In vivo characterization of the novel ebolavirus Bombali virus suggests a low pathogenic potential for humans.

Ebolaviruses cause outbreaks of haemorrhagic fever in Central and West Africa. Some members of this genus such as Ebola virus (EBOV) are highly pathogenic, with case fatality rates of up to 90%, whereas others such as Reston virus (RESTV) are apathogenic for humans. Bombali virus (BOMV) is a novel ebolavirus for which complete genome sequences were recently found in free-tailed bats, although no infectious virus could be isolated. Its pathogenic potential for humans is unknown. To address this question, we first determined whether proteins encoded by the available BOMV sequence found in Chaerephon pumilus were functional in in vitro assays. The correction of an apparent sequencing error in the glycoprotein based on these data then allowed us to generate infectious BOMV using reverse genetics and characterize its infection of human cells. Furthermore, we used HLA-A2-transgenic, NOD-scid-IL-2γ receptor-knockout (NSG-A2) mice reconstituted with human haematopoiesis as a model to evaluate the pathogenicity of BOMV in vivo in a human-like immune environment. These data demonstrate that not only does BOMV show a slower growth rate than EBOV in vitro, but it also shows low pathogenicity in humanized mice, comparable to previous studies using RESTV. Taken together, these findings suggest a low pathogenic potential of BOMV for humans.

Perioperative blood loss: the effect of valproate.

The purpose of this investigation was to determine the effect of the use of valproate (VPA) on bleeding and requirement for replacement blood products in patients undergoing major surgical procedures. One hundred thirty-nine patients had posterior spinal fusion performed by 1 of 3 surgeons at our institution from 1987 to 1993. The clinical status of the patient, pre- and postoperative laboratory values, type and extent of instrumentation, surgeon performing the procedure, and medications (including VPA) were variables considered. The outcome measures were intra- and postoperative blood loss and number of blood products used. Intraoperative blood loss was correlated with the method of instrumentation, platelet count, and the surgeon performing the procedure. Postoperative blood loss was correlated with the diagnosis of cerebral palsy. By hierachical stepwise regression analysis, the only outcome measure correlated with VPA was the number of blood products used.

Emergency transumbilical embolization of bleeding esophageal varices.

Eight patients had major hemorrhage from esophageal varices; in seven, one or two embolizations of the coronary and short gastric veins resulted in cessation of hemorrhage. This procedure can be used in patients with massive ascites, severe coagulopathy, or profound liver failure, as the access route through the dilated umbilical vein can be reached via a supraumbilical incision done with the patient under local anesthesia. All patients died; two deaths were attributable to complications of the procedure, the other six to the severity of the cirrhosis. Sclerotherapy may be combined with coronary vein embolization, but the risk of esophageal perforation may be greater than with sclerotherapy alone.

Antimitochondrial antibodies: reagent variables may lead to diagnostic error.

Laboratory-prepared and commercially obtained fluorescein-labeled rabbit antihuman IgG were compared in performing the antimitochondria antibody (AMA) assay. Identical results were obtained using either of the fluorescent antisera at protein concentrations of 1.5 mg/ml and 1:10 dilutions of patients' sera. Positive AMA tests with either antisera were observed in each of 7 patients with primary biliary cirrhosis (PBC), 2 of 83 patients with miscellaneous hepatic diseases, and in 1 of 24 patients with extrahepatic biliary obstruction (EBO) of 2-24 weeks duration. However, when undiluted commercial fluorescent antiserum (15.8 mg protein/ml) was substituted in the assay, sera from 11 of 23 AMA-negative patients with EBO and 12 of 15 with miscellaneous liver diseases demonstrated an atypical fluorescence located primarily along the periphery of the rat renal tubules. Thus, if the conjugated antibody is not adjusted to an optimal protein concentration, this atypical fluorescence could be interpreted as a positive AMA test and lead to diagnostic error.

The effects of 11-methyl 16,16 dimethyl prostaglandin E2 on gastric acid secretion in man.

11-Methyl 16,16 Dimethyl Prostaglandin E2 (TM-PGE) was administered orally to man in dosages of 2.5, 5,7.5 and 10 microgram/kg. Maximal inhibition of basal secretion was 52 and 78% and submaximal histamine-stimulated secretion 45 and 70% for volume and acid output, respectively. Secretory inhibition was observed for approximately two hours after ingestion of the drug. No effect was observed on serum gastrin levels. Side effects occurred with equal frequency in the placebo and drug groups. TM-PGE is well tolerated and inhibits both basal and submaximal histamine-stimulated acid secretion in man. Further evaluation may prove it to be helpful in the clinical treatment of acid hypersecretory states and peptic ulcer disease.