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Biomedical subjects

B G Williams

Publications and source records attributed to B G Williams.

At least 37 records · Page 2Linked to original sources

Prevalence of occupational lung disease in a random sample of former mineworkers, Libode District, Eastern Cape Province, South Africa.

BACKGROUND: Gold mineworkers in South Africa are exposed to high levels of silica dust as a result of which they are at risk of developing silicosis, which is a compensable disease. The incidence of tuberculosis is also high. METHODS: To determine the prevalence of occupational lung disease and the previous compensation history in former migrant mineworkers, a study was undertaken in a random sample of men living in Libode, a rural district of Eastern Cape Province, South Africa. Two hundred thirty-eight ex-mineworkers were examined according to a protocol that included chest radiography and spirometry. Chest radiographs were read into the International Labour Organisation (ILO) classification for pneumoconioses by two readers. RESULTS: The mean age was 52.8 years, and the mean length of service was 12.15 years. The prevalence of pneumoconiosis (> or = ILO 1/0) was 22% and 36% (variation by reader). For both readers, a significant association between length of service and pneumoconiosis and between pneumoconiosis and reduction in FVC and FEV was found. Twenty-four percent of study subjects were eligible for compensation. CONCLUSION: There is a high prevalence of previously undiagnosed, uncompensated pneumoconiosis in the study group. As a result of the failure to diagnose and compensate occupational lung disease, the social and economic burden of such disease is being borne by individuals, households, and the migrant labor-sending communities as a whole.

Adult↗

The lack of circadian timing in two intertidal invertebrates and its significance in the circatidal/circalunidian debate.

The control of the timing of gaping in the clam Austrovenus stutchburyi does not involve a circadian mechanism. The lack of a circadian timer is shown by the uniform pattern in gaping in constant conditions (CC) regardless of the relationship between the tidal cycle and the day/night cycle at the time of collection; it is also shown by the fact that, in nontidal conditions, a 24 h light-dark (LD) cycle fails to entrain persistent rhythmicity. The crab Macrophthalmus hirtipes also lacks a circadian oscillator. Both of these intertidal dwellers, however, exhibit endogenous tidal rhythmicity. The features of the tidal patterns they display in CC can be accounted for using the circalunidian (i.e., approximately 24.8 h) model of a tidal timing system but, as they lack circadian timers, cannot be explained by the circatidal (i.e., approximately 12.4 h)/circadian model. This demonstrates that, of the two hypothetical models of the clock system driving endogenous tidal rhythms, only the circalunidian one has universal applicability.

Animals↗

Infectious disease persistence when transmission varies seasonally.

The generation reproduction number, R0, is the fundamental parameter of population biology. Communicable disease epidemiology has adopted R0 as the threshold parameter, called the basic case reproduction number (or ratio). In deterministic models, R0 must be greater than 1 for a pathogen to persist in its host population. Some standard methods of estimating R0 for an endemic disease require measures of incidence, and the theory underpinning these estimators assumes that incidence is constant through time. When transmission varies periodically (e.g., seasonally), as it does for most pathogens, it should be possible to express the criterion for long-term persistence in terms of some average transmission (and hence incidence) rate. A priori, there are reasons to believe that either the arithmetic mean or the geometric mean transmission rate may be correct. By considering the problem in terms of the real-time growth rate of the population, we are able to demonstrate formally that, to a very good approximation, the arithmetic mean transmission rate gives the correct answer for a general class of infection functions. The geometric mean applies only to a highly restricted set of cases. The appropriate threshold parameter can be calculated from the average transmission rate, and we discuss ways of doing so in the context of an endemic vector-borne disease, canine leishmaniasis.

Animals↗

Multigenic drug resistance among inbred malaria parasites.

Recent population genetic studies on the malaria parasite Plasmodium falciparum have confirmed that selfing is more frequent where the transmission rate is lower, with inbreeding coefficients estimated to be 0.33 and 0.92 for sites in Tanzania and Papua New Guinea (PNG), respectively. These geographical differences in Plasmodium mating patterns have been linked to the rate of spread of chloroquine resistance CQR, which, according to some measures, has been slower in Tanzania than in PNG. It has been proposed that the former observation explains the latter, although the theoretical argument linking the two is based on limited simulation studies. Taking a more analytical approach here, we first establish the relevant relationship between the coefficient of inbreeding (F, within loci) and the recombination rate r, between loci, defining an 'effective recombination rate', r = r (1-F. We then show that the emergence of multigenic drug resistance can indeed be slowed (or even quickened) by more outcrossing, but only when resistance is determined by two or more genes, none of which independently confers significant protection. The resistance genes should both be initially rare, and subject to low selection pressure. The analysis does not completely discount the hypothesis that inbreeding significantly influences the spread of CQR, but we show that it can only do so under a restrictive set of conditions, and that these conditions are not satisfied by some laboratory and field data. We discuss some of the wider implications of these results for the evolution of multigenic resistance.

Animals↗

The entrainment of persistent tidal rhythmicity in a filter-feeding bivalve using cycles of food availability.

Austrovenus stutchburyi is an intertidal, burrowing, filter-feeding bivalve. It exhibits a strong, approximately tidal pattern in the time of gaping of its valves when in constant laboratory conditions. Individuals that have been held in laboratory conditions long enough to lose their overt gaping pattern will respond to pulses of algae made available at a tidal frequency by opening to coincide with the times when food is available and remaining closed at other times. The opening of the valves is not solely a response to the arrival of the food; usually, their opening anticipates the arrival of the regular food pulses. The tidal pattern seen during the pulsed food treatment will continue for two cycles when food is withheld, indicating the involvement of an internal timing mechanism that is responsive to pulses of food. The short persistence of the food-entrained rhythm in constant conditions suggests that the food-entrained oscillator is only a minor component of the timing system, and this conclusion is supported by the finding that for the first 4-5 days when freshly collected clams are held in the laboratory and supplied with food pulses around the times of expected high water, the "circa" period of their gaping rhythm is not adjusted to a strictly tidal one. The characteristics of the food-entrained oscillator are discussed in relation to existing knowledge of tidal oscillators and food-entrained circadian oscillators.

Animals↗

Measles vaccination policy.

Where immunization campaigns locally eliminate measles, it will be important to identify the vaccination policy most likely to prevent future epidemics. The optimum age for vaccination depends on the rate of decline of maternal antibody, because the presence of antibody reduces vaccine efficacy. The first part of this paper contains a quantitative reappraisal of the data on antibody decline and seroconversion rates by age. The decline in maternal antibody protection follows delayed exponentials, with delays of 2-4 months, and subsequent half-lives of 1-2 months. Using this result in an analytical mathematical model we find that the optimal age to administer a single dose of vaccine to children, which is independent of vaccine coverage, lies within the range 11-19 months. We also show that, where the optimal age cannot be met, it is better to err towards late rather than early vaccination. There are therefore two reasons why developing countries, which presently vaccinate during infancy because measles transmission rates are high should eventually switch to the second year of life. The possible gains from two-dose vaccination schedules are explored with respect to both coverage and efficacy. A two-dose schedule will be beneficial, in principle, only when there is a need to increase net vaccine efficacy, after coverage has been maximized with a one-dose schedule.

Antibodies, Viral↗

Interferon response in chronic myeloid leukaemia correlates with ABL/BCR expression: a preliminary study.

alpha-Interferon (IFN) has been used to induce cytogenetic remission in chronic myeloid leukaemia (CML), but there are few indicators to predict IFN response. The role of the chimaeric BCR/ABL gene in the malignant process is undisputed. There are, however, conflicting views as to whether the breakpoint site within the BCR gene, and the type of mRNA produced determine disease prognosis and progression. The function and clinical significance of the newly discovered ABL/BCR mRNA has not been investigated for a correlation with CML prognosis or response to therapy. We have used a two-step reverse transcriptase polymerase chain reaction (RT-PCR) to detect the transcripts of the chimaeric genes BCR/ABL, ABL/BCR, as well as the normal ABL and BCR genes in 24 CML patients treated with IFN. Because of the variable expression of the four transcripts at presentation, a correlation between gene expression, prognosis and clinical progression was examined. No correlation between prognosis and gene expression was seen. Also, no correlation was found between expression of BCR, ABL or BCR/ABL mRNA and response to treatment with IFN. However, 7/10 ABL/BCR mRNA positive patients achieved a major cytogenetic response to IFN; but of the 13 ABL/BCR mRNA negative patients, only two achieved a major cytogenetic response (P = 0.013). Further studies are required to confirm these findings.

Adolescent↗

A cost-benefit analysis of feeding in female tsetse.

Three models for feeding in female tsetse are considered. Model I: there is a prolonged non-feeding phase after each meal followed by feeding at a constant rate, with a constant probability of dying as a consequence of feeding. Model II: the feeding rate increases linearly after each meal. Model III: the feeding rate increases exponentially after each meal. In Models II and III the feeding hazard is a linear function of the probability of feeding. Production of viable female offspring is estimated under each model, making allowance for losses of adults due to starvation and to background and feeding mortality, losses of pupae due to predation and parasitization, and losses of young flies if their mothers take insufficient blood during pregnancy. Under Model I, if females require three meals to produce viable pupae in 9 days, then for a non-decreasing population with a background mortality of 1%/day, and 25% pupal losses due to predation and parasitism, the feeding risk must be < or = 5%/feed. At this maximum level the non-feeding phase should be 2-2.5 days for optimal productivity, with a mean feeding interval of 60-72 h. If the background mortality is 2%/day, feeding losses cannot exceed 1%/feed for a non-decreasing population. If four or five meals are required for the production of fully viable pupae, the optimal values of the non-feeding phase and mean feeding interval tend towards 1 and 2 days respectively. Under Models II and III the mean feeding interval is 50-60 h for optimal productivity (with variances 3 times as large as for Model I), in good agreement with estimates from recent models for feeding and digestion. Field evidence suggests that feeding tsetse take greater risks as their fat levels dwindle. This should result in feeding (and feeding mortality) rates which increase during the feeding phase--as assumed in Models II and III but not in Model I. These models allow greater flexibility than Model I, because flies can feed early in the hunger cycle, at low probability, as long as the feeding risk is also low.

Animals↗

Activated protein c resistance (APC) and inherited factor V (FV) mis-sense mutation in patients with venous and arterial thrombosis in a haematology clinic.

BACKGROUND: Inherited factor V (FV) mis-sense point mutation has recently been identified as a major cause of familial venous thrombosis. The incidence of this congenital haemostatic disorder in Australia is unknown. AIM: To examine the incidence of this congenital defect in patients with thrombosis attending a haematology clinic. METHODS: Individuals investigated or treated for venous and arterial thrombosis over a four month period, as well as those who were on anticoagulant for valvular replacement or arrhythmia were studied for the presence of FV mis-sense point mutation, FV Q506 (G to A at nucleotide position 1691) by a polymerase chain reaction based test, and activated protein C (APC) resistance using an APTT based coagulation assay. RESULTS: Forty-five patients with venous thromboembolism (VTE), 20 patients with coronary artery disease and 25 patients with valvular replacement or arrhythmia who were on anticoagulant were examined. The frequency of FV mis-sense point mutation in these three groups was 26.7%, 15% and 4% respectively. In this study, patients with FV Q506 were of a younger age and had a higher incidence of extensive thrombosis or recurrence as compared to those with the normal factor V gene. This mutation was found in a diverse group of people (four of the 12 patients were of non-European origin). Nearly 50% of these patients had other risk factors for VTE. The number of patients with a family history of VTE was similar for those with the FV mutation and the normal FV. CONCLUSION: This study confirms the high incidence of FV Q506 mutation in patients with VTE reported overseas. Several clinical features, i.e. young age of onset of VTE, high recurrence rate, diverse ethnic background and importance of associated risk factors are highlighted. The findings in this study also raise the possibility that this mutation may be a risk factor for arterial thrombosis. Large studies are required to substantiate these findings.

Adult↗

A measurement of self-esteem in pregnant teenagers.

Low self-esteem is often viewed as an important factor in unprotected sexual activity and pregnancy in adolescents. The purpose of this pilot study was to determine the level of self-esteem in single pregnant teenagers. The Culture-Free Self-Esteem Inventory (CFSEI) and a researcher-developed demographic questionnaire were used to measure self-esteem in 19 pregnant teenagers and to gather demographic information about them. The mean score for total self-esteem was 16.4, which is an intermediate level of self-esteem according to Battle's classification of scores. Mean scores for general self-esteem (6.31), academic self-esteem (3.68), parental self-esteem (3.37), and social self-esteem (3.15) were also at intermediate levels. The pregnant teenagers in this study did not have low self-esteem, according to Battle's general population norms. Suggestions for further research include replication of this study with a larger sample and comparison of self-esteem in pregnant and nonpregnant teenagers.

Adolescent↗

Maximum likelihood for parasitologists.

In quantitative biology, observed data are fitted to a model that captures the essence of the system under investigation in order to obtain estimates of the parameters of the model, as well as their standard errors and interactions. The fitting is best done by the method of maximum likelihood, though least-squares fits are often used as an approximation because the calculations are perceived to be simpler. Here Brian Williams and Chris Dye argue that the method of maximum likelihood is generally preferable to least squares giving the best estimates of the parameters for data with any given error distribution, and the calculations are no more difficult than for least-squares fitting. They offer a relatively simple explanation of the methods and describe its implementation using examples from leishmaniasis epidemiology.

Journal Article↗

Influence of needle gauge in Mantoux skin testing.

STUDY OBJECTIVE: To determine the influence of needle gauge in Mantoux skin testing for tuberculosis. DESIGN: Randomized selection of either a 27- or 30-gauge needle for Mantoux skin test placement; observer-blinded. SETTING: Annual hospital employee screening. PARTICIPANTS: Six hundred twenty-five employees working in clinical and laboratory research environments. RESULTS: Blinded observers found that the use of 27-gauge needles caused increased bleeding and bruising compared with 30-gauge needles (p < or = 0.007 for each). However, the 27-gauge needle produced larger blebs and less leakage of tuberculin solution (p < or = 0.0003). CONCLUSION: Smaller gauge needles could potentially cause false-negative screening results because of decreased antigen delivery. Use of needle gauges smaller than 27 gauge should be avoided until their reliability is validated.

Evaluation Studies as Topic↗

A Ph+ acute myeloid leukaemia expressing both CML-type and ALL-type BCR/ABL mRNA transcripts.

This report describes a patient presenting with acute myeloid leukaemia (AML-FAB classification M2). Phenotypic markers were positive for cells of the myeloid lineage, but negative for monocyte/macrophage, megakaryocyte, and T-cell lineages. The occasional blast was positive for CALLA. All blasts carried the Philadelphia chromosome (Ph+), with 20% also harbouring a monosomy 7 (a cytogenetic marker for AML). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the presence of two BCR/Abl mRNA transcripts; b2a2, the CML-type and E1a2, the ALL-type. Immunoglobulin (Ig) gene analysis demonstrated the presence of a small population of cells containing rearranged Ig genes. After a short remission, the patient relapsed. At relapse the leukaemia had undergone a major phenotypic switch from AML to ALL, with blasts bearing B-cell markers. Ig gene analysis confirmed a monoclonal population of B-cells. The Ph+ persisted, but the monosomy 7 had disappeared. The same two BCR/Abl mRNA transcripts were found at relapse as at presentation. To our knowledge, this is the first report of an AML simultaneously expressing BCR/Abl transcripts from both the minor and major BCR. The possible mechanisms of this dual expression are discussed.

Base Sequence↗

Malnutrition, age and the risk of parasitic disease: visceral leishmaniasis revisited.

Children are said to be at greater risk of developing visceral leishmaniasis (VL) when they are younger and more malnourished. If malnutrition really is associated with VL, this potentially fatal and visible disease may be a general indicator of community health among the rural and suburban poor. Previous conclusions reached about the roles of malnutrition and age in VL epidemiology are questionable because they may have been confounded by transmission rate, because they have not been able to distinguish between different mechanisms of acquiring immunity, and because empirical observations have not been compared with theoretical expectations. Here we offer a framework with which to investigate these questions quantitatively, and do so with published data from endemic areas of Brazil. We conclude that children are indeed more susceptible to VL when they are younger and more malnourished, but it remains unclear whether the immunity to VL acquired with age is always acquired as a result of infection. The significance for leishmaniasis control, and for the control of other diseases associated with malnutrition, will depend on underlying mechanisms, which are not yet understood.

Adolescent↗

Isolation of a tomato alcohol dehydrogenase 2-encoding cDNA using phage-promoted antibody screening of a plasmid cDNA library.

We describe the cloning of a cDNA encoding tomato alcohol dehydrogenase 2 (Adh2) by screening plasmid cDNA clones in phage plaques. A cDNA library constructed in a plasmid vector containing a unique SstI site at the 5' end of the cDNA insert was transferred into the SstI site of the lacZ gene of phage lambda Charon16, and screened by anti-Adh2 antibody to identify reactive plaques. Plasmid cDNA clones were recovered by SstI digestion, ligation, and transformation from phage minipreps for subsequent characterization. This system preserves the original plasmid library for subsequent screening with nucleic acid probes to identify full-length, multiple independent, or related cDNA clones not subject to the selection pressure of phage growth or lysogeny, or negative antibody reactivity. Thirty-two cDNA clones were identified with polyclonal antiserum to Adh2. Three of these reacted with monoclonal anti-Adh2 and only those three hybridized to maize adh1 sequence. One of these cDNAs, Adh31, was further characterized as encoding Adh2 by hybrid-selected translation and high sequence homology with the maize adh1 gene.

Alcohol Dehydrogenase↗

Monitoring trypanosomiasis in space and time.

The paper examines the possible contributions to be made by Geographic Information Systems (GIS) to studies on human and animal trypanosomiasis in Africa. The epidemiological characteristics of trypanosomiasis are reviewed in the light of the formula for the basic reproductive rate or number of vector-borne diseases. The paper then describes how important biological characteristics of the vectors of trypanosomiasis in West Africa may be monitored using data from the NOAA series of meteorological satellites. This will lead to an understanding of the spatial distribution of both vectors and disease. An alternative, statistical approach to understanding the spatial distribution of tsetse, based on linear discriminant analysis, is illustrated with the example of Glossina morsitans in Zimbabwe, Kenya and Tanzania. In the case of Zimbabwe, a single climatic variable, the maximum of the mean monthly temperature, correctly predicts the pre-rinderpest distribution of tsetse over 82% of the country; additional climatic and vegetation variables do not improve considerably on this figure. In the cases of Kenya and Tanzania, however, another variable, the maximum of the mean monthly Normalized Difference Vegetation Index, is the single most important variable, giving correct predictions over 69% of the area; the other climatic and vegetation variables improve this to 82% overall. Such statistical analyses can guide field work towards the correct biological interpretation of the distributional limits of vectors and may also be used to make predictions about the impact of global change on vector ranges. Examples are given of the areas of Zimbabwe which would become climatically suitable for tsetse given mean temperature increases of 1, 2 and 3 degrees Centigrade. Five possible causes for sleeping sickness outbreaks are given, illustrated by the analysis of field data or from the output of mathematical models. One cause is abiotic (variation in rainfall), three are biotic (variation in vectorial potential, host immunity, or parasite virulence) and one is historical (the impact of explorers, colonizers and dictators). The implications for disease monitoring, in order to anticipate sleeping sickness outbreaks, are briefly discussed. It is concluded that present data are inadequate to distinguish between these hypotheses. The idea that sleeping sickness outbreaks are periodic (i.e. cyclical) is only barely supported by hard data. Hence it is even difficult to conclude whether the major cause of sleeping sickness outbreaks is biotic (which, in model situations, tends to produce cyclical epidemics) or abiotic.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗