Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.     

Significance of platelet and monocyte activation for therapeutic immunoglobulin-induced thromboembolism

Objectives

Thromboembolic events (TEE) in patients receiving infusions of intravenous immunoglobulin (IVIG) products have recently been associated with contaminating factor XIa. We studied whether platelet and monocyte activation could also be involved.

Methods

Twenty IVIG samples from five manufacturers were tested for the induction of visible whole blood clot formation. A selection of TEE-associated and not associated lots was further analyzed for effects on thromboelastometry, platelet activation and adhesion, as well as monocyte tissue factor surface expression. Pure factor XIa was included for comparison. Western blotting was applied to analyze anti-CD154-reactive proteins in IVIG.

Results

In whole blood, IVIG enhanced macroscopic clotting additively with factor XIa. In monocytes, all IVIG products induced the FcγRII-dependent tissue factor expression to a similar extent, which was not affected by addition of factor XIa. Testing platelet aggregation, IVIG strengthened the ADP and TRAP-6-elicited response. Furthermore, IVIG increased platelet-monocyte adhesion and annexin V binding to platelet microvesicles, and promoted platelet adhesion to IVIG-coated surfaces. The strongest effects were observed with TEE-associated lots. CD154-related proteins were detected in all IVIG products. CD154-related high molecular weight complexes were particularly found in the TEE-associated IVIG. In platelet aggregation, recombinant soluble CD154 enhanced aggregate formation and stability.

Conclusion

Our data demonstrate that IVIG modulate platelet and monocyte activation and can thereby affect the hemostatic balance. These effects are either additive to or independent from factor XIa. CD154-related proteins are assumed to be involved in these interactions, the mechanism of which needs to be elucidated in further studies.     

Cost-Effectiveness Models for Chronic Obstructive Pulmonary Disease: Cross-Model Comparison of Hypothetical Treatment Scenarios

ObjectivesTo compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios.MethodsCOPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared.ResultsSeven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was €17,000/quality-adjusted life-year (QALY) for two models, €25,000 to €28,000/QALY for three models, and €47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of €50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively.ConclusionsMortality was the most important factor determining the differences in cost-effectiveness outcomes between models.     

Panic attacks caused by temporal tumors: An exemplary new case and a review

A patient is described with a ruptured temporal cavernous hemangioma clinically presenting with recurrent panic attacks mimicking panic disorder. The role of temporal lobe structures in the pathogenesis of anxiety spells is highlighted, reviewing the published cases of temporal tumors leading to panic attacks. Depression and Anxiety 4:243–245, 1996/1997. © 1997 Wiley-Liss, Inc.     

Dynamics of impulsive–compulsive behaviors in early Parkinson’s disease: a prospective study

Journal of Neurology - Impulsive compulsive behaviors (ICBs) in Parkinson’s disease (PD) are debilitating disorders of repetitive, excessive, and compulsive nature affecting up to one third...     

Inter-organizational continuity of care and the electronic patient record: a concept development

There is an expectation that the use of electronic patient records will contribute to continuity of care across organizations for the growing number of elderly and chronically ill people who need continuing nursing care after an episode of hospitalization. This article aims to explore the concept of inter-organizational continuity of care and to address the contribution, expectations and promises associated with the advent of the electronic patient record. A content analysis of the literature concerning concept development provided a model which indicates that inter-organizational continuity is a multidimensional concept, comprising individual and organizational perspectives with qualitative and quantitative properties.     

Dopamine release and synthesis in the neurointermediate lobe of the rat hypophysis in vitro after electrical stimulation of the pituitary stalk

The isolated neurointermediate lobe of the rat hypophysis was incubated in Krebs solution and the stalk was electrically stimulated. The endogenous dopamine (DA) released into the medium was estimated by HPLC with electrochemical detection. Stimulation with biphasic pulses (1 ms, 10 Hz) in the presence of pargyline elicited a mean DA output of 200 fg X pulse-1. This release was calcium-dependent but was only partially inhibited by tetrodotoxin (TTX) (1 microM), effects typical for direct electrical depolarization of the nerve endings. Reducing the duration of the electric pulses to 0.2 ms (15 Hz) caused a reduction in DA output to about 40 fg X pulse-1 which was completely blocked by TTX indicating that it was evoked by propagated action potentials. DA overflow was enhanced when the action potential was prolonged with tetraethylammonium (TEA) or when DA uptake was inhibited with GBR 12921. Evidence for a calcium-dependent increase in DA synthesis in electrically stimulated NILs has been obtained when monoamine oxidase was inhibited and TEA or GBR 12921 was present in the Krebs solution. The present results complete the requirements for the DA in the NIL to be classified as a neurotransmitter substance. The NIL-pituitary stalk preparation is a useful model for studying regulatory mechanisms in dopaminergic nerve terminals.