Antioxidant supplementation and subsequent oxidative stress of horses during an 80-km endurance race.

This study tested the development of oxidative stress and the effects of antioxidant supplementation in an 80-km ride. A precompetition survey revealed that no competitor would participate without vitamin E supplementation; therefore, 46 horses were paired for past performances and randomly assigned to two groups of 23 each for 3 wk of supplementation before the ride. One group (E) was orally supplemented with 5,000 IU of vitamin E per day; the other group (E+C) received that dose of vitamin E plus 7 g/d of vitamin C. Blood samples, temperature, and heart rate were taken the day before the race, at 21 and 56 km during the ride, at completion, and after 20 min of recovery. Plasma was assayed for lipid hydroperoxides, alpha-tocopherol, total ascorbate, albumin, creatine kinase (CK), and aspartate aminotransferase (AST). Total glutathione and glutathione peroxidase activity were determined in red blood cells and white blood cells. Thirty-four horses completed the race, 12 horses (six in E and six in E+C) did not finish for reasons including lameness, metabolic problems, and rider option. Plasma ascorbate was higher (P = 0.045) in the E+C group than in the E group. Other than ascorbate, neither antioxidant status nor CK and AST activities were affected by supplementation with E+C vs. E. Red blood cell glutathione peroxidase, white blood cell total glutathione, lipid hydroperoxides, CK, and AST increased, and red blood cell total glutathione and white blood cell glutathione peroxidase activity decreased with distance (P < 0.001). Positive correlations were found for plasma lipid hydroperoxides on CK (r = 0.25; P = 0.001) and AST (r = 0.33; P < 0.001). These results establish an association between muscle leakage and a cumulative index of oxidative stress.

Antioxidant status and muscle cell leakage during endurance exercise.

Antioxidant status of 35 endurance horses was studied during an 80 (OD80) or 160 km (OD160) race. Packed cell volume (PCV), total plasma protein (TPP), plasma ascorbic acid (VIT C), plasma alpha-tocopherol (VIT E) and erythrocyte glutathione (GSH) concentrations, erythrocyte glutathione peroxidase (GPX), plasma aspartate aminotransferase (AST) and plasma creatine kinase (CK) activities were measured at 0, 40, 80 km and 60 min of recovery (REC) at OD80, and 0, 64, 106, 142, 160 km and REC at OD160. In both races, no changes were found in plasma VIT E concentration, but VIT C and GSH concentrations decreased (P<0.05), and mean GPX, AST and CK activities increased from 0 km (P<0.05). Indices of muscle cell leakage (plasma AST and CK) were correlated (r = 0.36 to 0.67; P<0.03) with indices of antioxidant status (VIT C, GSH and GPX). Associations between increased muscle leakage and decreased antioxidant status may, in part, reflect oxidative stress and suggest the testing of antioxidant supplements in endurance horses to improve performance and welfare.

A comparison of published head and neck stage groupings in carcinomas of the tonsillar region.

BACKGROUND: The combination of T, N, and M classifications into stage groupings was designed to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. The authors tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer to determine their ability to meet these expectations in a specific site: carcinoma of the tonsillar region. METHODS: The authors defined four criteria to assess each stage grouping scheme: 1) The subgroups defined by T and N comprising a given group within a grouping scheme have similar survival rates (hazard consistency); 2) The survival rates differ across the groups (hazard discrimination); 3) The prediction of cure is high (outcome prediction); and 4) The distribution of patients among the groups is balanced. The authors identified or derived a measure for each criterion and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). Data were from a retrospective chart review on 642 cases of carcinoma of the tonsillar region treated with radiotherapy for cure at the Princess Margaret Hospital from 1970-1991. None of the patients had distant metastases. RESULTS: The scheme proposed by Synderman and Wagner, which was published in Otolaryngology Head and Neck Surgery in 1995 (vol.112, pages 691-4), scored best at 1.2. The UICC/AJCC scheme scored worst at 6.1. The hazard consistency ranged from a 3.1% average survival difference to 6.7% across the 8 schemes. The hazard discrimination measure varied by 28% from the best to worst scheme. Prediction varied by up to almost twofold across the schemes assessed. The distribution of patients varied from expected by between 0.13% and 0.57%. CONCLUSION: UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform as well as any of seven empirically-derived schemes the authors evaluated. The results of the current study suggest that the usefulness of the TNM system can be enhanced by optimizing the design of stage groupings through empirical investigation.

A retrospective analysis of 52 cases of spinal cord glioma managed with radiation therapy.

PURPOSE: To describe the outcome of primary spinal cord glioma treated with radiation therapy after surgery and to identify variables predictive of outcome. METHODS AND MATERIALS: A chart review of 52 patients with a diagnosis of spinal cord non-ependymoma glioma at the Princess Margaret Hospital was conducted. Thirty-two patients (62%) were male and 20 (38%) were female. Median age was 32 years (2-76 years). Median follow-up was 3.7 years (2 months to 27 years). Initial surgical management consisted of biopsy alone in 27 (52%) cases, subtotal resection in 20 (38%) cases, and gross total resection in 5 (10%) cases. All patients received postoperative radiation therapy; median total dose was 50 Gy, given in 25 daily fractions (20-60 Gy). Actuarial survival rates were calculated and the influence of patient-, tumor-, and treatment-related variables on outcome was determined. RESULTS: Five-year overall, cause-specific, and progression-free survivals were 54%, 62%, and 58%, respectively. Ten-year survivals were 45%, 50%, and 43%, respectively. A total of 29 (56%) patients died during the period of review. For 23 (79%) of these patients, death was cancer specific. Progression of tumor was documented in 28 of 52 (54%) patients. The following factors predicted for improved outcome on univariate analysis: age < 18 years, low-grade histology, and length of symptoms prior to diagnosis > 6 months. CONCLUSION: The outcome of patients in this series is consistent with that of other similar published reports. Specific recommendations are made for the management of this tumor.

Carcinoma of the maxillary antrum: a retrospective analysis of 110 cases.

BACKGROUND AND PURPOSE: Cancer of the maxillary antrum is a rare disease with a variety of treatment options. The present study was undertaken to review the outcome of patients with carcinoma of the maxillary antrum managed at a single institution. MATERIALS AND METHODS: A retrospective analysis of 110 cases of carcinoma of the maxillary antrum managed with curative intent during the time period 1976-1993 was performed. There were 33 females and 77 males; the median age was 64 years (range 38-89). The median follow-up time was 4 years (range from 2 months to 17 years). The majority of patients presented with locally advanced disease (78 T4 tumours); nodal involvement was observed in 17/110 cases. Histologic subtypes included in the analysis were limited to squamous cell carcinoma (95 cases) and undifferentiated carcinoma (15 cases). Patients were managed with either primary radiation therapy with surgery reserved for salvage (83/110) or with a planned combined approach with surgery and either pre or postoperative radiation (27/110). RESULTS: The actuarial 5-year cause-specific survival rate was 43%. The 5-year local control rate was 42%. Of 63 patients with local failure, 25 underwent salvage surgery with a subsequent 5-year cause-specific survival of 31%. Multiple regression analysis of patient, disease and treatment related variables identified local disease extent and nodal disease at presentation as the only variables independently associated with cause-specific survival. CONCLUSIONS: This analysis indicates that survival from carcinoma of the maxillary antrum is poor with outcome strongly related to local disease extent. The best treatment strategy for this disease remains undefined. Salvage surgery can result in prolonged survival in selected patients experiencing local failure.

Ethmoid sinus cancer: twenty-nine cases managed with primary radiation therapy.

PURPOSE: To describe the outcome of patients with carcinoma of the ethmoid sinus managed with a policy of primary radiation therapy with surgery for salvage of persistent or progressive disease. METHODS AND MATERIALS: A retrospective chart review was undertaken of 29 patients with the diagnosis of carcinoma of the ethmoid complex who underwent treatment in the period between January 1976 and December 1994 at the Princess Margaret Hospital. Analysis was confined to those patients with epithelial invasive histology (squamous carcinoma, adenocarcinoma, or undifferentiated carcinoma) managed with curative intent with primary radiation therapy. The median patient age was 62, with a median follow-up time of 4 years. Staging was assigned according to a modification of the UICC 1997 system with 19 (66%) of patients presenting with T4 category tumors. The most common radiation dose regimes were 60 Gy in 30 daily fractions over 6 weeks, or 50 Gy in 20 daily fractions over 4 weeks. Outcome was analyzed with respect to overall survival, cause-specific survival, and local progression-free survival. The influence of a variety of clinical and therapeutic factors on outcome is discussed, the patterns of disease failure are described, and the rationale for this treatment approach is outlined. RESULTS: The 5-year rates of overall survival, cause-specific survival, and local progression-free survival were 39%, 58%, and 41%, respectively. A total of 18 of 29 patients died during the period of review. Of these, 12 deaths were due to ethmoid cancer, one was due to a second primary lung cancer, and five were attributed to nononcologic causes. No patients died due to treatment-related toxicity. Increasing T category predicted for worse outcome on univariate analysis. Local progression was the major cause of treatment failure and was documented in 15 of 29 patients treated (52%). Six patients were offered salvage surgery for local progression, of whom two remained disease free at 15 and 17 months follow-up. CONCLUSIONS: Outcome of patients with ethmoid cancer managed with primary radiation therapy with surgery for salvage is comparable to that achieved with planned combined modality approaches. Nevertheless, outcome remains poor and is dependent on the local extent of tumor, with 40-50% of patients eventually succumbing to disease.

Spinal cord ependymomas: a retrospective analysis of 59 cases.

PURPOSE: To determine the outcome of patients with primary spinal ependymoma treated with postoperative radiotherapy and to identify clinical and treatment variables predictive of outcome. METHODS AND MATERIALS: A retrospective chart review was undertaken of 59 spinal ependymoma patients referred to the Princess Margaret Hospital between 1958 and 1987. All patients were treated with radiation therapy to either the site of the primary tumor or the craniospinal axis. There were 23 female and 36 male patients with a median age of 37 years (range: 8-66 years). Median follow-up was 130 months (range: 1-371 months). Clinical variables including age, sex, length of symptoms, functional status, tumor location, and grade as well as treatment variables including extent of surgery, radiation dose and treatment volume were analyzed for influence on outcome. RESULTS: Treatment was well-tolerated with no cases of radiation myelopathy identified. Overall actuarial survival at 5 and 10 years was 83% and 75%, respectively. Eleven patients had recurrent tumor with the 9/11 having a component of their recurrence within the treatment field. Median time to recurrence was 2 years with 9 of the 11 recurrences within the first 3 years. Tumor grade was the only independent variable identified as predictive of outcome. Patients with well differentiated tumors had a 5-year cause-specific survival of 97% compared to 71% for those with intermediate or poorly differentiated tumors (p = 0.005). CONCLUSION: We conclude that postoperative irradiation for patients with spinal ependymomas is associated with a favorable outcome and that tumor grade is a major prognostic factor. Based on results of this series and a review of the literature, specific management recommendations are made for this rare tumor.

Multiple inputs to a population of thalamocortical neurons projecting to cat somatosensory cortex.

Ninety thalamocortical (TC) neurons were recorded extracellularly in ventrobasal thalamus of halothane-anesthetized cats. Projections of all of these neurons to specific subdivisions of somatosensory cortex were identified by their antidromic invasion following intracortical microstimulation restricted to these subdivisions. Collision-extinction tests were used to document excitatory inputs to TC neurons from afferent fibers of forelimb nerves stimulated electrically. Thirty-nine TC neurons (43% of sample) were excited from at least one forelimb nerve. Fifteen TC neurons were activated from two or more forelimb nerves. Combinations of effective nerves included ones innervating topographically different regions of forelimb. Neurons projecting to area 1-2 were least likely to be activated from more than one nerve. Seven TC neurons activated by electrical stimulation of nerve trunks were tested also with two distinct forms of mechanical somatic stimuli, i.e., hair bending and vibration, and with intradermal electrical stimuli. These tests revealed convergent inputs from hairy and glabrous skin. We conclude that there is a population of neurons, located in ventrobasal thalamus, which is capable of conveying multiple inputs to each of the subdivisions of primary somatosensory cortex. These neurons could be involved in forming properties of feature-extracting neurons of somatosensory cortex.