VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity

Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.     

Primary sternal osteomyelitis presenting as a pleural-based mass

Osteomyelitis in uncommon locations can present unusual diagnostic difficulties. A patient with primary sternal osteomyelitis who presented with pain over the right supraclavicular area and a radiologic picture of a pleural-based right upper lung mass is discussed. A triple-phase bone scan was consistent with the diagnosis, and a needle aspiration of the mass revealed a staphylococcal abscess. Percutaneous drainage of the contiguous abscess and a prolonged course of antibiotic therapy cured the infection.     

Comparison of three fully implantable venous access systems. A randomized study

Three different fully implantable venous access devices were randomly inserted in 72 patients. Comparison both from the point of view of their ease of insertion and their later use failed to show any significant difference between the three systems.     

Differential activity of the G protein beta5 gamma2 subunit at receptors and effectors

The G protein beta5 subunit differs substantially in amino acid sequence from the other known beta subunits suggesting that beta gamma dimers containing this protein may play specialized roles in cell signaling. To examine the functional properties of the beta5 subunit, recombinant beta5 gamma2 dimers were purified from baculovirus-infected Sf9 insect cells using a strategy based on two affinity tags (hexahistidine and FLAG) engineered into the N terminus of the gamma2 subunit (gamma2HF). The function of the pure beta5 gamma2HF dimers was examined in three assays: activation of pure phospholipase C-beta in lipid vesicles; activation of recombinant, type II adenylyl cyclase expressed in Sf9 cell membranes; and coupling of alpha subunits to the endothelin B (ETB) and M1 muscarinic receptors. In each case, the efficacy of the beta5 gamma2HF dimer was compared with that of the beta1 gamma2HF dimer, which has demonstrated activity in these assays. The beta5 gamma2HF dimer activated phospholipase C-beta with a potency and efficacy similar to that of beta1 gamma2 or beta1 gamma2HF; however, it was markedly less effective than the beta1 gamma2HF or beta1 gamma2 dimer in its ability to activate type II adenylyl cyclase (EC50 of approximately 700 nM versus 25 nM). Both the beta5 gamma2HF and the beta1 gamma2HF dimers supported coupling of M1 muscarinic receptors to the Gq alpha subunit. The ETB receptor coupled effectively to both the Gi and Gq alpha subunits in the presence of the beta1 gamma2HF dimer. In contrast, the beta5 gamma2HF dimer only supported coupling of the Gq alpha subunits to the ETB receptor and did not support coupling of the Gi alpha subunit. These results suggest that the beta5 gamma2HF dimer binds selectively to Gq alpha subunits and does not activate the same set of effectors as dimers containing the beta1 subunit. Overall, the data support a specialized role for the beta5 subunit in cell signaling.     

The use of the scanning electron microscope in the determination of the mineral composition of Ballachulish slate

Slate is a fine-grained, low-grade metamorphic rock derived from argillaceous sediments or occasionally volcanic ash. Although most slates contain mainly quartz, chlorite and white mica, they vary considerably in their durability, some lasting centuries while others fail after a few years of service. A detailed characterisation of their mineralogy is required for the assessment of performance, and to establish the provenance of a used slate. A combination of methods was used to examine Ballachulish slates; XRD analysis to determine the principal minerals present, XRF analysis to determine the total chemical composition, and scanning electron microscopy to determine the chemical composition of individual minerals. It was found that the white mica in Ballachulish slate is phengite and the chlorite is ripidolite. Feldspar is present as albite and carbonate as ferroan dolomite. Several accessory minerals were also identified, including chloritoid, monzonite and zircon. There was considerable variation in the ratio of the principal minerals, making it impossible to identify used slates by this criterion. Instead, chemical composition of the individual minerals, and possibly key accessory minerals, should be used to determine the provenance of slates.     

Psychopathy, IQ, and Violence in European American and African American County Jail Inmates.

The accuracy of the prediction of criminal violence may be improved by combining psychopathy with other variables that have been found to predict violence. Research has suggested that assessing intelligence (i.e., IQ) as well as psychopathy improves the accuracy of violence prediction. In the present study, the authors tested this hypothesis by using a contemporary measure of psychopathy, the Psychopathy Checklist-Revised (R. D. Hare, 2003), in a sample of 326 European American and 348 African American male offenders. The postdictive power of psychopathy was evident for both ethnic groups and robust across most changes in the operationalization of violence and the analysis conducted, whereas the postdictive power of IQ was not. No Psychopathy x IQ interactions were identified. Implications of these results for violence prediction are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical and experimental studies of intraoperative autotransfusion using a new filtration device

The Haemocell S-350 device has recently been introduced for intraoperative autotransfusion. The system uses a novel membrane filter to process shed blood. In the first part of this study a 0.2-micron pore size filter was used in a randomized trial comparing the use of autotransfusion (n = 8) with bank blood controls (n = 9) during aortic reconstruction. This part of the trial was abandoned because of unexpected non-surgical bleeding. Bank blood requirements fell from a median of 3.0 (range 0.0-9.0) units to 1.5 (range 0.0-7.0) units when autotransfusion was used, but these patients had a greater perioperative blood loss (1791 (range 932-3104) versus 1140 (range 440-3840) ml). There was evidence of postoperative heparin excess with an activated partial thromboplastin time ratio of 1.3 (range 0.9-3.0) versus 1.0 (range 1.0-1.2) in controls and an activated clotting time of 206 (range 143-280) versus 137 (range 107-142) s. This was confirmed by raised plasma heparin levels and a prolonged thrombin time normalized by protamine. To improve performance a 0.6-micron pore size filter was studied in ten patients. Filtration efficiency doubled from 19 to 38 per cent. Electron micrographs demonstrated better filter clearance, but 44 per cent of the original concentration of heparin remained in the reinfusate. The S-350 device may be an attractive alternative to centrifugation for intraoperative autotransfusion but, until efficiency is improved, it should only be used for cardiovascular surgery when excess heparin can be reversed with protamine.     

Change of foot size with weightbearing. A study of 2829 children 3 to 18 years of age

The change of foot length and width with age has been reported in a few anthropometric studies in the literature. However, the relationship with body height rarely is reported, and the dynamic effect of weightbearing on foot size has not been documented. In this series, 2829 children 3 to 18 years of age of equal gender distribution were included in the study. The foot length and width on weightbearing and nonweightbearing were measured with a special precision electronic caliper. The foot length and width were found to increase linearly from the age of 3 years until 12 years in girls and 15 years in boys. This was followed by a phase during which the increase plateaued. The foot length and width increased significantly on weightbearing at all ages in both genders with a mean of 2.1 to 4.4 mm or 3.1% to 4.8%, respectively. The foot length and width also were found to correlate significantly with the body height in both genders, with a correlation coefficient of 0.96 to 0.98. No significant differences were found between the sizes of the dominant and nondominant foot in either gender.