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Biomedical subjects

T Kraus

Publications and source records attributed to T Kraus.

At least 19 recordsLinked to original sources
PubMed2003

Can aerosol-derived airway morphometry detect early, asymptomatical lung emphysema?

The aerosol-derived airway morphometry technique (ADAM) can be used to assess non-invasively peripheral airspace dimensions. It has been shown that this technique can identify permanent peripheral airspace enlargement in patients with lung emphysema, but it is yet unknown if early stages of emphysema can be detected. In this study, 89 aluminum welders were investigated. Although all (except two subjects) showed normal spirometry, in 29% of the subjects visual signs of early emphysema were observed with high-resolution computed tomography (HRCT) in a previous study. Using the ADAM technique, 28% of the subjects showed increased peripheral airspace dimensions. However, both groups with positive findings overlapped only in about half of the cases. Peripheral airspace dimensions correlated significantly with the mean lung density calculated from the HRCT scans, and lung density was significantly decreased in the group with increased airspace dimensions. The poor overlap of the positive findings observed with both techniques can be explained if it is considered that the visual HRCT technique and ADAM focus on different aspects of emphysematous changes in the lungs. Whereas visual HRCT is a powerful tool to identify focal changes in lung density but cannot detect mild homogeneous emphysema, ADAM delivers a measure for homogeneously distributed emphysema but cannot detect focal emphysema or regions with emphysema which are badly ventilated. Since ADAM is easy to perform, non-invasive, and can be repeatedly applied to human subjects without radiological concerns, this technique might become a useful tool for the detection and monitoring of lung emphysema in occupational medicine, epidemiology, and pharmaceutics.

Adult↗
PubMed2003

Exposure to nitroaromatic explosives and health effects during disposal of military waste.

AIMS: To investigate the exposure to dinitrotoluene (DNT) and trinitrotoluene (TNT) and the resulting effects in workers which occur during the disposal of military waste. METHODS: Eighty two employees from a mechanical plant in Germany were studied, of whom 51 were regularly exposed to ammunition containing TNT and DNT, 19 occasionally, and 12 not at all. RESULTS: Air analyses yielded maximum concentrations of 20 micro g/m(3) for 2,4-DNT and 3250 micro g/m(3) for 2,4,6-TNT, respectively. The maximum concentrations in the urine of workers regularly exposed amounted to 5.0 micro g/l of 2,4,6-TNT, 1464.0 micro g/l of 2-amino-4,6-dinitrotoluene, 6693.0 of micro g/l 4-amino-2,6-dinitrotoluene, 2.1 micro g/l of 2,4-DNT, 95.0 micro g/l of 2,4-dinitrobenzoic acid, and 3.6 micro g/l of 2,6-DNT. There was a highly significant linear correlation between the urinary concentrations of the two main metabolites of TNT, 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene. In 63 persons TNT or DNT or metabolite concentrations above the analytical detection limit were found in urine. These persons reported more frequently symptoms like bitter taste, burning eyes, and discoloration of the skin and hair than persons (n = 19) without detectable TNT and/or DNT exposure. CONCLUSION: During the disposal of military waste containing relevant TNT and DNT, exposure can occur of occupational-medical relevance. Biological monitoring is suitable for the early detection of possible adverse effects at workplaces exposed to TNT. Protective measures should be improved, together with adequate occupational-medical surveillance of persons exposed to nitroaromatic explosives. Further studies are necessary to exclude possible long term effects.

Adult↗
PubMed2002

[Documentation of surgical performance--does more really help more? Comparison of the effects of maximum and limited documentation depth of clinical patient data on theoretical revenue volume of a surgical clinic after introduction of the DRG-based reimbursement system].

INTRODUCTION: The forthcoming introduction of a DRG-based account system in Germany aims at higher transparency and economic efficiency, particularly in the sector of in-patient health care. The availability of documentation of the highest quality, taking into account all potentially relevant diagnoses, appears to be the best method for achieving maximum revenue in individual surgical units. The aim of the study was to determine the relevance of various degrees of documentation depth on calculated DRG-based revenue. Furthermore, we evaluated whether improvements in the quality of documentation can be realized in current hospital organization. METHODS: In a prospective study, clinical data from 402 in-patients were collected and revenues were calculated based on the Australian-Refined DRG system. Various qualities of documentation were defined. In order to find the medical sectors most sensitive to "under-documentation", homogenous cases were classified into 23 treating groups, according to diagnosis. RESULTS: In 267 cases, maximum revenue was determined only by one main diagnosis, while better results could be achieved in 137 cases (34%) by extended documentation quality. Half of this gain could only be achieved by an independent medical documentation specialist. An upper limit of documentation intensity (number of diagnoses) could be defined. Maximum gain did not require maximum number of diagnoses. CONCLUSIONS: Documentation depth has an important influence on the calculated revenue of surgical therapy based on AR-DRG system. The quality and depth of the documentation is not, in itself, sufficient. In order to be really effective, it requires the highest degree of professionalism from hospital staff.

Cost-Benefit Analysis↗
PubMed2002

[Structural development of ambulatory surgical care in the United States of America. What can we learn or apply?].

Expansion of ambulatory surgical care is a major focus in United States health politics. In 1996 a total of 31.5 million ambulatory operations were performed, currently accounting for 45% of yearly procedures. Operations in ophthalmology and gastroenterology are predominant. Ambulatory surgery is organized in different forms: "office-based surgery," "hospital outpatient departments," and "ambulatory surgery centers" (ASC). The numbers of ASCs are rapidly increasing. The current proportion of ASCs is 16% of all operations. The type of ambulatory surgery is primarily defined by payors. Medicare standards are the benchmark for private organizations. Recovery care centers now offer postoperative care beyond the former 23-h threshold. This may lead to a further expanded ASC access. Revenues for ambulatory surgery were so far mostly based on fees for service. The implementation of an outpatient prospective payment system ("OPPS") is planned by Medicare, using fixed package prices within a newly defined ambulatory payment classification ("APC"). The dimension of structural changes could be enormous and possibly be compared with the implementation of DRGs in 1983.

Ambulatory Surgical Procedures↗
PubMed2002

[Findings in a high-risk group following asbestos exposure. Benefit of ENT examinations in patients with long-term exposure to asbestos].

BACKGROUND AND OBJECTIVE: Laryngeal diseases caused by exposure to asbestos are listed in the current German list of occupational diseases under number 4104. Parallel to a multicenter study to evaluate whether a CT scan should be included in the examinations for occupational diseases according to the German surveillance guidelines, an additional ENT examination was evaluated. PATIENTS AND METHODS: One hundred workers with a mean exposure time to asbestos of 20.9 years were given a complete ENT examination in 4 consecutive years (1993-1996). Radiological signs for asbestosis were observed in 21 cases and 58 participants had pleural affections caused by asbestos. Significant nicotine abuse was reported by 15 persons: 61 participants were ex-smokers and 24 had never smoked. Regular alcohol consumption was reported by 90% (11% more than 80 g/day). RESULTS: As documented in the literature, we found a high prevalence of laryngitis, especially in smoking patients. One patient had early laryngeal cancer (T1). CONCLUSION: The integration of an ENT examination into the German surveillance guidelines for occupational diseases should be discussed for patients with a high exposure to asbestos.

Aged↗
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

Respiratory symptoms and diseases among workers in the soft tissue producing industry.

AIMS: To correlate the prevalence of respiratory tract symptoms and diseases with dust and fibre exposure in the soft tissue industry in Germany. METHODS: Ambient monitoring was performed for inhalable, respirable dust and fibres in seven soft tissue producing factories. In 441 workers (72 controls, 90 moderate, 279 high exposure) a standardised questionnaire on respiratory symptoms, diseases, occupational history, and smoking habits was used. Crude differences in the prevalence of respiratory symptoms and diseases were assessed. Logistic regression analysis was used to determine the relation between the respiratory symptoms/diseases and the cumulative dust and fibre exposure, respectively, while adjusting for age, gender, smoking habits, and factory. The effects of exposure intensity and duration were differentiated by categorising dust/fibre concentrations and years of exposure separately and setting up logistic regression models. RESULTS: The mean concentrations for inhalable, respirable, and fibrous dusts were 10.3 mg/m(3), 0.22 mg/m(3), and 415,000 fibres/m(3). Adjusted odds ratios (OR) with relation to cumulative dust exposure intensity were significantly raised for blocked nose (18.2), mucosal irritation (6.5), dry nose (8.9), cough (3.5), phlegm (7.5), exercise induced dyspnoea (2.6), hoarseness (11.3), and sneezing attacks (7.9) (ORs for highest exposure categories). Cumulative dust or fibre exposure had no significant effects on the prevalence of respiratory diseases. For all symptoms with significantly raised ORs, combined effects of intensity and duration of exposure were found. CONCLUSIONS: Because of the high prevalence of respiratory symptoms a reduction of dust exposures is recommended. Chronic exposure effects could not be found in this study, however, a healthy worker effect has to be considered.

Adult↗
PubMed2001

Regulation of class II expression in monocytic cells after HIV-1 infection.

Human macrophage hybridoma cells were used to study HLA-DR expression after HIV-1 infection. HLA-DR surface expression was lost 2 wk after infection that was associated with decreased mRNA transcription. Transfecting HLA-DR-alpha and HLA-DR-beta cDNA driven by a nonphysiological CMV promoter restored expression, suggesting that regulatory DNA-binding proteins may be affected by HIV-1 infection. There was no protein binding to conserved class II DNA elements (W/Z/S box, X-1 and X-2 boxes, and Y box) in a HIV-1-infected human macrophage hybridoma cell line, 43(HIV), and in primary monocytes that lost HLA-DR expression after HIV-1(BaL) infection. PCR analysis of the HIV-1-infected cells that lost HLA-DR expression revealed mRNA for W/Z/S (RFX-5), X-1 (RFX-5), X-2 (hX-2BP), and one Y box DNA-binding protein (NF-YB), and CIITA, a non-DNA-binding protein necessary for class II transcription. There was no mRNA for the Y box-binding protein, NF-YA. However, HLA-DR expression could be restored by transfection with NF-YA driven by a CMV promoter, although HLA-DR failed to localize in either the late endosomes, lysosomes, or acidic compartments. This was associated with a loss of class II-associated invariant chain peptide and leupeptin-induced protein in the 43(HIV) cells. To address this further, non-HIV-1-infected 43 cells were infected with vaccinia virus containing HIV-1 gag, nef, pol, and env proteins. HLA-DR failed to localize in neither the late endosomes, lysosomes, or acidic compartments in the vaccinia-infected cells containing HIV-1 env protein. HIV-1 appears to have multiple effects on class II expression in monocytic cells that may contribute to the immune defects seen in HIV-1-infected patients.

Antigens, Differentiation, B-Lymphocyte↗
PubMed2001

General approach to the synthesis of persubstituted hydrophilic and amphiphilic beta-cyclodextrin derivatives.

Heptakis(2,3,6-tri-O-allyl)-beta-cyclodextrin 2 was converted to heptakis[2,3,6-tri-O-(2,3-dihydroxypropyl)]-beta-cyclodextrin 3 by osmium tetroxide-catalyzed dihydroxylation. A diastereomeric mixture of 3 was treated with sodium periodate followed by sodium borohydride to give heptakis[2,3,6-tri-O-(2-hydroxyethyl)]-beta-cyclodextrin 5 in 86% yield. Compound 5 could be quantitatively transformed into heptakis(2,3,6-tri-O-carboxymethyl)-beta-cyclodextrin 6 by TEMPO-mediated oxidation. The same reaction sequence was also applied to heptakis(2,6-di-O-allyl-3-O-methyl)-beta-cyclodextrin 8, heptakis(2,3-di-O-allyl-6-O-methyl)-beta-cyclodextrin 12, and heptakis(2,3-di-O-allyl-6-O-butyl)-beta-cyclodextrin 16; the analogous corresponding hydroxyethyl and carboxymethyl derivatives were isolated in high yields. All products were proved to be chemically uniform.

Cyclodextrins↗
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

Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos.

OBJECTIVE: The aim of this study was to determine low molecular weight (LMW)-DNA fragmentation changes after white blood cell (WBC) incubation in lysis buffer followed by constant-field gel electrophoresis (CFGE). WBCs were isolated from blood samples of workers highly exposed to asbestos fibres at the workplace in Germany, and were compared with those from healthy adults. This study was conducted parallel to the study presented in our preceding paper (Marczynski et al. 2000b) in which we described significant increases in the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells from the same highly exposed workers relative to the levels found in the control group in all three study years (1994 to 1997). METHOD: We found that 15-h incubation in lysis buffer of WBCs embedded in agarose-plugs from healthy control donors with 2% SDS, proteinase K and Na2-EDTA at 42 degrees C followed by 0.5 h at 4 degrees C produced a characteristic DNA fragmentation pattern below 23 kbp using CFGE. RESULTS: In the 1st year of the study (1994-1995) changes were found in LMW-DNA fragmentation in 54.8% of the asbestos workers studied, compared with the DNA fragmentation pattern of controls. Interestingly, in the 2nd year of the study (1995 1996) changes in DNA fragmentation were found in only 39.9% of exposed subjects. In the 3rd year of the study (1996-1997) the highest number of workers exposed to asbestos (67.3%) with changes in the LMW-DNA fragmentation pattern was found. The Chi-square test for each year of the study revealed significant changes (P < 0.001). These changes may be due to the presence of hydrogen peroxide (H2O2), as has been shown in vitro. It is likely that a Fenton reaction involving the heterolytic reduction of H2O2 by traces of reduced transition metals such as Fe2+ and Cu+ is involved in the fragmentation of DNA. No difference was found in the changes in DNA fragmentation between asbestos-exposed subjects with and without benign asbestos-associated diseases (asbestosis, asbestos-associated pleural plaques). Significant correlations were not found after analysis of the changes in DNA fragmentation in relation to different possible occupational and non-occupational confounding factors, such as the duration of asbestos exposure, the latency period, estimated cumulative fibrous dust dose ("fibre-years"), and non-occupational confounding factors, such as age, smoking status, acute febrile infections, the intake of medicines, aspirin, Ca2+, Mg2+ and/or hormones, the intake of vitamins, and cases of cancer. CONCLUSIONS: Our data confirm that oxidative stress occurs in the WBCs of workers highly exposed to asbestos fibres, thus supporting the hypothesis that asbestos fibres damage cells through an oxidative mechanism. Oxidative stress and oxidative DNA damage may be induced by long-term exposure to asbestos. The new insights into the oxidative effects of asbestos fibres are of great importance because they provide a way forward for new preventive strategies. Preventive and therapeutic approaches using antioxidants should be taken into consideration.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Characterization of renal parenchymal perfusion during experimental infrarenal aortic clamping and declamping with enhanced thermodiffusion electrodes.

Despite multiple previous experimental and clinical investigations, it has not been fully clarified until now whether infrarenal aortic cross-clamping (IRAC) induces a significant disturbance of renal parenchymal perfusion. Most renal cortical flow data collected thus far have been heterogenous because of inherent limitations of available measurement technology. The enhanced thermal diffusion (TD) electrode is a newly developed and previously validated prototype device that allows continuous quantification of parenchymal kidney perfusion after local probe implantation. We monitored renal perfusion during experimental IRAC with TD for the first time, thereby also evaluating the potential applicability of the method in clinical aortic surgery. IRAC (20 min) followed by sudden declamping was performed in pigs under general anesthesia (n = 14). Renal cortical blood flow (RCBF) was continuously quantified by TD, total aortic flow (TABF) and renal artery flow (RABF) were measured by ultrasonic flow probes, and parameters of systemic circulation were determined by Swan-Ganz catheter. Our results showed that kidney perfusion can be continuously quantified using TD electrodes during experimental aortic surgery in a porcine model. IRAC does not lead to a significant impairment of RCBF in young pigs as measured by TD. Renal perfusion appears to be predominantly pressure driven. Consequently, abrubt aortic declamping can bring about prolonged renal ischemia. Transfer of the TD method to RCBF monitoring during clinical aortic surgery appears to be feasible and should be investigated in selected cases.

Animals↗
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

Dacron vs. polytetrafluoroethylene grafts for femoropopliteal bypass: a prospective randomised multicentre trial.

OBJECTIVES: To compare the patency of PTFE (Polytetrafluoroethylene) and unsealed knitted Dacron femoro-popliteal bypasses. DESIGN: Multi-centre prospective randomised trial. MATERIALS AND METHODS: Of 203 patients randomised, 194 were included in the final analysis (103 Dacron grafts and 91 PTFE grafts). The median follow-up was 36 months (range: 6-72 months); the distal anastomosis was above-knee in 141 and below-knee in 53 cases. Univariate comparisons of patency were made by the Kaplan-Meier method, multivariate calculations on the effects of covariables by a Cox regression analysis. RESULTS: There was no difference regarding primary and secondary patency or limb salvage between Dacron and PTFE. The primary 3-year patency for Dacron grafts was 64% (95% confidence interval [C.I.] 55-74%) and for PTFE grafts 61% (C.I. 49-72%). The corresponding 3-year secondary patency was 81% (C.I. 73-89%) and 75% (C.I. 65-86%) respectively, the limb salvage rate 90% (C.I. 84-96%) and 91% (C.I. 84-97%). Upon multivariate analysis below-knee anastomosis was the principal independent predictor of primary graft failure (risk ratio 1.7 [C.I. 1.05-2.8]), impaired secondary patency was associated with infragenicular bypass (risk ratio 3.3 [C.I. 1.8-6.3]) and distal gangrene (risk ratio [C.I. 1.01-3.8]p=0.048), major amputation was independently predicted by below-knee bypass, tissue necrosis, and poor run-off index. CONCLUSIONS: PTFE and Dacron are equally suitable for femoro-popliteal bypass.

Adult↗
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↗