Pulmonary carcinogenicity of relatively low doses of beta-particle radiation from inhaled 144CeO2 in rats

This study was conducted to examine the carcinogenic effects of inhaled beta-particle-emitting radionuclides, particularly in lower dose regions in which there were substantial uncertainties associated with available information. A total of 2751 F344/N rats (1358 males and 1393 females) approximately 12 weeks of age at exposure were used. Of these, 1059 rats were exposed to aerosols of 144CeO2 to achieve mean desired initial lung burdens (ILBs) of 18 kBq (low level), 247 rats to achieve mean ILBs of 60 kBq (medium level) and 381 rats to achieve mean ILBs of 180 kBq (high level). Control rats (total of 1064) were exposed to aerosols of stable CeO2. Based on the 95% confidence intervals of the median survival times and the cumulative survival curves, there were no significant differences in the survival of groups of female and male exposed rats relative to controls. The mean lifetime beta-particle doses to the lungs of the rats in the four groups were: low level, 3.6 +/- 1.3 (+/-SD) Gy; medium level, 12 +/- 4.5 Gy; and high level, 37 +/- 5.9 Gy. The crude incidence of lung neoplasms increased linearly with increasing doses to the lungs (controls, 0.57%; low level, 2.0%; medium level, 6.1%; and high level, 19%). The estimated linear risk coefficients for lung neoplasms per unit of dose to the lung were not significantly different for the three dose levels studied. The risk coefficient at the lower level was 39 +/- 14 (+/-SE) excess lung neoplasms per 10(4) rat Gy; at the medium level the risk was 47 +/- 12; and at the higher level the risk was 50 +/- 9.0. The relationship of beta-particle dose to the lung and the crude incidence of lung neoplasms was described adequately by a linear function. We concluded that the risk of lung neoplasms in rats per unit of radiation dose did not increase with decreasing mean beta-particle dose to the lung over the range of 3.6 to 37 Gy. The weighted average of these three values was 47 +/- 6.4 (+/-SE) excess lung neoplasms per 10(4) rat Gy. To extend the risk coefficients for lung neoplasms to lower doses by experimentation will require much larger numbers of rats than used in this study.     

Posterior fast atrioventricular node pathways: implications for radiofrequency catheter ablation of atrioventricular node reentrant tachycardia

OBJECTIVES: This study sought to present evidence that fast atrioventricular (AV) node pathways with posterior exit sites may participate in typical AV node reentry. BACKGROUND: Catheter ablation of the slow AV node pathway in the posteroseptal right atrium is the preferred therapeutic approach in patients with AV node reentrant tachycardia. Despite the success achieved with this approach, electrophysiologic changes consistent with fast pathway ablation are occasionally observed. One potential explanation is the presence of an aberrant posterior fast pathway. METHODS: The location of fast and slow AV node pathways was determined by atrial activation mapping along the tricuspid valve annulus during tachycardia and was further confirmed by the effect of radiofrequency catheter ablation. RESULTS: Seven patients with AV node reentrant tachycardia had evidence of a posterior fast pathway near the coronary sinus os. Abolition of anterograde and retrograde fast pathway conduction followed radiofrequency ablation in the posteroseptal region in six patients. Consistent with fast pathway ablation, the AH interval increased from 70 +/- 24 to 195 +/- 35 ms (mean +/- SD), and tachycardia was no longer inducible. Selective slow pathway ablation was performed in one other patient with a posterior fast pathway. CONCLUSIONS: Functionally fast AV node pathways may be located in the posteroseptal right atrium, where slow pathway modification is performed. These data delineate the limitation of an anatomically guided slow pathway ablative approach and emphasize the importance of detailed mapping and localization of the retrograde fast pathway exit site before ablation. Failure to recognize the presence of posterior fast AV node pathways may account for sporadic examples of AV block, complicating posteroseptal ablation in patients with AV node reentry.     

Long-duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions

18 patients with malignant effusions were treated with continuous intraperitoneal, intrapleural, or intrapericardial infusion of methotrexate (MTX) 30 mg/m2 per d combined with simultaneous intravenous administration of leucovorin at a dose rate calculated to yield an equimolar concentration in the serum. In the serum the geometric mean steady-state MTX concentration was 0.95 microM, whereas it was 24 microM in the peritoneal, 213 microM in the pleural, and 434 microM in the pericardial cavities. Mean clearance was 6.6 ml/min from the peritoneal cavity, 2.6 ml/min from the pleural cavity, and 0.14 ml/min from the pericardial cavity. Leucovorin provided sufficient protection to allow the duration of infusion to be escalated from 24 to 120 h before myelosuppression was encountered. Marrow thymidylate synthetase activity was inhibited by an average of 46% compared to 86% inhibition in malignant cells in the effusions. Flow cytometric analysis showed no perturbation of the cell cycle phase distribution of marrow cells. All eight of the evaluable patients have responded: three received no other form of therapy, five also received systemic hormonal or chemotherapy. This study demonstrated that tumors confined to third space body fluids can be given very high concentration x time exposures to MTX with minimal systemic toxicity.     

Serologic survey of Toxoplasma gondii in grizzly bears (Ursus arctos) and black bears (Ursus americanus), from Alaska, 1988 to 1991

We tested 644 serum samples from 480 grizzly bears and 40 black bears from Alaska (USA), collected between 1988 and 1991, for Toxoplasma gondii antibodies, using a commercially available latex agglutination test (LAT). A titer > or = 64 was considered positive. Serum antibody prevalence for T. gondii in grizzly bears (Ursus arctos) was 18% (87 of 480). Prevalence ranged from 9% (seven of 77) on Kodiak Island to 28% (15 of 54) in northern Alaska. Prevalence was directly correlated to age. No grizzly bears < 2-year-old had T. gondii antibody. High antibody titers were found mainly in grizzly bears captured north of the Arctic Circle. Antibody prevalence in black bears (Ursus americanus) from Interior Alaska was 15% (six of 40), similar to the prevalence in grizzly bears from the same area (13%; five of 40).     

Carbohydrate molecular weight profiling, sequence, linkage, and branching data: ES-MS and CID

This section summarizes several strategies for a more complete understanding of carbohydrate structure with a focus on glycolipids and glycoprotein glycans. The techniques include periodate oxidation to impart greater molecular specificity to isomeric glycans, methylation to improve sensitivity and the information content within CID spectra, electrospray for "soft" and efficient ionization, and CID to obtain structural detail. The lipophilicity of the products following derivatization contributes to product cleanup by solvent extraction and enhances sensitivity during ES. When combined with CID information, this yields sequence, linkage, and branching information. Oxidation and reduction preceding methylation augments CID analysis with an altered structure that can be profiled at the same sensitivity. Within the context of established motifs, these contrasting profiles corroborate glycan structure and specifically identify isobaric elements transparent in the initial profile. An earlier report indicating ring-opening fragments were essentially absent in low-energy collisions of methylated and natriated oligosaccharides contrasts our observations. However, as this report used a methylated oligomer containing an internal N-acetylhexose as an illustration, the conclusion is plausible (cf., Figure 9). The poor ionization efficiency of FAB and the high matrix background limit the dynamic range in the CID spectrum and, thereby, the ability to unambiguously identify weaker peaks. It would be expected that high-energy CID affords a broader range of fragment types, including ring-opening fragments. In terms of a structural methodology, this is ambivalent since the increase in fragmentation pathways also applies to small molecule eliminations which are usually less informative. In ES-CID-MS, the carbohydrate chemist has a powerful new tool in hand for structural elucidations that can be conducted at the low-picomole level. Parallel developments can be expected to continue for other ionization methods, in particular matrix-assisted desorption/ionization on linear and reflectron time of flight mass spectrometers, and improvement in the performance and sensitivity of high-resolution mass analyzers through the use of focal plane detectors and more sophisticated hardware and software for Fourier transform ion cyclotron resonance mass measurements. These have, as yet, only begun to be applied to carbohydrate structural analysis but should add still more versatility to experimental design in the future.     

A case of paracetamol retard poisoning with fatal outcome

A case of fatal paracetamol (acetaminophen) poisoning in a 26-year-old woman who developed liver necrosis is described. The patient reported having ingested 11 g of a slow-release paracetamol preparation and a certain amount of alcohol and benzodiazepine. An unknown dose of phenobarbital (phenemal) had been ingested 24 hours previously, leading to a serum phenobarbital concentration of 0.195 mmol/l at the time of admission. The patient was initially treated with N-acetylcysteine intravenously. This treatment was discontinued after five hours due to a serum paracetamol concentration of 0.49 mmol/l, well below the "treatment line" paracetamol concentration of 0.8 mmol/l six hours after ingestion. Possible aggravating factors are discussed, including sustained high serum concentration of paracetamol due to the slow-release preparation and enzyme induction caused from concomitant phenobarbital and alcohol intake, as well as benzodiazepines displacing paracetamol from liver enzymes. These factors make serum paracetamol concentrations undependable; the importance of continuing N-acetylcysteine treatment in spite of "safe" serum concentrations in the above cases is stressed.     

Determining priorities for family physician education in substance abuse by the use of a survey

As the initial stage in developing a curriculum to assist family physicians to diagnose and manage alcohol abuse in their practices, questionnaires were mailed to a selected group of family physicians. A total of 117 physicians (34%) completed the questionnaire. The majority of physicians (70.1%) reported that fewer than 10% of their caseload experienced alcohol-related problems. Most physicians (59.3%) did not use any of the standard diagnostic instruments but reported that screening and detection was the most challenging alcohol-related problem along with patient management. The questionnaire identified a number of areas that could be used in the development of educational strategies to increase the expertise of primary care physicians in the diagnosis and management of alcohol-related problems.