Post-injury regeneration in rat sciatic nerve facilitated by neurotrophic factors secreted by amniotic fluid mesenchymal stem cells.

Amniotic fluid mesenchymal stem cells have the ability to secrete neurotrophic factors that are able to promote neuron survival in vitro. The purpose of this study was to evaluate the effects of neurotrophic factors secreted by rat amniotic fluid mesenchymal stem cells on regeneration of sciatic nerve after crush injury. Fifty Sprague-Dawley rats weighing 250-300 g were used. The left sciatic nerve was crushed with a vessel clamp. Rat amniotic fluid mesenchymal stem cells embedded in fibrin glue were delivered to the injured nerve. Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect neurotrophic factors secreted by the amniotic fluid mesenchymal stem cells. Nerve regeneration was assessed by motor function, electrophysiology, histology, and immunocytochemistry studies. Positive CD29/44, and negative CD11b/45, as well as high levels of expression of brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor, ciliary neurotrophic factor (CNTF), nerve growth factor, and neurotrophin-3 (NT-3) were demonstrated in amniotic fluid mesenchymal stem cells. Motor function recovery, the compound muscle action potential, and nerve conduction latency showed significant improvement in rats treated with amniotic fluid mesenchymal stem cells. ELISA measurement in retrieved nerves displayed statistically significant elevation of CNTF and NT-3. The immunocytochemical studies demonstrated positive staining for NT-3 and CNTF in transplanted cells. The histology and immunocytochemistry studies revealed less fibrosis and a high level of expression of S-100 and glial fibrillary acid protein at the crush site. Rat amniotic fluid mesenchymal stem cells may facilitate regeneration in the sciatic nerve after crush injury. The increased nerve regeneration found in this study may be due to the neurotrophic factors secreted by amniotic fluid mesenchymal stem cells.     

Clinicopathological Feature and Surgical Outcome of Choledochal Cyst in Different Age Groups: The Implication of Surgical Timing

Background/aims  Surgical resection of choledochal cysts (CC) has become standard treatment. However, surgery is not universally recommended in early infancy and/or asymptomatic patients. In order to investigate the optimal timing of CC excision, we analyzed clinicopathological data and surgical results from different age groups. Material and methods  This retrospective review included 107 patients (77 females, 30 males) who underwent CC resection at the National Taiwan University Hospital between January 1988 and December 2005. Patient demographic, clinical, and surgical data were collected and analyzed. Results  The patients were divided into three groups according to age at the time of surgery: <1 year old (group I, n = 26), 1−16 years old (group II, n = 48), and >16 years old (group III, n = 33). About two thirds of the patients in group I had jaundice, while abdominal pain related to inflammation was the commonest symptom in groups II and III. Group I suffered significantly fewer surgical complications and less severe liver fibrosis than groups II or III. Conclusion  CC surgery in infancy and in asymptomatic patients is safe and may prevent the complications of this condition. The results support a recommendation for early excision.     

第一、二鳃弓综合征颜面不对称的整形外科矫治

目的探讨第一、二鳃弓综合征面部不对称畸形的整形外科矫治方法。方法根据第一、二鳃弓综合征患者临床及X线所示面部双侧不对称情况,采用健侧下颌骨外板去除、颧骨截骨降低;患侧下颌体、颧骨应用健侧下颌骨外板贴附植骨或高密度多孔聚乙烯(Medpor)假体置入等术式,配合颏部水平截骨颏成形术,以缩小面部双侧宽度的差异,矫治颜面不对称畸形。结果共矫治23例,经6个月至3年的术后随访观察,双侧面部宽度差异明显缩小,正面观面部不对称明显改善。结论第一、二鳃弓综合征面部骨骼发育畸形是三维方向的,双侧面骨宽度的差异,是造成正面观面部不对称的重要因素,根据受术者的具体情况,采用以上术式的组合,扩充患侧或同时缩窄健侧骨骼,进行面部骨性支架重建,可以取得良好的矫治效果。     

Assessing the capacity to make everyday decisions: a guide for clinicians and an agenda for future research.

Assessing the capacity of patients to make decisions about their functional problems has substantial ethical, clinical, and financial implications. The growing population of older adults with cognitive impairment either in the community or in long-term care and medical facilities increase the importance of adequately assessing this capacity. This review examines the current approaches to making this assessment, demonstrates how they are incomplete, and considers potential approaches for improving these evaluations. Future research should develop and validate methods to identify patients with impaired capacity to make everyday decisions. These data will supplement functional, cognitive, and medical assessments.     

Chronic Inhalation Toxicity and Carcinogenicity Testing of Respirable Fibrous Particles

On May 8–10, 1995, a workshop on chronic inhalation toxicity and carcinogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina. The workshop was sponsored by the Office of Pollution Prevention and Toxics, U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scientific community on a number of issues related to fiber testing. Major issues for discussion were: (i) the optimal design and conduct of studies of the health effects of chronic inhalation exposure of animals to fibers; (ii) preliminary studies which would be useful guides in designing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better interpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be used to develop a minimum data set for (a) making decisions about the potential health hazard of the fibers and (b) prioritizing the need for further testing in a chronic inhalation study. After extensive discussion and debate of the workshop issues, the general consensus of the expert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk of fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rodents were recommended. For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fluid analysis to assist in establishing the chronic exposure levels. Lung burden data are also important for quantifying aspects of risk assessment related to dosimetric adjustments before extrapolation. Although mechanistic studies are not recommended as part of the standard chronic inhalation studies, the expert panel stressed the need for obtaining mechanistic information as far as possible during the course of subchronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inhalation bioassay with respect to carcinogenic effects. Meanwhile, several short-termin vitroandin vivostudies that may be useful to assess the relative potential of fibrous substances to cause lung toxicity/carcinogenicity have been identified.     

The synthesis and antiallergy activity of 1-(aryloxy)-4-(4-arylpiperazinyl)-2-butanol derivatives

A series of 1-(aryloxy)-4-(4-arylpiperazinyl)-2-butanol derivatives were prepared and evaluated for antiallergy activity in the passive foot anaphylaxis (PFA) assay in rats. Twenty-seven derivatives had activity equal to or greater than the parent, alpha-(phenoxymethyl)-4-phenyl-1-piperazinepropanol. Six derivatives that possessed greater activity in the PFA than the parent compound were then tested in the guinea pig anaphylaxis (GPA) assay. Five of the derivatives were more potent than the parent (PD50 = 40 mg/kg) in the GPA with alpha-[(4-fluorophenoxy)methyl]-4-(4-fluorophenyl)-1-piperazinepropan ol (PD50 = 3 mg/kg) having the greatest potency.     

光照疗法对新生儿红细胞谷胱甘肽还原酶活性的影响

作者对光照疗法（光疗）前及光疗后于口服维生素Ｂ＿２（４３例）和不予口服维生素Ｂ＿２（１７例）的黄疸新生儿的红细胞谷胱甘肽还原酶（ＧＲ）的活性进行了动态观察。结果显示，接受短期光疗的黄疸新生儿其红细胞ＧＲ活性较光疗前的ＧＲ活性有显著下降，光疗后予口服维生素Ｂ＿２可使下降的红细胞ＧＲ活性回升，而不予补充维生素Ｂ＿２者的红细胞ＧＲ活性继续下降。光疗的时间越长，红细胞ＧＲ活性的下降越明显，补充维生素Ｂ＿２使红细胞ＧＲ活性回复到正常水平所需的时间也越长。短期光疗也可引起体内维生素Ｂ＿２的降解，导致红细胞ＧＲ活性的下降，为避免因红细胞ＧＲ活性下降引起的红细胞额外破坏，对接受光疗的黄疸新生儿常规补充维生素Ｂ＿２的是必要的。     

Lack of biliary excretion of Cd linked to an inherent defect of the canalicular isoform of multidrug resistance protein (cMrp) does not abnormally stimulate accumulation of Cd in the Eisai hyperbilirubinemic (EHB) rat liver

A new mutant, the Eisai hyperbilirubinemic (EHB) rat, shows no inherent expression of the canalicular isoform of the multidrug resistance protein (cMrp) in the liver. It has defective biliary secretion of organic anions such as bilirubin glucuronides, bromosulfophthalein (BSP), cysteinyl leukotrienes, glutathione (GSH) and bile acid sulfate and glucuronides. When rats were injected intravenously with CdCl₂, biliary excretion of Cd over 30 min was 0.28% and 0.004% of the total dose in Sprague-Dawley (SD) and EHB rats, respectively. Six SD rats and five EHB rats were fed a diet containing Cd. Bile Cd was detected at the level of 2 ng/20 min in SD rats, but not in EHB rats. There was no significant difference of hepatic Cd concentration between SD and EHB rats. Furthermore, there were no significant differences of renal and intestinal Cd, and hepatic and renal metallothionein (MT) concentrations between the SD and EHB groups. Biliary excretion of reduced-GSH for 20 min was 1.3 ± 0.3 mg and 3.6 ± 0.9 μg in SD and EHB rats, respectively. Our results suggest that hepatobiliary excretion of exogenous Cd is mediated mainly via carrier transport, including a cMrp or GSH carrier, but that the lack of the transport pathway does not contribute to abnormal accumulation of Cd in the liver. Received: 12 August 1996 / Accepted 7 November 1996     

The future of outcomes measurement: item banking,tailored short-forms,and computerized adaptive assessment

The use of item banks and computerized adaptive testing (CAT) begins with clear definitions of important outcomes, and references those definitions to specific questions gathered into large and well-studied pools, or “banks” of items. Items can be selected from the bank to form customized short scales, or can be administered in a sequence and length determined by a computer programmed for precision and clinical relevance. Although far from perfect, such item banks can form a common definition and understanding of human symptoms and functional problems such as fatigue, pain, depression, mobility, social function, sensory function, and many other health concepts that we can only measure by asking people directly. The support of the National Institutes of Health (NIH), as witnessed by its cooperative agreement with measurement experts through the NIH Roadmap Initiative known as PROMIS (www.nihpromis.org), is a big step in that direction. Our approach to item banking and CAT is practical; as focused on application as it is on science or theory. From a practical perspective, we frequently must decide whether to re-write and retest an item, add more items to fill gaps (often at the ceiling of the measure), re-test a bank after some modifications, or split up a bank into units that are more unidimensional, yet less clinically relevant or complete. These decisions are not easy, and yet they are rarely unforgiving. We encourage people to build practical tools that are capable of producing multiple short form measures and CAT administrations from common banks, and to further our understanding of these banks with various clinical populations and ages, so that with time the scores that emerge from these many activities begin to have not only a common metric and range, but a shared meaning and understanding across users. In this paper, we provide an overview of item banking and CAT, discuss our approach to item banking and its byproducts, describe testing options, discuss an example of CAT for fatigue, and discuss models for long term sustainability of an entity such as PROMIS. Some barriers to success include limitations in the methods themselves, controversies and disagreements across approaches, and end-user reluctance to move away from the familiar.