Case report: Fatal hepatic failure after aortic valve replacement and sevoflurane exposure

PURPOSE: To report a case of lethal hepatotoxicity possibly caused by sevoflurane. CLINICAL FEATURES: A 76-yr-old woman with a history of four previous minor surgical procedures developed acute liver failure after general anesthesia with sevoflurane, sufentanil and propofol for aortic valve replacement. After an uneventful procedure the patient was extubated 4.5 hr after surgery. On the second postoperative day, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased. On the third postoperative day liver failure occurred, ALT peaked at 10504 UxL(-1) and AST at 15516 UxL(-1), and coagulopathy with an international normalized ratio of 4.6 developed. Liver transplantation was considered but rejected as a therapeutic option. The patient died three days after the operation in multiple organ failure triggered by hepatic failure. Other possible causes for liver failure were excluded. CONCLUSIONS: Sevoflurane hepatitis as a cause for liver failure may be implicated in this patient undergoing valve surgery. Unlike other halogenated anesthetic drugs, sevoflurane is not metabolized to hepatotoxic trifluoroacetyl proteins. However, compound A may react with proteins and may be transformed into antigenic material. We suggest that all halogenated anesthetics may be implicated with acute liver injury.     

Comparative effects of enoximone and theophylline on plasma catecholamines and haemodynamics in cardiosurgical patients

Summary The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n=10), 4.0 mg/kg theophylline (n=10) or saline solution (control,n=10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+ 40% in the 1st min) and a marked increase in A (approximately + 7000% in the 1st min), which still remained elevated at the end of the investigation period (+ 220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index (CI; + 35%) and a decrease in pulmonary capillary wedge pressure (PCWP; −27%), pulmonary artery pressure (PAP; −21%), RVEDV and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an increase in HR (+ 26%; arrhythmia in 3 patients), PAP (+ 22%), and RVEDV (+ 19%), while REVESV (+ 26%), MAP (−16%), CI (−14%), and RVEF (−15%) fell significantly. It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline.     

Flow cytometric analysis of induced human graafian follicles. I. Demonstration and sorting of two luteinized cell populations.

STUDY OBJECTIVE: To test the hypothesis that induced human graafian follicles consist of different steroidogenic cell types on the basis of their light scatter characteristics as determined by flow cytometry. DESIGN: Cross-sectional, observational study. SETTING: Flow cytometry laboratory. PATIENTS: Thirty-six follicular aspirates from nine consecutive patients undergoing in vitro fertilization for tubal factor infertility were evaluated. RESULTS: Two distinct luteal cell populations were recovered. Both populations were positive by Oil Red O staining, suggesting the presence of intracellular lipid. Neither population stained positively for the presence of HLe-1/CD45, an antigen present on all human leukocytes. CONCLUSIONS: Cellular heterogeneity exists within the granulosa cell compartment.     

Concurrent ferromagnetic hyperthermia and 125I brachytherapy in a rabbit choroidal melanoma model.

Ferromagnetic (FM) thermoseeds and radioactive (125I) seeds were combined in an episcleral plaque to give concurrent hyperthermia and irradiation for enhanced tumour destruction. A Greene melanoma cell line was utilized to study the interaction between these treatment modalities. We attached five FM thermoseeds (with an operating temperature of 48 degrees C) in parallel with alternating rows of 125I seeds onto the inner surface of each 14 mm Silastic plaque. Plaques were centred over a 3-6 mm (diameter) intraocular melanoma in each rabbit. Some rabbits were then placed within a heating coil, and their eye tumours were warmed rapidly to therapeutic temperatures (43.6 degrees C across the tumour base) while the temperature of normal conjunctiva across the globe did not exceed 38.5 degrees C. Analysis of 49 treated eye melanomas showed 50% local tumour control at 41.7 Gy for 125I alone, whereas only 9.5 Gy were needed to give the same local control rate after 125I with concurrent FM hyperthermia. Thus, a thermal enhancement ratio of 4.4 was obtained. Hyperthermia alone gave a 20% tumour response rate, but responses were only temporary. We conclude that FM thermoseeds can be used to deliver biologically effective hyperthermia concurrently with radiation, thereby reducing the dose of radiation needed for tumour control.     

LPS resistance in monocytic cells caused by reverse signaling through transmembrane TNF (mTNF) is mediated by the MAPK/ERK pathway

The transmembrane form of tumor necrosis factor (mTNF), expressed on activated monocytes (MO) and macrophages (MPhi), is able to induce apoptosis in human endothelial cells (EC). Apoptosis is mediated by two distinct mechanisms: direct cell contact and a yet-unidentified soluble protein, death factor X. In addition, mTNF acts as a receptor that transduces a "reverse signal" into MO/MPhi when bound to the TNF receptor on EC. Reverse signaling by mTNF confers resistance to bacterial lipopolysaccharide (LPS). Stimulation of reverse signaling by mTNF blocks the ability of MO/MPhi to produce death factor X and proinflammatory cytokines. We have investigated which signaling pathways are used by mTNF acting as receptor. Reverse signaling triggers two independent pathways that can be distinguished by protein kinase C (PKC) inhibitors. The suppression of LPS-induced death factor X is dependent on PKC, whereas the suppression of LPS-mediated cytokine release is not. LPS and reverse signaling stimulate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. It is interesting that the activation of reverse signaling by mTNF renders MO/MPhi refractory to a subsequent activation of the MAPK/ERK pathway by LPS. Thus, reverse signaling achieves LPS resistance in monocytic cells through interference with key signal-transduction pathways.     

Meptazinol, a new analgesic. Hemodynamic and respiratory effects

In a prospective, randomized double-blind study the hemodynamic and respiratory effects of i.v. meptazinol, a new synthetic narcotic agonist-antagonist analgesic given in 2 dosages (2 mg/kg and 4 mg/kg), were compared over 15 min to a control group that received 0.9% saline solution as placebo. In a total of 80 patients scheduled for elective aortocoronary bypass surgery, the study was performed before and during general anesthesia and during extracorporeal circulation (ECC). A dose-dependent increase in mean arterial pressure (MAP) and total systemic resistance (TSR) were the predominant hemodynamic effects of meptazinol before and during anaesthesia (Tables 1 and 2). Within the study period no change in heart rate (HR) or cardiac index (CI) could be observed. Directly measured left ventricular parameters revealed a significant increase in left ventricular pressure (LVEDP, and dp/dtmax (Fig. 1). During ECC meptazinol injection was followed by a dose-dependent increase in perfusion pressure, indicating a direct vasoconstrictive effect; no influence on the capacitance system ("venous pooling") could be observed (Fig. 2). In the spontaneously breathing, premedicated patients (morphine hydrochloride 0.15 mg/kg and flunitrazepam 0.03 mg/kg) paO2 increased and paCO2 decreased, especially after injection of the higher dosage of meptazinol; there was no influence on intrapulmonary right-to-left shunting (Qs/Qt).(ABSTRACT TRUNCATED AT 250 WORDS)     

Primäres Osteosarkom der Leber Fallbericht und Literaturübersicht

Primary sarcomas of the liver are rare. Most of them are angiosarcomas often related to exposure to thorotrast or polyvinyl chloride. We report a case of primary osteosarcoma of the liver in a 72-year-old man and compare it with the seven cases from the literature     

Prognostic significance of CD38 and CD20 expression as assessed by quantitative flow cytometry in chronic lymphocytic leukaemia

CD38 expression on chronic lymphocytic leukaemia (CLL) cells is a poor prognostic factor, however, methods for measuring this vary. The QuantiBRITETM flow cytometry (FC) system yields an absolute antigen expression value (antibodies bound/cell, ABC) and may be useful in standardizing CD38 expression analysis. We evaluated cryopreserved pretreatment CLL cells for CD20 ABC, CD38 ABC, and percentage of CD38+ B cells from 131 patients requiring therapy. The 92 patients (70%) with >/= 100 CD38 ABC had worse overall survival (OS; 34% at 5 years) compared with those with < 100 CD38 ABC (70% at 5 years, mortality hazard ratio 2.30, 95% confidence interval 1.28-4.12; two-tailed P = 0.003). Among the 64 patients with < 30% CD38+ cells, OS of the 25 with >/= 100 ABC was worse than that of the 39 with < 100 ABC (P = 0.018). OS of patients with < 30% CD38+ cells and >/= 100 ABC was actually similar to that of patients with >/= 30% CD38+ cells. BrightCD20 expression (>/= 20 000 ABC) was not associated with a worse OS (P = 0.10). The presence of >/= 100 CD38 ABC in CLL patients requiring therapy is an unfavourable prognostic factor for OS and quantitative FC may be superior to percentage CD38+ cell assessment. Prospective trials are required to determine more precisely the prognostic significance of absolute expression levels in fresh CLL cells.