Political change and course of affective psychoses: Berlin 1989-90

In this study, the political change associated with the fall of the Berlin Wall in November 1989 was examined as a shared life event for the population of West Berlin. Its influence on the course of affective psychoses was studied in 67 patients in long-term treatment. Recurrences from November 1989 to March 1990 were compared with the same period 1 year before. While patients with bipolar affective psychosis did not show a difference in recurrences between the two periods, patients with unipolar depression had a significantly better and those with schizoaffective psychosis a significantly worse course of illness after November 1989 than in the year before.     

Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma PANC02

Summary PANC02 is a ductal adenocarcinoma of the pancreas that is resistant to every known class of clinically active antitumor agent. To study the mechanism(s) underlying the intrinsic drug resistance of this tumor, a mammary adenocarcinoma (CA-755) that also grows in C57/BL mice and is known to be drugsensitive was used for comparison. PANC02 resistance and CA-755 sensitivity to several antitumor agents and to X-ray therapy was confirmed in mice, and PANC02 also demonstrated relative resistance in tissue culture. Relative to Chinese hamster ovary (CHO) and CA-755 cells, PANC02 did not appear to show a higher rate of mutation to drug resistance in culture as based on the 6-thioguanine resistance marker. Although P-glycoprotein characteristic of the multidrug resistance (MDR) phenomenon could be demonstrated at the mRNA level using a sensitive RNAse protection assay, the level of expression found was several orders of magnitude lower than that observed in phenotypic MDR cell lines. Furthermore, quinidine failed to increase the sensitivity of PANC02 cells to Adriamycin under conditions that clearly potentiated the toxicity of the drug to a CHO cell line exhibiting classic MDR traits. The heterogeneity in the distribution of drugs was inferred as being significantly greater in PANC02 versus CA-755 cells in vivo as based on measurements of within-animal, within-tumor variance in the distribution of the marker compounds inulin and antipyrine. Although it may not be the only mechanism involved, this greater intratumor heterogeneity in drug distribution could theoretically play a major role in the intrinsic drug resistance of PANC02 in vivo.Supported by grant CH-458 from the American Cancer Society, by grant CA-28034 from the National Cancer Institute, and in part by Cancer Center Core Support grant, NIH-NCI-CA-16672. Animals were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current United States Department of Agriculture, Department of Health and Human Services, and National Institutes of Health regulations and standards     

Social disability in different mental disorders.

ObjectiveTo assess the social disability of people with different psychiatric disorders.MethodsCross-site survey in five psychiatric hospitals (Dresden, Wrocław, London, Michalovce and Prague). Working-aged patients diagnosed (ICD-10) with schizophrenia and related disorders (F2), affective disorders (F3), anxiety disorders (F4), eating disorders (F5) and personality disorders (F6), were assessed at admission (n = 969) and 3 months after discharge (n = 753) using the Brief Psychiatric Rating Scale and the Groningen Social Disability Schedule. The main outcome measure was Interviewer-rated social disability.ResultsDuring acute episodes patients with personality, eating and schizophrenic disorders functioned less effectively than those with affective or anxiety disorders. After controlling for age and severity of psychopathology, there was no significant effect of the diagnosis (during remission), sex, education and history of disorder on disability. Site, employment and partnership were significant factors for the level of social disability in both measure points.ConclusionSeverity of psychopathological symptoms, not the diagnosis of a mental disorder, was the most significant factor in determining the level of social functioning, particularly during the remission period. Site, employment and partnership appeared as significant factors influencing the level of social disability.     

Molecular pathology of well-differentiated thyroid carcinomas

The newly discovered molecular features of well-differentiated thyroid carcinomas derived from follicular cells are reviewed, within the frame of the 2004 WHO classification of thyroid tumours, under the following headings: “Follicular carcinoma”, “Papillary carcinoma”, “Follicular variant of papillary carcinoma” and “Hürthle cell tumours”. A particular emphasis is put on the meaning of PAX8–PPARγ rearrangements, RAS and BRAF mutations, and deletions and mutations of mitochondrial genes and of nuclear genes encoding for mitochondrial enzymes, for thyroid tumorigenesis.     

Construction and characterization of a live, attenuated aroA deletion mutant of Pseudomonas aeruginosa as a candidate intranasal vaccine

Antibodies to the lipopolysaccharide O antigen of Pseudomonas aeruginosa mediate high-level immunity, but protective epitopes have proven to be poorly immunogenic, while nonprotective or minimally protective O-antigen epitopes often elicit the best immune responses. With the goal of developing a broadly protective P. aeruginosa vaccine, we used a gene replacement system based on the Flp recombinase to construct an unmarked aroA deletion mutant of the P. aeruginosa serogroup O2/O5 strain PAO1. The resultant aroA deletion mutant of PAO1 is designated PAO1 Delta aroA. The aroA deletion was confirmed by both PCR and failure of the mutant to grow on minimal media lacking aromatic amino acids. When evaluated for safety and immunogenicity in mice, PAO1 Delta aroA could be applied either intranasally or intraperitoneally at doses up to 5 x 10(9) CFU per mouse without adverse effects. No dissemination of PAO1 Delta aroA to blood, liver, or spleen was detected after intranasal application, and histological evidence of pneumonia was minimal. Intranasal immunization of mice and rabbits elicited high titers of immunoglobulin G to whole bacterial cells and to heat-stable bacterial antigens of all seven prototypic P. aeruginosa serogroup O2/O5 strains. The mouse antisera mediated potent phagocytic killing of most of the prototypic serogroup O2/O5 strains, while the rabbit antisera mediated phagocytic killing of several serogroup-heterologous strains in addition to killing all O2/O5 strains. This live, attenuated P. aeruginosa strain PAO1 Delta aroA appears to be safe for potential use as an intranasal vaccine and elicits high titers of opsonic antibodies against multiple strains of the P. aeruginosa O2/O5 serogroup.     

Subjective quality of life in female in-patients with depression: a longitudinal study

This study investigated Subjective Quality of Life (SQOL) in 42 women with depression, 70 women with alcoholism, and 73 women with schizophrenia within 3 weeks after hospital admission. Twenty-eight of the depressive patients were re-examined after 6 months. SQOL was assessed using the German version of the Lancashire Quality of Life Profile. On average, depressive women expressed dissatisfaction with life as a whole and with 4 out of 8 life domains, and had a lower SQOL than the other two diagnostic groups. Differences remain statistically significant when the influence of age and anxiety/depression is controlled for. SQOL in depressive women improved significantly within the follow up period. Positive SQOL change was moderately correlated with an improvement of depressive symptoms. The results indicate that depressive women after hospital admission express an unusually low SQOL, which seems to have some diagnostic specificity and improves over time. Changes in depressive symptoms do not fully explain SQOL changes.     

Prediction of hospitalizations by schizophrenia patients' assessment of treatment: an expanded study

This study examines whether schizophrenia patients' global assessment of treatment predicts outcome in community care. Eighty-five patients rated the extent to which their treatment was right for them. The outcome measure was assessed by means of a hospitalization index reflecting the duration of full and partial hospitalization within a follow-up period of 24 months. Patients who dropped out (n = 21) assessed their treatment more negatively than those who remained in the care system during follow-up. Patients with no hospitalization (n = 25) expressed a more negative assessment than patients who were hospitalized in the follow-up period at least once (n = 39). In this latter subgroup, however, patients with a more negative assessment had a longer duration of hospitalization during follow-up, and patients' assessment of treatment was the best single predictor of outcome (r = -0.50, P < 0.01). In a multiple regression analysis, patients' assessment of treatment, the number of previous hospitalizations and the hospitalization index in the two years prior to the interview, together, explained approximately half of the variance of outcome (adjusted R2 = 0.46). The findings underline the relevance of asking patients whether treatment is right for them, although the relationship between patients' assessment of treatment and long-term outcome seems more complex than previous studies suggested.     

Smoothing bandwidth selection for response latency estimation

Stimulus response latency is the delay between stimulus onset and the evoked modulation in neural activity. A common technique to estimate latencies involves binning the spike arrival times to form a peri-stimulus histogram. This histogram is smoothed using a fixed bandwidth. The estimated latency is the first time following stimulus onset in which the smoothed histogram exceeds the midpoint between the minimum and maximum of the smoothed histogram. We demonstrate that the choice of smoothing bandwidth is critical to the accuracy of this latency estimation technique. We suggest a bootstrap resampling technique for bandwidth selection which results in a robust latency estimate.     

Culture at low glucose up-regulates mitochondrial function in pancreatic β cells with accompanying effects on viability

We tested whether exposure of β cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike. An increased release of lactate dehydrogenase that followed exposure to hypoxia was attenuated in rat islets which had been pre-cultured at half standard glucose. In INS-1 cells exposure to half standard glucose attenuated hypoxia-induced effects on several viability parameters (MTT, cell number and incremental apoptotic DNA). Thus culture at reduced glucose of pancreatic islets and clonal β cells leads to mitochondrial adaptions which possibly lessen the negative impact of hypoxia on β cell viability. These findings appear relevant in the search for optimization of pre-transplant conditions in a clinical setting.