The aim of this study was to compare functional nerve recovery after reconstruction with a biodegradable p(DLLA-epsilon-CL) nerve guide filled with modified denatured muscle tissue (MDMT), or an autologous nerve graft. We evaluated nerve recovery using walking track analysis (measurement of the sciatic function index [SFI]) and electrostimulation tests. Functional nerve recovery after reconstruction with a biodegradable p(DLLA-epsilon-CL) nerve guide filled with MDMT was faster when compared with nerve reconstruction using an autologous nerve graft. We conclude that in case of a short nerve gap in the rat, reconstruction can best be carried out using a p(DLLA-epsilon-CL) biodegradable nerve guide filled with MDMT. 相似文献
Background: The authors have previously observed an apparent association between rostral spread of spinal anesthesia and choice of intravenous vasopressor given to maintain maternal systolic arterial pressure during cesarean delivery. This study tested the hypothesis that an intravenous infusion of phenylephrine can reduce rostral spread of spinal anesthesia in pregnancy, compared with ephedrine.
Methods: The study was randomized and double blind. It compared phenylephrine 100 [mu]g/ml (phenylephrine group, n = 30), and ephedrine 3 mg/ml (ephedrine group, n = 30), given by infusion, to prevent maternal hypotension during combined spinal-epidural anesthesia for cesarean delivery. Two ml intrathecal plain levobupivacaine, 0.5%, combined with 0.4 ml intrathecal fentanyl, 50 [mu]g/ml, and 10 ml epidural saline was given with the patient in the sitting position. The upper level of neural blockade to cold and light touch sensation was recorded at 10 and 20 min postspinal. Epidural space pressure was recorded at 5, 10, 15, and 20 min.
Results: At 20 min, the upper dermatome blocked to cold sensation was median T3 (interquartile range, T2-T4) for the phenylephrine group, compared with T1 (T1-T2) for the ephedrine group (P = 0.001). At 20 min, the upper dermatome blocked to light touch sensation was median T5 (T4-T8) for the phenylephrine group, compared with T3 (T2-T6) for the ephedrine group (P = 0.009). The mean epidural space pressure in the phenylephrine group was 16 (13-19) mmHg, compared with 16 (13-18) mmHg in the ephedrine group (P = 0.63). 相似文献
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs; encoded byPRKDC) functions in DNA non-homologous end-joining (NHEJ), themajor DNA double strand break (DSB) rejoining pathway. NHEJ also functions duringlymphocyte development, joining V(D)J recombination intermediates during antigenreceptor gene assembly. Here, we describe a patient with compound heterozygousmutations in PRKDC, low DNA-PKcs expression, barely detectableDNA-PK kinase activity, and impaired DSB repair. In a heterologous expression system,we found that one of the PRKDC mutations inactivated DNA-PKcs, whilethe other resulted in dramatically diminished but detectable residual function. Thepatient suffered SCID with reduced or absent T and B cells, as predicted fromPRKDC-deficient animal models. Unexpectedly, the patient was alsodysmorphic; showed severe growth failure, microcephaly, and seizures; and hadprofound, globally impaired neurological function. MRI scans revealedmicrocephaly-associated cortical and hippocampal dysplasia and progressive atrophyover 2 years of life. These neurological features were markedly more severe thanthose observed in patients with deficiencies in other NHEJ proteins. Although loss ofDNA-PKcs in mice, dogs, and horses was previously shown not to impair neuronaldevelopment, our findings demonstrate a stringent requirement for DNA-PKcs duringhuman neuronal development and suggest that high DNA-PK protein expression isrequired to sustain efficient pre- and postnatal neurogenesis. 相似文献
A bile fistula patient was administered intravenously a constant infusion of [3H]mevalonic acid for 4 hrs, and then after 2 weeks he was given a pulse of [3H]mevalonic acid. Bile and blood were collected at frequent intervals. The specific activity-time course curves did not show a precursor-product relationship between biliary cholesterol, plasma free cholesterol and bile acids. Both the constant infusion and pulse labeling data indicated that the bile acid precursor had a more rapid rate of turnover than plasma or biliary cholesterol; the biliary cholesterol precursor turned over more rapidly than plasma cholesterol. The data suggest the presence of multiple hepatic cholesterol precursor compartments. Bile acids may be derived predominantly from newly synthesized cholesterol in man. 相似文献
A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor- risk ALs. 相似文献
Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial. 相似文献