How I do it: endoscopic-microscopic anterior skull base reconstruction.

Reconstruction of the anterior skull base must be secure and watertight. Failure to achieve this places the patient at risk of the development of cerebral sepsis. We have developed the technique of endonasal duraplasty and have achieved a 90% long-term success rate. In this article we described the key elements of our technique starting with radiographic and fluorescein localization of a skull base defect. The main steps in reconstruction and materials used are detailed, together with modifications of our technique for certain difficult situations and tips for success. Attention is drawn to potential pitfalls that have been identified over 25 years of clinical practice.     

Sites in the brain at which cholecystokinin octapeptide (CCK-8) acts to suppress feeding in rats: a mapping study

In this study, an examination was made of the sites in the brain of the rat at which the injection of cholecystokinin octapeptide (CCK-8) would alter food intake. Rats fasted for 24 hr received intracerebral injections of CCK-8 (1 nmol) or an equal volume of saline (0.5 microliters), into various sites in the brain through permanently implanted stainless steel cannulae. After prior acclimatisation to individual plexiglass compartments, latency to feed, as well as consumption of food and water during 0-20, 20-40 and 40-60 min after the injection, were recorded. The available food was the standard rat pellets, to which the animal otherwise had constant daily access. With this paradigm, active sites at which CCK-8 suppressed feeding were defined as sites at which consumption of food for 0-20 min was reduced by 25% or more, or the latency to feed was increased by 3 min or more after the injection of CCK-8, as compared to the effect of the injection of saline, made at the same site. Such active sites were most densely distributed in the rostral diencephalon, e.g. hypothalamus, the medial pontine area and lateral medulla, in the vicinity of the nucleus tractus solitarii (NTS). By grouping data for injections according to histologically identified sites, statistical analysis of groups of injections confirmed that these three major areas of the brain were active with regard to the suppression of feeding by CCK-8. These data suggest that CCK may not only initiate satiety messages, as a circulating hormone at peripheral sites, but also participate in the conduction of such information to the target in the brain by serving as a neurotransmitter in the lateral medulla (e.g. NTS), medial pontine area (e.g. relay station between the NTS and hypothalamus) and the lateral hypothalamus, where local release of CCK-8 after stomach loading has been observed.     

Anti-idiotypic antibodies against a monoclonal antibody specific for the trichothecene mycotoxin T-2

A BALB/c murine monoclonal antibody against the trichothecene mycotoxin T-2 was generated. The antibody, designated HD11, specifically bound T-2 mycotoxin. The binding of HD11 to T-2 conjugated to bovine serum albumin was inhibited by free T-2 toxin but not by the water-soluble heterocyclic guanidines saxitoxin and tetrodotoxin. The T-2 detection limit in an enzyme-linked immunosorbent assay with HD11 was in the nanogram range. The in vitro cytotoxicity of T-2, as measured by the inhibition of radiolabeled leucine uptake of the human epidermoid carcinoma Hep-2 and KB cell lines, was completely reversed by the addition of HD11. Rabbit anti-idiotypic antibodies specific for HD11 were generated and characterized.     

Magnetic susceptibility effects secondary to out-of-plane air in fast MR scanning

Areas of signal loss in brain overlying air-containing structures at the skull base are commonly observed on axial fast MR images. The nature of this effect, which can mimic the appearance of cerebral hemorrhage, is investigated in a phantom study and in a normal volunteer. The magnitude of the signal loss is found to be inversely related to the distance of the scanning plane from the air-containing structure and directly related to the echo time.     

The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Wirkung des Äthylazetatextraktes von Chrysanthemum morifolium auf Plasmodium falciparumIn Vitro

Zusammenfassung Die Wirkung des ?thylazetatextraktes von Chrysanthemum morifolium auf P. falciparum wurde in vitro untersucht. W?hrend sich die Parasit?mie bei der Kontrollgruppe bis zu 10. 90 % entwickelte, wurde bei dem mit ?thylazetatextrakt in einer Konzentration von 100 μg/ml Medium am 5. Tag der Kultur eine signifikante Hemmwirkung auf die Parasiten beobachtet. Die Parasit?mie blieb bei 1. 00 %.

Diese Arbeit wurde durch die Stiftung von “National Nature Science Foundation of China” finanziert (No. 39260066)     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

Building research administration applications for the academic health center: a case study.

The academic health center information environment is saturated with information of varying quality and overwhelming quantity. The most significant challenge is transforming data and information into knowledge. The University of Cincinnati Medical Center's (UCMC) focus is to develop an information architecture comprising data structures, Web services, and user interfaces that enable individuals to manage the information overload so that they can create new knowledge. UCMC has accomplished much of what is reported in this article with the help of a four-year Integrated Advanced Information Management Systems (IAIMS) operation grant awarded by the National Library of Medicine in 2003. In the UCMC vision for knowledge management, individuals have reliable, secure access to information that is filtered, organized, and highly relevant for specific tasks and personal needs. Current applications and tool sets will evolve to become the next generation knowledge management applications or smart digital services. When smart digital services are implemented, silo applications will disappear. A major focus of UCMC's IAIMS grant is research administration. Testing and building out existing and new research administration applications and digital services is underway. The authors review UCMC's progress and results in developing a software architecture, tools, and services for research administration. Included are sections on the evolution to full integration, the impact of the work at UCMC to date, lessons learned during this research and development process, and future plans and needs.