Direct evidence for hydroxyl radical-induced damage to nucleic acids by chromium(VI)-derived species: implications for chromium carcinogenesis

Reduction of Cr(VI) by NADH and NADPH has been shown to yieldCr(V) species, which have been detected by electron paramagneticresonance (EPR) spectroscopy. The fine structure on the EPRsignal of the Cr(V) species is consistent with the presenceof two NAD(P)H ligands in a square-pyramidal arrangement witha single oxygen (oxo) group at the apex. Neither this speciesnor the initial Cr(VI) complex damage DNA components as evidencedby the lack of effect of these compounds on the optical andEPR signals of the Cr(VI) and Cr(V) species respectively. Additionof hydrogen peroxide to the Cr(V) species is shown to resultin the formation of a further transient EPR signal, the parametersof which are consistent with an assignment to a Cr(V)-peroxidecomplex. Inclusion of the spin trap 5,5-dimethyl-l-pyrroline-N-oxidein this system demonstrates that hydroxyl radicals are alsogenerated, possibly via the decomposition of the peroxide complex.Inclusion of DNA components in this system together with thespin trap 2-methyl-2-nitrosopropane results in the detectionof base- and sugar-derived radicals; the characteristic EPRsignals of these species have allowed both the identificationof these species and their mechanism of formation to be determined.The signals from the former species are consistent with radicaladdition to the base, whereas the sugar-derived species arebelieved to be formed via hydrogen atom abstraction. In eachcase, this behaviour is consistent with hydroxyl radicals beingthe damaging species in systems where Cr(V) is generated inthe presence of hydrogen peroxide. These results therefore suggestthat it may be the hydroxyl radical that is the ultimate carcinogenicspecies in cells and systems exposed to Cr(VI).     

Severe rheumatic mitral stenosis with pericardial effusion causing left ventricular tamponade.

A woman of 38 was admitted for urgent surgery of severe mitral stenosis causing pulmonary oedema. Echocardiography showed a pericardial effusion with apparent distortion and collapse of the left ventricle. Urgent drainage of the effusion before mitral valve surgery led to an improvement in cardiac output with no detectable change in right heart pressures.     

Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder.

In a preliminary trial, five oral-clomipramine-refractory patients with obsessive-compulsive disorder (OCD) were treated openly with 14 intravenous clomipramine infusions each. Using standardized assessments, three patients were rated as much improved, one as unchanged, and one as minimally improved. Statistically significant improvements were noted on both the Yale-Brown Obsessive Compulsive Scale and the NIMH Global OCD scores. No patient discontinued treatment because of side effects. Although the results are provocative in that three of five patients were much improved at the end of the protocol, conclusions about preferential efficacy for the intravenous route must await a placebo-controlled trial.     

Noncompression unicortical miniplate osteosynthesis of mandibular fractures.

The use of transoral noncompression unicortical miniplates in treating 42 consecutive patients with 64 displaced mandibular fractures (excluding subcondylar) was reviewed. Titanium miniplates (Wurzburg) were used for fixation. The principles set forth by Champy and colleagues, with two plates for body and symphyseal fracture fixation and one plate superiorly along the oblique ridge for angle fractures, were performed. Intermaxillary fixation was not used postoperatively. Results compared favorably with other forms of treatment with no evidence of postoperative malocclusion, with an overall complication rate of 3%. The advantage of no external incision, avoidance of intermaxillary fixation, and normal postoperative incisal opening and occlusion make this technique our treatment of choice.     

Thrombin activity by intrinsic activation of plasma in-vitro accelerates with increasing age of the donor.

Thrombotic diseases increase in incidence with advancing years and this might be partly due to an increased propensity for fibrin formation in older individuals. Accordingly we decided to investigate whether the time taken to generate 50% thrombin activity in vitro varied with the age of the plasma donor. Coagulation was initiated in defibrinated, diluted plasma by contact activation and thrombin activity measured using the chromogenic substrate, S2238. The rate of thrombin generation was assessed by measuring the time taken to reach 50% maximal activity (T50/s). There was a highly significant negative correlation between T50 and age, T50 declining from 93 s at 19 years to 71 s at 65 years (r = -0.637, p less than 0.0001). A strong negative correlation was demonstrated between T50 and FVII level (r = -0.415, p = 0.0007) and FVIII:C level (r = -0.465, p = 0.0001). Although FVII concentration correlated with age (r = 0.307, p = 0.014) no relationship was seen between age and FVIII:C. These data suggest that coagulation rates in plasma accelerate with age.     

Tumorous space occupying lesions of the scapula. An analysis of preoperative assessment of invasion

The radiographic and histological morphology of 38 tumors lesions of the scapula are analyzed. Osteochondromas (n = 12), chondrosarcomas (n = 7), plasmacytomas (n = 4) and Ewing's sarcomas (n = 3) were the most frequent neoplasms. The radiographically determined growth rates allowed an estimate of the dignity in all cases. Benign lesions were only observed in the first five decades of life, and were mostly located in the scapular blade. Most tumors found in the acromion and in the glenoid region and all lesions diagnosed in the 6th to the 8th decades of life were malignant. In 63.2% of cases correct diagnosis of the type of lesion present was possible on radiographic examination.     

AIDS and South Africa--towards a comprehensive strategy. Part II. Screening and control

In this, the second of a three-part series of articles in which we propose steps towards a comprehensive strategy for the control of HIV infection, we consider controversies relating to screening for HIV, the indications for and desirability of mandatory testing of certain groups at risk, and the place of voluntary testing in the control of HIV transmission and infection. Key recommendations are that mandatory testing of donors of blood and other vital tissues, patients on haemodialysis and haemodialysis unit staff is justified, and that children put up for adoption may require testing. We make further recommendations regarding HIV testing as a prerequisite for life insurance and recommend that voluntary testing be offered, supported by adequate pre- and post-test counselling. We consider that all health care workers should accept as their moral obligation the care and management of HIV-infected individuals, and that they should be adequately educated and skilled in such work. These recommendations were reached largely by consensus, although there were occasions when individual authors condoned recommendations with which they did not personally agree.