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51.
52.
High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy 总被引:2,自引:0,他引:2
Daily prednisone improves strength in boys with Duchenne muscular dystrophy, but side effects are almost universal. We used a different dosing regimen of prednisone to determine if benefit to boys with Duchenne muscular dystrophy might be maintained with fewer side effects. Twice weekly oral prednisone was given each Friday and Saturday (5 mg/kg/dose). This total dose is twice as high as the daily low dosage prednisone regimen (0.75 mg/kg/day). Twenty boys (8.0±1.2 years) were treated. Historical control groups included 18 untreated boys (6.1±1.6 years) and four boys (7.3±0.6 years) treated with daily prednisone. Strength (using a hand-held manometer and grip meter) and timed functional testing were measured. There was an improvement in upper extremity strength for 95% of boys (n=20) at 6 months using quantitative strength testing. Improvement in lower extremity strength occurred in all boys with antigravity quadriceps strength (17/17). The improvement (P=0.001 for proximal upper extremities; P=0.002 for grip; and P<0.0001 for proximal lower extremities) was significant compared to untreated boys. Sixteen boys were treated continuously for more than 12 months (22±1.5 months). Of these, 15 remained significantly stronger than prior to treatment and 8/16 showed additional gains in strength after six months of treatment. Six boys were on the weekly prednisolone 2 years or longer without interruption. All six had upper and lower extremity strength at follow-up that was as good or better than at baseline. Functional testing improved in boys less than 8 years without contractures. Three boys without antigravity quadriceps strength at the start of treatment lost the ability to walk unassisted within 6 months. Eight other boys lost the ability to ambulate unassisted between 12 and 24 months of treatment. In each, progressive contractures developed. Linear growth was maintained in all boys on weekly treatment. Obesity rates did not differ from untreated boys. Twice weekly prednisone improved strength over 6–12 months in the majority of boys, but did not slow contracture development. Sustained benefit beyond 12 months is possible with fewer side effects compared to daily prednisone. 相似文献
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Ami J Shah Neena Kapoor Gay M Crooks Kenneth I Weinberg Hisham Abdel Azim Renna Killen Lily Kuo Teresa Rushing Donald B Kohn Robertson Parkman 《Biology of blood and marrow transplantation》2007,13(5):584-593
Graft-versus-host disease (GVHD) is a cause of serious morbidity and mortality in >50% of recipients of unrelated hematopoietic stem cell transplantation (HSCT). We performed a trial using Campath 1 H pre- and post-HSCT in an attempt to decrease the incidence of GVHD without increasing the risk of infection or relapse. Patients were retrospectively compared to a population of patients who received antithymocyte globulin (ATG) pre- and post-HSCT. Twenty-seven patients were evaluated for this study. Fourteen patients received Campath 1H and 13 patients received ATG. Demographics of patients who received Campath 1H consisted of 9 males and 5 females, with a median age of 13 years (3-17.8 years). Thirteen patients received unrelated bone marrow and 1 patient received unrelated PBSC. Demographics of patients receiving ATG consisted of 9 males, 4 females with a median age of 7.4 years (21 months-19 years). Twelve patients received unrelated bone marrow and 1 patient received unrelated PBSC. Diagnoses were similar between the 2 groups. Patients who received Campath1H received a total dose of 52 mg/m(2) pre-HSCT and 20 mg/m(2) post-HSCT. Patients who received ATG received a total dose of 60 mg/kg pre-HSCT and 100 mg/kg post-HSCT. GVHD prophylaxis and supportive care measures were similar in both groups, including aggressive antimicrobial therapy. There was a significant difference in the incidence of severe (grade III and grade IV) GVHD between the 2 groups (Campath [0 of 14] versus ATG [6 of 13], P = .006). Among the patients who were transplanted for leukemia, there was no significant difference between the 2 groups in terms of relapse (Campath [2 of 14] versus ATG [4 of 9], P = 0.16). The 100-day survival between the 2 groups was not significantly different. Patients receiving Campath 1H had the presence of CD3(+) T cells (>30 cells/mL) in their peripheral blood later than in those who received ATG (64.5 days [Campath 1H] versus 27days [ATG], P = .001). The median time to the development of a normal PHA response occurred later in the Campath 1H arm (283 days[(Campath 1H] versus 88 days [ATG], P = .0001). The median time to an antigen specific response also occurred later in those receiving Campath 1H (365 days [Campath 1H] versus 150 days [ATG], P = .004). There was no significant difference between the 2 groups in terms of fungal or viral infections. Campath 1H is effective in decreasing the incidence of GVHD without increasing the risk of relapse. Although there is a significant delay in immune reconstitution, there was no increase in infectious complications or relapse in recipients of Campath 1H. Further studies are warranted to assess if a lack of difference in infection rates are still demonstrated in larger cohorts. 相似文献
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Due to increasing life expectancy and a rising elderly population in Europe, the incidence of mild cognitive impairment which may predict diseases like Alzheimer's Disease or Vascular Dementia, is rising. Neurophysiological techniques are simple and inexpensive tools for early diagnosis and provide useful and objective correlates of cognitive activity both in normal subjects and patients suffering from the above conditions. Cognitive impairment due to different mental disease is characterized by decreased power and coherence in the alpha/beta band, which suggests functional disconnection among cortical areas, whereas both power and coherence in the delta and theta bands increase as a sign of cortical deafferentation from subcortical structures. Quantification of power and phase relationship by bispectral analysis suggests the Bispectral Index could be a useful but simple tool for early diagnosis of mental disease. 相似文献
57.
Coenzyme Q10, exercise lactate and CTG trinucleotide expansion in myotonic dystrophy. 总被引:1,自引:0,他引:1
G Siciliano M Mancuso D Tedeschi M L Manca M R Renna V Lombardi A Rocchi F Martelli L Murri 《Brain research bulletin》2001,56(3-4):405-410
Steinert's myotonic dystrophy (DM) is a genetic autosomal dominant disease and the most frequent muscular dystrophy in adulthood. Although causative mutation is recognized as a CTG trinucleotide expansion on 19q13.3, pathogenic mechanisms of multisystem involvement of DM are still under debate. It has been suggested that mitochondrial abnormalities can occur in this disease and deficiency of coenzyme Q 10 (CoQ10) has been considered one possible cause for this. The aim of this investigation was to evaluate, in 35 DM patients, CoQ10 blood levels and relate them to the degree of CTG expansion as well as to the amount of lactate production in exercising muscle as indicator of mitochondrial dysfunction. CoQ10 concentrations appeared significantly reduced with respect to normal controls: 0.85 +/- 0.25 vs. 1.58 +/- 0.28 microg/ml (p < 0.05). Mean values of blood lactate were significantly higher in DM patients than controls (p < 0.05) both in resting conditions (2.9 +/- 0.55 vs. 1.44 +/- 1.11 mmol/L) and at the exercise peak (6.77 +/- 1.79 vs. 4.90 +/- 0.59 mmol/L), while exercise lactate threshold was anticipated (30-50% vs. 60-70% of the predicted normal maximal power output, p < 0.05). Statistical analysis showed that serum CoQ10 levels were significantly (p < 0.05) inversely correlated with both CTG expansion degree and lactate values at exercise lactate threshold level. Our data indicates the occurrence of reduced CoQ10 levels in DM, possibly related to disease pathogenic mechanisms associated with abnormal CTG trinucleotide amplification. 相似文献
58.
Strychnine is considered a selective competitive antagonist of glycine gated Cl- channels (Saitoh et al., 1994) and studies have used strychnine at low micromolar concentrations to study the role of glycine in rabbit retina (Linn, 1998; Protti et al., 2005). However, other studies have shown that strychnine, in the concentrations commonly used, is also a potent competitive antagonist of alpha7 nicotinic acetylcholine receptors (nAChRs; Matsubayashi et al., 1998). We tested the effects of low micromolar concentrations of strychnine and 3-[2'-phosphonomethyl[1,1'-biphenyl]-3-yl] alanine (PMBA), a specific glycine receptor blocker (Saitoh et al., 1994; Hosie et al., 1999) on the activation of both alpha7 nAChRs on retinal ganglion cells and on ganglion cell responses to a light flash. Extracellular recordings were obtained from ganglion cells in an isolated retina/choroid preparation and 500 microM choline was used as an alpha7 agonist (Alkondon et al., 1997). We recorded from brisk sustained and brisk transient OFF cells, many of which have been previously shown to have alpha7 receptors (Strang et al., 2005). Further, we tested the effect of strychnine, PMBA and alpha-bungarotoxin on the binding of tetramethylrhodamine alpha-bungarotoxin in the inner plexiform layer. Our data indicates that strychnine, at doses as low as 1.0 microM, can inhibit the alpha7 nAChR-mediated response to choline, but PMBA at concentrations as high as 0.4 microM does not. Binding studies show strychnine and alpha-bungarotoxin inhibit binding of labeled alpha-bungarotoxin in the IPL. Thus, the effects of strychnine application may be to inhibit glycine receptors expressed by ganglion cell or to inhibit amacrine cell alpha7 nAChRs, both of which would result in an increase in the ganglion cell responses. Further research will be required to disentangle the effects of strychnine previously believed to be caused by a single mechanism of glycine receptor inhibition. 相似文献
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