Over-representation of specific regions of chromosome 22 in cells from human glioma correlate with resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea

Background  

Glioblastoma multiforme is the most malignant form of brain tumor. Despite treatment including surgical resection, adjuvant chemotherapy, and radiation, these tumors typically recur. The recurrent tumor is often resistant to further therapy with the same agent, suggesting that the surviving cells that repopulate the tumor mass have an intrinsic genetic advantage. We previously demonstrated that cells selected for resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are near-diploid, with over-representation of part or all of chromosomes 7 and 22. While cells from untreated gliomas often have over-representation of chromosome 7, chromosome 22 is typically under-represented.     

The validity of the letter memory test as a measure of memory malingering: robustness to coaching.

The letter memory test (LMT) is a computerized forced-choice test of malingering detection including two face valid difficulty manipulations: increase in target stimulus length and increase of response foils. Prior research suggests the LMT shows promise as a malingering detection measure. In the present study, the utility of the LMT in the identification of malingering was further explored, using a counterbalanced design in a simulated malingering sample. Prior work was extended by assessing the robustness of the LMT to coaching and assessing the effectiveness of an additional scoring method, utilizing the face valid difficulty manipulations. Results were consistent with prior research on the LMT, with the standard cutoff score yielding high indices of accuracy. The LMT showed no order effects and was superior to the 15-item test in accuracy indices. Both the standard LMT score and the proposed score based on difficulty manipulations were relatively robust to coaching. Overall, findings indicate the LMT is a viable contender among measures of memory malingering.     

Impact of a region-wide approach to improving systems for heart attack care: the West Midlands thrombolysis project.

OBJECTIVE: To describe changes in delay to administration of thrombolytic therapy associated with a region-wide audit. DESIGN: Observational study of patients admitted with suspected myocardial infarction (MI) based on continuous audit. SUBJECTS: 18877 patients admitted to 23 hospitals with suspected MI between April 1995 and March 1998. RESULTS: Of 11232 patients with a discharge diagnosis of definite MI, 8802 (46.6%) received thrombolytic therapy during hospitalisation, with 5155 patients eligible for treatment on admission to hospital on the basis of established indications. Call-to-needle time for those eligible for treatment on admission fell from median 105 min in the first year of the project to 85 min in year 3 (P<0.001), and door-to-needle time fell from 45 to 35 min (P<0.001). Forty percent of eligible patients were treated within the then current national standard of 90 min from time of call for help, with nearly 49% in the final year and 20% being treated within the new national standard of 60 min, by the third year. CONCLUSION: The proportion of eligible patients receiving thrombolysis within 1 h of the call for help doubled during the 3-year project but the majority of patients still wait longer than 60-min 'call-to-needle'. New systems to reduce delays to administration of thrombolysis to within 60 min of call for help are required, including consideration of pre-hospital treatment.     

Acute resynchronization with inhaled iloprost in a pregnant woman with idiopathic pulmonary artery hypertension.

We describe the case of a pregnant woman with idiopathic pulmonary arterial hypertension, a responder in right heart catheterization, followed since the first trimester in outpatient consultations, admitted to hospital at 23 weeks gestation. She was treated with inhaled iloprost until delivery (at 34 weeks gestation) and continuous infusion of iloprost throughout the perioperative period and following days. This line of therapy has proved efficacious in previous cases. The authors present echocardiographic images that document acute changes in ventricular synchrony during inhalation of iloprost.     

Relationship of early life stress and psychological functioning to adult C-reactive protein in the coronary artery risk development in young adults study.

BACKGROUND: Low socioeconomic status (SES) and a harsh family environment in childhood have been linked to mental and physical health disorders in adulthood. The objective of the present investigation was to evaluate a developmental model of pathways that may help explain these links and to relate them to C-reactive protein (CRP) in the Coronary Artery Risk Development in Young Adults (CARDIA) dataset. METHODS: Participants (n = 3248) in the CARDIA study, age 32 to 47 years, completed measures of childhood SES (CSES), early family environment (risky families [RF]), adult psychosocial functioning (PsyF, a latent factor measured by depression, mastery, and positive and negative social contacts), body mass index (BMI), and C-reactive protein. RESULTS: Structural equation modeling indicated that CSES and RF are associated with C-reactive protein via their association with PsyF (standardized path coefficients: CSES to RF, RF to PsyF, PsyF to CRP, CSES to CRP, all p < .05), with good overall model fit. The association between PsyF and CRP was partially mediated by BMI (PsyF to BMI, BMI to CRP, both p < .05). CONCLUSIONS: Low childhood SES and a harsh early family environment appear to be related to elevated C-reactive protein in adulthood through pathways involving psychosocial dysfunction and high body mass index.