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.     

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).     

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.      

Secretion of vascular endothelial growth factor/vascular permeability factor from human luteinized granulosa cells is human chorionic gonadotrophin dependent

Vascularization is a prominent event during corpus luteum formation, providing low density lipoproteins for steroid biosynthesis and enabling transport of secreted steroids. The process of vascularization is controlled by specific regulators. Vascular endothelial growth factor (VEGF), otherwise named vascular permeability factor (VPF), induces endothelial cell proliferation as well as angiogenesis in vivo and increases capillary permeability. Here we report the expression of VEGF/VPF mRNA by cultured human luteinized granulosa cells (GC) for at least 10 days. Without HCG VEGF/VPF expression declined after day 4 and by day 10 was reduced to approximately 30% of the value at day 4. However, after culture in the presence of 1 U/ml human chorionic gonadotrophin (HCG), expression of VEGF/VPF mRNA by GC was four times greater than control experiments by day 10, and increased 100% from day 4 to day 10. Simultaneously, HCG supplementation increased VEGF/VPF secretion by GC. Medium VEGF/VPF on day 3 was 13 pM without and 11 pM with HCG. Medium VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with HCG. These results suggest that vascularization of the corpus luteum is induced by HCG-mediated effects of VEGF/VPF.      

Expression of BCL-2 and p53 in oncocytic (Hürthle cell) tumors of the thyroid: An immunohistochemical study

Previous studies have established that thyroid follicular neoplasms of higher malignant potential show a high p53 and low bc1-2 expression. This however has not been well studied in Oncocytic (Hürthle cell) neoplasms, the management of which remains controversial. We therefore studied the expression of p53 and bc1-2 in 18 Hürthle cell adenomas (HCA) and 8 Hürthle cell carcinomas (HCC) and compared them with their benign and malignant counterparts, respectively, including 16 follicular adenomas (FA) and 68 papillary carcinomas (PC). All 16 FA were bc1-2 positive, 4 were 2+, and 12 were 3+. On the other hand, 14/18 (78%) HCA showed bc1-2 expression, 5 were 1+, 6 were 2+, and only 3 were 3_. Similarly, HCC showed a weaker bc1-2 staining pattern compared to PC. Only 1 FA showed grade 1, p53 staining, the remaining 15 were negative, and 15/18 HCA showed p53 expression of varying grades. This difference in p53 staining was statistically significant (p=0.005). A significant p53 overexpression was also seen in HCC compared to PC (p=0.005). In conclusion, there appears to be an inverse relationship between p53 and bc1-2 expression in thyroid follicular neoplasms. A higher expression of p53 and lower levels bc1-2 in Hürthle cell neoplasms may have biological and clinical implications. This may support a more aggressive surgical treatment for HCA compared to FA.     

Estimation of the minimum number of test specimens for fatigue testing of acrylic bone cement

In the literature on fatigue testing of acrylic bone cements, data sets of various sizes have been used in different test series for the same cement formulation. There are two important consequences of this situation. First, it means that some test series last much longer than others, with all the implications for the cost of testing. Second, it makes drawing conclusions about the fatigue performance of a cement, based on the results of different literature series, a problematic issue. Clearly then, a recommendation as to what should be the minimum number of test specimens to use that would allow for confidence in the results of the statistical treatment of the test results (Gmin) would be desirable. In the present work, a method that could be used to culminate in such a recommendation is described. This method involves (i) obtaining experimental fatigue test results and (ii) analyzing those results using the Weibull probability distribution function and other statistical methods. This methodology is illustrated using fatigue life results obtained from uniaxial tension-compression fatigue tests on specimens fabricated from the polymerizing dough of one commercially available acrylic bone cement. For a tolerable error of 5%, we estimated Gmin to be either 7 (if the fatigue life results are treated using the two-parameter Weibull distribution function) or 11 (if the fatigue life results are treated using the three-parameter Weibull distribution function). To be on the conservative side, we therefore recommend that Gmin be 11. Three key limitations of the methodology presented here are discussed.