PubMed Health⌕ Search

Biomedical subjects

S Floyd

Publications and source records attributed to S Floyd.

At least 19 recordsLinked to original sources

Time delays between patient and laboratory selectively affect accuracy of helminth diagnosis.

Studies of intestinal helminth infections are influenced by the constraints of sample collection, as identification of helminth ova in stools is affected by the time since evacuation from the host. Different methods may be required to optimise diagnostic sensitivity under different study conditions. In the context of studies in rural Malawi, we collected stool samples with different time delays from production by subjects to sample collection by field staff, to examination in the laboratory. Stools were processed by Kato-Katz (KK) or formol-ether concentration (FEC) methods. Hookworm and Schistosoma mansoni were the most common helminths identified. The prevalence of hookworm was higher with KK (270/988, 27%) than with FEC (191/988, 19%). Comparison was made between the results from the two methods according to the timing of the processing steps. Delays in processing did not affect retrieval of S. mansoni. A decrease in sensitivity of almost 50% for detection of hookworm was observed with either method when preservation/refrigeration was delayed by more than 3h. A delay of 1 day from refrigeration or preservation to laboratory processing also reduced the sensitivity for hookworm by 50% for both methods. Care must be taken in studies of multiple helminth infections owing to the selective reduction of hookworm ova during transport. This is particularly critical when samples are not preserved, even over short periods of time, and even with formalin preservation.

Animals↗

The influence of previous exposure to environmental mycobacteria on the interferon-gamma response to bacille Calmette-Guérin vaccination in southern England and northern Malawi.

We report a large study of the effect of BCG vaccination on the in vitro 6-day whole blood interferon-gamma (IFN-gamma) response to antigens from eight species of mycobacteria among schoolchildren in south-eastern England, where bacille Calmette-Guérin (BCG) vaccination is highly protective against pulmonary tuberculosis, and among young adults in northern Malawi, where BCG vaccination is not protective. In the UK children, BCG induced an appreciable increase in IFN-gamma response to antigens from most species of mycobacteria. The degree of change was linked to the relatedness of the species to Mycobacterium bovis BCG, and provides further evidence of the cross-reactivity of mycobacterial species in priming of the immune system. IFN-gamma responses to purified protein derivatives (PPDs) from M. tuberculosis and environmental mycobacteria were more prevalent in the Malawian than the UK group prior to vaccination; BCG vaccination increased the prevalence of responses to these PPDs in the UK group to a level similar to that in Malawi. There was no evidence that the vaccine-induced change in IFN-gamma response was dependent upon the magnitude of the initial response of the individual to environmental mycobacteria in the United Kingdom or in Malawi. These observations should assist the development and interpretation of human clinical trials of new vaccines against M. tuberculosis in areas of both low and high exposure to environmental mycobacteria.

Adolescent↗

Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption: effects on plasma lipoprotein and carotenoid metabolism.

BACKGROUND: Regular intake of plant sterol (phytosterol)-enriched foods enhances the cholesterol lowering effect of diets. One side effect associated with plant sterol consumption is a modest reduction in plasma carotenoid concentrations. This study investigated the effect of consuming a low-fat National Cholesterol Education Programme (NCEP) Step 1 diet, including a low-fat plant sterol ester (PSE)-enriched spread on cholesterol metabolism to determine if specific dietary advice to increase daily fruit and vegetable intake could prevent reduced plasma carotenoid concentrations. MATERIALS AND METHODS: In this randomised, crossover double-blind trial, 48 hypercholesterolaemic men received 21 g day(-1) of a low-fat PSE-enriched spread or placebo for 3 weeks, interrupted by 3 weeks washout. Individuals also adhered to a NCEP Step 1 diet and repeated 3-day food diaries monitored adherence. Specific advice was provided to increase dietary fruit and vegetable intakes. Fasting blood samples were collected at pre- and post-intervention for lipoprotein and carotenoid analysis. RESULTS: Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were significantly (P <0.05) reduced, by 4.6 and 7.1%, respectively, after the PSE-enriched low-fat spread. Plasma apo B concentrations were significantly (P <0.0005) lower after the PSE spread. PSE consumption was also associated with significantly (P <0.05) lower total plasma beta-carotene concentrations, but this change was not significant after lipid standardisation. PSE consumption had no effect on retinol, alpha-carotene, gamma-tocopherol, alpha-tocopherol, lutein, zeaxanthin, beta-crypyoxanthin or lycopene concentrations. CONCLUSION: Dietary advice to increase daily fruit and vegetable consumption may be effective in preventing a reduction in plasma carotenoid concentrations previously associated with PSE consumption. Further, PSE incorporated in a low-fat spread and consumed as part of a NCEP Step 1 diet are effective in reducing total and LDL cholesterol.

Adult↗

Tuberculosis and gender: exploring the patterns in a case control study in Malawi.

BACKGROUND: In many populations there is an excess of tuberculosis in young women and older men. We explored possible explanations for these patterns, concentrating on human immunodeficiency virus (HIV) status, pregnancy, smoking, cooking smoke exposure, contact with tuberculosis cases within the household or outside, and gender differences in health service usage and diagnostic delay. DESIGN: Case control study in Karonga District, Malawi. METHODS: Cases were new tuberculosis patients with bacteriological or histological evidence of tuberculosis. Controls were selected in the community using field-based random sampling. RESULTS: The study included 598 tuberculosis cases and 992 controls, with an excess of tuberculosis in young females and older males. This was more marked in HIV-positive individuals. HIV infection was a similarly strong risk factor for tuberculosis in both men and women. Tuberculosis was associated with having a family or household contact with tuberculosis for both men and women. For women, but not men, contacts outside the close family and household were also a risk factor for tuberculosis. Tuberculosis was not associated with current or recent pregnancy, or with smoking or smoke exposure. There were no differences between men and women in health service usage or delay. CONCLUSIONS: In this population, HIV infection and contacts with known tuberculosis patients are important determinants of the gender distribution of cases.

Adolescent↗

Interferon-gamma and skin test responses of schoolchildren in southeast England to purified protein derivatives from Mycobacterium tuberculosis and other species of mycobacteria.

The immune responses of schoolchildren in southeast England to Mycobacterium tuberculosis and other species of mycobacteria were studied prior to vaccination with bacille Calmette-Guérin (BCG). Data are presented for tuberculin (Heaf) skin test and interferon-gamma (IFN-gamma) responses to M. tuberculosis purified protein derivative (PPD), and IFN-gamma responses to PPDs from eight other environmental mycobacteria, measured in 424 schoolchildren (13-15 years of age). Responses to M. tuberculosis PPD were detected in 27% of schoolchildren by in vitro IFN-gamma response and in 20% by the Heaf test. IFN-gamma responses were more prevalent to PPDs from species of mycobacteria other than M. tuberculosis, predominantly those of the MAIS complex and M. marinum (45-60% responders). Heaf test and IFN-gamma responses were associated (P<0.001) for M. tuberculosis, MAIS and M. marinum. These findings have implications for appropriate implementation of vaccination against tuberculosis.

Adolescent↗

A comparison of dual skin test with mycobacterial antigens and tuberculin skin test alone in estimating prevalence of Mycobacterium tuberculosis infection from population surveys.

SETTING: City of Manaus, Amazonas, Brazil. OBJECTIVE: To compare estimates of Mycobacterium tuberculosis infection prevalence obtained using traditional tuberculin skin test (TST) criteria and dual skin test (DST) data. METHODS: A total of 1070 schoolchildren received DST with tuberculin and four environmental mycobacteria sensitins. Responses were classified as sensitin-dominant, tuberculin-dominant or non-dominant. Positive predictive values (PPV) were defined using 'narrow' and 'wide' standards based on DST responses. These predictive values were derived for each category of tuberculin indurations, and were used to calculate the prevalence estimates. RESULTS: Using DST data, the estimates of M. tuberculosis prevalence for scar-negative children were 7.4% (M. avium) and 7.8% (M. scrofulaceum) using the 'narrow' standard, and 16.9% (M. avium) and 15.2% (M. scrofulaceum) using the 'wide' standard. The percentage with TST > or =10 mm was 11.5%. Scar-positive children had higher estimates using both the 10 mm cut-off and DST data. CONCLUSION: In settings with a relatively low prevalence of M. tuberculosis infection and high cross-reactivity with environmental mycobacteria, DST can help to assess the validity of traditional thresholds for estimating the prevalence of M. tuberculosis infection. DST data with environmental antigens and tuberculin do not distinguish BCG-induced cross-reactivity.

Adolescent↗

Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi.

Interferon (IFN)-gamma responsiveness to 12 purified protein derivative (PPD) and new tuberculin antigens from 9 species of mycobacteria was assessed, using a whole blood assay, in 616 young adults living in northern Malawi, where Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination provides no protection against pulmonary tuberculosis. The prevalence of IFN-gamma responsiveness was highest for PPDs of M. avium, M. intracellulare, and M. scrofulaceum (the MAIS complex). Correlations between responsiveness paralleled genetic relatedness of the mycobacterial species. A randomized, controlled trial was carried out, to assess the increase in IFN-gamma responsiveness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccination. The BCG-attributable increase in IFN-gamma response to M. tuberculosis PPD was greater for individuals with low initial responsiveness to MAIS antigens than for those with high initial responsiveness. Although not statistically significant, the trend is consistent with the hypothesis that prior exposure to environmental mycobacteria interferes with immune responses to BCG vaccination.

Antigens, Bacterial↗

A comparison of two methods of assessment of maize varietal resistance to the maize weevil, Sitophilus zeamais Motschulsky, and the influence of kernel hardness and size on susceptibility.

Fifty-two maize varieties were screened for resistance to infestation by the maize weevil, Sitophilus zeamais, using assessment methods proposed by Dobie (J. Stored Products Res. 10 (1974) 183-197) and Urrelo et al. (J. Stored Products Res. 26 (1990) 100). The two methods gave similar assessments of maize susceptibility to S. zeamais. The Dobie method is preferred due to the lower total time required for assessment of relative susceptibility of maize varieties. The greatest disadvantage of the Urrelo method is the intensive labour requirements in the early stages of a trial, when numbers of eggs have to be counted, although it has the advantage that the assessment may be terminated upon emergence of the first F(1) adult. Two explanatory variables, kernel size and hardness, were investigated to determine whether they may be used as indicators of resistance. Results suggested that kernel size is the more important in determining resistance to attack by S. zeamais, with large kernels appearing to show greater resistance than small ones. Contrary to expectations, of the varieties tested, including local, hybrid and improved open pollinated (IOP) varieties, the local varieties were generally more susceptible. This may be related to kernel size, as all IOPs and hybrids tested had large kernels, whereas the majority of the local varieties had small ones. No clear relationship between weevil susceptibility and kernel hardness could be detected, although there was an indication that differences associated with kernel size varied depending on kernel hardness. None of the varieties tested showed high levels of resistance to attack by S. zeamais.

Journal Article↗

Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy.

More than 36000 individuals living in rural Malawi were skin tested with antigens derived from 12 different species of environmental mycobacteria. Most were simultaneously tested with RT23 tuberculin, and all were followed up for both tuberculosis and leprosy incidence. Skin test results indicated widespread sensitivity to the environmental antigens, in particular to Mycobacterium scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with evidence of exposure to 'fast growers' (i.e. with induration to antigens from fast growers which exceeded their sensitivity to tuberculin), but not those exposed to 'slow growers', were at reduced risk of contracting both tuberculosis and leprosy, compared to individuals whose indurations to the environmental antigen were less than that to tuberculin. This evidence for cross protection from natural exposure to certain environmental mycobacteria may explain geographic distributions of mycobacterial disease and has important implications for the mechanisms and measurement of protection by mycobacterial vaccines.

Adolescent↗

Relationship between IFN-gamma and skin test responsiveness to Mycobacterium tuberculosis PPD in healthy, non-BCG-vaccinated young adults in Northern Malawi.

SETTING: Rural northern Malawi, where vaccination with BCG Glaxo (1077) provides protection against leprosy but not against pulmonary tuberculosis. OBJECTIVE: To evaluate the patterns of responsiveness to purified protein derivative of Mycobacterium tuberculosis (PPD) in terms of delayed type hypersensitivity (DTH) and interferon-gamma (IFN-gamma) production. DESIGN: IFN-gamma was measured in 6 day whole blood cultures diluted 1 in 10, stimulated with PPD RT48, and the results compared to the DTH response to PPD RT23. A total of 633 individuals aged 12 to 28 years, without prior BCG vaccination, were recruited. RESULTS: Overall, 63% of subjects made a positive IFN-gamma response (defined as >62 pg/ml), and 37% gave a DTH induration of >5 mm. A strong correlation between skin test and IFN-gamma responses was observed, although with interesting exceptions: 13/270 individuals with zero DTH showed IFN-gamma responses >500 pg/ml, and 7/53 individuals with >10 mm induration showed IFN-gamma responses < or = 62 pg/ml. The prevalence of skin test responsiveness increased with age, and was higher among older males than females; age-sex patterns were less clear for IFN-gamma production. CONCLUSION: The 6 day IFN-gamma response to PPD correlates well with Mantoux skin test induration. The discordant individuals may represent important subsets in terms of protective immunity and risk of clinical tuberculosis.

Adolescent↗

Comparison of two versus three smears in identifying culture-positive tuberculosis patients in a rural African setting with high HIV prevalence.

SETTING: Karonga district, northern Malawi. OBJECTIVE: To compare the sensitivity and specificity of two versus three smears for the diagnosis of pulmonary tuberculosis in a setting with high HIV prevalence. DESIGN: A total of 1992 pulmonary tuberculosis suspects with three sputum smears taken over a 2-7 day period and at least one culture result were studied. Smears were auramine stained and examined using fluorescence microscopy, and positives were confirmed with Ziehl-Neelsen staining and light microscopy. Cultures were set up on Löwenstein-Jensen media. True negative and positive status was defined on the basis of culture. The sensitivity, specificity, and positive and negative predictive values of two and three smears were compared. RESULTS: Compared to culture, the sensitivity, specificity, and positive and negative predictive values of three smears were 70%, 98%, 92%, and 92%, respectively. Restriction to the first two smears gave similar results. Of those detected as smear-positive using three smears, at least 97% would have been detected by two. Among those with HIV serology results available, the sensitivity of two smears for detecting culture-positive tuberculosis was identical to that using three. CONCLUSION: In this setting, using fluorescence and light microscopy, collecting two smears rather than three would only marginally reduce sensitivity and would slightly improve the specificity of diagnosis of tuberculosis; this is unaffected by HIV status. The potential for improving specificity is important because of the costs of misdiagnosis. In practice, both sensitivity and specificity may be increased due to the time saved by examining two rather than three smears.

AIDS-Related Opportunistic Infections↗

A telemetry-based device to determine the force-displacement behaviour of materials in high impact loading situations.

Meaningful testing of stab resistant body armour requires the use of realistic body tissue simulants. A device for the determination of the force-displacement behaviour of materials in high impact loading situations has been developed for the testing of such simulants. Force measurement is achieved with the use of electrical foil strain gauges applied to a cylindrical load cell. A piezo-resistive accelerometer (+/- 500 g) is used to calculate the displacement of the device through double integration of its signal, with the impact velocity used as a boundary condition. The signals from the strain gauge circuit and the accelerometer are sampled at 2500 Hz. The data are transmitted to a receiver via telemetry using a 418 MHz FM transmitter and from the receiver to a laptop PC via the serial port. Calibration of the device is described and sample results showing forces up to 2500 N and displacements up to 0.04 m are presented.

Biomechanical Phenomena↗

BCG scars in northern Malawi: sensitivity and repeatability of scar reading, and factors affecting scar size.

SETTING: Karonga district, northern Malawi. OBJECTIVE: To assess the sensitivity and repeatability of BCG scar reading, and factors affecting scar size. DESIGN: Follow-up of individuals aged > 3 months who were recruited into a BCG vaccine trial (1986-1989), and of infants vaccinated in health centres (1989-1991), who were examined for presence and size of BCG scars in subsequent years. All examinations were carried out blind of information on true vaccination status or the results of previous examinations. RESULTS: For trial individuals who were considered scar negative at recruitment and received BCG, the sensitivity of scar reading was > or = 93%, repeatability was > or = 94% for those < 60 years old at vaccination, and only around 1% were assessed as having > 1 BCG scar post-vaccination. For infants vaccinated when < 1 month old in health centres, the proportion who still had recognisable scars 4 years later was < 80%. Scars were larger in individuals with a prior BCG vaccination, and for those aged 15-59 at vaccination the scars were approximately 1 mm larger for males than for females. CONCLUSIONS: A BCG scar is a highly sensitive and repeatable indicator of vaccination status when the vaccine is properly handled, delivered appropriately, and given at over 3 months of age, but not for vaccinations given within 1 month of birth. Given that most vaccinations in the world are given soon after birth, this low sensitivity will lead to both vaccine coverage and vaccine efficacy being underestimated in studies in which vaccination status is inferred from the presence/absence of a distinctive BCG scar. Age-sex patterns identified for scar size show important similarities to those found with skin test responses to tuberculin.

Adolescent↗

A novel antineuronal antibody in a motor neuron syndrome associated with breast cancer.

A 72-year-old woman developed a lower motor neuron syndrome (MNS) 4 months before the appearance of breast cancer. Monoparesis progressed to quadriparesis despite high-dose IV immunoglobulins, plasma exchange, and azathioprine, and high-dose IV methylprednisolone. The patient improved only after the removal of the tumor. MRI demonstrated hyperintensities in the cervical spinal cord. The patient had antibodies that reacted with axonal initial segments and nodes of Ranvier. The findings suggest that in this patient lower MNS may be a paraneoplastic condition associated with breast cancer.

Aged↗

Endocytosis proteins and cancer: a potential link?

Recent studies have shown that a variety of proteins participate with clathrin and clathrin adaptors in receptor-mediated endocytosis. The genes encoding some of these proteins are targets of chromosomal rearrangements in human haematopoietic malignancies. In addition, abnormal expression or mutation of some endocytosis proteins has been reported in human cancers. This article discusses these observations and elaborates the potential mechanisms by which the abnormal expression of endocytosis proteins might participate in the biology of cancer.

Animals↗

Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer.

Amphiphysin I is a 128 kD protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. It is a dominant autoantigen in patients with stiff-man syndrome associated with breast cancer, as well as in other paraneoplastic autoimmune neurological disorders. To elucidate the connection between amphiphysin I autoimmunity and cancer, we investigated its expression in breast cancer tissue. We report that amphiphysin I was expressed as two isoforms of 128 and 108 kD in the breast cancer of a patient with anti-amphiphysin I antibodies and paraneoplastic sensory neuronopathy. Amphiphysin I was also detectable at variable levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a variety of other non-neuronal tissues. The predominant amphiphysin I isoform expressed outside the brain in humans is the 108 kD isoform which represents an alternatively spliced variant of neuronal amphiphysin I missing a 42 amino acid insert. Our study suggests a link between amphiphysin I expression in cancer and amphiphysin I autoimmunity. The enhanced expression of amphiphysin I in some forms of cancer supports the hypothesis that amphiphysin family members may play a role in the biology of cancer cells.

Alternative Splicing↗