Biomedical subjects
Publications and source records attributed to B J Fisher.
A rare occurrence of solitary intracranial plasmacytoma arising from the meninges over the left hemisphere is reported. Clinical features and management of the case are described with review of literature.
An Ontario cancer agency started an initiative to improve and promote effective communications between health care providers and their patients, using a 4.5-hour workshop developed by the Bayer Institute for Health Care Communications. Each of the eight regional cancer centers in Ontario sent two people, one physician and one other health care professional, for training in delivery of the workshop. Subsequently, each center provided workshops for physicians, nurses, pharmacists, physicists, social workers, psychologists, radiotherapists, and secretarial staff. The ongoing workshops are multiprofessional in composition and interactive and participatory in design. Between September 1996 and September 1997, the workshops involved over 400 cancer care professionals. Their success has been attributed to the knowledge, skills, and enthusiasm of the trained pair of facilitators; the interactive and participatory nature of the workshop design; the multiprofessional participation; and the support of the board of directors and senior management and the administration of each cancer center.
OBJECT: The authors conducted a retrospective review to examine and document the frequency, degree, and timing of the radiologically confirmed response to radiotherapy of low-grade gliomas in children. METHODS: Between 1963 and 1995, 80 patients 17 years of age or younger were referred to the London Regional Cancer Centre in London, Ontario after diagnosis of a low-grade glioma. All patients underwent surgical resection or biopsy procedures and 47 underwent radiotherapy (40 postoperatively and seven at the time of tumor progression). Nineteen patients with residual measurable lesions who received radiation therapy were selected for volumetric analysis of tumor response to this treatment. The extent and timing of response to radiation were determined by the process of comparing postoperative, preirradiation computerized tomography (CT) scans with postirradiation, follow-up CT scans. For one patient the comparison was made by using serial magnetic resonance images. Residual tumor was found on postoperative CT scans in all cases. The mean preradiotherapy tumor volume was 17.1 cm3, and the postradiotherapy volume was reduced to a mean of 11.5 cm3. A reduction in tumor volume was demonstrated in eight patients by the time of their first postirradiation follow-up CT scan and in two patients a slower reduction in volume over time was shown, bringing the total number of "responders" to 10. In five of these 10 patients the tumor had shown a maximum response by the time of the first postirradiation CT scan; the median time to response was 3.3 months. A 25% or greater reduction in tumor volume was seen in eight (42%) of the 19 patients. A 50% or greater reduction was noted in five (26%) of the patients. A complete response was demonstrated at 7, 12, and 15 months, and 5 years, respectively, in four patients (21%). One responder's tumor eventually increased in size after radiotherapy and he died of his disease. The magnitude of the radiographically demonstrated response to radiation did not correlate significantly with clinical outcome (that is, survival or symptom improvement). CONCLUSIONS: On the basis of this CT scan analysis of the response of low-grade gliomas in children to radiotherapy, the authors suggest that these lesions respond to radiation, as demonstrated by tumor shrinkage on serial imaging. Major or complete responses occur occasionally. However, low-grade gliomas in children mimic other benign brain tumors such as pituitary adenomas and meningiomas in that, although growth is frequently arrested after radiotherapy, residual tumor can persist for many years, illustrating that tumor shrinkage may not be a good measure of treatment efficacy. Nevertheless, radiation therapy can result in improvement of clinical symptomatology in association with or independent of visible tumor reduction. As radiation treatment techniques become increasingly conformal and because studies indicate that lower doses of radiation may be equally effective, improvement of symptoms may be an important consideration when weighing treatment options, particularly in patients with residual or unresectable disease.
PURPOSE: Prognostic factors for locoregional failure have been poorly documented. The purpose of this retrospective review is to examine the patterns of failure of 320 patients with Stage II or III axillary node-positive breast cancer who received adjuvant chemotherapy without locoregional radiation. METHODS AND MATERIALS: The records of 735 patients who were referred to the London Regional Cancer Centre between 1980 and 1989 with a diagnosis of Stage II or III breast cancer were reviewed. Three hundred and twenty patients were identified who underwent segmental mastectomy with axillary dissection or modified radical mastectomy and adjuvant chemotherapy without adjuvant locoregional radiation. Seventy-one percent of these patients had undergone a modified radical mastectomy, 40% had T1 tumors, 49% T2, and 11% T3. Resection margins were positive in 13 patients. The median number of axillary nodes removed was 11. Fifty-four percent had one to three positive axillary nodes, 27% had four to seven positive nodes, and 19% had in excess of seven positive nodes. RESULTS: Median follow-up for the 320 patients was 77 months. One hundred and fourteen patients developed a locoregional recurrence as the site of first relapse (31 in the intact breast, 29 on the chest wall, 21 in the axilla, 22 in the supraclavicular fossa, 1 in the internal mammary chain, and 10 in multiple sites). Thirty-three percent of segmental mastectomy patients and 13% of modified radical mastectomy patients developed local recurrence. Seven percent of patients recurred in axillary or supraclavicular nodes each. Factors with regard to locoregional recurrence which on univariate analysis were significant included type of mastectomy (i.e., segmental vs. modified radical), size of primary tumor, positive resection margins, and percentage of ideal chemotherapy dose intensity (< 66% vs. > or = 66%). After multivariate analysis, only type of mastectomy, size of primary tumor, and percentage of ideal chemotherapy dose intensity retained significance. The number of positive axillary nodes was not a significant factor. Number of positive axillary nodes plus the above four clinical factors were analyzed in terms of regional recurrence specifically. By univariate and multivariate analysis, only size of primary tumor retained significance. Again, the number of positive axillary nodes was not a relevant factor. CONCLUSION: Patients receiving adjuvant chemotherapy who are at high risk of locoregional recurrence include those who undergo segmental mastectomy and those with larger tumors (> 5 cm in diameter). Breast or chest wall radiation is recommended for these groups. Supraclavicular radiation is recommended for patients with tumors larger than 5 cm in diameter. Axillary recurrences were relatively infrequent in patients who had undergone an adequate Level I and II axillary dissection, and therefore, axillary radiation was not recommended.
PURPOSE: This is a retrospective review into the patterns of failure of 82 patients with Stage II or III breast cancer who had extracapsular extension (ECE) of axillary nodal metastases and who received systemic chemotherapy or hormonal therapy without loco-regional radiation. METHODS AND MATERIALS: The clinical records of patients with axillary node positive (T1-T3, N1, 2) Stage II or III breast cancer seen at the London Regional Cancer Centre between 1980-1989 were reviewed. Patients were identified who underwent segmental mastectomy with axillary node dissection or modified radical mastectomy and received adjuvant chemotherapy or tamoxifen but did not undergo loco-regional radiation. Eighty-two patients within this group had pathologic evidence of extracapsular axillary node extension (ECE). For 45 of these patients the extension was extensive, and for the remaining 37 it was microscopic. This ECE-positive group was compared to a subgroup of 172 patients who did not have pathologic evidence of extracapsular axillary node extension but had metastatic carcinoma confined within the nodal capsule. RESULTS: Median age of the 82 ECE-positive patients was 56 years. Twenty-five patients had had a segmental mastectomy, the remainder a modified radical mastectomy. Median actuarial survival was 60 months, with a median disease-free and loco-regional failure-free survival of 38 months. Seventy-eight percent of these patients developed a recurrence, which was loco-regional in 60% (21% local, 21% regional, 2% local and regional, and 16% loco-regional and metastatic). There was a 36% recurrence rate in intact breast, 14% the chest wall following modified radical mastectomy, 7% relapsed in the axilla, 12% in supraclavicular nodes, and 1% in the internal mammary nodes. A comparison of the 82 ECE-positive patients with a group of 172 ECE-negative patients determined that there was a statistically significant difference between the two groups in terms of survival (overall and disease-free) and loco-regional recurrence. Univariate analysis of the entire 254 node-positive patient group revealed extracapsular nodal extension (ECE) to be a prognostically significant factor for actuarial and disease-free survival as well as for loco-regional failure, but ECE did not remain an independently prognostic factor after multivariate analysis. Segmental mastectomy, positive resection margins, and ER negative status increased the risk of loco-regional recurrence within the ECE-positive group. CONCLUSIONS: Extracapsular axillary node extension is a prognostically significant factor for actuarial survival, disease-free survival, and loco-regional failure but not independent of other adverse prognostic factors. It is a marker for increased loco-regional recurrence associated with doubling of breast, chest wall, and supraclavicular recurrence rates. The risk of axillary relapse in patients who have had an adequate level I and II axillary dissection but demonstrate extracapsular extension is low (7%). We recommend breast/chest wall and supraclavicular radiation for all patients with pathologic evidence of such extranodal extension who have had a level I and II axillary dissection regardless of the number of positive axillary nodes. Axillary irradiation should be considered for patients who have had only an axillary sampling or level I axillary dissection.
OBJECTIVE: To determine the effect of delayed administration of inhaled nitric oxide (NO) on acute lung injury after the onset of gram-negative sepsis. DESIGN: Nonrandomized controlled study. SETTING: University medical center laboratory. SUBJECTS: Yorkshire swine. INTERVENTIONS: Five groups of swine were anesthetized, mechanically ventilated, and studied for 5 hours. After surgical preparation, control (n = 10) and NO-treated control (n = 6) animals received a 1-hour infusion of sterile saline solution. Sepsis was induced with a 1-hour intravenous infusion of live Pseudomonas aeruginosa. Untreated animals with sepsis (n = 10) received no treatment. Inhaled NO at 20 ppm was administered to NO30-treated animals with sepsis (n = 7) and NO60-treated animals with sepsis (n = 8) beginning at 30 and 60 minutes after bacterial infusion was begun, respectively. MAIN OUTCOME MEASURES: Systemic and pulmonary hemodynamics, arterial blood gas determination, bronchoalveolar lavage protein and neutrophil content, neutrophil oxidant burst, lung myeloperoxidase content, and scanning electron micrographic studies. RESULTS: A progressive, significant (P < .05) decline in PaO2 developed in untreated animals with sepsis, which was prevented in NO30- and NO60-treated animals with sepsis. A significant (P < .05) increase in bronchoalveolar lavage protein and neutrophil counts compared with baseline values was observed in untreated animals with sepsis, indicating acute lung injury. These variables exhibited no notable increase in NO30- and NO60-treated animals with sepsis and were significantly (P < .05) reduced compared with untreated animals with sepsis. The lung myeloperoxidase content was significantly (P < .05) elevated at 5 hours in all groups with sepsis compared with baseline values and the control and NO-treated control groups. The total phorbol myristate acetate-induced polymorphonuclear leukocyte oxidant burst at 5 hours was significantly (P < .05) decreased in the NO30- and NO60-treated animals with sepsis compared with untreated animals with sepsis. Untreated and NO30- and NO60-treated animals with sepsis showed a significant (P < .05) increase in pulmonary artery pressure at 30 minutes, followed by a progressive decline. These changes were significant (P < .05) compared with baseline values and the control groups. No significant (P < .05) difference in pulmonary artery pressure or systemic arterial pressure was found at any time between untreated and NO30- and NO60-treated animals with sepsis. CONCLUSIONS: The delayed administration of inhaled NO preserves alveolar-capillary membrane integrity in this porcine model of gram-negative sepsis. The inhibition of neutrophil transendothelial migration, rather than neutrophil rolling or tight adhesion, may be a critical mechanism by which inhaled NO produces this effect. Decreased oxidant production by activated neutrophils may be a secondary mechanism by which inhaled NO reduces acute lung injury.
A large body of evidence has demonstrated that inhibition of the neutrophil's oxidant burst attenuates sepsis-induced acute lung injury. The present study sought to evaluate the ability of OPC-6535, a superoxide anion production inhibitor, to attenuate sepsis-induced acute lung injury. Four groups of swine were anesthetized, ventilated, and studied for 5 hr. Following surgical preparation, control (n = 10) and OPC-control (n = 2) animals received a 1-hr infusion of sterile saline. Sepsis was induced with a 1-hr intravenous infusion of live Pseudomonas aeruginosa. Untreated septic animals (n = 10) received no treatment. Animals treated with OPC-6535 (n = 6) received a 1 mg/kg bolus of OPC-6535 15 min prior to initiation of the bacterial infusion. Changes in systemic and pulmonary hemodynamics, arterial oxygen tension, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin expression, neutrophil oxidant burst, and lung myeloperoxidase content were used as outcome measures. Treatment with OPC-6535 significantly reduced acute lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. Treatment with OPC-6535 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with both treated and untreated sepsis exhibited significant up-regulation of CD18 and production of increased levels of oxidants, indicating significant activation when compared to neutrophils from control animals. Although animals treated with OPC-6535 produced 25% less superoxide anion than untreated septic animals, this decrease was not statistically significant. Treatment of animals with OPC-6535 prior to the onset of sepsis produced significant protection against acute lung injury but failed to attenuate hemodynamic derangements associated with sepsis.
A biplanar z-gradient coil has been designed using a genetic algorithm, and its efficiency for producing a gradient along the axis of a solenoid magnet compared to that of a conventional Maxwell coil set. Coils of 21.8 cm by 20.9 cm area and 10 cm separation give 0.37 m Tm-1 A-1 with standard and maximum deviations of 2.6 and 13.1% of this value over an optimised cuboid region of 12 by 15 by 1.8 cm. The experimentally useable linear volume extends beyond this to 50% of the separation between the planes. Design data are also given for a transverse gradient set.
OBJECTIVE: To determine if, and by what mechanisms, inhaled nitric oxide attenuates acute lung injury in a porcine model of adult respiratory distress syndrome induced by Gram-negative sepsis. DESIGN: Nonrandomized, controlled study. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty pathogen-free Yorkshire swine (15 to 20 kg). INTERVENTIONS: Four groups of swine were anesthetized, mechanically ventilated, and studied for 5 hrs. Both control-nitric oxide and septic-nitric oxide animals received inhaled nitric oxide at 20 parts per million throughout the study. Control (n = 10) and control-nitric oxide (n = 5) animals received a 1-hr infusion of sterile saline. Sepsis was induced in septic (n = 10) and septic-nitric oxide (n = 5) animals with a 1-hr intravenous infusion of live Pseudomonas aeruginosa. MEASUREMENTS AND MAIN RESULTS: Untreated septic animals developed a progressive decrease in Pao2 that was prevented in septic-nitric oxide animals (73 +/- 4 vs. 214 +/- 23 torr [9.7 +/- 0.5 vs. 28.5 +/- 3.1 kPa], respectively, at 5 hrs, p < .05). Untreated septic animals showed a significant increase in bronchoalveolar lavage protein and neutrophil count at 5 hrs, compared with the baseline value, indicating acute lung injury. Septic-nitric oxide animals showed no significant increase in these parameters. Peripheral blood neutrophils from untreated septic animals and septic-nitric oxide animals exhibited significant (p < .05) up-regulation of CD18 receptor expression and oxidant activity (10.5 +/- 0.9 and 5.0 +/- 0.9 nmol of superoxide anion/10(6) neutrophils/10 mins, respectively) compared with both control and control-nitric oxide animals (3.0 +/- 0.6 and 2.6 +/- 0.2 nmol of superoxide anion/10(6) neutrophils/10 mins, respectively). Also, priming for the oxidant burst at 5 hrs was decreased by 50% in septic-nitric oxide animals compared with untreated septic animals. Both untreated septic and septic-nitric oxide animals showed a significant increase in pulmonary arterial pressure at 30 mins (47.5 +/- 2.4 and 51.0 +/- 3.0 mm Hg, respectively), followed by a progressive decrease (32.8 +/- 2.6 and 31.3 +/- 5.4 mm Hg, respectively, at 5 hrs). Both of these changes were significant (p < .05) compared with baseline values and compared with the control groups. There was no significant difference in pulmonary arterial pressure or systemic arterial pressure at any time between untreated septic and septic-nitric oxide animals. CONCLUSIONS: These results demonstrate that inhaled nitric oxide attenuates alveolar-capillary membrane injury in this porcine model of Gram-negative sepsis but does not adversely affect systemic hemodynamics. The data suggest that inhaled nitric oxide preserves alveolar-capillary membrane integrity by the following means: a) inhibiting transendothelial migration of activated, tightly adherent neutrophils; and b) possibly by attenuating the neutrophil oxidant burst.
Proper engagement of leukocyte and endothelial cell selectins with their counterreceptors is an initial step in neutrophil trafficking to sites of inflammation. Certain fucosylated carbohydrate determinants such as sialyl Lewis-x are proposed to act as these counterreceptors. We studied the effects of a synthetic sialyl Lewis-x analog, CY-1503, on the course of hemodynamic derangements and acute lung injury during experimental gram-negative sepsis. Anesthetized ventilated swine were made septic with an infusion of live Pseudomonas aeruginosa. A treatment group received an initial bolus of CY-1503 (60 mg/kg) before sepsis, followed by continuous infusion of CY-1503 (15 mg.kg-1.h-1). Treatment with CY-1503 did not prevent the development of pulmonary hypertension, systemic hypotension, decline in cardiac output, or severe neutropenia. However, CY-1503 significantly attenuated lung injury, demonstrated by decreased bronchoalveolar lavage protein content and neutrophil influx, lowered lung myeloperoxidase activity, and improved arterial oxygenation. Neutrophils from septic and CY-1503 animals showed significant activation, reflected by upregulated CD18 expression and priming for oxidant burst compared with control animals. This study suggests blockade of selectin interactions as a potential therapeutic intervention in sepsis-induced lung injury.
E-selectin, an early mediator of leukocyte-endothelial adhesion, is expressed on activated endothelium. Soluble E-selectin is present in the supernatant of cytokine-activated endothelial cells and elevated serum levels are found in a variety of inflammatory conditions. We documented elevated E-selectin serum levels in 119 critically ill medical ICU patients (log transformed mean E-selectin level, measured by ELISA, was 5.28 ng/ml) compared to normal volunteers (1 ng/ml). Forty-three patients with culture-positive sepsis had higher (p < 0.05) E-selectin levels (15.39 ng/ml) than 24 patients with culture-negative sepsis (4.87 ng/ml), 44 with noninfectious SIRS (2.33 ng/ml), and eight without SIRS (1.97 ng/ml). E-selectin levels related strongly to the degree of hemodynamic compromise (p < 0.0001). Further analysis demonstrated microbiological status and hemodynamic status to be independent variables related to E-selectin level. Day 1 E-selectin levels correlated positively with peak organ failure score over the course of ICU hospitalization (r = 0.30, p = 0.001) and were higher (p < 0.05) for nonsurvivor (10.61 ng/ml, n = 26) than survivors (4.35 ng/ml, n = 93). We conclude that soluble E-selectin levels are higher in serum of patients with microbiologically documented sepsis than in other critically ill medical ICU patients. Day 1 E-selectin levels correlate highly with hemodynamic compromise and modestly with subsequent organ dysfunction and survival.
OBJECTIVE: We report three patients with malignant rhabdoid tumor (MRT) of the brain, two children and an adult. There were three purposes to this report: to describe the clinical course in an adult with MRT; to describe the interesting histopathological metamorphosis of one of the tumors; and to report the outcome of the treatment regimens we used in order to help guide future treatment. Since these tumors are quite rare it is important to continue to try new regimens in the search for effective therapy rather than to repeat ineffective ones. METHOD: Report of three patients. RESULTS: The clinical course in all three patients was typical of these aggressive neoplasms in that chemotherapy and radiotherapy were ineffective in modifying the rapid deterioration leading to death. CONCLUSIONS: MRT can occur in adults. Autopsy in one patient showed that the tumor seemed to undergo an evolution in appearance when compared with the original pathology specimen from craniotomy. Administration of systemic therapy should be prompt and include intrathecal chemotherapy.
UNLABELLED: Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been determined. Recently, however, specific bradykinin (BK) antagonists have become available and we sought to determine the effects of a BK antagonist, NPC17731, in a model of sepsis-induced acute lung injury (ALI). METHODS: Anesthetized swine were studied for 5 hours, receiving a 1-hour infusion of saline (Controls) or live Pseudomonas aeruginosa (Septic untreated). Treatment groups received a 5 mg/kg bolus of NPC17731 followed by a 1 mg/kg bolus hourly commencing either just before sepsis (Pretreatment) or 30 minutes following the onset of sepsis (Posttreatment). RESULTS: Septic untreated animals showed a rapid, progressive decline in arterial PaO2 compared to controls, and this was significantly improved in both treatment groups. Bronchoalveolar lavage at 5 hours in both treatment groups also showed significant decreases in neutrophil (PMN) counts and protein content compared to untreated septic animals, indicating decreased PMN migration and alveolar-capillary membrane damage. Both treatment groups also showed reduced PMN sequestration in the lung compared to untreated animals, although PMNs did exhibit significant upregulation of PMN CD18 receptor expression and superoxide generation. CONCLUSIONS: These data imply a significant role for BK in the pathogenesis of sepsis-induced ALI. Use of a competitive BK antagonist significantly attenuated the development of ALI without inhibiting PMN activation. BK antagonists may be a useful adjunct in the armamentarium against sepsis-induced ALI.
Adhesion molecules play a critical role in the interaction of circulating neutrophils with vascular endothelium during inflammation. Increased quantities of soluble, circulating intercellular adhesion molecule-1 (cICAM-1) are present in various inflammatory conditions. The purpose of this investigation was to measure cICAM-1 levels in septic adults, as well as to examine the relationship between this potential marker of endothelial-cell activation and the consequences of sepsis (i.e., multiple organ failure and death). Using a sandwich-type enzyme-linked immunosorbent assay (ELISA), we measured cICAM-1 in blood samples obtained within 12 h of admission to an intensive care unit (ICU) for sepsis and other conditions. We found cICAM-1 levels to be increased in 25 septic patients (1,259 +/- 159 ng/ml, mean +/- SEM) as compared with 12 healthy volunteers (355 +/- 41 ng/ml, p < 0.0001) and four ICU patients without systemic inflammatory response syndrome (SIRS) (585 +/- 76 ng/ml, p < 0.001). Twenty-five patients with SIRS but no evidence of causative infection also had elevated levels of cICAM-1 (937 +/- 144 ng/ml, p = 0.12 versus sepsis). Serial measurements over the first week of sepsis demonstrated persistent elevation in most patients. Day 1 cICAM-1 levels were higher (p = 0.017, ANOVA) in 16 patients with septic shock than in seven with severe sepsis and two with sepsis but without hypotension or hypoperfusion. There was a positive correlation (r = 0.50, p = 0.009) between Day-1 cICAM-1 measurements and severity of shock as determined by the presence of hypotension and vasopressor use.(ABSTRACT TRUNCATED AT 250 WORDS)
Many studies indicate a pivotal role for neutrophil adhesion in sepsis-associated lung injury. Neutrophil adhesion to endothelium depends on activation and expression of selectin and integrin adhesion receptors. We studied the effects of pretreatment with a dual-binding porcine anti-E- and anti-L-selectin monoclonal antibody (EL-246) on a porcine model of sepsis-induced lung injury. Four groups were studied for 5 h. Group 1 (control animals) received intravenous saline only. Group 2 (septic) received a 1-h infusion of Pseudomonas aeruginosa. Group 3 (EL-246 pretreatment) received EL-246 (1 mg/kg) prior to Pseudomonas infusion. Group 4 (EL-246 controls) received EL-246 infusion only. Group 2 animals showed rapid, significant decline in arterial pH and oxygen tension whereas, in Group 3, physiologic deterioration was significantly attenuated. Bronchoalveolar lavage at 5 h showed a significant increase in neutrophil count and protein content in Group 2. Group 3, however, showed no significant differences in these parameters compared with control animals. Despite severe neutropenia, lung myeloperoxidase content at 5 h was significantly reduced in Group 3 compared with Group 2. There was no significant difference in pulmonary and systemic hemodynamics between Groups 2 and 3. Group 4 animals exhibited a transient neutropenia, but otherwise no other differences in measured parameters were found compared with Group 1 control animals. In conclusion, EL-246 significantly reduced neutrophil accumulation in lung and attenuated sepsis-induced lung injury, but failed to attenuate deranged pulmonary and systemic hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)
This article explores the meanings older people attach to successful aging and life satisfaction and how these concepts can be differentiated. Forty elderly employees of the Ozarks Area Foster Grandparent Program (ages 61-92) were randomly selected and interviewed using an open-ended survey questionnaire. These questions explored understandings of successful aging and life satisfaction, the factors essential for each, and the differences perceived between these concepts. Qualitative data were coded by two independent reviewers. Respondents' understandings of successful aging involved attitudinal or coping orientations nearly twice as often as those for life satisfaction. Descriptions of life satisfaction emphasized the fulfillment of basic needs and was viewed as a precursor to successful aging. Content analysis confirmed five features of successful aging: interactions with others, a sense of purpose, self-acceptance, personal growth, and autonomy. The findings suggest that generativity contributes to successful aging and remains a vital developmental task in later life.
PURPOSE: Older age and poor performance status at presentation are unfavorable prognostic factors for patients with glioblastoma multiforme. Some studies suggest a shorter, palliative course of radiotherapy may confer similar benefits as compared to a radical course in such patients. We report a prospective, single arm trial, describing the use of a short-course of radiation in patients with glioblastoma and poor prognostic features. METHODS AND MATERIALS: Twenty-nine patients with pathologically confirmed glioblastoma and age > or = 65 years or with initial KPS < or = 50 were treated with a short-course of whole brain radiotherapy (30 Gy/10 fractions/2 weeks). Computer tomography tumor volume, dexamethasone requirements, Spitzer quality of life index, and Karnofsky performance status were measured pre and 1 month postradiation. Overall survival for the study patients was compared with that of radically treated and supportive care only historical controls. RESULTS: Indices of tumor response were stable or improved in 60% of patients evaluable 1 month postradiotherapy. Median survival for all study patients was 6 months. Median survivals in similar groups of radically treated and supportive care only patients were 10 and 1 month(s), respectively. A survival advantage for the radical vs. short-course treatment was observed for the subset of patients with a pretreatment KPS > 50. CONCLUSION: Elderly patients with a low pretreatment KPS (< or = 50) may be treated adequately with a short, palliative course of radiotherapy. Elderly patients with a higher pretreatment KPS (> 50), however, may benefit from a higher dose radiotherapy regimen.
OBJECTIVE: To ascertain the effect of delayed tumor necrosis factor alpha (TNF-alpha) on the evolution of systemic and pulmonary injury after the onset of sepsis. DESIGN: Prospective controlled trial. INTERVENTION: Anesthetized swine were made septic with a 1-hour infusion of live Pseudomonas aeruginosa, following which a treatment group received an infusion of anti-TNF-alpha monoclonal antibody (5 mg/kg). Control animals received 0.9% saline. RESULTS: Delayed anti-TNF-alpha treatment had no effect on septic pulmonary hypertension or decline in cardiac output. Late recovery in systemic arterial hypotension was associated with a reversal of arterial acidosis (P < .05 by t test and analysis of variance with Tukey's Studentized Range Test) compared with unprotected septic animals. Septic animals had a significant increase in mean (+/- SEM) plasma lactate levels at 5 hours compared with baseline values (3.8 +/- 0.7 vs 2 +/- 0.4, P < .05), but remained unchanged from baseline following anti-TNF-alpha treatment (1.5 +/- 0.1 vs 1.6 +/- 0.2, not significant). Characteristic septic neutropenia was dramatically reversed by anti-TNF-alpha treatment and was associated with downregulation (P < .05 by t test and analysis of variance) of polymorphonuclear neutrophil (PMN) leukocyte CD18 adhesion receptors and reduction (P < .05 by t test and analysis of variance) in lung PMN sequestration measured by myeloperoxidase activity. The mean (+/- SEM) decrease in bronchoalveolar lavage protein indicated an attenuated permeability injury in anti-TNF-alpha animals (septic animals at 5 hours compared with baseline value, 1044 +/- 270 vs 149 +/- 28 micrograms/mL; control animals at 5 hours compared with baseline value, 217 +/- 83 vs 129 +/- 19 micrograms/mL; P < .05 by t test and analysis of variance). CONCLUSIONS: These data show that delayed anti-TNF-alpha treatment reversed metabolic acidosis associated with sepsis. Furthermore, anti-TNF-alpha treatment reversed septic neutropenia, reduced PMN sequestration, and was associated with attenuated lung injury in a model of fulminant sepsis. This supports evidence of PMN-mediated tissue injury in sepsis and suggests mechanisms for potential therapeutic benefit of anti-TNF-alpha treatment in clinical practice.