A patient's right to a good death.
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Biomedical subjects
Publications and source records attributed to J D Buchanan.
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Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. We evaluated NAC and methylprednisolone in two rat models of inhalational injury: 40-hr exposure to greater than 97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). For oxygen toxicity, NAC (80 mg) or methylprednisolone (10 mg) were given IP every 2 or 6 hr, respectively. For acrolein, single doses of NAC (1 g/kg) and methylprednisolone (30 mg/kg) were given intravenously 15 min before exposure. In sham-exposed control animals, neither treatment favorably effected mortality, lung wet/dry weight ratios, or pulmonary histology. The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. We caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.
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The medical history, clinical and neuropathological findings at necropsy are described in a 50-year-old male amateur diver who suffered from Type II decompression sickness, a spinal 'bend'. He survived as a paraplegic for 4 years. In the spinal cord upward Wallerian degeneration in the posterior columns and downward degeneration in the corticospinal tracts was explained by multiple small and medium sized infarcts affecting the centripetal blood supply to the cord. There was preservation of a rim of subpial fibres on the surface of the posterior and lateral columns. The grey matter and nearby white matter (supplied by the centrifugal arterial supply) was unaffected.
Recent studies from specialist breast centres have suggested that fine needle aspiration cytology in conjunction with mammography and clinical examination can provide a prompt and accurate diagnosis of breast lumps. These three methods of diagnosis have been assessed in the context of a district general hospital by analysing 104 consecutive breast lesions with known histology, of which 75 were benign and 29 malignant. The results are presented in terms of the sensitivity and specificity for each method. Fine needle aspiration cytology had a sensitivity for malignancy of 88% (n = 26) and a specificity of 97% (n = 58). Similarly, sensitivity for mammography was 95% (n = 20) and clinical examination 90% (n = 29). Respective specificities were 96% (n = 45) and 83% (n = 75). In none of the 29 patients with breast cancer were all three modalities negative. It is concluded that without specialist breast clinicians and cytologists, a combination of fine needle aspiration cytology, clinical examination and mammography can still provide a degree of preoperative diagnostic accuracy comparable with specialist centres, allowing prompt counselling with all the subsequent benefits.
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Calcium binding isotherms were determined for thermolysin in the range pH 5.6-10.5, and from 5 to 45 degrees C. An extensive statistical analysis of the binding data suggests that at least two of the four binding sites bind Ca2+ with complete positive cooperativity and independently of the other two. Nonlinear regression analysis of the binding data was used to calculate cooperative (K1) and independent (K2) binding constants for the four calcium sites. Thermodynamic parameters obtained from a van't Hoff analysis indicate that calcium binding to both cooperative and independent sites is an entropy-driven process. At pH 7.0, delta H1 = 90.4 kJ/mol; delta H2 = 97.5 kJ/mol; delta S1 = 456 J K-1 mol-1; delta S2 = 262 J K-1 mol-1. These results are compared to those obtained for other calcium-binding proteins. An analysis of the pH dependence of the calcium binding constants indicates that the binding of four protons at the cooperative site and one to two protons at the independent sites, modulates the calcium affinity. This confirms an earlier structural assignment of the double-site as the locus of the two cooperatively binding Ca2+. Calcium binding to thermolysin is enhanced in the presence of an active site directed inhibitor, suggesting that there may be positive cooperativity between substrate and calcium binding.
A 60 year old man with features of osteogenesis imperfecta presented in biventricular failure with evidence of mitral regurgitation. He responded to conventional treatment but later collapsed and died at home. Necropsy showed a haemopericardium caused by a tear in the left atrium. There was also rupture of the mitral chordae tendineae.
26 patients referred for colonoscopy with unexplained anaemia or blood loss per rectum were found to have angiodysplasia located in the caecum and/or ascending colon. All patients had undergone previous extensive investigation. After endoscopic photography of the lesions coagulation and biopsy were carried out in 23 patients. In 3 patients the extent of the lesion demanded surgical management, and right hemicolectomy was carried out without prior coagulation biopsy, 3 other patients underwent surgery at a later date-2 for further bleeding and 1 for complications of coagulation biopsy. Colonoscopy with photography and coagulation biopsy proved a safe and effective approach to the management of angiodysplasia in the majority of patients. It provided successful treatment and confirmation of the diagnosis without resort to major surgery, which in elderly patients is associated with high morbidity and mortality.
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The yields in molecules per 100 eV for active-site and sulphydryl loss from glyceraldehyde-3-phosphate dehydrogenase have been determined in nitrous-oxide-saturated, aerated and argon-saturated solutions. Molecular hydrogen peroxide produces a sulphenic acid product, which can be repaired by post-irradiation treatment with dithiothreitol. Comparison of the yields under various conditions showed that in aerated solutions both .OH and .O2-radicals inactivated the enzyme with an efficiency of about 26 per cent. However, the efficiency of .OH in air-free solutions was less, and inactivation by .H and eaq- did not appear to be appreciable. There is a correlation between SH loss and loss of active sites.
Pulse radiolysis has been used to study the interaction of aminoacridines with nucleic acids. The data confirm that there are two modes of binding. These are: a weak interaction which has a maximum binding ratio of one site per dye; and a strong binding process effected by both electrostatic and Van der Waals interactions. The limit of this latter, strong binding mode is approximately six sites per dye. The radiation-induced transient absorption spectrum of benzoflavine is characterized by a pronounced bleaching at 440 nm, which is quenched by the addition of nucleic acids. Mechanisms have been proposed for the reactions of both eaq-and .OH with benzoflavine which account both for the observed bleaching of benzoflavine solutions and for the protective effect of nucleic acids. It is proposed that eaq-reacts with benzoflavine to form a stable benzoflavine semiquinone radical and that .OH reacts with subsequent formation of a very stable benzoflavine hydroxycyclohexadienyl radical.
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Pulse radiolysis has been used to investigate the rates and transient spectra for the reactions of free radicals with beef heart lactate dehydrogenase at pH 7. Analysis of the results leads to second-order rate-constants for eaq-, .OH, .I, .Br2-, .I2- and .(CNS)2- which are, respectively, 24, 21, 10, 0.55, 0.43 and 0.15 in units of 10(10) M-1 s-1 with uncertainties of +/- 20 per cent. Those for .I and .I2- are similar to the corresponding rate-constants for the related enzyme alcohol dehydrogenase. The spectra of the transient species produced by .OH, .Br2- and .(CNS)2- all showed evidence for reactions with tyrosine and tryptophan residues, and in general terms the magnitudes of the rate-constants appeared to increase with the oxidizing abilities of the radicals. The implication of the results for understanding the mechanism of deactivation by free radicals is discussed.