The Leicestershire local guideline adaptation and implementation programme: a model for clinical effectiveness?
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Evidence-Based Medicine↗
Biomedical subjects
K Stevenson
Publications and source records attributed to K Stevenson.
What proportion of patients refuse consent to data collection from their records for research purposes?
In a randomised trial of the implementation of guidelines for asthma and angina, we sent questionnaires that included a request for consent to collect data from the patient's clinical records to 5069 patients in 81 general practices. Of these 3429 (67.6%) responded, of whom 335 (9.8% [95%, CI = 8.8%-10.8%]) refused consent. We conclude that consent should always be sought unless a research ethics committee has waived this requirement for pressing reasons.
Aged↗
Invariant or highly conserved TCR alpha are expressed on double-negative (CD3+CD4-CD8-) and CD8+ T cells.
TCR alpha (TCRA) expression was examined in RNA samples from PBMC and isolated populations of CD4+, CD8+, and DN T cells from 15 healthy individuals. The expressed TCR repertoire was surveyed using spectratype analysis, a technique that displays the distribution of complementarity determining region 3 (CDR3) lengths for each TCRAV gene family. The results revealed the presence of unusual populations of double-negative (DN; CD4-CD8-CD3+) T cells that express invariant or conserved TCRAV4A, AV7, AV19, and AV24 chains. Each of the conserved TCRA families was over-represented in >70% of the individuals studied, and all individuals expressed at least one of the over-represented TCRAV families. Over-represented conserved AV4A or AV7 sequences were also present in CD8+ T cells from most donors. The extent of TCRA sequence conservation is unparalleled. TCRAV4A, AV19, and AV24 sequences were invariant, although AV4A and AV19 transcripts contained N region additions. TCRAV24 transcripts derived from the direct juxtaposition of V and J gene segments. TCRAV7 sequences showed some diversity in two amino acids encoded at junctions of V and J gene segments. Although derivation of DN T cells with conserved TCRA chains is puzzling, the wide-spread expression of these unusual cells suggests an important function.
Adult↗
Epidemiological study of paratuberculosis in wild rabbits in Scotland.
A survey of 22 farms confirmed the presence of paratuberculosis in wild rabbits in Scotland. Regional differences were apparent in the prevalence of the disease in rabbits, with a significantly higher incidence occurring in the Tayside region. Statistical analysis showed a significant relationship between a previous history or current problem of paratuberculosis in cattle and the presence of paratuberculosis in rabbits on the farms. Molecular genetic typing techniques could not discriminate between selected rabbit and cattle isolates from the same or different farms, suggesting that the same strain may infect and cause disease in both species and that interspecies transmission may occur. The possibility of interspecies transmission and the involvement of wildlife in the epidemiology of paratuberculosis have important implications for the control of the disease.
Animals↗
Feline skin granuloma associated with Mycobacterium avium.
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Animals↗
Early immunopathological events in experimental ovine paratuberculosis.
An experimental oral infection of neonatal (< 2 weeks old) lambs with a cervine isolate of Mycobacterium avium subspecies paratuberculosis (M.a. paratuberculosis), the causal agent of ruminant paratuberculosis (Johne's disease) was used to investigate bacteriological, histopathological and immunological changes during the early (up to 8 weeks) post-infection phase. In vitro culture for mycobacteria was positive in one faecal and three mesenteric lymph node (MLN) samples from the eight infected lambs. All mycobacterial isolates from MLN were identified as M.a. paratuberculosis by polymerase chain reaction (PCR). Small-to-medium sized focal granulomata were observed in jejunal (JPP) and ileal Peyer's patches (IPP) from four of the eight infected lambs. Compared with controls, JPP from all infected lambs had significantly (p < 0.05) higher proportions of CD8+ and CD2+ lymphocytes, and there were significantly (p < 0.05) fewer cells expressing B lymphocyte-associated markers in IPP and MLN. The T/B cell ratio was significantly (p < 0.05) increased in both JPP and MLN from infected lambs. The expression of a range of genes for cytokines was examined using specific reverse transcriptase PCR (RT-PCR) amplification of messenger RNA (mRNA) template isolated from MLN, JPP and IPP from both groups of animals. Densitometric analyses indicated that, in infected animals, MLN expressed significantly (p < 0.05) more mRNA for TNF-alpha: JPP had significantly increased (p < 0.05) mRNA for GM-CSF and significantly decreased (p < 0.05) mRNA for IL-4 and IFN-gamma. Infected lambs had significantly (p < 0.05) decreased titres of both circulating IgG and gut mycobacteria-associated IgG antibody. Infection was not associated with any consistent changes in lymphocyte reactivity to specific mycobacterial antigens, IFN-gamma release into supernatants from in vitro intestinal lymphocyte cultures or gut IgA antibody levels.
Animals↗
Paratuberculosis in wild rabbits (Oryctolagus cuniculus)
A survey of wild rabbits in Tayside, Scotland revealed that 67 per cent were infected with Mycobacterium avium subspecies paratuberculosis. In general, the infected rabbits had histopathological changes within the lymph nodes and intestines which were consistent with the changes due to paratuberculosis in ruminants. The survey raises the possibility that rabbits and other wildlife may be involved in the epidemiology of paratuberculosis, a possibility which has important implications for the control of the disease.
Animals↗
Prospective prenatal diagnosis of Prader-Willi syndrome due to maternal disomy for chromosome 15 following trisomic zygote rescue.
We present a prenatal predictive diagnosis of Prader-Willi syndrome arising as a result of maternal heterodisomy for chromosome 15. The diagnosis arose following chorionic villus sampling which showed a mosaic trisomy 15 karyotype with a chromosomally normal follow-up amninocentesis. Molecular studies on DNA extracted from cultured amniocytes showed no evidence of a paternal allele at two widely separated loci and this was taken as evidence of maternal disomy predictive of Prader-Willi syndrome in the fetus.
Adult↗
The contribution of molecular biology to Mycobacterium avium subspecies Paratuberculosis research.
Molecular biology has contributed to our knowledge and understanding of the structure of Mycobacterium avium subspecies paratuberculosis and has been particularly useful in determining those components that elicit immune responses in the host or discriminate M. avium paratuberculosis from other closely related environmental mycobacteria. As such, it has made a significant impact in the field of diagnosis, and has been instrumental in the development of specific and sensitive diagnostic tests. The next decade will see exciting new developments in paratuberculosis research as a consequence of substantial advances made in the construction of gene transfer systems in mycobacteria. These will provide opportunities for applying new strategies to determine the genetic basis for pathogenesis and the mechanisms of drug resistance and will offer new prospects for the rational design of efficient vaccines.
Animals↗
Pregnancy resulting from intracytoplasmic injection of cryopreserved spermatozoa recovered from testicular biopsy.
We report a clinical pregnancy occurring in a 31 year old patient following intracytoplasmic sperm injection (ICSI) of cryopreserved spermatozoa obtained from a testicular biopsy. This was the couple's second attempt at an ovarian stimulated cycle resulting in the collection of 17 metaphase II ova which were all injected with progressively motile spermatozoa. A fertilization rate of 58% and a cleavage rate of 90% were achieved. This report is our first case of ICSI using cryopreserved testicular spermatozoa which resulted in normal fertilization, embryo development and an on-going singleton pregnancy.
Adult↗
A prospective randomized study comparing short- and intermediate-term perioperative outcome variables after spinal or general anesthesia for lumbar disk and laminectomy surgery.
General or regional anesthesia may be used for lumbar laminectomy. To determine whether one method is superior, 122 patients were randomly assigned to receive either a standard general anesthetic (GA) or spinal anesthesia (SA) supplemented with intravenous (IV) propofol sedation. Data from the intraoperative period through hospital discharge were collected and compared. Demographically, both groups were similar. Total anesthesia (131.0 +/- 4.3 vs 106.6 +/- 3.2 min) and surgical times (81.5 +/- 3.6 vs 67.1 +/- 2.8 min) were longer in the GA group. Intraoperative hemodynamics were similar between groups except that the incidence of increased blood pressure was more frequent with GA (26.2% vs 3.3%). Blood loss was less during SA (133 +/- 18 mL vs 221 +/- 32 mL). Postanesthesia care unit (PACU) heart rates and mean arterial pressures were higher in the GA group. Peak pain scores in the PACU were higher after GA compared with SA (58 +/- 4 vs 22 +/- 3) as were the number of patients who required analgesics. Severe nausea was more common in the GA group both in the PACU and during the 24 h after surgery. Analgesic requirements after discharge from the PACU, urinary retention, and days in the hospital did not differ between groups. This study suggests that SA may be superior to GA both intraoperatively and postoperatively for lumbar spine procedures lasting less than 2 h.
Adult↗
Metabolic parameter, bleeding, and weight changes in U.S. women using progestin only contraceptives.
Our objective was to determine the effect of progestin-only contraceptives on metabolic parameters, bleeding patterns, and weight changes during the first year of use. Seventy-one women (> 95% Caucasian), who were advised regarding contraception alternatives, self-selected levonorgestrel implants (n = 44), depo-medroxyprogesterone acetate (n = 22), or oral norethindrone (n = 5). One year later, 11 levonorgestrel implant and five depomedroxyprogesterone acetate patients were randomly selected to compare (pre- and post-progestin use) levels of cholesterol, triglycerides, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), apolipoproteins A-1 and B-100, bilirubin, and sex hormone binding globulin. Monthly bleeding and spotting records were kept in each group. Body weights were also monitored in each group. No statistically significant differences in metabolic parameters were found between pre- and post-progestin use in the levonorgestrel implant and depo-medroxyprogesterone acetate groups. Continued bleeding patterns were more prominent in the levonorgestrel implant and oral norethindrone groups than in patients receiving depo-medroxyprogesterone acetate. No significant weight gain was detected in any group. No changes in metabolic parameters or weight were noted over the one year of use of levonorgestrel implants or depo-medroxyprogesterone acetate. Depo-medroxyprogesterone acetate had the highest incidence of amenorrhea.
Administration, Oral↗
Complete sequence of the gene encoding the bacterioferritin subunit of Mycobacterium avium subspecies silvaticum.
A gene encoding the bacterioferritin subunit (Bfr) of Mycobacterium avium (Ma) subspecies silvaticum has been cloned, sequenced and expressed. The 477-bp open reading frame codes for 159 amino acids, which were shown to share up to 92% identity with the Bfr of five bacterial genera. The recombinant Bfr exhibits serological cross-reactivity with Ma paratuberculosis antigen D, a protein of approx. 20 kDa in cell lysates of Ma paratuberculosis and Ma silvaticum and a protein of 20-22 kDa in sonicates of M. leprae.
Amino Acid Sequence↗
A rapid method for the extraction and detection of Mycobacterium avium subspecies paratuberculosis from clinical specimens.
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Animals↗
Cystic fibrosis in children from ethnic minorities in the West Midlands.
BACKGROUND: We have observed that Doctors often perceive that cystic fibrosis (CF) is exceptionally rare in non-whites, and that this bias has repeatedly resulted in diagnostic delay. We therefore compared the age at diagnosis, genetic features and relative prevalence of CF in non-whites and white patients in the West Midlands. METHODS: Analysis of data on all CF patients diagnosed in childhood and stored in the West Midlands CF register. RESULTS: Sixteen of the 514 children on the register were not of white European extraction, comprising 13 patients whose families originated from the Indian subcontinent, two of mixed AfroCaribbean/white European extraction and one of mixed Pakistani/white European extraction. The median age of diagnosis was similar in the white European and non-white patients (0.42 vs. 0.33 years, 95% CI for the difference of the medians -0.15, 0.37). However, in five cases with typical clinical features the diagnosis appears to have been delayed because of the child's racial origin (median age of diagnosis 3.87 years), and in five others the diagnosis was obvious (two siblings with CF, three had meconium ileus). There was a degree of consanguinity in nine cases. Five patients were homozygous or heterozygous for the delta F508 mutation, but no mutation could be identified in the remaining 11 patients. CONCLUSIONS: The possibility of CF needs to be considered in any patient with relevant clinical problems, regardless of racial origin. These findings need to be considered when planning any mass population screening programme for CF.
Bangladesh↗
Identification and characterization of a putative serine protease expressed in vivo by Mycobacterium avium subsp. paratuberculosis.
A putative serine protease expressed in vivo by Mycobacterium avium subsp. paratuberculosis was isolated from a lambda gt11 genomic expression library by screening with serum from a naturally infected sheep. The gene was contained in two overlapping clones, which were shown by antibody elution to encode a protein of 34 kDa in M. a. paratuberculosis. The clones were sequenced and database searches detected a motif identical to the active serine site in trypsin, and 30% homology to the putative serine proteases (HtrA proteins) of Escherichia coli, Salmonella typhimurium, Brucella abortus and Rochalimaea henselae.
Amino Acid Sequence↗
Members of the ALDH gene family are lens and corneal crystallins.
Many of the major lens proteins, known as crystallins, responsible for the structural integrity and functional utility of this visual tissue have been previously shown to be recruited proteins. This phenomena of a protein that is expressed and functions elsewhere acquiring a new function in another tissue has been termed 'gene sharing'. It is now becoming obvious that the cornea of vertebrates has similarly acquired proteins, and that at least one corneal protein, ALDH3 belongs to a gene family that has been previously identified as a lens crystallin. The recognition that both lens and corneal crystallins exist is a novel concept that has implications that involve the process by which multifunctional gene products have evolved. Members of the ALDH gene family function in both the cornea and lens as crystallins and the acquisition of multifunctionality by this gene family is unique. Based on our analysis we have deduced a supragene family relationship between the thiol protein esterases, aldehyde dehydrogenases, and the taxon-specific crystallins. Evolution of a complex organ such as the vertebrate eye is not a sequential and gradual process such as the Darwinian Giraffe's neck, since the eye can provide selective advantage only as a complete organ. Catastrophic theory proposes that the complex vertebrate eye with its lens, and focussing mechanism arose from the primitive eye spot which contained originally only the photoreceptor system by a one step event. In the evolution of the vertebrate eye it is evolutionarily plausible that several pre-existing proteins have been recruited to perform a structural role for this complex organ. It is also incumbent in evolutionary thought that any inherent enzymatic activity associated with this protein would be purely an incidental addition to the organ. However, the fact that most of these have pyridine nucleotide binding capacity, which is presumed important in giving protection from UV exposure, is noteworthy. Finally, to construct the vertebrate eye in one step from the existing visual pigment system such as the eyespot of unicellular organisms the following criteria would apparently be advantageous: (1) high water solubility; (2) transparency; and (3) common genetic regulatory elements (e.g. promoters/enhancers). Although it is an important observation that certain members of the aldehyde dehydrogenase gene family are present as structural proteins in the cornea and lens, it is not surprising that the phenomenon of gene sharing extends to another ocular tissue such as the cornea. In this context, it will be interesting to note if similar multifunctional gene products will be found as frequently in organs other than the eye.
Aldehyde Dehydrogenase↗