Search PubMed⌕ Search

Biomedical subjects

J M Bland

Publications and source records attributed to J M Bland.

At least 19 recordsLinked to original sources

Amino acid supplementation reveals differential regulation of aflatoxin biosynthesis in Aspergillus flavus NRRL 3357 and Aspergillus parasiticus SRRC 143.

Aflatoxins are toxic and carcinogenic secondary metabolites produced by the fungi Aspergillus flavus and Aspergillus parasiticus. To better understand the molecular mechanisms that regulate aflatoxin production, the biosynthesis of the toxin in A. flavus and A. parasticus grown in yeast extract sucrose media supplemented with 50 mM tryptophan (Trp) were examined. Aspergillus flavus grown in the presence of 50 mM tryptophan was found to have significantly reduced aflatoxin B(1) and B(2) biosynthesis, while A. parasiticus cultures had significantly increased B(1) and G(1) biosynthesis. Microarray analysis of RNA extracted from fungi grown under these conditions revealed 77 genes that are expressed significantly different between A. flavus and A. parasiticus, including the aflatoxin biosynthetic genes aflD (nor-1), aflE (norA), and aflO (omtB). It is clear that the regulatory mechanisms of aflatoxin biosynthesis in response to Trp in A. flavus and A. parasiticus are different. These candidate genes may serve as regulatory factors of aflatoxin biosynthesis.

Aflatoxins↗

Synergism of CAY-1 with amphotericin B and itraconazole.

BACKGROUND: CAY-1 is a fungicidal saponin from cayenne pepper whose mode of action differs from amphotericin B (AB) and itraconazole (IT). This work determined CAY-1 synergism with AB or IT. METHODS: CAY-1 was purified and used in checkerboard microdilution studies where CAY-1 and AB or IT were mixed with nongerminated (NG) and germinating (G) conidia of three Aspergillus species and Candida albicans. Inhibition was visually determined at 24 and 48 h. RESULTS: CAY-1 had predominantly additive-synergistic interaction with AB or IT against the Aspergillus NG and G conidia. Excellent synergy between CAY-1 and AB occurred at 24 and 48 h against C. albicans. Results suggest CAY-1 enhances AB and IT efficacy.

Amphotericin B↗

Assessment of the intraobserver variability in the measurement of fetal cardiothoracic ratio using ellipse and diameter methods.

OBJECTIVE: To assess the variability of fetal heart and thoracic area and circumference measurements using the ellipse and diameter methods at different gestational ages. DESIGN: This was a prospective cross-sectional study of 200 singleton pregnancies, with no apparent fetal abnormalities. The gestational age ranged between 19 and 42 weeks. At each examination, two transverse frames of the fetal chest at the level of the four-chamber view during diastole were obtained. For each frame, the area and the circumference of the heart and thorax were obtained by the ellipse and diameter methods. In the diameter method, cardiac and thoracic areas and circumferences were derived from the measured anteroposterior and transverse diameters. All measurements were made by the same observer. RESULTS: For the same method, intraobserver variability was good. Coefficient of variation for all measurements varied between 3-11%. The ellipse method tended to give larger measurements than did the diameter method, the absolute difference increasing with fetal age. The mean ellipse/diameter ratio was 1.10, 1.04, 1.05 and 1.02 for heart area, thorax area, heart circumference and thorax circumference, respectively. In most cases, intraobserver variability of the thorax measurements was independent of gestational age. In contrast, there was a greater variability of heart measurements with increasing gestational age. CONCLUSIONS: Both the ellipse and diameter methods of measuring cardiothoracic ratio are clinically useful and fairly reproducible at certain gestations, but are not interchangeable as the ellipse method overestimates measurements compared to the diameter method. The less reproducible measurement of heart size in later gestation should be taken into account when assessing cardiothoracic ratios.

Adult↗

Deaths certified as asthma and use of medical services: a national case-control study.

BACKGROUND: Studies have linked asthma death to either increased or decreased use of medical services. METHODS: A population based case-control study of asthma deaths in 1994-8 was performed in 22 English, six Scottish, and five Welsh health authorities/boards. All 681 subjects who died were under the age of 65 years with asthma in Part I on the death certificates. After exclusions, 532 hospital controls were matched to 532 cases for age, district, and date of asthma admission/death. Data were extracted blind from primary care records. RESULTS: The median age of the subjects who died was 53 years; 60% of cases and 64% of controls were female. There was little difference in outpatient attendance (55% and 55%), hospital admission for asthma (51% and 54%), and median inpatient days (20 days and 15 days) in the previous 5 years. After mutual adjustment and adjustment for sex, using conditional logistic regression, three variables were independently associated with asthma death: fewer general practice contacts (odds ratio 0.82 (95% confidence interval (CI) 0.74 to 0.91) per 5 contacts) in the previous year, more home visits (1.14 (95% CI 1.08 to 1.21) per visit) in the previous year, and fewer peak expiratory flow recordings (0.83 (95% CI 0.74 to 0.92) per occasion) in the previous 3 months. These associations were similar after adjustment for markers of severity, psychosocial factors, systemic steroids, short acting bronchodilators and antibiotics, although the association with peak flow was weakened and just lost significance. CONCLUSION: Asthma death is associated with less use of primary care services. Both practice and patient factors may be involved and a better understanding of these may offer possibilities for reducing asthma death.

Administration, Inhalation↗

Sex-specific antenatal reference growth charts for uncomplicated singleton pregnancies at 15-40 weeks of gestation.

OBJECTIVE: Female fetuses, on average, weigh less than male fetuses at all gestational ages. The purpose of this study was to compare female and male fetuses in terms of intrauterine ultrasound growth measurements and to develop gestational-age-related charts based on a computerized perinatal database. METHODS: This was a retrospective study of unselected women in the second and third trimesters of pregnancy, who had a normal scan at 10-14 weeks. Data analysis was performed using measurements obtained from a mixed-race population of 4234 women, who underwent 5198 ultrasound examinations. The scans were performed by four trained sonographers, according to a standardized protocol. Routine measurements included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The main end-points were sex- and race-specific differences in fetal biometry, which were also used to estimate fetal weight. RESULTS: The base-line demographic characteristics and risk factors were comparable in female and male fetuses. Significant differences in fetal BPD, HC, AC and estimated fetal weight, but not FL, were seen between male and female fetuses. Centile charts for each of these variables were constructed for both male and female fetuses. CONCLUSIONS: This study suggests that small but consistent sex-related differences in prenatal BPD, HC and AC measurements are established by as early as 15 weeks of gestation. The use of sex-specific nomograms may improve the prenatal assessment of fetal growth as well as the diagnosis of structural abnormalities.

Embryonic and Fetal Development↗

Meat flavor: contribution of proteins and peptides to the flavor of beef.

While the majority of meat flavor is lipid in origin, the contribution of peptides and amino acids to overall meat flavor should not be overlooked. Amino acids and peptide levels have been shown to change with postmortem aging in muscle and with dry-curing, a process similar to PMA. Variation in protein, peptide, and amino acid composition have also been shown to occur with heating and with post-heating storage of meat. This makes a large pool of reactive components that may directly affect flavor or indirectly affect flavor by reacting with reducing sugars to form Maillard reaction products and Strecker degradation products that impact meat flavor. Further research in this area should continue with particular emphasis on natural peptide flavor enhancers, modulators, and potentiators.

Animals↗

Serum cortisol reduction and abnormal prolactin and CD4+/CD8+ T-cell response as a result of controlled exercise in patients with rheumatoid arthritis and systemic lupus erythematosus despite unaltered muscle energetics.

OBJECTIVE: To investigate muscle energetics in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and measure serum cortisol, prolactin and CD4+/CD8+ T-cell levels during and after controlled exhaustive exercise. METHODS: Patients with RA (n = 7), patients with SLE (n = 6) and healthy individuals (HI) (n = 10) performed incremental cycle ergometry to the limit of tolerance. Ventilation, oxygen uptake (VO2) and carbon dioxide output were measured and the lactate threshold (LT) was estimated. Serum cortisol, prolactin, CD4+ and CD8+ lymphocyte subset levels were determined at baseline, peak exercise and 1 h after exercise. RESULTS: Exercise tolerance was reduced in patients with RA and patients with SLE, as reflected by peak VO2 and LT, but muscle energetics were not altered. In RA and SLE, there was significant reduction in cortisol levels at peak (-10%; P = 0.03) and post-exercise times (-36%; P = 0.05). Prolactin varied significantly at peak exercise in HI only (+60%; P = 0.05). There was a significant reduction in CD4+ T cells at peak exercise in RA (-15%; P = 0.02) and SLE patients (-8%; P = 0.04) and an increase after exercise in SLE patients (+11%; P = 0.03). In HI, CD8+ T cells increased significantly (+47%; P = 0.01) at peak exercise, but this was not found in RA and SLE patients. A significant reduction in CD8+ T cells was noted after exercise in SLE patients (-6%; P = 0.05). CONCLUSION: RA and lupus patients do not have significantly altered muscle energetics, but have abnormal cortisol, prolactin and CD4+/CD8+ T-cell responses to exercise. Further studies need to be carried out to evaluate whether short bouts of strenuous exercise have detrimental clinical effects.

Adult↗

Applying the right statistics: analyses of measurement studies.

The study of measurement error, observer variation and agreement between different methods of measurement are frequent topics in the imaging literature. We describe the problems of some applications of correlation and regression methods to these studies, using recent examples from this literature. We use a simulated example to show how these problems and misinterpretations arise. We describe the 95% limits of agreement approach and a similar, appropriate, regression technique. We discuss the difference vs. mean plot, and the pitfalls of plotting difference against one variable only. We stress that these are questions of estimation, not significance tests, and show how confidence intervals can be found for these estimates.

Confidence Intervals↗

Late onset microcephaly: failure of prenatal diagnosis.

We present a case of recurrent primary developmental microcephaly of late onset, the prenatal diagnosis of which could not be achieved despite performing targeted serial ultrasound scans that revealed no obvious fetal abnormality. Serial scans for head measurements and detailed examination of the brain anatomy by both transabdominal and transvaginal sonography including color and power Doppler assessment revealed no obvious brain abnormality. Frontal lobe distance and thalamic frontal lobe distance at 36 weeks were on the 30th and 50th centiles, respectively. Growth velocity remained on the 50th centile up to 36 weeks; between 36 and 38 weeks measurements were between the 35th and 40th centiles. The infant was delivered by Cesarean section at 38 weeks on parental request. On examination after birth the head circumference was on the 9th centile, but the facies was that of a microcephalic child with a sloping forehead and neurologically he was severely abnormal. The adequacy of the normal reference ranges used is reviewed: the use of sex-specific growth charts at 38 weeks would have demonstrated the biparietal diameter and the head circumference to be on the 20th and 15th centiles, respectively, rather than just below the 40th centile. However, even sex-specific charts may not allow the recognition of a substantial number of affected fetuses.

Brain↗

CAY-1, a novel antifungal compound from cayenne pepper.

CAY-1, a novel saponin from Capsicum frutescens (commercially known as cayenne pepper) was investigated to determine its in vitro antifungal activity, mechanism of action and mammalian cell cytotoxicity. CAY-1 was active against 16 different fungal strains, including Candida spp. and Aspergillus fumigatus [minimum inhibitory concentrations (MIC) ranging from 4 to 16 microg ml(-1)], and was especially active against Cryptococcus neoformans (90% inhibition at 1 microg ml(-1)). Synergistic activity was also observed between CAY-1 and amphotericin B against Candida albicans and A. fumigatus. No significant cytotoxicity was demonstrated when CAY-1 was tested against 55 mammalian cell lines at up to 100 microg ml(-1). Importantly, CAY-1 appears to act by disrupting the membrane integrity of fungal cells.

Antifungal Agents↗

CAY-I, a fungicidal saponin from Capsicum sp. fruit.

Saponins are steroidal or terpenoid-based glycosides with surface active properties. A steroidal saponin, CAY-1, with a molecular weight of 1243.35 Da, was isolated and purified to homogeneity from commercially available dry, ground fruit of Capsicum frutescens. CAY-1 was shown to be a potent fungicide for the germinating conidia of Aspergillus flavus, A. fumigatus, A. parasiticus and A. niger with species-dependent LD90 values between 3 and 20 microM. Activity against some Aspergillus species was affected by the test medium used. In vitro assays, CAY-1 was effective against Pneumocystis carinii (IC50): 9.5 microM) and Candida albicans (IC90: 6.2 microM). CAY-1 had no effect on the viability of the nongerminating conidia of the two filamentous fungi, P. carinii and C. albicans, nor on the conidial type of Fusarium oxysporum. It was ineffective against the bacteria Enterobacter agglomerans, Bacillus subtilis, Escherichia coli and Staphylococcus aureus. CAY-1 was not cytotoxic to A 549 lung carcinoma cells or HeLa cells at effective fungicidal concentrations. The results indicate that CAY-1 is an effective fungicide for Aspergillus species, C. albicans and P. carinii at concentrations below the threshold for mammalian cell toxicity.

Antifungal Agents↗

Psychological, social and health behaviour risk factors for deaths certified as asthma: a national case-control study.

BACKGROUND: Uncontrolled studies suggest that psychosocial factors and health behaviour may be important in asthma death. METHODS: A community based case-control study of 533 cases, comprising 78% of all asthma deaths under age 65 years and 533 hospital controls individually matched for age, district and asthma admission date corresponding to date of death was undertaken in seven regions of Britain (1994-98). Data were extracted blind from anonymised copies of primary care records for the previous 5 years and non-blind for the earlier period. RESULTS: 60% of cases and 63% of controls were female. The median age in both groups was 53. Cases had an earlier age of asthma onset, more chronic obstructive lung disease, and were more obese. 48% of cases and 42% of controls had a health behaviour problem; repeated non-attendance/poor inhaler technique was related to increased risk of death. Overall, 85% and 86%, respectively, had a psychosocial problem. Four psychosocial factors were associated with increased risk of death (psychosis, alcohol/drug abuse, financial/employment problems, learning difficulties) and two with reduced risk (anxiety/prescription of antidepressant drugs and sexual problems). While alcohol/drug abuse lost significance after adjustment for psychosis, other associations appeared independent of each other and of indicators of severity and co-morbidity. None of the remaining 13 factors including family problems, domestic abuse, bereavement, and social isolation were significantly related to risk of asthma death. CONCLUSION: There was an apparently high burden of psychosocial problems in both cases and controls. The associations between health behaviour, psychosocial factors, and asthma death are varied and complex with a limited number of factors showing positive relationships.

Adolescent↗

Effectiveness of acute postoperative pain management: I. Evidence from published data.

BACKGROUND: This review examines the evidence from published data concerning the incidence of moderate-severe and of severe pain after major surgery, with three analgesic techniques; intramuscular (i.m.) analgesia, patient controlled analgesia (PCA), and epidural analgesia. METHODS: A MEDLINE search of the literature was conducted for publications concerned with the management of postoperative pain. Over 800 original papers and reviews were identified. Of these 212 papers fulfilled the inclusion criteria but only 165 provided usable data on pain intensity and pain relief. Pooled data on pain scores obtained from these studies, which represent the experience of a total of nearly 20,000 patients, form the basis of this review. RESULTS: Different pain measurement tools provided comparable data. When considering a mixture of three analgesic techniques, the overall mean (95% CI) incidence of moderate-severe pain and of severe pain was 29.7 (26.4-33.0)% and 10.9 (8.4-13.4)%, respectively. The overall mean (95% CI) incidence of poor pain relief and of fair-to-poor pain relief was 3.5 (2.4-4.6)% and 19.4 (16.4-22.3)%, respectively. For i.m. analgesia the incidence of moderate-severe pain was 67.2 (58.1-76.2)% and that of severe pain was 29.1 (18.8-39.4)%. For PCA, the incidence of moderate-severe pain was 35.8 (31.4-40.2)% and that of severe pain was 10.4 (8.0-12.8)%. For epidural analgesia the incidence of moderate-severe pain was 20.9 (17.8-24.0)% and that of severe pain was 7.8 (6.1-9.5)%. The incidence of premature catheter dislodgement was 5.7 (4.0-7.4)%. Over the period 1973-1999 there has been a highly significant (P < 0.0001) reduction in the incidence of moderate-severe pain of 1.9 (1.1-2.7)% per year. CONCLUSIONS: These results suggest that the UK Audit Commission (1997) proposed standards of care might be unachievable using current analgesic techniques. The data may be useful in setting standards of care for Acute Pain Services.

Analgesia↗

Solid-phase microextraction for the detection of termite cuticular hydrocarbons.

Solid-phase microextraction (SPME)-gas chromatography-mass spectrometry was used to identify the cuticular hydrocarbons of the subterranean termite Coptotermes formosanus Shiraki. Headspace SPME and direct contact SPME methods were evaluated and compared to the hexane extraction method. Variables, such as temperature, time, number of termites, condition of the termites, and the type of SPME fiber were evaluated. Methods were refined to increase the reproducibility as well as the sensitivity. Both SPME methods were successfully used for the identification of all the major termite cuticular hydrocarbons. Using the headspace SPME method, other compounds of interest could also be identified, such as fatty acids. Using the direct contact SPME method, termites could be repeatedly studied over time to monitor chemical changes.

Animals↗

Unequal cluster sizes for trials in English and Welsh general practice: implications for sample size calculations.

Cluster randomized trials are often used in primary care settings. In the U.K., general practices are usually the unit of allocation. The effect of variability in practice list size on sample size calculations is demonstrated using the General Medical Services Statistics for England and Wales, 1997. Summary statistics and tables are given to help design such trials assuming that a fixed proportion of patients are to be recruited from each cluster. Three different weightings of the cluster means are compared: uniform, cluster size and minimum variance weights. Minimum variance weights are shown to be superior to uniform, particularly when clusters are small, and to cluster size weights, particularly when clusters are large. Where there are large numbers of participants per cluster and cluster size weights are used, the power actually falls as more patients are recruited to large clusters. When minimum variance weights are used the increase in the design effect due to variation in list size is small, regardless of the size of intracluster correlation coefficient or the number of participants per cluster, provided there is no loss of randomized units. When the expected number of participants per practice is low a greater loss in power comes from practices which fail to recruit patients. A method to estimate the likely effect and allow for it is presented.

Accidental Falls↗