Depressed antigen presentation function and membrane interleukin-1 activity of peritoneal macrophages after laparotomy

Although major tissue trauma produces profound depression of cell-mediated immunity, it is not known whether surgical trauma (i.e., midline laparotomy) has any adverse effect on the antigen presentation function and membrane interleukin-1 (IL-1) activity of peritoneal macrophages. To study this, C3H/HEJ (endotoxin-tolerant) mice were anesthetized. An approximately 1-inch midline abdominal incision was made, followed by abdominal closure. On days 1, 3, 5, and 7, peritoneal macrophages were harvested by means of peritoneal lavage, and antigen presentation capability was tested by incubating various numbers of peritoneal macrophages with 2 X 10(4) D10.G4.1 cells per well in the presence of conalbumin (400 micrograms/ml). The T helper cell clone (D.10.G4.1) proliferates on recognition of conalbumin in the context of Iak and also proliferates in the presence of membrane-bound IL-1 plus concanavalin A. To measure membrane IL-1 expression in peritoneal macrophages, Concanavalin A (10 micrograms/ml) was substituted for conalbumin. Cultures were incubated for 72 hours, pulsed with tritiated thymidine, and harvested. Peritoneal macrophages from laparotomized mice induced significantly less T helper cell proliferation on days 1 and 3 in the antigen presentation assay (37% and 30%, respectively; p less than 0.05) and in the membrane IL-1 assay (14% and 10%, respectively; p less than 0.05) as compared with the control. This difference was not detectable on day 5. More effective antigen presentation capability (167% of control; p less than 0.05) was seen on day 7. Thus laparotomy by itself produces marked depression of both antigen presentation function and membrane IL-1 activity of peritoneal macrophages, which may enhance susceptibility to intra-abdominal sepsis.     

Intracerebral hemorrhage: natural history and rationale of ultra-early hemostatic therapy

Stroke is a major health problem worldwide, causing high morbidity and mortality. Intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. It is less treatable than other forms of stroke and causes higher morbidity and disability. Data suggest that early hematomy growth is the principal cause of early neurological deterioration after ICH. Prospective and retrospective studies indicate that early hematoma growth occurs in 18–38% of patients scanned within 3 h of ICH onset, and that hematoma volume is an important predictor of 30-day mortality. As hematoma growth in acute ICH is a dynamic process, intervention with ultra-early hemostatic therapy could lead to minimization and even prevention of early hematomy growth. Recombinant activated factor VII (rFVIIa, ‘NovoSeven’), a powerful initiator of hemostasis, is approved for the treatment of bleeding in patients with hemophilia and inhibitors and may also promote hemostasis in patients with normal coagulation. rFVa acts locally at the bleeding site without activating systemic coagulation and may be a valuable therapy during the hyperacute stage of ICH. A randomized, double-blind, placebo-controlled, dose-ranging trial is currently in progress to investigate the potential of rFVIIa as an ultra-early hemostatic therapy to prevent or minimize hematoma growth in ICH patients without coagulopathy.     

Offene Rechtsfragen bei der Gründung Medizinischer Versorgungszentren?

Ohne Zusammenfassung     

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.     

Stereotactic brain biopsy in AIDS

Summary In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrastCT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.