[SSRI - treatment and bleeding. What risks do we take?]. / Blutungsrisiko unter SSRI-Behandlung.

Treatment with selective serotonin reuptake inhibitors (SSRI) increases the risk of gastrointestinal bleeding. The combination with non-steroidal anti-inflammatory drugs (NSAIDs) further augments this hazard. Particular precaution is also necessary in patients on platelet aggregation inhibitors, with a known bleeding disorder or preceding gastrointestinal lesions. The incidence of bleeding events apart from the gastrointestinal tract, e.g. intracerebral hemorrhages, is not cumulated under SSRI treatment. This also applies for the combination of SSRI and coumarin or aspirin. Prescribing doctors have to be aware of the bleeding risks of SSRI and should explain this to their patients. High-risk patients have to be followed up closely and an SSRI with a low potential for drug interaction should be used. The prescription of gastroprotective agents and a change of the antidepressant should be considered in particular cases. We provide a literature survey and recommendations for the clinical routine.

Behaviorally conditioned immunosuppression using cyclosporine A: central nervous system reduces IL-2 production via splenic innervation.

Bi-directional interactions between the central nervous system (CNS) and immune system are demonstrated by the modification of immune function using behavioral conditioning. However, the mechanisms by which the CNS achieves conditioned immunomodulation are still in question. Here, we report that the immunosuppressive effects of cyclosporine A (CsA) can be behaviorally conditioned in rats using saccharin as a gustatory conditioned stimulus. The conditioned effects were compared to control groups that received CsA paired with water (sham-conditioned), CsA injection on test days (CsA-treated), and unhandled rats (untreated). In conditioned animals, the mitogen-induced lymphocyte proliferation in the spleen is significantly suppressed, and the survival time of heterotopic heart allografts prolonged. These effects are paralleled by conditioned inhibition of IL-2 and IFN-gamma synthesis by splenocytes. Furthermore, the CNS-induced immunosuppression is mediated neuronally and not via the blood, since the conditioned reduction of proliferation and cytokine production is completely abrogated after surgical denervation of the spleen. Thus, during conditioning, the CNS learns to reinstate at demand a CsA-like immunosuppression via splenic innervation. This might be used as a supportive therapy for controlling immune functions.

The deceleration capacity - a new measure of heart rate variability evaluated in patients with schizophrenia and antipsychotic treatment.

BACKGROUND: Schizophrenia is associated with increased cardiac mortality. A disturbed autonomic modulation of heart rate (HR) has been described in patients with schizophrenia in whom antipsychotic medication may represent an additional cardiac risk. The novel measure deceleration capacity (DC) of heart rate predicts cardiac mortality in patients with cardiovascular illnesses. The aim of the present paper was to calculate DC in patients with schizophrenia and to compare this measure with established parameters of heart rate variability (HRV). METHODS: HRV and DC were calculated in 24-hour electrocardiogram (ECG) recordings of 20 unmedicated, 40 medicated patients with schizophrenia and 40 controls. As activity has a major influence on HRV, 4-hour periods of "sleep-" and "wake-" ECG were evaluated as additional parameters. Actigraphy was used to ensure comparable levels of activity in patients and controls. RESULTS: The DC as well as the other established HRV measures were not significantly different comparing unmedicated patients with schizophrenia to healthy controls. However, medicated patients showed a significant reduction of DC calculated from ECG recordings during 4 hour over night periods. CONCLUSION: Calculation of DC might contribute to a better monitoring and identification of an increased risk of cardiac mortality in patients with schizophrenia undergoing antipsychotic treatment.

[Attempted suicide by snake bite. Case report and literature survey]. / Suizidversuch durch Schlangenbiss. Kasuistik und Literaturübersicht.

Unusual suicide attempts often remain undetected, and bizarre methods can be a clue to psychotic origin. We report a suicide attempt by proxy--the bite of a puff adder--and provide a brief literature survey about further archaic self-injurious behaviour. Due to the easy availability of venomous snakes and the close networking of suicidal patients via the Internet, an increase in similar cases can be anticipated. A failed suicide attempt should always be considered in patients surviving bizarre accidents.

Conditioned alterations of specific blood leukocyte subsets are reconditionable.

Behavioral conditioning has the ability to produce changes in immune function. However, it is unknown whether conditioned changes of immune function can be recalled on multiple occasions. To address this issue we paired a novel saccharin drinking solution with intraperitoneal cyclosporin A (CsA) injection in rats. Saccharin re-presentation produced a reduction in splenocyte proliferation that mirrored the effect of CsA. Such functional changes were paralleled by a significant conditioned leukopenia in peripheral blood, which opposed the leukocytosis induced by CsA. Using the conditioned leukopenia in blood as a 'diagnostic window' of conditioned immunosuppression, the maintenance of CsA-induced changes was investigated by examining blood samples collected repeatedly. Experiments on the same group of animals over a period of 1 year showed that the conditioned leukopenia was reproducible on multiple occasions by reimplementing either the whole conditioning paradigm or reexposure to the saccharin solution only. These results demonstrate that behaviorally conditioned alterations of immune parameters are maintained in subsequent trials, indicating the potential clinical feasibility of behavioral conditioning procedures.

Conditioned immunosuppression makes subtherapeutic cyclosporin effective via splenic innervation.

The present study investigated the mechanisms by which conditioned immunosuppression enhances the effectiveness of cyclosporin A (CsA) treatment in prolonging heart allograft survival. Dark Agouti rats that were administered subtherapeutic CsA (7 x 2 mg/kg on alternate days) rejected heart allografts at the same time as non-CsA-treated rats. The addition of a behavioral conditioning regimen (conditioned stimulus, saccharin; unconditioned stimulus, 20 mg/kg CsA) to the subtherapeutic CsA protocol produced a significant prolongation of graft survival, including long-term survival (>100 days) in 20% of the animals. Prior sympathetic denervation of the spleen completely blocked this effect. In nontransplanted rats both conditioning and CsA treatment reduce interleukin-2 and interferon (IFN)-gamma in the supernatant of proliferating splenocytes. Additionally, therapeutic CsA treatment decreased the number of IFN-gamma-producing CD4(+) naive and memory T cells in the spleen. In contrast, behavioral conditioning increased that number. These data indicate that behavioral conditioning prolongs heart allograft survival by inhibiting the release of these cytokines in the spleen via sympathetic innervation, supplementing the inhibited cytokine production induced by CsA treatment.