Risk Score for Early Prediction of In-Hospital Mortality After Aneurysmal Subarachnoid Hemorrhage: Pooled Analysis With Score Construction and Validation.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) has a high complications burden, with in-hospital mortality as the most devastating outcome. We aimed to develop and validate a risk score for early prediction of in-hospital mortality after aSAH.

Methods: Data from 2 university hospitals were pooled (n = 1070), with cohorts for score construction (n = 886) and external validation (n = 184).

Reduced brain oxygen response to spreading depolarization predicts worse outcome in ischaemic stroke.

Spreading depolarization (SD) describes a propagating neuronal mass depolarization within the cerebral cortex that represents a mediator of infarct development and strongly stimulates the metabolic rate of O2 consumption. Here, we investigated the influence of Spreading Depolarization (SD) on brain tissue partial pressure of O2 (ptiO2) within the peri-infarct tissue of patients suffering malignant hemispheric stroke (MHS). This prospective observational trial included 25 patients with MHS that underwent decompressive hemicraniectomy followed by subdural placement of electrodes for electrocorticography (ECoG) and neighboring implantation of a ptiO2 probe within the peri-infarcted cortex.

Duration of spreading depression is the electrophysiological correlate of infarct growth in malignant hemispheric stroke.

Spreading depolarizations (SD) contribute to lesion progression after experimental focal cerebral ischemia while such correlation has never been shown in stroke patients. In this prospective, diagnostic study, we investigate the association of SDs and secondary infarct progression after malignant hemispheric stroke. SDs were continuously monitored for 3-9 days with electrocorticography after decompressive hemicraniectomy for malignant hemispheric stroke.

Cortical Spreading Depolarization in Moyamoya Vasculopathy: A Case Series.

Background: Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization.

Less-invasive subdural electrocorticography for investigation of spreading depolarizations in patients with subarachnoid hemorrhage.

Introduction: Wyler-strip electrodes for subdural electrocorticography (ECoG) are the gold standard for continuous bed-side monitoring of pathological cortical network events, such as spreading depolarizations (SD) and electrographic seizures. Recently, SD associated parameters were shown to be (1) a marker of early brain damage after aneurysmal subarachnoid hemorrhage (aSAH), (2) the strongest real-time predictor of delayed cerebral ischemia currently known, and (3) the second strongest predictor of patient outcome at 7 months. The strongest predictor of patient outcome at 7 months was focal brain damage segmented on neuroimaging 2 weeks after the initial hemorrhage, whereas the initial focal brain damage was inferior to the SD variables as a predictor for patient outcome.

Quantitative assessment of intraneural vascular alterations in peripheral nerve trauma using high-resolution neurosonography: technical note.

High-resolution neurosonography (HRNS) has become a major imaging modality in assessment of peripheral nerve trauma in the recent years. However, the vascular changes of traumatic lesions have not been quantitatively assessed in HRNS. Here, we describe the vascular-ratio, a novel HRNS-based quantitative parameter for the assessment of intraneural vascular alterations in patients with nerve lesions.

Rapid and efficient immunomagnetic isolation of endothelial cells from human peripheral nerves.

Endothelial cells (ECs) have gained an increased scientific focus since they were reported to provide guidance for Schwann cells and subsequently following axons after nerve injuries. However, previous protocols for the isolation of nerve-derived ECs from human nerves are ineffective regarding time and yield. Therefore, we established a novel and efficient protocol for the isolation of ECs from human peripheral nerves by means of immunomagnetic CD31-antibody conjugated Dynabeads and assessed the purity of the isolated cells.

Fascicular Ratio Pilot Study: High-Resolution Neurosonography-A Possible Tool for Quantitative Assessment of Traumatic Peripheral Nerve Lesions Before and After Nerve Surgery.

Background: Clinical and electrophysiological assessments prevail in evaluation of traumatic nerve lesions and their regeneration following nerve surgery in humans. Recently, high-resolution neurosonography (HRNS) and magnetic resonance neurography have gained significant importance in peripheral nerve imaging. The use of the grey-scale-based "fascicular ratio" (FR) was established using both modalities allowing for quantitative assessment.

Analysis of regeneration- and myelination-associated proteins in human neuroma in continuity and discontinuity.

Background: Neuromas are pathologic nerve distensions caused by a nerve's response to trauma, resulting in a dysfunctional to non-functional nerve. Depending on the severance of the affected nerve, the resulting neuroma can be differentiated into continuous and stump neuroma. While neuroma formation has been investigated in animal models with enormous regenerative capacity, the search for differences in human response to nerve trauma on a molecular level ultimately seeks to identify reasons for functionally successful versus unsuccessful regeneration after peripheral nerve trauma in man.

Validation of connectivity-based thalamic segmentation with direct electrophysiologic recordings from human sensory thalamus.

Connectivity-based segmentation has been used to identify functional gray matter subregions that are not discernable on conventional magnetic resonance imaging. However, the accuracy and reliability of this technique has only been validated using indirect means. In order to provide direct electrophysiologic validation of connectivity-based thalamic segmentations within human subjects, we assess the correlation of atlas-based thalamic anatomy, connectivity-based thalamic maps, and somatosensory evoked thalamic potentials in two adults with medication-refractory epilepsy who were undergoing intracranial EEG monitoring with intrathalamic depth and subdural cortical strip electrodes.

MLL fusion partners AF4 and AF9 interact at subnuclear foci.

The MLL gene is involved in translocations associated with both acute lymphoblastic and acute myelogenous leukemia. These translocations fuse MLL with one of over 30 partner genes. Collectively, the MLL partner genes do not share a common structural motif or biochemical function.

cDNA microarray analysis of macroregenerative and dysplastic nodules in end-stage hepatitis C virus-induced cirrhosis.

Hepatocellular carcinoma is a common malignancy causing significant morbidity and mortality worldwide. In this study we use expression microarray technology to identify novel genes that consistently displayed altered expression levels in the earliest identifiable precursors to hepatocellular carcinoma, dysplastic and macroregenerative nodules. The gene expression profiles from nine patients with end-stage hepatitis C cirrhosis that contained a combined 11 dysplastic or macroregenerative nodules were compared to the patient's matched cirrhotic liver tissue.

Identification of chromosomal translocations in leukemias by hybridization with oligonucleotide microarrays.

Background And Objectives: Identification of chromosomal rearrangements is important for a precise risk-stratified diagnosis of hematologic malignancies. As the number of known translocations, specific for different types of leukemia increases, it takes ever more time and increasing amounts of patient's material to screen a single patient with individual polymerase chain reactions (PCR). The aim of this study was to develop a new approach combining specificity with high-throughput sufficient for rapid screening of clinical samples for the presence of numerous translocations.

Current practice in administration and clinical criteria of emergent EEG.

Policies of administration and availability of EEG offered during nonbusiness hours vary widely among EEG laboratories. The authors surveyed medical directors of accredited EEG laboratories (n = 84) to determine the ranges of availability and clinical indications for approval of continuously available emergent EEG (E-EEG). Of 46 respondents, 37 (80%) offered E-EEG.

The clinical and pathologic implications of plasmacytic infiltrates in percutaneous renal allograft biopsies.

Plasmacytic infiltrates in renal allograft biopsies are uncommon and morphologically distinctive lesions that may represent variants of acute rejection. This study sought significant clinical and pathologic determinants that might have influenced development of these lesions and assessed their prognostic significance. Renal allograft biopsies (n = 19), from 19 patients, with tubulointerstitial inflammatory infiltrates containing abundant plasma cells, composing 32 +/- 8% of the infiltrating mononuclear cells, were classified using Banff '97 criteria.

Cloning and sequence analysis of four t(9;11) therapy-related leukemia breakpoints.

The t(9;11)(p22;q23) is the most common chromosomal translocation in topoisomerase II inhibitor therapy-related acute myeloid leukemia (tAML). This translocation fuses the MLL and AF9 proto-oncogenes producing a novel chimeric protein. In order to gain insight into the mechanism generating the t(9;11) and to clarify the role topoisomerase II inhibition may play in that mechanism we have cloned and sequenced the breakpoints from four tAML patients with the t(9;11).

Expression of lymphomagenic oncogenes in T-cell lymphomas of HPV 16 transgenic mice.

We have previously established that a dimer repeat of the complete HPV 16 genome is sufficient to cause multiple organ malignancies, either carcinomas or T-cell lymphomas, in transgenic mice. Here, we report the expression of oncogenes supporting the notion that these tumors arose via multiple oncogenic pathways. In these mice, the transgenic HPV 16 genome cosegregated with the tumor phenotype.

Pseudo-Gaucher histiocytes identified up to 1 year after transplantation for CML are BCR/ABL-positive.

The results of polymerase chain reaction (PCR) analysis after transplantation for chronic myelogenous leukemia (CML) are difficult to interpret clinically. Positive findings for BCR/ABL can be seen not only in patients who go on to relapse but also in patients who, after years of follow-up, remain in complete remission. The cause for the lack of concordance between PCR findings and relapse is not clear.

BCL-2 expression correlates with lower proliferative activity in the intermediate- and high-grade non-Hodgkin's lymphomas: an Eastern Cooperative Oncology Group and Southwest Oncology Group cooperative laboratory study.

An inverse relationship between BCL-2 expression and cell cycle transition has been suggested by recent studies in murine models. To investigate the clinical relevance of these laboratory studies, a group of 116 paraffin-embedded non-Hodgkin's lymphoma (NHL) biopsy specimens (Working Formulation Groups D-H, and J) from a cooperative group study of cellular DNA content were analyzed for the 14;18 translocation using polymerase chain reaction (PCR)-based methods and, if sufficient tissue remained, for BCL-2 and BAX expression by immunohistochemistry. The results of these studies were then compared with the results of the previously performed flow cytometric analysis of ploidy and proliferative activity (S-phase-fraction).

Cloning and developmental expression of the murine homolog of the acute leukemia proto-oncogene AF4.

AF4 is the 4q21 gene involved in the acute lymphoblastic leukemia associated t(4;11)(q21;q23) where it forms a fusion gene with MLL. In order to gain insight into AF4's role in leukemogenesis we have studied its functional domains and expression pattern during murine development. We have cloned the murine homolog, Af4.

Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and identification of topoisomerase II consensus-binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11).

Rearrangements of the MLL (Mixed Lineage Leukemia) gene in the human 11q23 cytogenetic locus have been detected in secondary (therapy-related) acute leukemias in patients who have received topoisomerase II inhibitors for prior, independent neoplasms. The topoisomerase II inhibitors implicated in MLL/11q23 secondary leukemias all inhibit the religation step of reaction catalyzed by topoisomerase II. This results in the stabilization of a 'cleavable complex' with double-strand DNA breaks at the point of topoisomerase II binding.

Guanine-rich (GGNNGG) elements at chromosomal breakpoints interact with a loop-forming, single-stranded DNA-binding protein.

Proto-oncogene-activation is frequently preceded by chromosomal translocations. Several models suggest that DNA single-strands and loops may serve as intermediates in the process of illegitimate recombination. Guanine-rich, repetitive elements are preferred sites of chromosomal exchange and can undergo conformational changes which result in the generation of single-stranded DNA.

The der(11)-encoded MLL/AF-4 fusion transcript is consistently detected in t(4;11)(q21;q23)-containing acute lymphoblastic leukemia.

The t(4;11)(q21;q23) is the most common translocation involving band 11q23 and is found predominantly in acute lymphoblastic leukemias (ALLs) of infants. Recent studies have shown that this translocation involves the MLL gene on chromosome 11 and the AF-4 gene on chromosome 4. Using oligonucleotide primers derived from these genes, we established reverse transcription-polymerase chain reaction (RT-PCR) assays for the detection of the fusion transcripts from both the der(11) and der(4) chromosomes.