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Biomedical subjects

C Mundy

Publications and source records attributed to C Mundy.

13 recordsLinked to original sources
PubMed2005

Evaluation and costs of different haemoglobin methods for use in district hospitals in Malawi.

AIMS: To evaluate the characteristics of manual haemoglobin methods in use in Malawi and provide evidence for the Ministry of Health in Malawi to enable them to choose a suitable method for district hospitals. METHODS: Criteria on accuracy, clinical usefulness, user friendliness, speed, training time, and economic costs were determined by local health professionals and used to compare six different manual haemoglobin methods. These were introduced sequentially into use in a district hospital in Malawi alongside the reference method. RESULTS: HemoCue was the optimal method based on most of the outcome measures but was also the most expensive (0.75 US dollars/test). DHT meter and Jenway colorimeter were the second choice because they were cheaper (0.20-0.35 US dollars/test), but they were not as accurate or user friendly as HemoCue. CONCLUSIONS: The process for choosing appropriate laboratory methods is complex and very little guidance is available for health managers in poorer countries. This paper describes the development and testing of a practical model for gathering evidence about test efficiency that could be adapted for use in other resource poor settings.

Clinical Competence↗
PubMed2001

The human genome project: a historical perspective.

Efforts in genomics over the last decade have created a stream of opportunities for drug discovery. High-throughput DNA sequencing has forced a re-definition of the paradigm for identification and validation of targets for drug development. One purpose of this review is to delineate the different approaches to sequence data generation and to establish their various uses for the definition of gene function. There still remain crucial dilemmas for the pharmaceutical industry. The multitude of potential targets can each absorb enormous validation costs and the vast majority are likely to prove academically interesting but useless for drug development. An additional dimension arises from the importance of sequence variation between different individuals. These differences can determine response to therapy and must inform both the drug development process and healthcare delivery. This presents great challenges and opportunities for drug companies, their customers and society as a whole. I will review the technological aspects in some detail and give my view of the legal and social aspects. The field of bioinformatics is at the core of functional and pharmacogenomics and advances will depend on the continuing evolution of tools to interpret data. For the most part this evolution is reviewed in the context of specific application areas rather than as a discrete field, in recognition of its all-pervasive effects.

Animals↗
PubMed2001

Serological and molecular screening for viruses in blood donors from Ntcheu, Malawi: high prevalence of HIV-1 subtype C and of markers of hepatitis B and C viruses.

The prevalence of antibodies to human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), human T lymphotropic virus I (HTLV-I), and hepatitis B (HBV) surface antigen (HBsAg) was determined in blood donors from Ntcheu, Malawi. Each donation was also screened for HIV-1 RNA and HCV RNA. Among 159 blood donations, the prevalence of HIV-1 infection was 10.7%, 8.1% for HBV carriage, 6.8% for anti-HCV, and 2.5% for anti-HTLV-I. HIV-1/HTLV-I and HIV-1/HCV dual infections were observed in 1.2% of the donations. Consequently, 13% of blood donors from Ntcheu should be deferred for retroviral infections and 15% for hepatitis viral infections. Sequence analyses of the HIV-1 strains revealed a relatively homogeneous circulation of subtype C viruses in Malawi. These findings confirm the high endemicity of blood-borne viruses in Malawi and the need for a sensitive viral screening of blood donations to improve blood safety.

Amino Acid Sequence↗
PubMed2000

Screening tuberculosis suspects using two sputum smears.

SETTING: Ntcheu district hospital, Malawi. OBJECTIVE: To assess a screening strategy for tuberculosis (TB) suspects using two sputum smears. DESIGN: A strategy of screening all TB suspects with two sputum smears for 6 months (1 July-31 December 1998) was compared with the period 1 January to 30 June 1998 during which the strategy of screening TB suspects with three sputum smears was in use. All chest radiographs of patients with negative sputum smears were assessed, and in those with pulmonary cavities and extensive disease a third sputum smear was examined. Data were collected from the laboratory sputum register and the TB register. The two 6-month periods were compared. RESULTS: In the laboratory register, using a two-sputum strategy, 186 (16%) of 1152 TB suspects were smear-positive, a result that was no different than when the three-sputum strategy was used, where 173 (16%) of 1106 TB suspects were smear-positive. The clinical pattern of TB using the different screening strategies was similar, with 58% of registered patients smear-positive with the two-sputum strategy and 54% smear-positive with the three-sputum strategy. In the first 6 months 3177 sputum smears were examined compared to 2266 smears in the second 6 months, a 29% reduction in the number of smears examined. The cost of consumables using the strategy of three sputum smears was USD $731 compared with USD $521 using the strategy of two sputum smears. C O N C L U S I O N S: Screening TB suspects using two sputum smears is as effective as screening using three sputum smears, and is associated with less laboratory work and savings in costs.

Cost Control↗
PubMed1999

Roles of the "dispensable" portions of RAG-1 and RAG-2 in V(D)J recombination.

V(D)J recombination is initiated by introduction of site-specific double-stranded DNA breaks by the RAG-1 and RAG-2 proteins. The broken DNA ends are then joined by the cellular double-strand break repair machinery. Previous work has shown that truncated (core) versions of the RAG proteins can catalyze V(D)J recombination, although less efficiently than their full-length counterparts. It is not known whether truncating RAG-1 and/or RAG-2 affects the cleavage step or the joining step of recombination. Here we examine the effects of truncated RAG proteins on recombination intermediates and products. We found that while truncated RAG proteins generate lower levels of recombination products than their full-length counterparts, they consistently generate 10-fold higher levels of one class of recombination intermediates, termed signal ends. Our results suggest that this increase in signal ends does not result from increased cleavage, since levels of the corresponding intermediates, coding ends, are not elevated. Thus, removal of the "dispensable" regions of the RAG proteins impairs proper processing of recombination intermediates. Furthermore, we found that removal of portions of the dispensable regions of RAG-1 and RAG-2 affects the efficiency of product formation without altering the levels of recombination intermediates. Thus, these evolutionarily conserved sequences play multiple, important roles in V(D)J recombination.

DNA Nucleotidyltransferases↗
PubMed1998

A high-resolution microsatellite map of the mouse genome.

The European Collaborative Interspecific Backcross (EUCIB) resource was constructed for the purposes of high-resolution genetic mapping of the mouse genome (). The large Mus spretus/C57BL/6 backcross of 982 progeny has a genetic resolution of 0.3 cM at the 95% confidence level ( approximately 500 kb in the mouse genome). We have used the EUCIB mapping resource to develop a genome-wide high-resolution genetic map incorporating 3368 microsatellites. The microsatellites are distributed among 2302 genetically separated bins with 1.46 markers per bin on average. Average bin separation is 0.61 cM. This high-resolution genetic map will aid the construction of a robust physical map of the mouse genome.

Animals↗
PubMed1998

District sputum smear microscopy services in Malawi.

SETTING: Government hospitals and health centres in 23 districts in Malawi. OBJECTIVE: To determine 1) the number and smear-positivity rate of sputum samples submitted at health centres and hospitals, and 2) the time for sputum samples to get from health centres to smear examination. DESIGN: Prospective data collection on sputum specimens coming from health centres to hospital laboratories, and over the equivalent time period, retrospective data collection from laboratory sputum registers. RESULTS: Information was collected over a period of 5.6 months during 1997. Of 21 527 patients submitting sputum samples, 16995 (79%) were from within the hospital and 4532 (21%) were from health centres. Of 15 833 new TB suspects, 12 804 (81%) submitted sputum within the hospital and 3029 (19%) were from health centres. The overall smear-positivity rate was 11.9%: the proportion of new suspects who were smear-positive was significantly higher in health centres (14.1%) compared with hospital-based patients (11.4%, P < 0.05); 27% of all sputum specimens from health centres took 8 days or longer to get to smear examination. Sputum smears were positive from 1-30 days between submission and laboratory examination. CONCLUSION: Fewer sputum samples are submitted at health centres compared with hospitals, and there may be long delays between sputum submission and smear examination. The precise reasons are unclear, but health centre staff need training about the importance of timely case finding procedures.

Community Health Centers↗
PubMed1997

High-throughput microsatellite analysis using fluorescent dUTPs for high-resolution genetic mapping of the mouse genome.

The use of fluorescent end-labeled primers has proved successful for rapid, semiautomated genotyping of microsatellite loci. However, custom synthesis is expensive and costs can be prohibitive when a wide range of markers is to be analyzed for only a few genotypings. This particularly applies to high-resolution genetic mapping in the mouse either in the construction of global maps or in the production of local high-resolution genetic maps for positional cloning. We demonstrate here the use of fluorescent dUTPs for cost-effective, high-throughput microsatellite genotyping in the mouse. This alternative to the use of fluorescent end-labeled primers for semiautomated genotyping is potentially applicable to the construction of linkage maps in other species.

Animals↗
PubMed1996

Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import.

The interaction of the human immunodeficiency virus type 1 (HIV-1) nucleoprotein complex with the cell nuclear import machinery is necessary for viral replication in macrophages and for the establishment of infection in quiescent T lymphocytes. The karyophilic properties of two viral proteins, matrix (MA) and Vpr, are keys to this process. Here, we show that an early step of HIV-1 nuclear import is the recognition of the MA nuclear localization signal (NLS) by Rch1, a member of the karyopherin-alpha family. Furthermore, we demonstrate that an N-terminally truncated form of Rch1 which binds MA but fails to localize to the nucleus efficiently blocks MA- but not Vpr-mediated HIV-1 nuclear import. Correspondingly, NLS peptide inhibits the nuclear migration of MA but not that of Vpr and prevents the infection of terminally differentiated macrophages by vpr-defective virus but not wild-type virus. These results are consistent with a model in which Rch1 or another member of the karyopherin-alpha family, through the recognition of the MA NLS, participates in docking the HIV-1 nucleoprotein complex at the nuclear pore. In addition, our data suggest that Vpr governs HIV-1 nuclear import through a distinct pathway.

Amino Acid Sequence↗
PubMedDate not supplied

Use of clinical judgement to guide administration of blood transfusions in Malawi.

The aim of this study was to investigate whether clinicians in Malawi could use clinical judgement alone to administer blood transfusions in accordance with guidelines. Clinicians at a district hospital did not use the Lovibond Comparator haemoglobin results provided by their laboratory as they felt them to be unreliable, preferring instead to rely on their clinical judgement alone to guide transfusion practice. Their transfusion practice and the Lovibond haemoglobin results were monitored against the World Health Organization recommended haemiglobincyanide method for haemoglobin measurement without the clinicians having access to this result. The Lovibond Comparator method was shown to have a sensitivity of only 21% to detect trigger haemoglobin values for transfusion published in local guidelines. Without access to a useful haemoglobin result, clinicians gave 67% of transfusions in accordance with the haemoglobin trigger values in the guidelines. This study shows that clinical features alone can provide a reasonable guide about the need for transfusion, and that poor quality laboratory tests limit the effectiveness of transfusion guidelines.

Anemia↗