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Biomedical subjects

J Born

Publications and source records attributed to J Born.

At least 127 records · Page 7Linked to original sources

Accelerated ST-segment reduction after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) compared to urokinase.

Effects of therapy with urokinase (UK) and with recombinant tissue plasminogen activator (rtPA) were compared in patients with acute myocardial infarction (AMI). To achieve homogenous therapeutic conditions the comparison was restricted to patients having their first AMI and to cases of clinically successful thrombolytic therapy (defined by non-invasive criteria, such as a 50% decrease in elevated ST-segment in the worst load of a 12 lead ECG within 300 min after onset of thrombolytic therapy, complete pain resolution during thrombolytic therapy, and later confirmed by angiography 10 days after AMI). Effects of UK and rtPA on continuous multilead ST-segment analysis and cardiac proteins (creatine kinase and its isoenzyme CK-MB, aspartate transaminase and hydroxybutyrate dehydrogenase) were analyzed during 24 hours following onset of therapy. Continuous ST analysis showed a faster resolution of the elevated ST-segments after thrombolytic therapy with rtPA than with UK(p < 0.01). Accelerated idioventricular rhythms (p < 0.05) occurred sooner following rtPA than UK treatment. The wash-out of creatine kinase was increased (p < 0.01) after rtPA. Although both drugs induced comparable, angiographically controlled reperfusion, the results suggest that the process of reperfusion was accelerated during thrombolysis with rtPA compared to UK. Thrombolytic therapy of AMI with rtPA may hence improve myocardial salvage.

Adult↗

[Electrophysiologic correlates of selective attention in children and adolescents at increased risk of schizophrenia].

Electrophysiological correlates of selective attention in children and adolescents at high risk for schizophrenia. As part of a research project on electrophysiological correlates of attention in young subjects at high genetic risk for schizophrenia, auditory event-related potentials (ERPs) associated with selective attention and automatic information processing were recorded in 21 adolescent (offspring of at least one parent with schizophrenia) and 21 control subjects matched for age, sex and socioeconomic status. The experimental task was a dichotic listening task, and accuracy of counting target pips served as a psychometric control variable. The results showed group-related differences in the ERPs, with a significant reduction being present in the high-risk group concerning the amplitude of the fronto-precentrally located negative difference (Nd) wave and the F3 component elicited by selectively attended stimuli. Comparison of individual matched pairs showed that reduced Nds, characterized 14/21 high-risk individuals and reduced P3s 16/21. Moreover, there were significant correlations between ERP reductions and psychometric deficit (counting accuracy). Finally, 13 latencies tended to be prolonged in the high-risk group. Mismatch negativity (MMN), an ERP correlate of automatic information processing, did not differ significantly in the two groups, although there was a marked reduction in amplitude in the high-risk group. The ERP alterations point to impaired selective attention in a considerable proportion of subjects at high genetic risk for schizophrenia.

Adolescent↗

Cytokine production and lymphocyte subpopulations in aged humans. An assessment during nocturnal sleep.

The view of a general impairment of immune functions associated with aging has been challenged by recent studies including a more detailed evaluation of various cytokines and lymphocyte subsets. In the present human study, effects of age on the production of cytokines by T cells and monocytes were assessed, together with age-dependent changes in subset populations of mononuclear cells (MNC). Blood was collected every 30 min during nocturnal sleep in 16 aged (mean: 79.6 +/- 7.5 years) and in 16 young controls (mean: 24.6 +/- 3.1 years). Nocturnal sleep was chosen as a well-defined period within the 24-h cycle with minimal exogenous influences. The in vitro production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) was measured after mitogen stimulation with lipopolisaccharide from E. coli (LPS). Production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) was measured after stimulation with phytohemagglutinin (PHA). Regarding MNC subsets, monocytes, lymphocytes, CD3+, CD4+, CD8+, HLA-DR, CD16+, CD25+, and CD19+ were determined. Advanced age was associated with a decreased number of T cells (CD3+) and decreases in the major T cell subsets (CD4+, CD8+, P < 0.001). Production of IL-2 was not affected. However, production of IFN-gamma tended to be enhanced, and numbers of activated T cells (HLA-DR/CD3+), natural killer cells (CD16+), and T cells expressing IL-2 receptors (CD25+/CD3+) were markedly increased in the aged. While monocyte counts were unchanged in the elderly production of IL-1 beta and TNF-alpha mainly derived from these cells, was enhanced (p < 0.05). Results indicate a state of enhanced responsiveness of the T cell compartment and of monocytes in aged which may compensate for the substantial decrease in T cells.

Adult↗

Improved event-related potential signs of selective attention after the administration of the cholecystokinin analog ceruletide in healthy persons.

Cholecystokinin (CCK) is co-localized with dopamine (DA) in neurons of the mesolimbic-frontocortical dopamine (DA) system, considered essential for the pathology of psychotic behavior and associated attention deficits. The present experiments in 13 healthy men aimed at examining the effects of the CCK analog ceruletide on attention as reflected by event-related brain potentials (ERPs). Subjects were tested according to a double-blind cross-over design on three occasions, following intravenous infusion of placebo, 0.5 microgram ceruletide, and 2.5 micrograms ceruletide. ERPs were recorded during the subject's performance on an auditory selective attention task including the concurrent presentation of frequent standard tones and infrequent deviant tones which the subject had to listen to, or to ignore. The processing negativity (PN) over frontocentral cortical areas, reflecting selective attention, was higher after ceruletide than placebo, this increase being most pronounced after the 2.5 micrograms dose (placebo -1.29 +/- 0.38 microV versus ceruletide -3.02 +/- 0.65 microV, p < .05). ERP signs of a general increase in cortical arousal after ceruletide did not reach significance. Likewise, mismatch negativity, an indicator of preattentive processing of stimulus deviance, was not significantly affected by the peptide. The results indicate that ceruletide affects human brain function primarily by improving selective attention.

Adult↗

Delta-sleep-inducing peptide does not affect CRH and meal-induced ACTH and cortisol secretion.

Besides sleep-promoting properties, delta-sleep-inducing peptide (DSIP) has been reported to act as a corticotropin-releasing inhibiting factor in vitro and in vivo. We examined, first, the influence of DSIP on ACTH and cortisol release following stimulation with human corticotropin-releasing hormone (h-CRH; 1.0 microgram/kg body weight, and 0.5 microgram/kg body weight, respectively) in healthy young men (n = 5 in each condition). DSIP (total doses of 3 and 4 mg, respectively, vs. placebo) was infused intravenously between 30 min prior to and 90 min after CRH injections. Responses of ACTH and cortisol were almost identical during and after infusion of DSIP and placebo. In a second experiment, the influence of DSIP (4 mg, also administered as intravenous infusion) on meal-related ACTH and cortisol secretion was studied in another 10 men. Meal-related midday surge of ACTH and cortisol was also not affected by DSIP. Our data do not support an inhibitory role of DSIP on ACTH and cortisol secretion in man.

Adolescent↗

Comparative assessment of saccadic eye movements, psychomotor and cognitive performance in schizophrenics, their first-degree relatives and control subjects.

This study is aimed at detecting biological markers for schizophrenia. For this purpose, a total of 70 subjects (21 schizophrenic patients, 27 first-degree relatives and 22 controls) performed a series of tests assessing various attentional, psychomotor and cognitive functions and saccadic eye movements. The schizophrenics performed significantly poorer than both high-risk and control subjects in most of the tests demanding attention, concentration and psychomotor speed (d2 concentration test, reaction times and Stroop test of perceptual interference) as well as cognition (Wechsler intelligence scales). On the other hand, these tests did not differentiate between the high-risk and control subjects. This distinction, however, could be made by two other parameters: hypometria score of saccadic eye movements and ratio of verbal to performance intelligence scores. Both parameters were significantly increased in both the schizophrenic and the high-risk group, distinguishing both from the control group. The relevance of these findings in indicating a schizophrenic disposition is discussed.

Adult↗

Hormonal secretion during nighttime sleep indicating stress of daytime exercise.

We tested the hypothesis that long-duration exercise (LDE) of moderate intensity, but not LDE of low intensity, during the daytime changes the typical temporal patterns of hormone release during subsequent nocturnal sleep. Ten trained healthy men participated in a balanced crossover study including three conditions: 1) no exercise, 2) LDE of low intensity (biking 40 km; 1800-2030), and 3) LDE of moderate intensity (biking 120-150 km; 1600-2030). During the subsequent night (2300-0700), somnopolygraphic sleep recordings were obtained, and concentrations of cortisol, growth hormone (GH), and testosterone were measured every 15 min. During the no exercise nights, the typical secretory patterns were present with peak concentrations of GH but nadir concentrations of cortisol during the first half of sleep but increased cortisol levels and minimum GH levels during the second part of sleep. Testosterone concentrations increased during the second half of sleep. LDE of moderate intensity reduced rapid-eye-movement sleep [13.9 vs. 16.9% (no exercise); P < 0.01]. Levels of testosterone decreased with increasing intensity of daytime exercise (P < 0.05). Moderate-, but not low-intensity, LDE decreased GH levels in the first half (P < 0.05) and increased GH levels in the second half (P < 0.005) of sleep. Also, LDE of moderate intensity but not LDE of low intensity increased cortisol levels during the first half (P < 0.005) and decreased cortisol secretion during the second half (P < 0.05) of sleep. Results suggest that nocturnal profiles of GH and cortisol concentrations may serve to indicate the disturbance of normal anabolic functions of sleep due to daytime exercise.

Adult↗

Nocturnal wakefulness inhibits growth hormone (GH)-releasing hormone-induced GH secretion.

Recent studies have suggested that spontaneous release of GH as well as GH secretion stimulated by exogenous GHRH are influenced by central nervous mechanisms that regulate sleep and wakefulness. Here, the effect of nocturnal wakefulness on GH secretion stimulated by i.v. administration of GHRH was examined in two experiments in healthy men. On all nights, GHRH (1 microgram/kg BW) was injected after the subjects had slept for about 2.5 h to minimize interference of endogenous release of GH during early sleep with the response to exogenous GHRH. Both experiments included a control condition to assess GH secretory responses to GHRH during undisturbed sleep and an experimental condition to assess the effect of wakefulness. In the control conditions, subjects slept throughout the night, and GHRH was administered 170 min after sleep onset. In the experimental condition of Exp I (n = 10), subjects were awakened 150 min after sleep onset and stayed awake. GHRH was given 20 min after awakening. In the experimental condition of Exp II (n = 8), subjects were awakened 30 min after GHRH treatment, which was administered 170 min after sleep onset. GHRH administrations during sleep fell into epochs of stage 2 sleep or rapid eye movement sleep. GH secretion and sleep characteristics before GHRH administrations were comparable for experimental and control conditions of both experiments. GH secretory responses were inhibited when the subject was awake at the time of GHRH administration compared to GH responses during undisturbed sleep. Awakening the subject 30 min after GHRH administration abruptly interrupted the initiated GH secretory response. The results demonstrate a profound inhibitory effect of nocturnal awakenings on GHRH-induced GH secretion. They indicate that the GH secretory response to GHRH is strongly determined by central nervous system sleep-wake activity.

Adult↗

Effects of age and gender on pituitary-adrenocortical responsiveness in humans.

This study compared plasma concentrations of adrenocorticotropin (ACTH) and cortisol in young men (N = 10, mean age 24.4 years), young women (N = 10, mean age 25.4 years), old men (N = 8, mean age 81.6 years) and old women (N = 8, mean age 83.5 years) under basal resting conditions and after stimulation with either human corticotropin-releasing hormone (hCRH, 100 micrograms iv) or a combined injection of hCRH (100 micrograms) and arginine vasopressin (VP, 0.5 IU iv). Basal secretion of cortisol did not differ among groups, but basal concentrations of ACTH were diminished in young women (p < 0.01), indicating an enhanced adrenal sensitivity to ACTH in these subjects. Pituitary responses to hCRH did not differ between young men and women. However, responses to hCRH/VP were stronger in the young females (p < 0.01), suggesting an enhanced pituitary responsiveness to the augmenting effect of VP on ACTH release in this group. Pituitary-adrenal secretory responses were greater in old than in young men after sole injection of hCRH (p < 0.05) and even more so after combined injection of hCRH/VP (p < 0.01). In old women, pituitary-adrenal secretory responses were also greater than in young women (p < 0.05). But, in particular for responses to hCRH/VP, these effects were less distinct than within the men. Results indicate an enhancing effect of age on pituitary responsiveness to the hypothalamic secretagogues hCRH and VP, modulated by the subject's gender.

Adrenocorticotropic Hormone↗

Scalp recorded direct current potential shifts associated with the transition to sleep in man.

Cortical direct current (DC) potentials are considered to reflect the state of cortical excitability which may change characteristically from wakefulness to sleep. The present experiments examined changes in the scalp recorded DC potential in 10 healthy humans at the transition from wakefulness to nocturnal sleep. For each subject, DC recordings obtained from Cz were evaluated for a 15 min pre-sleep onset interval and for a 20 min post-sleep onset interval, on 2 separate nights. Sleep stages were determined from standard sleep recordings. The transition from wakefulness to sleep coincided with a significant (P < 0.05) shift in the DC potential of negative polarity. Maximum negative potentials of (mean +/- S.E.M.) 500 +/- 130 microV (first night) and of 760 +/- 200 microV (second night) were reached at the end of the 20 min post-sleep onset interval. A number of possible technical and biological artifacts were controlled. It is reasonable to assume that the slow negative shift of the DC potential at the transition from wakefulness to sleep reflects increased cortical excitability. Whether the negative potential shift pertains during sleep, or is of transient nature and closely linked to the process of falling asleep, remains to be clarified.

Adolescent↗

Comparison of satiating effects of ceruletide and food intake using behavioral and electrophysiological indicators of memory.

Animal and human studies have suggested a satieting effect of ceruletide, an analog of cholecystokinin. In humans, signs of a selectively diminished central nervous processing of food stimuli may provide a more valid measure of satiety than overt eating behavior. To assess the satieting effects of ceruletide in humans, effects of ceruletide and food intake on memory of food stimuli and stimuli not related to food (neutral and sex) were compared with memory performance in fasted subjects. In experiment I, recall of slide-projected words was tested in 12 fasting men in a within-subject comparison (i) following intravenous administration of saline solution, (ii) of ceruletide (6.75 micrograms), and (iii) after having eaten a regular breakfast. The P3 component of the event-related potential to the stimuli was assessed as a physiological sign of memory processing. In experiment II, recognition of pictures was tested in a between-subject design in 36 fasting men following (i) administration of saline solution, (ii) of ceruletide (6 micrograms), and (iii) intake of an opulent meal. After food intake, recall and recognition of food and also of sex stimuli were diminished, but were increased for neutral stimuli. Ceruletide diminished recognition of food stimuli and increased that of neutral stimuli; similar effects on recall of food and neutral stimuli failed to reach significance. P3 amplitude did not reflect changes in memory performance. Memory of food stimuli declined after ceruletide as well as after food intake, suggesting ceruletide mediates satieting effects on memory processing.

Adult↗

Effects of menstrual cycle on creativity.

Seventeen healthy women (21-31 years) not taking oral contraceptives were tested at three phases of the menstrual cycle distinctly differing in hormonal patterns (menses, preovulatory phase, and midluteal phase). Phase detection was assured by determination of blood hormone concentrations. Another 17 women taking oral contraceptives (combined preparation of estrogen and progestin) served as age-matched controls, and were tested during menses and during phases corresponding to preovulatory and midluteal phase. On each test occasion, aspects of creativity were assessed by a battery of six tests measuring "semantic" and "figural" abilities of divergent thinking. Additionally, a test of motor perseveration (Mittenecker-Zeigeversuch) was presented. During the preovulatory phase, creativity was in general improved when serum concentrations of estrogen (E2) and luteinizing hormone (LH) were highest whereas motor perseveration decreased. In control women, there was no preovulatory improvement of divergent thinking and no preovulatory decrease in motor perseveration.

Adult↗

Cholinergic potentiation of the meal-related rise in ACTH and cortisol concentrations in men.

The present study examined the influence of physostigmine, an acetylcholine esterase inhibitor, on the secretory activity of the hypothalamo-pituitary-adrenocortical (HPA)--axis under basal (experiment I) and stimulated (experiment II) conditions in young healthy men. In a third experiment, the effect of scopolamine, a muscarinic acetylcholine receptor antagonist, on HPA secretory activity after physiological stimulation was tested. The experiments started between 09.00 and 10.00 a.m.. After a resting period of 1.5 h, either physostigmine (0.0125 mg per kg body weight soluted in isotonic saline) or placebo (saline) was infused within 15 min. In experiment I subjects (n = 7) remained fasting while in experiment II (n = 18) a standardized lunch was offered after the infusion. Experiment III (n = 7) was designed as experiment II but instead of physostigmine, scopolamine or placebo (0.5 mg) was subcutaneously injected 105 min before the meal. Blood for the determination of ACTH and cortisol was drawn in regular intervals during the experiments. Physostigmine did not change basal ACTH and cortisol secretion per se, excluding activation of basal HPA secretion due to acetylcholineesterase inhibition and its non specific side effects. Meal intake stimulated ACTH and cortisol secretion which was significantly enhanced when physostigmine was administered (p < 0.05). Scopolamine did not influence the meal related ACTH and cortisol secretion. These findings demonstrate that cholinergic neurotransmission is able to increase ACTH and cortisol concentrations in humans. This effect seems to be complementary to other stimulatory neurotransmitter systems, and is functional during stimulated HPA secretory activity and not under basal conditions.

Adrenocorticotropic Hormone↗

Effects of vasopressin on event-related potential indicators of cognitive stimulus processing in young and old humans.

BACKGROUND: Vasopressin has been shown to improve electrophysiological signs of cognitive stimulus processing in young human subjects. This study compared the effects of arginine vasopressin (AVP) on central nervous stimulus processing in old and young mentally healthy subjects. To assess aspects of cognitive stimulus processing, event-related potentials (ERPs) were recorded. METHOD: A total of 22 old and 28 young subjects were tested on two subsequent days. Substances were administered intranasally 22, 12, and 1 hour(s) prior to experimental sessions. Prior to the first session, all subjects received placebo. Prior to the second session, 11 of the elderly and 15 of the young subjects received AVP (3 x 10 IU in each nostril) while the remaining subjects again received placebo. The study was held double blind. The subjects performed an auditory "oddball" task consisting of rare target tones (requiring a button press response) interspersed throughout a sequence of frequent standard tones while an electroencephalogram was recorded. RESULTS: Differences between young and aged subjects were more pronounced for ERPs to targets than standard pips. Latencies of the N2 and P3 waves of the ERP to targets were significantly prolonged, and the P3 amplitude was diminished in the elderly subjects (p < .01). N2 amplitude was enhanced in both age groups by vasopressin (p < .05). However, AVP treatment significantly enlarged the N2-P3 difference amplitude only in young subjects. CONCLUSIONS: The results indicate that AVP improves ERP signs of stimulus processing associated with attentional mechanisms. However, the ERP signs of age-related cognitive impairment remained unimproved after AVP.

Administration, Intranasal↗

Effects of insulin and hypoglycemia on the auditory brain stem response in humans.

1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady-state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III-V (+71 microseconds; P < 0.001) and I-V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I-V and III-V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions.

Adolescent↗

Sleep and wakefulness affect the responsiveness of the pituitary-adrenocortical axis to arginine vasopressin in humans.

The secretory activity of the pituitary-adrenocortical axis at night is characterized by a quiescent period during the first hours of sleep, preceding a period of enhanced activity in the early morning hours. It is still controversial whether the typical nocturnal secretory pattern of adrenocorticotropic hormone (ACTH) and cortisol is a mere reflection of a circadian rhythm or whether mechanisms associated with the state of sleep influence the nocturnal secretion of these hormones. Here, we administered arginine vasopressin (AVP) to normal men during the first part of nocturnal sleep and compared the release of ACTH and cortisol with the release after a second administration during the second part of the same night and also with the release after administration of AVP at identical points of nighttime while subjects were kept awake in another night. Compared with wakefulness, the cortisol release in response to AVP was significantly lower during sleep, with this effect restricted to the early part of sleep. The ACTH release was lower after the first AVP administration during the early part of sleep as compared with the AVP injection during the second part of the same night. Our data demonstrate a sleep-associated inhibition of stimulated ACTH and cortisol release, suggesting a period of decreased responsiveness of the pituitary-adrenocortical axis during early sleep.

Adrenal Cortex↗

Effects of diurnal sleep on secretion of cortisol, luteinizing hormone, and growth hormone in man.

Evidence has been provided for an influence of nocturnal sleep on the secretion of cortisol, LH, and GH in man. Although nocturnal sleep inhibits cortisol secretion during the first hours, it augments the secretion of LH and GH. To separate the effects of circadian rhythm from those of sleep, the present experiments examined the influence of diurnal sleep on the release of cortisol, LH, and GH in 12 young men. Subjects slept on 2 different occasions. After a night of wakefulness, subjects were assigned to bed at 0800 h the following morning. Lights were turned off either at 1100 or 1500 h to enable sleep. Effects of diurnal sleep were evaluated by comparing blood hormone concentrations during the interval from 1100-1500 h between subjects when sleeping and awake. Comparing hormonal concentrations during the 4 h of sleep after 1100 h with those during the 4-h sleep interval after 1500 h provided evidence for an influence of circadian rhythm on cortisol and LH release. Diurnal sleep, as has been shown for nocturnal sleep, augmented the secretion of LH and GH. However, in contrast to nocturnal sleep, diurnal sleep failed to suppress cortisol release, suggesting that sleep does not inhibit cortisol release at any point of its circadian rhythm, but only within a limited range of entrainment.

Adult↗