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Biomedical subjects

G W Ellison

Publications and source records attributed to G W Ellison.

At least 19 recordsLinked to original sources

T-cell responses to oligodendrocyte-specific protein in multiple sclerosis.

Oligodendrocyte-specific protein (OSP) is concentrated in CNS myelin and is a potential autoantigen in the development of multiple sclerosis (MS). We performed proliferation assays with lymphocytes from MS patients and normal controls. OSP peptide-induced proliferation was common in relapsing-remitting MS and controls samples but was less pronounced in samples from secondary progressive MS subjects. These data demonstrate that OSP-reactive T cells are part of the normal immune repertoire and therefore have the potential to contribute to the pathogenesis of MS. Given the lack of specificity to MS, OSP-reactive T-cells are unlikely to be solely responsible for the disease process.

Adult↗

Factors related to agreement between self-reported and conventional Expanded Disability Status Scale (EDSS) scores.

BACKGROUND: Although the Expanded Disability Status Scale (EDSS) remains a widely used scale for evaluating impairments in people with multiple sclerosis (MS), EDSS assessments are infeasible in certain situations. A self-administered version of the EDSS would be potentially useful if it yielded similar results as the conventional physician-based version. METHODS: We developed a self-administered patient questionnaire to obtain ratings of neurologic impairments, and developed algorithms to estimate EDSS scores. We mailed the questionnaires to all new consecutive patients scheduled to be seen at an MS clinic. Questionnaires were completed prior to the visit and traditional EDSS ratings were made by one of two neurologists at the visit. One hundred and forty-six pairs of patient questionnaires and physician EDSS assessments were obtained. RESULTS: Kappa values for agreement between the physician's EDSS scores and the questionnaire-derived scores were 0.13 (for exact agreement), 0.39 (+/-0.5 EDSS steps), and 0.56 (+/-1.0 EDSS steps). A scatterplot showed that agreement was best at EDSS scores <3.0 and >5.0. Better agreement was obtained when patients had a higher level of education, and when the physician was more certain of the diagnosis of MS. CONCLUSIONS: While the self-assessed EDSS scores do not agree highly enough to take the place of conventional EDSS scores, they may be sufficient for MS trial screening or for assessing outcomes across broad categories of disability.

Adolescent↗

The effect of texturized vegetable protein from soy on nutrient digestibility compared to beef in cannulated dogs.

Texturized vegetable protein from soy (TVP) is widely used in canned dog foods, but its nutritional value remains in doubt. This study compared apparent prececal and total intestinal digestibility when four canned diets containing reciprocal proportions of protein from TVP (0 to 57%) and from beef (100 to 43%) were fed to eight cannulated dogs. As dietary TVP increased, the following linear changes were observed (P < 0.05): prececal and total intestinal protein digestibility decreased slightly from 77 to 71% and 86 to 80%, respectively; prececal amino acid digestibility decreased in parallel with protein; prececal carbohydrate digestibility decreased markedly from 80% to 62% and carbohydrate disappearance in the large intestine increased from 8 to 22%; prececal sodium digestibility decreased markedly (from 37 to 4%); and prececal potassium digestibility decreased (from 93 to 85%). Total intestinal digestibility of sodium and potassium decreased little (from 97 to 95% and from 98 to 97%, respectively); fecal mass and water content increased markedly (from 98 to 174 g/d and from 61 to 72%, respectively); and fat digestibility was unaffected. Prececal phosphorus digestibility from two diets containing TVP was lower than that from the all-beef diet (13 and 17%, vs 26%, P < 0.05). In conclusion, TVP is a useful source of protein in canine canned diets because amino acids from TVP are almost as digestible as those from beef in the canine intestine. Nevertheless, soy carbohydrate is poorly digested and large amounts of TVP inhibit small intestinal electrolyte digestibility and increase fecal water content.

Animals↗

Management of multiple sclerosis across managed care and fee-for-service systems.

OBJECTIVE: To measure and compare care for adults with MS across managed care and fee-for-service (FFS) health systems. METHODS: The authors sampled adults with MS having physician visits over a 2-year period from a group model health maintenance organization (HMO) in southern California, from a midwestern independent practice association (IPA) model managed care plan, and from the FFS portion of the practices of a random sample of southern California neurologists. The authors mailed surveys to subjects in mid-1996; 930 of 1,164 (80%) of those eligible responded. The authors measured sociodemographic and clinical characteristics, management of recent changes in mobility, bladder control, and fatigue, use of a disease-modifying agent, assessment of general health symptoms and issues, and unmet information needs. The authors adjusted comparisons between systems for comorbidity, disease severity, and disease type. RESULTS: The groups differed on most sociodemographic and clinical characteristics. There were few differences in symptom management; differences that did exist tended toward more referrals or treatment for the FFS group. Access to the disease-modifying agent available at the time of the survey did not differ across systems, although patients' perceptions of the rationale for not using the drug did vary. General health issues and symptoms were more often assessed in the FFS and IPA systems than in the HMO, but improvement was needed across all three systems of care. There were substantial unmet information needs in all groups and especially high ones in the FFS and HMO samples. CONCLUSIONS: Strategies to improve care for people with MS should be developed and evaluated, particularly in areas like symptom assessment and meeting patient information needs. Where variations in service delivery exist, longitudinal studies are also needed to evaluate the potential impact on outcomes and to evaluate reasons for variation.

Activities of Daily Living↗

Risk factors affecting the outcome of surgery for atlantoaxial subluxation in dogs: 46 cases (1978-1998).

OBJECTIVE: To identify risk factors for successful surgical management of dogs with atlantoaxial subluxation (AAS). DESIGN: Retrospective study. ANIMALS: 46 dogs managed surgically for AAS. PROCEDURE: Age at onset of clinical abnormalities, duration of clinical abnormalities prior to surgery, radiographic appearance of the dens, type (dorsal or ventral procedure) and number (1 or 2) of surgeries performed, grade of postoperative atlantoaxial joint reduction, and neurologic status prior to surgery (preoperative), when dogs were discharged from the hospital (postoperative), and during a follow-up evaluation (final) were obtained from the dogs' medical records. Risk factors for surgical success and degree of neurologic improvement were identified and analyzed for predictive potential. RESULTS: Age at onset of clinical abnormalities < or = 24 months was significantly associated with greater odds of a successful first surgery and final outcome and a lower postoperative neurologic grade. Duration of clinical abnormalities < or = 10 months was significantly associated with greater odds of a successful final outcome and a lower final neurologic grade. A preoperative neurologic grade of 1 or 2 was significantly associated with a lower final neurologic grade. Potential risk factors that did not affect odds of a successful outcome included type of surgery performed, grade of atlantoaxial joint reduction, radiographic appearance of the dens, or need for a second surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Age at onset of clinical abnormalities, duration of clinical abnormalities prior to surgery, and preoperative neurologic status are risk factors for success of surgical management of AAS in dogs.

Animals↗

The effect of texturized vegetable protein containing soy carbohydrate on oroileal transit of chromic oxide in cannulated dogs.

Texturized vegetable protein (TVP) from soy is widely used in dog foods but contains indigestible carbohydrate, which may affect intestinal transit. This study was conducted to determine whether TVP affects oroileal transit of the marker chromic oxide (Cr2O3). Four canned diets with Cr2O3 added were fed to eight cannulated mixed-breed dogs in a Latin-square design. The four diets contained reciprocal proportions of protein from TVP (0 to 57%) and from beef (100 to 43%). Ileal effluent was collected during wk 3 of each diet period, prececal apparent digestibility was measured on d 1 to 3 (eight dogs), and rate of appearance of Cr2O3 and chyme was measured on d 4 (six dogs). There was a postprandial delay before any chyme or Cr2O3 was collected, but from 2 to 8 h postprandially the rate of excretion was almost constant (approximately 11%/h). As TVP increased, mean prececal digestibility of protein and carbohydrate decreased from 77 to 71% and from 80 to 62%, respectively. Chyme excretion from 2 to 8 h postprandially increased from 5.8 to 8.3 g DM/h (P < .0001) as TVP increased but times for transit of Cr2O3 and appearance of chyme (as percentage total collected/hour) did not change. Mean times to first appearance and 15, 50, and 95% excretion were 76, 160, 347, and 707 min for Cr2O3 and 60, 147, 338, and 712 min for chyme, respectively. Mean Cr2O3 recovery was 93%. In conclusion, small intestinal transit of Cr2O3 was unaffected by increasing dietary TVP despite marked changes in carbohydrate digestibility.

Animal Feed↗

General neurologist and subspecialist care for multiple sclerosis: patients' perceptions.

OBJECTIVE: To compare general neurologists and MS specialists on patients' clinical characteristics and MS care as perceived by patients with MS. METHODS: We sampled all adult patients with MS having physician visits over a 2-year period from a Midwestern managed-care organization and from the fee-for-service portion of 23 randomly selected California neurologists' practices. In mid-1996, 694 subjects were mailed questionnaires; 532 (77%) responded. Sociodemographic/clinical characteristics, recent utilization of services/treatments, unmet needs, symptom care, and research participation were measured. Of 502 subjects (94%) who indicated their usual physician providing MS care was a neurologist, 217 (43%) reported having a general neurologist and 285 (57%) reported having an MS specialist. Comparisons between these two groups were adjusted for comorbidity and disease severity. RESULTS: General neurologist and MS specialist patient groups did not differ on any sociodemographic or clinical characteristic except age (p<0.05). Although health care utilization generally was similar, higher proportions of the MS specialist group were aware of or had discussed interferon beta-1b (IFNbeta-1b) with their physician (p<0.05) and were currently taking it (p<0.05); a smaller proportion of the MS specialist group reported stopping it because of side effects (p<0.01). Overall, levels of unmet need and care for recent symptoms were similar, but the MS specialist group reported more confidence in their physician/carefulness in listening (p<0.05). Twice as many MS specialist subjects had participated in nondrug research (p<0.05); drug study participation was similar. CONCLUSIONS: Patients' perceptions of their care were similar in most ways for those who designated their main MS provider as a general neurologist compared to an MS specialist; however, care differed in potentially important areas. Prospective, longitudinal studies are needed to measure and relate neurologists' training, experience, knowledge, and MS patient volume with both process and outcome measures of quality of MS care.

Adult↗

A humoral response to oligodendrocyte-specific protein in MS: a potential molecular mimic.

OBJECTIVE: To determine the antibody response to oligodendrocyte-specific protein (OSP) in patients with MS. BACKGROUND: OSP is a recently identified CNS-specific myelin protein that is abundant and therefore a candidate autoantigen in MS. METHODS: The presence of anti-OSP antibodies was determined using Western blot analysis, peptide blots, and ELISA in patients with MS and in other neurologic and normal control subjects. RESULTS: Using Western blot analysis, seven patients with relapsing-remitting MS (RRMS) were found to contain anti-OSP antibodies in their CSF that were not present in control subjects. Peptide mapping determined that the antibody response was directed to a seven aa peptide (OSP 114-120), which has 71% homology with several common pathogenic proteins. Using OSP 114-120 as antigen, ELISAs were performed on CSF from 85 MS and 51 control patients. Eighty percent of the samples from RRMS patients followed at the University of California at Los Angeles had an ELISA reading above 0.55 optical density units, whereas all 20 control CSF samples had values less than 0.55 U. Similar results were found in specimens from an outside research bank. ELISAs performed on CSF using homologous viral peptides as antigen showed a close correlation with anti-OSP 114-120 ELISA readings, and in some, the readings were higher than those using OSP peptides. CONCLUSIONS: There is a specific humoral response directed against a region of OSP in RRMS patients that cross-reacts with several common viral peptides. This suggests a possible role for molecular mimicry in the development of MS.

Adult↗

Development of a multiple sclerosis functional composite as a clinical trial outcome measure.

The primary clinical outcome measure for evaluating multiple sclerosis in clinical trials has been Kurtzke's expanded disability status scale (EDSS). New therapies appear to favourably impact the course of multiple sclerosis and render continued use of placebo control groups more difficult. Consequently, future trials are likely to compare active treatment groups which will most probably require increased sample sizes in order to detect therapeutic efficacy. Because more responsive outcome measures will be needed for active arm comparison studies, the National Multiple Sclerosis Society's Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis appointed a Task Force that was charged with developing improved clinical outcome measures. This Task Force acquired contemporary clinical trial and historical multiple sclerosis data for meta-analyses of primary and secondary outcome assessments to provide a basis for recommending a new outcome measure. A composite measure encompassing the major clinical dimensions of arm, leg and cognitive function was identified and termed the multiple sclerosis functional composite (MSFC). The MSFC consists of three objective quantitative tests of neurological function which are easy to administer. Change in this MSFC over the first year of observation predicted subsequent change in the EDSS, suggesting that the MSFC is more sensitive to change than the EDSS. This paper provides details concerning the development and testing of the MSFC.

Clinical Trials as Topic↗

Scintigraphic, sonographic, and histologic evaluation of renal autotransplantation in cats.

OBJECTIVE: To determine scintigraphic, sonographic, and histologic changes associated with renal autotransplantation in cats. ANIMALS: 7 adult specific-pathogen-free cats: 5 males, 2 females, 1 to 9 years old. PROCEDURE: Renal autotransplantation was performed by moving a kidney (5 left, 2 right) to the left iliac fossa. Before and at multiple times after surgery, for a total of 28 days, cats were evaluated by B-mode and Doppler ultrasonography, scintigraphy, and renal biopsy. RESULTS: By 24 hours after surgery, a significant decrease (42%) in mean glomerular filtration rate (GFR) and an increase in mean renal size (81% increase in cross-sectional area) were evident in the transplanted kidney, compared with preoperative values. By postsurgery day 28, reduction in GFR was 23%. Significant changes in renal blood flow velocity were identified in both kidneys. Consistent changes in resistive index or pulsatility index for either kidney could not be identified. When all postoperative histologic data were combined, the histologic score, indicating degree and numbers of abnormalities detected, for the transplanted kidney was significantly higher than that for the control kidney. CONCLUSIONS: Significant changes in renal function, size, and histologic abnormalities develop secondary to acute tubular necrosis in cats after uncomplicated renal autotransplantation. CLINICAL RELEVANCE: Evaluation of renal size and function may be of benefit for clinical evaluation of feline renal transplant patients, whereas measurement of the resistive index may be of little clinical value.

Animals↗

Aortic foreign body resulting in ischemic neuromyopathy and development of collateral circulation in a cat.

A cat evaluated for paraplegia had firm pelvic limb musculature and did not have femoral pulses. External wounds were not evident, but abdominal radiography revealed a round metallic foreign body on the midline ventral to the sixth lumbar vertebra. Angiography indicated stenosis or thrombosis of the aorta in association with the foreign body; collateral circulation arose from the fifth lumbar artery. Arteriotomy was performed to extract the foreign body and associated thrombi. Six weeks after surgery, angiography revealed blood flow in the abdominal portion of the aorta, but no evidence of obstruction or additional collateral vessels. The cat regained function of the pelvic limbs within 1 year after surgery. Ischemic neuromyopathy and paraplegia in cats is commonly associated with aortic thromboembolism. A thrombus is necessary to cause typical clinical signs, and vasoactive substances released by platelets in the thrombus are believed to cause ischemic neuromyopathy. Progression of the collateral circulation may allow for clinical improvement without surgical intervention.

Animals↗

Pentoxifylline is not a promising treatment for multiple sclerosis in progression phase.

Fourteen MS patients took pentoxifylline at varying doses for up to 24 months. In vitro production of tumor necrosis factor alpha was reduced in patients taking 2,400 to 3,200 mg/day of pentoxifylline for 12 weeks or more. Twelve of the 14 patients experienced worsening of the disease during the study according to clinical, MRI, or visual evoked potential criteria. These results provide no hint of efficacy for pentoxifylline as a treatment for MS in progression phase.

Adult↗

Long-term results of surgical correction of persistent right aortic arch in dogs: 25 cases (1980-1995).

OBJECTIVE: To evaluate long-term outcome of dogs with persistent right aortic arch that undergo surgical correction. DESIGN: Retrospective study. ANIMALS: 25 dogs. PROCEDURE: Surgical correction consisted of ligation and division of the ligamentum arteriosum through a left fourth intercostal thoracotomy. Long-term (> 6 months after surgery) follow-up information was obtained by means of a telephone survey of owners (22 dogs) and by means of reevaluations by a veterinarian (3). RESULTS: Median age at the time of surgical treatment was 12 weeks. Short-term (2 to 4 weeks after surgery) follow-up information was available for 14 dogs. Nine no longer regurgitated after eating, and 5 regurgitated infrequently. Follow-up esophagography (median time after surgery, 4 months) was performed in 13 dogs and revealed persistence of megaesophagus in all 13. At the time of long-term follow-up, 23 (92%) dogs no longer regurgitated after eating, and the remaining 2 (8%) had regurgitated less than once per week. CLINICAL IMPLICATIONS: Contrary to previous reports, surgical correction of persistent right aortic arch resulted in complete alleviation of clinical signs in most dogs and an improvement in signs in the remaining dogs. Persistence of megaesophagus and regurgitation in the early postoperative period did not indicate a poor long-term outcome.

Animals↗

Pulmonary lobectomy in the management of pneumonia in dogs: 59 cases (1972-1994).

OBJECTIVE: To evaluate the risk and efficacy of pulmonary lobectomy in dogs with pneumonia. DESIGN: Retrospective study. ANIMALS: 59 dogs with pneumonia. PROCEDURE: Review of medical records and telephone conversations. RESULTS: 54.2% of dogs had resolution of pneumonia after lobectomy, 20.3% died in the perioperative period, and 25.4% survived the perioperative period but pneumonia did not resolve. Pneumonia was caused by bacteria (25 dogs), fungi (12), foreign bodies (8), parasites (1), viruses (1), and allergies (1). In 11 dogs, the etiologic agent was not isolated. Bacterial or fungal pneumonias were significantly less likely to resolve compared with foreign body pneumonia or when an etiologic agent was not isolated. Perioperative mortality rate increased significantly with an increase in number of pulmonary lobes removed. Complications during surgery significantly increased perioperative mortality rate. Surgical era (1972 to 1983 vs 1984 to 1994) was a significant predictor of mortality, with the odds of dying in the perioperative period being 11 times greater between 1972 to 1983. The odds of failure to resolve pneumonia was 3 times greater during 1972 to 1983. CLINICAL IMPLICATIONS: Number of pulmonary lobes removed and complications during surgery significantly affect perioperative mortality rate. Identification of etiologic agents may help in predicting dogs likely to resolve pneumonia after surgery.

Animals↗

Comparison of a generic to disease-targeted health-related quality-of-life measures for multiple sclerosis.

Evaluation of the relative contributions of generic and disease-targeted measures to assessing health-related quality of life (HRQOL) for chronic conditions is needed to help in selection of appropriate measures. We administered a generic HRQOL measure (the Short Form-36 [SF-36]), three disease-targeted supplemental scales to the SF-36, and two disease-targeted HRQOL instruments to 171 adults with multiple sclerosis. Most scales yielded adequate variability, internal consistency reliability, and test-retest reliability. The relationship between each measure and four primary "criterion" variables were assessed: overall symptom severity in the prior year; ambulation status; days unable to work or attend school in the prior month: and a rating of overall quality of life. Results indicate that the disease-targeted scales provided unique information not captured by the generic measure. We conclude that if a generic measure of HRQOL is desirable for a given study of multiple sclerosis, additional information will be gained by supplementing that measure with selected scales.

Absenteeism↗

Pulmonary lobectomy in the management of pneumonia in five cats.

Five cats underwent lobectomy for the management of pneumonia. The mean presurgical duration of treatment was eight months. A potentially immunosuppressive disease process was present preoperatively in two of the five cats. Preoperatively, two of the cats had radiographically diffuse pneumonia, while three had focal pneumonia. A single pulmonary lobe was removed in four cats, with one cat having two pulmonary lobes removed. There were no life-threatening complications and no clinical recurrence noted during a mean follow-up period of 37.8 months. The benefit of pulmonary lobectomy in focal pneumonia may lie in removing the nidus of infection. In diffuse, chronic or medically refractory pneumonia, obtaining an aetiological diagnosis may be the main benefit of lobectomy. Selective lobectomy for the treatment of pneumonia may be beneficial but a thorough preoperative evaluation is warranted.

Animals↗

Antisense blockade of inducible nitric oxide synthase in glial cells derived from adult SJL mice.

Increasing evidence suggests a correlation between cytokine-induced nitric oxide synthase (iNOS) and demyelination in Multiple sclerosis (MS). Inhibition of iNOS may therefore be a novel therapeutic approach in MS. To test an antisense oligodeoxynucleotide (ODN) knockdown strategy for inhibiting iNOS, we used lipopolysaccharide (LPS) together with gamma-interferon (IFN-gamma) to induce iNOS in adult mouse mixed glial cell cultures. We administered an iNOS-derived antisense phosphorothiorate oligodeoxynucleotide (S-ODN) to block the induction. The antisense ODN treatment resulted in significant inhibition of LPS and IFN-gamma induced iNOS mRNA and protein expression. It also inhibited nitric oxide (NO) and cyclic GMP (cGMP) production in a dose dependent fashion. Sense and random S-oligo had no effect in any of these studies. These data indicate the efficacy and specificity of the antisense oligodeoxynucleotide approach in inhibiting iNOS in glial cells.

Animals↗

A comparison of health-related quality of life in patients with epilepsy, diabetes and multiple sclerosis.

The purpose of this investigation was to compare self-reported health-related quality of life (HRQOL) in epilepsy compared to another neurological condition or a non-neurological chronic illness. Patients with epilepsy (N = 271), multiple sclerosis (N = 85) and diabetes (N = 555) completed a generic measure of HRQOL (RAND 36-Item Health Survey 1.0 (SF-36)), and the eight SF-36 scale scores were compared across groups, adjusting for differences in sociodemographic characteristics and co-morbid medical conditions. Patients with multiple sclerosis reported significantly worse HRQOL compared to both the epilepsy and diabetes groups (who did not differ from one another) on the Physical Functioning, Role Limitations-Physical, Energy, and Social Function scales. Patients with epilepsy and multiple sclerosis did not differ from one another but reported significantly lower HRQOL scores than the diabetes group on the Emotional Well-Being and Role Limitations-Emotional scales. However, the epilepsy group reported better health perceptions compared to the diabetes and multiple sclerosis patients. Generic measures of HRQOL appear useful in identifying some effects of neurological disease, but disease-targeted supplements may be required to more clearly identify the impact of epilepsy on quality of life.

Adult↗