Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open randomized cress-over study

In an open, randomized cross-over study in 124 patients, we compared the efficacy, safety and patient preference of oral and subcutaneous sum triptan in the acute treatment of migraine. Patients were treated for 3 attacks or 3 months and then crossed over. Primary clinical efficacy was defined as a reduction in headache severity on a four-point self-rating scale from severe (3) or moderate (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h after the administration of subcutaneous and 4h after the administration of oral sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral sumatriptan in relieving headache (over all three attacks 78% vs 61% improvement), improving clinical disability (55% vs 41 % improvement) and relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h) than after oral sumatriptan (18 h); the number of patients experiencing a recurrence was similar Patients reported more adverse events after subcutaneous sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all adverse events were mild to moderate in intensity and of short duration. Patient opinion was more often positive after subcutaneous sumatriptan. These results may be useful in counselling patients to choose between the available marketed formulations of sumatriptan.     

Slipped capital femoral epiphysis

Slipped capital femoral epiphysis (SCFE) is an unusual disorder in which the epiphysis of the proximal femur slips through the growth plate in a posterior direction. Significant derangement of hip function results and can be accompanied by two complications: avascular necrosis and chondrolysis. The cause remains elusive although many theories have been advanced. This article provides an overview of the disease process, diagnostic guidelines, and current treatment considerations. A case study is included.     

超细β-磷酸三钙/聚-L-乳酸复合材料的制备与骨折内固定器的加工

目的：制备分散性良好的超细β-磷酸三钙(β-TCP)／聚-L-乳酸(PLLA)复合材料及新型可吸收骨折内固定器。方法：通过研磨方法制备β-TCP超细粒子，用一缩二乙二醇作分散剂研磨β-TCP后，再将β-TCP与PLLA超声混合，制得复合材料，经注塑加工制成可吸收骨钉，并采用扫描电镜等方法进行表征。结果与结论：用一缩二乙二醇作分散剂研磨β-TCP后再经超声混合，可以使β-TCP超细粒子在复合材料中分散均匀，粒子大小仅为300nm左右，β-TCP与PLlA基体之间结合良好。超细β-TCP／PLLA复合材料可加工成可吸收骨钉，弯曲强度达到100MPa左右，完全满足松质骨内固定的要求。     

Accelerating effects of epidermal growth factor on skin lesions of pemphigus vulgaris: a double-blind, randomized, controlled trial

BACKGROUND: Pemphigus vulgaris (PV) is a severe blistering disease involving the skin and mucous membranes. The most common causes of death in these patients are adverse effects of drugs, and infection. Skin lesions are one of the important sources of infection. Thus, any local treatment that could reduce healing time of lesions and consequently reduce the total dosage of drugs needed to treat is favourable. OBJECTIVE: To evaluate the efficacy of epidermal growth factor (EGF) in reducing healing time of lesions in patients with pemphigus vulgaris. METHODS: In this randomized, double-blind, within-patient, left/right, controlled trial, 20 hospitalized patients with pathologial and immunohistologial (direct and indirect immunoflourecence) proven pemphigus vulgaris (PV) were chosen. In addition, all patients had at least one appropriate pemphigus lesion on each side of the body that had not healed after 2-week systemic therapy and sterile saline washing. EGF (10 microg/g) in 0.1% silver sulfadiazine cream vs. 0.1% silver sulfadiazine cream alone was applied randomly on one side of the body. RESULTS: Kaplan-Meier survival analysis suggested that median time to heal with application of EGF plus silver sulfadiazine cream was 9 days, in comparison with 15 days for silver sulfadiazine cream alone (log-rank test, P=0.0003). No intervention-related adverse effect was observed during the study. CONCLUSIONS: EGF can significantly reduce healing time of skin lesions in patients with pemphigus vulgaris, at least when this cream base is applied (Cochrane skin group identifier: CSG20).     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.     

Experimental infection of cattle of different ages with infectious bovine rhinotracheitis virus (Strichen strain)

The clinical signs and pathological lesions which developed in various ages of cattle experimentally infected intranasally with the "Strichen" strain of IBR virus were similar to, but generally milder than, those of the field disease. The clinical signs were most severe 4 days after infection and had almost wholly regressed after 12 days. Serum neutralizing antibodies were detected in every animal. Virus was isolated from nasal and ocular swabs for up to 13 days and 10 days, respectively, after infection. The clinical signs and the pathological lesions were more severe in the younger animals.     

Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.