Expression and inducibility of cytoprotective heat shock proteins in the bone marrow of patients with myelodysplastic syndrome: correlation with disease progression

We determined the intracellular expression and inducibility of heat shock proteins (Hsps) 72, 73 and 27 in the bone marrow of patients with myelodysplastic syndrome (MDS) and controls. Hsps were overexpressed in MDS marrow especially in advanced disease, providing resistance to induction of apoptosis. These data suggest that Hsps could be implicated in the progression of MDS to acute myeloid leukemia.     

Psychotic (delusional) depression and completed suicide: a systematic review and meta-analysis

Background

It remains unclear whether psychotic features increase the risk of completed suicides in unipolar depression. The present systematic review coupled with a meta-analysis attempts to elucidate whether unipolar psychotic major depression (PMD) compared to non-PMD presents higher rates of suicides.

Methods

A systematic search was conducted in Scopus, PubMed, and “gray literature” for all studies providing data on completed suicides in PMD compared to non-PMD, and the findings were then subjected to meta-analysis. All articles were independently extracted by two authors using predefined data fields.

Results

Nine studies with 33,873 patients, among them 828 suicides, met our inclusion criteria. PMD compared to non-PMD presented a higher lifetime risk of completed suicides with fixed-effect pooled OR 1.21 (95% CI 1.04–1.40). In a sub-analysis excluding a very large study (weight?=?86.62%), and comparing 681 PMD to 2106 non-PMD patients, an even higher pooled OR was found [fixed-effect OR 1.69 (95% CI 1.16–2.45)]. Our meta-analysis may provide evidence that the presence of psychosis increases the risk of suicide in patients suffering from severe depression. The data are inconclusive on the contribution of age, mood congruence, comorbidity, and suicide method on PMD’s suicide risk. The lack of accurate diagnosis at the time of suicide, PMD’s diagnostic instability, and the use of ICD-10 criteria constitute the main study limitations.

Conclusions

The presence of psychosis in major depression should alert clinicians for the increased risk of completed suicide. Thus, the implementation of an effective treatment both for psychotic depression and patients’ suicidality constitutes a supreme priority.

     

Impaired clonogenic growth of myelodysplastic bone marrow progenitors in vitro is irrelevant to their apoptotic state

Excessive intramedullary apoptosis has been considered to account for the paradox of hypercellular marrow and refractory cytopenias in myelodysplastic syndrome (MDS). However, a causative relationship of apoptosis to the progenitor's defective clonogenic growth has not been sufficiently demonstrated. We investigated the degree of apoptosis and its contribution to ineffective hematopoiesis in MDS, by assessing the differential clonogenic capacity of purified "apoptotic" and "non-apoptotic" bone marrow progenitors in a short-term semisolid culture system. Although increased apoptosis was indeed detected in MDS bone marrow progenitors, there was no correlation between the existence of apoptosis and culture performance. Non-apoptotic as well as apoptotic CD34+ cells gave similar patterns of growth, both defective compared to normal. The ability of "apoptotic" CD34+ cells to proceed in colony formation as well as the abnormal growth of "non-apoptotic" progenitors are probably pointing towards the need to reconsider the role of apoptosis in the defective clonogenicity of MDS.     

Long-term survival of patients with advanced colorectal cancer may not be due to the response to chemotherapy

Our primary objective was to determine the median and overall survival and secondarily the response rate to first- and second-line chemotherapy of patients with advanced colorectal metastatic disease. Three-hundred and seventy-nine patients (median age 60 years, range 30-87 years) were enrolled from April 1993 to March 2000. Median follow-up was 6 years (range 3-10 years), until July 2003. All patients were evaluable for survival and 342 were evaluable for response and toxicity. Thirty-seven patients did not undergo chemotherapy. All patients had confirmed histology as well as metastatic disease based on radiological tests. First-line treatment was administered to 342 patients: leucovorin (LV) 30 mg/m2 and 5-fluorouracil (5-FU) 425 mg/m2. Three different combinations were given as second-line treatment during different chronological periods: i) 5-FU, mitomycin-C and doxorubicin (FAM); ii) 5-FU and cisplatin (CDDP) and iii) 5-FU, LV and irinotecan (CPT-II). Responses were observed as follows: first-line treatment 16.37%, after FAM 25%, following 5-FU-CDDP 26.83% and after 5-FU-LV-CPT-II, 30.61%. Survival of all patients was as follows: median 25 months (range 16.1-33.9 months). The longest survival was of patients on 5-FU-LV-CPT-II. Median survival of patients with stable disease was 19 months and of untreated patients 12 months. Patients with advanced colorectal cancer have a long median (25 months) and overall survival, despite low responsiveness to chemotherapy.     

The recombinant subdomain IIIB of human serum albumin displays activity of gonadotrophin surge-attenuating factor

BACKGROUND: Gonadotrophin surge-attenuating factor (GnSAF) is an as yet unidentified ovarian factor that acts on the pituitary to attenuate the pre-ovulatory LH surge. In a previous study, GnSAF bioactivity was proposed to derive, at least in part, from a C-terminal domain (95peptide) of human serum albumin (HSA). METHODS AND RESULTS: We employ here the expression-secretion system of Pichia pastoris to produce and assay selected recombinant polypeptides of HSA for GnSAF activity. We show that the C-terminal 95peptide of HSA (residues 490-585; subdomain IIIB) can be expressed from P.pastoris in secreted form and supernatants from clones expressing this polypeptide reduce the GnRH-induced LH secretion of primary rat pituitary cultures by 50-82%. When expressed in the same system, HSA domain III (residues 381-585) or full-length HSA (residues 1-585) are inactive. The bioactive subdomain IIIB is also separable from either domain III or full-length HSA on Blue Sepharose chromatography. CONCLUSIONS: Taken together, the findings highlight the putative importance of HSA subdomain IIIB as a GnSAF-bioactive entity and introduce a unique experimental tool to engineer this molecule for structure-function analysis.     

Reproducibility of pixel‐by‐pixel analysis of Heidelberg retinal flowmetry images: the Thessaloniki Eye Study

Purpose: To identify the investigator effect in the analysis results of Heidelberg retinal flowmetry (HRF) images when pixel‐by‐pixel analysis is performed. Methods: Thirty‐two of 732 HRF images were randomly selected from a population‐based study. Pixel‐by‐pixel analysis was performed by two trained masked graders in the following way: a square window of 40 × 40 pixels or two windows of 30 × 30 pixels or four windows of 20 × 20 pixels free from blood vessels at the peripapillary retina were identified. Using a 1 × 1‐pixel window, the grader performed pointwise analysis according to a specific protocol. The analysis process was performed by each observer three times (A, B, C) at 1‐week intervals. The percentage of pixels with < 1 arbitrary unit of flow (zero flow), the 10th, 25th, 50th, 75th and 90th percentiles and mean flow values were calculated. The difference between the results of analyses B?A and C?A for all HRF parameters was estimated using the Wilcoxon signed rank test. Mixed‐effect regression models were also used after controlling for grader effect and correlation within subjects. Results: There was no statistically significant difference between the results of analyses B?A and C?A or for any parameter in the mixed‐effect regression models. Intraclass correlation was 0.9665 for the percentage of zero flow pixels. Conclusions: Pixel‐by‐pixel analysis of HRF images by trained graders remains a highly reproducible method. No grader effect was found. If a precise protocol is followed, the results are independent of the exact placement of the analysis windows and the pointwise analysis of the identified and mapped retinal tissue.     

Highly increased CSF tau protein and decreased β-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease?

The aim was to quantify tau protein and beta-amyloid (Abeta42) in the CSF of patients with sporadic Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), and controls. Double sandwich enzyme linked immunosorbent assays (ELISAs) were used for measurements. Tau was increased 58-fold in CJD and 3.5-fold in AD compared with controls, whereas Abeta42 was decreased 0.5-fold in both CJD and AD. A cut off level for tau protein at 2131 pg/ml successfully discriminated CJD from AD (100% specificity and 93% sensitivity). Tau protein concentration in CSF is probably an additional useful marker in differentiating CJD from AD.     

Diabetic neuropathy: comparison between Bangladeshi immigrants and Greek‐born subjects

The aim of this study was to compare Bangladeshi immigrants with diabetes to native Greeks with diabetes and to distinguish the different risk factors for polyneuropathy (PN) in the two ethnic groups. Subjects were recruited from the outpatient diabetic clinic of a general hospital. A total of 111 Bangladeshi immigrants (97 men and 14 women of mean age 47 years) and 101 native Greeks (82 men and 19 women of mean age 49 years) were included in the study. Sex, mean age, age at diabetes diagnosis, and diabetes duration did not differ between the two groups. PN was diagnosed in 53 (48%) Bangladeshi and in 59 (58%) Greek patients (p = 0.12). Large fiber neuropathy was less prevalent among Bangladeshis (18%) than in Greeks (53%) (p < 0.01). Small fiber neuropathy on the contrary were more frequent in Bangladeshis (18% vs. 7%) (p < 0.02). Regarding the risk factors for PN, Greek patients were taller, with higher BMI, and smoked more cigarettes (p < 0.001). They were also treated with more anti‐lipid and antihypertensive agents. The higher percentage of SFN in Bangladeshi was mainly a result of the significantly greater incidence of erectile dysfunction (ED) in their group (68 Bangladeshi vs. 38 Greek men). It is well known that there are many causes of ED aside from SFN which were not evaluated in this study. Thus this conclusion should be taken with caution.     

Test of Everyday Attention for Children (TEA-Ch): Greek Normative Data and Discriminative Validity for Children with Combined Type of Attention Deficit-Hyperactivity Disorder

We examined the utility of the Test of Everyday Attention for Children (TEA-Ch) for Greek children. Discrete and regression-based norms, controlling for demographic characteristics and intelligence, were derived from the performance of 172 children. We also assessed the ability of the TEA-Ch to differentiate children with ADHD-Combined Type (ADHD-C) from healthy matched peers. Children with ADHD-C displayed dysfunction in multiple attentional domains. Discriminant function analysis indicated that two subtests (Sky Search and Walk, Don’t Walk) correctly classified 84.2% of children with ADHD-C.