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Biomedical subjects

C Talbot

Publications and source records attributed to C Talbot.

At least 19 recordsLinked to original sources
PubMed2006

Early experience with linezolid for infections in orthopaedics.

In infections following orthopaedic surgery, isolated staphylococci are reported to be methicillin resistant (MRSA) in up to 50% of cases. Linezolid, the first in a new class of antibiotics, has excellent efficacy against gram positive organisms that are resistant to other therapies and is 100% orally bioavailable. We report early results of its use for the treatment of resistant infections in orthopaedic practice. Infections were characterised according to the UK Nosocomial Infections National Surveillance Service classification of surgical infections as superficial, deep or organ/space. Osteomyelitis, joint sepsis and deep infection involving orthopaedic implants were included into the final category. Outcome was recorded as clinical, microbiological and blood parameter cure or fail. Over the 12-month study period, 54 patients received linezolid therapy, 41% of these had significant co-morbidity that might affect their ability to fight infection. Sixty-seven percent of infections were in association with implanted metal work. The majority of patients were treated with vancomycin for a short period before linezolid was used as oral 'switch' therapy for longer-term administration, allowing early discharge in all cases. MRSA was isolated in 87% of the patients treated. The mean length of linezolid therapy was 39 days (2-151). Clinical success was achieved in 90% of patients overall. Though there were no life-threatening complications, adverse event rates were significantly higher than those recorded in the literature, with 19% of patients needing to cease therapy. Linezolid offers an alternative to traditional treatments for resistant infections and can facilitate early discharge. Patients need to be monitored closely, particularly where long-term therapy is planned.

Acetamides↗
PubMed2005

Effects of temperature, salinity, desiccation and chemical treatments on egg embryonation and hatching success of Benedenia seriolae (Monogenea: Capsalidae), a parasite of farmed Seriola spp.

The effects of temperature and salinity on the embryonation period and hatching success of eggs of Benedenia seriolae were investigated. Temperature strongly influenced embryonation period; eggs first hatched 5 days after laying at 28 degrees C and 16 days after laying at 14 degrees C. The relationship between temperature and embryonation period is described by quadratic regression equations for time to first and last hatching. Hatching success was >70% for B. seriolae eggs incubated at temperatures from 14 to 28 degrees C. However, no B. seriolae eggs embryonated and hatched at 30 degrees C and <2% of eggs hatched when incubated at 24 degrees C after transfer to 30 degrees C for 48 h. Embryonation period was similar for eggs incubated in sea water at 25, 30 and 35 per thousand salinity, but increased for eggs incubated at higher or lower salinities. When incubated at salinities ranging from 25 to 45 per thousand, more than 70% of B. seriolae eggs embryonated and hatched. Hatching success was lower at 20 and 50 per thousand salinity and few or no eggs hatched at 10 and 15 per thousand. Hatching of B. seriolae eggs can be prevented by desiccation for 3 min, by immersion in water at 50 degrees C for 30 s or by treatment with 25% ethanol for 3 min.

Analysis of Variance↗
PubMed2005

Infliximab in the surgical management of complex fistulating anal Crohn's disease.

OBJECTIVES: To assess prospectively the efficacy and safety of treatment of perianal Crohn's disease by means of a combination of surgical management and a standardized protocol for the intravenous infusion of infliximab. METHODS: A consecutive series of patients who presented with complex perianal Crohn's fistulae between November 1999 and March 2003 were included in the study. Perianal sepsis was eradicated with drainage of collections and insertion of setons. Infliximab was infused at 5 mg/kg at 0, 2, and 6 weeks. Setons were removed after the second infliximab infusion. Endpoints were defined as either complete, partial or no response as noted at subsequent outpatient follow up. Adverse reactions were recorded. RESULTS: Twenty-one patients had a median of three fistulae per patient (range 1-9). All patients tolerated the initial protocol, receiving a median of five infusions of infliximab (range 3-19); median follow up 20 months (range 12-52). Eleven patients (53%) were continued on maintenance therapy with 12 weekly infusions of infliximab for either a perceived clinical need for treatment or after a relapse of their symptoms. Ten (47%) patients experienced a complete response to treatment and the remaining 11 (53%) experienced a partial response. No patient failed to respond to treatment. Four adverse reactions were noted (2 mild allergies, 1 rash and 1 patient experienced joint pains). All adverse reactions settled with cessation of the drug infusion. CONCLUSIONS: The combination of seton drainage and infusion of infliximab completely healed the perineum of 47% patients with complex fistulating perianal Crohn's disease. Partial response was seen in the remainder of patients. No serious adverse reactions reported.

Adult↗
PubMed2004

The themes expressed in suicide calls to a telephone help line.

BACKGROUND: Little is known about the suicidal ideation of callers to telephone help lines even though these services are in the front line of suicide prevention efforts. Where thematic data are collected by telephone counseling agencies, it is rarely clear how the categories were constructed and the measurement properties of the instruments are rarely reported. METHODS: The call sheets kept by counselors on 409 suicide calls were content-analyzed, resulting in a reliable checklist comprising nine major themes. The prevalence of these themes within the sample was then determined and age and gender differences in the themes expressed by first-time callers (n = 189) were examined using logistic regression analysis. RESULTS: Almost equal numbers of male and female calls were received and the nine themes were mentioned a total of 981 times. Among first-time callers, males under 35 years were around 75% more likely to refer to relationship breakdown in their calls than were same-age females. Male callers were also around twice as likely to refer to material hardship. Females were four times more likely to refer to being the victim of abuse and nearly 60% more likely to refer to interpersonal and family problems. CONCLUSION: The vast majority of suicide callers expressed dissatisfaction with the quality of their intimate relationships, which suggests that the promotion of intimacy and coping strategies for relationship breakdown are central to the primary prevention of suicide.

Adolescent↗
PubMed2004

FM-dyes as experimental probes for dissecting vesicle trafficking in living plant cells.

FM-dyes are widely used to study endocytosis, vesicle trafficking and organelle organization in living eukaryotic cells. The increasing use of FM-dyes in plant cells has provoked much debate with regard to their suitability as endocytosis markers, which organelles they stain and the precise pathways they follow through the vesicle trafficking network. A primary aim of this article is to assess critically the current status of this debate in plant cells. For this purpose, background information on the important characteristics of the FM-dyes, and of optimal dye concentrations, conditions of dye storage, and staining and imaging protocols, are provided. Particular emphasis is placed on using the FM-dyes in double labelling experiments to identity specific organelles. In this way, staining of the Golgi with FM4-64 has been demonstrated for the first time.

Biological Transport, Active↗
PubMed2002

Multiple cross mapping (MCM) markedly improves the localization of a QTL for ethanol-induced activation.

This study examines the use of multiple cross mapping (MCM) to reduce the interval for an ethanol response QTL on mouse chromosome 1. The phenotype is the acute locomotor response to a 1.5-g/kg i.p. dose of ethanol. The MCM panel consisted of the six unique intercrosses that can be obtained from the C57BL/6J (B6), DBA/2J (D2), BALB/cJ (C) and LP/J (LP) inbred mouse strains (N > or = 600/cross). Ethanol response QTL were detected only with the B6xD2 and B6xC intercrosses. For both crosses, the D2 and C alleles were dominant and decreased ethanol response. The QTL information was used to develop an algorithm for sorting and editing the chromosome 1 Mit microsatellite marker set (http://www.jax.org). This process yielded a cluster of markers between 82 and 85cM (MGI). Evidence that the QTL was localized in or near this interval was obtained by the analysis of a sample (n = 550) of advanced cross heterogenous stock animals. In addition, it was observed that one of the BXD recombinant inbred strains (BXD-32) had a recombination in the interval of interest which produced the expected change in behavior. Overall, the data obtained suggest that the information available within existing genetic maps coupled with MCM data can be used to reduce the QTL interval. In addition, the MCM data set can be used to interrogate gene expression data to estimate which polymorphisms within the interval of interest are relevant to the QTL.

Animals↗
PubMed1997

A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism.

Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the absorption of sodium through the highly selective, amiloride-sensitive epithelial sodium channel (ENaC) made of three homologous subunits (alpha, beta, and gamma). In human, autosomal recessive mutations of alpha, beta, or gammaENaC subunits cause pseudohypoaldosteronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldosterone, hyponatremia, life-threatening hyperkaliemia, and metabolic acidosis. In the mouse, inactivation of alphaENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype. Transgenic expression of alphaENaC driven by a cytomegalovirus promoter in alphaENaC(-/-) knockout mice [alphaENaC(-/-)Tg] rescued the perinatal lethal pulmonary phenotype and partially restored Na+ transport in renal, colonic, and pulmonary epithelia. At days 5-9, however, alphaENaC(-/-)Tg mice showed clinical features of severe PHA-1 with metabolic acidosis, urinary salt-wasting, growth retardation, and 50% mortality. Adult alphaENaC(-/-)Tg survivors exhibited a compensated PHA-1 with normal acid/base and electrolyte values but 6-fold elevation of plasma aldosterone compared with wild-type littermate controls. We conclude that partial restoration of ENaC-mediated Na+ absorption in this transgenic mouse results in a mouse model for PHA-1.

Amiloride↗
PubMed1997

Effect of exogenous cholecystokinin on the discharge of the gallbladder and the secretion of trypsin and chymotrypsin from the pancreas of the Atlantic salmon, Salmo salar L.

The humoral control of release of the proteases trypsin and chymotrypsin was investigated in the Atlantic salmon (Salmo salar L.). Intraperitoneal injection of a purified preparation of the peptide cholecystokinin (CCK) from pig into starved fish produces a dose-dependent release of both enzymes from the pyloric caeca/pancreas tissues which accumulate in the intestinal contents (digesta). It also induces release of the contents of the gallbladder. Isolated preparations of pyloric caeca/pancreas when incubated with CCK release trypsin and chymotrypsin. It is concluded that while a possible role for a neuronal component to the control and regulation of these enzymes cannot be ruled out, humoral control by a CCK-like peptide has been established. The fact that a mammalian-derived extract of CCK induces this response in fish indicates an early evolution and subsequent conservation of this control mechanism in the vertebrates.

Animals↗
PubMed1997

Visual assessment of human skin irritation: a sensitive and reproducible tool.

Human volunteer studies of skin irritation have been carried out for decades, both for research and for safety evaluation purposes. For the majority of this time, and consequently for the majority of the studies, assessment of the skin reactions has been made visually. Typical endpoints include erythema, oedema, dryness and scaling, some or all of which would be rated on a simple scale, eg 0, +/-, +, ++, + + +. Such approaches can be criticized as subjective, of poor reproducibility, lacking in sensitivity and highly variable between observers and/or institutions. In consequence, instrumental methods of assessment have been strongly promoted and do indeed offer several advantages, not least their objectivity. However, it is possible to use the human eye, which is a very sensitive tool, to make detailed, accurate and reproducible descriptions of skin irritation reactions. To achieve this, it is necessary to give prolonged and thorough training to each observer. In this paper, 3 examples of human volunteer studies, in which different pairs of trained observers independently carried out double blinded scoring of the irritation reactions, are reported. The grading patterns produced were almost identical; statistical analysis showed that properly trained observers are in fact able to reliably measure a grade of erythema to within +/- 1 on a 10 point scale; 97.6% of scores were within 2 grade points on this scale. These results provide evidence that visual scoring can be sensitive, reliable and reproducible within a testing institution.

Dermatitis, Irritant↗
PubMed1996

Structure and alternative splicing of the presenilin-2 gene.

Missense mutations in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes have been shown to be causes of autosomal dominant Alzheimer's disease (the AD3 and AD4 loci, respectively). Alternative splicing has previously been reported in the PS-1 gene. In this study, elucidation of intron/exon boundary sequences revealed that PS-2 is encoded by 10 coding exons. In addition, PS-2 cDNA cloning and RT-PCR using RNA from a variety of normal tissues revealed the presence of alternatively spliced products. These products included species with in frame omissions of exon 8 and simultaneous omissions of exons 3 and 4.

Alternative Splicing↗
PubMed1996

Isolation and characterization of conformation sensitive antierythropoietin monoclonal antibodies: effect of disulfide bonds and carbohydrate on recombinant human erythropoietin structure.

We have isolated and characterized three anti-recombinant human erythropoietin (rHuEPO) monoclonal antibodies (MoAbs) that recognize nonoverlapping epitopes on rHuEPO. Anti-EPO MoAb D11 neutralizes rHuEPO activity whereas MoAbs F12 and 9G8A do not. This suggests that D11 may bind to the rHuEPO active site. MoAbs F12 and D11 recognize conformation dependent epitopes whereas 9G8A does not. Immunoassays were developed for each monoclonal. The 9G8A immunoassay was novel and useful because immunoreactivity increased when rHuEPO was denatured. Disruption of disulfide bonds or removal of carbohydrate increased 9G8A immunoreactivity, which suggests that these elements are important for rHuEPO structure or stability.

Antibodies, Monoclonal↗
PubMed1996

Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease.

The presenilin 1 gene has recently been identified as the locus on chromosome 14 which is responsible for a large proportion of early onset, autosomal dominantly inherited Alzheimer's disease (AD). We have elucidated the intron/exon structure of the gene and designed intronic primers to enable direct sequencing of the entire coding region (10 exons) of the presenilin gene in a large number of families. This strategy has enabled us to find a further two novel mutations in the gene. We discuss the distribution of mutations and the proportions of autosomal dominant AD with a mean age of onset below 60 years caused by mutations in this gene.

Alzheimer Disease↗
PubMed1996

Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer's disease. Alzheimer's Disease Collaborative Group.

BACKGROUND: Mutations in the presenilin-1 (PS-1) gene are associated with early-onset Alzheimer's disease. 40-50% of the risk for late-onset disease has been attributed to alleles at the apolipoprotein E (ApoE) locus. We have looked for an association between PS-1 and late- onset disease. METHODS: We collected blood samples from 208 white cases of dementia of the Alzheimer type and from 185 age-matched controls (mean ages 76.9 and 76.2 years, respectively; 58% female in each series). Clinical diagnostic accuracy for Alzheimer's disease in our patients is 96%. We also studied 29 African-American patients with dementia of the Alzheimer type and 50 age-matched controls (cases vs controls, 77.2 vs 72.0 years; 72 vs 77% female). We used PCR to test for an association between Alzheimer's disease and a polymorphism within the intron 3' to exon 8 of the PS-1 gene. The ApoE genotype of most of the cases and controls was known from previous investigations. FINDINGS: Homozygosity of the 1 allele in the PS-1 gene was associated with a doubling of the risk for late-onset Alzheimer's disease compared with the [12]/[22] genotype (odds ratio 1.97, 95% Cl 1.29-3.00). The proportion of Alzheimer's disease cases in the white population that could be attributed to homozygosity at this locus, as estimated by the attributable fraction, was 0.22. This compares with 0.35 for a single copy of ApoE4 and 0.15 for two copies. The smaller African-American series showed similar distribution of PS-1 genotype between cases and controls. INTERPRETATION: In our white series of cases, PS-1 accounted for about half as much of the risk for late-onset Alzheimer's disease as did ApoE4.

Age Factors↗
PubMed1996

Polymorphism in AACT gene may lower age of onset of Alzheimer's disease.

The ApoE-epsilon 4 allele is a predisposing factor for late onset Alzheimer's disease (AD), however it is neither necessary nor sufficient to cause the disease. A candidate for explaining part of the remaining genetic component is alpha 1-antichymotrypsin (AACT). In a case-control study we genotyped a polymorphism within the AACT gene to test for association with the disease. No allele of this gene showed an increased incidence among the population with AD compared with controls, even when taking ApoE genotype into account. This contrasts with the results of a recently published report. The mean age of onset was apparently lowered by the presence of the AACT AA genotype among ApoE-epsilon 4 bearers. If AACT genotype has an effect on risk for AD it may be predominantly amongst individuals with early onset AD.

Age of Onset↗
PubMed1996

The role of presenilin 1 in the genetics of Alzheimer's disease.

Approximately 75% of AD patients have an onset of the disease after the age of 60 years, and 60% of AD patients have no family history of the disease. Some cases of EOAD are clearly inherited in an autosomal-dominant manner. The beta APP gene on chromosome 21, the PS-1 gene on chromosome 14, and the PS-2 gene on chromosome 1 have all been characterized as genes in which mutations lead to familial EOAD. For LOAD, the work on ApoE indicates that the epsilon 4 allele is a risk factor for developing AD. However, 35-50% of all AD patients do not have an epsilon 4 allele. Other loci contributing to LOAD remain to be mapped and characterized. As in other complex disorders, these additional loci may involve genetic interactions with the known AD loci. Identification of all susceptibility loci for AD is a major goal in resolving the pathogenesis of AD.

Alternative Splicing↗
PubMed1995

A yeast artificial chromosome contig from human chromosome 14q24 spanning the Alzheimer's disease locus AD3.

Familial Alzheimer's disease has been previously linked to three genetic loci on chromosomes 21, 19 and 14. The AD3 locus on chromosome 14 has not been cloned and the molecular defect in chromosome 14-linked AD3 families has yet to be identified. Genetic linkage analysis has placed the AD3 locus in band 14q24 between the dinucleotide markers D14S61 and D14S289, a genetic distance of approximately 6.4 cM. We have constructed a yeast artificial chromosome (YAC) contig that covers the entire minimal region, encompassing all genetic markers that are non-recombinant for the disease in AD3-linked families. This contig, constructed by using a combination of YAC end sequence walking and sequence-tagged site (STS) mapping, consists of 63 YACs from three different libraries. The AD3 contig contains 12 polymorphic dinucleotide repeat markers from D14S61 to D14S251, as well as an additional 43 non-polymorphic STSs. This contiguous physical map of the region will allow the physical distances between the markers to be determined, as well as providing a framework for the identification of candidate genes.

Aged↗
PubMed1995

Effect of dietary salt load on transepithelial Na+ exchange in freshwater rainbow trout (Oncorhynchus mykiss)

Dietary Na+ loads (0.5&shy;70 mmol kg-1 fish) were almost completely absorbed within 7 h, and branchial Na+ excretion commenced within 1 h. Na+ loads of less than 1 mmol kg-1 were lost through the gills through a significant decrease in Na+ influx with unaltered Na+ efflux rate (compared with Na+ fluxes in unfed fish). At higher salt loads (>18 mmol kg-1), Na+ loss increased as a result of significantly higher Na+ efflux rates, with no further decrease in Na+ influx rate. Tissue Na+ concentrations were unchanged, apart from a significant increase in blood plasma Na+ concentration in fish loaded above 18 mmol kg-1. The results show that branchial Na+ fluxes may be rapidly adjusted in response to prevailing conditions, and possible control mechanisms are discussed.

Journal Article↗