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Biomedical subjects

P Boyd

Publications and source records attributed to P Boyd.

At least 19 recordsLinked to original sources

The stability of micro-organisms preserved in LENTICULE discs, demonstrated by repeat sample distributions of the EQUAL Scheme for Indicator Organisms (water microbiology).

AIMS: To demonstrate the stability of microorganisms preserved in LENTICULE discs, employed by the EQUAL Scheme for Indicator Organisms. METHODS AND RESULTS: Five sample batches containing several indicator organism parameters were each despatched in two separate distributions at intervals of up to 24 months apart. A comparison of participants' median counts and bar charts of their cumulated results was then made. CONCLUSIONS: The results demonstrated that LENTICULE discs provided a remarkably stable preparation format for the maintenance of viable organisms in reproducible numbers. SIGNIFICANCE AND IMPACT OF THE STUDY: Complex mixtures of organisms can be maintained in stable numbers for extended periods of time at a freezer temperature of -20 degrees C and satisfactorily transported without the requirement for cold chain conditions.

Clostridium perfringens↗

Prevalence of congenital anomalies in five British regions, 1991-99.

AIMS: To describe trends in total and live birth prevalence, regional differences in prevalence, and outcome of pregnancy of selected congenital anomalies. METHODS: Population based registry study of 839,521 births to mothers resident in five geographical areas of Britain during 1991-99. Main outcome measures were: total and live birth prevalence; pregnancy outcome; proportion of stillbirths due to congenital anomalies; and secular trends. RESULTS: The sample consisted of 10,844 congenital anomalies, giving a total prevalence of 129 per 10,000 registered births (95% CI 127 to 132). Live birth prevalence was 82.2 per 10,000 births (95% CI 80.3 to 84.2) and declined significantly with time. The proportion of all stillbirths with a congenital anomaly was 10.5% (453 stillbirths). The proportion of pregnancies resulting in a termination increased from 27% (289 cases) in 1991 to 34.7% (384 cases) in 1999, whereas the proportion of live births declined from 68.2% (730 cases) to 58.5% (648 cases). Although similar rates of congenital anomaly groups were notified to the registers, variation in rates by register was present. There was a secular decline in the total prevalence of non-chromosomal and an increase in chromosomal anomalies. CONCLUSIONS: Regional variation exists in the prevalence of specific congenital anomalies. For some anomalies this can be partially explained by ascertainment variation. For others (neural tube defects, diaphragmatic hernia, gastroschisis), higher prevalence rates in the northern regions (Glasgow and Northern) were true differences. Live birth prevalence declined over the study due to an increase in terminations of pregnancy.

Abortion, Spontaneous↗

An aetiological classification of birth defects for epidemiological research.

BACKGROUND: Congenital anomaly registers collect data on antenatally and postnatally detected anomalies for surveillance, research, and public health purposes. Each anomaly is coded using the International Statistical Classification of Diseases and Related Health Problems (ICD-9/ICD-10) based on body systems, allowing accurate comparisons between registers for individual anomalies. When commencing an environmental, epidemiological study, it became clear to us that there is no standard classification that takes aetiology into account. This paper describes a new classification for use in studies addressing aetiology. METHOD: A classification system was evolved and piloted using cases in a study of geographical variation in congenital anomaly prevalence.1 Cases that were difficult to categorise were noted, and after discussion with a team of experts, the classification was adjusted accordingly. RESULTS AND CONCLUSION: A robust, hierarchical method of classifying birth defects into eight categories has been produced, for use at source of data registration in conjunction with, but independent of, ICD coding.

Congenital Abnormalities↗

Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women.

BACKGROUND AND AIMS: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signalling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT or 5-HTT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. It has been speculated that such functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhoea predominant IBS (dIBS) phenotype. SUBJECTS: A total of 194 North American Caucasian female dIBS patients and 448 female Caucasian controls were subjected to genotyping. METHODS: Leucocyte DNA of all subjects was analysed by polymerase chain reaction based technologies for nine SERT polymorphisms, including the insertion/deletion polymorphism in the promoter (SERT-P) and the variable tandem repeat in intron 2. Statistical analysis was performed to assess association of any SERT polymorphism allele with the dIBS phenotype. RESULTS: A strong genotypic association was observed between the SERT-P deletion/deletion genotype and the dIBS phenotype (p = 3.07x10(-5); n = 194). None of the other polymorphisms analysed was significantly associated with the presence of disease. CONCLUSIONS: Significant association was observed between dIBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for dIBS in women.

Adolescent↗

The requirements of the Data Protection Act 1998 for the processing of medical data.

The Data Protection Act 1998 presents a number of significant challenges to data controllers in the health sector. To assist data controllers in understanding their obligations under the act, the Information Commissioner has published guidance, The Use and Disclosure of Health Data, which is reproduced here. The guidance deals, among other things, with the steps that must be taken to obtain patient data fairly, the implied requirements of the act to use anonymised or psuedonymised data where possible, an exemption applicable principally to records based research, the right of patients to object to the processing of their data, and the interface of the act and the common law duty of confidence.

Confidentiality↗

Metabolic control of recombinant monoclonal antibody N-glycosylation in GS-NS0 cells.

Variable N-glycosylation at Asn(297) in the Fc region of recombinant therapeutic immunoglobulin G (IgG) molecules, specifically terminal galactosylation and sialylation, may affect both pharmacokinetic behavior and effector functions of recombinant therapeutic antibodies. We investigated the hypothesis that IgG Fc glycosylation can be controlled by manipulation of cellular nucleotide-sugar metabolism. In control cultures, N-glycans associated with the Fc domain of a recombinant humanized IgG1 produced by GS-NS0 cells in culture were predominantly biantennary, variably beta-galactosylated (average 0.3 mol galactose complex N-glycan(-1)) structures with no bisecting N-acetylglucosamine residues, sialylation, or alpha1,3-linked galactosylation evident. However, a variable proportion (5% to 15%) of high-mannose (Man5 to Man9) oligosaccharides were present. To manipulate the cellular content of the nucleotide sugar precursor required for galactosylation, UDP-Gal, we included either 10 mM glucosamine or 10 mM galactose in the culture medium. In the case of the former, a 17-fold increase in cellular UDP-N-acetylhexosamine content was observed, with a concomitant reduction (33%) in total UDP-hexose, although the ratio of UDP-Glc:UDP-Gal (4:1) was unchanged. Associated with these alterations in cellular UDP-sugar content was a significant reduction (57%) in the galactosylation of Fc-derived oligosaccharides. The proportion of high-mannose-type N-glycans (specifically Man5, the substrate for N-acetylglucosaminyltransferase I) at Asn(297) was unaffected. In contrast, inclusion of 10 mM galactose in culture specifically stimulated UDP-Gal content almost five-fold. However, this resulted in only a minimal, insignificant increase (6%) in beta1,4-galactosylation of Fc N-glycans. Sialylation was not improved upon the addition of the CMP-sialic acid (CMP-SA) precursor N-acetylmannosamine (20 mM), even with an associated 44-fold increase in cellular CMP-SA content. Analysis of recombinant IgG1 Fc glycosylation during batch culture showed that beta1,4-linked galactosylation declined slightly during culture, although, in the latter stages of culture, the release of proteases and glycosidases by lysed cells were likely to have contributed to the more dramatic drop in galactosylation. These data demonstrate: (i) the effect of steric hindrance on Fc N-glycan processing; (ii) the extent to which alterations in cellular nucleotide-sugar content may affect Fc N-glycan processing; and (iii) the potential for direct metabolic control of Fc N-glycosylation.

Amidohydrolases↗

Health beliefs and endoscopic screening for colorectal cancer: potential for cancer prevention.

BACKGROUND: Colorectal cancer can be prevented through endoscopic removal of adenomatous polyps. Because screening endoscopy rates are low, it is critical to identify correlates of screening behavior that are amenable to interventions to improve screening rates. Our purpose was to identify the correlates of endoscopic screening among persons at risk for colorectal cancer. METHODS: We surveyed 1,160 healthy, adult, first-degree relatives of colorectal cancer patients in 583 kindreds, for a 43% response rate. Using multiple logistic regression analysis, we tested the association between screening behavior and perceived risk for colorectal cancer, the belief that colorectal cancer can be prevented, demographic factors, strength of family history, and practical barriers to screening. RESULTS: Persons screened at least once were older, were male, had stronger family histories, had a regular doctor, and had health insurance. After these fixed factors were accounted for, the belief that colorectal cancer can be prevented and higher perceived risk were associated with significantly greater odds of screening. CONCLUSIONS: This study establishes the need for trials evaluating the cancer prevention potential of the link between screening behavior and health beliefs. Physicians must be aware of their patients' family colorectal cancer history and recommend appropriate endoscopic screening for those at increased risk, particularly women. Patients should be educated about their cancer risk and about preventing colorectal cancer.

Adult↗

Prenatal diagnosis of an epignathus: a case report and review of the literature.

An epignathus is an extremely rare form of teratoma that arises from the oral cavity, most commonly from the palate. We describe a case identified sonographically at 17 weeks' gestation after a raised maternal serum alpha-fetoprotein was recorded. This pregnancy was terminated but we review the literature over the last 10 years and describe the management options available in such cases.

Adult↗

Correlations between microbial parameters from water samples: expectations and reality.

Data which are collected in order to estimate the correlation between parameters must be analysed with caution. Classical statistics of correlation are often inappropriate. The "r" statistic is very easily distorted by non-Normal data. Non-parametric statistics can be helpful. The interpretation and usefulness of the estimates of correlation will depend on the study plan. If water samples come from disparate sources (e.g. upstream or downstream from sewage outlets) then parameters A and B may occur in their highest and lowest numbers according to how close the samples were to contamination sources thus correlating closely. However, if all samples come from sources with similar pollution levels then plots of A and B will show considerable scatter and apparently little correlation. So what is the relationship between A and B? An example of "perfect" correlation, as demonstrated by replicate counts of a single parameter from split samples, gave an r value of only 0.63 (p = 0.62) due to random variation in numbers of organisms between the two halves of the sample. Thus large amounts of data are needed for studying true correlation because relationships between parameters are embedded in the natural variation. This also illustrated that Standards for a single parameter can be "passed" or "failed" by two halves of the same sample. Study design is clearly of fundamental importance. Consideration must be given to the appropriate way of asking questions about correlation between different parameters.

Data Collection↗

Use of coping strategies and breast cancer survival: results from the Black/White Cancer Survival Study.

This analysis was designed to evaluate the association between coping strategies and breast cancer survival among Black and White women in a large population-based study. A total of 442 Black and 405 White US women diagnosed with invasive breast cancer during 1985-1986 and actively followed for survival through 1994 were administered a modified Folkman and Lazarus Ways of Coping questionnaire. Coping strategies were characterized via factor analyses of the responses. Hazard ratios associated with coping strategies were estimated using Cox proportional hazards models, with adjustment for age, race, tumor stage, study location, tumor hormone responsiveness, comorbidity, health insurance status, smoking, relative body weight, and alcohol consumption. Emotion-focused coping strategies were significantly associated with survival. Expression of emotion was associated with better survival (hazard ratio = 0.6; 95% confidence interval: 0.4, 0.9). When it was considered jointly with the presence or absence of perceived emotional support, women reporting low levels of both emotional expression and perceived emotional support experienced poorer survival than women reporting high levels of both (hazard ratio = 2.5; 95% confidence interval: 1.7, 3.7). Similar risk relations were evident for Blacks and Whites and for patients with early and late stage disease. These results suggest that the opportunity for emotional expression may help improve survival among patients with invasive breast cancer.

Adaptation, Psychological↗

Determination of the isotopic composition of uranium in urine by inductively coupled plasma mass spectrometry.

A simple method based on inductively coupled plasma mass spectrometry (ICP-MS) was developed to identify exposure to depleted uranium by measuring the isotopic composition of uranium in urine. Exposure to depleted uranium results in a decreased percentage of 235U in urine samples causing measurements to vary between natural uranium's 0.72% and depleted uranium's 0.2%. Urine samples from a non-depleted uranium exposed group and a suspected depleted uranium exposed group were processed and analyzed by ICP-MS to determine whether depleted uranium was present in the urine. Sample preparation involved dry-ashing the urine at 450 degrees C followed by wet-ashing with a series of additions of concentrated nitric acid and 30% hydrogen peroxide. The ash from the urine was dissolved in 1 M nitric acid, and the intensity of 235U and 238U ions were measured by ICP-MS. After the samples were ashed, the ICP-MS measurements required less than 5 min. The 235U percentage in individuals from the depleted uranium exposed group with urine uranium concentrations greater than 150 ng L(-1) was between 0.20%-0.33%, correctly identifying depleted uranium exposure. Samples from the non-depleted uranium exposed individuals had urine uranium concentration less than 50 ng L(-1) and 235U percentages consistent with natural uranium (0.7%-1.0%). A minimum concentration of 14 ng L(-1) uranium was required to obtain sufficient 235U to allow calculating a valid isotopic ratio. Therefore, the percent 235U in urine samples measured by this method can be used to identify low-level exposure to depleted uranium.

Humans↗

Identification and semi-quantitation of Ostertagia ostertagi eggs by enzymatic amplification of ITS-1 sequences.

A region within the first internal transcribed spacer (ITS-1) of the ribosomal DNA repeat of Ostertagia ostertagi has been identified that is 408 base pairs (bp) in length and is comprised of a 2 x 204 bp repeat. Universal polymerase chain reaction (PCR) primers which span this region, as well as a portion of the 5.8S rDNA, generate a 1011 bp fragment using genomic DNA from O. ostertagi. However, these same primers generate only a 600 bp (approximate) fragment using DNA from Haemonchus contortus, Cooperia oncophora and Oesophagostomum radiatum, as well as other species within the genus Ostertagia. When DNA samples derived from adult parasites of the different genera were mixed and simultaneously amplified, the O. ostertagi component could be identified within the mixed DNA populations. Furthermore, a correlation was observed between relative fluorescence intensities of the 1011 bp and the 600 bp PCR fragments and the percentage of O. ostertagi DNA within a mixture of parasite DNAs. A similar high correlation was obtained between the percentage of O. ostertagi DNA and percent O. ostertagi eggs in feces containing eggs of other nematode genera. This resulted in the generation of a protocol that can determine the percentage of O. ostertagi eggs within a mixed population of gastrointestinal nematode eggs. Results indicate a detection equivalent to 0.05 eggs.

Animals↗

Overview of the Second International Workshop to define swine cluster of differentiation (CD) antigens.

The aim of the Second International Swine Cluster of Differentiation (CD) Workshop, supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters. At the summary meeting of the workshop in July, 1995, revisions in the existing nomenclature for Swine CD were approved, so that the rules are now in accord with those for human and ruminant CD. Swine CD numbers will now be given to clusters of mAb to swine orthologues of human CD molecules when homology is proven by (1) suitable tissue distribution and lymphoid cell subset expression, (2) appropriate molecular mass of the antigen recognized by the mAbs, and (3) reactivity of mAbs with the cloned swine gene products, or cross-reactivity of the mAb on the human gene products. In some cases, this reactivity would not be fully proven, mainly due to the lack of cloned gene products; for these CD antigens, the respective clusters will be assigned by the prefix 'w' which will lead to 'wCD' antigens. As a result of the Second International Swine CD Workshop the assignment of 16 mAb to existing CD groups (CD2a, CD4a, CD5a, wCD6, wCD8, CD14, CD18a, wCD21, wCD25) was confirmed, and 2 mAb to existing swine workshop clusters (SWC). More importantly, for the work on the porcine immune system, was the definition of 5 new swine CD antigens, namely CD3 (recognized by 6 new mAb and 3 epitopes), CD16 (1 new mAb), wCD29 (2 mAb), CD45RA (3 mAb) and CD45RC (1 new mAb). Finally, the demarcation of two new SWC molecules in swine, SWC8 (2 mAb) and SWC9 (2 mAb) was confirmed.

Animals↗

Summary of the first round analyses of the Second International Swine CD Workshop.

The reactivity of 176 monoclonal antibodies (mAb) submitted to the Second International Swine CD Workshop, together with 19 internal standards, was analyzed by flow cytometry on 16 different cell types as a means of establishing the proper cell subset for later detailed clustering analyses. The exact CD subset reactivity of the 19 internal standard mAb had been characterized in the First International Swine CD Workshop. The flow cytometric analyses resulted in 40 data sets which were then subjected to statistical clustering using the Leukocyte Typing Database IV (LTDB4) software. As result of this work, 22 clusters were defined. After review of these results, panels of mAb from the defined first round clusters were assigned to cell subsets. The respective mAb in those first round clusters were then distributed to subset group researchers for further examination during the second round of the workshop.

Animals↗

Report on the analyses of mAb reactive with porcine CD8 for the second international swine CD workshop.

Based on an analysis of their reactivity with porcine peripheral blood lymphocytes (PBL), only three of the 57 mAbs assigned to the T cell/activation marker group were grouped into cluster T9 along with the two wCD8 workshop standard mAbs 76-2-11 (CD8a) and 11/295/33 (CD8b). Their placement was verified through the use of two-color cytofluorometry which established that all three mAbs (STH101, #090; UCP1H12-2, #139; and PG164A, #051) bind exclusively to CD8+ cells. Moreover, like the CD8 standard mAbs, these three mAbs reacted with two proteins with a MW of 33 and 35 kDa from lymphocyte lysates and were, thus, given the wCD8 designation. Because the mAb STH101 inhibited the binding of mAb 76-2-11 but not of 11/295/33, it was given the wCD8a designation. The reactivity of the other two new mAbs in the T9 cluster with the various subsets of CD8+ lymphocytes were distinct from that of the other members in this cluster including the standards. Although the characteristic porcine CD8 staining pattern consisting of CD8low and CD8high cells was obtained with the mAb UCP1H12-2, a wider gap between the fluorescence intensity of the CD8low and CD8high lymphocytes was observed. In contrast, the mAb PG164A, not only exclusively reacted with CD4-/CD8high lymphocytes, but it also failed to recognize CD4/CD8 double positive lymphocytes. It was concluded that this mAb is specific for a previously unrecognized CD8 epitope, and was, thus, given the wCD8c designation. A very similar reactivity pattern to that of PG164A was observed for two other mAbs (STH106, #094; and SwNL554.1, #009). Although these two mAbs were not originally positioned in the T cell subgroup because of their reactivity and their ability to inhibit the binding of PG164A, they were given the wCD8c designation. Overall, five new wCD8 mAbs were identified. Although the molecular basis for the differences in PBL recognition by these mAbs is not yet understood, they will be important in defining the role of CD8+ lymphocyte subsets in health and disease.

Animals↗

Family history of cancer and risk of lung cancer among lifetime nonsmoking women in the United States.

In a multicenter study of lung cancer in lifetime nonsmokers in the United States, 646 female lung cancer patients and 1,252 population controls were interviewed regarding history of cancer in their first-degree relatives. A 30% increased risk (95% confidence interval 0.9-1.8) was found for a history of respiratory tract cancer in parents or siblings after adjustment for exposure to environmental tobacco smoke (ETS) in adult life. Lung cancer, which represented approximately two thirds of the respiratory tract cancers, occurred more frequently in first-degree relatives of lung cancer patients than in comparable relatives of population controls (ETS-adjusted odds ratio = 1.29, 95% confidence interval 0.9-1.9). In particular, a significant threefold increased risk for lung cancer was associated with lung cancer diagnosed in mothers and sisters. The increased risk in relation to family history of lung cancer was observed among parents and siblings who were smokers as well as in those who were nonsmokers. The association with family history of lung cancer was strengthened when the analysis was restricted to adenocarcinoma of the lung (ETS-adjusted odds ratio = 1.50, 95% confidence interval 1.0-2.2). However, there was no association between family history of other cancers and risk of lung cancer in nonsmokers.

Adenocarcinoma↗

Chilling, oxidative stress and antioxidant responses in Arabidopsis thaliana callus.

Chilling of Arabidopsis thaliana (L.) Heynh. callus tissue to 4 degrees C led to conditions of oxidative stress, as indicated by increased levels of the products of peroxidative damage to cell membranes. Cellular H2O2 was also observed to increase initially upon chilling but by day 8 cellular levels had declined to below control levels. Although levels of catalase activity remained similar to those in unchilled tissue, activity of ascorbate peroxidase increased between days 4 and 8 of chilling to 4 degrees C. In callus held at 23 degrees C, levels of reduced glutathione remained static whereas they rose in callus held at 4 degrees C. Levels of oxidised glutathione were initially low but increased significantly by day 4 in the chilled callus. At 23 degrees C, however, levels of oxidised glutathione remained low. Between days 1 and 3 at 4 degrees C, levels of glutathione reductase activity increased but by day 8 glutathione reductase activity was similar to that in cells held at 23 degrees C. Exposure of callus to abscisic acid at 23 degrees C also led to increased activities of ascorbate peroxidase and glutathione reductase.

Antioxidants↗