Metastases in Cases with Hepatocellular Carcinoma in Relation to Clinicopathologic Features of the Tumour An autopsy study from a low endemic area

In order to study clinicopathologic features of hepatocellular carcinoma (HCC) and their relation to metastatic growth, all autopsied cases with confirmed HCC (n = 490) from a period with a high autopsy frequency in a well-defined population were analyzed. Cirrhosis, usually of micronodular type, was found in 72%. The gross appearance of the tumour was predominantly massive (46%) or multinodular (42%). The tumour involved both liver lobes in 72% or the right lobe alone in 20%. Histologically, trabecular growth (79%) and grade II of differentiation (52%) prevailed. Vascular invasion was noted in 56%, whereas involvement of the biliary tract was unusual (4%). Metastases especially involved lymph nodes (42%), lungs (18%) and skeleton (17%). Increased weight of the liver, multinodular appearance, involvement of both liver lobes, low grade of differentiation and vascular invasion were significantly associated with presence of metastases.     

Serum erythropoietin levels and blood component therapy after autologous bone marrow transplantation: implications for erythropoietin therapy in this setting.

To determine the potential impact of recombinant human erythropoietin (EPO) therapy in patients undergoing autologous bone marrow transplantation (BMT) and colony-stimulating factor therapy, we assayed endogenous serum EPO levels and noted blood transfusion requirements in relapsed non-Hodgkin's lymphoma patients treated with high-dose chemo-radiation therapy and autologous BMT. Hematocrit and reticulocyte counts were determined daily, and hematocrit was maintained in the 25-30% range by transfusion according to criteria established by our hospital transfusion committee. EPO levels were measured by radioimmunoassay and were determined at baseline, throughout therapy, and 2 and 3 months after BMT. Serum EPO levels increased more than 25-fold above baseline in most subjects after initiating chemoradiation therapy. No correlation was noted between serum EPO and hematocrit, reticulocyte count or serum creatinine. Total red blood cell units transfused ranged from 4 to 15 (mean 7.7). Mean total donor exposures (red blood cell plus platelet units transfused) were 83.6 units (range 16-175). Serum EPO levels increased early in the course of preparation for autologous BMT and remained elevated for at least 2-3 weeks thereafter although at a lower level. Red blood cell transfusions were required despite very high EPO levels after BMT. Red cell transfusions, moreover, accounted for only 9.2% (69 of 746) of total donor exposures and only 5.8% (42 of 746) of donor exposures during the interval when pharmacologic doses of erythropoietin might be of benefit. In contrast to the potential benefit of colony-stimulating factors such as G-CSF and GM-CSF in BMT, our study suggests limited value for erythropoietin therapy in this setting.     

T cell activation and thymic tolerance induction require different adhesion intensities of the CD8 co-receptor.

Activation of mature lymphocytes requires in addition to the TCR contact with the corresponding antigen the binding of the CD8 or CD4 co-receptors to MHC class I or class II proteins respectively. To investigate the contribution of the CD8-class I interaction to the elimination of autoreactive T cells during negative selection in the thymus we generated two types of transgenic mice. One set expressed a modified Kb molecule which contained a human HLA-A2 alpha 3 domain, thereby missing the binding residues for the murine CD8 molecules. The second set of mice expressed an anti-Kb specific TCR. Both lines were crossed and in the resulting double transgenic mice the development of Kb-reactive T cells was followed with an anti-clonotypic antibody. Surprisingly, efficient clonal deletion in the thymus was still observed, although the reduced CD8-class I adhesion abrogated effector functions in vivo and in vitro. These results imply that even T cells with intermediate affinity for self are negatively selected in the thymus despite the fact that they are not able to react against self antigens in the periphery. Thus a safety window is created which decreases the risk of autoaggression.     

3D reconstruction of the cardiovascular and central nervous system of a human embryo Carnegie-stage 15--case report.

A human embryo at Carnegie stage 15 was serially sectioned and 3D computer aided reconstructions were made to demonstrate the cardiovascular system and cranial structures and to study developmental variations at this stage. The development of the heart and pharyngeal arteries was according to the existing literature. Differences were found in the development of the arterial circle of Willis and the central nervous system. The cranial venous system seemed to show great variability. Whereas the telencephalon was not developed according to the stage, the development of the hypophysis had occurred prior to stage 15. From the results we conclude that there are remarkable individual differences in embryological differentiation of structures which have to be taken into account during staging of human embryos.     

Molecular Interaction of Droperidol with Human Ether-a-go-go-related Gene Channels: Prolongation of Action Potential Duration without Inducing Early Afterdepolarization

Background: The cardiac safety of droperidol given at antiemetic doses is a matter of debate. Although droperidol potently inhibits human ether-a-go-go-related gene (HERG) channels, the molecular mode of this interaction is unknown. The role of amino acid residues typically mediating high-affinity block of HERG channels is unclear. It is furthermore unresolved whether droperidol at antiemetic concentrations induces action potential prolongation and arrhythmogenic early afterdepolarizations in cardiac myocytes.

Methods: Molecular mechanisms of HERG current inhibition by droperidol were established using two-electrode voltage clamp recordings of Xenopus laevis oocytes expressing wild-type and mutant channels. The mutants T623A, S624A, V625A, Y652A, and F656A were generated by site-directed mutagenesis. The effect of droperidol on action potentials was investigated in cardiac myocytes isolated from guinea pig hearts using the patch clamp technique.

Results: Droperidol inhibited currents through HERG wild-type channels with a concentration of half-maximal inhibition of 0.6-0.9 [mu]m. Droperidol shifted the channel activation and the steady state inactivation toward negative potentials while channel deactivation was not affected. Current inhibition increased with membrane potential and with increasing duration of current activation. Inhibition of HERG channels was similarly reduced by all mutations. Droperidol at concentrations between 5 and 100 nm prolonged whereas concentrations greater than 300 nm shortened action potentials. Early afterdepolarizations were not observed.     

Spread of local anaesthetic solution in epidural space visualisation with ultrasound in single shot caudals

Background: Ultrasonography is becoming an important adjunct in paediatric neuraxial blockade. Ultrasound guidance helps in visualisation of relevant neuraxial structures, predicting depth of epidural space from skin, reduction in bony contact and faster epidural placement. The visibility of neuraxial structures declines in patients as age increases. To date, there are no studies looking at the extent of spread of local anaesthetic solution in the epidural space and its correlation to the volume used, under ultrasound guidance. We report the results of our audit on spread of local anaesthetic solution in the epidural space in single shot caudal blocks. This abstract is based on the first 17 patients, the presentation will be based on all 50 patients. Methods: This audit was approved by the local audit committee. We aimed to follow the extent of the spread of local anaesthetic within the epidural space with real time ultrasonography. Patients were selected when the planned anaesthetic included a single shot caudal block. The anaesthetists performing the anaesthetic and the caudal block consented to our ultrasound visualisation. All patients were below 5 years of age. No attempt was made to standardise the technique, the dose, or the speed of injection. After the placement of the caudal cannula by the primary anaesthetist involved in patient care, a separate anaesthetist, experienced in using ultrasound, visualised the neuraxial structures and subsequent spread of the local anaesthetic solution with real time ultrasound. The spread was followed during the injection and for 10 s after the completion of the injection. A 5 cm 7.5–12 MHz linear array was used longitudinally with either midline or paramedian approach. Results: We are reporting the preliminary results from 17 patients. Patients were aged between 1 day and 1 year 10 months. They weighed between 3.3 kg and 14.6 kg. Either 22 gauge Jelco or Abbocath were used to perform the procedure; 0.25% or 0.20% L‐bupivacaine was used on all occasions. The volume administered per kg ranged between 0.33 and 1.27 ml. The visibility of neuraxial structures was good on all occasions. On calculating the Spearmans correlation coefficient, the extent of spread of local anaesthetic in the epidural space was positively correlated with the volume used by a correlation coefficient of 0.64, with a P value of 0.008. The postoperative pain score in recovery was 0 in 16 out of the 17 cases. The one failure occurred when the observed spread would not have been expected to provide analgesia for the performed operation. Conclusions: Among children below 5 years of age, there seems to be a positive correlation between the volume of local anaesthetic injected into the epidural space and the extent of its spread. This needs to be further investigated by a prospective randomised control trial. The utility of real time ultrasound to allow a reliable achievement of a desired level of sensory block, should be investigated i.e, whether the volume used in achieving a desired level of local anaesthetic spread, as guided by ultrasound, provides superior analgesia and fewer adverse effects compared with the volume calculated using the Armitage regimen. References 1 Rapp HJ, Folger A, Grau T. Ultrasound guided epidural catheter insertion in children. Anesth Analg 2005; 101 : 333–339. 2 Willschke H, Marhofer P, Bosenberg A, et al. Epidural catheter placement in children: comparing a novel approach using ultrasound guidance and a standard loss of resistance technique. Br J Anaesth 2006; 97 : 200–207. 3 Marhofer P, Bosenberg A, Sitzwohl C et al. Pilot study of neuraxial imaging by ultrasound in infants and children. Pediatr Anesth 2005; 15 : 671–676.     

Analysis of three-dimensional sinter shrinkage of copings made from alumina in an innovative direct shaping process.

The three-dimensional (3D) evaluation and comparison of free-form-surfaces is a complex problem [Dent. Mater. 8 (1992) 49; J. Dent. Res. 76 (1997) 1799; Dent. Mater. 16 (2000) 145; J. Prosthet. Dent. 70 (1993) 457; Dent. Mater. 19 (2003) 19]. However, it is essential in order to analyze the sinter shrinkage of dental ceramic-restorations where isotropic and linear shrinkage is desired for accurate fit on the prepared teeth. In this article, we examine the 3D sinter shrinkage in general and for nine copings from alumina in particular. Using various scaled CAD-models in an iteration scheme, each model was compared to the filtered point cloud of the coping, determining the surface-cloud difference. The magnitude of deviations from linear sinter shrinkage was investigated. Furthermore, a new fabrication process for ceramic-restorations is introduced.     

Cerebral Cortical Aquaporin-4 Expression in Brain Edema following Cardiac Arrest in Rats

OBJECTIVES: Brain edema occurs following clinical as well as experimental cardiac arrest (CA) and predicts a poor neurologic outcome. The objective of this study was to determine the expression of cerebral cortex aquaporin (AQP)-4, a member of a family of membrane water-channel proteins, in brain edema formation following normothermic or hypothermic CA. METHODS: Twenty-four rats were subjected to time-matched normothermic (N-Sham, 37.5 degrees C +/- 0.5 degrees C, n = 6) or hypothermic (H-Sham, 34 degrees C +/- 0.5 degrees C, n = 6) sham experiments and normothermic (N-CA, n = 6) or hypothermic (H-CA, n = 6) CA induced by asphyxiation for 8 minutes. Hypothermia was induced before CA. The animals were resuscitated with cardiopulmonary resuscitation, ventilation, and epinephrine administration. Brain edema was determined by brain wet-to-dry weight ratio at one hour of resuscitation. AQP4 immunoactivity in the cerebral cortex was determined using immunohistochemical staining and was semiquantified as an intensity of staining with an automated cell imaging system. RESULTS: Mild hypothermia in the sham experiments did not alter cerebral cortex AQP4 immunoactivity (mean +/- SD) (55.0 +/- 3.7 in H-Sham vs. 53.3 +/- 1.7 in N-Sham, p > 0.05). N-CA resulted in a significant increase in AQP4 immunoactivity (61.8 +/- 4.5) compared with N-Sham (p = 0.01) and H-Sham (p = 0.03). H-CA attenuated AQP4 compared with N-CA (53.4 +/- 1.3, p = 0.01). Brain wet-to-dry weight ratios were 4.41 +/- 0.07 in N-Sham, 4.40 +/- 0.08 in H-Sham (p > 0.05 vs. N-Sham), 4.55 +/- 0.04 in N-CA (p = 0.004 vs. N-Sham; p = 0.005 vs. H-Sham), and 4.43 +/- 0.09 in H-CA (p = 0.02 vs. N-CA; p > 0.05 vs. N-Sham and H-Sham). CONCLUSIONS: Cerebral cortical AQP4 expression is up-regulated after normothermic CA, which is attenuated by hypothermia induced before CA.