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Biomedical subjects

K Wiedemann

Publications and source records attributed to K Wiedemann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intermittent capnography during high-frequency jet ventilation for prolonged rigid bronchoscopy.

BACKGROUND: Gas exchange during high-frequency jet ventilation (HFJV) for prolonged rigid bronchoscopy (RBS) is usually monitored by arterial blood gas analysis. Capnography of expired gases during brief HFJV discontinuation may be a reliable and noninvasive supplemental method. Capnography can be performed either for single breaths or with respiratory rate (RR) reduced to 10 x min(-1). The aim of this study was to demonstrate that capnography during short periods of HFJV discontinuation represents a reliable measure of PaCO2 during prolonged RBS. METHODS: We prospectively investigated 100 consecutive patients (75 male and 25 female) undergoing HFJV for RBS. HFJV was delivered through the rigid bronchoscope at the following settings: working pressure 1.2 bar, rate 100 x min(-1), FIO2 0.99, t(i)/t(tot)0.6. The light guiding channel ending at the distal tip of the rigid bronchoscope was used for gas sampling. Capnograms were assessed at 5 min intervals and compared to PaCO2 from arterial blood samples drawn simultaneously. The accuracy of single breath CO2 sampling was compared with sampling at RR=10 x min(-1). RESULTS: Mean duration of RBS was 30+/-21 min. A significant correlation between capnography (PetCO2) and arterial blood gas analysis (PaCO2) was observed, being r=0.90 for the RR= 10 x min(-1) method and r=0.91 for the single breath method. Mean difference between PaCO2 and PetCO2 was 0.37+/-0.2 kPa throughout the entire study period. No significant differences between single breath sampling or sampling at RR=10 x min(-1) were observed. CONCLUSION: Capnography performed during short periods of HFJV discontinuation reliably and noninvasively reflects PaCO2 during prolonged endoscopic procedures. Capnography during HFJV for RBS may reduce the frequency of arterial blood gas sampling, the duration of unmonitored intervals and costs.

Adult↗
PubMed2000

Effects of natriuretic peptides upon hypothalamo-pituitary-adrenocortical system activity and anxiety behaviour.

Natriuretic peptides (ANP, BNP and CNP) comprise a family of structurally related peptides, which are derived from three different genes and which share a 17-amino acid internal ring. Besides their peripheral involvement in diuresis and blood pressure regulation these peptides, their bioactive fragments and their corresponding receptors (natriuretic peptide receptors NPR-A, NPR-B and NPR-C) are found throughout the central nervous system (CNS): NPR-A and NPR-C are found on neurons and astrocytes, while NPR-B is located mainly on neurons and partially colocalizes with NPR-A. In the CNS of man and rodents NPR-A is found mainly in cortex and hippocampus, whereas NPR-B is present in the amygdala and several brainstem regulatory sites. NPR-C is found widely within the CNS i.e. in neocortex, limbic cortex, the hippocampal area and the amygdala. These peptides and their receptors represent an important neuromodulatory system within the CNS, which is involved not only in the regulation of fluid homeostasis but also directly influences emotional behaviour, such as anxiety and arousal, and the sequelae of stress hormone release and autonomic nervous system activation. Natriuretic peptides are specifically involved in the regulation of the hypothalamo-pituitary-adrenocortical (HPA) system: in man and rodents ANP inhibits the HPA system at all regulatory levels, while CNP stimulates the release of cortisol. Complementarily, the anatomic structure of natriuretic peptide systems within the CNS supports an important role for these in normal and pathologic emotional behaviour (e.g. anxiety and panic): in rodents ANP was found to reduce anxiety levels, whereas CNP induced the opposite effect. In patients with panic disorder basal ANP plasma levels are lower in comparison to healthy volunteers, but ANP secretion is faster and more pronounced during experimentally induced panic attacks. The inhibitory potency of ANP could explain the unexpected and so far unresolved failure of autonomic and HPA system activation during panic attacks. Moreover, panic anxiety and concomitant ACTH and cortisol secretion elicited by stimulation with the panicogen cholecystokinin-tetrapeptide were also attenuated by ANP infusions in patients as well as in healthy volunteers. Hence, it may be surmised that in man and rodents ANP reduces anxiety and terminates panic attacks and their neuroendocrine sequelae.

Adrenal Cortex↗
PubMed2000

Comparison of the effects of endothelin-1 and -3 on secretion of pituitary hormones in healthy male volunteers.

The investigation was conducted to study the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on adrenocorticotropin (ACTH), cortisol and prolactin release in man. The design was a prospective placebo controlled double-blind study, including 7 healthy males studied on three occasions. After infusion of either 20 ng/min x kg ET-1, ET-3 or normal saline, venous blood samples were drawn 12 times for determination of ACTH, cortisol and prolactin during the pre- within- and postinfusion period. ET-1 infusion induced a significant increase of plasma ACTH (p< 0.009) and prolactin (p<0.0001) whereas cortisol levels increased without reaching significance (p<0.074). Infusion of ET-3 induced no changes in plasma levels of ACTH, cortisol or prolactin. The parallel increase of ACTH and prolactin induced by infusion of ET-1 could indicate an involvement of corticotropin-releasing hormone (CRH) in mediating the ET-1 effect on the HPA-axis in man. Whether this supports a possible role of ET-1 as a modulator of the hypothalamo-pituitary-adrenal (HPA) axis remains to be clarified.

Adrenocorticotropic Hormone↗
PubMed2000

Carbon dioxide elimination during high-frequency jet ventilation for rigid bronchoscopy.

Oxygen saturation and carbon dioxide values should be monitored during high-frequency jet ventilation (HFJV). Modern transcutaneous PCO2 (PtcCO2) measurement allows the estimation of ventilation efficiency. We studied how tests of lung function could predict carbon dioxide elimination during HFJV. Lung function tests from 180 adult patients undergoing rigid bronchoscopy were analysed as factors affecting carbon dioxide elimination. The lung function test results showed a significant relationship with the efficiency of carbon dioxide elimination; the greatest impairment of carbon dioxide elimination was found in patients with combined abnormalities of lung function. Further factors associated with difficult carbon dioxide elimination were male gender and elevated body weight. Of the patients investigated, 72% had normal carbon dioxide elimination, whereas in 23% hypercapnia could be avoided only by increasing the driving pressure. The prevalence of abnormal preoperative lung function test results predicts (sensitivity 76%, positive predictive value 27%) impaired carbon dioxide elimination during jet ventilation and rigid bronchoscopy.

Adolescent↗
PubMed2000

Influence of airway-occluding instruments on airway pressure during jet ventilation for rigid bronchoscopy.

We measured changes in airway pressure (Paw) caused by microsurgical instruments introduced into a rigid bronchoscope during high frequency jet ventilation (HFJV). With approval of the institutional Ethics Committee, 10 adults undergoing elective tracheobronchial endoscopy and endosonography during general anaesthesia were investigated. Inflation of an endosonography probe balloon in the left main stem bronchus caused airway obstruction. Pressure measurements proximal and distal to the obstruction were compared after three degrees of obstruction (0%, 50% and 90%) and with two different driving pressure settings. Airway obstruction increased the mean (SD) peak inspiratory pressure (PIP) from 7.5 (2.6) to 9.5 (3.5) mm Hg for 2 atm (P = 0.0008) and from 9.7 (3.7) to 13.0 (5.1) mm Hg for 3 atm (P = 0.0001). Airway obstruction did not alter peripheral PIP (7.2 (4.1) to 7.1 (3.7) mm Hg for 2 atm and 8.8 (4.3) to 9.4 (5.2) mm for 3 atm), but resulted in an end-expiratory pressure (EEP) beyond the narrowing being significantly greater than in the unobstructed airway (2.5 (3.4) to 5.5 (3.7) mm Hg for 2 atm; P = 0.0005) and 3.2 (3.6) to 8.0 (4.3) mm for 3 atm; P < 0.0001). Severe airway narrowing increases inspiratory pressure proximal and expiratory pressure distal to the obstruction in relation to the applied driving pressure. Since the distal EEP never exceeded PIP, even near-total airway obstruction should not cause severe lung distension or barotrauma in subjects with normal lungs.

Aged↗
PubMed1999

Behavioral, neuroendocrine, and cardiovascular response to flumazenil: no evidence for an altered benzodiazepine receptor sensitivity in panic disorder.

BACKGROUND: Flumazenil is a benzodiazepine receptor antagonist thought to be panicogenic in patients with panic disorder but not in control subjects. The present study was undertaken to compare the effects of flumazenil in patients with panic disorder and those in healthy control subjects, and also to determine whether panic disorder is characterized by a hypothesized shift in the benzodiazepine receptor "set-point" and a differential response to flumazenil. METHODS: Eight patients with panic disorder and 8 matched control subjects were given infusions of saline and flumazenil in randomized order. Psychopathological changes, cardiovascular parameters, together with adrenocorticotropic hormone (ACTH) and cortisol secretion were recorded. RESULTS: Patient and control subjects responded to flumazenil uniformly; there was no evidence for an anxiogenic activity of flumazenil in control subjects or panic disorder patients. ACTH and cortisol levels were also not differentially influenced by flumazenil or panic disorder diagnosis. Heart rate and systolic blood pressure in both groups were slightly but significantly reduced by flumazenil compared to saline. CONCLUSIONS: These findings do not support the view that panic disorder patients and control subjects respond differentially to flumazenil or that the suggested shift in the benzodiazepine receptor "set-point," which leads to an inverse agonistic activity of flumazenil, characterizes panic disorder.

Adrenocorticotropic Hormone↗
PubMed1998

C-type natriuretic peptide exerts effects opposing those of atrial natriuretic peptide on anxiety-related behaviour in rats.

As evidence exists that C-type natriuretic peptide (CNP) exerts effects opposing those of atrial natriuretic peptide (ANP), we studied the behavioural properties of CNP after central infusion in rats by their performance in the elevated plus maze. Doses of 0.5 microg and 5 microg i.c.v. had distinct anxiogenic properties. Our data suggest opposing effects of CNP and ANP on anxiety-related behaviour in rats, which appear to be mediated via different receptor occupation and brain regions by a corticotropin-releasing hormone (CRH)-dependent mechanism.

Animals↗
PubMed1998

Atrial natriuretic hormone decreases endocrine response to a combined dexamethasone-corticotropin-releasing hormone test.

BACKGROUND: An escape from the dexamethasone-induced suppression of pituitary-adrenocortical activity can be provoked by corticotropin-releasing hormone (CRH) in depressed patients, but not in healthy controls. One important antagonist of the CRH-stimulated secretion of corticotropin (ACTH) and cortisol is atrial natriuretic hormone (ANH). METHODS: To study a potential role of ANH in the dexamethasone-CRH test, we investigated 7 healthy men who did not suppress cortisol below 40 ng/mL after they had received 0.5 mg dexamethasone the evening before. RESULTS: We found 1) that the CRH-stimulated ACTH and cortisol secretion was significantly reduced by the administration of ANH in comparison to saline; and 2) that there was an increased pituitary-adrenocortical ratio. CONCLUSIONS: Our results support the view that ANH may also be involved in the frequently observed nonsuppression after dexamethasone during depression. Biol Psychiatry.

Adrenocorticotropic Hormone↗
PubMed1998

Sleep endocrine effects of megestrol acetate in healthy men.

Synthetic and naturally occurring steroids exert a variety of neural effects that include modulation of nocturnal sleep. The present study focuses on the effect of progesterone receptor (PR) activation on the nocturnal sleep electroencephalogram (EEG) in male volunteers. As a PR ligand, the synthetic progesterone megestrol was used, which has the advantage over progesterone in that it is not metabolized into other steroid compounds which could cloud the progesterone-mediated effects through their own neuroactive properties. Nine healthy male volunteers were investigated in a prospective single-blind randomized study design. They received either placebo tablets or megestrol acetate dosages of 160, 320 or 480 mg at 14.00 h and 19.00 h. Blood samples were drawn half-hourly from 22.00 h until 07.00 h. After 320 mg megestrol, plasma adrenocorticotropin secretion was lower and growth hormone secretion was higher than after 160 mg and 480 mg megestrol or placebo. Similarly, the reduction in the relative amount of rapid eye movement sleep was most pronounced after 320 mg. Thus, progesterone receptor activation, as reflected by the sleep EEG and associated pituitary hormone secretion, follows a nonlinear U-shape dose dependency of a well-defined PR ligand, which may explain the unresolved inconsistencies of neuroendocrine progesterone effects to date. Moreover, employing a CV1 cell line, contransfected with a human glucocorticoid receptor expression vector and a reporter gene-based detection system for transcriptional activity, revealed that a PR agonist such as megestrol may also activate glucocorticoid receptors. This may account for some of the neuroendocrine effects of megestrol and other progestins.

Adrenocorticotropic Hormone↗
PubMed1998

Sleep-endocrine effects of mifepristone and megestrol acetate in healthy men.

Administration of steroid hormones was demonstrated to modulate the sleep electroencephalogram (EEG) and sleep-associated hormonal secretion in specific ways. The present study was conducted to compare the effects of mifepristone (Mif), a mixed glucocorticoid (GR) and progesterone receptor (PR) antagonist, and megestrol acetate (Meg), a PR agonist. Nine healthy men were pretreated with either placebo or 200 mg Mif or 320 mg Meg, or a combination of both. Changes in plasma adrenocorticotropic hormone (ACTH), cortisol, and growth hormone concentrations were registered every 30 min; sleep EEG recordings were obtained continuously. Administration of Mif increased the morning plasma ACTH and cortisol surges, whereas Meg had the opposite effect. Growth hormone secretion was lowered by Mif pretreatment and enhanced by Meg. Simultaneous administration of both compounds led to largely compensated effects. The sleep EEG changes induced by Mif were a slight increase in the time awake and a delayed onset of slow-wave sleep. Meg led to a reduction of rapid-eye-movement sleep. Simultaneous administration of Mif and Meg showed a synergism in increasing time awake and shallow sleep: it therefore may be concluded that the sleep EEG effects are mediated by an interaction of GR and PR in unknown mechanisms.

Adrenocorticotropic Hormone↗
PubMed1998

Effect of flumazenil in lactate-sensitive patients with panic disorder.

OBJECTIVE: Flumazenil is a benzodiazepine receptor antagonist that has been reported to provoke panic attacks in patients with panic disorder. This study was undertaken to compare the effects of flumazenil and sodium lactate, the most widely studied panic provocation agent. METHOD: Ten patients with panic disorder were given infusions of saline, sodium lactate, and flumazenil in randomized order. Panic attacks, psychopathological changes, heart rate, and cortisol and ACTH secretion were recorded. RESULTS: Eight of the 10 patients experienced a panic attack after sodium lactate, but none did after flumazenil or saline. Cortisol and ACTH secretion were not enhanced by any of the treatments. Sodium lactate increased heart rate, whereas flumazenil had the opposite effect. CONCLUSIONS: These findings do not lend support to the view that the benzodiazepine receptors of lactate-susceptible patients with panic disorder are hypersensitive and that flumazenil can therefore act as an inverse agonist.

Adrenocorticotropic Hormone↗
PubMed1997

The effect of repeated human corticotropin-releasing hormone administration on dexamethasone-suppressed pituitary-adrenocortical activity in healthy subjects.

A dexamethasone suppression test (DST) using a dosage of 1.5 mg dexamethasone was administered two times in randomized order to 10 healthy male subjects. From 2300 hours to 0700 hours subjects were injected repeatedly with either increasing dosages of human corticotropin-releasing hormone (hCRH) or 0.9% saline. In comparison to saline administration, in which cortisol levels remained suppressed, the time course of cortisol concentrations with hCRH stimulation showed a biphasic secretory pattern. According to a criterion level of a minimum of 40 ng/mL plasma for nonsuppression, the majority of the subjects changed their DST status to nonsuppression with hCRH. Adrenocorticotropic hormone secretion also differed significantly between saline and hCRH administration. During stimulation with hCRH, plasma dexamethasone levels were slightly and nonsignificantly reduced in the morning hours. Our results indicate that repeated dosages of hCRH impair the dexamethasone-induced suppression in man and support an involvement of CRH also in mediation of the DST nonsuppression during depressive illness.

Adrenocorticotropic Hormone↗
PubMed1997

Induction of IL-15 messenger RNA and protein in human blood-derived dendritic cells: a role for IL-15 in attraction of T cells.

IL-15 is a pleiotropic cytokine with IL-2-like functions. As IL-15 was shown to be mitogenic for T cells, we wondered whether human blood-derived dendritic cells (DC), as the primary stimulators of T cell responses, are able to produce IL-15. To test our hypothesis, DC were grown under serum-free conditions from human peripheral blood using granulocyte-macrophage CSF and IL-4. Cultures were assayed for IL-15 mRNA production at various times by semiquantitative reverse transcription-PCR. Low baseline signals were detected from days 0 to 5 of culture. A significant increase was detected from days 5 to 9 of the culture. When DC were further enriched by immunomagnetic beads to >98% purity as determined by CD83 staining, IL-15 mRNA signals were exclusively found in the CD83+ fraction. This increase in mRNA signals was paralleled by IL-15 protein release from days 9 to 12 as detected by CTLL-2 assay and ELISA. In addition, protein levels were increased >10-fold by adding paramagnetic beads to the cultures, thereby inducing phagocytic activity. Furthermore, DC supernatants were tested for chemokinetic and chemotactic activities for T cells in a checkerboard filter assay. It was shown that supernatants express chemokinetic and chemotactic activity for T cells. This activity was blocked almost completely by addition of an anti-IL-15 mAb. Our data show that human blood DC contain IL-15 mRNA and produce functional protein that is induced in culture. Protein release is triggered by phagocytic activity. Furthermore, DC-derived IL-15 has chemotactic and chemokinetic activities for T cells, suggesting a role for IL-15 as an attractant of T cells during the initial DC/T cell interaction.

Cells, Cultured↗
PubMed1997

Open clinical trial on the sigma ligand panamesine in patients with schizophrenia.

The sigma (sigma) receptor has been proposed as a target of neuroleptic drugs. Preclinical data suggest that panamesine (EMD 57445), a novel sigma ligand, has antipsychotic effects and is free of side effects related to the extrapyramidal motoric system (EPMS). Here we report the results of an exploratory study aimed at determining the appropriate dose range and the safety of panamesine in patients with an acute episode of schizophrenia. The first trial with four patients revealed insufficient clinical efficacy of a protocol where the daily dosage was increased stepwise from 7.5 mg during week 1, up to 30 mg during weeks 3 and 4. In a second set of trials, 12 patients received 15 mg at the beginning, this being increased up to 60 mg/day within 3 days and then maintained at this level for 4 weeks. As assessed by a decrease in the Brief Psychiatric Rating Scale score by at least 50%, five patients were judged as responders, whereas six patients showed only a slight improvement, and one deteriorated. Moreover, intent-to-treat analysis showed significant improvement in psychometric variables. In all patients prolactin levels increased during treatment, probably due to an active metabolite with weak dopamine-2-receptor antagonistic effects. No major side effects occurred, and in particular, no EPMS symptoms were seen.

Acute Disease↗