Cytogenetic,spectral karyotyping,fluorescence in situ hybridization,and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions,and MYC and MLL amplification

Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML.     

Effect of a brief cognitive training programme in patients with long-lasting back pain evaluated as unfit for surgery

The aim of the study was to evaluate the effect of cognitive intervention (information and physical exercise), on patients with long-lasting back pain referred for surgical evaluation at an orthopaedic hospital, but evaluated as unfit for surgery. One hundred and fifty-two patients were randomized to a five days intervention or control. The intervention had no significant effects on pain. At three-month follow-up, the patients in the intervention group used significantly more active strategies to cope with the back pain compared to the control group. This effect seemed to increase over time, being more pronounced at one-year follow-up evaluation.     

Characteristics of older adults referred to a psychiatric emergency outreach service

Although older adults typically underutilize mental health services, problems associated with dementing illnesses, chronic medical illnesses, affective disorders, social isolation, and multiple medication use, among other phenomena, have increased referrals of the elderly to psychiatric emergency services. The present study reviewed characteristics of elderly adults referred to a psychiatric emergency outreach/screening service. Of all individuals for whom a referral was made, 24% were aged 60 or older. Among those older adults referred, 63% were seen by screening service personnel; 37% did not meet screening criteria or voluntarily sought mental health services. Diagnoses of individuals evaluated included dementia (27%), affective disorders (27%), schizophrenia (16%), psychosis (12%), alcohol abuse (7), and diagnosis deferred (11%). Findings highlight the limited options available for mental health care of the aged.     

TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer.

PURPOSE: Recent studies have found an association between certain TP53 mutations and resistance to anthracycline-based primary medical therapy in breast cancer. The purpose of this study was to investigate whether TP53 mutational status also might influence the response to a non-anthracycline-containing regimen in primary breast cancer. EXPERIMENTAL DESIGN: Thirty-five patients with locally advanced breast cancer were investigated for TP53 mutations before receiving combination chemotherapy with 5-fluorouracil (1000 mg/m(2) on days 1 and 2) and mitomycin (6 mg/m(2) on day 2), administered every 3 weeks for 2-10 cycles in the neoadjuvant setting. RESULTS: Mutations in the TP53 gene, in particular those affecting loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (i.e., increase in the diameter product of tumor lesion by >/=25%; P = 0.177 for all mutations and P = 0.006 for those affecting L2/L3 domains, respectively). No statistically significant correlation between TP53 LOH and response to therapy was seen. CONCLUSION: This study revealed a significant association between lack of response to 5-fluorouracil and mitomycin and mutations affecting the L2/L3 domains of the p53 protein. Together with our previous finding that such mutations predict resistance to weekly doxorubicin, our data suggest that mutations affecting this particular domain of the p53 protein may cause resistance to several different cytotoxic compounds applied in breast cancer treatment.     

Molecular Regulation of Cell Death and Therapeutic Strategies for Cell Death Induction in Prostate Carcinoma

Many of the common molecular alterations associated with prostate cancer progression involve genes known to regulate cell death susceptibility. The significance of these molecular events is discussed in the context of developing and implementing new strategies designed to restore cell death susceptibility in prostate cancer cells and overcome therapeutic resistance.     

Patient perspective in outcome assessments--perceptions or something more?

Health status measures constitute an essential part of outcome assessments in patients with rheumatic diseases. Currently used health status measures typically assess patient perceptions within various dimensions of health. The issue of widening patient perspective in outcome assessments was raised at OMERACT 2000 and further activities were initiated at the subsequent American College of Rheumatology meetings. Measuring patient perceptions of health is considered the standard approach in clinical practice, controlled clinical trials, and longitudinal observation studies, as well as in other types of epidemiological research. However, the traditionally used instruments also have limitations based on the relevance of the questionnaire items, sensitivity to change in longitudinal observational studies, and intraindividual variations over time. Patient priorities or preferences for improvement in health may be an alternative for the assessment of important patient outcomes. Data support that patient priorities for improvement in health are associated with their perception, but that overlap is incomplete and that complimentary information may be achieved. Expectations about future health and satisfaction with health may also represent alternative approaches. Thus, an open research agenda is required for the future, including different approaches regarding both endpoints and methodological issues.     

Disease-stabilizing treatment with all-trans retinoic acid and valproic acid in acute myeloid leukemia: serum hsp70 and hsp90 levels and serum cytokine profiles are determined by the disease, patient age, and anti-leukemic treatment

Heat shock protein (HSP) 70 and HSP90 are released by primary human acute myeloid leukemia (AML) cells during stress-induced spontaneous in vitro apoptosis. The AML cells also show constitutive release of several cytokines and the systemic serum levels of several soluble mediators are altered in patients with untreated AML. In the present study, we have investigated serum levels of HSP70/HSP90 and the serum cytokine profiles of patients with untreated AML and patients receiving AML-stabilizing palliative treatment based on all-trans retinoic acid (ATRA) plus valproic acid. Patients with untreated AML showed increased HSP90 levels and a distinct serum cytokine profile when compared with healthy controls, and low pre-therapy HSP90 levels were associated with a prolonged survival during treatment with ATRA + valproic acid + theophyllin. Hierarchical cluster analysis showed a close association between HSP70, HSP90, IL-1 receptor antagonist (IL-1ra), and hepatocyte growth factor (HGF) levels. Furthermore, disease-stabilizing therapy altered the serum-cytokine profile, but the correlations between HSP70/HSP90/IL-1ra/HGF were maintained only when ATRA + valproic acid were combined with theophyllin but not when combined with cytarabine. We conclude that both HSP levels and serum cytokine profiles are altered and may represent possible therapeutic targets or prognostic markers in human AML.     

Dichotic listening performance predicts language comprehension

Dichotic listening performance is considered a reliable and valid procedure for the assessment of language lateralisation in the brain. However, the documentation of a relationship between language functions and dichotic listening performance is sparse, although it is accepted that dichotic listening measures language perception. In particular, language comprehension should show close correspondence to perception of language stimuli. In the present study, we tested samples of reading-impaired and normally achieving children between 10 and 13 years of age with tests of reading skills, language comprehension, and dichotic listening to consonant-vowel (CV) syllables. A high correlation between the language scores and the dichotic listening performance was expected. However, since the left ear score is believed to be an error when assessing language laterality, covariation was expected for the right ear scores only. In addition, directing attention to one ear input was believed to reduce the influence of random factors, and thus show a more concise estimate of left hemisphere language capacity. Thus, a stronger correlation between language comprehension skills and the dichotic listening performance when attending to the right ear was expected. The analyses yielded a positive correlation between the right ear score in DL and language comprehension, an effect that was stronger when attending to the right ear. The present results confirm the assumption that dichotic listening with CV syllables measures an aspect of language perception and language skills that is related to general language comprehension.     

Symptoms and lifetime treatment experiences in psychotic patients with and without substance abuse

The main objective of this study was to compare symptom load and lifetime treatment experiences between psychotic patients with substance abuse problems and psychotic patients without substance abuse problems. This is a cross-sectional study of 48 patients (26 inpatients and 22 outpatients) in a clinic for early intervention in psychosis. Patients’ were grouped into two categories based on whether they had a substance abuse problem or not. Twenty-one (43.8%) had a substance abuse problem and 27 (56.2%) had not. We used the Positive and Negative Symptom Scale (PANSS) scale to measure symptoms and several scales to measure substance abuse. Parametric tests (independent t-tests) were used to compare continuous variables, and chi-square tests were used to compare frequencies. Positive symptoms, negative symptoms, general psychopathology symptoms and the total score of psychotic symptoms did not differ significantly between the groups with psychosis alone and psychosis with substance abuse. The delusion subscore was significantly higher in the group with psychosis alone (t=?2.3, df=41, P<0.05), and the anxiety subscore was significantly higher in the group with psychosis with substance abuse (t=?2.3, df=41, P<0.05). There were no significant differences in the subscores for negative symptoms. The absence of differences in psychotic symptoms between the two groups with psychosis does not imply a strong relationship between psychotic symptoms and substance abuse. These results do not support the self-medication hypothesis. The higher rates of institutionalization among substance abusers may be explained by mechanisms other than exacerbations of psychotic symptoms, as there are few differences in symptoms among abusers and non-abusers.