ABSTRACT
The transcriptome has considerable potential for improving biopsy diagnoses. However, to realize this potential the relationship between the molecular phenotype of disease and histopathology must be established. We assessed 186 consecutive clinically indicated kidney transplant biopsies using microarrays, and built a classifier to distinguish rejection from nonrejection using predictive analysis of microarrays (PAM). Most genes selected by PAM were interferon-gamma-inducible or cytotoxic T-cell associated, for example, CXCL9, CXCL11, GBP1 and INDO. We then compared the PAM diagnoses to those from histopathology, which are based on the Banff diagnostic criteria. Disagreement occurred in approximately 20% of diagnoses, principally because of idiosyncratic limitations in the histopathology scoring system. The problematic diagnosis of 'borderline rejection' was resolved by PAM into two distinct classes, rejection and nonrejection. The diagnostic discrepancies between Banff and PAM in these cases were largely due to the Banff system's requirement for a tubulitis threshold in defining rejection. By examining the discrepancies between gene expression and histopathology, we provide external validation of the main features of the histopathology diagnostic criteria (the Banff consensus system), recommend improvements and outline a pathway for introducing molecular measurements.
Subject(s)
Graft Rejection/diagnosis , Kidney Transplantation/pathology , Kidney/metabolism , Kidney/pathology , Oligonucleotide Array Sequence Analysis/methods , Biopsy , Chemokine CXCL11/genetics , Chemokine CXCL11/metabolism , Chemokine CXCL9/genetics , Chemokine CXCL9/metabolism , Female , GTP-Binding Proteins/genetics , GTP-Binding Proteins/metabolism , Graft Rejection/metabolism , Graft Rejection/pathology , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Male , Phenotype , Predictive Value of Tests , Retrospective Studies , Sensitivity and SpecificityABSTRACT
A number of side effects occurring during IFN therapy have been described. Psychiatric side effects include cognitive, behavioural and affective changes, confusion and, less commonly, psychotic symptoms. We report the case of a 52-year-old patient who had been treated for almost three years with IFN alpha for a chronic myelogenous leukemia and who presented an acute confusional episode with delusions, following the reintroduction of IFN alpha after a therapy suspension of 2 weeks. Clinical improvement occurred quite rapidly after cessation of the IFN treatment; this evolution and the normality of the biological tests, EEG and cerebral imagery suggest a causal relationship between this treatment and the psychiatric symptoms.
Subject(s)
Confusion/drug therapy , Delusions/drug therapy , Immunologic Factors/therapeutic use , Interferon-alpha/therapeutic use , Humans , Immunologic Factors/adverse effects , Interferon-alpha/adverse effects , Male , Middle AgedABSTRACT
We present a modular concept of a cognitive training relevant to the demands of everyday life of community dwelling older adults. The concept has three major advantages. First, it takes into account the current performance levels and needs of the trainees. Second, the training is economical in aiming at selecting the most effective training elements. Third, the concept allows the evaluation of single elements of the training. The application of this concept points at the importance of training content being relevant to trainees' everyday lives. Results indicate that training effectiveness depends on the starting level of performance and the cognitive domain being trained. Overall, the results demonstrate the possibility to maximize training gains of older adults by designing adequate trainings for well-defined subgroups of normal older adults.
Subject(s)
Behavior Therapy , Dementia/rehabilitation , Mental Recall , Retention, Psychology , Activities of Daily Living/psychology , Aged , Aged, 80 and over , Behavior Therapy/economics , Cost-Benefit Analysis , Dementia/economics , Dementia/psychology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Transfer, Psychology , Treatment Outcome , Verbal LearningABSTRACT
Thousands of adolescents use neuroleptic drugs over extended periods of time for a wide range of mental disorders. One of the most severe adverse effects of neuroleptic drugs is tardive dyskinesia (TD), for which no successful treatment is currently available. Clozapine is a known atypical neuroleptic drug with few extrapyramidal side effects. It has been suggested that clozapine may be beneficial for the treatment of tardive dyskinesia in adolescents. However, the efficacy of the drug in adolescents is unknown. This report describes the beneficial effect of clozapine on tardive dyskinesia in two adolescents with schizophrenia.
