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Biomedical subjects

J Wheeler

Publications and source records attributed to J Wheeler.

At least 19 recordsLinked to original sources
PubMed2006

First combined electron backscatter diffraction and transmission electron microscopy study of grain boundary structure of deformed quartzite.

The structures of boundaries in a deformed and dynamically recovered and recrystallized quartz polycrystal (mylonite) were characterized by transmission electron microscopy, after the misorientation angles across the same grain boundaries had been analysed using electron backscatter diffraction in a scanning electron microscope. In this new approach, a specific sample area is mapped with electron backscatter diffraction, and the mapped area is then attached to a foil, and by the ion beam thinned for transmission electron microscopy analysis. Dislocations in grain boundaries were recognized as periodic and parallel fringes. The fringes associated with dislocations are observed in boundaries with misorientations less than 9 degrees , whereas such fringes cannot be seen in the boundaries with misorientations larger than 17 degrees . Some boundaries with misorientations between 9 degrees and 17 degrees generally have no structures associated with dislocation. One segment of a boundary with a misorientation of 13.5 degrees has structures associated with dislocations. It is likely that the transition from low-angle to high-angle boundaries occurs at misorientations ranging from approximately 9 degrees to 14 degrees . Change in the grain boundary structure presumably influences the mobility of the boundaries. In the studied deformed quartz vein, a relative dearth of boundaries between misorientation angles of theta = 2 degrees and theta = 15 degrees has previously been reported, and high-angle boundaries form cusps where they intersect low-angle boundaries, suggesting substantial mobility of high-angle boundaries.

Journal Article↗
PubMed2005

Mobile phone technology in the management of asthma.

Peak flow monitoring is widely recommended as part of a self-management plan for asthma. We conducted an observational study using electronic peak flow monitoring and mobile phone technology in a UK general practice population over a nine-month period. Patients between 12 and 55 years of age who required treatment with regular inhaled steroids and (as needed) bronchodilators were recruited from nine general practices. Patients were included if their asthma was considered stable (i.e. no exacerbation in the previous three months). No therapeutic intervention was proposed. The primary outcome measure was compliance. In all, 69% of the 46 participants who filled in the post-study questionnaire were 'satisfied' or 'very satisfied' by the study, citing the ease of use and the increased autonomy and understanding of asthma as the main advantages. In total, 74% indicated that the system had helped to improve their ability to manage their symptoms. The most positive features of the telemedicine system were described as follows: increased awareness and information about asthma, improved ability to monitor/manage the condition with the feedback screens on the mobile phone and ease of use.

Adolescent↗
PubMed2003

The study of infectious intestinal disease in England: socio-economic impact.

To assess the socio-economic impact of infectious intestinal disease (IID) on the health care sector, cases and their families, cases of IID ascertained from a population cohort component and those presenting to general practices were sent a socio-economic questionnaire 3 weeks after the acute episode. The impact of the illness was measured and the resources used were identified and costed. The duration, severity and costs of illness linked to viruses were less than those linked to bacteria. The average cost per case of IID presenting to the GP was Pound Sterling253 and the costs of those not seeing a GP were Pound Sterling34. The average cost per case was Pound Sterling606 for a case with salmonella, Pound Sterling315 for campylobacter, Pound Sterling164 for rotavirus and Pound Sterling176 for SRSV. The estimated cost of IID in England was Pound Sterling743m expressed in 1994/5 prices. The costs of IID are considerable and the duration of the illness was found to be longer than previous reports have suggested.

Adolescent↗
PubMed2001

Characterization of murine polyreactive antigen-binding B cells: presentation of antigens to T cells.

Monoclonal polyreactive antibodies (Ab) can bind, at low affinity, a variety of different self and non-self antigens (Ag). Recent studies in humans showed that polyreactive Ab are expressed on the surface of a subset of peripheral B lymphocytes and clonal analysis revealed that a variety of different Ag can bind to single cells expressing these Ab. To see if these polyreactive Ag-binding B (PAB) cells also are present in mice, fluorescein-conjugated Ag and FACS sorting were used to identify and separate PAB cells from non-polyreactive Ag-binding B cells. Depending on the Ag used for screening, up to one-third of mouse splenic B cells displayed polyreactive Ag-binding properties. Confirmation that the Ag actually bound to surface Ig came from treating PAB cells with anti-Ig which inhibited Ag binding by up to 80 %. Further studies showed that PAB cells could present Ag to Ag-specific T cells, but despite their Ag-presenting ability, PAB cells from normal mice failed to trigger Ag-specific T cells to proliferate. Analysis of the co-stimulatory molecules B7-1 and B7-2 showed that these molecules were not expressed on PAB cells from normal mice. These findings argue that the lack of co-stimulatory molecules on PAB cells is the most likely explanation for their failure to stimulate Ag-specific T cells. The ability of PAB cells from normal mice to bind and present Ag to Ag-specific T cells, without causing them to proliferate, suggests that PAB cells may contribute to the induction and / or maintenance of immunological tolerance.

Animals↗
PubMed2001

Improvement of in-rumen digestibility of alfalfa forage by genetic manipulation of lignin O-methyltransferases.

Lignin inhibits forage digestibility by ruminant animals, and lignin levels and the proportion of dimethylated syringyl (S) lignin monomers increase with progressive maturity in stems of forage crops. We generated transgenic alfalfa (Medicago sativa L.) with reduced lignin content and altered lignin composition. Down-regulation of caffeic acid 3-O-methyltransferase (COMT) reduces lignin content, accompanied by near total loss of S lignin, whereas down-regulation of caffeoyl coenzyme A 3-O-methyltransferase (CCoAOMT) reduces lignin content without reduction in S lignin. These changes are not accompanied by altered ratios of cell wall polysaccharides. Analysis of rumen digestibility of alfalfa forage in fistulated steers revealed improved digestibility of forage from COMT down-regulated plants, but a greater improvement in digestibility following down-regulation of CCoAOMT. The results indicate that both lignin content and composition affect digestibility of alfalfa forage, and reveal a new strategy for forage quality improvement by genetic manipulation of CCoAOMT expression.

Animals↗
PubMed2001

Comparison of fluorescence and rinsing methods for assessing dermal exposure.

There are a number of methods of estimating dermal contamination. "Potential exposure" methods, such as patch and whole-body oversuit sampling, intercept the contaminant before it reaches the skin. "Actual exposure" measurements recover the contaminant from the skin by wiping, stripping, or rinsing, or, in the case of fluorescent tracer dye monitoring, assess it in-situ on the skin. These different methods can give rise to very different results. Comparison of methods is difficult, because they usually interfere within-subject. This presentation is a comparison of two compatible 'actual dermal contamination' measurement techniques. They are: (1) fluorescence monitoring of a tracer dye in-situ on the skin, using ultraviolet light and a video camera linked to an image processor; (2) rinsing of the skin to recover a metal tracer salt for later assay in solution. Several painting and spraying application tasks were carried out by a panel of volunteers who wore T-shirts, shorts, and open sandals. The exercises simulated domestic or nonoccupational tasks. Results showed excellent agreement, with discrepancies identified and explained. The good agreement of the two completely different, independent tracer methods for measuring skin contamination contributes to their mutual validation.

Environmental Exposure↗
PubMed2000

APC mutations in sporadic colorectal tumors: A mutational "hotspot" and interdependence of the "two hits".

Although APC mutations occur at a high frequency in colorectal cancers, few studies have performed a comprehensive analysis by screening the whole gene for mutations and assessing allelic loss. APC seems to act as a tumor-suppressor gene in a "nonclassical" fashion: data from familial adenomatous polyposis (FAP) show that the site of the germ-line mutation determines the type of "second hit" in FAP tumors, and simple protein inactivation is selected weakly, if at all. In this study, we screened the entire coding region of APC for mutations and assessed allelic loss in a set of 41 colorectal cancer cell lines. Of 41 cancers, 32 (83%) showed evidence of APC mutation and/or allelic loss. We identified several APC mutations and found a "hotspot" for somatic mutation in sporadic colorectal tumors at codon 1,554. Our results suggest that APC mutations occur in the great majority of colorectal cancers, the exceptions almost all being RER+ tumors, which may substitute for altered APC function by mutations in beta-catenin and/or at other loci. When combined with previously published data, our results show that there is interdependence of the "two hits" at APC in sporadic colorectal tumors as well as in FAP. APC mutations in the "mutation cluster region," especially those close to codon 1,300, are associated with allelic loss, whereas tumors with mutations outside this region tend to harbor truncating mutations. The causes of this phenomenon are probably selection for retained N-terminal and lost C-terminal APC functions, effects on beta-catenin levels, and APC protein stability.

Base Sequence↗
PubMed2000

The role of laparoscopy in preoperative staging of esophageal cancer.

BACKGROUND: Diagnostic laparoscopy has been used to determine resectability and to prevent unnecessary laparotomy in patients with advanced esophageal cancer. The objective of this prospective study was to evaluate the role of laparoscopy in conjunction with computed tomography (CT) scan in staging patients with esophageal cancer. METHODS: From March 1995 to October 1998, 59 patients with biopsy-proven esophageal cancer underwent diagnostic laparoscopy with concurrent vascular access device and feeding jejunostomy tube placement. RESULTS: Laparoscopy changed the treatment plan in 10 of 59 patients (17%). Of the patients with normal-appearing regional or celiac nodes, 78% were confirmed by biopsy to be tumor free, whereas 76% of patients with abnormal-appearing nodes were confirmed by biopsy to have node-positive disease. CONCLUSIONS: Diagnostic laparoscopy is useful for detecting and confirming nodal involvement and distant metastatic disease that potentially would alter treatment and prognosis in patients with esophageal cancer.

Adult↗
PubMed2000

Feeding outcomes and influences within the neonatal unit.

This study examined the feeding intention of mothers (n = 100), and the factors and beliefs, and changes in those factors or beliefs that influenced their choices, in the challenging environment of the neonatal unit. Mothers' experience and the frequency of nurse-assisted feeding activities were examined in mothers intending and not intending to breast-feed on discharge. Eighty-one per cent of mothers were either partially or fully breast-feeding or intending to do so on discharge. The most important factors identified as influencing this feeding choice included personal choice, with other influences being special benefits, more natural and feeling closer to the baby. Experiences such as infants receiving their first sucking feed from either the breast or bottle (inclusive of breast milk) and mothers expressing breast milk more frequently, were found to be significantly different and increased in frequency, in mothers intending to breast-feed. Differences in the mean weighted total daily nurse-assisted feeding score confirmed that these activities varied with gestational age (< or = 32 weeks [2.57], 32 to less than 35 weeks [3.86], and > or = 35 weeks [4.91]; F = 7.04, d.f. 55, P = 0.002), although there was insufficient power to determine differences between breast-feeding and non-breast-feeding mothers. The use of the Feeding Activities Calendar may have contributed to increased activity and high levels of breast-feeding in this preterm group.

Adult↗
PubMed2000

Community acquired pneumonia--a prospective UK study.

BACKGROUND: There are few data on paediatric community acquired pneumonia (PCAP) in the UK. AIMS: To investigate the aetiology and most useful diagnostic tests for PCAP in the north east of England. METHODS: A prospective study of hospital admissions with a diagnosis of PCAP. RESULTS: A pathogen was isolated from 60% (81/136) of cases, and considered a definite or probable cause of their pneumonia in 51% (70/136). Fifty (37%) had a virus implicated (65% respiratory syncytial virus) and 19 (14%) a bacterium (7% group A streptococcus, 4% Streptococcus pneumoniae), with one mixed infection. Of a subgroup (51 patients) in whom serum antipneumolysin antibody testing was performed, 6% had evidence of pneumococcal infection, and all were under 2 years old. The best diagnostic yield was from paired serology (34%, 31/87), followed by viral immunofluorescence (33%, 32/98). CONCLUSION: Viral infection accounted for 71% of the cases diagnosed. Group A streptococcus was the most common bacterial infective agent, with a low incidence of both Mycoplasma pneumoniae and S pneumoniae. Pneumococcal pneumonia was the most common bacterial cause of pneumonia in children under 2 years but not in older children. Inflammatory markers and chest x ray features did not differentiate viral from bacterial pneumonia; serology and viral immunofluorescence were the most useful diagnostic tests.

Adolescent↗
PubMed1999

Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guérin vaccination.

Data obtained in animals indicate that neonatal immune responses are biased toward Th2. This could reduce the efficacy of vaccines against viral and mycobacterial diseases. The ability of human newborns to develop a Th1 immune response upon immunization has not been studied. Since the vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers a Th1-type response in adults, we investigated whether it induces a similar response in newborns and whether age at vaccination influences immunogenicity. We found that BCG vaccination at birth induces a memory Th1-type response of similar magnitude to that when given later in life. This study demonstrates that human newborns can be immunized against pathogens controlled by a Th1 immune response.

Antigens, Bacterial↗
PubMed1999

Rapid detection of methicillin-resistant staphylococci by multiplex PCR.

A multiplex PCR was developed to detect the coagulase gene (coa; pathognomic of Staphylococcus aureus) and the mecA gene (characteristically encoding for methicillin resistance in staphylococci) in a single, rapid test. Suitable primers for the gene targets and an internal, amplification control were incorporated into a multiplex PCR assay, which was then optimized on a capillary air thermal cycler to improve the turnaround time of the test to approximately 1.5 hours. The assay was evaluated with 111 fresh clinical isolates of staphylococci. The multiplex PCR correctly distinguished between isolates of S. aureus, which were sensitive to methicillin (MSSA) and those resistant to it (MRSA). It also correctly differentiated between similar isolates of coagulase negative staphylococci (MSSE and MRSE respectively). It was concluded that this multiplex PCR was a rapid and reliable method for the detection of methicillin-resistant staphylococci.

Coagulase↗
PubMed1999

Investigation of under-ascertainment in epidemiological studies based in general practice.

BACKGROUND: One of the aims of the Study of Infectious Intestinal Disease (IID) in England is to estimate the incidence of IID presenting to general practice. This sub-study aims to estimate and correct the degree of under-ascertainment in the national study. METHODS: Cases of presumed IID which presented to general practice in the national study had been ascertained by their GP. In 26 general practices, cases with computerized diagnoses suggestive of IID were identified retrospectively. Cases which fulfilled the case definition of IID and should have been ascertained to the coordinating centre but were not, represented the under-ascertainment. Logistic regression modelling was used to identify independent factors which influenced under-ascertainment. RESULTS: The records of 2021 patients were examined, 1514 were eligible and should have been ascertained but only 974 (64%) were. There was variation in ascertainment between the practices (30% to 93%). Patient-related factors independently associated with ascertainment were: i) vomiting only as opposed to diarrhoea with and without vomiting (OR 0.37) and ii) consultation in the surgery as opposed to at home (OR 2.18). Practice-related factors independently associated with ascertainment were: i) participation in the enumeration study component (OR 1.78), ii) a larger number of partners (OR 0.3 for 7-8 partners); iii) rural location (OR 2.27) and iv) previous research experience (OR 1.92). Predicted ascertainment percentages were calculated according to practice characteristics. CONCLUSION: Under-ascertainment of IID was substantial (36%) and non-random and had to be corrected. Practice characteristics influencing variation in ascertainment were identified and a multivariate model developed to identify adjustment factors which could be applied to individual practices. Researchers need to be aware of factors which influence ascertainment in acute epidemiological studies based in general practice.

Adolescent↗