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Biomedical subjects

A Robinson

Publications and source records attributed to A Robinson.

At least 145 records · Page 8Linked to original sources

Valuing health status using VAS and TTO: what lies behind the numbers?

It is well known that different methods of eliciting the valuations attached to various health states, such as the Visual Analogue Scale (VAS) and the Time Trade Off (TTO), yield different results. This study gathers qualitative data from a group of 43 respondents who had previously taken part in a large scale national study which set out to elicit the values attached by individuals to various health states using both the VAS and the TTO techniques. The findings of this study raised three questions which are of particular interest here: (1) Why are some states that are rated better than dead on the VAS often rated as worse than dead in TTO? (2) Why are some respondents unwilling to trade off any time at all in order to avoid a health state that they place below full health on the VAS? (3) Why are TTO valuations of older respondents for the more severe health states lower than those of the younger age groups? This study has uncovered qualitative evidence on each of these three key issues. Regarding the first question, many respondents did not appear to interpret a better than dead VAS score as a strict preference for spending 10 years in a health state over immediate death. Several different factors appeared to contribute towards this, an important one being the tendency of respondents to ignore the duration of the health state during the VAS task. Regarding the second question, there is evidence of the existence of a "threshold of tolerability" below which states would have to fall before some respondents would be willing to give up any time at all on the TTO. Regarding the last question, it appears that older respondents are less likely to find the worse than dead TTO scenario plausible than those in the younger age groups. However, whilst this may explain why older respondents attach lower worse than dead valuations to health states, it does not appear to account for the entire difference in TTO valuations between the two age groups. In addition, it appears that older respondents may be less prepared to live for the next 10 years in a diminished health state.

Adolescent↗

Cognition and multiple sclerosis: a historical analysis of medical perceptions.

The earliest descriptions of multiple sclerosis (MS) rarely distinguished cognitive impairment from the general category of "mental symptoms", which also encompassed a broad range of affective disorders. Case-study methods led to disputes about the extent and nature of these symptoms, exacerbated by different national medical traditions. Appropriate scientific methods were only used to investigate cognitive performance in a modest number of studies up to the 1960s, and it was being argued as late as the mid 1970s that affective processes rather than cognitive processes were the key to understanding the psychological aspects of MS. However, the early 1980s, saw major developments in test procedures for the detection of subtle and selective cognitive changes, in the use of brain imaging techniques, and in collaboration between neurologists and neuropsychologists. Pressure to use research findings to improve patients' daily lives suggests a need to reconsider the connection between affective and cognitive processes in MS.

Cognition↗

Sleep-disordered breathing and hypertension: past lessons, future directions.

That obstructive sleep apnea syndrome is an independent risk factor for the development of hypertension was established in the 1970s, and recent works on large samples have confirmed this fact. Investigations of the mechanisms that may lead to the development of hypertension with sleep-disordered breathing will allow not only confirmation of the relationship but also creation of better treatment. There is a multigenic basis of blood pressure regulation, and genetic factors play a role in the development of sleep-disordered breathing. Genes that may have little role in the physiologic variation of blood pressure may be more important in the manifestation of pathology. And one hypothesis is that genes involved in the development of a morphotype may also have a role in the development of hypertension. Furthermore, sleep-disordered breathing may be associated with abnormal sympathetic discharge during sleep, as shown by microneurography. This mechanism may explain how a sleep disorder leads to hypertension, but impairment of vascular endothelial controls may also be involved. Investigation of vascular endothelial vasodilation as demonstrated by forearm plethysmography or the dorsal hand vein technique indicates that impairment of endothelium-dependent vasodilation during wake is associated with sleep-disordered breathing. This endothelium-dependent vasodilation appears to be more frequently impaired than the endothelium-independent vasodilation, and the former impairment can be reversed by nasal continuous positive airway pressure. These findings are supportive fo the role of sleep-disordered breathing in the development of hypertension in man.

Endothelium, Vascular↗

Dissociative symptoms in panic disorder.

The present study examined the prevalence and correlates of dissociative symptoms in patients with panic disorder and patients with other nonpanic anxiety disorders. A total of 56 patients with anxiety disorders (13 with panic disorder alone, 16 with comorbid panic and other anxiety, and 27 with other anxiety disorders) were assessed with structured clinical interviews and a battery of questionnaires. Although 69% of patients with panic disorder experienced depersonalization or derealization during their panic attacks, panic disorder patients were no more likely to experience dissociative experiences as assessed by the Dissociative Experience Scale than patients with other anxiety disorders. In the entire sample, the prevalence of dissociative experiences was very low and well within nonpathological ranges. The correlates of dissociative symptoms were severity of depression, social anxiety, and personality disorders. The implications of these findings for conceptualizing the nature of dissociative symptoms within an anxiety population are discussed.

Adult↗

Analysis of the human Ig isotype response to individual transferrin binding proteins A and B from Neisseria meningitidis.

Subcapsular antigens, including transferrin binding proteins, are being considered as potential vaccines against serogroup B meningococci. This study examined the human isotype antibody responses in cases of meningococcal disease to meningococcal TbpA (transferrin binding protein A) and TbpB (transferrin binding protein B) from two strains (SD and B16B6) expressing high and low molecular mass TbpB respectively. TbpA isolated from both strains were recognised more frequently and higher durable ELISA absorbance values were detected than those detected against TbpB from either strain. These antibody responses to Tbps were independent of the infecting meningococcal strain type. The antibody response to the four proteins was highly variable between individuals and differed significantly against all four antigens. The variability of immune responses to each Tbp from the two strains suggests that a successful vaccine would need to include TbpA and TbpB from a number of strains.

Antibodies, Bacterial↗

Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant.

The PARI-IS Study is a double-blind placebo-controlled randomized clinical trial to study the effect of an immunostimulating agent to prevent acute respiratory exacerbation in patients with COPD. Three hundred eighty-one ambulatory patients (190 placebo and 191 immunostimulant) were followed at home for 6 mo by experienced research nurses. The risk of having at least one episode of acute exacerbation (primary outcome) was similar in the two groups (p = 0.872). In contrast, the total number of days of hospitalization for a respiratory problem was 55% less in the group treated with OM-85 BV (287 d) than in the group treated with placebo (642 d). Patients treated with OM-85 BV spent an average of 1.5 d in hospital compared with 3.4 d for patients treated with placebo (p = 0.037). The risk of being hospitalized for a respiratory problem was 30% lower in the treated group (16.2%) than in the placebo group (23.2%); p = 0.089. Eight deaths were observed: two in patients treated with OM-85 BV and six in patients treated with placebo (p = 0.153). During the course of the study dyspnea improved slightly in patients treated with OM-85 BV, whereas it deteriorated slightly in patients receiving placebo (p = 0.028). These results suggest that this immunostimulating agent may be beneficial for patients with COPD by reducing the likelihood of severe respiratory events leading to hospitalization.

Acute Disease↗

Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-dichloro-2-propanol and selectively inhibits CYP2E1 activity in the rat.

The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, and provided substantial protection against DCP hepatotoxicity. At a higher dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 activity and provided complete protection against DCP hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is mediated principally by CYP2E1, with a possible contribution from CYP1A2.

Animals↗

Comparison of MRC-5 and primary rabbit kidney cells for the detection of herpes simplex virus.

OBJECTIVE: To compare MRC-5 and primary rabbit kidney (PRK) cells to either cell monolayer alone for the recovery of herpes simplex virus (HSV). DESIGN: A total of 2476 specimens received for HSV culture during a 3-year period were cultured on MRC-5 and PRK cells. Detection rates and the time to first detection were determined for each cell type used. A cost analysis was also performed for the isolation and identification of HSV using both cell types, the MRC-5 cell line alone, and PRK cell culture alone. SETTING: Large, urban, tertiary-care, university-affiliated hospital. RESULTS: Of the 2476 specimens cultured for HSV, 535 (21.6%) were positive. The MRC-5 cell line detected 531 (99.3%), and the PRK cell culture detected 522 (97.6%) of the positive specimens. Thirteen HSV isolates were detected only in MRC-5 cells, and four were isolated only in PRK cells. Approximately 44% of the cultures were positive by day 1, 84% by day 2, and 98% by day 3, regardless of the cell type used. The total cost per culture was comparable for MRC-5 and PRK cells. CONCLUSIONS: There was no difference in the sensitivity or time to detection of HSV between PRK and MRC-5 cells either alone or in combination. Either cell type alone represents an efficient, cost-effective method for the isolation of HSV.

Animals↗

Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking.

Glutathione-S-transferase (GST)-Grb2 fusion proteins have been used to identify the potential role of Grb2-binding proteins in platelet activation by the platelet low-affinity IgG receptor, Fc gamma RIIA. Two tyrosine phosphoproteins of 38 and 63 kD bind to the SH2 domain of Grb2 following Fc gamma RIIA stimulation of platelets. Both are located in the particulate fraction following platelet activation and are also able to bind to a GST-construct containing the SH2 and SH3 domains of phospholipase C gamma 1. p38 also forms a complex with the tyrosine kinase csk in stimulated cells and is a substrate for the kinase. The SH3 domains of Grb2 form a stable complex with SOS1 and two proteins of 75 kD and 120 kD, which undergo tyrosine phosphorylation in Fc gamma RIIA stimulated cells. The 75-kD protein is recognized by antibodies to SLP-76, which has recently been isolated from T cells and sequenced. Tyrosine phosphorylation of p38 and p63 is also observed in platelets stimulated by the tyrosine kinase-linked receptor agonist collagen and by the G protein-coupled receptor agonist thrombin, although phosphorylation of SLP-76 is only observed in collagen-stimulated platelets. p38 and p63 may provide a docking site for Grb2, thereby linking Grb2 SH3-binding proteins SOS1, SLP-76, and p120 to downstream signalling events.

Adaptor Proteins, Signal Transducing↗

The Ku autoantigen: cast in a new light.

With his associates at the University of Ottawa, Dr. Robert Haché has demonstrated that the Ku autoantigen, a protein that plays a role in DNA repair and in immunoglobulin gene recombination, also modifies the action of steroid hormones. This finding has potential implications for the treatment of tumours whose growth is influenced by steroid hormones. The researchers suggest that Ku could be involved in the control of gene expression through a mechanism involving protein phosphorylation. They hope that a better understanding of the role Ku plays in many cellular processes may improve our understanding of autoimmune diseases, diseases of immune deficiency and cancer.

Antigens, Nuclear↗

An artificial heart with the right connection.

Led by Dr. Tofy Mussivand at the University of Ottawa Heart Institute, a team of Canadian medical scientists, engineers, economists, physicians and medical devices manufacturers is working to bring a prototype artificial heart closer to clinical trials. Key to this effort is the development of an electrical connector that can function for a long period in the harsh environment of the human body. Such a connector will enable various components of the artificial heart, such as the internal battery, to be replaced independently. As well as being of obvious benefit to people with end-stage heart disease, a Canadian-made artificial heart has export potential that should help to redress the country's large trade deficit in medical devices.

Canada↗

Inhibiting calpain, rescuing cells.

Drs. John Elce and Peter Davies, biochemists at Queen's University, Kingston, Ont., are investigating the molecular structure of calpain, an enzyme that has been implicated in the cellular damage that occurs after such events as myocardial infarction and stroke. This damage is precipitated by an imbalance in the regulation of calpain that arises as an indirect result of ischemia. Elce and Davies hope that their research, which involves techniques such as recombinant DNA technology and x-ray crystallography, will lead to the development of a calpain inhibitor that will prevent such damage from occurring and enhance recovery.

Calpain↗

Mycophenolate mofetil immunosuppression in rat pancreas allotransplantation.

Prolongation of pancreas allograft survival has been difficult to achieve in rodent models despite use of immunosuppression regimens that successfully increase graft survival of other organs. The purpose of this study was to evaluate a new immunosuppressive agent, mycophenolate mofetil (MM), for its ability to prevent rejection in a rat pancreas transplant model. In addition, using congenic strains of rats, the efficacy of MM in rat pancreas transplantation was treated in the context of isolated class I or class II major histocompatibility (MHC) differences. MM in doses of 12.5 to 37 mg/kg significantly prolonged BUF to LEW heart transplant survival beyond a 14-day course of therapy thereby demonstrating its immunosuppressive efficacy. In similar pancreas transplant experiments, however, most grafts were rejected during the period of MM administration. Combination therapy with MM and cyclosporine did not extend pancreas survival beyond that achieved with MM alone (Mean Survival Time of 13.8 +/- 2.7 vs 11.7 +/- 1.6 days, respectively). Conversely, combined therapy with MM and antilymphocyte serum achieved a mean survival for BUF to LEW pancreas transplants of 52.3 +/- 24.8 days, which was significantly longer than that observed for either MM (11.7 +/- 1.6) or ALS (18.0 +/- 7.6) alone. MM therapy doubled pancreas allograft survival when used in the face of class I MHC disparity and compared to controls (19.5 +/- 1.0 vs 10.0 +/- 1.9 days) but did not prolong grafts that were disparate at only the class II locus (12.6 +/- 1.5 vs 12.0 +/- 1.2 days, respectively, for MM vs control). These data indicate that MM may not be an effective single agent immunosuppressive for pancreas transplantation except when MHC disparity is limited to the class I locus.

Animals↗

Intrauterine diagnosis of sex chromosome aneuploidy.

OBJECTIVE: To provide current information on sex chromosome aneuploidies to obstetricians who encounter such diagnoses and who counsel prospective parents faced with the prenatal diagnosis of a sex chromosome aneuploidy. DATA SOURCES: Unbiased information about the natural course of sex chromosome aneuploidy has become available only in the last few years. Current knowledge is based on seven prospective studies on unselected individuals with sex chromosome aneuploidy identified 20-30 years ago. All literature on sex chromosome aneuploidy was reviewed. Karyotypes specifically addressed included the following: 47,XXY, 47,XXX, 47,XYY, 45,X, 45,X/46,XX, 46,XX/47,XXX, and 46,XY/47,XXY. METHODS OF STUDY SELECTION: The international studies followed the affected subjects from birth to young adulthood. All published reports, case studies, and articles were reviewed. TABULATION, INTEGRATION, AND RESULTS: All prospective studies were included in the course of determining necessary information for obstetricians and prospective parents. Points addressed for each of the aneuploid karyotypes included expected phenotype, reproductive competence, developmental risks, and intervention therapies. CONCLUSION: Information about sex chromosome aneuploidy can assist obstetricians in providing accurate and comprehensive genetic counseling to parents of affected fetuses, and thereby facilitate the process of making an informed decision about pregnancy management.

Aneuploidy↗