Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse

Gene therapy of human T-lymphocyte disorders, including acquired immunodeficiency syndrome (AIDS), would be greatly facilitated by the development of an in vivo system in which transduced human hematopoietic stem cells can be used to reconstitute the T-lymphoid compartment. Here we use the SCID-hu mouse as a recipient for human CD34+ hematopoietic progenitor cells transduced in vitro with a retroviral vector carrying the neomycin resistance gene (neoR). The transduced cells engraft and reconstitute the lymphoid compartments of the human thymus implant with as few as 5 x 10(4) CD34+ cells. The neoR gene was expressed at low levels in human thymocytes and there was no apparent effect on thymocyte differentiation as a result of vector transduction. Thus, this SCID-hu mouse system is the first in vivo model showing human thymopoiesis after transduction of exogenous vectors, and should allow preclinical testing of gene therapeutic reagents designed to function in human cells of the T-lymphoid lineage. Because human immunodeficiency virus type 1 infection induces depletion of human thymocytes in SCID-hu mice, this system may be particularly valuable in evaluating efficacy of gene therapies to combat AIDS.     

Concurrent reactivation of latent EBV with hepatitis A can affect clinical feature of childhood hepatitis

Aims: Some children with acute hepatitis A virus (HAV) infection have concurrent Epstein–Barr virus (EBV) reactivation serologically. We studied the frequency of EBV reactivation during HAV infection and determined whether simultaneous occurrence of EBV reactivation and HAV infection affected the clinical features of HAV infection. Methods: The medical records of patients under 19 years of age diagnosed with acute hepatitis A between January 1996 and June 2009 were reviewed. Results: Among 72 patients with acute hepatitis A, 22 patients (30.6%) had EBV reactivation. A markedly prolonged duration of full recovery from hepatitis was observed in reactivated group. The peak levels of AST and ALT in reactivated group were higher than non‐reactivated group (p = 0.012 and p < 0.001, respectively). Higher peak levels of AST and ALT in reactivated subgroups over 10 years old were observed compared to non‐reactivated subgroup (p = 0.027 and p = 0.001, respectively). Duration of recovery showed significant differences between two subgroups. Conclusions: Concurrent reactivation of latent EBV and HAV infections is common. EBV reactivation with HAV infection adversely affects the clinical feature of hepatitis. Therefore, we should keep in mind that the concurrence especially in older children may cause worse injury to the liver.     

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。