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Biomedical subjects

M Semple

Publications and source records attributed to M Semple.

13 recordsLinked to original sources

HIV-1 RNA serum-load and resistant viral genotypes during early zidovudine therapy.

The response of HIV-1 to initial zidovudine (ZDV) treatment was assessed in 11 patients with severe HIV disease. We quantified serum HIV-1 concentrations and mutations associated with ZDV resistance by culture-independent methods. There was a prompt fall in serum HIV-1 RNA within 1-2 days of treatment with maximum suppression by seven days, which was paralleled by changes in serum p24 antigen (p24 Ag). Serum RNA started to return to pretreatment levels within weeks. The HIV reverse transcriptase (RT) gene in most patients developed mutations associated with drug resistance within months and as early as 25 days on therapy in one patient. The codon changes were not sufficient to explain the early return of serum HIV-1 RNA levels and their patterns continued to evolve after patients stopped taking ZDV. The significance of these findings is discussed in relation to the limited long-term efficacy of ZDV. The dynamic time course of viral load and RT responses to ZDV is of particular importance in short-term interventions such as pregnancy.

Adult↗

A study of the early signs of drug induced parkinsonism.

Postural tremor was recorded from psychiatric patients who had been treated with phenothiazine or butyrophenone neuroleptic drugs. None of the patients had previously been diagnosed as having extrapyramidal dysfunction. A significant number of these patients had abnormally low tremor frequencies. Low frequency tremors are often associated with Parkinson's disease (PD) so that some of these patients may have early signs of drug induced Parkinsonism (DIP). The results indicate that DIP is not necessarily characterised by a bilateral slow frequency tremor, but may initially be similar to idiopathic PD, even though its cause and prognosis are different.

Adolescent↗

Direct measurement of viraemia in patients infected with HIV-1 and its relationship to disease progression and zidovudine therapy.

Cell-free human immunodeficiency virus type-1 (HIV-1) was precipitated from archival serum with polyethylene glycol (PEG), and HIV-1 RNA was detected and quantified by reverse transcription and amplification in a nested polymerase chain reaction (PCR). The assay of end-point dilutions cDNA in nested PCRs allowed an estimation of the minimum RNA copies per unit volume of serum. RNA titres correlated with the classification of HIV-1 infection by CDC disease groups (30 patients). The geometric mean titres of HIV-1 serum RNA from patients grouped by disease stage gave minimum estimates of 340 and 400 virions per millilitre of serum in CDC groups II and III (n = 6 and 10, respectively) and 4,240 virions per millilitre in CDC group IV (n = 14). An overall fall in viral titre measured in this way was observed in 3 patients during zidovudine treatment. HIV-1 titres increased in a further 4 patients when therapy was interrupted, stopped, or complicated by secondary infection.

Base Sequence↗