Spinal radiation before surgical decompression adversely affects outcomes of surgery for symptomatic metastatic spinal cord compression.

STUDY DESIGN: A retrospective chart review was performed. OBJECTIVE: To determine whether preoperative spinal radiation increases the number of major wound complications in patients with cancer who have symptomatic spinal cord compression. SUMMARY OF BACKGROUND DATA: Many factors have increased the number of patients hospitalized with symptomatic spinal cord compression after spinal irradiation. The surgical management of metastatic spinal cord compression may be complicated by preoperative radiation. METHODS: A retrospective review of 123 patients admitted with symptomatic metastatic spinal cord compression from 1970 through 1996 was conducted. The final study population of 85 patients was separated into three treatment groups: 1) radiation only, 2) radiation followed by surgery, and 3) de novo surgery followed by radiation. RESULTS: The major wound complication rate for patients who had radiation before surgical decompression and stabilization was 32%, or threefold, higher than the 12% observed in patients who had de novo surgery (P < 0.05). No other clinical factor or condition predicted the development of a major wound complication. Patients treated initially with surgery had superior functional outcomes in an analysis stratified by Frankel grade (P < 0.05). Of the ambulatory patients who underwent de novo surgery, 75% remained ambulatory and continent 30 days after treatment, whereas only 50% of those treated with radiation before surgery had similar outcomes. CONCLUSIONS: Spinal radiation before surgical decompression for metastatic spinal cord compression is associated with a significantly higher major wound complication rate. In addition, preoperative spinal irradiation might adversely affect the surgical outcome.

Intramedullary cavernous malformations of the spinal cord.

Cavernous malformations of the spinal cord are extremely rare lesions. The 58 reported cases in the English literature and 9 of the authors' own cases are reviewed. The clinical presentation, patient characteristics, radiographic appearance, and histopathologic features are reviewed. The optimal surgical management and outcomes of treatment for intramedullary spinal cord cavernous malformations are discussed in detail.

Distal basilar perforator artery aneurysm: case report.

OBJECTIVE AND IMPORTANCE: Distal basilar artery aneurysms represent 5 to 8% of intracranial aneurysms. It is crucial to preserve all of the basilar apex perforating vessels when dissecting in this region. This report is the first to describe a rostral basilar perforating artery that was the anatomic origin of a cerebral aneurysm. CLINICAL PRESENTATION: A 56-year-old woman presenting with subarachnoid hemorrhage underwent initial four-vessel cerebral angiography that did not demonstrate the source of her hemorrhage. A follow-up cerebral angio-gram 9 days later suggested a small aneurysm in the region of the left superior cerebellar artery. INTERVENTION: A left pterional craniotomy was performed. An aneurysm arising from the origin of a distal basilar perforating artery was identified and obliterated with a small vascular clip. Flow was preserved in the perforating vessel, and the patient had an excellent outcome. CONCLUSION: The findings in the report illustrate the novel anatomic principle that a distal basilar perforating vessel can serve as the anatomic origin of a cerebral aneurysm. Knowledge of this entity would be helpful in avoiding complications at surgery, including perforator injury or aneurysmal rupture in such cases.

Enhanced T cell migration to sites of microscopic CNS disease: complementary treatments evaluated by 2- and 3-D image analysis.

Novel therapies are being developed to attack tumour or other abnormal cells within the brain. A general problem is the need for delivery to sites of microscopic disease. Leukocytes offer an attractive solution; they are able to both move through tissue and recognize abnormal targets. Leukocytes may act as effectors, or as vehicles for drugs, retroviral vectors or other agents. Here, we illustrate complementary ways of enhancing leukocyte migration to sites of microscopic central nervous system (CNS) disease. Enhanced T cell migration to sites of disseminated tumour is used as the example. Computer-assisted image analysis is used to evaluate migration patterns in 2 and 3 dimensions. Shared regulatory features in the migration of tumour and responding cells, and the opportunities and questions they imply, are discussed.

Clival chondroma in a child with Ollier's disease. Case report.

An 8-year-old female with Ollier's disease (multiple enchondromatosis) developed an intracranial chondroma arising from the clivus, which was diagnosed by both computed tomography and magnetic resonance imaging. The clinical presentation, differential diagnosis, and management of this rare pediatric intracranial tumor are discussed.

In vitro and in vivo bactericidal activities of 10%, 2.5%, and 1% povidone-iodine solution.

The bactericidal action of three formulations of a povidone-iodine (PVI) complex in vitro, in vivo, and in the presence of competing organic matter was evaluated. Bacterial organisms included Staphylococcus aureus ATCC 25923 and 25 clinical isolates of Staph. aureus, designated KU 1-25. For the in vitro studies, 1.0 mL of bacterial inoculum containing 10(7) organisms was introduced into 9.0 mL of chemically stable 10% and 1% PVI formulations in sterile culture tubes, and 1.0-mL samples were withdrawn at set intervals. Samples were plated by using standard techniques and incubated for 24 hours, after which colony-forming units were counted. For in vivo studies, 0.1 mL of 10(6) Staph. aureus ATCC 25923 or KU inoculum was deposited on the dorsum of the hand of healthy human subjects. This area was wiped with a cotton swab saturated with 1%, 2.5%, or 10% PVI formulations. Samples were taken at 15 and 30 seconds after application of the iodophor. To test the bactericidal activity of the three formulations in the presence of a competing substrate, a swab soaked with sterile sheep's blood was applied to the skin and allowed to dry. The percentage of 10(4) Staph. aureus inoculum recovered allowed for comparison of the three products. In vitro, the 1% PVI formulation was bactericidal for 10(7) Staph. aureus within two minutes, as compared with the four minutes required by 10% PVI. On the skin contaminated with 10(6) organisms, the rates of killing within 30 seconds were comparable for both solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

An intronic 10-base-pair deletion in a class II A beta gene affects RNA processing.

Several biologically important examples of posttranscriptionally regulated genes have recently been described (T. Gerster, D. Picard, and W. Schaffner, Cell 45:45-52, 1986; R. Reeves, T.S. Elton, M.S. Nissen, D. Lehn, and K.R. Johnson, Proc. Natl. Acad. Sci. USA 84:6531-6535, 1987; H.A. Young, L. Varesio, and P. Hwu, Mol. Cell. Biol. 6:2253-2256, 1986). Little is known, however, regarding sequences that mediate posttranscriptional RNA stability. Characterization in our laboratory of a mutant murine B lymphoma, M12.C3, revealed a posttranscriptional defect affecting the synthesis of a major histocompatibility complex class II gene (A beta d) whose product normally controls both the specificity and magnitude of the immune response. Molecular studies revealed that the mutation responsible for diminished A beta d gene expression was an intronic deletion of 10 base pairs (bp) located 99 bp 5' of the third exon. This deletion lies in a region not known to be critical for accurate and efficient splicing. Furthermore, sequence analysis of amplified A beta-specific cDNA demonstrated that the small number of A beta d transcripts produced in the mutant cells was correctly spliced. It appears that the mechanism by which this intronic 10-bp deletion acts to decrease RNA stability is unlikely to be at the level of RNA splicing.

A functional role for signal transduction via the cytoplasmic domains of MHC class II proteins.

B cell transfectants expressing MHC class II (Ia) molecules with truncated cytoplasmic domains are defective in both antigen presentation and in anti-Ia induced intracellular signaling. In this report we show that the Ag presentation defect in a truncated-Ia expressing transfectant can be overcome by providing the second messenger for the Ia-mediated signaling event. Preincubation with dibutyryl-cAMP restored the ability of the truncated Ia expressing-transfectant to stimulate IL-2 release by otherwise nonresponsive T hybrids. This provides direct functional evidence that signaling via the cytoplasmic domains of MHC class II proteins leads to the generation of accessory signals in the B cell that are important in T cell activation. The dibutyryl-cAMP induced signal must be on the same cell as the restricting element, does not bypass the requirement for occupancy of the T cell receptor with its normal ligand, and is lost upon fixation of the cells. Thus T cell-B cell interaction involves a two way communication in which both cells sense and respond to the formation of the antigen/MHC/TCR complex.

Antigen presentation abrogated in cells expressing truncated Ia molecules.

Oligonucleotide site-directed mutagenesis was used to introduce a premature stop codon in wildtype A beta k and A alpha k cDNA clones to create truncated A beta k and A alpha k molecules lacking the cytoplasmic domain. Transfected B lymphoma cells expressing an I-Ak molecule with a truncated beta-chain or with truncated alpha- and beta-chains showed profound defects in two Ia-related functions: Ia-restricted Ag presentation and intracytoplasmic signaling. The ability of these transfected cell lines to activate autoreactive T hybrids was markedly impaired whereas loss of Ag presentation to nominal Ag-specific T hybrids was more subtle. Ia-mediated transmembrane signaling as measured by PKC translocation from cytosol to nucleus after stimulation with anti-Ak antibody was greatly affected by truncation of the A beta and A alpha cytoplasmic domains. These results indicate an important role for the highly conserved cytoplasmic domain in Ia-mediated responses.

Cytoplasmic domain affects membrane expression and function of an Ia molecule.

The association of foreign antigen with Ia molecules on the surface of antigen-presenting cells is necessary for the interaction with the clonally distributed antigen receptor on T cells and is therefore critical in the initiation and regulation of immune responses. Ia polypeptides (alpha and beta) are composed of two extracellular domains, a transmembrane domain and a cytoplasmic domain. Although exon-shuffling experiments have demonstrated that antigen associates with the NH2-terminal alpha 1 and beta 1 domains, the roles that the other domains play in Ia function are still poorly understood. The B-hybridoma cell line 2B1 was selected in a series of positive and negative immunoselection steps for a mutation in the Ek alpha polypeptide. It was found to fortuitously contain a mutation in the Ak alpha polypeptide as well. Sequence analysis of the Ak alpha gene showed that a single base transition (C----T) resulted in a stop codon at amino acid residue 222. This caused the loss of 12 amino acids from the cytoplasmic domain of the mature polypeptide. This mutation results in a decreased level of Ak alpha polypeptide expression on the cell surface (50% of wild-type levels), an increased half-life of Ak alpha polypeptide in the cell, and a specific limited defect in antigen presentation.

Structural mutation affecting intracellular transport and cell surface expression of murine class II molecules.

We have selected Ia variants from the Ia+ (H-2d) M12.4.1 B cell lymphoma that are negative on the cell surface for one or both Ia isotypes. The molecular analysis of two such independently selected cell lines, M12.A2 and M12.C3, is reported here. This analysis revealed that the genes encoding Ad beta (M12.A2) and Ed beta (M12.C3) contained identical single-nucleotide transitions that resulted in the substitution of Ser (mutant) for Asn (wild-type) at residue 82/83 of the extracellular NH2-terminal (membrane distal) beta 1 domain. This conservative substitution caused a cytoplasmic accumulation of I-A or I-E molecules in the respective cell line although predicted secondary-structure analysis suggests a minimal effect on protein conformation. Thus, the mutation appears to have either created a negative signal that stops transport or eliminated a positive signal that is required for transport and targeting to the cell surface.