Vigabatrin as Initial Therapy for Infantile Spasms: A European Retrospective Survey

Purpose: The efficacy and tolerability of vigabatrin (VGB) as an add-on therapy in the treatment of infantile spasm (IS) prompted physicians to explore its use as the first drug in this seizure type. Methods: Our retrospective study included 250 infants diagnosed with IS; the data obtained were subjected to peer-group review. Of this infant population, 192 infants were considered to have classic IS and had received VGB as their first treatment for the spasms. There was a slight preponderance of boys (57%) in this population. Mean age of IS onset was 5.8 months; 60% had typical hypsarrhythmia. Results: Initial suppression of spasms was obtained in 68% of infants with a median time to response of 4 days at an average VGB dose of 99 mg/kg/day. The best response was seen in those infants with tuberous sclerosis (96% response) and in those younger than 3 months at onset of spasms (90% response). Of these infants, 43 (22%) of 192 subsequently had other types of seizures, and a recurrence of infantile spasms occurred in 28 (21%) of 131 responders. At the end of this study, 96 of 192 infants who could be evaluated were seizure free with VGB monotherapy. Treatment appeared to be well tolerated, with only 33 (13%) infants with adverse events, of which the most common were somnolence (15 patients) and hyper-kinesia (eight patients). In only two cases did adverse events require VGB withdrawal. Conclusion: This study supports the opinion that VGB may be considered an initial treatment for IS regardless of cause.     

Effect of a digital imaging network on physician behavior in an intensive care unit

This study examined the effect of a medical image management network on the behavior of physicians working in a medial intensive care unit (MICU). For 1 year, 8-week periods during which chest radiographs were digitized and made available to MICU physicians on a digital display console were alternated with 8-week periods during which only film images were available. Clinical efficacy during the periods was compared by measuring the time between completion of imaging examinations and initiation of specific clinical actions such as placement and positioning of tubes. Results indicate that the time required to take some clinical actions decreased with the immediate availability of images on the digital display console. Established procedures for obtaining radiologic information were altered by the digital imaging network. The time at which physicians viewed images changed, and consultations between MICU staff and radiologists decreased. These results indicate that behavior patterns are altered when a new technology replaces an existing one. Optimal use of this technology may require changes in the logistics of clinical practice.     

情绪突然应激引致心脏顿抑的神经内分泌特征

情绪应激能触发可逆性左心室功能不良，但机制未明。作者评估突然情绪应激后左心室功能不良19例，均经血管影像和系列超声心动图检查，5例作心肌心内膜活检，对13例与7例KillipⅢ级的心肌梗死病人的血浆儿茶酚胺水平作比较。病人中位年龄63岁。妇女占95％。临床症状有胸痛、肺水肿、心源性休克，多数有散在性T波倒置和QT间期延长。     

Challenges in current drug delivery from the potential application of pharmacogenomics and personalized medicine in clinical practice

The recent technological achievements in biotechnology and recombinant DNA technology have provided multiple new methods, molecular targets, and DNA-based diagnostics to pharmaceutical research that can be utilized in assays for screening and developing potential biotechnology-based drugs, as well as in biomedicine, health and pharmaceutical care. Furthermore, such advances opened up new opportunities by applying genetic information data in pharmacotherapy and drug delivery, thus ensuring better drug efficacy and safety in clinical practice. Now the concepts of personalized medicine and pharmacogenomics are likely improving the area of pharmacodynamics and pharmacokinetics, since they favor differentiation of the conventional clinical diagnosis and drug selection into separate molecular subtypes of individuals belonging within a group of patients suffering from the same disease. Genetic polymorphisms have already been detected and analyzed in genes encoding drug-metabolizing enzymes, transporters as well as targets (e.g. receptors). The potential of applying genotyping and haplotyping analysis in future pharmaceutical care could eventually lead to pharmacotyping, i.e. individualized drug delivery profiling based on genetic-bioinformatic data in routine patient care. However, the steps towards this direction of drug delivery in clinical practice still have a long way to go to be fully achieved; until then, the critical evaluation of all available clinical data including pharmacodynamic, pharmacokinetic and genomic must be assessed for ensuring drug efficacy and safety. In this way, there has been great progress in elucidating genetic determinants contributing to the observed interindividual differences in drug disposition and effects, thus implementing current drug delivery with molecular genetics and diagnostics.     

Dominant-negative E-cadherin alters adhesion and reverses contact inhibition of growth in breast carcinoma cells

Cadherins play a crucial role in epithelial morphogenesis and mediate intercellular adhesion. These receptors bind catenins and are involved in signal transduction pathways that regulate cell growth and apoptosis, and are frequently down-regulated in invasive and metastatic carcinomas. In order to assess the role of E-cadherin in cell adhesion and growth, we transfected MCF-7 cells, a human breast cancer cell line, with a dominant-negative construct of E-cadherin (H-2kd-E-cad). The dominant-negative form of E-cadherin disrupted cell-cell adhesion of monolayer cells and induced an epithelial-to-fibroblastic conversion without any significant change in integrin profiles. Whereas control cells rapidly formed multicellular aggregates that tightly compacted into spheroids, dominant-negative transfected cells failed to compact and remained as loosely-associated cells. The transfectants exhibited down-regulation and redistribution of endogenous E-cadherin as well as increased levels of alpha- and beta-catenin. Importantly, the H-2kd-E-cad-transfected cells, when grown as multicellular aggregates, showed an increase in cell proliferation rate, compared to control cells. Overall, these observations suggest that in breast carcinoma, disruption of E-cadherin and catenin function modulates both cell-cell adhesion and permits escape from cell-cell contact-involved inhibition of cell growth.