PubMed Health⌕ Search

Biomedical subjects

S Ryder

Publications and source records attributed to S Ryder.

At least 19 recordsLinked to original sources

Best practice in primary care pathology: review 5.

This fifth best practice review examines three series of common primary care questions in laboratory medicine: (1) minor liver function test abnormalities; (2) laboratory monitoring of patients receiving lithium; and (3) investigation of possible venous thromboembolism. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus-based rather than evidence-based. They will be updated periodically to take account of new information.

Antimanic Agents↗

Tissue distribution of bovine spongiform encephalopathy infectivity in Romney sheep up to the onset of clinical disease after oral challenge.

Sixty Romney sheep of three prion protein genotypes were dosed orally at six months of age with an inoculum prepared from the brains of cattle clinically affected with BSE, and 15 sheep were left undosed as controls. They were randomly assigned within genotype to groups and were sequentially euthanased and examined postmortem at intervals of six or 12 months, depending on their predicted susceptibility. Tissue pools prepared from the three, four or five dosed animals in each group were inoculated into groups of 20 RIII mice as a bioassay for infectivity. Separate inocula were prepared from the matched control sheep killed at each time. In the ARQ/ARQ sheep killed four months after inoculation, infectivity was detected in the Peyer's patch tissue pool, and at 10 months it was detected in the spleen pool; from 16 months, infectivity was detected in a range of nervous and lymphoreticular tissues, including the spinal cord pool, distal ileum excluding Peyer's patches, liver, Peyer's patches, mesenteric and prescapular lymph nodes, spleen, tonsil and cervical thymus. No infectivity was detected in the tissue pools from the ARQ/ARR and ARR/ARR sheep killed 10 months or 22 months after infection.

Animals↗

The measurement properties and performance characteristics among older people of TURN180, a test of dynamic postural stability.

OBJECTIVES: To establish the measurement properties of TURN180, a test of dynamic postural stability. DESIGN: One physiotherapist conducted three trials of TURN 180, one of which was also observed by a second therapist. SETTING: A day unit for elderly people accepting both inpatients and outpatients. SUBJECTS: Sixty-six people (mean age 82.45 years), only six (9.1%) of whom could walk without using a walking aid. MAIN MEASUREMENT: The number of steps that a person takes to step around 180 degrees. A step is defined as any attempt on the subject's part to take a step, successful or not. RESULTS: Repeatability is good, intraclass correlation coefficient = 0.828; the minimal detectable change revealed that in order to be considered a real improvement the number of steps the person takes to complete the postintervention TURN180 must be 28-29% fewer than the preintervention count. As long as the protocol is followed carefully, between-observer agreement is good, with differences between two observers rarely exceeding one step. People who had fallen in the previous year took statistically significantly more steps than those who had not done so to complete TURN180. Requesting written as well as oral consent seems to reduce the likelihood of an elderly patient agreeing to participate in a study. CONCLUSION: TURN180 yields repeatable (retest reliable) and valid data about a person's dynamic postural stability, especially the minimal detectable change which allows clinicians to judge whether any change in their patient's performance is real.

Accidental Falls↗

Clinical findings in 78 suspected cases of bovine spongiform encephalopathy in Great Britain.

The clinical findings in 59 cows with bovine spongiform encephalopathy (BSE) were compared with those in 19 cattle that were submitted as BSE suspects but not confirmed by immunohistochemistry. Both groups were also compared with a control group of 20 healthy cows. Abnormalities in behaviour, temperament, mental status and activity, neurogenic disorders of gait and hyperreactivity to touch were frequently observed in the cattle with BSE. Not every animal with BSE displayed clinical signs in all these categories, and the severity of the signs was not always useful for differentiating them from the BSE suspects that were not confirmed by pathology. The neurological examination was better than passive observations for the clinical diagnosis of BSE. Tests of the animals' responses to sudden auditory, visual and tactile stimuli were very useful for distinguishing cases of BSE from unconfirmed BSE suspects if the cases did not display signs in all the categories.

Animals↗

Demonstration of lateral transmission of scrapie between sheep kept under natural conditions using lymphoid tissue biopsy.

Scrapie free adult sheep were introduced to a sheep flock specifically maintained to maximise scrapie infection. Native born sheep of the highly susceptible VRQ/VRQ genotype in this flock show highly efficient transmission, evidenced by 100% infection, with an age at death of less than 2 years. Infection in introduced sheep was identified by biopsy of tonsilar and nictitating membrane lymphoid tissue. Progeny of these sheep were monitored and clinical disease confirmed by examination of the brain using routine diagnostic methods. Naïve sheep of New Zealand origin introduced to the flock in adulthood became infected, demonstrating that lateral transmission had occurred. Lambs born to introduced ewes became infected and died at the same age as lambs born to native ewes, consistent with lateral transmission of scrapie to lambs. Although maternal transmission cannot be totally excluded for the lambs in this study, the data are consistent with lateral transmission being the most important means of spread leading to the high incidence of scrapie observed in this flock.

Alleles↗

Evaluation of the effects of controlled autolysis on the immunodetection of PrP(Sc) by immunoblotting and immunohistochemistry from natural cases of scrapie and BSE.

Seventeen clinically suspect scrapie sheep, and twelve suspected BSE-affected cattle were confirmed using routine histopathological examination by the detection of characteristic spongiform change in the medulla brain region taken at the level of the obex. Three sheep and four cows acquired as controls showed no spongiform change. Five aliquots of brain tissue from each of four brain regions were taken (cerebellum, medulla, frontal cerebral cortex and occipital cerebral cortex) from each of the 36 animals. One aliquot was frozen at -70 degrees C, the others were subjected to one of four autolysis regimes at 3 or 7 days at 25 degrees C or 37 degrees C. All samples were tested by Western immunoblotting for detection of PrP(Sc) using the Prionics - Check test (Prionics AG, Zurich, Switzerland). Further samples of medulla from 15 suspect scrapie cases, 10 healthy sheep, 13 suspect BSE cows and 5 healthy cows, were taken adjacent to the obex, and subjected to autolysis at 37 degrees C for 6, 12, 24 and 48 hours before being fixed in 10 per cent formal saline and subsequently examined by a routine immunohistochemical technique for detection of PrP(Sc) protein. The abnormal protein could not be detected in any of the control animals by either technique. PrP(Sc) could be detected by Western immunoblotting in at least one brain area from all the positive animals after autolysis for 7 days at 37 degrees C. The protein could be detected by immunohistochemistry in all cases which were positive by histopathological examination using all autolysis conditions. From the results of this study it is concluded that autolysis does not significantly compromise the diagnosis of scrapie or BSE by either of these diagnostic methods.

Animals↗

Analysis of gene expression in the bovine blastocyst produced in vitro using suppression-subtractive hybridization.

Successful embryonic development is dependent on time and location-specific expression of appropriate genes. Unfortunately, information on stage-specific gene expression during early embryonic development in the bovine is lacking. In the present study, we compared gene expression between in vitro-produced Day 7-8 intact blastocysts (driver) and Day 9-10 hatched blastocysts (tester) using suppression-subtractive hybridization. Pools of 30 embryos for both driver and tester were used in the RNA extraction process. From limited amounts of starting material ( approximately 400 ng of total RNA), a reverse transcription-polymerase chain reaction (PCR) procedure was used to amplify the mRNA and generate sufficient cDNA to conduct suppression-subtractive hybridization. The subtracted cDNA products were cloned, and 126 cDNAs representing expressed mRNAs were isolated, sized, single-pass sequenced, and compared to known sequences in GenBank. Ninety-two clones provided sequence information for further analysis. Among these, 31 exhibited high homology to known genes. Three, 26S proteasomal ATPase (PSMC3), casein kinase 2 alpha subunit (CK2), and phosphoglycerate kinase (PGK) were selected and further characterized using real-time quantitative PCR to assess their differential expression in hatched blastocysts. Overall, a 1.3-, 1.6-, and 1.5-fold increase in expression level was observed in hatched blastocysts compared with intact blastocyst for PSMC3, CK2, and PGK, respectively. These results show that construction of subtracted cDNA libraries from small numbers of embryos is feasible and can provide information on gene expression patterns during preattachment embryogenesis.

Adenosine Triphosphatases↗

How are abnormal results for liver function tests dealt with in primary care? Audit of yield and impact.

OBJECTIVE: To determine whether abnormal results for liver function tests are investigated in primary care and findings on full investigation. DESIGN: Retrospective audit and prospective clinical investigation. SETTING: University hospital and surrounding general practices serving around 330 000 people. SUBJECTS: Adults with abnormal results for liver function based on tests requested by their doctor between 1 January and 30 June 1995. INTERVENTIONS: All patients with gamma-glutamyltransferase, alanine aminotransferase, or alkaline phosphatase concentrations at least twice the upper limit of the reference range were studied. A median of 15 months later (range 12-21) records of hospital attendances and further investigations were examined. Where investigations were incomplete the records from the general practice were examined, and suitable patients were invited to attend the liver clinic. MAIN OUTCOME MEASURES: Investigations requested by the doctor and final diagnoses reached. RESULTS: 933 patients with abnormal liver function tests were identified; follow up data were obtained in 873 (94%). 531 patients were already under hospital review. Of the remaining 342 patients, 157 were suitable for investigation; the others had died, moved away, were elderly, or had repeat liver function tests with normal results. No further tests were requested for 91 (58%) of these patients. 66 had been partially investigated by their doctor, and in seven patients results suggesting a treatable chronic liver disease had not been followed up. On investigation, 97 (62%) had an identifiable diagnosis requiring hospital intervention or follow up, or both. CONCLUSIONS: Abnormal results for liver function are often not adequately investigated, missing an important chance of identifying treatable chronic liver disease.

Alanine Transaminase↗

Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection.

The role of intrahepatic lymphocytes in the control of hepatitis C virus (HCV) infection and the pathology associated with it is not understood; most studies of the immunology of this infection use peripheral blood lymphocyte populations. To address this further, we examined in detail the IHL from HCV-infected patients and controls, focusing on the antigen-specific CD8(+) T lymphocyte component. Individual T cells from needle liver biopsies and peripheral blood were isolated from patients with chronic HCV infection and examined directly ex vivo. We used RT-PCR spectratyping to compare the breadth of the T cell receptor usage in the liver in comparison with the peripheral blood, and applied MHC class I tetramer technology to investigate the numbers of HCV-specific CD8(+) cells in the two compartments. T cell receptor usage in the liver of HCV-infected patients was broad, comparable with that in the peripheral blood of the same patients. A much higher proportion of liver CD8(+) cells expressed receptors specific for HCV antigens compared with paired peripheral blood CD8(+) cells. A greater proportion of the liver tetramer-positive cells expressed the activation marker CD69, compared with those in the periphery or other CD8(+) cells in the liver. In the course of chronic HCV infection, HCV-specific CD8 cells, which have been recently activated, appear to accumulate specifically in the livers of infected patients but are present in much lower numbers in the peripheral circulation. Further studies are needed to determine the function of these cells and their role in protection and immunopathology.

CD8-Positive T-Lymphocytes↗

BRIDGE (building the relationship between body image and disordered eating graph and explanation): a tool for parents and professionals.

BRIDGE (Building the Relationship Between Body Image and Disordered Eating Graph and Explanation) is a tool for mental health professionals, parents, teachers, and the general public. BRIDGE offers the potential for a new level of understanding between body image and disordered eating behaviors. This tool provides a framework that describes the connection between the attitudes we hold about our bodies and the corresponding behaviors we may practice. This practical tool takes fundamental concepts established in the eating disorder literature and presents them in a basic and easily understood manner. This paper invites further testing of this educational tool for parents, teachers, and professionals in a number of contexts including prevention and treatment programs.

Journal Article↗

Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera.

Sixty-three Romney sheep aged 6 months, consisting of three groups (PrP(ARQ/ARQ), PrP(ARQ/ARR), and PrP(ARR/ARR)genotypes) of 21 animals, were infected orally with brain tissue from BSE-infected cattle. Sub-groups of the 21 PrP(ARQ/ARQ) animals were killed, together with uninfected controls 4, 10, 16, 22 or 24-28 (after the development of full clinical disease) months post-inoculation (mpi). One sheep from each of the two groups of four killed at 4 or 10 mpi were shown by immunohistochemical examination to possess disease-specific PrP accumulations in single lymph nodes. At 16 mpi, such accumulations were detected in two of four infected sheep in some viscera and in the spinal cord and brain. At 22 mpi, three of five infected sheep had widespread disease-specific PrP accumulations in all tissues examined, but the remaining two animals gave positive results only in the central nervous system. Clinical disease appeared at 20-28 mpi. Three sheep killed with advanced clinical signs showed widespread PrP accumulation in brain, spinal cord and peripheral tissues. These results confirmed that PrP(ARQ/ARQ) Romney sheep are susceptible to experimental infection with the BSE agent. The different sites at which initial PrP accumulations were detected suggested that the point of entry of infection varied. Once established, however, infection appeared to spread rapidly throughout the lymphoreticular system. The results suggested that in some BSE-infected sheep neuroinvasion occurred in the absence of detectable PrP accumulations in the viscera or peripheral nervous system. In contrast to cattle with BSE, however, most sheep showed disease-specific PrP accumulations in the lymphoreticular system. In this respect, BSE-infected resembled scrapie-infected sheep; it is possible, however, that future research will reveal differences in respect of targeting of cell types within the lymphoreticular and peripheral nervous systems. The PrP(ARQ/ARR)and PrP(ARR/ARR)sheep were also killed in sub-groups at intervals after inoculation. Up to 24 mpi, however, none of these animals showed disease-specific PrP accumulations. Further results will be reported later.

Administration, Oral↗

BRIDGE 2 (Building the Relationship Between Body Image and Disordered Eating Graph and Explanation): interventions and transitions.

BRIDGE 2 (Building the Relationship Between Body Image and Disordered Eating Graph and Explanation): Interventions and Transitions, builds upon the framework presented in the first publication of BRIDGE. BRIDGE 2 moves beyond increasing the understanding of the relationship between body image and eating disorders and encourages a movement into action. First, it suggests the appropriate point of intervention for both parents and teachers. Second, the continuum of health care from promotion to prevention, to early intervention, and to basic and specialized treatment services is positioned on the BRIDGE framework. This added dimension offers a new level of understanding specific to eating disorders by utilizing concepts from mental health promotion and mental illness prevention literature.

Journal Article↗

Utilisation of bacteriophage display libraries to identify peptide sequences recognised by equine herpesvirus type 1 specific equine sera.

Three filamentous phage random peptide display libraries were used in biopanning experiments with purified IgG from the serum of a gnotobiotic foal infected with equine herpesvirus-1 (EHV-1) to enrich for epitopes binding to anti-EHV-1 antibodies. The sequences of the amino acids displayed were aligned with protein sequences of EHV-1, thereby identifying a number of potential antibody binding regions. Presumptive epitopes were identified within the proteins encoded by genes 7 (DNA helicase/primase complex protein), 11 (tegument protein), 16 (glycoprotein C), 41 (integral membrane protein), 70 (glycoprotein G), 71 (envelope glycoprotein gp300), and 74 (glycoprotein E). Two groups of sequences, which aligned with either glycoprotein C (gC) or glycoprotein E (gE), identified type-specific epitopes which could be used to distinguish between sera from horses infected with either EHV-1 or EHV-4 in an ELISA using either the phage displaying the peptide or synthetic peptides as antigen. The gC epitope had been previously identified as an immunogenic region by conventional monoclonal antibody screening whereas the gE antibody binding region had not been previously identified. This demonstrates that screening of phage display peptide libraries with post-infection polyclonal sera is a suitable method for identifying diagnostic antigens for viral infections such as EHV-1.

Amino Acid Sequence↗

Altered activation of phospholipase D by lysophosphatidic acid and endothelin-1 in mouse embryo fibroblasts lacking phospholipase C-gamma1.

Lysophosphatidic acid (LPA) and endothelin-1 (ET-1) activate phospholipase D (PLD) in many cell types. To see if phospholipase C-gamma1 plays a role, we used embryonic fibroblasts from mice in which the PLCgamma1 gene was disrupted. Surprisingly, the effect of LPA on inositol phosphate accumulation was increased in these PLCgamma1-/- cells, whereas that of ET-1 was completely abrogated. When PLD activity was measured, the response to LPA was also enhanced and the response to ET-1 lost in the PLCgamma1-/- cells. Treatment of these cells with ionomycin and oleoyl acetyl glycerol to mimic PLC stimulation restored PLD activity. Treatment of either PLCgamma1+/+ and PLCgamma1-/- cells with tyrosine kinase inhibitors did not inhibit LPA- or ET-1-induced PLD activity. Moreover, LPA and ET-1 treatment of PLCgamma1+/+ and PLCgamma1-/- cells did not cause tyrosine phosphorylation of PLC-gamma1 or PLC-gamma2. In summary, these results show that the altered PLD responses to LPA and ET-1 in PLCgamma1-/- are due to changes in PLC activity and do not involve tyrosine kinase activity.

Animals↗