Siete años de experiencia en pacientes intervenidos por patología proctológica bajo modalidad cirugía mayor ambulatoria y estudio del grado de satisfacción usuaria

Objetivo: Exponer los resultados de 7 años de cirugía proctológica por cirugía mayor ambulatoria (CMA) y determinar el grado de satisfacción usuaria. Material y Método: Se realizó un estudio observacional descriptivo de pacientes sometidos a cirugía proctológica bajo modalidad CMA en el Hospital Regional de Concepción entre los años 2012 y 2019. Se realizó la encuesta telefónica de satisfacción SUCMA-14. Resultados: Se evaluaron a 632 pacientes en el período de estudio. Con diferencias estadísticamente significativas entre patologías para edad, género e IMC. Se aplicó la encuesta a 270 pacientes que contestaron y respondieron. Los resultados mostraron que en general la percepción de los pacientes es positiva salvo puntuales excepciones, como el dolor postoperatorio para condilomas y hemorroides, y las complicaciones postoperatorias para la enfermedad pilonidal. Cuando se realiza el análisis multivariado a los datos correspondientes a la encuesta, no se logran diferencias significativas entre los diagnósticos, pero al aplicarlo a las variables clínico-quirúrgicas se evidencia, claramente, que existe una distinción entre éstas, en especial para la enfermedad pilonidal. Discusión: Las diferencias en términos de tiempos quirúrgicos, complicaciones y re-hospitalizaciones, no necesariamente afectan la percepción que los pacientes tienen de la CMA, ya que ésta depende de otros factores y no solo de los resultados quirúrgicos. Conclusión: Se obtuvieron resultados acorde a la literatura internacional, con peores resultados para enfermedad pilonidal. La satisfacción usuaria fue positiva en general, sin una clara distinción por patologías. Creemos que la CMA es recomendable en patología proctológica tanto por sus resultados, como por la satisfacción que genera en los pacientes.

Objective: To present the results of 7 years of colorectal surgery on mayor ambulatory surgery (MAS) and to determine patient satisfaction. Methods: A descriptive observational study of patients undergoing proctological surgery under the MAS modality was carried out at Regional Hospital of Concepción between 2012 and 2019. The SUCMA-14 satisfaction survey was applied. Results: 632 patients were evaluated in the study period. With statistically significant differences between pathologies for age, gender and BMI. The survey was applied to 270 patients who answered and responded. The results showed that, in general, the perception of the patients is positive, with exceptions, such as postoperative pain for warts and hemorrhoids, and postoperative complications for pilonidal disease. When the multivariate analysis corresponding to the survey is performed, it does not allow distinguishing between the diagnoses, but when applied to the surgical variables, it clearly shows that there is a distinction between them, with a disadvantage for pilonidal disease. Discussion: The differences in terms of surgical times, complications and re-hospitalizations do not necessarily affect the perception that patients have of the MAS, since it depends on other factors and not only on the surgical results. Conclusion: Results were concordant to what is described in the international literature, with worse results for pilonidal disease. Patient satisfaction was positive in general, without a clear distinction by pathology. We believe that MAS is recommended in proctological pathology both for its results and for the satisfaction it generates in patients.

Death in four RHDV2-vaccinated pet rabbits due to rabbit haemorrhagic disease virus 2 (RHDV2).

OBJECTIVES: To create awareness of single RHDV2 infections and cases of death despite immunisation with RHDV2-specific vaccine. MATERIALS AND METHODS: Retrospective case series of four companion rabbits. Patient signalment, vaccination history, pathology and molecular examinations were obtained from the medical records. RESULTS: The animals died peracutely or with nonspecific symptoms like apathy and inappetence. Pathological examination indicated and molecular biological findings confirmed RHDV2 infection in four animals. Several partner animals died at the same time under the same circumstances. CLINICAL SIGNIFICANCE: This is the first report of fatalities in RHDV2-vaccinated companion rabbits due to rabbit haemorrhagic disease virus 2 infection with documented case and vaccination history. Veterinarians should be aware of possible single fatal RHDV2 infections despite vaccination, should initiate the clarification of suspected cases and inform vaccine manufacturers and competent authorities.

Clogging Transition of Vibration-Driven Vehicles Passing through Constrictions.

We report experimental results on the competitive passage of elongated self-propelled vehicles rushing through a constriction. For the chosen experimental conditions, we observe the emergence of intermittencies similar to those reported previously for active matter passing through narrow doors. Noteworthy, we find that, when the number of individuals crowding in front of the bottleneck increases, there is a transition from an unclogged to a clogged state characterized by a lack of convergence of the mean clog duration as the measuring time increases. It is demonstrated that this transition-which was reported previously only for externally vibrated systems such as colloids or granulars-appears also for self-propelled agents. This suggests that the transition should also occur for the flow through constrictions of living agents (e.g., humans and sheep), an issue that has been elusive so far in experiments due to safety risks.

Effects of contextual information and stimulus ambiguity on overt visual sampling behavior.

The sampling of our visual environment through saccadic eye movements is an essential function of the brain, allowing us to overcome the limits of peripheral vision. Understanding which parts of a scene attract overt visual attention is subject to intense research, and considerable progress has been made in unraveling the underlying cortical mechanisms. In contrast to spatial aspects, however, relatively little is understood about temporal aspects of overt visual sampling. At every fixation, the oculomotor system faces the decision whether to keep exploring different aspects of an object or scene or whether to remain fixated to allow for in-depth cortical processing - a situation that can be understood in terms of an exploration-exploitation dilemma. To improve our understanding of the factors involved in these decisions, we here investigate how the level of visual information, experimentally manipulated by scene context and stimulus ambiguity, changes the sampling behavior preceding the recognition of centrally presented ambiguous and disambiguated objects. Behaviorally, we find that context, although only presented until the first voluntary saccade, biases the perceptual outcome and significantly reduces reaction times. Importantly, we find that increased information about an object significantly alters its visual exploration, as evident through increased fixation durations and reduced saccade amplitudes. These results demonstrate that the initial sampling of an object, preceding its recognition, is subject to change based on the amount of information available in the system: increased evidence for its identity biases the exploration-exploitation strategy towards in-depth analyses.

C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma.

The pathways underlying dendritic cell (DC) activation in allergic asthma are incompletely understood. Here we demonstrate that adoptive transfer of ovalbumin-pulsed wild-type (wt) but not of C5a receptor-deficient (C5aR⁻/⁻) bone marrow (BM)-derived DCs (BMDCs) induced mixed T helper type 2 (Th2)/Th17 maladaptive immunity, associated with severe airway hyperresponsiveness, mucus production, and mixed eosinophilic/neutrophilic inflammation. Mechanistically, antigen uptake, processing, and CD11b expression were reduced in C5aR⁻/⁻ BMDCs. Further, interleukin (IL)-1ß, -6, and -23 production were impaired resulting in reduced Th17 cell differentiation, associated with accelerated activated T-cell death in vitro and in vivo. Surprisingly, we found an increased frequency of CD11b(hi)CD11c(int)Gr1⁺F4/80⁺ cells, expressing arginase and nitric oxide synthase in C5aR⁻/⁻ BM preparations. Intratracheal administration of ovalbumin-pulsed wt DCs and sorted CD11b(hi)CD11c(int)Gr1⁺F4/80⁺ C5aR⁻/⁻ cells reduced Th2 immune responses in vivo. Together, we uncover novel roles for C5aR in Th17 differentiation, T-cell survival, and differentiation of a DC-suppressor population controlling Th2 immunity in experimental allergic asthma.

[Soft tissue balanced navigation of total knee arthroplasties]. / Navigierte Implantation weichteilbalancierter Knieendoprothesen.

OBJECTIVE: Implantation of a total knee arthroplasty with a correct mechanical axis, a rectangular joint gap and a reconstructed joint line by use of an imageless computer navigation device INDICATIONS: Symptomatic gonarthrosis if non operative treatment or joint preserving operations remains ineffective CONTRAINDICATIONS: Infections; soft tissue damage in the approach area; massive instability of the collateral ligaments SURGICAL TECHNIQUE: Medial parapatellar approach to the knee joint; diminution of the patella; fixation of the reference arrays in tibia and femur; registration of leg axis, ligament balance and surface of the knee joint by use of the navigation system; tibial resection perpendicular to the mechanical axis; ligament balancing to achieve a rectangular extension gap; femoral implant planning to maintain the original joint line and reconstruct an equal joint gap in extension and flexion; femora resection perpendicular to the mechanical axis; reconstruction of the rectangular flexion gap by rotation of the femoral resection; two stage cementing technique for fixation of the original implants; check of the final mechanical axis and symmetry of the joint gap over the whole range of motion; wound closure. POSTOPERATIVE MANAGEMENT: Physiotherapy; continuous passive motion treatment; mobilization with 20 kg weight bearing with 2 crutches for 2 weeks, thereafter with 2 crutches and incremental full weight bearing for 4 weeks. RESULTS: The analysis of 582 consecutive navigated total knee arthroplasties showed one case of extension gap instability > 3 mm (0.2%) and 8 patients with flexion gap instability > 3 mm (1.4%). A too tight flexion gap was registered in 23 patients (4.4%), a too wide flexion gap in 13 cases (2.5%). The joint line was reconstructed with an average inaccuracy of 0 mm, in 17 patients the joint line was elevated > 3 mm (2.9%).

Clinical course and pathology in rats (Rattus norvegicus) after experimental cowpox virus infection by percutaneous and intranasal application.

Recently, several cases of human cowpox virus (CPXV) infections were reported in France and Germany, which had been acquired through close contact with infected pet rats. The animals exhibited respiratory signs or skin lesions and died shortly after purchase. After natural infection of white rats with CPXV in the USSR in 1978, a peracute pulmonary form, a milder dermal form, and a mixed form exhibiting features of both have been described. To the best of the authors' knowledge, 3 experimental cowpox virus infection studies using rats have been performed to date; however, neither results of histomorphological examinations nor immunohistochemical analyses have yet been reported in rats after experimental infections. To investigate the impact of the infection route on the clinical course, the development of lesions, and tropism, rats were infected intradermally, intranasally, or by a combination of both routes. The authors found a correlation between clinical manifestation, pathology, and infection routes. Intradermal and contact exposure yielded a mild dermal form, characterized by the development of vesiculopustular dermatitis. In contrast, intranasally infected animals died peracutely, showing severe dyspnea. Occasionally, a combination of the dermal and the respiratory form occurred after intranasal infection. Immunohistochemically, CPXV antigen was detected in the epithelial and mesenchymal cells of the upper respiratory tract and affected skin lesions and rarely in mesenchymal cells of lymph nodes. This is the first histomorphological and immunohistochemical analysis of CPXV in rats after experimental infection.

Equid herpesvirus 5-associated dermatitis in a horse--Resembling herpes-associated erythema multiforme.

An equid herpesvirus 5 (EHV-5) infection was detected in lesioned skin from a nine-year-old Holsteiner stallion in the south of Germany. Macroscopically, the animal displayed a non-pruritic, multifocal, pustular dermatitis around both eyes, nostrils and the muzzle, which had been ongoing for one year. Histopathologically, skin lesions were characterized by orthokeratotic to parakeratotic hyperkeratosis, pustular dermatitis, epidermal hyperplasia, apoptotic keratinocytes, a lympho-plasmahistiocytic interface dermatitis with hydropic degeneration of keratinocytes, and perivascular to diffuse, lympho-histiocytic infiltrations. The stratum granulosum and the upper part of the stratum spinosum contained multiple amphophilic, intranuclear inclusion bodies. By in situ hybridization and immunohistochemistry herpesvirus DNA and protein, respectively, were detected within keratinocytes containing inclusion bodies. Sequencing of the PCR-product revealed the presence of EHV-5 DNA. This is the first description of a dermatitis associated with EHV-5 in a horse, indicating that EHV-5 should be considered as an etiology of lymphohistiocytic interface dermatitis with intranuclear inclusion bodies in horses and is similar to herpes-associated erythema multiforme in humans.

Characterisation of a new infectious full-length cDNA clone of BVDV genotype 2 and generation of virus mutants.

Based on their genomic sequences, two genotypes of Bovine viral diarrhea virus (BVDV) can be differentiated, BVDV type 1 (BVDV-1) and BVDV type 2 (BVDV-2). The complete genomic sequence of the highly virulent BVDV-2 strain 890 was cloned as cDNA to establish the infectious cDNA clone p890FL. In vitro-synthesised full-length RNA of p890FL was transfected into bovine cells and infectious virus could be recovered (v890FL). In vitro, recombinant v890FL showed similar growth characteristics as wild type virus v890WT. However, infection experiments in calves revealed an attenuation of recombinant v890FL in comparison to the parental isolate. Both leukocytopenia and fever were less pronounced in v890FL-infected calves. Nevertheless, viremia and virus shedding were comparable between recombinant and parental BVDV 890. Furthermore, mutants with partial deletions of the genomic region encoding for the autoprotease N(pro) (p890DeltaN(pro)) or the capsid protein (p890DeltaC) were constructed and characterised. In order to generate pseudovirions, replicon p890DeltaC was efficiently trans-complemented on a helper cell line. In summary, the newly developed construct p890FL represents the first infectious full-length cDNA clone for the BVDV-2 strain 890 and offers a useful tool for further studies on the pathogenesis of BVDV-2 and the development of novel recombinant BVDV-2 specific vaccine candidates.

Timothy grass pollen major allergen Phl p 1 activates respiratory epithelial cells by a non-protease mechanism.

BACKGROUND: Group 1 allergens from grass pollen (e.g. Phl p 1, the major allergen of timothy grass Phleum pratense) cause IgE reactivity in about 95% of allergic subjects and exist in all grass species. The respiratory epithelium represents a first line of contact of the immune system with airborne allergens, functions as physical barrier and is an important immunological regulation system. OBJECTIVE: The aim of this study was to investigate the interaction of Phl p 1 with human respiratory epithelium to elucidate the contribution of epithelial cells to the development of allergic reactions. METHODS: Purified Phl p 1 was used to stimulate A549 cells and transient transfected HEK293 cells. mRNA level of different mediators were investigated by real-time PCR, release of the mediators was determined by ELISA. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and an ex vivo model of the murine trachea were used to investigate a potential proteolytic activity of Phl p 1. RESULTS: Phl p 1 activates respiratory epithelial cells as measured by induction of IL-6, IL-8 and TGF-beta mRNA and release. Phl p 1, in contrast to Der p 1 from the house dust mite, does not exert proteolytic activity, as investigated by microscopic observation and MTT test. In an ex vivo model of the murine trachea we were able to show that Der p 1, in contrast to Phl p 1, enhances the transportation velocity of particles by the trachea, presumably by ATP released from the injured epithelium. CONCLUSION: We conclude that under physiological conditions Phl p 1 affects tracheal epithelial cells through a non-proteolytic activity. Enhancement of TGF-beta expression induced by Phl p 1 together with the increased release of IL-6 and IL-8 might provide an indirect mechanism through which the allergen may cross the epithelial barrier and attracts immunocompetent cells.

Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development.

Ciliary beating of airway epithelial cells drives the removal of mucus and particles from the airways. Mucociliary transport and possibly airway epithelial development are governed by muscarinic acetylcholine receptors but the precise roles of the subtypes involved are unknown. This issue was addressed by determining cilia-driven particle transport, ciliary beat frequency, and the composition and ultrastructural morphology of the tracheal epithelium in M1-M5 muscarinic receptor gene-deficient mice. Knockout of M3 muscarinic receptors prevented an increase in particle transport speed and ciliary beat frequency in response to muscarine. Furthermore, the ATP response after application of muscarine was blunted. Pretreatment with atropine before application of muscarine restored the response to ATP. Additional knockout of the M2 receptor in these mice partially restored the muscarine effect, most likely through the M1 receptor, and normalised the ATP response. M1, M4 and M5 receptor-deficient mice exhibited normal responses to muscarine. None of the investigated mutant mouse strains had any impairment of epithelial cellular structure or composition. In conclusion, M3 receptors stimulate whereas M2 receptors inhibit cilia-driven particle transport. The M1 receptor increases cilia-driven particle transport if the M3 and M2 receptors are missing. None of the receptors is necessary for epithelial development.

Depletion forces between nonspherical objects.

We extend the insertion approach for calculating depletion potentials to the case of nonspherical solutes. We suggest to employ the recently developed curvature expansion of density profiles close to complexly shaped walls. The approximations introduced in the calculation by the use of the curvature expansion and of weight functions for nonspherical objects can be tested independently. As an application for our approach we calculate and discuss the depletion potential between two hard oblate ellipsoids in a solvent of hard spheres. For this system we calculate the entropic force and torque acting on the objects.

Post-traumatic stress disorder and amygdala-hippocampectomy.

OBJECTIVE: The case report suggests the indispensability of preoperative accurate psychiatric checkups especially in temporal resections. METHOD: A single case was reported. RESULTS: We report the case of a 20-year-old woman suffering for 12 years from primary generalized epilepsy, attributed to left-sided hippocampal sclerosis. Because seizures were resistant to drug therapy, she underwent amygdala-hippocampectomy at the age of 18. Furthermore, she had previously been victim of childhood sexual abuse. Two weeks after epilepsy surgery, she manifested symptoms of post-traumatic stress disorder (PTSD). CONCLUSION: There is evidence that the amygdala-hippocampal region is both functionally and morphologically involved in the aetiology of PTSD. The removal of this marked neuroanatomical region and the resulting disconnection and asymmetry between right and left amygdala-hippocampal region might be seen as an evidence for this region aetiologically being involved in the patient's PTSD symptoms.

Toward theoretical analysis of long-range proton transfer kinetics in biomolecular pumps.

Motivated by the long-term goal of theoretically analyzing long-range proton transfer (PT) kinetics in biomolecular pumps, researchers made a number of technical developments in the framework of quantum mechanics-molecular mechanics (QM/MM) simulations. A set of collective reaction coordinates is proposed for characterizing the progress of long-range proton transfers; unlike previous suggestions, the new coordinates can describe PT along highly nonlinear three-dimensional pathways. Calculations using a realistic model of carbonic anhydrase demonstrated that adiabatic mapping using these collective coordinates gives reliable energetics and critical geometrical parameters as compared to minimum energy path calculations, which suggests that the new coordinates can be effectively used as reaction coordinate in potential of mean force calculations for long-range PT in complex systems. In addition, the generalized solvent boundary potential was implemented in the QM/MM framework for rectangular geometries, which is useful for studying reactions in membrane systems. The resulting protocol was found to produce water structure in the interior of aquaporin consistent with previous studies including a much larger number of explicit solvent and lipid molecules. The effect of electrostatics for PT through a membrane protein was also illustrated with a simple model channel embedded in different dielectric continuum environments. The encouraging results observed so far suggest that robust theoretical analysis of long-range PT kinetics in biomolecular pumps can soon be realized in a QM/MM framework.

Effect of nebulized albuterol on blood glucose in patients with diabetes mellitus with and without cystic fibrosis.

Over 90% of cystic fibrosis (CF) patients are treated with bronchodilators, and 6% have diabetes. Some with asthma also have diabetes, and most are treated with bronchodilators. Systemic administration of adrenergic agents can cause increases in blood glucose, but the effect of inhaled agents is unclear. A double-blind study was performed on 10 patients with type 1 diabetes mellitus (DM) without CF (3 male, 7 female, mean age 25.5 years) and 9 patients with insulin-dependent CF-related diabetes (CFRD) (8 male, 1 female, mean age 21.9 years). On 2 separate days before 9 AM fasting and the morning dose of insulin, 2.5 mg of albuterol or nebulized placebo were given. Blood glucose was measured by finger stick with a glucose reflectance meter before and 15, 30, 45, and 60 min after treatment. No significant changes from baseline or differences between placebo and albuterol occurred in either group. The mean maximum increase from baseline in DM was 20 mg/dl on placebo, and 38 mg/dl on albuterol; in the CFRD, the respective changes were 7 and 7 mg/dl. Two DM patients had a > 50 mg/dl increase on albuterol vs. placebo; no CFRD patients had differences of such magnitude. DM patients had greater increases from baseline than CFRD patients on placebo and albuterol. Differences reached statistical significance at 30 and 45 min on placebo, and 45 min on albuterol. Albuterol 2.5 mg by nebulizer causes no clinically significant increases in blood glucose in DM or CFRD patients. Diabetes patients without CF have a significantly greater increase of glucose with time (placebo or albuterol) than CFRD patients.

A critical evaluation of different QM/MM frontier treatments with SCC-DFTB as the QM method.

The performance of different link atom based frontier treatments in QM/MM simulations was evaluated critically with SCC-DFTB as the QM method. In addition to the analysis of gas-phase molecules as in previous studies, an important element of the present work is that chemical reactions in realistic enzyme systems were also examined. The schemes tested include all options available in the program CHARMM for SCC-DFTB/MM simulation, which treat electrostatic interactions due to the MM atoms close to the QM/MM boundary in different ways. In addition, a new approach, the divided frontier charge (DIV), has been implemented in which the partial charge associated with the frontier MM atom ("link host") is evenly distributed to the other MM atoms in the same group. The performance of these schemes was evaluated based on properties including proton affinities, deprotonation energies, dipole moments, and energetics of proton transfer reactions. Similar to previous work, it was found that calculated proton affinities and deprotonation energies of alcohols, carbonic acids, amino acids, and model DNA bases are very sensitive to the link atom scheme; the commonly used single link atom approach often gives error on the order of 15 to 20 kcal/mol. Other schemes give better and, on average, mutually comparable results. For proton transfer reactions, encouragingly, both activation barriers and reaction energies are fairly insensitive (within a typical range of 2-4 kcal/mol) to the link atom scheme due to error cancellation, and this was observed for both gas-phase and enzyme systems. Therefore, the effect of using different link atom schemes in QM/MM simulations is rather small for chemical reactions that conserve the total charge. Although the current study used an approximate DFT method as the QM level, the observed trends are expected to be applicable to QM/MM methods with use of other QM approaches. This observation does not mean to encourage QM/MM simulations without careful benchmark in the study of specific systems, rather it emphasizes that other technical details, such as the treatment of long-range electrostatics, tend to play a more important role and need to be handled carefully.

Quantification of venlafaxine and O-desmethylvenlafaxine in human serum using HPLC analysis.

We describe an isocratic reversed-phase liquid chromatographic method for the determination of venlafaxine (VLX) and its main active metabolite O-desmethylvenlafaxine (ODV) in serum, using haloperidol as internal standard and liquid/liquid extraction for sample preparation. VLX and ODV were separated on a C18 column with a mobile phase of acetonitrile/buffer (30/70, v:v) at 60 degrees C and a flow rate of 1.5 ml/min. The measurement of the native fluorescence signals of the eluted compounds were carried out at 227/300 nm (excitation/emission) without interference from endogenous components in serum. High linearities for VLX and ODV for concentrations between 20 and 500 microg/l were obtained (r = 0.9997). A large spectrum of routinely prescribed drugs did not interfere in the assay. The coefficients of variation for repeatability varied between 5.40% and 5.99% and for reproducibility between 9.43% and 21.63%. Absolute recoveries were more than 52% for both substances.

Morphological thermodynamics of fluids: shape dependence of free energies.

We examine the dependence of a thermodynamic potential of a fluid on the geometry of its container. If motion invariance, continuity, and additivity of the potential are satisfied, only four morphometric measures are needed to describe fully the influence of an arbitrarily shaped container on the fluid. These three constraints can be understood as a more precise definition for the conventional term extensive and have as a consequence that the surface tension and other thermodynamic quantities contain, aside from a constant term, only contributions linear in the mean and Gaussian curvature of the container and not an infinite number of curvatures as generally assumed before. We verify this numerically in the entropic system of hard spheres bounded by a curved wall.

Therapeutic drug monitoring of trazodone: are there pharmacokinetic interactions involving citalopram and fluoxetine?

OBJECTIVE: Therapeutic drug monitoring (TDM) of the new generation antidepressants is subject of controversial discussion. Nonetheless, TDM may safeguard against drug-drug interactions, can be used to control compliance and is valuable in the investigation of overdose. METHOD: The aim of this prospective study was to investigate serum levels of trazodone when prescribed as monotherapy or when used in combination with the selective serotonin reuptake inhibitors citalopram and fluoxetine in a simultaneous assay using high-performance liquid chromatography (HPLC). Over a 1-year period, we studied 97 patients (63 females) with depressive syndrome who were subdivided into 3 main diagnostic groups. Fifty-two patients were smokers, the mean age was 39.9 years and the mean weight was 72.4 kg; 40 patients were taking trazodone alone, 41 trazodone in combination with citalopram and 16 patients trazodone in combination with fluoxetine. RESULTS: The use of citalopram and fluoxetine in combination with trazodone had no significant impact on trazodone serum levels, and the same was true for differences in body weight and smoking behavior. On the other hand, age and sex had a significant influence on the pharmacokinetic pattern of trazodone, causing higher concentrations in females and in older patients. Since the polypharmacy investigated did not change the serum levels of trazodone, we assume that there is no metabolic interaction between trazodone and citalopram and trazodone and fluoxetine. We observed none of the adverse effects which might have been expected, including dizziness, severe headache, daytime sedation, fatigue or the serotonin syndrome even in a mild form. CONCLUSION: A "double-tracked" antidepressive treatment using trazodone and the SSRIs citalopram and fluoxetine is associated with a wide safety margin.