Vault prolapse and rectocele assessment of repair using sacrocolpopexy with mesh interposition.
Explore the source record for details and available documents.
Constipation↗
Biomedical subjects
G M Taylor
Publications and source records attributed to G M Taylor.
Genetic diversity among Mycobacterium bovis isolates: a preliminary study of strains from animal and human sources.
Mycobacterium bovis has the broadest host range of species in the Mycobacterium tuberculosis complex and is responsible for disease in humans and diverse animal species. We report on genotypic differences at multiple loci among 13 isolates derived from a range of human and animal infections. All isolates were classified as M. bovis by phenotypic analysis but could be subdivided into five distinct genotypes based on polymorphisms at the pncA and oxyR loci, the status of the RD5 deletion region, and the spoligotype pattern. These findings suggest the existence of a spectrum of strains with genotypic characteristics between those of M. tuberculosis and M. bovis.
Aged↗
Fv-4: identification of the defect in Env and the mechanism of resistance to ecotropic murine leukemia virus.
Mice expressing the Fv-4 gene are resistant to infection by ecotropic murine leukemia viruses (MuLVs). The Fv-4 gene encodes an envelope (Env) protein whose putative receptor-binding domain resembles that of ecotropic MuLV Env protein. Resistance to ecotropic MuLVs appears to result from viral interference involving binding of the endogenously expressed Fv-4 env-encoded protein to the ecotropic receptor, although the immune system also plays a role in resistance. The Fv-4 env-encoded protein is processed normally and can be incorporated into virus particles but is unable to promote viral entry. Among the many sequence variations between the transmembrane (TM) subunit of the Fv-4 env-encoded protein and the TM subunits of other MuLV Env proteins, there is a substitution of an arginine residue in the Fv-4 env-encoded protein for a glycine residue (gly-491 in Moloney MuLV Env) that is otherwise conserved in all of the other MuLVs. This residue is present in the MuLV TM fusion peptide sequence. In this study, gly-491 of Moloney MuLV Env has been replaced with other residues and a mutant Env bearing a substitution for gly-487 was also created. G491R recapitulates the Fv-4 Env phenotype in cell culture, indicating that this substitution is sufficient for creation of an Env protein that can establish the interference-mediated resistance to ecotropic viruses produced by the Fv-4 gene. Analysis of the mutant MuLV Env proteins also has implications for an understanding of the role of conserved glycine residues in fusion peptides and for the engineering of organismal resistance to retroviruses.
Amino Acid Sequence↗
The evolution of armament strength: evidence for a constraint on the biting performance of claws of durophagous decapods.
Performance data for the claws of six sympatric species of Cancer crabs confirmed a puzzling pattern reported previously for two other decapod crustaceans (stone crabs, Menippe mercenaria, and lobsters, Homarus americanus): Although biting forces increased, maximum muscle stresses (force per unit area) declined with increasing claw size. The negative allometry of muscle stress and the stress at a given claw size were fairly consistent within and among Cancer species despite significant differences in adult body size and relative claw size, but were not consistent among decapod genera. Therefore, claw height can be used as a reliable predictor of maximum biting force for the genus Cancer, but must be used with caution as a predictor of maximum biting force in wider evolutionary and biogeographical comparisons of decapods. The decline in maximum muscle stress with increasing claw size in Cancer crabs contrasts with the pattern in several other claw traits. Significantly, three traits that affect maximal biting force increased intraspecifically with increasing claw size: relative claw size, mechanical advantage, and sarcomere length of the closer muscle. Closer apodeme area and angle of pinnation of the closer muscle fibers varied isometrically with claw size. The concordant behavior of these traits suggests selection for higher biting forces in larger crabs. The contrast between the size dependence of muscle stress (negative allometry) and the remaining claw traits (isometry or positive allometry) strongly suggests that an as yet unidentified constraint impairs muscle performance in larger claws. The negative allometry of muscle stress in two distantly related taxa (stone crabs and lobsters) further suggests this constraint may be widespread in decapod crustaceans. The implications of this performance constraint for the evolution of claw size and the "arms-race" between decapod predators and their hard-shelled prey is discussed.
Animals↗
Epstein-Barr Virus and HLA-DPB1-*0301 in young adult Hodgkin's disease: evidence for inherited susceptibility to Epstein-Barr Virus in cases that are EBV(+ve).
Cases of Hodgkin's disease (HD) may be distinguished by whether they do [EBV-positive ((+ve)) cases] or do not [EBV-negative ((-ve)) cases] have evidence of EBV DNA in the Reed-Sternberg cells. Only one study has attempted to distinguish epidemiological risk factors for EBV(+ve) and EBV(-ve) HD, and none have compared inherited susceptibility. The present study involves a population-based case series of HD, diagnosed in patients between 16-24 years of age in the United Kingdom (n = 118), of whom 87% were classified by EBV status (EBV(+ve), 19, EBV(-ve), 84). History of infectious illness, EBV antibody titers, and HLA-DPB1 type have been compared in EBV(+ve) and EBV(-ve) cases. Reported infectious mononucleosis was more frequent in EBV(+ve) cases (odds ratio (OR), 5.10; 95% confidence interval (CI), 1.12-24.4). EBV antibody titers to viral capsid antigen were significantly higher in EBV(+ve) cases (P for trend = 0.02). Higher proportions of EBV(+ve) (43%) than EBV(-ve) (31%) cases typed positive for HLA-DPB1*0301, but this was not statistically significant; the association of infectious mononucleosis with EBV(+ve) cases was stronger in this HLA subgroup (OR, 17.1; 95%CI, 1.06-1177) than in other cases (OR, 1.24; 95% CI, 0.02-15.4). Although these results are based on small numbers of HD cases, they provide suggestive evidence that the etiology of EBV(+ve) HD may involve inherited susceptibility to EBV.
Adolescent↗
Incidence of childhood precursor B-cell acute lymphoblastic leukaemia in north-west England.
A temporal increase in the incidence of childhood acute lymphoblastic leukaemia (ALL) in the UK has been noted. We present data from the Manchester Children's Tumour Registry which provide strong evidence that the increase is a result of an increase in the precursor B-cell subtype. In the childhood peak (age 1-4 years), the annual increase in precursor B-cell ALL between 1980 and 1998 was 3.0% (p=0.024). Recent findings are consistent with the causal involvement of infections in precursor B-cell ALL.
Adolescent↗
Maximum force production: why are crabs so strong?
Durophagous crabs successfully hunt hard-shelled prey by subjecting them to extremely strong biting forces using their claws. Here I show that, for a given body mass, six species of Cancer crabs (Cancer antennarius, Cancer branneri, Cancer gracilis, Cancer magister, Cancer oregonensis and Cancer productus) were able to exert mean maximum biting forces greater than the forces exerted in any other activity by most other animals. These strong biting forces were in part a result of the high stresses (740-1350 kN m(-2)) generated by the claw closer muscle. Furthermore, the maximum muscle stress increased with increasing mean resting sarcomere length (10-18 microm) for the closer muscle of the claws of these six Cancer species. A more extensive analysis incorporating published data on muscle stresses in other animal groups revealed that stress scales isometrically with the resting sarcomere length among species, as predicted by the sliding filament model of muscle contraction. Therefore, muscle or filament traits other than a very long mean sarcomere length need not be invoked in explaining the high stresses generated by crustacean claws.
Animals↗
Investigation of the melanocyte stimulating hormones on food intake. Lack Of evidence to support a role for the melanocortin-3-receptor.
The melanocortin receptors, melanocortin-3-receptor (MC3-R) and melanocortin-4-receptor (MC4-R), are expressed in many discrete medial hypothalamic nuclei implicated in feeding regulation. The pro-opiomelanocortin product alpha-melanocyte stimulating hormone (alpha-MSH), an MC3/4-R agonist, decreases food intake following intracerebroventricular (ICV) injection in rats. MC4-R's involvement in feeding has been established although a function for the MC3-R is unclear. We investigated endogenous melanocortin ligand binding and activation at the MC3-R and MC4-R and their effects on feeding. We have shown that alpha-MSH, desacetyl-alpha-MSH and beta-MSH bound to the MC3-R and MC4-R with similar affinity and stimulated cAMP with similar potency in HEK 293 cells transfected with MC3-R and MC4-R. In contrast gamma(2)-MSH showed selectivity for the MC3-R over the MC4-R both in binding affinity and cAMP stimulation. alpha-MSH and beta-MSH injected ICV into fasted rats at doses of 1, 3 and 6 nmol resulted in a decrease in food intake, (2 h food intake: alpha-MSH 6 nmol, 1.7+/-0.3 g; beta-MSH 6 nmol, 1.5+/-0.3 g vs. saline 6.0+/-0.5 g, P<0.001). Desacetyl alpha-MSH did not reduce food intake at low doses but was significant at 25 nmol (2 h food intake: desacetyl-alpha-MSH 6.1+/-1.0 g vs. saline 9.5+/-1.4 g, P<0.05). In contrast, gamma(2)-MSH had no effect on food intake when administered ICV to fasted rats. We were unable to establish a role for the MC3-R in feeding regulation. Our evidence, however, strengthens the hypothesis that the melanocortin's effects on food intake are mediated via the MC4-R.
Animals↗
Comparison of Mycobacterium tuberculosis genomes reveals frequent deletions in a 20 kb variable region in clinical isolates.
The Mycobacterium tuberculosis complex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity in M. tuberculosis, we have identified a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of the M. tuberculosis-specific IS6110 insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identified, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110 element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110 elements as the most likely mechanism of the deletion events. IS6110 insertion into hot-spots within the genome of M. tuberculosis provides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.
Carboxylic Ester Hydrolases↗
Treatment-related leukaemia--a clinical and scientific challenge.
The development of a second tumour, including treatment-related leukaemia (TRL), is the most devastating complication of intensive cancer chemotherapy. This is especially relevant in the paediatric population as over 70% of children diagnosed with a malignancy will now live at least 5 years. Most TRLs are myeloid leukaemias and carry an overall poor prognosis when compared with their de novo counterparts. Despite the well known association with specific cytotoxic agents, improved understanding of the pathogenesis and risk factors of TRL is ultimately essential if we are to develop successful strategies for prevention and treatment. Here we review these aspects, together with the clinical and diverse biological features of this complication and the efficacy of current therapy.
Antineoplastic Agents, Alkylating↗
Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents.
A UK population-based case-control study of Hodgkin's disease (HD) in young adults (16-24 years) included 118 cases and 237 controls matched on year of birth, gender and county of residence. The majority (103) of the cases were classified by Epstein-Barr virus (EBV) status (EBV present in Reed-Stenberg cells), with 19 being EBV-positive. Analyses using conditional logistic regression are presented of subject reports of prior infectious disease (infectious mononucleosis (IM), chicken pox, measles, mumps, pertussis and rubella). In these analyses HD cases are compared with matched controls, EBV-positive cases and EBV-negative cases are compared separately with their controls and formal tests of differences of association by EBV status are applied. A prior history of IM was positively associated with HD (odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.10-5.33) and with EBV-positive HD (OR = 9.16, 95% CI = 1.07-78.31) and the difference between EBV-positive and EBV-negative HD was statistically significant (P = 0.013). The remaining infectious illnesses (combined) were negatively associated with HD, EBV-positive HD and EBV-negative HD (in the total series, for > or =2 episodes compared with < or =1, OR = 0.45, 95% CI = 0.25-0.83). These results support previous evidence that early exposure to infection protects against HD and that IM increases subsequent risk; the comparisons of EBV-positive and EBV-negative HD are new and generate hypotheses for further study.
Adolescent↗
Space-time clustering patterns in childhood leukaemia support a role for infection.
Previous studies of space-time clustering in childhood leukaemia have produced equivocal and inconsistent results. To address this issue we have used Manchester Children's Tumour Registry leukaemia data in space-time clustering analyses. Knox tests for space-time interactions between cases were applied with fixed thresholds of close in space, <5 km and close in time <1 year apart. Addresses at birth as well as diagnosis were utilized. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. All methods showed highly significant evidence of space-time clustering based on place of birth and time of diagnosis, particularly for all leukaemias aged 0-14 and 0-4 years, and acute lymphoblastic leukaemia (ALL) 0-4 years. Some results based on location at diagnosis were significant but mainly gave larger P-values. The results are consistent with an infectious hypothesis. Furthermore, we found an excess of male cases over females involved in space-time pairs. We suggest this may be related to genetic differences in susceptibility to infection between males and females. These findings provide the basis for future studies to identify possible infectious agents.
Adolescent↗
The development and validation of an algorithm for real-time computerised fetal heart rate monitoring in labour.
OBJECTIVE: To develop and validate a computerised algorithm for the interpretation of the characteristics of fetal heart rate monitoring in labour. DESIGN: Prospective observational study. SETTING: Labour ward in a tertiary hospital. SAMPLE: Intrapartum cardiotocograms from 24 pregnancies. METHODS: A computerised algorithm was developed to assess the fetal heart baseline rate, variability, the number of accelerations and the number of decelerations. Twenty five minute segments of cardiotocograms were interpreted by the algorithm and also by seven expert reviewers independently. The reviewers were unaware of the outcome of labour. The reliability of the characteristics of cardiotocography and the validity of the computerised algorithm were assessed using the intraclass correlation coefficient and weighted kappa statistic for continuous and ordinal variables respectively. RESULTS: The inter rater reliability of the baseline fetal heart rate and the number and type of decelerations was good (intraclass correlation coefficient 0.93, 0.93 and 0.79, respectively). The reliability of baseline variability (kappa = 0.27) and accelerations (intraclass correlation coefficient = 0.27) was poor. The computerised algorithm had good agreement with the reviewers for the baseline fetal heart rate (intraclass correlation coefficient 0.91 to 0.98) and the number of decelerations (intraclass correlation coefficient 0.82 to 0.91), but was less valid as regards the number of late decelerations (intraclass correlation coefficient 0.68 to 0.85) and the number of accelerations (intraclass correlation coefficient 0.06 to 0.80), and was invalid as regards baseline variability (kappa 0.00 to 0.34). CONCLUSIONS: The high level of validity of the computerised algorithm for the estimation of the baseline fetal heart rate and the number of decelerations justifies its further technical development.
Adolescent↗
Use of a computerised maternity information system to improve clinical effectiveness: thromboprophylaxis at caesarean section.
An audit of the introduction of a protocol for thromboprophylaxis at caesarean section revealed over treatment of low risk women and the under treatment of high risk women. A routine computer generated risk assessment profile was introduced as part of a maternity information system. Reaudit showed a significant improvement in adherence to the thromboprophylaxis protocol in all risk groups.
Cesarean Section↗
An audit of the implementation of guidelines to reduce wound infection following caesarean section.
OBJECTIVE: National guidelines suggest that antibiotic prophylaxis should be given at all emergency Caesarean sections and considered at elective procedures in an attempt to reduce wound infection rates. It is recommended that both infection rates and the administration of antibiotics should be audited. In the absence of a local protocol an audit was designed aiming to audit the infection rate against a gold standard of a wound infection rate less than 5%. METHODOLOGY: A retrospective case note review was performed for all Caesarean section occurring over a six month period. Guidelines were introduced to address deficiencies and the audit repeated a year later. RESULTS: The wound infection rate in the absence of local guidelines for antibiotic prophylaxis was 10%. The major factor related to infection was a failure to give antibiotics particularly at elective Caesarean section. Re-audit following the introduction of a protocol for the administration of antibiotics at all Caesarean sections found a compliance rate of over 97% with a reduction of the infection rate to around 3%. CONCLUSION: This study supports the use of audit in the implementation of guidelines based on published evidence and local results.
Antibiotic Prophylaxis↗
A lack of a functional NAD(P)H:quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. United Kingdom Childhood Cancer Study Investigators.
Rearrangements and fusion of the MLL gene with various alternative partner genes occur in approximately 80% of infant leukemias and are acquired during fetal hemopoiesis in utero. Similar MLL gene recombinants also occur in topoisomerase II-inhibiting drug-induced leukemias. These data have led to the suggestion that some infant leukemia may arise via transplacental fetal exposures during pregnancy to substances that form cleavable complexes with topoisomerase II and induce illegitimate recombination of the MLL gene. A structural feature shared by many topoisomerase II-inhibiting drugs and other chemicals is the quinone moiety. We assayed, by PCR-RFLP, for a polymorphism in an enzyme that detoxifies quinones, NAD(P)H:quinone oxidoreductase (NQO1), in a series (n = 36) of infant leukemias with MLL rearrangements versus unselected cord blood controls (n = 100). MLL-rearranged leukemias were more likely to have genotypes with low NQO1 function (heterozygous CT or homozygous TT at nucleotide 609) than controls (odds ratio, 2.5; P = 0.015). In contrast, no significant allele bias was seen in other groups of pediatric leukemias with TEL-AML1 fusions (n = 50) or hyperdiploidy (n = 29). In the subset of infant leukemias that had MLL-AF4 fusion genes (n = 21), the bias increase in low or null function NQO1 genotypes was more pronounced (odds ratio, 8.12; P = 0.00013). These data support the idea of a novel causal mechanism in infant leukemia involving genotoxic exposure in utero and modulation of impact on a selective target gene by an inherited allele encoding a rate-limiting step in a carcinogen detoxification pathway.
Acute Disease↗
Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes.
It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously reported associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gender showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females with NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance with *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorphic amino-acid frequencies in patients and controls showed that susceptibility to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly associated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 alleles and individual DPbeta1 polymorphic amino acid residues may thus affect susceptibility and resistance to specific HD subtypes. This may be through their influence on the binding of peptides derived from an HD-associated infectious agent, and the consequent effect on immune responses to the agent.
Adolescent↗
Characterization of receptors for calcitonin gene-related peptide and adrenomedullin on the guinea-pig vas deferens.
1. The receptors which mediate the effects of calcitonin gene-related peptide (CGRP), amylin and adrenomedullin on the guinea-pig vas deferens have been investigated. 2. All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD2s for CGRP, amylin and adrenomedullin of 7.90+/-0.11, 7.70+/-0.19 and 7.25+/-0.10 respectively). 3. CGRP8-37 (1 microM) and AC187 (10 microM) showed little antagonist activity against adrenomedullin. 4. Adrenomedullin22-52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin. 5. [125I]-adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC50 of 8.91 and a capacity of 643 fmol mg(-1). Its selectivity profile was adrenomedullin> AC187>CGRP=amylin. It was clearly distinct from a site labelled by [125I]-CGRP (pIC50=8.73, capacity=114 fmol mg(-1), selectivity CGRP>amylin=AC187>adrenomedullin). [125I]-amylin bound to two sites with a total capacity of 882 fmol mg(-1). 6. Although CGRP has been shown to act at a CGRP2 receptor on the vas deferens with low sensitivity to CGRP8-37, this antagonist displaced [125I]-CGRP with high affinity from vas deferens membranes. This affinity was unaltered by increasing the temperature from 4 degrees C to 25 degrees C, suggesting the anomalous behaviour of CGRP8-37 is not due to temperature differences between binding and functional assays.
Adrenomedullin↗