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Objective: To evaluate the safety and efficacy of an ultrasonically activated scalpel for performing splenectomy, with minimal ligation, in dogs., Study Design: Prospective clinical study., Animals: Dogs (10) with naturally occurring splenic disease., Methods: Between October 2003 and February 2004, splenectomy was performed using an ultrasonically activated scalpel and a double seal method, in 10 dogs with naturally occurring splenic disease. Time for splenectomy and number of ligatures required were recorded. Intraoperative hemostasis, device ease of use, postoperative hemorrhage, and short-term survival were evaluated., Results: Mean operative time for splenectomy, exclusive of celiotomy and closure, was 18 minutes (range, 8-25 minutes). The mean number of ligatures needed to perform splenectomy was 1 (range, 0-2 ligatures). One dog hemorrhaged from the splenic vein after ultrasonic scalpel transection of a vessel >5-mm diameter and required a ligature. The ultrasonic scalpel was easy to use, with a minimal learning curve. None of the dogs had postoperative abdominal hemorrhage; 9 dogs were discharged and 1 dog was euthanatized because of septicemia., Conclusion: Ultrasonic activated scalpel may be used to achieve efficient and safe hemostasis of the splenic vascular pedicle in dogs with minimal need for vascular ligation., Clinical Relevance: Ultrasonic scalpels can be used to perform splenectomy in dogs with naturally occurring splenic disease.

A retrobulbar malignant fibrous histiocytoma was diagnosed in a 12-year-old castrated male Keeshond dog. The mass was excised with a lateral orbitotomy and zygomatic arch resection. Vision was preserved in the affected eye, and no recurrence was noted up to 10 months postoperatively. Malignant fibrous histiocytoma originates from primitive mesenchymal stem cells. The malignant fibrous histiocytoma seen in our patient was most consistent with the storiform-pleomorphic variant, given the storiform arrangement of spindle cells, the presence of histiocytoid cells, and a mixed inflammatory infiltrate, without giant cells. The metastatic potential of malignant fibrous histiocytoma in general, and the storiform variant in particular, is unknown. Seventeen months later the dog was presented to the referring veterinarian with anorexia, diarrhea, weight loss and bilateral purulent nasal exudates. The dog was euthanized without necropsy.

Alapexy involves the creation and apposition of two small elliptical incisions, which fix the alae in an abducted position. Permanent alapexy was achieved in four of five dogs (eight of nine nostrils) that were operated. Four animals had significant improvement in their respiratory efforts because of reduced nasal obstruction. Although the alapexy procedure was somewhat more difficult to perform than simple wedge resection techniques, it may be a viable option in those animals where other techniques have failed or in animals that have dystrophic or flaccid alar cartilage. The alapexy technique may also improve the diameter of the nares compared to previously described techniques.

The purpose of this study was to identify oxidative damage to renal allografts during graft rejection by evaluating changes in oxidative markers and plasma lactate levels in feline renal allotransplant recipients. Heterotopic renal allotransplantations were performed between 8 adult feline cross-matched donors. Following 14 d of immunosuppression, the drugs were discontinued to allow allograft rejection. Baseline and serial postoperative evaluations of serum creatinine, plasma lactate, plasma thiobarbituate reactive substances (TBARS), plasma creatol, urine creatol, and renal sonographic cross-sectional area were performed. When sonographic evaluation revealed the absence of blood flow to the allograft, the rejected kidney was nephrectomized and evaluated histopathologically. Allograft rejection occurred in all cats by day 26. A significant elevation in body temperature occurred during the rejection period. No significant change was observed between any of the time periods for plasma TBARS, creatol, or urine creatol. There was a significant decrease in plasma lactate levels throughout the study. Markers of oxidative stress from venous blood did not reflect renal allograft rejection in cats with a normally functioning native kidney. Renal allograft rejection may be associated with significant increases in body temperature and warrants further investigation.

Major resections of the tongue have not been commonly performed in animals because of concerns about the unfavorable postoperative effects of diminished lingual function. Five dogs were retrospectively reviewed to determine prehensile function and quality of life after glossectomies. Examinations were performed 1 week to 8 years after glossectomy, and owner interviews were conducted 10 months to 8 years after the surgery. All five dogs had acceptable and functional outcomes. Based on these five cases, glossectomy was well tolerated by dogs and may be a viable treatment option for aggressive tongue tumors and other conditions that render the tongue unsalvageable.

The sonographic features of acute renal allograft rejection in humans and dogs are manifested by increase in renal cross-sectional area and reduction in renal cortical blood flow. These changes have not been investigated in cats. The objectives of this study were to evaluate sonographic and scintigraphic changes during acute renal allograft rejection in cats. Eight SPF, intact, adult, male cats received heterotopic renal allotransplantations. Immunosuppressive doses of cyclosporine and prednisolone were administered for 14 days and then discontinued to allow acute allograft rejection to occur. Serial measurements of renal cross-sectional area, resistive index (RI), echogenicity, and glomerular filtration rate (GFR) were performed to evaluate changes during acute rejection. Upon sonographic confirmation of absent diastolic blood flow or a 20% increase in cross-sectional area of the allograft, a nephrectomy and histopathologic evaluation were performed. Acute allograft rejection was confirmed histologically in all cats. Significant increases in renal cross-sectional area (P < 0.001) occurred postoperatively and during rejection. There were no significant changes in RI (P = 0.43) at any time. A subjective increase in medullary echogenicity and a decrease in corticomedullary demarcation were observed in the rejection period. While GFR decreased significantly in the immediate postoperative period (P < 0.001), no further change occurred during rejection (P = 0.42). Changes in RI and GFR do not appear to be sensitive indicators of acute renal allograft rejection in cats. Serial measurements of renal cross-sectional area appear to be a sensitive method for the early diagnosis of allograft rejection in feline renal transplant recipients.

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.

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., (Copyright 2001 Wiley-Liss, Inc.)

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.

The purpose of this study was to evaluate the surgical outcomes of 28 dogs with generalized septic peritonitis treated without postoperative abdominal drainage. The overall mortality rate was 46%, with most cases of peritonitis being caused by leakage of the gastrointestinal tract (75%). Etiology of peritonitis, abdominal cytopathology, total white blood cell count, packed cell volume, total protein, and results of serum biochemistries were not statistically different between survivors and nonsurvivors. The mortality rate of 46% is similar to other studies in which the abdomen was left open postoperatively for the management of septic peritonitis, although more advanced medical treatment than that used in earlier studies may have positively affected the outcome. The results of this study show that closure of the abdomen after the source of contamination has been successfully corrected, in combination with thorough intraoperative peritoneal lavage and appropriate postoperative medical management, may be an acceptable alternative method for the management of septic peritonitis.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

There remains controversy regarding the most sensitive and valid outcome assessments to use in multiple sclerosis (MS) clinical trials. A double blind, placebo controlled, parallel group multicenter clinical trial to evaluate the clinical efficacy of cyclosporine A in chronic progressive MS incorporated several major clinical and performance outcome assessment modalities and a large sample size, both of which provide a unique opportunity to explore the relationship among MS disease status and the various outcome measures over time. The measures included a structured neurological examination, the Kurtzke Functional System scales and Expanded Disability Status Score, and the Incapacity Status Scale from the MS Minimal Record of Disability, the Harvard Ambulation Index, and neuroperformance testing. A test-retest reliability index, principal component analyses and a signal-to-noise ratio metric were used to comparatively evaluate the reliability, validity and sensitivity to disease progression of the various outcome assessments. The goal was to provide a rational basis for selection of behavioral outcome assessments in future MS clinical trials by identifying the primary dimensions of MS measured by the candidate outcome assessments and providing an objective basis for selecting tests that are most sensitive to MS disease and its progression over a two year trial period. We conclude that the components of the major clinical and performance measures show excellent reliability and cross validation. Principal component analyses of all outcome assessments yielded six primary underlying factors for describing disease status in chronic progressive MS that included lower extremity/pyramidal dysfunction, cerebellar/brainstem and upper extremity dysfunction, somatosensory dysfunction, visual dysfunction, mental or intellectual dysfunction and bowel/bladder problems. Signal-to-noise ratios indicated that upper and lower extremity composites of neuroperformance test items provided the most sensitive indicators of MS disease progression in the placebo group over the 2 year trial period.

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.

Small intestinal digestibility can be measured by comparing feed with effluent collected from an ileal T-cannula. Nevertheless, a nondigestible, nonabsorbable marker, such as chromic oxide (Cr2O3), must be included in the diet because simple T-cannulae do not divert chyme completely. This study was conducted to evaluate the excretion pattern of Cr2O3 in cannulated dogs because the kinetics of Cr2O3 has not been previously investigated in this nonruminant species. Chromic oxide was added to four diets fed to eight cannulated mixed-breed dogs in a Latin-square design. The four diets contained reciprocal proportions of protein from texturized vegetable protein (0% to 57%) and from beef (100% to 43%), so protein and carbohydrate digestibility varied among diets. All feces were collected during wk 2 and all ileal effluent during wk 3 of each diet period. Ileal recovery of Cr2O3 was almost complete (94%) and was greater than fecal recovery (87%) (P < or = .03). Recovery was not different among diet groups. Ileal DM digestibility was approximately 2 percentage units lower on d 1 (P < or = .007) than on d 2 to 4. Nevertheless, ileal DM digestibility varied little on these subsequent days so single-day collections should be accurate. Chromic oxide concentration in chyme varied widely during each collection but increased at the start and declined towards the end of each collection. Spot sampling may therefore result in inaccurate estimates of nutrient digestibility. In conclusion, Cr2O3 may be used as a marker to measure digestibility in dogs with simple T-cannulae, but total collections should be attempted for greater accuracy.

Accurate measurement of small intestinal digestibility is important in dogs because it allows the formulation of pet foods that provide optimal nutrition at minimal cost. Digestibility measured by comparing nutrient intake to fecal excretion in intact animals does not distinguish small intestinal digestion from large intestinal bacterial fermentation. Ileal cannulation allows small intestinal digestion to be measured alone by comparing nutrient intake with ileal excretion of chyme. Nevertheless, ileal cannulation and its associated complications are not well documented in dogs. We describe the implantation of a simple T-cannula in the ileum of nine dogs for an average duration of 26 weeks. Established cannulas were well tolerated, and one dog retained the cannula for 14 months. Nevertheless, ileal effluent proved extremely caustic, and the incidence of complications in the immediate postoperative period was high. Only one dog had an unremarkable postoperative course. Complications included abscessation and cannula extrusion, followed by severe excoriation and ulceration of the skin. This excoriation could be prevented only by immediate surgical closure of the fistula. Chronic ileal cannulation is therefore a viable technique in dogs, but careful monitoring of the cannula site is essential. Dogs should be subjected to this procedure only if adequate veterinary and nursing care is available. It is preferable to maintain a colony of long-term cannulated dogs rather than to implant cannulas as needed.

Plain film radiography, magnetic resonance imaging, and histologic evaluation were used to diagnose nasopharyngeal epidermal cyst in a 12-year-old male Miniature Poodle with inspiratory stridor. The cyst was lined with stratified squamous epithelium, with variable keratinization. Most of the epithelium was well-differentiated and supported by a fibrovascular tissue separating it from underlying woven bone. One margin of the mass had a transition from stratified squamous to columnar respiratory epithelium. Other reported epidermal cysts in dogs have been confined to the middle ear or intracranial area. This case was unique, because the mass was located in the nasopharyngeal area, causing airway obstruction. This lesion was most likely acquired rather than congenital, because the dog had a history of middle ear inflammation, as well as bite wound trauma to the throat region. The mass was successfully removed by use of a transpalatal approach, and signs attributable to respiratory obstruction were alleviated. The dog had no abnormal clinical signs several months after the procedure.

The need for measures of health-related quality of life (HRQOL) for clinical effectiveness research and for quality of care research, particularly for chronic diseases, is increasingly recognized. We assessed a measure of HRQOL for people with multiple sclerosis, a chronic neurological condition. We used the RAND 36-Item Health Survey 1.0 (aka SF-36) as a generic core measure, to enable comparisons of HRQOL of patients with multiple sclerosis to those of other patient populations and to the general population. To enhance comparisons within groups of multiple sclerosis patients, these items were supplemented with 18 additional items in the areas of health distress (four items), sexual function (four items), satisfaction with sexual function (one item), overall quality of life (two items), cognitive function (four items), energy (one item), pain (one item), and social function (one item). The final measure, the Multiple Sclerosis Quality of Life (MSQOL)-54 Instrument, contains 52 items distributed into 12 scales, and two single items. Internal consistency reliability estimates for the 12 multi-item scales ranged from 0.75 to 0.96 in a sample of 179 patients with multiple sclerosis. Test-retest intraclass correlation coefficients ranged from 0.66 to 0.96. Exploratory factor analysis confirmed two underlying dimensions of physical health and mental health. Construct validity was supported by significant associates between MSQOL-54 scales and degree of multiple sclerosis symptom severity in the prior year, level of ambulation, employment limitations due to health, admission to hospital in the previous year, and depressive symptoms.

Excision of perianal fistulas using a 1.064 micron wavelength neodymium:yttrium aluminum garnet (ND:YAG) contact tipped laser with primary wound closure was used to treat 20 dogs with perianal fistulas. Overall, 19 of 20 (95%) dogs had resolution of fistulas after one or more ND:YAG treatments. The period of resolution ranged from 10 to 42 months with a mean of 22.9 months. Sixteen of 20 (80%) dogs had resolved fistulas after one laser excision. Three of the four recurrences underwent additional laser treatments with successful results. The total number of laser procedures ranged from one to three with a mean of 1.2 procedures. Postoperatively, anal tone as judged by digital rectal examination was reduced in about 60% of the cases, but clinical evidence of fecal incontinence only occurred in four of 20 cases. This was managed effectively with diet modification. The tendency toward loss of anal tone or fecal incontinence depended on the severity of preexisting anal stenosis. On a client survey, 19 of 20 owners believed that their animals experienced less pain during defecation after surgery and rated the results as excellent or good. The overall success rate using ND:YAG laser excision compared very favorably with previously reported studies of other methods of treatment for perianal fistulas in dogs.

After analyzing our natural history data on the course of multiple sclerosis (MS) in more than 500 patients followed for 20 years and our experience in several therapeutic trials, we concluded that a phase III (full) trial for efficacy should have certain properties. For a power of 0.8, alpha of 0.05, and attrition rate of 10% per year, we think the trial should have a minimum sample size of 130 (65 in each arm; placebo versus active) if the design is based upon the proportion of subjects worsening by clinical measures. No stratification by entry Extended Disability Status Scale score is needed if worsening is defined as a change of 1.0 units (2 to 0.5 steps) maintained for 90 days for an entry score of 1 to 5.0 units; or 0.5 units (1 to 0.5 steps) if the entry score is 5.5 to 7 units. We need not stratify by course (relapsing-remitting versus relapsing-progressive) but are less certain about progression from the onset. No run-in period is required to define "activity." Minimum time for treatment is 3 years. We review the justification for our conclusions; modifications in sample size that are necessary if survival analysis is used; impact of the interferon-beta trial (future trials will have an "active" control); and alternative strategies possible if magnetic resonance imaging serves as the primary outcome.

Definitive surgical management of gastric dilatation volvulus involves gastric repositioning, gastric resection when indicated and surgical formation of a permanent adhesion to prevent recurrence of the problem. Derotation and gastropexy procedures are recommended as soon as the patient is a reasonable anesthetic risk. Splenectomy and pyloric outlet procedures are of questionable value in preventing recurrence in the majority of cases. In North America, most veterinary surgeons perform right-sided antral gastropexy as a means of preventing recurrence. The technical advantages and disadvantages and experimental and clinical results of several techniques, including the tube gastrostomy, incisional gastropexy, circumcostal gastropexy, and belt-loop gastropexy, are discussed.

Gastric myoelectric activity was measured in 10 dogs with spontaneous gastric dilatation-volvulus (GDV). Myoelectric activity was recorded with temporary, retrievable wire electrodes placed on the serosal surface of the stomach after derotation and tube gastrostomy. Gastric myoelectric activity was recorded for 1 hour daily, beginning with the day of surgery (less than 24 hours), 24, 48, 72, 96, 120, 144, and 168 hours after surgery. Recordings were also obtained for 1 hour daily after feeding, beginning 24 hours after surgery. Bradygastria was the predominate dysrhythmia immediately after surgery and at hour 24. The mean slow wave frequency was more than normal at hours 48 to 168 due to an increase in tachygastria and arrhythmias. The slow wave frequency significantly decreased after feeding at hours 120 and 144. The overall mean percentage of dysrhythmias was significantly decreased after feeding at hour 72 only. The mean percentage of spike activity ranged from 37.7 +/- 12.5 to 75.7 +/- 6.2 throughout the 8-day study period. Thus, gastric myoelectric activity was disrupted in these dogs with spontaneous GDV and subsequent tube gastrostomy. Feeding did not greatly diminish these dysrhythmias.

A dog with a rectal adenomatous polyp had extreme neutrophilic leukocytosis, monocytosis, and eosinophilia consistent with a paraneoplastic syndrome. Resolution of the leukogram abnormalities after tumor excision supported this belief. Except for a lack of circulating myeloblasts, the dog had leukogram findings consistent with a neutrophilic leukemoid reaction.

After surgical removal of a primary intranasal neoplasm, an implant device, designed to deliver 192iridium (192Ir) brachytherapy, was positioned in the nasal cavity of 8 dogs. Ribbons containing 192Ir seeds were placed in the device, using an afterloading technique. Dosimetry, to a dose of 7,000 to 10,000 centiGray (cGy), was calculated to encompass the site previously occupied by the tumor and a 1-cm margin of surrounding normal tissue. The quantity of 192Ir implanted varied between 16.69 and 100.80 mg of radium equivalent. The duration of implantation ranged from 90 to 168 hours. All dogs tolerated the implant well, but had a mucoid nasal discharge after radiotherapy. The implant device allowed rapid application and removal of the radioactive ribbons. Mean (+/- SD) radiation exposure to each radiotherapist during seed loading and unloading was 14.4 (+/- 5.3) and 4.5 (+/- 0.9) mrem, respectively. A uniform dose distribution around the intranasal implant device was achieved; however, dogs that received doses in excess of 9,400 cGy at the dorsolateral surface of the nose and/or hard palate had bone and soft tissue necrosis between 70 and 120 days after treatment. One dog was euthanatized 50 days after treatment because of metastatic disease, and 2 dogs were euthanatized because of local tumor recurrence at 125 and 212 days. Death, considered unrelated to treatment, occurred in 1 dog that was euthanatized 27 days after treatment and in 3 dogs that died 30, 93, and 456 days after treatment. Necropsy was performed on 3 of these dogs and evidence of intranasal neoplasia was not observed. One dog remained disease-free at 587 days after treatment.

This study examined the linkage between elevated blood serotonin in autism and the presence of circulating autoantibodies against the serotonin 5HT1A receptor. Information was also obtained on the diagnostic and receptor specificity of these autoantibodies. Blood serotonin was measured as was inhibition of serotonin binding to human cortical membranes by antibody-rich fractions of blood from controls and from patients with childhood autism, schizophrenia, obsessive-compulsive disorder, Tourette's, and multiple sclerosis. The results showed elevated blood serotonin was not closely related to inhibition of serotonin binding by antibody-rich blood fractions. Inhibition of binding was highest for patients with multiple sclerosis and was not specific to the 5HT1A receptor as currently defined. Although inhibition was not specific to autism, the data were insufficient to establish if people with autism differed from normal controls on this measure.

Gastric myoelectric activity was measured after experimental gastric dilatation-volvulus (GDV), GDV and tube gastrostomy, or tube gastrostomy in 12 dogs. Gastric myoelectric activity was recorded for 1 hour before (hour 0) and at hours 5, 24, 48, 72, and 96 after surgically induced GDV in six dogs. Three dogs with induced GDV and tube gastrostomy, and three dogs with tube gastrostomy only were also studied at hours 120, 144, and 168. The only significant change in the slow wave appearance or frequency from hours 0 to 48 was bradygastria at hour 5 in all three groups. A relative increase in the mean percentages of dysrhythmia from hours 72 to 168 in the dogs with a tube gastrostomy was caused by increases in tachygastria and arrhythmias. Dogs with GDV and tube gastrostomy had the greatest mean percentages of dysrhythmia, which were significantly more than those in dogs with GDV alone at hours 48, 72 and 96. The mean percentage of spike activity was less than or equal to 31 and varied widely. In general, there was less spike activity when the frequency of dysrhythmias was high. Thus, gastric myoelectric activity was disrupted from hours 48 to 168 after GDV with tube gastrostomy and after tube gastrostomy alone. Surgically induced GDV alone did not produce any significant or sustained dysrhythmias.

The efficacy of azathioprine in the treatment of multiple sclerosis was assessed by meta-analysis of the results of all published blind, randomised, controlled trials. 793 patients were enrolled in 5 double-blind and 2 single-blind studies. After 1 year of treatment, the increase in Kurtzke disability status score was no different in treated and control groups, but at 2 years there was a small difference (-0.22; 95% confidence interval [CI] -0.43, 0.003) in favour of azathioprine treatment; this difference was sustained, but not increased, after 3 years. The probability of freedom from any relapse during 1, 2, and 3 years' treatment was significantly greater in the azathioprine-treated group (relative odds over 3 years 1.97; 95% Cl 1.27, 3.04), but it is debatable whether the slight clinical benefits of azathioprine outweigh its side-effects.

Thirty-three patients with chronic progressive multiple sclerosis (MS) were assigned to intervention groups receiving monthly pulses of chlorambucil (CB) for about one year. The monthly doses ranged from 0.4 to 1.5 mg/kg. Administration of CB resulted in preferential reduction in different lymphocyte subsets which was dose- and time-dependent. The number of B-cells (CD20) decreased more rapidly than NK-cells (CD16, CD56, CD16+CD56+) or T-cell (CD3) and T-cells subsets (CD4 and CD8). At 1.2 mg/kg, CB administration resulted in a preferential drop of T-suppressor/cytotoxic cells (CD8) compared with T-helper cells (CD4), and of the less mature "virgin" CD4 cells (CD4+CD45RA+) compared with "memory" CD4 cells (CD4+CD45RA-). The expression of activation markers (transferrin receptor, CALLa, HLA-Dr and CD38[OKT10]) within CD4, CD8 or CD20 lymphocytes was not altered by CB administration. Our data, which show that CB administration results in a preferential fall in B-cell numbers, contrast with the effects of long-term administration of the related immunosuppressive drugs, azathioprine and cyclophosphamide.

We tested 11 patients with multiple sclerosis for the presence of human T-cell leukemia virus type I (HTLV-I)- or type II (HTLV-II)-related sequences. DNA from blood mononuclear cells was analyzed by the polymerase chain reaction utilizing three different oligonucleotide primer pairs. Two of these primer pairs detect sequences shared between HTLV-I and HTLV-II in either p24, gag protein, or in p21, env transmembrane protein. The third primer pair was synthesized based on regions in the pol gene where amino acid sequences are conserved between HTLV-I, HTLV-II, and the related bovine leukemia virus. The multiple sclerosis samples were consistently negative while appropriate control samples were positive. We conclude that viruses related to HTLV-I, HTLV-II, or bovine leukemia virus are not present in the blood of patients with multiple sclerosis and, therefore, that HTLV-bovine leukemia virus-related viruses are not likely to be involved in the pathogenesis of multiple sclerosis.

Because the immune response appears important in the pathogenesis of MS, anti-inflammatory and immunomodulatory drugs and agents are used as a palliative treatment. Azathioprine alone is minimally efficacious and probably not worth the bother and risk. Cyclophosphamide alone is too toxic. Although cyclosporine A may slow the rate of deterioration in chronic progressive MS, adverse effects may limit its use outside major centers. Gamma interferon provokes exacerbations and should not be used. We do not recommend copolymer-1, alpha or beta interferon, monoclonal antibodies, plasmapheresis, and total lymphoid irradiation except in well-designed experimental protocols. Combination therapy of adrenal cortical steroids (ACS) with other immunosuppressants (cyclophosphamide or cyclosporine) merits further study. We think "pulse" synthetic ACS therapy has advantages over corticotropin and will become the "standard of care" for exacerbations. We also would try it for chronic progression. Even then, with the pulse treatment we still must determine the optimum dose, route, duration, and need for "taper."

Magnetic resonance imaging (MRI) of the cerebrum, cerebellum, brain stem, and upper cervical cord was performed in 62 individuals with clinically definite chronic, progressive multiple sclerosis (MS). The total area of MRI-demonstrated lesions was measured from film enlargements for each region using an interactive image analysis system. While the MRI was abnormal in 60 (97%) of 62 patients, the visual-evoked potentials in 51 (85%) of 60 patients, the brain stem auditory-evoked potentials (BAEPs) in 24 (46%) of 52 patients, and the somatosensory-evoked potentials (SSEPs) in 45 (89%) of 54 patients, an abnormal intra-blood-brain barrier (BBB) IgG synthesis rate, IgG oligoclonal bands, or both were found in all 62 patients. The total area of MRI abnormality in the cerebrum was significantly correlated only with the intra-BBB IgG synthesis rate, abnormal visual-evoked potentials, impaired performance on the Symbol Digit Modalities Test (SDMT), and one test of standing duration in the quantitative examination of neurologic function (QENF). The brain stem lesion area correlated with the Kurtzke expanded disability status scale and brain stem functional systems score, the ambulation index, abnormal BAEPs, and impaired performance on the SDMT as well as multiple tests of upper and lower extremity function in the QENF. The cerebellar lesion area correlated with impaired performance on the SDMT and primarily upper extremity testing in the QENF.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs were available on a selected number of multiple sclerosis and control subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control groups. A greater number of reduced ratios of serum:CSF IgG antibody to EBV-capsid antigen and antibody to EBV-early antigen components than to adenovirus, a reference or control virus, were found in the multiple sclerosis group. Reduced ratios of these EBV antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the results of an earlier report and strengthen the association between EBV and multiple sclerosis.

A 6-year-old male Doberman Pinscher developed multiple organ infarctions secondary to vegetative endocarditis. Clinical signs included fever, nystagmus, head-tilt, inappetence, dehydration, hematuria, and dysuria. The dog was azotemic and anemic and had a high WBC count and high liver enzyme activities. Disseminated intravascular coagulation was diagnosed on the basis of thrombocytopenia and prolonged activated clotting times. Vegetative mitral valvular lesions were evident on M-mode echocardiography. The dog underwent diuresis with physiologic saline solution and was treated parenterally with antibacterial and anticoagulant agents. Surgery was performed to remove an infarcted kidney and an infarcted spleen and to relieve urethral obstruction caused by a large blood clot. Gram-positive cocci were noticed in the biopsy specimens. Mortality associated with organ infarctions secondary to bacterial endocarditis is high, and combined medical and surgical therapy is rarely reported. This dog survived and was alive 38 months after surgery.

Recovery of various components of the immune system was followed in eight patients with multiple sclerosis who had received monthly pulses of cyclophosphamide (CY) for approximately one year. CD8 cell numbers and NK and ADCC functions recovered in 1-2 months; B cells and FcR+ cell numbers recovered in 2-4 months. The recovery of CD4 cells and total T cell numbers, CD4/CD8 ratio and proliferative responses to PHA took more than 4 months. The impaired proliferation was not attributable to low IL-2 receptor expression. Once immunosuppression has been achieved pulse administration of CY at 2- to 4-month intervals may be feasible for long-term maintenance treatment.

In an effort to further characterize the defective proliferative response of T lymphocytes to mitogens in multiple sclerosis (MS) patients, we examined the response to and production of interleukin 2 (IL 2) by both peripheral blood lymphocytes (PBL) and cerebrospinal fluid mononuclear cells. We also examined the proportion of cells bearing receptors for IL 2 and transferrin. Chronic progressive MS patients have an abnormally low response to exogenous IL 2 as compared to controls. Whereas acute relapse patients' PBL demonstrated a normal IL 2 response during an exacerbation, they showed reduced responsiveness during remission. These abnormalities could not be explained by different dose or kinetic response optima to PHA or IL 2, nor could they be explained by depressed numbers of IL 2 or transferrin receptor-bearing lymphocytes. Production of IL 2 by PBL was also abnormal in MS patients. Chronic progressive patients produced elevated levels of IL 2, whereas acute relapse patients undergoing an exacerbation produced diminished levels of IL 2. During remission, these levels returned to that of controls'. The effect of 1200 rad x-irradiation or nylon wool removal of adherent cells was a significantly greater augmentation of IL 2 production in MS patients than in other neurologic disease or normal controls. Cerebrospinal fluid lymphocytes from MS patients had normal proportions of IL 2 receptor-bearing cells, but were deficient in their IL 2 response and production as compared to autochthonous or control PBL. The inability of some MS patients' lymphocytes to clonally expand in response to IL 2 might contribute to the pathogenicity of the disease.