Preoperative care of infants with nephroblastoma. The International Society of Pediatric Oncology 6 experience.

The International Society of Pediatric Oncology (SIOP) recommends preoperative treatment in the management of eligible patients with Wilms' tumor. Until 1980, children younger than 12 months of age (infants) at diagnosis had been excluded from the SIOP trials. SIOP 6, conducted from 1980 to 1987, was the first SIOP study to include infants older than 6 months of age. This retrospective analysis of 145 infants registered to SIOP 6 demonstrates that in infants older than 6 months and having favorable histology (FH), a two-drug preoperative chemotherapy (CT) regimen of 4 weeks significantly ameliorated stage distribution as determined at delayed surgery but did not affect a good outcome. However, the CT dose utilized in SIOP 6 resulted in an unacceptable toxicity in this age group, and SIOP 9, the new SIOP study of Wilms' tumor, recommends a reduced dose of CT in infants. Preoperative CT is not recommended in infants younger than 6 months of age. Specifically, the high incidence (29%) of mesoblastic nephroma in this age group does not justify such an approach. Histopathologic diagnosis should be obtained in these patients before any treatment.     

A comparative study of the anatomical,radiological and therapeutic features of the lumbar facet joints

Summary An anatomical study of the lumbar apophyseal joints was carried out to facilitate recognition of facet joint lesions, which we now examine routinely by percutaneous arthrography. Special attention was given to the configuration of the different compartments of the joint space and to its relationships with the contents of the intervertebral foramen. The abnormalities seen on lumbar facet joint arthrography are very varied; two major groups should be stressed: synovial fringe hypertrophy and pseudodiverticular synovial ectasia. The percutaneous approach to lumbar facet joint arthrography allows it to be used a therapeutic measure, with injection of anti-inflammatory drugs into the joint space, the beneficial effects of which were confirmed in our series. The precision, efficiency and cost-effectiveness of this outpatient technique justify and should encourage its more widespread application in the diagnosis and treatment of low back pain.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.      

Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography

In this study, we have used time-lapse video cinematography to study fertilization in 50 human oocytes that had undergone intracytoplasmic sperm injection (ICSI). Time-lapse recording commenced shortly after ICSI and proceeded for 17-20 h. Oocytes were cultured in an environmental chamber which was maintained under standard culture conditions. Overall, 38 oocytes (76%) were fertilized normally, and the fertilization rate and embryo quality were not significantly different from 487 sibling oocytes cultured in a conventional incubator. Normal fertilization followed a defined course of events, although the timing of these events varied markedly between oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular waves of granulation within the ooplasm which had a periodicity of 20-53 min. The sperm head decondensed during this granulation phase. The second polar body was then extruded, and this was followed by the central formation of the male pronucleus. The female pronucleus formed in the cytoplasm adjacent to the second polar body at the same time as, or slightly after, the male pronucleus, and was subsequently drawn towards the male pronucleus until the two abutted. Both pronuclei then increased in size, the nucleoli moved around within the pronuclei and some nucleoli coalesced. During pronuclear growth, the organelles contracted from the cortex towards the centre of the oocyte, leaving a clear cortical zone. The oocyte decreased in diameter from 112 to 106 microm (P < 0.0001) during the course of the observation period. The female pronucleus was significantly smaller in diameter than the male pronucleus (24.1 and 22.4 microm respectively, P = 0.008) and contained fewer nucleoli (4.2 and 7.0 respectively, P < 0.0001). After time-lapse recording, oocytes were cultured for 48 h prior to embryo transfer or cryopreservation. Embryo quality was related to fertilization events and periodicity of the cytoplasmic wave, and it was found that good quality embryos arose from oocytes that had more uniform timing from injection to pronuclear abuttal and tended to have a longer cytoplasmic wave. In conclusion, we have shown that time-lapse video cinematography is an excellent tool for studying fertilization and early embryo development, and have demonstrated that human fertilization comprises numerous complex dynamic events.      

Interventional Radiology for Treating Soft Tissue Sarcomas

The role of interventional radiology for soft tissue sarcomas is only occasionally addressed in the literature. However, different techniques such as embolization, selective chemotherapy, chemoembolization, and acrylic cement osteoplasty can be helpful with the primary tumor, recurrences, and metastases. This article discusses these techniques and their complications in treatment of soft tissue sarcomas.     

Le syndrome de Smith-Magenis

Smith-Magenis syndrome is caused by a 17p11.2 deletion. It associates mental retardation, facial dysmorphism and brachydactyly; aberrant behavior and major sleep problems are present in 70% of the cases. It is probably under-diagnosed because the facial abnormalities are mild and the behavioral problems with hyperactivity and self-injuries are dominant, leading to the diagnosis of psychiatric pathology. However these behavioral problems are sufficiently characterized to allow the diagnosis of the syndrome and look for a 17p11.2 microdeletion. Otorhinolaryngologic, ophtalmologic, cardiac and renal abnormalities can be associated and their evaluation is necessary. Smith-Magenis syndrome is considered as a contiguous gene syndrome. Genes have been mapped and isolated to the critical region, but their participation in the pathogenesis of the syndrome remains unclear.