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Biomedical subjects

G Pasvol

Publications and source records attributed to G Pasvol.

99 records · Page 6Linked to original sources
PubMedDate not supplied

Human haemoglobin genetics.

The genes which direct the structure of human fetal and adult haemoglobin consist of a linked pair of alpha-chain loci on chromosome 16 and the G gamma-A gamma-delta-beta loci complex on chromosome 11. The delta-and beta-chain genes contain inserts similar to those of the mouse and rabbit globin genes. The structure of the various messenger RNAs transcribed from these loci is now worked out although the function of the non-coding regions is not known. The abnormal haemoglobin disorders and thalassaemias result from a variety of lesions at these loci which include single base substitutions, deletions of one or more bases or entire loci, insertions, frame-shifts, fusion genes caused by abnormal crossing over, chain termination mutations and ill-defined defects which lead to a reduced rate of transcription or abnormal structure of messenger RNA. Some progress has been made towards an understanding of the cellular mechanisms whereby the haemoglobin polymorphisms have been maintained. Very little is known about the regulatory mechanisms involved in the switch from fetal to adult haemoglobin production, although it is likely that certain specific areas of the gamma-delta-beta gene complex are involved in its control.

Anemia, Sickle Cell↗
PubMedDate not supplied

Towards optimal regimens of parenteral quinine for young African children with cerebral malaria: the importance of unbound quinine concentration.

Young African children with severe malaria are given quinine using a regimen designed for Thai adults. We measured quinine in the blood, plasma and plasma water of young children in Kenya after rapid intravenous and intramuscular dosing, and calculated the therapeutic range of unbound quinine. The peak plasma quinine concentration after rapid intravenous dosing was 12.3 +/- 3.7 mg/L (mean +/- SD), 43% higher than in adults given the same regimen previously; this was due to a smaller apparent volume of distribution in the children. The therapeutic range of unbound quinine was calculated as 0.2-2.0 mg/L. Simulations of unbound quinine were made for the standard quinine regimen: unbound drug concentrations rose above the therapeutic range after each dose. The possible risks of quinine-induced visual impairment are discussed. Alternative, lower dose regimens for young African children with severe malaria are described.

Child↗
PubMedDate not supplied

Rapid diagnosis and determination of duration of viraemia in dengue fever using a reverse transcriptase polymerase chain reaction.

A rapid, simple diagnostic polymerase chain reaction (PCR) method for the diagnosis of dengue fever was developed using a pair of consensus oligonucleotide primers and validated with laboratory-derived strains of dengue serotypes 1-4 and other common flaviviruses. A cluster of 13 patients with clinical dengue fever admitted to a single infectious diseases unit over a period of 3 months allowed evaluation of this technology. The PCR was positive in all 11 acute dengue cases and negative in 2 convalescent cases and 10 febrile patients recently returned from the tropics in whom an alternative diagnosis was established. In some of the acute cases, viraemia was detected before the development of a diagnostic antibody response (indirect immunoglobulin (Ig) G enzyme-linked immunosorbent assay (ELISA) and capture IgM ELISA). In patients from whom sequential sera were taken, defervescence and recovery from thrombocytopenia coincided with the disappearance of dengue ribonucleic acid from the blood. Nucleotide sequencing of the PCR products was undertaken in 2 cases (from India and Guyana) and the results showed a close match with previously reported serotype 2 sequencies, suggesting a potential for use of this region of the genome in epidemiological studies.

Adult↗
PubMedDate not supplied

Cell-cell interaction in the pathogenesis of severe falciparum malaria.

One of the major unresolved questions in malaria is why some patients with Plasmodium falciparum infection become so sick and die. Cell-cell interactions between the parasite and the host involving adherence/invasion appear generally, but not exclusively, to correlate with severity. The most important of these interactions in the asexual blood cycle are: (i) the invasion of red cells by merozoites, (ii) the binding of parasitised red blood cells (PRBC) to uninfected red cells (rosetting), (iii) the binding of PRBC to endothelial cells in critical organs (cytoadherence) and (iv) the induction of pro-inflammatory cytokines by PRBC, notably tumour necrosis factor (TNFalpha). The resulting clinical manifestations are protean. Analysis of these cellular interactions has revealed marked heterogeneity in molecular specificity which highlights the complexity of pathogenesis, but also opens the way to new modalities for treating this deadly infection.

Acute Disease↗