The effect of strength and endurance training on gait, balance, fall risk, and health services use in community-living older adults

BACKGROUND: The study tested the effect of strength and endurance training on gait, balance, physical health status, fall risk, and health services use in older adults. METHODS: The study was a single-blinded, randomized controlled trial with intention-to-treat analysis. Adults (n = 105) age 68-85 with at least mild deficits in strength and balance were selected from a random sample of enrollees in a health maintenance organization. The intervention was supervised exercise (1-h sessions, three per week, for 24-26 weeks), followed by self-supervised exercise. Exercise groups included strength training using weight machines (n = 25), endurance training using bicycles (n = 25), and strength and endurance training (n = 25). Study outcomes included gait tests, balance tests, physical health status measures, self-reported falls (up to 25 months of follow-up), and inpatient and outpatient use and costs. RESULTS: There were no effects of exercise on gait, balance, or physical health status. Exercise had a protective effect on risk of falling (relative hazard = .53, 95% CI = .30-.91). Between 7 and 18 months after randomization, control subjects had more outpatient clinic visits (p < .06) and were more likely to sustain hospital costs over $5000 (p < .05). CONCLUSIONS: Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults. In community-living adults with mainly mild impairments in gait, balance, and physical health status, short-term exercise may not have a restorative effect on these impairments.     

Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation

Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic, and functional analysis of three hepatosplenic gammadelta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe neutropenia; terminal blastlike transformation occurred in one patient. Combination chemotherapy had no response in two patients, but induced complete remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta gene rearrangements were documented in each case. Two different subsets of gammadelta TCL were identified based on delta chain variable region usage; two lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligand) were expressed by each lymphoma; dense core cytolytic granules were observed by electron microscopy in both lymphomas studied. Functional studies performed in two cases showed TCR-mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CD3 in a redirected cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two gammadelta T cell subsets.     

Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes

Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P < 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPBL model.     

Outcome assessment for carpal tunnel surgery: the relative responsiveness of generic, arthritis-specific, disease-specific, and physical examination measures

Clinical evaluation of outcome after treatment of carpal tunnel syndrome has not been standardized. To assess the value of various clinical and questionnaire measures for the assessment of outcome after carpal tunnel surgery, we surveyed 22 patients 1 day before and 3 months after carpal tunnel release with the following measures: the Medical Outcomes Study 36-item short form health survey, the Arthritis Impact Measurement Scale, the Brigham and Women's Hospital carpal tunnel questionnaire, wrist range of motion, power pinch grip strength, pressure sensibility, and dexterity. Significant changes, all in the direction of improved health status postoperatively, were noted in the following scales or measures: the Arthritis Impact Measurement Scale pain, satisfaction, health perception, arthritis impact, and symptom scales; the Brigham and Women's Hospital symptom and function scales; the short form health survey's physical role, emotional role, and bodily pain scales; and the measurement of dexterity. In this study, standardized questionnaires were more sensitive to the clinical change produced by carpal tunnel surgery than many commonly performed physical measures of outcome. The condition-specific questionnaire was more sensitive to change than were more generic questionnaires.     

Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma

BACKGROUND: The objective of this study was to investigate whether luminal perfusion with glutamine or with oxygenated glutamine solutions prevents endotoxin-induced changes in mucosal permeability. METHODS: Three 15-cm segments of distal ileum were isolated in anesthetized 21-day-old piglets (n = 4) and perfused (50 mL/h) with Ringer's lactate solution, Ringer's lactate solution with 2% glutamine (wt/vol), glutamine, or glutamine purged with oxygen at 37 degrees C for 280 minutes. Plasma-to-lumen clearances of 51Cr-EDTA and urea were measured to assess mucosal permeability. At time 0 minutes, loading and maintenance IV infusions of markers were begun. Baseline permeabilities were obtained from time 60 to 80 minutes, and IV endotoxin (50 micrograms/kg) was introduced from time 80 to 140 minutes. RESULTS: Results are expressed as the ratio of the clearances of the two probes (CEDTA/CUREA). Permeability increased from baseline in loops perfused with Ringer's lactate solution vs loops perfused with glutamine purged with oxygen and with glutamine alone (p < .01). Saturation with oxygen was without effect inasmuch as glutamine alone negated permeability increases. Intestinal myeloperoxidase activity did not differ with perfusate (p > .05). CONCLUSIONS: These data suggest that endotoxin-induced permeability changes can be prevented or delayed by the supply of luminal glutamine at the time of insult.     

Radioimmunotherapy of medullary thyroid cancer with iodine-131-labeled anti-CEA antibodies

This study evaluates the pharmacokinetics, dosimetry, toxicity and therapeutic potential of radiolabeled NP-4 and MN-14 anti-CEA antibodies in medullary thyroid cancer (MTC). METHODS: Eighteen patients with advanced MTC entered exploratory clinical studies with therapeutic doses of 131I-labeled NP-4 and MN-14 murine monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). Doses administered ranged from 46 mCi for 131I-MN-14 lgG to 195 mCi for 131I-MN-14 F(ab)2 in patients negative for human anti-mouse antibodies (HAMA). RESULTS: The radioconjugate blood half-life (T1/2) for the whole lgG was 42.5+/-5.0 hr compared to 18.8+/- 4.1 hr for the bivalent fragments. Tumor doses of 17.5+/-11.0 and 11.4+/-6.3 cGy/mCi were estimated for 131I-MN-14 lgG and F(ab)2, respectively. Tumor/red marrow dose ratios exceeded 3:1 for most lesions. Red marrow doses of up to 350 cGy generally could be delivered with < grade 4 toxicity. Seven of 14 evaluable patients showed evidence of anti-tumor effects lasting up to 26 months, based on physical exam, tumor markers or computed tomography. CONCLUSION: This study demonstrates that anti-CEA MAbs may be suitable for radioimmunotherapy of metastatic or recurrent MTC.     

Follow up and maintenance of implant supported prostheses: a comparison of 20 complete mandibular overdentures and 20 complete mandibular fixed cantilever prostheses

Two independently selected groups of 20 patients who were edentulous in te mandible, were followed up on a regular basis over a 5-year period following restoration with a lower implant stabilised prosthesis and conventional upper denture. Significantly more treatment was required by those who received complete mandibular overdentures than those provided with complete fixed mandibular prostheses. In addition to adjustment for the relief of denture trauma to the mucosa, more mechanical problems arose with overdenture implant prostheses.     

Safety and immunogenicity of Env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59. NIAID AIDS Vaccine Evaluation Group

We investigated the safety and immunogenicity of a candidate HIV-1 vaccine, Env 2-3 (Chiron Biocine Co.), in combination with an adjuvant emulsion, MF59, with or without an additional immune modulator, MTP-PE 78 healthy HIV-1-seronegative adults. Sixteen subjects participated in a dose escalation study of MTP-PE in MF59 without Env 2-3, given at 0 and 1 months; 48 subjects participated in a study of a fixed dose of 30 micrograms of Env 2-3 in MF59 with increasing doses of MTP-PE (0, 5, 10, 25, 50, and 100 micrograms), and 14 subjects participated in a study of 100 micrograms of Env 2-3 in MF59 without MTP-PE. Subjects were assigned to study groups under a randomized, double-blind allocation. Subjects received immunization at 0, 1, and 6 months, and had the option of receiving a fourth dose at 12-18 months. Env 2-3 in MTP-PE/MF59 was associated with significant reactogenicity, in that severe, although self-limited systemic and/or local reactions occurred in 15 of 30 vaccinees. In contrast, Env 2-3 in MF59 without MTP-PE was relatively well tolerated, and severe local and/or systemic reactions occurred in only 2 of 18 subjects. Env 2-3 stimulated serum antibodies to HIV-1 envelope protein (gp120) as detected by Western blot in 39 of 43 subjects and to HIV-1 virus lysate by EIA in 28 of 43 subjects after three injections. The majority of subjects also developed EIA antibodies to recombinant gp120 (SF-2), gp120 (LAI), and V3 peptide (SF-2). Neutralizing antibodies to the homologous SF-2 strain developed in 30 of 43 and 27 of 34 subjects, and fusion inhibition antibodies in 25 of 43 and 15 of 36 subjects after three and four injections, respectively. Lymphoproliferative responses to the immunogen, Env 2-3 were observed in over 80% of the vaccinees examined, and CD4+ cytotoxic T cell activity directed against HIV-1 was noted transiently in 2 of 20 vaccinees. Addition of MTP-PE to Env 2-3 or increasing the dose of Env 2-3 from 30 to 100 micrograms did not augment immunogenicity. Env 2-3 in MF59 was well tolerated and immunogenic in HIV-1-seronegative individuals. The addition of MTP-PE significantly increased reactogenicity, but had little, if any, effect on immunogenicity.