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.     

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.     

Coil embolization of major bleeding after femoral fracture: A case report

Successful internal arterial embolization with steel coils in life-threatening bleeding after femoral fracture is described in an older patient.     

Guanylnucleotide specificity for muscarinic receptor inhibitory coupling to cardiac adenylate cyclase.

The guanylnucleotide specificity of muscarinic acetylcholine receptor (MR) inhibitory coupling to cardiac adenylate cyclase (AC) was investigated under low MgCl2 (i.e., 0.5 mM) conditions. In purified cardiac sarcolemma, carbachol maximally inhibited AC activity 60% in the presence of GTP. Carbachol-dependent inhibition in the presence of guanosine 5'-O-(3-thiotriphosphate (GTP gamma S) or guanylylimidodiphosphate [Gpp(NH)p] was of lesser magnitude (i.e., 30%) and was evident only during short incubation periods. Of greater interest, carbachol maximally inhibited AC activity in the presence of GDP and guanosine 5'-O-(2-thiodiphosphate (GDP beta S) by 35 and 60%, respectively. Control studies ruled out transphosphorylation of GDP and GDP beta S by nucleoside diphosphate kinase or guanylnucleoside triphosphate contamination as reasons for the inhibitory effects of GDP and GDP beta S. Furthermore, isoproterenol stimulated AC in the presence of GTP, GTP gamma S, and Gpp(NH)p but not in the presence of GDP or GDP beta S. Therefore, GDP and GDP beta S may serve as agonists on MR-activated Gi but not on beta-adrenergic receptor-activated Gs in these membranes. Time course studies revealed that carbachol-dependent inhibition of AC in the presence of either GTP or GDP occurred without a detectable lag period, and this inhibition was rapidly reversed by atropine. In contrast, a 1-2-min lag time was required for carbachol- and GDP beta S-dependent inhibition of AC to occur, and inhibition, once developed, was only partially and slowly reversed by atropine. Preincubation of sarcolemma with carbachol and GDP beta S, in the absence of ATP or under nonphosphorylating conditions, eliminated the lag time for inhibition of AC activity. Although it is unlikely that GDP and GDP beta S have physiological relevance of MR-Gi-AC coupling, these studies provide unique insights into this coupling mechanism in cardiac membranes.     

Effects of exposure to an estrous female on forebrain monoaminergic neurotransmission in the non-copulating male rat

Regional changes in the rate of brain monoamine synthesis were monitored in male rats exposed to, but prevented from physical contact with, an estrous or an ovariectomized female. The in vivo rate of tyrosine and tryptophan hydroxylase activities were estimated by measuring the accumulation of DOPA and 5-HTP following inhibition of cerebral aromatic l-amino acid decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015) treatment (100 mg/kg i.p.) 5 min upon NSD-1015 treatment, the males were exposed to an intact estrous female or an ovariectomized female for 20 min before decapitation and brain dissections. Exposure to an estrous female produced an increased rate of tyrosine and tryptophan hydroxylase activity in the medial prefrontal cortex, the dorso-lateral neostriatum and in the ventral neostriatum, in comparison with home-cage controls. By the same comparison, exposure to an ovariectomized female resulted in an increased rate of tyrosine hydroxylase activity in the medial prefrontal cortex, byt not in the neostriatal areas, whereas tryptophan hydroxylase activity was unaffected. Finally, exposure to the empty test cage, with no stimulus females present, did not produce any statistically significant changes in the rate of tyrosine or tryptophan hydroxylase activity in any of the brain areas sampled. Taken together with recent findings from this laboratory, the present results demonstrate that the level of sexual motivation brought about by the olfactory, auditory and/or visual stimulation of a receptive female is associated with an increased demand on catecholamine and 5-hydroxytryptamine synthesis in the limbic forebrain of the male rat. The finding that the presence of an unestrous female produced an enhanced demand on tyrosine hydroxylase activity in the medial prefrontal neocortex demonstrates that the sexual incentive provided by the estrous female may not be the only factor responsible for all the effects observed in the present study. In fact, there is a distinct possibility that the intense challenge produced by sexually significant stimuli is but an endpoint, and that the changes found in forebrain monoamine synthesis is a reflection of an environmental challenge not necessarily specifically linked to the sexual behavior.     

Corneal D.C. recordings of slow ocular potential changes such as the ERG c-wave and the light peak in clinical work

A set-up for D.C. recordings of slow ocular potentials such as the c-wave of the electroretinogram (ERG) as well as the fast oscillation (FO), the light peak (LP) and the dark trough (DT) in both clinical and experimental work is described. It includes matched calomel half-cells connected by saline-agar bridges to a corneal contact lens on the eye and a reference chamber on the forehead, a low-drift differential-input D.C. amplifier, an A/D converter, a computer, a thermoprinter, a flexible disc memory, a plotter, and a device for light stimulation controlled by the computer.Examples of the usefulness of the set-up in clinical work are shown in the form of D.C. c-wave ERGs of normal subjects as well as of patients with vitelliform macular degeneration, choriocapillaris atrophy, and retinitis pigmentosa. The direct corneal recording of the FO and LP is demonstrated as well. The different origins of the standing potential (SP) of the eye, the ERG c-wave, the FO and the LP are reviewed briefly.     

Die zweizeitige Unterkieferrekonstruktion mit einer 2,7-mm-Überbrückungsplatte

The two-phase reconstruction of the mandible with a 2.7-mm-Martin-reconstruction-plate creates a tumor free period that is followed by bone grafting to the embedded plate. We have treated 61 patients following this pattern from 2000 to 2005, follow-up was done in 56. 14 patients had received radiotherapy of 70?Gy. 43 plates healed in without any complications. Until 2005 bone grafting had been performed in 18 patients, in ten patients the plate had been removed.     

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population.