摘要:

Many adolescents with cancer are denied the benefits of protocol inclusion and optimal supportive care. More than 70% of older adolescent patients are not treated at institutions representing pediatric cooperative groups and are not enrolled in clinical trials, despite a demonstrated survival advantage for patients registered in protocols. Failure to refer adolescent cancer patients to specialized pediatric oncology treatment centers also has an impact on their quality of care. The challenge before both the medical and pediatric health care communities is to assure adolescent patients the benefits of inclusion in clinical trials and treatment in age-appropriate settings.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The past decade has witnessed substantial growth in our knowledge of the genes and loci that are altered in Wilms tumor. Although Wilms tumor was one of the original paradigms of Knudson's two-hit model of cancer formation, it has become apparent that several genetic events contribute to Wilms tumorigenesis. Recent research has identified targets and regulators of the first Wilms tumor gene,WT1, has uncovered several candidate genes at the second Wilms tumor locus,WT2, and has identified two familial Wilms tumor loci,FWT1andFWT2.The recent discovery of activating &bgr;-catenin mutations in some Wilms tumors has also implicated the Wnt signaling pathway in this neoplasm. Recurrent abnormalities of other loci, including 16q, 1p, and 7p, have indicated that these sites may harbor Wilms tumor genes. An enhanced understanding of these and other genetic lesions will provide the foundation for novel targeted Wilms tumor therapies.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Recent advances in the field of gene transfer are producing tantalizing results suggesting that the potential to correct disease at a molecular level may be at hand. Genetic correction of the hemophilias—bleeding disorders that stem from the deficiency of functional factor VIII or IX—represent models for the development of a basic understanding of how gene therapy will be achieved. The goals for hemophilia gene transfer are to produce therapeutic amounts of the coagulant protein while minimizing an immune response or antibody inhibitor. This requires the use of nontoxic vectors to deliver genes that express the protein in a functional form for the life of the patient. Based on a scientific understanding of the molecular and cellular defects leading to the bleeding phenotype, gene transfer studies at the laboratory and clinic have produced exciting results. The author here provides a critical assessment of the state of hemophilia gene transfer and its relevance to the field as a whole.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Allogeneic stem cell transplantation has proven an effective means of treatment for a variety of malignant and nonmalignant conditions. Stem cell transplantation has traditionally been preceded by the patient receiving high (myeloablative) doses of chemotherapy and total body irradiation, which have been associated with significant transplant-related morbidity and mortality. This finding has precluded some older or heavily pretreated patients from being offered stem cell transplantation and has made other populations, such as those with nonmalignant conditions, reluctant to consider this therapy. Preclinical studies demonstrated that engraftment of donor stem cells could be achieved with nonmyeloablative, but immunosuppressive, preparative regimens that are significantly less toxic. Preliminary clinical studies have shown that patients previously ineligible for allogeneic stem cell transplantation can frequently be safely transplanted and that an immune-mediated graft-versus-malignancy effect plays an important role in the antitumor efficacy of this treatment. The potential to use this nonmyeloablative approach in nonmalignant disorders in which regimen-related toxicity must be minimized is of particular interest in children.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

von Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 and 3) or qualitative (type 2) defects of von Willebrand factor (VWF). The mechanisms of most inherited VWD types have been recently elucidated by genetic and molecular diagnosis, but the phenotypic tests based on measurements of plasma and platelet VWF, the ability of VWF to interact with its platelet receptor, and the analysis of the multimeric composition of VWF are always essential to identify patients with different VWD subtypes. The aim of treatment is to correct the dual defects of hemostasis,ie, abnormal coagulation expressed by low levels of factor VIII (FVIII) and abnormal platelet adhesion expressed by prolonged bleeding time (BT). Desmopressin is the treatment of choice in most patients with type 1 and type 2 VWD, who account for 60 to 70% of cases. In type 3 and in some severe forms of type 1 and type 2 VWD, desmopressin is not effective, and it is necessary to resort to plasma concentrates containing FVIII and VWF. Treated with virucidal methods, these concentrates are effective and currently safe, but they do not always correct the BT defect. Platelet concentrates or desmopressin can be used as adjunctive treatments when poor correction of the BT after concentrates is associated with continued bleeding.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Marfan syndrome is an autosomal dominant disorder of connective tissue that affects the cardiac, eye, and skeletal systems. More than 135 mutations have been identified in the fibrillin-1 gene, localized on chromosome 15q(21.1) and responsible for the clinical manifestations of Marfan syndrome. The major orthopedic manifestations of Marfan syndrome include scoliosis, chest wall deformity, dural ectasia, joint hypermobility, and acetabular protrusion. In addition, decreased bone mineral density has been reported in patients with Marfan syndrome. This review summarizes recent developments in the genetic and orthopedic aspects of Marfan syndrome. Increased practitioner awareness of the clinical features associated with Marfan syndrome may facilitate earlier diagnosis and optimize patient treatment.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Hemophilic arthropathy occurs in all patients with severe and moderate hemophilia A and B in early adolescence after repeated bleeding in a major joint unless treated with replacement of the missing factor. Regular infusions of recombinant factor or treated plasma derived factor given prophylactically to prevent spontaneous bleeding are recommended for all children to maintain a plasma factor level of >1%. Recombinant factor product or treated plasma derived product should be used. Prophylaxis should begin when bleeding occurs repeatedly and is superior to on-demand therapy. Hypertrophied synovium should be removed surgically or with a sclerosing agent, either radioactive or chemical material, to impede further cartilaginous and bony deterioration. Arthroplasty of the knee and hip have been successful in reducing pain and loss of motion when other efforts to control synovial hypertrophy fail.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Muscular dystrophy is a collective group of inherited, noninflammatory, progressive muscle wasting diseases. The initial pathologic feature is an abnormality in the genetic code for dystrophin or one of its associated glycoproteins, which leads to the various clinical syndromes. Despite minor variations between the different types, all muscular dystrophies have in common progressive muscle weakness, which is best typified by Duchenne muscular dystrophy. The weakness occurs in a proximal to distal direction and can compromise ambulatory status as well as cardiopulmonary function. Additionally, structural soft tissue contractures and spinal deformities may develop from poor posturing secondary to the progressive muscle weakness and imbalance. The rapidly developing scoliosis and its associated pelvic obliquity can even compromise sitting. Recent advances in molecular biology and gene therapy research raise the hope for a cure for muscular dystrophy in the near future. Until that time, however, the role of orthopedic surgeons in treating patients with muscular dystrophy is to preserve or prolong their functional status for as long as possible. This can be achieved by physical therapy, bracing, soft tissue releases for joint contractures, and early stabilization of the spine.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The discoid meniscus is the most common abnormal meniscal variant in children. It is most likely a congenital deviation and usually occurs laterally. The discoid shape results in greater coverage of the tibia and usually is associated with increased thickness of the meniscus that may lead to abnormal shearing forces across the knee joint. The Watanabe classification divides this anomaly into three distinct types: complete, incomplete, and Wrisberg ligament. The complete and incomplete types are often asymptomatic; unless symptomatic, they generally should be left alone. Tears should be treated with resection back to a stable rim. The Wrisberg ligament type is a hypermobile meniscus secondary to a lack of posterior tibial attachment. This type may or may not be associated with an abnormal shape and may appear in childhood as a classic snapping knee syndrome. These children complain of intermittent popping and snapping within the knee that clinically manifests as a dramatic audible and visible adjustment of the knee with each flexion and extension. Treatment of a symptomatic Wrisberg ligament type requires surgical repair of the posterior disruption. Saucerization of the remaining meniscus may be required to protect the repair from abnormal shear forces.

ISSN:1040-8703    

出版商:OVID    

年代:2002

数据来源: OVID