Temperature-resistant variants in clonal populations of pig kidney cells.
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Biomedical subjects
Publications and source records attributed to M Harris.
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Three non-nucleoside reverse transcriptase inhibitors (NNRTIs) are currently available for treatment of HIV-1 as part of combination antiretroviral therapy. Oral dosing is administered three times daily for delavirdine (DLV), twice daily for nevirapine (NVP), and once daily for efavirenz (EFV). Rash is a common side effect of all three NNRTIs, and early CNS side effects are also frequent with EFV. Hepatotoxicity is relatively uncommon but requires appropriate monitoring. Drug interactions mediated by the cytochrome P450 system are an important consideration when the NNRTIs are administered concomitantly with other drugs, including protease inhibitors (PIs). HIV strains with reduced susceptibility to NNRTIs can occur with a single mutation in the reverse transcriptase (RT) gene. The available NNRTIs exhibit overlapping genotypic resistance patterns, but newer agents may overcome this problem. NNRTIs have been studied in combination with nucleoside RT inhibitors for first-line HIV therapy, where they have shown at least equivalent antiviral efficacy compared with PI-based regimens over 1-2 years of therapy. NVP and EFV have also been studied as a replacement for a PI within a virologically successful regimen, with the aim of preventing or reducing PI toxicities and simplifying the dosing regimen. Such 'switch' strategies are successful for certain patients in maintaining virologic suppression for 6 months or more and result in varying degrees of improvement in PI-associated toxicities. NNRTIs may offer a benefit when included in salvage regimens for patients failing PI-based therapy, particularly in patients who have not previously been treated with NNRTIs. NVP has been shown to have a substantial favourable impact on the rate of vertical HIV-1 transmission with a simple, cost-effective regimen.
One hundred and fourteen patients with clinical or pathological stages IIIB and IV Hodgkin's disease have been treated with MVPP chemotherapy followed by radiotherapy to sites of previously bulky disease. The minimum follow-up is 2 years with a median of 5 years. The overall remission rate was 92 per cent with 74 per cent achieving CR. A discriminant analysis showed that the presence of bulky disease was the only independent factor that predicted a lower chance of CR (66 per cent vs 82 per cent, P = 0.045). The 5-year survival was 70 per cent overall and 85 per cent for CR patients. A Cox multivariate analysis demonstrated that stage III disease, age less than 36 years and female sex were all variables which independently predicted a more favourable prognosis in terms of overall survival. However, a similar analysis for survival of CR patients showed that age less than 36 years and the absence of bulky disease were the only two factors to independently predict a more favourable outcome. Of 14 patients who did not receive the chemotherapy according to protocol 5 have relapsed compared to 7 of 70 who did. A Cox analysis confirmed that this variable was the only one of significant prognostic import in predicting relapse-free survival. Using the Cox analyses we have been able to devise a scoring system which accurately predicts the outcome for these patients. This model may be useful in determining which patients have a worse prognosis following treatment with MVPP thus allowing more intensive therapy to be given to such patients while minimising treatment for those with favourable features.
The clinical features of 13 patients with non-secretory myeloma from a series of 172 consecutive multiple myelomas are presented. The non-secretors survived significantly longer that the secretors, median 46 months versus 21 months (p less than 0.01). Non-secretory myeloma was associated with a higher incidence of neurological presentation, minimal lytic bone disease, a lower median percentage of plasma cells in the marrow and a lower incidence of hypogammaglobulinaemia. The median survival of the non-secretors with minimal lytic bone lesions was 74 months compared to 21 months for those with extensive bone disease. The superior survival of non-secretors is thus thought to be due to earlier presentation possibly as a result of a tendency to form symptomatic local tumours. Retrospective immunoperoxidase staining of stored tissue was performed in nine cases. In only one of these was a monoclonal immunoglobulin not detected indicating that true 'non-production' is rare. In four patients who produced a biochemically detectable paraprotein during the course of their disease and in whom immunoperoxidase data was available the immunoglobulin was of the same type. Immunoperoxidase staining may help in the initial diagnosis of non-secretory myeloma but did not contribute any prognostic information.
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The present paper introduces the concept of the narcissistically vulnerable system by suggesting that organizations may manifest some of the same pathological characteristics as narcissistic individuals. The public mental hospital was chosen as an example of such a system. Reasons for its vulnerability were suggested and specific defenses, employed at the system level, were discussed. Finally, remedies for the repair of the narcissistically vulnerable system were considered.
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