Are children really safeguarded in the UK health service?
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Attitude of Health Personnel↗
Biomedical subjects
C Graham
Publications and source records attributed to C Graham.
Human Papillomavirus testing for the management of low-grade cervical abnormalities in the UK--Influence of age and testing strategy.
BACKGROUND: The results of the UK pilot studies were encouraging with respect to the introduction of Human Papillomavirus (HPV) testing as a means to improve the management of low-grade cytological abnormalities. However, several important unresolved issues related to HPV triage remain, two of which are: what type of HPV test should be used and what age group should be targeted. OBJECTIVES: To perform an evaluation of two commercial HPV detection tests and to correlate disease persistence and clearance with age and HPV status by the two tests. STUDY DESIGN: We performed an evaluation of two commercial HPV tests in a cross-sectional analysis of 322 cervical cytology specimens with low-grade abnormalities. A subset of these specimens were then examined longitudinally, in order to correlate disease persistence and clearance with age and HPV status by the two detection tests. RESULTS: The two tests performed similarly with respect to the longitudinal identification/prediction of high-grade cervical disease. Age did not appear to be a factor in determining which cases went on to manifest high-grade disease within 3 years of a low-grade result (p=0.678). CONCLUSIONS: This study weakens the case for age-adjusted HPV triage of low-grade cervical abnormalities.
Adult↗
Expression and localization of monocarboxylate transporters and sodium/proton exchangers in bovine rumen epithelium.
Monocarboxylate-H+ cotransporters, such as monocarboxylate transporter (MCT) SLC16A, have been suggested to mediate transruminal fluxes of short-chain fatty acids, ketone bodies, and lactate. Using an RT-PCR approach, we demonstrate expression of MCT1 (SLC16A1) and MCT2 (SLC16A7) mRNA in isolated bovine rumen epithelium. cDNA sequence from these PCR products combined with overlapping expressed sequence tag data allowed compilation of the complete open reading frames for MCT1 and MCT2. Immunohistochemical localization of MCT1 shows plasma membrane staining in cells of the stratum basale, with intense staining of the basal aspects of the cells. Immunostaining decreased in the cell layers toward the rumen lumen, with weak staining in the stratum spinsoum. Immunostaining in the stratum granulosum and stratum corneum was essentially negative. Since monocarboxylate transport will load the cytosol with acid, expression and location of Na+/H+ exchanger (NHE) family members within the rumen epithelium were determined. RT-PCR demonstrates expression of multiple NHE family members, including NHE1, NHE2, NHE3, and NHE8. In contrast to MCT1, immunostaining showed that NHE1 was predominantly localized to the stratum granulosum, with a progressive decrease toward the stratum basale. NHE2 immunostaining was observed mainly at an intracellular location in the stratum basale, stratum spinosum, and stratum granulosum. Given the anatomic localization of MCT1, NHE1, and NHE2, the mechanism of transruminal short-chain fatty acid, ketone body, and lactate transfer is discussed in relation to a functional model of the rumen epithelium comprising an apical permeability barrier at the stratum granulosum, with a cell syncitium linking the stratum granulosum to the blood-facing stratum basale.
Acids↗
New football boots and toxic shock syndrome.
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Adolescent↗
Giant cell arteritis--part of a spectrum of autoimmune disease?
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Aged↗
Campylobacter in chicken livers and their destruction by pan frying.
AIM: To enumerate Campylobacter spp. on the external surface and internal portions of chicken livers, and to assess the cooking required to inactivate naturally present cells. METHODS AND RESULTS: Of 30 livers tested all yielded Campylobacter spp. on their surfaces and 90% were found to contain the organism in internal tissue. Four (13%) livers contained >10(4) MPN campylobacters, and an additional seven (23%) contained >10(3) MPN campylobacters per liver. The internal temperature of pan-fried livers under the conditions used reached a maximum of 70-80 degrees C, and maintaining this temperature for 2-3 min was necessary to inactivate naturally occurring Campylobacter spp. All isolates identified were either C. jejuni or C. coli. CONCLUSIONS: Chicken livers represent a potential source of human campylobacteriosis as they contained >10(4) MPN per liver in 13% of the samples tested. Pan-frying can produce an acceptable product that is safe to eat. SIGNIFICANCE AND IMPACT OF THIS STUDY: The data provided can be used in exposure assessments of Campylobacter in poultry products in terms of both quantitative data and assessing pan-frying and its ability to destroy campylobacters.
Animals↗
UT-B is expressed in bovine rumen: potential role in ruminal urea transport.
The UT-A (SLC14a2) and UT-B (SLC14a1) genes encode a family of specialized urea transporter proteins that regulate urea movement across plasma membranes. In this report, we describe the structure of the bovine UT-B (bUT-B) gene and characterize UT-B expression in bovine rumen. Northern analysis using a full-length bUT-B probe detected a 3.7-kb UT-B signal in rumen. RT-PCR of bovine mRNA revealed the presence of two UT-B splice variants, bUT-B1 and bUT-B2, with bUT-B2 the predominant variant in rumen. Immunoblotting studies of bovine rumen tissue, using an antibody targeted to the NH2-terminus of mouse UT-B, confirmed the presence of 43- to 54-kDa UT-B proteins. Immunolocalization studies showed that UT-B was mainly located on cell plasma membranes in epithelial layers of the bovine rumen. Ussing chamber measurements of ruminal transepithelial transport of (14)C-labeled urea indicated that urea flux was characteristically inhibited by phloretin. We conclude that bUT-B is expressed in the bovine rumen and may function to transport urea into the rumen as part of the ruminant urea nitrogen salvaging process.
Amino Acid Sequence↗
Superficial adnexal lymphangioma.
An 11-year old girl presented with a painless fleshy lesion involving the plica, caruncle and medial bulbar and palpebral conjnctiva of the right eye since birth. The patient underwent debulking and cryotherapy. Biopsy showed lymphatic vessels lined with one flattened layer of endothelial cells devoid of smooth muscles or pericytes. Most of the lumens contained pink amorphous lymph with lymphoid aggregates.
Child↗
Cystic fibrosis genotype and bacterial infection: a possible connection.
Patients with cystic fibrosis (CF) have repeated bacterial infection of the airways, which can lead to chronic infection. There is evidence that disease severity is determined by the genetic mutations present. This study aims to establish if CF genotype is related to the frequency and types of airway bacterial infection. Adult patients attending the regional CF unit are followed for two years and assigned to one of three groups depending on whether they are chronically infected with Burkholderia cepacia complex (BCC) organisms, Pseudomonas aeruginosa, or neither of these organisms. Genotype analysis is performed on all patients to determine which of the cystic fibrosis transmembrane regulator (CFTR) gene mutations are present. The numbers and types of organism with the CFTR mutations isolated from sputum are identified. Data are available on 59 patients: 15 colonised with BCC, 24 colonised with P. aeruginosa, and 20 not colonised with either organism. Twenty patients were homozygous for deltaF508, 25 were heterozygous, and the deltaF508 mutation was not present in the remaining 14 patients. Patients homozygous or heterozygous for the deltaF508 mutation had an increased likelihood of colonisation with BCC or P. aeruginosa, an increased number of positive sputum cultures and a higher frequency of multiple infecting organisms. Cystic fibrosis mutational analysis identified seven patients who had the R117H mutation. These patients were less likely to be colonised with BCC or P. aeruginosa. In conclusion, patients homozygous or heterozygous for the deltaF508 deletion are more likely to suffer airway colonisation with BCC or P. aeruginosa, with increased numbers of positive sputum cultures and infecting organisms. Those with the R117H mutation are less likely to be colonised by Gram-negative organisms.
Adult↗
Polymorphisms in the interleukin-4 and IL-4 receptor genes and multiple sclerosis: a study in Spanish-Basque, Northern Irish and Belgian populations.
Cytokine gene polymorphisms are known to influence susceptibility and disease course of many autoimmune diseases. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and axonal damage. We analysed both the well-known intronic variable number of tandem repeat (VNTR) and +33 C/T single-nucleotide polymorphisms (SNP) in the IL-4 gene, as well as the functional Q551R SNP in the IL4-R gene in a cohort of three distinct populations comprising sporadic cases and controls from the northern Spanish Basque Country and Northern Ireland, as well as family trios from Belgium. The IL-4 +33 TT genotype was decreased in primary progressive (PP) versus relapsing-remitting (RR) patients in the Northern Irish population (OR = 0.14; 95% CI = 0.018-1.09). Two-marker haplotype distribution of the VNTR and +33 C/T SNP in PP patients differed from that seen in RR patients in Northern Ireland (P = 0.03). The R allele of the Q551R SNP was significantly under-transmitted in the Belgian trio families (P = 0.003), although this effect was not seen in the Northern Irish and Basque data sets. We did not identify IL-4-IL4-R gene-gene interaction in determining susceptibility or clinical parameters of MS. Disease or genetic heterogeneity or both may be responsible for the observed lack of reproduction in different populations. Our data reinforce recent findings for a role of IL4-R in susceptibility to MS.
Adult↗
Persistent high risk HPV infection associated with development of cervical neoplasia in a prospective population study.
AIMS: To monitor the association between the course of high risk human papillomavirus (HR-HPV) infection and the development of cervical neoplasia over time, from a baseline of normal cervical cytology. METHODS: This paper presents the follow up data from a previous cross sectional analysis. Women from a screening population who had normal cytology and who were HR-HPV positive were recalled after two to three years for cytology and HPV genotyping. The development of cervical neoplasia at follow up was related to the course of HPV infection (clearance, persistence, or sequential infection) and the presence of single or multiple HPV infections at baseline. A comparator control group of women who were HPV and cytologically negative at baseline were selected from the same population. RESULTS: Twelve cases of dyskaryosis were found in women who were HPV positive at baseline; four were high grade. Only three cases of low grade dyskaryosis were found in the control group. Women with type specific persistent infections were significantly more likely to develop cervical neoplasia than women who cleared the infection (p = 0.0001) or were sequentially infected with different types (p = 0.001). Women with multiple HPV infections at baseline were no more likely to develop cervical dyskaryosis than those with a single infection. CONCLUSIONS: Type specific persistent HR-HPV infection as monitored by genotyping can identify women at increased risk of cervical neoplasia more accurately than a single or repeated presence/absence HPV test. The cost effectiveness of such an approach should be investigated by an appropriate, large scale cost-benefit analysis.
Adult↗
Rates of drug resistance and risk factor analysis in civilian and prison patients with tuberculosis in Samara Region, Russia.
BACKGROUND: Tuberculosis (TB) and HIV rates continue to escalate in Russia, but true rates for drug resistance, especially multidrug resistant tuberculosis (MDR TB), are unknown. A study was conducted with the aims of identifying first line drug resistance, both in the civilian and prison sectors, for new and previously treated cases; and risk factors for the development of drug resistance. METHODS: A cross sectional survey was undertaken of 600 patients (309 civilians, 291 prisoners) with bacteriologically confirmed pulmonary TB over a 1 year period during 2001-2 in Samara Oblast, Russia. RESULTS: The prevalence of isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide resistance in new TB cases (civilian and prison patients) was 38.0%, 25.2%, 34.6%, 14.7%, and 7.2%, respectively. The prevalence of MDR TB was 22.7%, 19.8%, and 37.3% in all new cases, new civilian cases, and new prison cases, respectively, with an overall prevalence of 45.5% and 55.3% in previously treated cases. Factors associated with resistance included previous TB treatment for more than 4 weeks, smoking (for isoniazid resistance), the presence of cavitations on the chest radiograph, and imprisonment. HIV was not associated with resistance in all patients. The rates of resistance were significantly higher in prisoners, with rate ratios (RR) of 1.9 (95% CI 1.1 to 3.2) for MDR TB, 1.9 (95% CI 1.1 to 3.2) for rifampicin, and 1.6 (95% CI 1.0 to 2.6) for isoniazid. CONCLUSIONS: Rates of first line drug resistance are high, particularly in prisoners and previously treated cases. TB control programmes should initially focus on standardised treatment to maximise cure, combined with measures to reduce institutional TB spread (particularly in prisons) coupled with early diagnosis of MDR TB to reduce the spread and development of resistance.
Adult↗
Tuberculosis, HIV seroprevalence and intravenous drug abuse in prisoners.
High rates of tuberculosis (TB) and HIV are believed to exist in Russian prisons. Prisoners with TB were studied in order to identify the following: 1) prevalence of HIV, and risk factors for HIV and other blood-borne virus infections; and 2) clinical and social factors that might compromise TB treatment effectiveness and/or patient adherence and, hence, encourage treatment failure. A 1-yr cross-sectional prevalence study of 1,345 prisoners with TB was conducted at an in-patient TB facility in Samara, Russian Federation. HIV and hepatitis B and/or C co-infection occurred in 12.2% and 24.1% of prisoners, respectively, and rates were significantly higher than in civilians. Overall, 48.6% of prisoners used drugs, of which 88.3% were intravenous users. Prisoners were more likely to be intravenous drug users and HIV positive compared with civilians with TB, and 40.2% of prisoners shared needles. Two-thirds of prisoners (68.6%) had received previous TB drug therapy (frequently multiple, interrupted courses) and were significantly more likely than civilians to have had previous therapy consistent with the high drug-resistance rates seen. Prisons are major drivers of the tuberculosis and HIV epidemics. Novel strategies are needed to reduce the spread of blood borne diseases, particularly in intravenous drug users.
Adult↗
Functional organization of the bovine rumen epithelium.
The functional organization of the bovine rumen epithelium has been examined by electron and light microscopy combined with immunocytochemistry to define a transport model for this epithelium. Expression of connexin 43, an integral component of gap junctions, the tight-junction molecules claudin-1 and zonula occludens 1 (ZO-1), and the catalytic alpha-subunit of Na(+)-K(+)-ATPase was demonstrated by SDS-PAGE and Western blotting. From the lumen surface, four cell layers can be distinguished: the stratum corneum, the stratum granulosum, the stratum spinosum, and the stratum basale. Both claudin-1 and ZO-1 immunostaining showed plasma membrane staining, which was present at the stratum granulosum with decreasing intensity through the stratum spinosum to the stratum basale. The stratum corneum was negative for claudin-1 immunostaining. Transmission electron microscopy confirmed that occluding tight junctions were present at the stratum granulosum. Plasma membrane connexin 43 immunostaining was most intense at the stratum granulosum and decreased in intensity through stratum spinosum and stratum basale. There was intense immunostaining of the stratum basale for Na(+)-K(+)-ATPase, with weak staining of the stratum spinosum. Both the stratum granulosum and the stratum corneum were essentially negative. Stratum basale cells also displayed a high mitochondrial density relative to more apical cell layers. We conclude that epithelial barrier function may be attributed to the stratum granulosum and that cell-cell gap junctions allow diffusion to interconnect the barrier cell layer with the stratum basale where Na(+)-K(+)-ATPase is concentrated.
Animals↗
Crystal structure of eta-crystallin: adaptation of a class 1 aldehyde dehydrogenase for a new role in the eye lens.
Eta-crystallin is a retinal dehydrogenase that has acquired a role as a structural protein in the eye lens of elephant shrews, members of an ancient order of mammals. While it retains some activity toward retinal, which is oxidized to retinoic acid, the protein has acquired a number of specific sequence changes that have presumably been selected to enhance the lens role. The crystal structure of eta-crystallin, in common with class 1 and 2 ALDHs, is a dimer of dimers. It has a better-defined NAD binding site than those of related mammalian ALDH1 enzymes with the cofactor bound in the "hydride transfer" position in all four monomers with small differences about the dimer dyads. Although the active site is well conserved, the substrate-binding site is larger in eta-crystallin, and there are some mutations to the substrate access tunnel that might affect binding or release of substrate and product. It is possible that eta-crystallin has lost flexibility to improve its role in the lens. Enhanced binding of cofactor could enable it to act as a UV/blue light filter in the lens, improving visual acuity. The structure not only gives a view of a "natural mutant" of ALDH1 illustrating the adaptive conflict that can arise in multifunctional proteins, but also provides a well-ordered NAD binding site structure for this class of enzymes with important roles in development and health.
Aldehyde Dehydrogenase↗
Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis.
OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.
Adult↗
A national outbreak of multi-resistant Salmonella enterica serovar Typhimurium definitive phage type (DT) 104 associated with consumption of lettuce.
Between 1 August and 15 September 2000, 361 cases of Salmonella enterica serotype Typhimurium definitive phage type (DT) 104, resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, spectinomycin and tetracycline (R-type ACSSuSpT), were identified in England and Wales residents. Molecular typing of 258 isolates of S. Typhimurium DT104 R-type ACSSuSpT showed that, although isolates were indistinguishable by pulsed-field gel electrophoresis, 67% (174/258) were characterized by a particular plasmid profile. A statistically significant association between illness and consumption of lettuce away from home was demonstrated (OR = 7.28; 95% CI=2.25-23.57; P=0.0006) in an unmatched case-control study. Environmental investigations revealed that a number of food outlets implicated in the outbreak had common suppliers of salad vegetables. No implicated foods were available for microbiological testing. An environmental audit of three farms that might have supplied salad vegetables to the implicated outlets did not reveal any unsafe agricultural practices. The complexity of the food supply chain and the lack of identifying markers on salad stuffs made tracking salad vegetables back to their origin extremely difficult in most instances. This has implications for public health since food hazard warnings and product withdrawal are contingent on accurate identification of the suspect product.
Bacteriophage Typing↗