period a TRH-test (200 micrograms iv) was performed and serum GH and PRL levels were determined. Serum TSH and thyroid hormones were determined after 0, 2, 3, and 4 weeks. In the whole group unstimulated PRL levels were 18 micrograms/l +/- 5 before and 7 micrograms/l +/- 1 during octreotide treatment (p < 0.01). The PRL lowering effect of octreotide was significantly more pronounced in hyperprolactinemic patients compared to normoprolactinaemic patients (p < 0.05). Patients with the highest pretreatment PRL levels had the most pronounced percentage suppression of unstimulated PRL levels during octreotide treatment. Eight out of 12 patients had a TRH-stimulated PRL response > or = 100%, both during placebo and octreotide treatment, but in the group as a whole maximal TRH-stimulated PRL levels were suppressed during octreotide treatment, PRL levels were 50 micrograms/l +/- 20 before and 18 micrograms/l +/- 3 during octreotide treatment (p < 0.05). Unstimulated GH levels were 48 mU/l +/- 15 before and 13 mU/l +/- 2 during octreotide treatment (p < 0.01). Serum total T3 was significantly reduced during octreotide treatment (p < 0.05); serum TSH, total T4 or free T4 index were not significantly changed during treatment. We conclude that patients with acromegaly and hyperprolactinemia will normalize PRL levels during 4 weeks of octreotide treatment and octreotide will reduce total T3 levels in acromegalic patients.

Acromegaly↗

Whole body and regional soft tissue changes in growth hormone deficient adults after one year of growth hormone treatment: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: Adults with GH deficiency (GHD) exhibit changes in body composition. Studies of the effects of GH substitution on body composition have been short-term or not adequately controlled. The purpose of this study was to evaluate the long-term effects of GH on soft tissue using dual-energy X-ray absorptiometry (DEXA). This technique enables assessment of whole body as well as regional soft tissue composition. DESIGN: A double-blind, randomized, placebo-controlled study in patients with acquired GHD. The therapeutic regime consisted of biosynthetic human GH (2.0 IU/m2 per day) or placebo, given as a daily subcutaneous injection at 2000 h for 12 months. PATIENTS: Twenty-nine patients with acquired GHD (GH < 10 micrograms/l (< 20 mU/l) following standard provocative tests) in whom additional hormone replacement was maintained. MEASUREMENTS: Soft tissue determinations by DEXA scan, height, weight, foot volume and finger circumference were recorded together with serum IGF-I at baseline and after 12 months. RESULTS: Twelve months of GH therapy induced a total fat mass (FM) reduction of (mean +/- SEM) 4.88 +/- 0.58 kg (P < 0.002) (n = 13) corresponding to 21.5% of the total FM. The reduction in fat was most marked in the trunk, i.e. 3.07 +/- 0.29 kg (P < 0.002) corresponding to 61% of the total FM reduction. Total lean soft tissue mass (LSTM) increased by 3.31 +/- 0.81 kg (P < 0.001). Regional changes for arm and leg in the GH group amounted to 0.32 +/- 0.08 kg (P < 0.002) and 0.71 +/- 0.14 kg (P < 0.002), respectively, without accompanying significant changes in truncal LSTM between the groups. The foot volume was increased by 55.8 +/- 15.7 ml (P < 0.007) and the finger circumference by 2.67 +/- 0.5 mm (P < 0.005) on active treatment with no significant changes in the placebo group. CONCLUSIONS: Twelve months of GH therapy induced marked changes in soft tissue; fat mass was reduced, particularly in the trunk (61% of total fat mass reduction) whereas lean soft tissue mass increased more in the extremities. The data imply that GH-induced changes in body composition are maintained with long-term therapy.

Absorptiometry, Photon↗

Dopaminergic inhibition of pulsatile luteinizing hormone secretion is abnormal in regularly menstruating women with insulin-dependent diabetes mellitus.

OBJECTIVE: To examine the influence of low doses of dopamine (DA) (0.4 micrograms/kg per minute), on the secretion pattern of LH. DESIGN: Prospective randomized, single blind, placebo-controlled crossover study with infusion of DA or placebo in the follicular phase in regularly menstruating women with insulin-dependent diabetic mellitus (IDDM) and controls during 9.5 hours. SETTING: Department of Endocrinology, Odense University Hospital, Odense, Denmark. PATIENTS: Eight regularly menstruating IDDM women and eight controls. MAIN OUTCOME MEASURES: Mean LH, LH pulse amplitude, and LH pulse frequency. RESULTS: During placebo infusion no significant differences in basal LH values, pulse amplitude, and pulse frequency were seen between IDDM women and controls. In diabetics, basal LH levels and pulse amplitude decreased significantly during DA infusion (3.1 +/- 1.2 mIU/mL (conversion factor to SI unit, 1.00; mean +/- SD) and 0.9 +/- 0.3 mIU/mL, respectively) compared with placebo (4.5 +/- 1.1 and 1.2 +/- 0.4 mIU/mL, respectively). In normal women no significant changes were observed (basal LH 3.0 +/- 1.8 versus 3.2 +/- 1.6 mIU/mL and pulse amplitude 1.6 +/- 0.6 versus 1.5 +/- 0.9 mIU/mL). The LH pulse frequency during DA infusion was not different from placebo in either normal (9.0 +/- 2.7 versus 10.3 +/- 4.0) or diabetic women (11.8 +/- 2.1 versus 10.9 +/- 1.8). CONCLUSION: These results suggest that diabetic women are more sensitive to a small increase in peripheral DA concentration. An abnormal permeability of the blood-brain barrier in IDDM patients could explain a greater exposure of the hypothalamic structures, regulating the pituitary gonadotropin hormone secretion.

Adult↗

[Menstruation disorders in insulin-dependent diabetes mellitus--epidemiology and causes].

About 20% of all women with insulin-dependent diabetes mellitus (IDDM) have menstrual irregularities. Eight percent have amenorrhea. Fluctuations in blood glucose and insulin concentration are probably contributing factors, but the irregular menstrual cycles are mainly caused by disorders in the central ovulatory mechanisms. Hypothalamic GnRH release is regulated by several neuropeptides. Dopamine and opiates exert an inhibitory effect, and there is evidence for an abnormally high dopaminergic hypothalamic activity among women with IDDM. There might also be disorders of the opioid, serotonergic and GABA'ergic systems, but the consequences of there possibilities remain uncertain.

Diabetes Mellitus, Type 1↗

[Infertility and pregnancy outcome in women with insulin-dependent diabetes. An epidemiological study].

A questionnaire survey comprising an unselected group of 18-49-year old women with insulin-dependent diabetes mellitus and an age comparable control group was performed. Two hundred and forty-five (94%) of the diabetic women and 253 (88%) of the controls answered questions concerning fertility, pregnancy planning and pregnancy outcome. There was no difference in the cumulative rate of pregnancies in the two groups. The prevalence of involuntary infertility among the diabetic women was 17% and similar to that of controls. Compared to controls, diabetic women had significantly fewer pregnancies (mean 1.4 versus 1.7) and fewer births per pregnancy (70% versus 77%), and significantly more diabetic women were nulliparous (48% versus 38%). Only about half of all pregnancies were planned. In general the diabetic women reported that their diabetes had a negative influence on their attitude towards having children.

Adult↗

A method to measure quality of diabetes treatment: results from an outpatient clinic.

It is essential for patients, hospital staff and hospital administrators to know the quality of hospital care. We have developed a system to evaluate the quality in an outpatient clinic. The aims of this study are: to develop a system for quality monitoring of outpatient diabetes care, to evaluate the effectiveness of this system and to develop procedures for feedback to the patients and the staff. In this paper we report on the results related to the first two aims. The metabolic control of diabetes mellitus is evaluated by measurement of serum HbA1c, serum triglyceride, serum total cholesterol, body weight and blood pressure, and the result is used in the calculation of a metabolic score. Diabetic nephropathy and retinopathy are evaluated once a year according to international classifications. The data were collected from 1 January to 31 December 1991. We were able to collect data on HbA1c in 94% of the diabetic patients, but we obtained data in only 46-75% of the patients for all other parameters. Concerning glycemic regulation, 52.3% of the insulin-dependent diabetes millitus patients and 41.5% of the non-insulin-dependent diabetes mellitus patients had poor regulation. The results for the other parameters included in the metabolic score were more satisfactory. There was a significant correlation between the number of days the patients were in hospital and the HbA1c value. In conclusion, the system enables us to determine the degree of metabolic regulation and regular evaluation of diabetic late complications. Through the measurement of outcome parameters we have discovered failure in process quality in our hospital department.

Adult↗

Body composition in active acromegaly during treatment with octreotide: a double-blind, placebo-controlled cross-over study.

OBJECTIVE: In active acromegaly body composition is characteristically altered by an increase in lean body mass and a corresponding reduction in fat mass. These changes are induced by an excessive secretion of GH and insulin-like growth factor I (IGF-I). Growth hormone is an anabolic hormone and leads to stimulation of protein synthesis and an increased lipolysis in adipose tissue. Treatment with the somatostatin analogue, octreotide, has been shown to reduce GH levels causing reduced hormonal effects on target tissues. We have studied changes in body composition during short-term reduction in GH level by octreotide in active acromegaly. DESIGN: Octreotide was compared to placebo in a double-blind, cross-over trial. Dual-energy X-ray absorptiometry scanning was employed to calculate body composition. Relations between body composition parameters and clinical signs of acromegaly (finger circumference and foot volume) were studied. PATIENTS: Twelve patients with active acromegaly, confirmed by lack of GH suppression during oral glucose loading, were included. All had pituitary adenomas diagnosed by computed tomography. MEASUREMENTS: Serum GH and IGF-I. Lean body mass, fat mass and total weight, foot volume and finger circumference. RESULTS: Four weeks of octreotide treatment caused a 75% decrease in GH levels (n = 10), a reduction in IGF-I from 476 +/- 51.9 (mean +/- SEM) to 233 micrograms/l +/- 46.3 (P < 0.005) and a corresponding decrease in both body weight (2.51 kg +/- 0.41) (P < 0.005) and lean body mass (2.44 kg +/- 0.48) (P < 0.005). No significant changes in fat mass were observed. These findings were paralleled by significant reductions in foot volume (44.50 ml +/- 17) (P < 0.05) and finger circumference (1.3 mm +/- 0.3) (P < 0.05). CONCLUSIONS: Short-term octreotide therapy reduces growth hormone levels leading to a significant reduction in lean body mass as assessed by dual-energy X-ray absorptiometry. Alterations in lean body mass were positively correlated with reductions in foot volume. Thus, simple clinical tests may be valuable in judging the effects of treatment in active acromegaly.

Absorptiometry, Photon↗

Metabolic remission with octreotide in patients with insulinoma.

OBJECTIVES: The efficacy of octreotide was studied in a group of patients with biochemical evidence of insulinoma. DESIGN: A phase-II study. SETTING: A university department of internal medicine. SUBJECTS: Seven patients with biochemical evidence of insulinoma and without metastatic lesions. INTERVENTION: Daily treatment with octreotide, a somatostatin analogue, mainly within the dosage of 100-300 micrograms day-1. The treatment was continued in patients with biochemical evidence of response or until surgery was undertaken. MAIN OUTCOME: Five patients avoided hypoglycaemic symptoms and had normalization of blood glucose values for a median of 15+ months (range 0.2-54 months). Two did not improve metabolically. The treatment was well tolerated and had no deleterious effects on blood glucose regulation. CONCLUSION: Octreotide seems to be a promising treatment for many of the patients with insulinoma who are not suitable for surgery.

Adult↗

Plasma oestrogens in postmenopausal women with endometrial cancer.

OBJECTIVE: To study plasma levels of estrogens and androgens, sex hormone-binding globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients with endometrial cancer. DESIGN: Patients and controls were matched for age, body mass index, parity and years since menopause. SETTING: Department of Obstetrics and Gynaecology, Hvidovre Hospital, Denmark. SUBJECTS: Fifty postmenopausal patients with endometrial cancer and 54 matching controls. MEASUREMENTS: Plasma levels of SHBG, FSH, oestrone, oestradiol, oestrone-sulphate, dehydro-epiandrosterone sulphate, testosterone, and androstenedione were measured by radio-immunoassays. Free fractions of oestradiol and testosterone were calculated according to levels of SHBG and albumin. RESULTS: The levels of oestradiol, free oestradiol, and oestrone were elevated (P < 0.001) in patients compared with controls (oestradiol: 51 (45-59) vs 37 (34-41) pmol/l; free oestradiol: 0.69 (0.59-0.80) vs 0.48 (0.42-0.54) pmol/l; oestrone: 180 (159-204) vs 119 (107-133) pmol/l (mean values (95% CI) in patients vs controls)). Furthermore, an increased oestrone:androstenedione ratio (0.095 vs 0.072, P < 0.01) was found in patients. SHBG correlated negatively (P < 0.001) with body mass, while the free fractions of oestradiol and testosterone correlated positively (P < 0.01) with body mass, in both patients and controls. Multiple regression analysis showed that the differences in oestrogen levels between the two groups persisted when controlling for the effect of body mass, age, years since menopause, parity, and levels of SHBG and FSH. CONCLUSION: Patients with endometrial cancer exhibit increased plasma levels of oestradiol and oestrone. Speculatively, these oestrogens may result from an increased oestrone conversion from androstenedione, an increased ovarian and adrenal secretion of androstenedione, or alternative oestrogen production routes. The present findings support the hypothetical role for oestrogens in the aetiology of endometrial cancer.

Aged↗