Health-related quality of life among patients with major depression

The study compared health-related quality of life in 165 patients with major depression and 165 randomly selected and with age- and gender-matched controls from a population sample. Health-related quality of life was measured with the self-report questionnaire (RAND-36), which consists of eight dimensions. Overall, perceived quality of life was broadly reduced among depressive outpatients, and as compared with the control group, significant impairment was observed for all eight dimensions of health-related quality of life. Accompanying somatic diseases causing disability had no additional impact on the reduction of quality of life in depressive patients. Depression per se impairs an individual's functioning ability in a number of ways. It has a significant effect not only on mental well-being but also on perceived physical functioning and bodily pain, and even on general health perceptions. Major depression seems to explain the broad decline in the quality of life among depressive patients.     

Autologous stem cell transplantation in patients with mantle cell lymphoma

High-dose therapy followed by autologous stem cell transplantation (ASCT) has been considered a potential treatment approach in order to improve the poor prognosis in mantle cell lymphoma (MCL), but its role has not yet been clearly established. We analyzed retrospectively the outcome and prognostic factors in 48 consecutive patients with MCL scheduled for ASCT in five transplant centers. In 14 patients (29%), a sufficient amount of stem cells could not be collected. Mobilization failure was associated with female sex, blastoid cytology, and low hemoglobin level. Altogether 35 patients underwent ASCT, 24 patients as part of the first-line treatment and 11 patients later. After transplantation 28 patients (80%) remained in or achieved remission. Two patients died of transplant-related complications. During the median follow-up time of 38 months, nine patients have relapsed. The median event-free survival (EFS) was 39 months. Age over 60 years and elevated C-reactive protein level at diagnosis were associated with poorer outcome after transelantation. ASCT is an effective treatment in MCL with a high response rate and a longer survival than seen in conventionally treated patients. However, no plateau was seen in the EFS curve after ASCT. Whether cure Can be achieved in a proportion of patients with ASCT is currently unknown and should be studied in larger patient series with a longer follow-up.     

Evaluation of cocktail approach to standardise Caco-2 permeability experiments.

The purpose of this study was to investigate the suitability and reliability of n-in-one approach using FDA suggested compounds for standardising Caco-2 permeability experiments. Special attention was paid to the evaluation of rank order correlation and mechanistic insights of compound permeability. Transport studies with antipyrine, metoprolol, ketoprofen, verapamil, hydrochlorothiazide, ranitidine, mannitol and fluorescein were performed in 12- and 24-well formats, as single compounds and in cocktails under iso-pH 7.4 and pH-gradient (pH 5.5 vs. 7.4) conditions. Compounds were quantified using n-in-one LC/MS/MS analysis. The cocktail-dosing proved to be a feasible method to determine the permeability of the Caco-2 cell line and to introduce external standards for permeability tests. Even though sink conditions were lost in cocktail experiments for highly permeable compounds, the rank order of compound permeability and the classification to low and high permeability compounds remained unchanged between single and cocktail studies and permeability values of 12- and 24-well formats were directly comparable. Under pH-gradient conditions the margin between high and low permeability compounds was narrower due to the lower permeability (higher fraction of ionisation) of basic molecules. Of the compounds studied, antipyrine, metoprolol, hydrochlorothiazide and mannitol are suitable for evaluation and standardisation purposes of passive permeability, while fluorescein would function as paracellular marker under iso-pH 7.4. As efflux activity may vary between cell batches, verapamil is a useful marker for P-glycoprotein.     

Analysis of gene and protein expression in healthy and carious tooth pulp with cDNA microarray and two-dimensional gel electrophoresis

Complementary DNA (cDNA) microarray and two-dimensional (2-D) gel electrophoresis, combined with mass spectrometry, enable simultaneous analysis of expression patterns of thousands of genes, but their use in pulp biology has been limited. Here we compared gene and protein expression of pulp tissues from sound and carious human teeth using cDNA microarray and 2-D gel electrophoresis to evaluate their usefulness in pulp biology research and to identify the genes with changes in carious teeth. The cDNA microarray revealed several differentially expressed genes and genes with a high expression in both tissues. These genes have various functions, e.g. effects on vascular and nerve structures, inflammation, and cell differentiation. Variability between cDNA hybridizations indicates that the overall gene expression pattern may vary significantly between individual teeth. The 2-D gel electrophoresis revealed no change between healthy and diseased tissue. The identification of 96 proteins in the pulp tissue revealed none of the gene products with corresponding high/different mRNA expression in cDNA microarray. Interestingly, we detected also a hypothetical protein (putative nucleoside diphosphate kinase), and present therefore the first evidence for the existence of this protein. Even though the methods reveal potentially important gene expression, they may currently have only limited value in in vivo pulp biology research.     

Increased cerebrospinal fluid A beta38/A beta42 ratio in Alzheimer disease

We quantitated amyloid beta peptide (A beta) 38, A beta40 and A beta42 levels in matched CSF and plasma from Alzheimer disease (AD) patients and controls. CSF A beta38 and A beta40 levels were similar in AD patients and in controls; however, they were higher in controls with APOE upsilon4 allele than those without. CSF A beta42 levels were lower in AD patients than in controls. The CSF A beta38/42 ratio was higher in AD patients than controls, consistent with the previously reported higher A beta40/42 ratio. A beta38, A beta40 and A beta42 levels in plasma were similar in AD patients and in controls and showed no relationship to levels in CSF. Our findings suggest that the increased CSF A beta38/42 ratio found in AD patients is derived entirely from reduction of CSF A beta42 levels.     

Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia

Intracytoplasmic aggregation of alpha-synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson's disease, whereas if this process also occurs in the cortical neurons, it is considered pathognomonic for dementia with Lewy bodies. However, the link between alpha-synuclein incorporation into inclusions, neuronal dysfunction, and clinical symptoms needs to be clarified. Another important issue of the pathogenetic puzzle is to understand where alpha-synuclein pathology begins and how it progresses in the brain. To study this, we collected all cases from autopsy material (N = 904) that had alpha-synuclein pathology in the dorsal motor nucleus of vagus, substantia nigra, and/or basal forebrain nuclei. In this way, our study has a unique design because the selection of material is entirely based on the presence of alpha-synuclein pathology regardless of clinical phenotype. Retrospective clinical assessment then showed that only 32 (30%) of 106 alpha-synuclein-positive cases were diagnosed with a neurodegenerative disorder. The distribution or load of alpha-synuclein pathology did not permit a dependable postmortem diagnosis of extrapyramidal symptoms or cognitive impairment. Some neurologically unimpaired cases had a reasonable burden of alpha-synuclein pathology in both brainstem and cortical areas, suggesting that alpha-synuclein-positive structures are not definite markers of neuronal dysfunction.     

Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers

Alzheimer's disease, the most common cause of dementia, is multifactorial and heterogeneous; its diagnosis remains probable. We postulated that more than one disease mechanism yielded Alzheimer's histopathology, and that subgroups of the disease might be identified by the cerebrospinal fluid (CSF) levels of proteins associated with senile (neuritic) plaques and neurofibrillary tangles. We immunoassayed levels of tau, ubiquitin, and Abeta(1-42) in retrospectively collected CSF samples of 468 clinically diagnosed Alzheimer's disease patients (N = 353) or non-Alzheimer's subjects (N = 115). Latent profile analysis assigned each subject to a cluster based on the levels of these molecular markers. Alzheimer's disease was subdivided into at least five subgroups based on CSF levels of Abeta(1-42), tau, and ubiquitin; each subgroup presented a different clinical profile. These subgroups, which can be identified by CSF analysis, might benefit differently from different therapeutic drugs.     

Interactive skills of infants with their high-risk mothers

In this pilot study, the interactive skills of infants with their high-risk, substance-dependent mothers were explored in residential treatment from pregnancy until the infant was 6 months of age. Fourteen mother-infant pairs were videotaped in feeding and free play situations at 6 months after birth. A comparison, low-risk group consisted of 12 ordinary Finnish mother-infant pairs with minimal clinical risks. The findings show significantly higher levels of dyadic interactive deficiencies among the high-risk mother-infant pairs compared to the low-risk pairs, displayed especially in the feeding situation as lack of mutuality and flat, empty, constricted affective tone of interaction. Also, more interactive deficiencies were found among the high-risk infants compared to the low-risk infants, but the differences were not significant. In this study, this finding might reflect the reduced amount of somatic complications and the benefits of treatment, the impacts of which were not explored. The differences between the high- and low-risk infants were displayed as more withdrawal, depressed mood and avoiding behavior and as less alertness and attentional abilities, robustness and focus on parent's emotional state among the high-risk group.