Tetranectin and apolipoprotein A-I in cerebrospinal fluid as potential biomarkers for Parkinson's disease.

OBJECTIVE: The application of biomarkers may potentially improve the efficiency of the diagnosis for Parkinson's disease (PD). However, no reliable biomarker has been identified to date. This study is aimed to identify proteins that might serve as potential biomarkers for PD diagnosis or pathogenesis. MATERIALS AND METHODS: Two-dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), was used to determine the differentially expressed cerebrospinal fluid (CSF) proteins in PD patients (n = 3) compared with normal controls (n = 3). Selected proteins were further confirmed by Western blotting analysis in the CSF of PD patients (n = 8), Alzheimer's disease (AD) patients (n = 6) and normal control subjects (n = 7). RESULTS: Eight proteins were identified after MS and protein database interrogation. In the CSF of PD patients, the expression levels of one isoform of apolipoprotein A-I (apoA-I), tetranectin, myosin phosphatase target subunit 1 (MYPT1), and two unknown proteins were down-regulated, whereas the expression levels of another apoA-I isoform, proapolipoprotein, and lipoprotein were up-regulated. Western blotting indicates that the expression of tetranectin was reduced in the CSF from PD patients and elevated in AD, while the expression of apoA-I was changed only in the CSF from PD patients. CONCLUSION: Our preliminary results suggest that tetranectin and apoA-I may serve as potential biomarkers for PD, though further validation is needed.

Biologic features and treatment outcome of secondary acute lymphoblastic leukemia--a review of 101 cases.

BACKGROUND: Secondary acute lymphoblastic leukemia (sALL) is a rare disease and its biologic features are not well characterized. PATIENTS AND METHODS: We describe a cohort of seven patients and discuss 94 additional cases from the literature for whom biological parameters were described. Cases with incomplete data were excluded. RESULTS: Hodgkin's disease (HD) was more common in the 18-59 age group while breast and prostate cancers were prevalent only in the >or=18-year-old patients. The time interval to develop sALL was similar among all age groups but was significantly longer for HD and neuroblastoma primary diagnoses and sALL with complex karyotype. T-cell immunophenotype was more common in the <18 age group. Complete remission was infrequent in the >or=60 age group. The overall survival was poor for all sALL regardless of age, primary diagnoses, cytogenetic subgroups, or immunophenotype. Allogeneic transplantation most probably represents the only chance of cure. CONCLUSION: Better identification of prognostic factors to prevent the occurrence of sALL is indicated.

Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission: a phase 2 Cancer and Leukemia Group B Study (CALGB 10503).

In this prospective phase 2 clinical trial conducted by Cancer and Leukemia Group B (CALGB, now the Alliance), we studied decitabine as maintenance therapy for younger adults with acute myeloid leukemia (AML) who remained in first complete remission (CR1) following intensive induction and consolidation. Given that decitabine is clinically active in AML and with hypomethylating activity distinct from cytotoxic chemotherapy, we hypothesized that 1 year of maintenance therapy would improve disease-free survival (DFS) for AML patients <60 years, who did not receive allogeneic stem cell transplantation in CR1. After blood count recovery from final consolidation, patients received decitabine at 20 mg/m2 intravenously daily for 4-5 days, every 6 weeks for eight cycles. One hundred and thirty-four patients received decitabine and 85 (63%) had favorable risk AML. The median number of cycles received was 7 (range: 1-8) and the primary reason for discontinuation was relapse. DFS at 1 year and 3 years was 79% and 54%, respectively. These results are similar to the outcomes in the historical control comprising similar patients treated on recent CALGB trials. Thus, maintenance with decitabine provided no benefit overall. Standard use of decitabine maintenance in younger AML patients in CR1 is not warranted. This trial was registered at www.clinicaltrials.gov as NCT00416598.

The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia.

Recurrent chromosomal abnormalities and gene mutations detected at the time of diagnosis of acute myeloid leukemia (AML) are associated with particular disease features, treatment response and survival of AML patients, and are used to denote specific disease entities in the World Health Organization classification of myeloid neoplasms and acute leukemia. However, large studies that integrate cytogenetic and comprehensive mutational information are scarce. We created a comprehensive oncoprint of mutations associated with recurrent cytogenetic findings by combining the information on mutational patterns of 80 cancer- and leukemia-associated genes with cytogenetic findings in 1603 adult patients with de novo AML. We show unique differences in the mutational profiles among major cytogenetic subsets, identify novel associations between recurrent cytogenetic abnormalities and both specific gene mutations and gene functional groups, and reveal differences in cytogenetic and mutational features between patients younger than 60 years and those aged 60 years or older. The identified associations between cytogenetic and molecular genetic data may help guide mutation testing in AML, and result in more focused application of targeted therapy in patients with de novo AML.

The clinical efficacy of neuronavigation-assisted minimally invasive operation on hypertensive basal ganglia hemorrhage.

OBJECTIVE: To explore the therapeutic effect of neuronavigation-assisted minimally invasive operation on hypertensive basal ganglia hemorrhage patients with hematoma volume less than 30 mL. PATIENTS AND METHODS: 25 hypertensive basal ganglia hemorrhage patients with hematoma volume varied from 15 to 30 mL were enrolled. 13 patients were recuited to undertook puncture aspiration and catheter drainage under real-time neuronavigation. The operations were carried out under CT imaging guidance. Twelve patients with conservative treatment were recruited as control. RESULTS: Neuronavigation operation group was superior to the conservative treatment group in terms of hematoma clearance time, duration of hospitalization, 6-month Glasgow coma score (GCS) scores and neurological deficiency scores. CONCLUSIONS: Neuronavigation-assisted minimally invasive operation is suitable for low volume hypertensive basal ganglia hemorrhage and improves the prognosis of these patients significantly.

Acute myeloid leukemia with t(5;18)(q35;q21).

A case of acute myelocytic leukemia with a translocation (5;18)(q35;q21) is reported. Cytogenetic abnormalities of the long arm of chromosome 5 have long been known to affect hematopoiesis. Although translocations between 5q and other chromosomes have been associated with malignancy, this is the first reported case of a t(5;18) resulting in acute myeloid leukemia. Possible molecular mechanisms underlying the pathogenesis of the disease are discussed.

Molecular epidemiology and risk factors for colonization by vancomycin-resistant Enterococcus in patients with hematologic malignancies.

OBJECTIVE: To study the molecular epidemiology of vancomycin-resistant Enterococcus (VRE) colonization and to identify modifiable risk factors among patients with hematologic malignancies. SETTING: A hematology-oncology unit with high prevalence of VRE colonization. PARTICIPANTS: Patients with hematologic malignancies and hematopoietic stem cell transplantation recipients admitted to the hospital. METHODS: Patients underwent weekly surveillance by means of perianal swabs for VRE colonization and, if colonized, were placed in contact isolation. We studied the molecular epidemiology in fecal and blood isolates by pulsed-field gel electrophoresis over a 1-year period. We performed a retrospective case-control study over a 3-year period. Cases were defined as patients colonized by VRE, and controls were defined as patients negative for VRE colonization. Case patients and control patients were matched by admitting service and length of observation time. RESULTS: Molecular genotyping demonstrated the primarily polyclonal nature of VRE isolates. Colonization occurred at a median of 14 days. Colonized patients were characterized by longer hospital admissions. Previous use of ceftazidime was associated with VRE colonization (P < .001), while use of intravenous vancomycin and antibiotics with anaerobic activity did not emerge as a risk factor. There was no association with neutropenia or presence of colonic mucosal disruption, and severity of illness was similar in both groups. CONCLUSION: Molecular studies showed that in the majority of VRE-colonized patients the strains were unique, arguing that VRE acquisition was sporadic rather than resulting from a common source of transmission. Patient-specific factors, including prior antibiotic exposure, rather than breaches in infection control likely predict for risk of fecal VRE colonization.

Cocaine-induced iritis.

The case of a 31-year-old man who presented to the emergency department with iritis from intranasal cocaine use is described. This was the second episode of iritis in this patient after casual cocaine use. The differential diagnosis of iritis and a proposed pathophysiologic mechanism are discussed.

Correlation of end-tidal CO2 measurements to arterial PaCO2 in nonintubated patients.

STUDY OBJECTIVE: To determine the accuracy of end-tidal carbon dioxide levels as a measure of arterial carbon dioxide levels in nonintubated patients presenting to an emergency department for care. DESIGN: A prospective, cross-sectional analysis. SETTING: University hospital ED. TYPE OF PARTICIPANT: Nonintubated adult patients presenting to the ED for care of a variety of problems. INTERVENTIONS: Patients who had arterial blood gas samples taken as part of their ED evaluation were asked to breathe normally through an endotracheal tube adapter or a modified nasal cannula connected to a side port sampling capnometer while a sample for arterial blood gas was drawn from the radial artery. MEASUREMENTS: End-tidal carbon dioxide levels (mm Hg) were recorded at the time of arterial blood gas sampling. The difference between end-tidal carbon dioxide and PaCO2 was tested with the paired t-test at a significance level of .05. The correlation of end-tidal carbon dioxide to PaCO2 was tested in all patients and in subgroups using simple linear regression. RESULTS: Seventy-six patients were enrolled. In all patients, end-tidal carbon dioxide was 3.5 mm Hg lower than PaCO2 and correlated well with PaCO2 (r2 = .772). In patients with hypocapnia, there was no significant difference between end-tidal carbon dioxide and PaCO2 (P = .17), and the correlation of end-tidal carbon dioxide to PaCO2 was stronger (r2 = .838). In patients with a respiratory or metabolic acidosis, the difference between end-tidal carbon dioxide and PaCO2 was 6 mm Hg (P = .005), but end-tidal carbon dioxide correlated well to PaCO2 (r2 = .899). CONCLUSION: Measurements of end-tidal carbon dioxide concentrations correlate well with PaCO2 values in nonintubated patients presenting with a variety of conditions to EDs. End-tidal carbon dioxide measurements may be sufficient measures of PaCO2 in selected patients and obviate the need for repeat arterial blood gas determination. Further study is warranted.

Subtilisin BPN' variants: increased hydrolytic activity on surface-bound substrates via decreased surface activity.

Site-directed mutagenesis and random mutagenesis were used to produce variants of subtilisin BPN' (Bacillus amyloliquefaciens) protease with variable surface adsorption properties. Protease adsorption and peptide hydrolysis rate were measured for these variants using a model substrate consisting of a peptide covalently bound to a surface. While most variants adsorb at a level very similar to that of native BPN', several variants were identified which adsorb either more or less. For surface-bound substrates we report a linear dependence between the concentration of adsorbed protease enzyme and substrate hydrolysis, similar to the linear dependence between enzyme solution concentration and hydrolysis of soluble substrates. On the basis of this knowledge we hypothesized that variants designed to adsorb at a higher level on a surface-bound peptide substrate would hydrolyze that surface-bound substrate faster. Contrary to our original expectations, the variants that adsorb more on the covalently bound peptide surface hydrolyze this substrate slower. In addition, variants of BPN' which adsorb at a lower level than native BPN' hydrolyze the surface-bound substrate faster. Enzyme adsorption and the subsequent peptide hydrolysis are altered by substituting amino acids that modify the surface charge or hydrophobicity of the native enzyme. This effect is most dramatic when the changes were made at surface-exposed sites around the binding pocket/active site of the enzyme. One mechanism that is consistent with the data is based on the relationship between the level of adsorption and the enzyme's affinity for the surface. In this mechanism weakly adsorbed enzymes are postulated to move more rapidly from site to site on the surface, thereby increasing substrate hydrolysis.