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Biomedical subjects

M Haack

Publications and source records attributed to M Haack.

At least 19 recordsLinked to original sources
PubMed2006

[Airway management in pediatric anesthesia].

Airway management in newborns, infants, and children is a challenge to anesthesia practitioners due to the particular anatomic and physiological characteristics. The larynx is positioned more cephalad, the occiput is protuberant, and the neck is short, which makes a special position for anesthesia induction necessary. The high respiratory frequency due to high oxygen demand and carbon dioxide production has to be taken into consideration during manual as well as mechanical ventilation. Different devices are available for airway management. Simple mask ventilation can be improved by a Wendl tube. The classic laryngeal mask can be recommended as a safe airway device in many indications, specifically in children with an upper respiratory airway infection. If intubation is indicated, an optimal size and position of the endotracheal tube has to be provided. Fiberoptic endotracheal intubation is recommended if a difficult airway is known or anticipated due to a craniofacial syndrome.

Airway Obstruction↗
PubMed2006

Low doses of dexamethasone affect immune parameters in the absence of immunological stimulation.

Recent findings suggest an important role of subtle changes in the plasma levels of inflammatory cytokines within the brain-immune interplay. It is unclear how such changes are regulated in the absence of acute inflammatory or infectious stimuli. Endocrine systems are a good candidate, because innate immunity and the hypothalamo-pituitary-adrenal (HPA)-system are closely related: glucocorticoids have immunosuppressive properties and modulate cytokine release from stimulated mononuclear blood cells in vitro and the immune response in vivo, but it still remains unclear, whether they also modulate circulating cytokine levels in the absence of immunological stimuli. We measured the influence of 1.5 or 3.0 mg dexamethasone (DEX) per os at 09:00 or 21:00 hours on body temperature, cortisol plasma levels, differential white blood cell counts, and cytokine plasma levels in 40 healthy male volunteers using a double-blind, placebo-controlled study design. In addition to significant morning-evening differences in tympanic temperature and several immune parameters, we found that DEX-intake significantly increased tympanic temperature, decreased cortisol plasma levels, altered differential white blood cell counts and induced changes in unstimulated plasma cytokine levels. Whereas the levels of TNF-alpha and sTNF-R p75 were reduced, the levels of sTNF-R p55 increased after a transient decrease.

Administration, Oral↗
PubMed2002

Endotoxin-induced changes in food consumption in healthy volunteers are associated with TNF-alpha and IL-6 secretion.

This study examined the effects of endotoxin administration on food and water consumption in humans, and the associations between these changes and endotoxin-induced secretion of cytokines, cortisol, and fever. Twenty healthy male volunteers received an i.v. injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in two experimental sessions. Blood samples were collected hourly, and rectal temperature was monitored continuously. Food consumption was significantly reduced at 0-4 h and significantly elevated at 4-5 h after the endotoxin injection. Endotoxin administration had no significant effect on water consumption. Endotoxin-induced secretion of TNF-alpha and IL-6 was positively associated with the decrease in food consumption (r=0.61 and 0.68), and negatively associated with the rebound increase in food consumption (r=-0.53 and -0.45). Neither the febrile response, nor the secretion of cortisol was associated with the changes in food consumption. These results suggest that TNF-alpha and IL-6 are involved in endotoxin-induced anorexia in humans.

Adult↗
PubMed2002

Body weight, the tumor necrosis factor system, and leptin production during treatment with mirtazapine or venlafaxine.

Weight gain is a frequent and important side effect of psychopharmacotherapy. Recent studies suggest that the fat-cell-derived hormone leptin and the tumor necrosis factor-alpha (TNF-alpha) cytokine system are pathophysiologically involved. No information is available concerning the influence of the antidepressants mirtazapine and venlafaxine on these immunoendocrine variables. An open-labeled study was performed in 20 patients suffering from major depression treated with either mirtazapine (N = 11) or venlafaxine (N = 9). During 4 weeks, the patients' weight, body mass index (BMI), and plasma levels of leptin, TNF-alpha, sTNF-R p55, and sTNF-R p75 were assessed. Mirtazapine induced a significant increase in weight (mean weight gain: 2.4 kg) that was evident after the first week of treatment. In parallel, the plasma levels of TNF-alpha and both soluble TNF receptors increased. In addition, a slight rise in leptin levels, which occurred slowly and was significant only at the end of the 4 th week of treatment, was observed. Weight decreased slightly but significantly in patients treated with venlafaxine (mean weight loss: 0.4 kg), whereas plasma levels of leptin, TNF-alpha, or soluble TNF receptors did not change significantly. The present results further support the notion that the activation of the TNF-alpha cytokine system is an early, sensitive, and specific marker of weight gain induced by psychotropic agents. In contrast, the effects of such drugs on leptin production seem to be less sensitive with respect to weight gain and more variable.

Adult↗
PubMed2002

The endotoxin-induced increase of cytokines is followed by an increase of cortisol relative to dehydroepiandrosterone (DHEA) in healthy male subjects.

Dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) inhibit T-helper lymphocyte type 2 immune reactions and exert anti-inflammatory effects in some chronic inflammatory diseases. Both DHEA and, in particular, DHEAS levels are dramatically decreased in chronic inflammatory diseases whereas cortisol levels remain stable or are elevated. However, the time course of cortisol relative to DHEA production is not known. We tested whether administration of endotoxin to healthy male subjects can induce an early predominance of cortisol relative to DHEA and DHEAS. It is demonstrated that endotoxin induces a dose-dependent increase of cortisol in relation to DHEA (no effect at 0.2 ng endotoxin/kg body weight (b.w.), clear effect at 0.4 and 0.8 ng/kg b.w., p<0.05) and DHEAS (tested at 0.4 ng/kg b.w., P=0.014). The increase of cortisol relative to DHEA appears 4 h after endotoxin injection and 2 h after a strong increase of interleukin (IL)-6 relative to tumour necrosis factor (TNF). In addition, an increase of cortisol relative to 17OH-progesterone was observed. The ratio of serum IL-6/TNF was positively correlated with the ratio of serum cortisol/DHEA (R(Rank)=0.472, P=0.041) and serum cortisol/17OH-progesterone (R(Rank)=0.514, P=0.048). In conclusion, dissociation of cortisol relative to DHEA, DHEAS or 17OH-progesterone appears very early during a systemic inflammatory response which is associated with an increase of IL-6 relative to TNF. As in chronic inflammatory diseases, during an acute inflammatory response with endotoxin, these physiological hormone changes are probably necessary to achieve adequate cortisol levels at the expense of adrenal androgens.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients.

Deficient orexin signaling has been shown to cause narcolepsy-like conditions in animals. In human narcolepsy, CSF levels of orexin A (hypocretin-1) were reported to be low in most cases. The authors measured CSF and plasma orexin A levels in patients with narcolepsy and in controls. Confirming earlier studies, they found CSF orexin A levels to be extremely low in patients with narcolepsy. However, plasma orexin A levels did not differ from those observed in controls. These results suggest that orexin deficiency in patients with narcolepsy is a phenomena restricted to the CNS.

Adult↗
PubMed2001

Cytokine-associated emotional and cognitive disturbances in humans.

BACKGROUND: Infectious, autoimmune, and neurodegenerative diseases are associated with profound psychological disturbances. Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes. However, the mechanisms underlying the respective psychological alterations in humans have not been established yet. Therefore, we investigated the effects of low-dose endotoxemia, a well-established and safe model of host-defense activation, on emotional, cognitive, immunological, and endocrine parameters. METHODS: In a double-blind, crossover study, 20 healthy male volunteers completed psychological questionnaires and neuropsychological tests 1, 3, and 9 hours after intravenous injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in 2 experimental sessions. Blood samples were collected hourly, and rectal temperature and heart rate were monitored continuously. RESULTS: Endotoxin had no effects on physical sickness symptoms, blood pressure, or heart rate. Endotoxin caused a mild increase in rectal temperature (0.5 degrees C), and increased the circulating levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors, interleukin (IL)-6, IL-1 receptor antagonist, and cortisol. After endotoxin administration, the subjects showed a transient significant increase in the levels of anxiety (effect size [ES] = 0.55) and depressed mood (ES = 0.66). Verbal and nonverbal memory functions were significantly decreased (ES = 0.55 to 0.64). Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety (r = 0.49 to r = 0.60), depressed mood (r = 0.40 to r = 0.75), and decreases in memory performance (r = 0.46 to r = 0.68). CONCLUSIONS: In humans, a mild stimulation of the primary host defense has negative effects on emotional and memory functions, which are probably caused by cytokine release. Hence, cytokines represent a novel target for neuropsychopharmacological research.

Adult↗
PubMed2001

Effects of dexamethasone on cytokine plasma levels and white blood cell counts in depressed patients.

In major depression, alterations of some aspects of the host defense system and the hypothalamo-pituitary-adrenal (HPA) system have been reported. Both systems are closely related, but their interaction in major depression has not yet been explored. Moreover, little is known about the effects of glucocorticoids on the circulating amounts of cytokines in humans in the absence of immunological challenges. Therefore, we investigated the effects of dexamethasone (DEX) in 17 depressed patients who underwent a combined DEX-suppression and corticotropine-releasing-hormone (CRH)-stimulation test on white blood cell counts, and on the plasma levels of granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, and soluble TNF-receptors (sTNF-R) p55 and p75. DEX induced an increase in granulocyte counts, which was positively correlated with increases in the circulating amounts of G-CSF and paralleled by decreased lymphocyte and monocyte counts. Moreover, DEX reduced the plasma levels of IL-6, TNF-alpha and sTNF-R p75. The levels of sTNF-R p55 and IL-10 were not affected. DEX-induced changes in immunological parameters did not differ between patients who had different amounts of HPA-system alteration, and were neither related to the severity of depressive symptomatology or to other clinical features. We conclude that a single oral dose of DEX, even in the absence of infection and inflammation, affects the circulating amounts of cytokines and soluble cytokine receptors, further supporting the pivotal role of these immune-mediators in glucocorticoid-induced immunomodulation. Neuroendocrinological alterations associated with major depression seem to be independent from these processes.

Adrenal Glands↗
PubMed2001

[The physiopathology of weight regulation during treatment with psychotropic drugs].

Weight changes during pharmacological treatment are a well-known phenomenon and they have been an object of research since the 1950's. Weight gain occurs during treatment with drugs of different chemical structures and is an important problem when patients are treated with antidepressants, antipsychotics, or mood stabilizers. The clinical relevance of drug-induced weight changes is due to increased rates of morbidity and reduced treatment compliance. Regarding the underlying causes, the important role of neurotransmitter systems and in particular the blockade of serotonin and histamine receptors has been discussed since decades. Only recently, however, research has been started on the effects of psychotropic agents on major neuroendocrine systems involved in appetite and weight regulation. These studies suggest that the fat-cell derived hormone leptin might play an important role. Leptin signals to the brain the size of the adipose tissue and is probably the most important peripheral signal for the long-term regulation of weight. In addition to the neuroendocrine systems, weight gain induced by psychotropic agents might also involve immune modulators, in particular the proinflammatory cytokine tumor-necrosis-factor-alpha (TNF-alpha) and soluble TNF-receptors. Some psychotropic agents influence the TNF system very rapidly, already prior to any obvious increases in weight. Hence, changes in the TNF-alpha system might be of predictive value for drug-induced weight gain. Strategies to minimize or to counteract weight gain induced by psychotropic agents include psychotherapeutic and pharmacological approaches. Although numerous psychotherapeutic approaches are available, they are only of limited usefulness in severely ill psychiatric patients. Fortunately, a number of promising pharmacological approaches to reduce weight have been introduced into clinical practice during the last years; however, so far there is no knowledge on pharmacodynamic and -kinetic interactions with psychotropic drugs, and there is no clinical data on the usefulness and safety of such drug combinations.

Animals↗
PubMed2001

[On the clinical relevance of clozapine-triggered release of cytokines and soluble cytokine-receptors].

Cytokines are pivotal mediators of the interaction between immunocompetent cells. Moreover, they mediate the interaction between the immune system and other physiological systems, including the CNS. It has been shown recently that the antipsychotic drug clozapine stimulates in vivo the release of cytokines and soluble cytokine receptors. This holds true for the tumor necrosis factor(TNF)-system, the interleukin(IL)-2-system, IL-6, and granulocyte colony-stimulating factor (G-CSF). The present paper discusses the clinical relevance of these findings for the pathophysiology of clozapine-induced side-effects. It is very probable that TNF-alpha plays an important role in clozapin-induced fever and in the hematopoetic side effects, including agranulocytosis. Moreover, it is likely that TNF-alpha and other cytokines are involved in metabolic (weight gain, diabetes), cardiac (myocarditis), CNS (sedation) and other rare side effects. The mechanisms underlying clozapine-induced immunomodulation are unknown. Hence, further studies are very important to enhance our understanding of clozapins's side effects and to develop strategies for prevention and treatment.

Antipsychotic Agents↗
PubMed2001

Low leptin levels but normal body mass indices in patients with depression or schizophrenia.

Appetite, food intake and weight are frequently altered in psychiatric disorders such as major depression and schizophrenia. The few studies investigating weight and the body mass index (BMI) have yielded variable results. Leptin, a fat cell-derived hormone signalling to the brain the size of the adipose tissue, plays a pivotal role in the regulation of weight and food intake. Moreover, leptin is involved in the control of other behaviors and in brain development. There is almost no information about the amounts of circulating leptin in major depression or schizophrenia. We investigated the BMI and plasma leptin levels in patients with major depression (n = 62), schizophrenia (n = 42), and in healthy controls (n = 64). Mean BMIs did not differ between groups. However, leptin levels were significantly lower in both patient groups compared to healthy controls. Moreover, patients suffering from schizophrenia showed significantly lower leptin levels than depressed patients. Decreased leptin levels were independent of psychotropic medication. We conclude that depression and schizophrenia go along with decreased systemic leptin concentrations that cannot be explained by medication or an altered BMI. Hence, leptin might play an important pathophysiological role in these psychiatric disorders that deserves further scientific attention.

Adult↗
PubMed2000

Effects of an intravenous catheter on the local production of cytokines and soluble cytokine receptors in healthy men.

Like many aspects of physiology, functions of the immune system show considerable diurnal variation. Studies investigating diurnal variations in the circulating amounts of cytokines, in general, used blood samples obtained from an intravenous catheter. The results of such studies may be confounded by an effect of the catheter on local cytokine production. We measured the levels of IL-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors (sTNF-R) p55 and p75 in 20 healthy men between 09:00 and 19:00 h in plasma samples obtained from an intravenous catheter and in one additional sample obtained by a simple needle stick in the contralateral arm 10 h after baseline. In plasma from the catheter the levels of IL-6 increased significantly over time, TNF-alpha levels slightly decreased and the time courses of TNF receptor levels showed significant trends of a higher order. Control levels of IL-6, TNF-alpha and sTNF-R p75 measured in plasma obtained by needle stick after 10 h did not differ from baseline, and those of sTNF-R p55 were even higher. We conclude that local alterations in the production of cytokines and soluble cytokine receptors induced by an intravenous catheter represent an important confounding factor for studies investigating diurnal variations in immune functions.

Adult↗
PubMed2000

Effects of antidepressants on weight and on the plasma levels of leptin, TNF-alpha and soluble TNF receptors: A longitudinal study in patients treated with amitriptyline or paroxetine.

Leptin, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptors are involved in weight regulation. Antipsychotic agents, such as clozapine, induce weight gain and increase circulating levels of these cytokines. To assess whether obesity-inducing antidepressants have a similar effect, we measured plasma cytokine levels in depressive inpatients during the first six weeks of treatment with tricyclic agents (amitriptyline or nortriptyline, n = 12), with paroxetine (n = 10), or without medication (n = 14). There was an increase in the body mass index at week 6 of treatment with the tricyclics, which was preceded by a significant increase in soluble TNF receptor p75 plasma levels. Circulating levels of leptin were not affected. Paroxetine and drug-free treatment did not affect any of these parameters. We conclude that weight gain induced by psychotropic agents may occur without increased circulating levels of leptin. However, activation of the TNF-alpha system might be an early and sensitive marker of ensuing weight gain.

Adult↗
PubMed2000

Granulocyte colony-stimulating factor plasma levels during clozapine- and olanzapine-induced granulocytopenia.

OBJECTIVE: Recent case studies suggest that impaired granulopoiesis, well-known to occur during clozapine treatment, may also be observed when olanzapine is administered. The underlying mechanisms are unknown, but haematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF) are likely to be involved. METHOD: We measured the plasma levels of G-CSF and of other cytokines longitudinally in a female patient who developed granulocytopenia twice, first during clozapine treatment and again when olanzapine was administered. RESULTS: G-CSF levels, but not those of other cytokines, closely paralleled granulocyte counts, yielding a significant positive correlation. G-CSF was not detectable in plasma when granulocytopenia occurred. Granulocytopenia resolved spontaneously despite continuing treatment with olanzapine. CONCLUSION: The present case suggests that clozapine and olanzapine both are able to induce transient granulocytopenia through a similar or common mechanism that does not involve a compensatory increase in G-CSF levels.

Adult↗
PubMed2000

A comparison of the effects of clozapine and olanzapine on the EEG in patients with schizophrenia.

Clozapine is known to induce epileptic seizures and changes in EEG-patterns, including slowing and the appearance of epileptiform activity. Olanzapine, a new antipsychotic drug, shares many pharmacological and clinical properties with clozapine. However, in patients treated with olanzapine, no case of seizure induction has been reported so far, and the EEG has not been studied systematically. We examined the EEGs of patients with schizophrenia treated with either olanzapine (N = 9) or clozapine (N = 9) prior to medication and 3 to 7 weeks afterwards. Clozapine induced significant EEG slowing present in 78% of the patients, and definite epileptiform activity appeared in 33%. Olanzapine also induced significant EEG slowing, but less frequently (in 44% of the patients) and less pronounced than clozapine. Olanzapine had no significant effect an epileptiform activity, but in one patient, an isolated sharp/slow-wave complex was observed. These preliminary data suggest that olanzapine induces EEG slowing to a lower extent than clozapine. Olanzapine's possible effect an the seizure threshold deserves further attention.

Adult↗
PubMed2000

Experimental immunomodulation, sleep, and sleepiness in humans.

Infection, inflammation, and autoimmune processes are accompanied by serious disturbances of well-being, psychosocial functioning, cognitive performance, and behavior. Here we review those studies that have investigated the effects of experimental immunomodulation on sleep and sleepiness in humans. In most of these studies bacterial endotoxin was injected intravenously to model numerous aspects of infection including the release of inflammatory cytokines. These studies show that human sleep-wake behavior is very sensitive to host defense activation. Small amounts of endotoxin, which affect neither body temperature nor neuroendocrine systems but slightly stimulate the secretion of inflammatory cytokines, promote non-rapid-eye-movement sleep amount and intensity. Febrile host responses, in contrast, go along with prominent sleep disturbances. According to present knowledge tumor necrosis factor-alpha (TNF-alpha) is most probably a key mediator of these effects, although it is likely that disturbed sleep during febrile host responses involves endocrine systems as well. There is preliminary evidence from human studies suggesting that inflammatory cytokines such as TNF-alpha not only mediate altered sleep-wake behavior during infections, but in addition are involved in physiological sleep regulation and in hypnotic effects of established sedating drugs.

Humans↗
PubMed2000

Reduced leptin levels in human narcolepsy.

Recently, hypocretins have been implicated in the pathophysiology of narcolepsy, a sleep disorder characterized particularly by the occurrence of excessive daytime sleepiness and cataplexy. Hypocretins, which stimulate food intake, have been reported to be absent in the cerebrospinal fluid (CSF) of the majority of patients suffering from narcolepsy. Because these patients also display an increased body mass index (BMI), it has been suggested that disturbances in metabolism and food intake regulation may be present. To further investigate these presumed alterations, we studied the production of leptin, a fat-cell-derived hormone signaling to the brain the size of the adipose tissue. We measured the levels of leptin in serum and CSF from 15 narcoleptic patients and compared the results to those from age-, sex- and BMI-matched control groups of depressive patients and patients suffering from a noninflammatory neurological disorder. Compared to both control groups, leptin levels in serum, but not in the CSF, were significantly reduced in narcoleptic patients by more than 50%. These results support the hypothesis that human narcolepsy is accompanied by complex alterations of the regulation of food intake and metabolism. The significance of these alterations for the core symptomatology of narcolepsy should be a target of future research.

Major Depressive Disorder↗