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Biomedical subjects

S Abdulla

Publications and source records attributed to S Abdulla.

At least 19 recordsLinked to original sources
PubMed1998

Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1-5 years.

A randomized, open trial involving 260 Tanzanian children, aged 1-5 years, with acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the combination antimalarial CGP 56697 (artemether and benflumetol), and to compare it with chloroquine, the standard drug used for malaria treatment in the Kilombero area. Children who had received rescue medication within the first 48 h or had a negative slide at the same time were excluded. Seven-day parasitological cure rates were 94% (95% CI 88-97.5) for CGP 56697 and 35.4% (95% CI 25.9-45.8) for chloroquine. Using the same definition, the 14-day parasitological cure rates were 86.4% (95% CI 78.5-92.2) for CGP 56697 and 10.3% (95% CI 5.1-18.1) for chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by chloroquine. There were no major adverse events with either drug. CGP 56697 is highly efficacious against P. falciparum in this area of Tanzania. The study contributes to the discussion on treatment strategies, particularly whether chloroquine may still fulfil its role as first-line drug in an area of high malaria transmission and very high levels of chloroquine resistance.

Acute Disease↗
PubMed1998

Distinction of recrudescences from new infections by PCR-RFLP analysis in a comparative trial of CGP 56 697 and chloroquine in Tanzanian children.

OBJECTIVE: To test the efficacy of a new compound drug (CGP 56697) against acute, uncomplicated falciparum malaria. METHOD: Reappearing parasites were analysed by PCR-RFLP within a randomized controlled trial. 130 patients received chloroquine and 130 patients were treated with CGP 56697. Samples from 96 patients with parasitological failure were tested by PCR-RFLP for MSP2 of Plasmodium falciparum. Seven days after treatment 32 patients of the chloroquine control group with reappearing parasites were tested by PCR and one infection was unequivocally determined as a new infection. After 7 days, in the CGP 56697 group, 6 samples were tested in which one new infection was identified. Similar observations were made one and three weeks later in both groups. RESULTS: Although a high multiplicity of infections on admission was observed, there was no significant correlation between multiplicity and either recrudescence or new infection. Patients in both treatment groups with subsequent recrudescent parasites had higher initial mean parasite densities than patients who cleared. Those of the patients with recrudescent parasites who were treated with CGP 56697 had higher initial parasite densities than those treated with chloroquine. The rate of re-infection increased with time as expected in holoendemic areas and appeared to be higher in chloroquine patients. Generally, CGP 56697 showed a superior clearance rate, successfully cleared higher parasite densities and suppressed new infections over a longer period of time. CONCLUSION: The PCR analysis confirmed that reinfections beyond day 7 are significant in areas highly endemic for malaria and showed the necessity of excluding these when estimating 14 day clearance rates. Provided new infections are excluded, the 28-day clearance rate can also be used to determine the efficacy of antimalarial drugs in highly endemic areas, and adds to our knowledge of drug resistance and dynamics of infections in people living in such areas.

Acute Disease↗
PubMed1996

Evolutionary dynamics of non-coding sequences within the class II region of the human MHC.

About 40% (350 kb) of the human MHC class II region has been sequenced and a coordinated effort to sequence the entire MHC is underway. In addition to the coding information (22 genes/pseudogenes), the non-coding sequences reveal novel information on the organisation and evolution of the MHC as demonstrated here by the example of a 200 kb contig that has been analysed for local and global features. In conjunction with cross-species comparisons, our results present new evidence on the structure of isochores, the evolutionary dynamics of repeat-mediated recombination and its effect on certain MHC encoded genes, and a higher than average degree of natural polymorphism that has implications for sequencing the human genome. We also report the finding of a class I-related pseudogene (HLA-ZI) in the middle of the class II region, which provides the first direct evidence for DNA exchange between these two related regions in man.

Amino Acid Sequence↗
PubMed1996

Divergent intron arrangement in the MB1/LMP7 proteasome gene pair.

We sequenced the human MB1 gene from a cosmid clone mapping to chromosome 14q11.2-12. The gene spans about 6 kilobases and contains three exons and two introns. There was no evidence of an alternative leader exon, which is a characteristic of the major histocompatibility complex (MHC)-encoded LMP7 gene, the closest relative of MB1, with which it shares 67% amino acid identity. Conceptual translation of the 5' end of the gene calls for a cleaved leader sequence of 59 amino acids, consistent with western blot data. None of the MB1 gene's three exons were coincident with any of the six exons in LMP7. In contrast, in the delta-encoding gene and its counterpart, the MHC-encoded LMP2 gene (59% amino acid identity), all six exons are arranged at equivalent positions in respect to the coding frame. The unique structure of MB1 implies a separate origin or different selection pressures acting at this particular locus. DNA repeat analysis provides information on the minimum time of separation of the MB1/LMP7 pair of genes.

Base Sequence↗
PubMed1996

DNA sequencing of the MHC class II region and the chromosome 6 sequencing effort at the Sanger Centre.

The human Major Histocompatibility Complex (MHC) is located on the short arm of chromosome 6 (6p21.3) and spans about 4 Mb. According to different gene families the MHC is subdivided into a class I, class II and class III region and many of its gene products are associated with the immune system and the susceptibility to various diseases. To date, we have sequenced about 40% (400 kb) of the class II region between HLA-DP and HLA-DQ and a coordinated effort to sequence the entire MHC is well underway. Analysis of the sequence revealed several novel genes and provides new insights into the molecular organisation and evolution of the MHC. All our data are publicly available via the MHC database (MHCDB) which allows rapid access, retrieval and display in the context of other MHC associated data. MHCDB is online available at (http:(/)/www.hgmp.mrc.ac.uk/) and, together with all our sequences also via anonymous ftp (ftp.icnet.uk/icrf-public).

Animals↗