Sex-specific differences in plasma levels of FXII, HK, and FXIIa-C1-esterase inhibitor complexes in community-acquired pneumonia.

Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high-molecular-weight kininogen (HK) in plasma of patients with CAP and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of patients with CAP (n = 139) as compared with age-matched donors (n = 58). No simultaneous decrease in FXII levels, indicating its consumption, was observed. Stratification by sex revealed augmented FXII levels in plasma of women with CAP as compared with sex-matched donors yet no apparent differences in men. This sex-specific effect was, however, attributable to lower FXII levels in female donors relative to men donors. Plasma estradiol levels mirrored those for FXII. Levels of HK/albumin ratio were decreased in CAP plasma as compared with donors, however, after stratification by sex, this difference was only observed in women and was related to higher HK/albumin values in female donors as opposed to male donors. Finally, strong negative correlation between plasma levels of HK/albumin ratio and CAP severity, as assessed by CRB65 score, in males and females was observed. Our study identifies sex-dependent differences in plasma levels of the contact phase proteins in elderly subjects that may contribute to specific clinical outcomes in CAP between men and women.

Multiple electrode whole blood aggregometry, PFA-100, and in vivo bleeding time for the point-of-care assessment of aspirin-induced platelet dysfunction in the preoperative setting.

BACKGROUND: Acquired platelet dysfunction due to aspirin ingestion may increase bleeding tendency during surgery. Thus, we examined the diagnostic accuracy of in vivo bleeding time (BT) and 2 platelet function assays for the preoperative assessment of a residual antiplatelet effect in patients treated with aspirin. METHODS: Consecutive patients scheduled for surgery were prospectively enrolled in this study. The patients' last aspirin ingestion had occurred within the previous 48 hours before blood sampling in the "full aspirin effect" group, between 48 and 96 hours before in the "variable aspirin effect" group, and >96 hours before in the "recovered aspirin effect" group. The control group had not taken any aspirin. Multiple electrode aggregometry, platelet function analyzer (PFA)-100, and in vivo BT were performed to assess the effects of aspirin. One-way analysis of variance on ranks with a post hoc multiple-comparison procedure (Dunn) was used to detect differences among the groups. Categorical data were compared using the z test. Receiver operating characteristic (ROC) curves were created to determine the diagnostic accuracy of the platelet function assays investigated. The area under the ROC curve (AUC), sensitivity, and specificity of the assays were calculated. The level of statistical significance was set at P < 0.05. RESULTS: Three hundred ninety-four patients were included in the analysis (133 control and 261 aspirin-treated patients). All 3 methods were able to detect the antiplatelet effect of aspirin in the full aspirin effect group. Furthermore, no difference in the measurement values between the recovered aspirin effect and control group was found, irrespective of the assay performed. Measurement values in the variable aspirin effect group were different from those of the control group in the ASPItest using multiple electrode aggregometry and COL-EPI using PFA-100 but not in BT. ROC analysis showed the highest diagnostic accuracy in excluding the residual aspirin effect in the ASPItest (AUC 0.81, P < 0.001), followed by COL-EPI (AUC 0.78, P < 0.001) and BT (AUC 0.56, P = 0.05). The cutoff value of 53 U in the ASPItest excluded the effect of aspirin with a sensitivity of 88% and specificity of 71%. CONCLUSIONS: The full therapeutic antiplatelet effects of aspirin can be expected within 48 hours of the patient's last aspirin ingestion. Platelet function recovered in our study if aspirin cessation occurred >96 hours (4 days) before; thus, in these patients, preoperative platelet function testing is not useful. To quantify any residual aspirin effect in patients who ceased their intake of aspirin between 48 and 96 hours before surgery, the ASPItest might have the highest diagnostic accuracy.

Antipsychotic polypharmacy in the emergency treatment of highly aggressive schizophrenic prisoners - a retrospective study.

In past years, Zuclopenthixolacetate as well as Flupentixoldecanoate have each proven to be reliable and efficient in the treatment of schizophrenic psychoses. In a specially implemented psychiatric treatment unit (PTU) we administered a high-dose depot neuroleptic combination therapy initially consisting of both substances to seriously ill schizophrenic prisoners who exhibited highly aggressive behaviour (N=20). We initially used both antipsychotics at the same time as a simple regimen in order to restore the prisoners' health to enable them to return to their home prisons. A single coercive intervention was performed in 14 out of 20 prisoners which was followed by a second one in two cases according to Article 101 of the German Code of Criminal Procedure. On average, prisoners needed a treatment course of 30.4 days. Within this time PANSS global scores were reduced by approximately 40%. Side effects occurring as a consequence of neuroleptic treatment were negligible and could be dealt with.

Subarachnoid-pleural fistula as a complication of malignant pleural mesothelioma.

We report a 62-year-old male patient with asbestos-related malignant pleural mesothelioma who developed recurrent pleural effusions after surgical resection of paravertebral tumour masses. Pleural effusions were drained on several occasions with the patient suffering severe headaches and vascular dysregulation. Cytological studies of the pleural fluid showed no evidence of inflammatory or malignant cells. The fluid was interpreted as seroma despite its unusual transparency until magnetic resonance imaging was suggestive of a subarachnoid-pleural fistula; its presence was confirmed when beta-trace protein--a specific marker for cerebrospinal fluid--was added to the standard laboratory testing of the pleural effusion. A subarachnoid-pleural fistula has to be included in the differential diagnosis of patients with recurrent pleural effusions after surgical debulkment of malignant pleural mesothelioma. The beta-trace protein may help to establish this diagnosis especially in cases where important therapeutic consequences may need to be drawn.

Phospholipase A2 degradation products modulate epithelial and stromal 5alpha-reductase activity of human benign prostatic hyperplasia in vitro.

BACKGROUND: Recent studies have demonstrated the inhibition of 5alpha-reductase activity in human prostate by phospholipases. Among those phospholipases, phospholipase A2 cleaves one of the acyl chains from phospholipids, thereby producing fatty acids and lysophospholipids such as LPC, LPS, and LPE. Therefore, we were interested in the effect of those lysophospholipids on 5alpha-reductase activity in human benign prostatic hyperplasia (BPH). METHODS: In a first set of experiments, cell homogenates were incubated with phospholipase A2 either in the presence or absence of albumin, which is known to bind fatty acids and lysophospholipids. Thereafter, the effect of lysophospholipids of known structure on 5alpha-reductase activity was investigated. RESULTS: In epithelium and stroma of human BPH, 5alpha-reductase activity was inhibited in a dose-dependent manner by phospholipase A2. In the presence of albumin, this inhibition was enhanced. In epithelium, LPC at low concentration yielded a dose-dependent stimulation of 5alpha-reductase activity up to 167%. At higher concentrations, epithelial as well as stromal 5alpha-reductase activity was inhibited significantly. As indicated by results of enzyme kinetic analyses, the LPC-mediated activation in the epithelium results from an increase of the active population of 5alpha-reductase. In contrast, LPC reduces the affinity of epithelial 5alpha-reductase to testosterone. LPE had no effect on epithelial 5alpha-reductase, whereas stromal 5alpha-reductase was inhibited in a dose-dependent manner up to 46%. Finally, LPS stimulated epithelial and stromal 5alpha-reductase activity; this stimulation was significantly stronger in epithelium (296%) than in stroma (163%). The LPC-mediated effects could be neutralized by the addition of albumin. CONCLUSIONS: The present data on BPH tissue suggest that lysophospholipids may play a specific and structure-related role in the posttranslational regulation of human prostatic 5alpha-reductase.