The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

PURPOSE: This study aims to propose and validate a new unified "Risser+" grade that combines the North American (NA) and European (EU) variants of the classic Risser score. The "Risser+ " grade can effectively combine the North American and European Risser Classifications for skeletal maturity with adequate intra-rater/inter-rater reliability and agreement. METHODS: Agreement and reliability were evaluated for 6 raters (3-NA, 3-EU) who assessed 120 pelvic radiographs from the BrAIST trial, all female, average age 13.4 (range 10.1-16.5 years). Blinded raters reviewed x-rays at two time-points. Intra- and inter-rater agreement (RA) were established with Krippendorff's alpha (k-alpha), while intra- and inter-rater reliability (RR) were established with intraclass correlation coefficients (ICC). Acceptable agreement and reliability were set a priori at 0.80. RESULTS: Inter-RA for the second reading met study requirements (k-alpha = 0.86 [0.81-0.90]) compared to the first reading (0.72 [0.63-0.79]) while combined readings was close to target agreement (0.79 [0.74-0.84]). Removal of 20 readings demonstrating outlier tendencies increased agreement for the first, second, and combined reads (k-alpha = 0.85, 0.89, 0.87, respectively). Intra-RA was sufficient for 4 out of 6 raters (k-alpha > 0.80) and one rater from EU and NA presented subpar intra-RA (k-alpha = 0.64 and 0.74, respectively). Inter-RR met study requirements overall reads (ICC = 0.96 [0.95-0.97]) including the first (0.94 [0.92-0.95]) and second (0.97 [0.97-0.98]) reads, independently. CONCLUSIONS: The Risser+ system showed excellent reliability across multiple reads and raters and demonstrated 79% agreement overall reads and ratings. Agreement increased to over 85% when raters could distinguish Risser 0 + from Risser 5. These slides can be retrieved from electronic supplementary material.

Correction to: The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

Unfortunately, the affiliation of the author Negrini S has been incorrectly published in the original version. The complete correct affiliation of this author should read as follows.

Light and electronmicroscopy of the bowel in an unusual form of Hirschsprung's disease.

In a histological and histochemical study of multiple biopsies of unaffected segments of the bowel from 15 patients with Hirschsprung's Disease (H.D.), the AChE or non-specific esterase and the NADPH tetrazolium reductase enzyme reactions proved to be useful in identification of myenteric plexus islands; and acid phosphatase for the delineation of individual neurones. In the affected segment (usually aganglionic), this myenteric plexus tissue was not reactive for esterase, but individual nerve fibres among muscle fibres of the two muscle coats showed the enzyme product in a third of the cases. Fine structural study of biopsies from a typical case of H.D., showed normal looking axons and Schwann cytoplasm with terminals bearing both andrenergic and cholinergic vesicles in the unaffected colon, smooth muscle fibres with normal fine structure in all parts of the bowel, and loss of neurons with myenteric plexus replaced by nerve fibre groups in the affected rectosigmoid. One patient clinically presenting as a case of severe H.D., with histologically and histochemically normal myenteric and submucous ganglion cells, and not responding to resection of the bowel, showed degeneration of the unmyelinated axons with prominent Schwann cytoplasm, depleted cholinergic but persistent adrenergic vesicles, and markedly thinned and degenerating smooth muscle fibres and myofilaments, suggesting either a primary disorder of muscle tissue of the colon or, less likely, a denervation atrophy with secondary degeneration of the smooth muscle fibres.

Microsatellite instability in malignant melanoma.

Defective mismatch repair has been detected in human colorectal and endometrial carcinomas which exhibit microsatellite instability (MIN). The purpose of this study was to search for MIN in melanoma. Paraffin-embedded neoplastic and non-neoplastic control cells were obtained from 20 untreated individuals with cutaneous malignant melanoma. Breslow thickness ranged from 0.2-7.4 mm (mean 1.4). Cells were carefully scraped from glass slides so that tumor and control DNA could be isolated and then amplified by polymerase chain reaction (PCR) at seven separate microsatellites localized to specific chromosome regions: 1p22 (D1S187), 5q11.2-13.3 (D5S107), 6q21-23.3 (D6S357), 9p21 (IFNA), 11p15.2 (D11S861), 17p13.1 (D17S786), and 18q11 (D18S34). Heterozygosity indices were > or = 0.70. Loci from these chromosome regions were chosen because of cytogenetic abnormalities reported in melanoma (1p, 6q, 9p), location of common oncogenes (11p-HRAS, 17p-TP53), or use in other MIN studies (5q, 18q). Five individuals (25%) demonstrated MIN. There was no correlation with tissue thickness. One individual demonstrated MIN at two loci and one individual demonstrated loss of heterozygosity. The results indicate that MIN occurs in melanoma, albeit less frequently than reported in carcinomas.

Development of an injectable two-phase drug delivery system for sequential release of antiresorptive and osteogenic drugs.

Unlike controlled release systems that deliver a single drug, dual or multidrug delivery systems with distinct release profiles are more likely to promote timely and effective tissue regeneration as they provide both temporally and concentration-dependent release of different molecules to mimic natural biological events. In this study, an injectable and biodegradable delivery system was developed to sequentially release an antiresorptive drug (clodronate) followed by an osteogenic agent (simvastatin) to treat bone disease. The injectable delivery system comprised simvastatin-loaded gelatin microspheres suspended in a viscous solution of carboxymethylcellulose (CMC) containing clodronate. Several factors (CMC concentration, glutaraldehyde concentration, simvastatin loading, and gelatin microsphere processing conditions) were investigated for their effects on drug release. Clodronate release was not affected by CMC concentration, with complete delivery within 12 hr, and simvastatin release could be modulated by cross-linking of the gelatin microspheres, loading, and washing conditions. Burst release of simvastatin was reduced from 70% to 6% in conjunction with sustained release for up to 3 weeks. The combined system showed early release of the antiresorptive clodronate sequentially followed by sustained delivery of the osteogenic simvastatin. This robust and flexible two-phase delivery system may prove useful for applications in which multiple drug delivery is desired.

Meningoceles and neurological involvement.

The term meningocele is used in this communication to include all lesions presenting as swellings associated with spina bifida, when neural tissue is not exposed on the surface. 144 meningoceles were operated on during an 18-year period. The stalk of the meningocele was connected with the neural tissue in 113 of them. Two distinct types of lesions have been noted in these patients and have been designated "meningocele with tethered cord" (52) and "meningocele with tethered roots" (56). In both conditions about half the number of cases presented clinically before the age of 3 months, when paraplegia was evident in only 5 of the 26 infants with tethered cord and 3 of the 25 with tethered roots. In contrast, all or the majority of babies reporting after the age of one year, had paraplegia. Hence, a case is made out for an early operation in all these patients. At surgery the main lesion was a fatty mass in 29 babies with tethered cord, and a cystic mass in 30 with tethered roots. While hydrocephalus was virtually absent in these babies, there were 5 others who manifested obstructive hydrocephalus with meningocele. "Meningomyelocele", the commonest lesion associated with spina bifida, presents with an exposed spinal cord at birth, is associated with communicating hydrocephalus, and can be clearly distinguished from the meningocele.

Posterior spinal fusion in paralytic scoliosis and myelomeningocele.

The Shriners Hospital, Lexington, KY, experience with posterior spinal fusion for scoliosis in 50 patients with myelomeningocele was reviewed. Six patients were fused with Harrington rods and 47 of 50 patients were treated with some form of segmental fixation. The complication rate was 48% (24/50) resulting in 1.48 procedures per patient. The deep infection rate was 8% (4/50) and the pseudarthrosis rate was 16% (8/50). The use of modern segmental instrumentation systems has improved the pseudarthrosis rates for posterior spinal fusion in scoliosis associated with myelomeningocele but not to the point of displacing the current approach of an anterior and posterior spinal fusion.

Rapid analysis of estrogen and progesterone receptors using gel-exclusion high-performance liquid chromatography.

Estrogen and progesterone receptors prepared from mouse, rat, and human uteri, as well as from human breast cancers, have been characterized by gel-exclusion high-performance liquid chromatography. The qualitative relationships previously established by sedimentation analysis between the cytoplasmic [aggregated (approximately 8S), deaggregated (approximately 4S), and trypsinized (approximately 3.6S)] and nuclear (approximately 5S) forms of the rat uterine estrogen receptor were maintained by this technique. Differences in the partition of estrogen and progesterone receptors from the same species as well as interspecies differences in these receptors were reproducibly observed. Multiple forms of human estrogen and progesterone receptors could clearly be resolved in a single analysis and were distinct from serum steroid binding tissue contaminants. Separation analyses, performed at flow rates up to 2 mL min-1, were capable of resolving all receptor forms in 10--12 min with the column returning to base line in 25 min. With this exclusion gel column (TSK-G3000SW) as a background upon which to reference different receptor forms, eight distinct partitions or elution positions have been enumerated. This approach has considerable promise for the rapid characterization of different forms of steroid-receptor proteins. Moreover, it should provide a critical advantage in minimizing the opportunities for receptor modification during separation analysis and in maximizing the opportunity to study short-lived interactions between receptors and physiologic or pharmacologic ligands.