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1.
Arthrograms of the temporomandibular joint were obtained in 20 symptomatic joints that had previous reconstructive arthroplasty with disk repositioning because of internal derangements. Preoperative arthrograms were available for comparison in 18 joints. Symptoms resulting in a postoperative arthrogram included pain, limited ability to open the mouth, and clicking of the joints. Postoperative arthrographic findings included limited anterior translation of the condyle (90%), irregularity in outline of the intraarticular contrast agent (60%), a conical configuration of the posterior recess (25%), decreased size of the joint (28%), anterior displacement of the meniscus (25%), and perforated meniscus (15%). Many of these findings may have resulted from fibrosis and scarring, which may be a response to intraarticular bleeding. The mechanism by which the fibrosis causes the postsurgical arthrographic features is discussed. 相似文献
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Luoma PT Luo N Löscher WN Farr CL Horvath R Wanschitz J Kiechl S Kaguni LS Suomalainen A 《Human molecular genetics》2005,14(14):1907-1920
Defects of mitochondrial polymerase gamma (POLG) underlie neurological diseases ranging from myopathies to parkinsonism and infantile Alpers syndrome. The most severe manifestations have been associated with mutations of the 'spacer' region of POLG, the function of which has remained unstudied in humans. We identified a family, segregating three POLG amino acid variants, A467T, R627Q and Q1236H. The first two affect the spacer region and the third is a polymorphism, allelic with R627Q. Three grades of disease severity appeared to correlate with the genotypes. The patient with the most severe outcome, cerebellar ataxia syndrome, had all three variants, those with R627Q and Q1236H had juvenile-onset ptosis and gait disturbance and those with a single A467T allele had late-onset ptosis. To evaluate the molecular pathogenesis of these spacer defects, we expressed and purified the mutant proteins and studied their catalytic properties in vitro. The A467T substitution resulted in clearly decreased activity, DNA binding and processivity of the polymerase. Our biochemical data, the dominant manifestation of A467T and its previously reported high frequency in the Belgian population (0.6%), emphasize the role of this mutation as a common cause of neurological disease. Further, biochemical evidence that a polymorphic variant may modify the function of a mutant POLG, if occurring in the same polypeptide, is shown here. Finally, and surprisingly, other pathogenic spacer mutants showed DNA-binding affinities and processivities similar to or higher than the controls, suggesting that the disease-causing mechanisms of spacer mutations extend beyond the basic catalytic functions of POLG. 相似文献
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Han JY; Kim HK; Choi BG; Moon H; Hong YS; Lee KS 《Japanese journal of clinical oncology》1998,28(12):749-753
BACKGROUND: Quality of life (QOL) assessment has emerged to measure and
quantify the balance between treatment benefit and toxicity, and has a
value in predicting response and overall survival in cancer patients.
METHODS: From July 1995 to February 1997, 38 symptomatic patients with
advanced non-small cell lung cancer (NSCLC) were treated with MIP
chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50
mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including
physical well-being, general symptoms and lung cancer-specific symptoms, as
well as objective response. RESULTS: The overall response rate was 38.9%
(14/36, all were partial response) and the median duration of response was
3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of
overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of
QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of
chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using
multiple clinical predictors of survival (age, histology, stage,
performance status), only change of QOL emerged significantly (P = 0.0007).
CONCLUSIONS: MIP had an endurable response and low toxicity profile, and
provided good QOL. Integral QOL data in our study provided the strong
prediction of survival in advanced NSCLC. Further experienced QOL study
will provide greatly enhanced outcome data in clinical trials.
相似文献
6.
W E R Berkhout A Suomalainen D Brüllmann R Jacobs K Horner H C Stamatakis 《Dento maxillo facial radiology》2015,44(6)
Handheld portable X-ray devices are increasingly used for intraoral radiography. This development introduces new challenges to staff and patient safety, for which new or revised risk assessments must be made and acted upon prior to use. Major issues might be: difficulties in using rectangular collimation with beam aiming devices, more complex matching of exposure settings to the X-ray receptor used (e.g. longer exposure times), movements owing to the units'' weight, protection of the operator and third persons, and the use in uncontrolled environments. These problems may result in violation of the “as low as reasonably achievable’’, that is, ALARA principle by an increase in (re)exposures compared with the other available intraoral X-ray devices. Hence, the use of handheld portable X-ray devices should be considered only after careful and documented evaluation (which might be performed based on medical physics support), when there is evidence that handheld operation has benefits over traditional modalities and when no new risks to the operators and/or third parties are caused. It is expected that the use of handheld portable X-ray devices will be very exceptional, and for justified situations only. Special attention should be drawn to beam-aiming devices, rectangular collimation, the section of the X-ray receptor, focus–skin distance, and backscatter shielding, and that the unit delivers reproducible dose over the full set of environmental conditions (e.g. battery status and temperature). 相似文献
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Sanna Matilainen Pirjo Isohanni Liliya Euro Tuula L?nnqvist Helena Pihko Tero Kivel? Sakari Knuutila Anu Suomalainen 《European journal of human genetics : EJHG》2015,23(3):325-330
Mutations in SUCLA2, encoding the ß-subunit of succinyl-CoA synthetase of Krebs cycle, are one cause of mitochondrial DNA depletion syndrome. Patients have been reported to have severe progressive childhood-onset encephalomyopathy, and methylmalonic aciduria, often leading to death in childhood. We studied two families, with children manifesting with slowly progressive mitochondrial encephalomyopathy, hearing impairment and transient methylmalonic aciduria, without mtDNA depletion. The other family also showed dominant inheritance of bilateral retinoblastoma, which coexisted with mitochondrial encephalomyopathy in one patient. We found a variant in SUCLA2 leading to Asp333Gly change, homozygous in one patient and compound heterozygous in one. The latter patient also carried a deletion of 13q14 of the other allele, discovered with molecular karyotyping. The deletion spanned both SUCLA2 and RB1 gene regions, leading to manifestation of both mitochondrial disease and retinoblastoma. We made a homology model for human succinyl-CoA synthetase and used it for structure–function analysis of all reported pathogenic mutations in SUCLA2. On the basis of our model, all previously described mutations were predicted to result in decreased amounts of incorrectly assembled protein or disruption of ADP phosphorylation, explaining the severe early lethal manifestations. However, the Asp333Gly change was predicted to reduce the activity of the otherwise functional enzyme. On the basis of our findings, SUCLA2 mutations should be analyzed in patients with slowly progressive encephalomyopathy, even in the absence of methylmalonic aciduria or mitochondrial DNA depletion. In addition, an encephalomyopathy in a patient with retinoblastoma suggests mutations affecting SUCLA2.Mitochondrial diseases are caused by genetic defects in nuclear or mitochondrial DNA (mtDNA) that disrupt function of the respiratory chain, compromising the synthesis of ATP. Most childhood-onset phenotypes are caused by autosomal recessive mutations in nuclear-encoded mitochondrial proteins. Mitochondrial diseases can manifest at any age, with almost any symptom, in almost any tissue, although the tissues with the largest dependence on oxidative energy supply, such as the central nervous system, sensory organs and skeletal muscle,1 are most commonly affected. The wide clinical and genetic heterogeneity with overlapping phenotypes makes the diagnostics of mitochondrial diseases challenging.2mtDNA depletion syndrome is associated with many clinical phenotypes and has a variable genetic background. It can be caused by several nuclear genes, which typically impair mtDNA replication, repair or nucleotide synthesis.3 One of these genes is SUCLA2, encoding the β-subunit of the Krebs cycle enzyme ADP-forming succinyl-CoA synthetase (SCS-A). SCS catalyzes the reversible conversion of succinyl-CoA to succinate, accompanied by substrate-level phosphorylation of ADP or GDP.4 The enzyme is a heterodimer composed of a catalytic α-subunit, encoded by SUCLG1 and a β-subunit that determines the enzymes'' substrate specificity for either ADP (SUCLA2) or GDP (SUCLG2). SCS is widely expressed in mammalian tissues, with predominance of either the ADP- or GDP-forming form in each tissue. SUCLG1 is ubiquitously expressed, whereas expression of SUCLA2 dominates in catabolic tissues, in which the main source of energy is ATP, such as the brain, and is induced in heart and skeletal muscle.4, 5 Patients with SUCLA2 mutations typically have progressive childhood-onset Leigh-like encephalomyopathy associated with dystonia, hypotonia, sensorineural hearing deficit, lesions of the basal ganglia, depletion of mtDNA and methylmalonic aciduria.3, 6 Over 20 patients and five different mutations in SUCLA2 have been described.6, 7, 8, 9, 10We report here molecular basis of mitochondrial encephalomyopathy, also combined with bilateral retinoblastoma, in patients with clinical symptoms or signs previously described in association with SUCLA2 mutations: encephalomyopathy with hearing deficit and methylmalonic aciduria. 相似文献
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The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI). 相似文献