Esophageal replacement with colon interposition in children.

During a 21-year period, 39 colon interposition operations were performed on 37 children at the UCLA Medical Center and the Childrens Hospital of Los Angeles. The average age at the time of operation was 5.8 years. The indications for operation were esophageal atresia in 23 patients and other benign strictures in 14 patients. The duration of patient follow-up ranged from 6 months to 21 years (mean: 9.7 years). The most common complications were esophagocolonic anastomotic leak (12), esophagocolonic anastomotic stricture (14), pneumonia, and pneumothorax. Fourteen of the 25 patients with retrosternal colon interposition had complications (56%), whereas 10 of 14 patients with left thoracic colon interposition had complications (71%). One patient died (mortality: 3%) after left thoracic interposition because of severe respiratory distress associated with other malformations. Each of the 18 patients with isoperistaltic colon interposition showed rapid transit and emptying, provided that obstruction or extensive dilatation did not occur; reverse colon segments were more dilated and emptied more slowly. The 25 patients with retrosternal colon segments had less colonic distension with better emptying than did the 14 patients with left thoracic interposition. Thirty-two of the 36 children increased their weight percentile after colon interposition. Within 2 years after cervical anastomotic stricture or leak, 78% of these children were asymptomatic and gaining weight. Thirty-one of the 37 patients (84%) had excellent results with colon interposition, with a mean follow-up of 9.7 years. Most of the major postoperative complications occurred within the first few weeks and were corrected during the first few months after operation. Preservation of the esophagus should be the surgeon's first priority; however, prolonged attempts to elongate the esophagus for anastomosis in certain patients with long-gap esophageal atresia have been more hazardous in our experience than has colon interposition.     

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.     

Shoulder instability: impact of glenohumeral arthrotomography on treatment

We used arthrotomography to study the glenoid labrum in 114 patients. Sixty-nine of the patients had anatomic instability of the shoulder (including recurrent dislocation and subluxation of the shoulder), and 45 patients had functional instability of the shoulder (denoted by chronic pain, clicking of the joint, and the sensation that an unstable condition exists without the objective signs of it). Labral tears were revealed arthrotomographically in 86% of the patients with anatomic instability, while only 40% of the patients with functional instability had labral abnormalities, and these were primarily of minor severity. Fifty-six patients (44 of whom had anatomic instability; 12, functional instability) required surgery. The surgical findings were correlated with the arthrotomographic findings, and no false-positive results were revealed. However, arthrotomography demonstrated only part of the pathologic condition of two patients. These results confirm that there is a strong correlation between labral pathologic conditions and anatomic instability of the shoulder. Arthrotomographic studies have a great impact on the selection of therapy in cases of both anatomic and functional instability of the shoulder.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Characterization of a nuclear localization signal in the C-terminus of the adeno-associated virus Rep68/78 proteins

Adeno-associated virus (AAV) replicates in the nucleus of infected cells, and therefore multiple nuclear import events are required for productive infection. We analyzed nuclear import of the viral Rep proteins and characterized a nuclear localization signal (NLS) in the C-terminus. We demonstrate that basic residues in this region constitute an NLS that is transferable and mediates interaction with the nuclear import receptor importin alpha in vitro. Mutant Rep proteins are predominantly cytoplasmic and are severely compromised for interactions with importin alpha, but retain their enzymatic functions in vitro. Interestingly, mutations of the NLS had significantly less effect on importin alpha interaction and replication in the context of Rep78 than when incorporated into the Rep68 protein. Together, our results demonstrate that a bipartite NLS exists in the shared part of Rep68 and Rep78, and suggest that an alternate entry mechanism may also contribute to nuclear localization of the Rep78 protein.     

The inferior alveolar artery in its bony course

Based on the dissection of 30 hemi-mandibles, the authors report a study of the inferior alveolar artery in its intraosseous course. On morphologic considerations they propose a classification of the collaterals into two groups: the principal collaterals destined for the teeth and the bony alveolar tissue and the secondary collaterals destined for the sheath and the nerve as well as the bony tissue around the canal. Loss of the teeth and absorption of the alveolar bone modify the caliber of the inferior alveolar arterial axis, the distribution of its collaterals and possibly its mode of termination. These facts suggest a consideration of the vascularization of the mandible in terms of four sectors. They arrive at practical conclusions that may be drawn from this study in stomatology.