Mild hyperhomocysteinemia is associated with a decreased fibrinolytic activity in patients after ST-elevation myocardial infarction

BACKGROUND: Elevated homocysteine (Hcy) levels have been associated with increased risk for cardiovascular disease and it has been shown that hyperhomocysteinemia is associated with increased levels of t-PA antigen in individuals without evidence for coronary artery disease (CAD). The aim of this study was to examine if Hcy plasma levels are associated with plasma levels of fibrinolytic factors in patients with CAD and a history of acute myocardial infarction. METHODS: We measured in 56 patients with CAD, 1 month after their first ST-elevation myocardial infarction, plasma levels of Hcy, the fibrinolytic parameters tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-type-1 (PAI-1), and t-PA-PAI-1 complexes. RESULTS: Hcy plasma levels inversely correlated with t-PA activity (r=-0.303, p<0.05). Patients with mild hyperhomocysteinemia (Hcy>15 micromol/L, n=8) showed significantly lower plasma levels of t-PA activity (p<0.05). Regression analysis revealed that out of cardiovascular risk factors and medical treatment only Hcy was significantly associated with t-PA activity. CONCLUSIONS: Patients with CAD after a first myocardial infarction and hyperhomocysteinemia show a reduced t-PA activity independently from cardiovascular risk factors and medical treatment. Homocysteine lowering therapies may increase fibrinolytic activity and thereby may help to avoid atherothrombotic events in patients with CAD after a first myocardial infarction.     

Differential effects on forelimb grasping behavior induced by fetal dopaminergic grafts in hemiparkinsonian rats

Skilled forelimb movements depend on an intact dopaminergic (DA) neurotransmission and are substantially impaired in the unilateral rat model of Parkinson's disease. It has remained unclear, however, to what extent reaching and grasping movements can be influenced by intrastriatal transplantation of fetal DA neurons. Here an extensive behavioral assessment of skilled forelimb movement patterns in hemiparkinsonian and DA-grafted rats was carried out. Good DA graft survival was accompanied by a compensation of drug-induced rotational asymmetries. Interestingly, skilled forelimb use was significantly improved in transplanted animals as compared to lesion-only animals in the staircase test. Qualitative analysis of single forelimb reaching movement components revealed dissociable patterns of graft effects: while some movement components in grafted animals improved, others remained unchanged or even deteriorated. These findings provide novel insights into the complex interactions of graft-derived restoration of DA neurotransmission and skilled forelimb behavior.     

TNM staging with FDG-PET/CT in patients with primary head and neck cancer

Purpose PET/CT, PET+CT, and CT were compared concerning accuracies in TNM staging and malignancy detection in head and neck cancer. The impact of PET/CT compared to the other imaging modalities on therapy management was assessed. Materials and methods Fifty-five patients with suspected head and neck primary cancer underwent whole-body FDG-PET/CT. PET/CT and PET+CT were evaluated by a nuclear medicine physician and a radiologist; CT was evaluated by two radiologists, PET by two nuclear physicians. Histopathology served as the standard of reference. Differences between the staging modalities were tested for statistical significance by McNemar’s test. Results Overall TNM-staging and T-staging with PET/CT were more accurate than PET+CT and CT alone (p < 0.05). PET/CT was marginally more accurate than CT alone in N-staging (p = 0.04); no statistically significant difference was found when compared to PET+CT for N-staging. PET/CT altered further treatment in 13 patients compared to CT only and in 7 patients compared to PET+CT. Conclusion Combined PET/CT proved to be partly more accurate in assessing the overall TNM-stage than CT and PET+CT. These results were based on a higher accuracy concerning the T-stage, mainly in patients with metallic implants and marginally the N-stage. Therapy decisions have been influenced in a substantial number of patients. PET/CT might be considered as a first line diagnostic tool in patients with suspected primary head and neck cancer.     

Accuracy of psychiatric diagnosis performed under indirect supervision

This work aimed at comparing the accuracy of the psychiatric diagnoses made under indirect supervision to the diagnoses obtained through Structured Clinical Interview for DSM-III-R (SCID). The study was conducted in 3 university services (outpatient, inpatient and emergency). Data from the emergency service were collected 3 years later, after changes in the training process of the medical staff in psychiatric diagnosis. The sensitivity for Major Depression (outpatient 10.0%; inpatients 60.0%, emergency 90.0%) and Schizophrenia (44.4%; 55.0%; 80.0%) improved over time. The reliability was poor in the outpatient service (Kw = 0.18), and at admission to the inpatient service (Kw = 0.38). The diagnosis elaborated in the discharge of the inpatient service (Kw = 0.55) and in the emergency service (Kw = 0.63) was good. Systematic training of supervisors and residents in operational diagnostic criteria increased the accuracy of psychiatric diagnoses elaborated under indirect supervision, although excellent reliability was not achieved.     

Autologous bone marrow transplantation in adult patients with acute lymphoblastic leukemia

Autologous bone marrow transplantation (ABMT) was introduced as a treatment for terminal leukemic relapse more than 40 years ago. For childhood acute lymphoblastic leukemia (ALL) the role of ABMT is well defined. Some studies suggest that it is also beneficial for adult patients with high-risk factors or with relapse. However, these inferences are based on a relatively small number of patients with short follow-up. Nevertheless patients with high-risk ALL are candidates for ABMT if no histocompatible sibling is available. Similarly patients in second or later complete remission (CR) in the absence of a histocompatible donor may derive benefit from ABMT. The different conditioning regimens used by the treatment centers are associated with different toxicities but none has been proven to be superior than others. In the majority of studies the marrow has been purged of leukemic cells, but this maneuver has never been evaluated in a randomized comparative trial. Transplant related mortality rate of ABMT is low compared to allogeneic transplantation. The GvL effect, which is important to eliminate malignant cells in acute and chronic myelocytic leukemia, has not been definitively demonstrated in ALL. The tyrosine-kinase inhibitor STI 571 offers new perspectives for patients with the Phl/bcr/abl translocation. It may be especially useful for treating minimal residual disease (MRD) before and/or after ABMT.     

Dendritic cells cross-presenting viral antigens derived from autologous cells as a sensitive tool for visualization of human cytomegalovirus-reactive CD8+ T cells

BACKGROUND: CD8+ T lymphocytes are essential to contain viral infections, such as human cytomegalovirus (HCMV). To visualize these clinically important effector cells, we used dendritic cells (DC), which efficiently present exogenous antigens by MHC class I molecules (cross-presentation). METHODS AND RESULTS: Immature DC were fed with apoptotic debris derived from autologous HCMV-infected macrophages. After maturation, the antigen-loaded DC were used to stimulate lymphocytes from the same donor. We could detect high numbers of interferon-gamma producing CD8+ T cells in HCMV-seropositive but not in HCMV-seronegative healthy individuals and in only one of five HCMV-seropositive immunosuppressed patients. In contrast, autologous DC infected with live HCMV virions stimulated antiviral CD8+ T lymphocytes to a lesser extent. CONCLUSION: We suggest that DC cross-presenting HCMV antigens derived from autologous macrophages could serve as a valuable tool to monitor and possibly enhance the antiviral T-cell response in patients after transplantation.     

The immunophenotype of 325 adult acute leukemias: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination

Bone marrow cells of 325 adults with acute leukemia were immunophenotyped using a panel of monoclonal antibodies proposed by the European Group for the Immunological Characterization of Leukemias (EGIL). Of these, 97.2% could be assigned clearly to myeloid or lymphoid lineage (254 acute myeloid leukemias [AMLs], 48 B-cell lineage acute lymphoblastic leukemias [ALLs], 14 T-cell lineage ALLs), 1.8% as biphenotypic, and less than 1% as undifferentiated. Immunologic subtyping of ALLs revealed an association between early precursor phenotypes and coexpression of myeloid antigens, particularly CD15/CD65s coexpression and pre-pre-B cell-specific phenotypes and genotypes. The common ALL phenotype was associated with BCR-ABL translocation. Among AMLs, CD2 coexpression was almost exclusively restricted to French-American-British subtypes M3 variant and M4Eo and related molecular aberrations. The most valuable markers to differentiate between myeloperoxidase-negative AML subtypes M0 and ALLs were CD13, CD33, and CD117, typical of M0, and intracytoplasmic CD79a, intracytoplasmic CD3, CD10, and CD2, typical of B cell- or T cell-lineage ALL. Our results confirm excellent practicability of the EGIL proposalfor immunologic classification of acute leukemias. For myeloperoxidase-negative AMLs, we suggest a scoring system based on markers most valuable to distinguish between AML-M0 and ALLs.     

Dietary restriction alters fine motor function in rats

A number of standard behavioral tasks in animal research utilize food rewards for positive reinforcement. In order to enhance the motivation to participate in these tasks, animals are usually placed on a restricted diet. While dietary restriction (DR) has been shown to have beneficial effects on recovery after brain injury, life span and aging processes, it might also represent a stressor. Since stress can influence a broad range of behaviors, the purpose of this study was to assess whether DR may have similar effects on skilled movement. Adult male Long-Evans rats were trained and tested in a skilled reaching task both prior to and during a mild food restriction regimen that maintained their body weights at 90-95% of baseline weight for eight days. The observations revealed that DR decreased reaching success and increased the number of attempts to grasp a single food pellet. The animals appeared to be more frantic when attempting to reach for food pellets, and the time taken to reach for 20 pellets decreased following the onset of DR. A second experiment investigating behaviors that do not require food rewards, including a ladder rung walking task and an open field test, confirmed that rats on DR display deficits in skilled movements and are hyperactive. These findings suggest that results obtained in motor tasks using food rewards need to be interpreted with caution. The findings are discussed with respect to stress associated with DR.