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Biomedical subjects

E Endert

Publications and source records attributed to E Endert.

At least 19 recordsLinked to original sources

Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men.

The steroid hormone dehydroepiandrosterone (DHEA) has been reported to protect against certain viral infections in animal models and to be a modest inhibitor of human immunodeficiency virus type 1 (HIV-1) infection in vitro. Serum DHEA levels were determined in 41 asymptomatic HIV-1-seropositive subjects, who progressed to AIDS within 5 years after entering a cohort study, in 41 HIV-1-seropositive controls, who remained asymptomatic, and in 41 HIV-1-seronegative controls. At entry, DHEA levels were higher in the seronegative group (median, 13.3 nmol/l) than in either the seropositive nonprogressors (median, 9.2 nmol/l; P = .01) or the progressors (median, 7.2 nmol/l; P less than .001). DHEA levels in the progressors approximately 5 months before the diagnosis of AIDS were lower than the levels in the nonprogressors after the same follow-up (median, 5.6 vs. 8.8 nmol/l; P = .007). DHEA levels less than 7 nmol/l and CD4+ cell counts less than 0.5 x 10(9)/l both proved to be independent predictors for disease progression in HIV-1-infected men.

Acquired Immunodeficiency Syndrome

Circadian changes in pulsatile TSH release in primary hypothyroidism.

OBJECTIVE: We evaluated pulsatile and circadian TSH secretion in primary hypothyroidism. DESIGN: In a prospective study, blood was sampled every 10 minutes during 24 hours for assay of TSH (IRMA). Thyroid hormones and TSH responsiveness to TRH were then measured. SUBJECTS: Nine patients with overt primary hypothyroidism, seven patients with subclinical hypothyroidism and 16 healthy controls. MEASUREMENTS: Computer-assisted analysis by the Desade and Cluster programs. RESULTS: Both computer-assisted programs revealed an increased TSH pulse amplitude in both overt and subclinical hypothyroidism versus controls (Desade: 36.9 +/- 31.4 (mean +/- SD) (P < 0.001) and 2.8 +/- 1.9 (P < 0.001) vs 0.4 +/- 0.2 mU/l; Cluster: 25.6 +/- 25.1 (P < 0.001) and 2.4 +/- 1.4 (P < 0.001) vs 0.4 +/- 0.2 mU/l). TSH pulse frequency remained unchanged with approximately 10 pulses/24 hours. A highly significant correlation was found between the mean 24-hour TSH concentration and the TSH pulse amplitude in all controls and patients but not to TSH pulse frequency. The nocturnal TSH surge was absent in six out of nine patients with overt primary hypothyroidism. The deficient nocturnal rise of TSH in primary hypothyroidism vs controls (22 +/- 51 vs 82 +/- 41%, P < 0.001), was associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency. CONCLUSIONS: Mean 24-hour TSH pulse amplitude is increased in primary hypothyroidism, but TSH pulse frequency remains unchanged. The decrease of the nocturnal TSH increase in primary hypothyroidism is associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency.

Adult

The nocturnal thyroid-stimulating hormone surge is absent in overt, present in mild primary and equivocal in central hypothyroidism.

UNLABELLED: The nocturnal TSH surge was studied in controls, in 34 patients with hypothalamic/pituitary disease and in 21 patients with primary hypothyroidism. It was absent in 5/12 hypothyroid patients and in 5/22 euthyroid patients with hypothalamic/pituitary disease (42% vs 23%, NS). Central hypothyroidism relative to euthyroidism was associated with a lower absolute (0.3 +/- 0.4 vs 0.9 +/- 1.0 mU/l, p less than 0.05) and relative (24 +/- 31 vs 63 +/- 51%, p less than 0.05) nocturnal rise in TSH. In primary hypothyroidism, the nocturnal TSH surge was absent in eight of ten patients with overt, in one of five patients with mild and in none of six patients with subclinical hypothyroidism. The relative nocturnal rise in TSH was normal in mild (54 +/- 33%) and subclinical (92 +/- 69%), but decreased in overt hypothyroidism (2 +/- 10%). Plasma T4 was positively and 09.00 plasma TSH negatively related to the relative nocturnal TSH surge in primary hypothyroidism, but not in central lesions. In both conditions, however, a positive relationship was observed between the relative nocturnal TSH surge and the relative increase of TSH to TRH. IN CONCLUSION: (a) The nocturnal TSH surge is usually absent in overt hypothyroidism but present in mild primary hypothyroidism and equivocal in central hypothyroidism. This limits its usefulness as an adjunct in the diagnosis of central hypothyroidism. (b) The magnitude of the nocturnal TSH surge in patients with hypothalamic/pituitary disease or primary hypothyroidism is directly related to the TSH response to TRH, and thus appears to be determined by the directly releasable TSH pool of the pituitary.

Circadian Rhythm

Improved method for the determination of serotonin in plasma by high-performance liquid chromatography using on-line sample pre-treatment.

An improved method for the determination of serotonin in platelet-rich plasma (PRP) and platelet-poor plasma (PPP), by reversed-phase high-performance liquid chromatography with electrochemical detection and direct plasma injection, is described. The chromatographic system comprises a strong cation-exchange pre-column and a C18 analytical column. The method is selective, rapid, simple and sensitive, and offers good reproducibility and recovery. Reference values for serotonin concentrations in healthy adults (n = 10) are 31 nM for PPP and 6 nmol per 10(9) platelets for PRP. The conditions used for the preparation of PRP and PPP may influence the serotonin concentration in PRP.

Adult

Glucose and fat metabolism during short-term starvation in cirrhosis.

To evaluate the metabolic consequences of short-term (i.e., less than 24 hours) starvation, glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16-hour and again after 22-hour starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect calorimetry. Although patients and controls showed significant increases in free fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16- and after 22-hour starvation were higher in cirrhosis. Fat oxidation was enhanced in the patients, but did not increase during fasting in contrast to controls (increase 19% +/- 17%, P less than 0.05). Net glucose oxidation was decreased in postabsorptive cirrhotics (P less than 0.05). Although postabsorptive glucose turnover was not different from controls, starvation induced a greater decrease in glucose turnover in the patients (25% +/- 3% vs. 10% +/- 3%, P less than 0.05). This was not reflected in plasma glucose concentrations. In conclusion, the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose. It remains to be established whether these changes are merely explained by defective liver function, per se.

Adult

Insulin sensitivity and insulin clearance in human immunodeficiency virus-infected men.

To test whether clinically stable human immunodeficiency virus (HIV) infection, like other infections, is associated with insulin resistance and increased insulin clearance, we measured the sensitivity to insulin and insulin clearance using the euglycemic insulin clamp technique in 10 clinically stable outpatients with symptomatic HIV infection (Centers for Disease Control [CDC] group IV) and 10 healthy controls. During administration of 0.8 and 4 mU insulin.kg-1.min-1, HIV-infected men had 40% (P less than .02) and 83% (P less than .01) higher rates of insulin clearance when compared with healthy controls. Despite significantly lower steady-state insulin concentrations (42 +/- 2 v 52 +/- 4 microU/mL, P less than .05, and 255 +/- 17 v 392 +/- 14 microU/mL, P less than .001, patients v controls), patients and controls had similar total glucose uptake (7.99 +/- 0.81 v 7.92 +/- 0.44 mg.kg-1.min-1 and 14.00 +/- 0.81 v 13.65 +/- 0.65 mg.kg-1.min-1, patients v controls). In the postabsorptive state, no differences were found between patients and controls in insulin levels (7 +/- 1 microU/mL in both) and endogenous glucose production (2.52 +/- 0.07 and 2.24 +/- 0.17 mg.kg-1.min-1, respectively), but plasma glucose levels in the patients (5.02 +/- 0.15 mmol/L) were significantly lower when compared with controls (5.46 +/- 0.14 mmol/L, P less than .05). The results indicate that HIV-infected men have increased rates of insulin clearance and increased sensitivity of peripheral tissues to insulin, which makes HIV infection unique with regard to glucose and insulin metabolism.

Adult

Sex- and time-dependent changes in neurochemical and hormonal variables induced by predictable and unpredictable footshock.

Previous experiments have revealed sex-dependent effects of inescapable shock in rats. Behavior of male rats was more severely disrupted by inescapable shock than behavior of female rats. These sex differences were found after 1- and 24-hour intervals but not after a 72-hour interval. The present experiment was designed to study various physiological parameters at 1-, 4- and 24-hour intervals after inescapable footshock. The predictability of shock was manipulated by adding a compound light and tone stimulus that preceded shock presentation for one group but was not correlated with shock presentation for another group of subjects. Noradrenaline, dopamine, serotonin, and metabolites of these 3 transmitters were measured in the frontal cortex. Transient shock-induced increments in dopamine and metabolites of dopamine and serotonin were found, but the sex of the animal did not differentially affect this neurotransmitter response. In addition to neurotransmitter concentrations in the frontal cortex, levels of corticosterone were measured in plasma. The pituitary-adrenal axis was activated for a longer period in females than males after shock. The present data do not provide evidence that behavioral sex differences induced by inescapable shock are paralleled by sex differences in neurotransmitter activity. In addition, sex-dependent effects of predictability of shock on neurotransmitter activity were not detected. The relevance of the observed sex-dependent responses in the pituitary-adrenal system is discussed.

Animals

Basal fuel homoeostasis in symptomatic human immunodeficiency virus infection.

1. In eight clinically stable symptomatic human-immunodeficiency-virus-infected patients and in seven healthy control subjects, glucose and fat metabolism were studied, using indirect calorimetry and primed continuous infusions of [3-3H]glucose and [14C]palmitate. 2. Studies were performed in the post-absorptive state (16 h of overnight fasting) and again after 22 h of overnight fasting. 3. In the post-absorptive state, net fat oxidation and triacylglycerol ('triglyceride') concentrations were significantly higher in the patients, but concentrations and turnover of free fatty acids were not significantly different between patients and control subjects. After 22 h of overnight fasting, free fatty acid turnover in the patients rose to significantly higher levels when compared with the control subjects. 4. Post-absorptive glucose oxidation, glucose turnover and glucose clearance did not differ between patients and control subjects. Although fasting induced a significantly greater decline in glucose turnover in the patients, plasma glucose concentrations decreased comparably in patients and control subjects. 5. No differences were found in plasma concentrations of insulin or of the counter-regulatory hormones between patients and control subjects. 6. It is concluded that the metabolic adaptation to short-term starvation in clinically stable human-immuno-deficiency-virus-infected patients differs from that in healthy control subjects. Short-term starvation results in a significantly greater fall in glucose turnover, whereas fat metabolism is clearly stimulated. These alterations cannot be explained by differences in the concentrations of insulin or of the counter-regulatory hormones.

Acquired Immunodeficiency Syndrome

Resting energy expenditure and substrate oxidation in human immunodeficiency virus (HIV)-infected asymptomatic men: HIV affects host metabolism in the early asymptomatic stage.

To study the effect of persistent human immunodeficiency virus (HIV) infection on host metabolism, we performed indirect calorimetry in 11 asymptomatic HIV-infected patients (Centers for Disease Control group II or III) who were seropositive for greater than or equal to 1 y, but who still had normal numbers of circulating CD4+ T cells, and in 11 healthy control subjects of similar age and relative body composition. HIV-infected patients had 8% (P less than 0.05) higher rates of resting energy expenditure than did control subjects. Fat-oxidation rates were significantly higher in the patients (means +/- SE: 2.90 +/- 0.08 vs 2.19 +/- 0.17 g.kg FFM-1.d-1, patients vs control subjects, P less than 0.01) whereas no significant differences in carbohydrate-oxidation rates between patients and control subjects were found. These alterations in metabolism were not associated with increased concentrations of catecholamines, cortisol, or thyroid hormones. Mean concentrations of interleukin 6 in the patients were increased only twofold when compared with healthy control subjects. The results indicate that HIV infection affects host metabolism in the early asymptomatic stage, before CD4+ T cell numbers start to decline.

Adult

Effects of interpleurally administered bupivacaine 0.5% on opioid analgesic requirements and endocrine response during and after cholecystectomy: a randomized double-blind controlled study.

In 30 patients undergoing cholecystectomy, a randomized double-blind saline-controlled study was performed using interpleural 0.5% bupivacaine with or without epinephrine (5 micrograms.ml-1) in combination with 0.8% halothane inspired concentration in oxygen. The aim of the study was to investigate whether interpleural 0.5% bupivacaine could decrease the intraoperative opioid requirements and attenuate the metabolic endocrine response to surgical stress. Patients were randomly allocated to one of three groups: Group 1: 0.5% bupivacaine; Group 2: 0.5% bupivacaine with epinephrine (5 micrograms.ml-1); and Group 3: saline. The interpleural catheter was inserted after induction of anesthesia in the spontaneously breathing patient. The study drug was injected 30 min prior to surgery. Peak plasma bupivacaine concentrations in the respective groups were 1.30 +/- 0.78 and 1.16 +/- 0.48 micrograms.ml-1. In all patients concentrations were below suggested convulsive level. Two patients in Group 1 and two in Group 2 required intraoperative fentanyl (0.1 mg each). In contrast, eight patients in the saline group received an average of 0.21 mg (range 0.1 +/- 0.4 mg) fentanyl (P less than 0.05). Postoperatively, a second dose of the study drug was given. Subsequently, pain was assessed using a visual analog score and a verbal rating scale. Pain scores decreased significantly 30 min after the interpleural injection in both bupivacaine groups and remained unchanged in the saline group (P less than 0.05). Pain management by means of interpleural bupivacaine was successful in 17 of the 20 patients. In the saline group seven out of ten patients needed additional analgesics (P less than 0.05). Cortisol levels increased in response to surgery in all groups: maximum levels in Groups 1, 2 and 3 were: 1.09 +/- 0.29, 1.11 +/- 0.20 and 1.19 +/- 0.16 mumol.l-1, respectively. Plasma glucose concentrations increased significantly in all groups: maximum levels in Groups 1, 2 and 3 were: 7.6 +/- 1.3, 7.3 +/- 1.7 and 8.3 +/- 1.7 mmol.l-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans.

To evaluate the role of tumor necrosis factor (TNF) in the initiation of the metabolic response to acute infection, we performed a crossover saline-controlled study in six healthy postabsorptive men, investigating the metabolic effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a transient stress hormone response, associated with an early and sustained rise in plasma glucose concentrations (percentage increase at 2 h 23 +/- 7; P less than 0.05). Glucose turnover, measured 7.5 h postinjection, was 10 +/- 3% higher after TNF administration (P less than 0.05). Plasma free fatty acids (FFA) and glycerol concentrations increased transiently after TNF injection, peaking after 4 h (percentage increase 363 +/- 83 and 67 +/- 14, respectively; both P less than 0.05). FFA turnover, determined 6.5 h postinjection, increased in five subjects to a variable extent (percentage increase 126 +/- 55; P less than 0.05). Finally, resting energy expenditure showed a transient rise after TNF injection (34 +/- 2% at 4 h; P less than 0.05). We conclude that intravenous TNF reproduces many of the metabolic changes observed in septicemia, suggesting that TNF may be an initiating factor in the development of the metabolic response to acute infection.

Acute Disease

Decreased glucose oxidation during short-term starvation.

Prolonged fasting (for days or weeks) decreases glucose production and oxidation. The effects of short-term starvation (ie, less than 24 hours) on glucose metabolism are not known. To evaluate this issue, glucose oxidation and glucose turnover were measured after 16-hour and subsequently after 22-hour fasting. Glucose oxidation was calculated by indirect calorimetry in 12 healthy men (age 22 to 44 years); glucose turnover was measured by primed, continuous infusion of 3-3H-glucose in eight of these 12 volunteers. After 16-hour fasting net glucose oxidation was 0.59 +/- 0.17 mg x kg-1 x min-1 and glucose tissue uptake 2.34 +/- 0.12 mg x kg-1 x min-1. No correlation was found between net glucose oxidation and glucose tissue uptake. Prolonging fasting with an additional 6 hours resulted in decreases of respiratory quotient (0.77 +/- 0.01 v 0.72 +/- 0.01) (P less than .005), plasma glucose concentration (4.7 +/- 0.1 v 4.6 +/- 0.1 mmol/L) (P less than .05), glucose tissue uptake (2.10 +/- 0.12 mg x kg-1 x min-1) (P less than .05), net glucose oxidation (0.09 +/- 0.04 mg x kg-1 x min-1) (P less than .005), and plasma insulin concentration (8 +/- 1 v6 +/- 1 mU/L) (P less than .005). Net glucose oxidation expressed as a percentage of glucose tissue uptake decreased from 22% +/- 8% to 2% +/- 1% (P less than .05). There was no net glucose oxidation in seven of 12 controls after 22-hour fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Increased resting energy expenditure in human immunodeficiency virus-infected men.

Even in the absence of anorexia and malabsorption, weight loss is frequently observed in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). To investigate whether increased resting energy expenditure (REE) might be responsible for this weight loss, indirect calorimetry was performed in 18 human immunodeficiency virus (HIV)-infected men free of clinically active opportunistic infections for at least 2 months. Patients with AIDS (n = 11) or ARC (n = 7) had 9% higher rates of REE when compared with 11 healthy volunteers (P less than .05) with similar food intake and of the same body composition. The results obtained from patients with AIDS or ARC were identical. As no differences were found between patients and controls in plasma concentrations of catecholamines, thyroid hormones, cortisol, or tumor necrosis factor, except for lower concentrations of norepinephrine in the patients (mean +/- SD, 233 +/- 111 v 367 +/- 125 ng/L, patients v controls, P less than .01), this hypermetabolism is not explained by higher levels of these catabolic hormones. The results indicate that even in the absence of acute concomitant infections, increased REE may contribute to the weight loss in patients with AIDS or ARC.

AIDS-Related Complex

Pulsatile secretion of thyrotropin during fasting: a decrease of thyrotropin pulse amplitude.

The effect of fasting on circadian and pulsatile TSH secretion was investigated in eight healthy subjects (four men and four women in the follicular phase). Each subject was studied twice, once during 24 h with normal food intake and once during the last 24 h of a 60-h fast. Blood was sampled every 10 min during 24 h for measurement of TSH by a sensitive immunoradiometric assay. Fasting induced a decrease in plasma T3 [1.73 +/- 0.06 vs. 1.36 +/- 0.04 nmol/L; P less than 0.01 (mean +/- SE), control period vs. fasting] and thyroglobulin (52 +/- 8 vs. 35 +/- 7 pmol/L; P less than 0.001) and an increase in plasma rT3 (0.30 +/- 0.06 vs. 0.44 +/- 0.09 nmol/L; P less than 0.02). Plasma T4, thyroid hormone binding index, and free T4 were not statistically different in both periods. The mean plasma 24-h TSH concentration was lower during fasting than in the control period (2.0 +/- 0.3 vs. 1.0 +/- 0.2 mU/L; P less than 0.005). This was associated with a decrease in mean TSH pulse amplitude during fasting (Desade program: 0.6 +/- 0.1 vs. 0.3 +/- 0.1 mU/L; P less than 0.01; Cluster program: 0.5 +/- 0.1 vs. 0.2 +/- 0.1 mU/L; P less than 0.05), whereas TSH pulse frequency during fasting was unchanged (Desade program: 8.4 +/- 0.9 vs. 9.8 +/- 0.8 pulses/24 h; Cluster program: 9.5 +/- 0.5 vs. 7.9 +/- 0.9 pulses/24 h). There was a highly significant correlation between the mean 24-h TSH concentration and the mean TSH pulse amplitude during both the control period and fasting. Although the decrease in TSH concentration during fasting was evident over 24 h, fasting especially decreased the absolute (1.3 +/- 0.3 vs. 0.4 +/- 0.1 mU/L, P less than 0.02) and the relative (101 +/- 18% vs. 40 +/- 14%; P less than 0.02) nocturnal TSH surge (mean TSH 0000-0400 h vs. mean TSH 1500-1900 h). The decreased nocturnal TSH surge during fasting was associated with a significantly decreased TSH pulse amplitude, but with an unaltered number of TSH pulses between 2000-0400 h. In conclusion, fasting decreases 24-h TSH secretion and the nocturnal TSH surge in the absence of a change in plasma T4 concentration. This is associated with a decreased TSH pulse amplitude, whereas TSH pulse frequency remains unchanged.

Adult

Orthostatic hypotension caused by sympathectomies performed for hyperhidrosis.

We studied sympathetic cardiovascular control in a patient after sympathectomies and found severe hypoadrenergic orthostatic hypotension before and after, but not during upright exercise. This report is the first to correlate in man anatomical sympathetic lesions with autonomic function test results and to document that in a sequence of sympathectomies orthostatic hypotension does not develop until the major part of splanchnic sympathetic outflow is destroyed.

Adult

Lesions of the SDN-POA inhibit sexual behavior of male Wistar rats.

Discrete bilateral lesions in the SDN-POA of sexually naive adult male rats were found to decrease the number of animals ejaculating and/or to increase latencies to the first mount, intromission and ejaculation. The deleterious effects of the lesions disappeared after 4 tests for sexual behavior but were reinstated when the males were tested under suboptimal conditions, i.e., when they were tested with a marginally receptive female or when they had only limited access to the stimulus female. It was subsequently shown that males with a bilaterally lesioned SDN-POA still showed an increase in plasma testosterone. LH and prolactin levels in response to sexual stimulation. Effects of the lesions on scent marking were not found. Together with previous data indicating that SDN-POA-lesions disrupt masculine sexual behavior in females, these data are taken as evidence that the SDN-POA plays a role in the regulation of masculine sexual behavior. The data further suggest that previously reported negative results of SDN-POA-lesions on masculine sexual behavior in male rats might be attributed to the use of sexually experienced instead of sexually inexperienced animals.

Animals

Comparison of beclomethasone dipropionate (2 and 3 mg) and prednisolone sodium phosphate enemas (30 mg) in the treatment of ulcerative proctitis. An adrenocortical approach.

Twenty-three patients with attacks of distal ulcerative colitis were treated randomly with either 2 or 3 mg of topically administered beclomethasone dipropionate (BDP) or 30 mg of prednisolone sodium phosphate (PP). The effect of the steroid enemas on adrenocortical function was assessed by ACTH tests, which were performed before and after treatment. Endoscopic, clinical and histological scores were comparable in the three treatment groups in this pilot trial. Fasting cortisol in the PP group decreased significantly from 0.47 +/- 0.12 mumol/l before to 0.22 +/- 0.14 mumol/l (P less than 0.05) after therapy; in the BDP group no significant changes were found. Urinary cortisol excretion in the PP group was not detectable after therapy; in the BDP group no changes were found. It is concluded that in the topical treatment of ulcerative colitis, BDP may be preferable to PP because it exerts a promising anti-inflammatory action without affecting adrenocortical function.

Adult