Slipped upper femoral epiphysis with hemophilia A

A 13-year-old boy who had hemophilia A was reported with pain in the left thigh and hip on walking. He had no history of trauma. Severe hemophilia A is diagnosed with a Factor VIII level of <1 iu/dl. The presumptive diagnosis was that of a spontaneous bleed into the hip joint. Factor VIII mutational analysis revealed a C to G substitution at nucleotide 6683 which results in a cystine change at codon 2194. However, the symptoms persisted and an X-ray demonstrated the presence of an acute on chronic slip of the upper femoral epiphysis. The patient was transferred to the center treating his hemophilia where the hip was pinned in situ under cover with Factor VIII. This case demonstrates the need to be aware of a possible traumatic diagnosis of hip pain in a hemophiliac child with a longstanding history of spontaneous bleeding into joints.     

Epidemiological considerations following long-term surveillance of invasive group A streptococcal disease in The Netherlands, 1992–2003

A nationwide laboratory-based surveillance system for invasive group A streptococcal (GAS) infections was conducted in The Netherlands from March 1992 until December 2003. Until 1996, all isolates submitted were evaluated clinically and demographically. During this period there was a transition from passive to active surveillance for some of the participating laboratories, corresponding to a national coverage of 50%. During active surveillance, participating laboratories submitted twice as many isolates from invasive GAS disease, whereas the relative submission of isolates representing very severe manifestations (toxic shock-like syndrome, fatality) did not increase. From 1997 onwards, invasiveness was defined solely on the basis of source of isolation (without clinical evaluation). During the period of microbiological and clinical evaluation, microbiological evaluation alone was found to be specific (> 99%), but had limited sensitivity (66%). Estimation of the true rate of invasive GAS disease should be based on an active surveillance system with inclusion of both microbiological and clinical data.     

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.     

Clinical efficacy, safety and pharmacokinetic properties of the factor VIII concentrate Haemoctin® SDH in previously treated patients with severe haemophilia A

Clinical efficacy, safety and pharmacokinetic properties of the high-purity double-virus inactivated plasma-derived factor VIII concentrate Haemoctin SDH (pdFVIII) were evaluated in three prospective open-label uncontrolled studies in previously treated patients (PTPs) with severe haemophilia A. The pharmacokinetic properties assessed at baseline and after 3 months of treatment are in accurate accordance with published data and remain unchanged over time (study A, n = 12). Mean terminal elimination half-life was 11.8 and 11.9 h, mean incremental recovery (IU dL(-1)/IU kg(-1)) was 2.3 and 2.0, respectively. Long-term efficacy and safety, in particular the potential immunogenicity, were investigated in a total of 53 PTPs (studies A and B) treated prophylactically and on-demand, as required. PdFVIII has shown to be effective in preventing and controlling bleeding episodes; 23.5% of patients were free of bleeding events. A total of 177 haemorrhages occurred with 74.0% resolving after a single infusion, 87.6% within two infusions. 98.3% of responses reported on haemorrhages were rated as 'excellent' or 'good'. Moreover, 'excellent' haemostatic efficacy has been demonstrated in 10 surgical procedures including general and severe orthopaedic interventions (study C). No complication occurred in any surgery. Few adverse events were reported, one patient developed a high-titre FVIII inhibitor without clinical relevance. In all three studies, over 6 million units were administered in nearly 4300 infusions, approximately 94% units or infusions were given for prophylaxis and only 6% for treatment on-demand. In conclusion, pdFVIII has shown to be effective, safe and well tolerated in long-term prophylaxis and treatment on-demand as well as after minor and major surgical procedures.     

蛇毒Ⅱ类磷脂酶A2功能分化的分析研究

目的：研究蛇毒Ⅱ类磷脂酶A2(PLA2)中D49 PLA2和K49 PLA2的功能分化及其功能分化决定位点的鉴定。方法：运用序列比较分析，进化树构建和DIVERGE v1．04软件计算研究D49 PLA2和K49 PLA2的功能分化情况及其分化位点。结果：序列比较分析，进化树构建和DIVERGE v1．04软件计算结果表明蛇毒Ⅱ类PLA2中D49 PLA2和K49 PLA2的确发生了功能分化，对于K49 PLA2来说，1S，7K，11Q，E12，R34，T56，N88，L92，E108，K116，K128可能为功能分化决定位点。对于D49 PLA2，L2，G33，G35，F46和Y118可能为功能分化决定位点。结论：我们首次通过序列比较分析，进化树构建和DIVERGE v1．04软件计算鉴定出蛇毒Ⅱ类PLA2中D49 PLA2和K49 PLA2可能的功能分化位点，为今后通过基因重组和定点突变方法研究蛇毒Ⅱ类PLA2结构功能关系提供了线索。     

Constitutive secretion of the granule chymase mouse mast cell protease-1 and the chemokine, CCL2, by mucosal mast cell homologues

BACKGROUND: The mucosal mast cell (MMC) granule-specific beta-chymase, mouse mast cell protease-1 (mMCP-1), is released systemically into the bloodstream early in nematode infection before parasite-specific IgE responses develop and TGF-beta1 induces constitutive release of mMCP-1 by homologues of MMC in vitro. Intraepithelial MMC may also express the chemokine CCL2 (monocyte chemotactic protein-1) during nematode infection but the expression of this chemokine by MMC homologues has not been investigated. OBJECTIVE: To investigate the expression and to compare the mechanisms of constitutive release of the chymase, mMCP-1, and the chemokine, CCL2. METHODS: MMC homologues were generated by culturing bone marrow cells in the presence of TGF-beta1, IL-3, IL-9 and stem cell factor (SCF). The intracellular distribution of mMCP-1 and CCL2 was examined by confocal microscopy. The involvement of the Golgi complex and of protein synthesis in the constitutive release of mMCP-1 and CCL2 was investigated using the Golgi-disrupting agent brefeldin A and cycloheximide to block protein synthesis. Secreted analytes were quantified by ELISA. RESULTS: mMCP-1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex. Extracellular release of mMCP-1 was significantly inhibited ( approximately 40%) by cycloheximide and by the Golgi-disrupting agent brefeldin A, indicating both continuous protein synthesis and transportation via the Golgi complex are required for optimal mMCP-1 secretion. A similar but more marked inhibitory effect with both compounds was demonstrated on the constitutive secretion of CCL2. CONCLUSION: The culture conditions that promote mMCP-1 expression and release by MMC homologues also promote the expression and release of CCL2. Constitutive release involves de novo protein synthesis and requires a functional Golgi complex, suggesting that similar mechanisms of extracellular secretion operate for both mediators.     

高效液相色谱法测定石杉碱甲片的含量

采用高效液相色谱法测定石杉碱甲片的含量。固定相为μＢｏｎｄａｐａｋ Ｃ１８，流动相为乙腈－０．０２ｍｏｌ／Ｌ磷酸二氢钾溶液（１２：８８），以对乙酰氨基酚为内标，石杉碱甲浓度在１０￣５０ｍｇ／Ｌ范围内与峰面积呈良好的线性关系，平均回收率为９９．９３％，ＲＳＤ为０．４１％（ｎ＝９）。     

硒和维生素A对支原体肺炎的治疗效果观察

观察硒和维生素A(VA)对支原体肺炎的治疗效果.方法 采用双盲随机对照2×2析因实验设计,选择100例住院支原体肺炎患儿,分为补硒组26例,补VA组23例,补硒和VA组30例以及病例对照组21例,正常组21例.一次补硒量为1mg亚硒酸钠和/或15万单位VA,对照病例组给予常规治疗.结果 与对照组比,治疗后3个补充组的症状和体征缓解天数均有不同程度缩短(P<0.05),补硒组白细胞硒和谷胱甘肽过氧化物酶水平显著上升(P<0.05),补VA、补硒组血清VA水平上升(P<0.01),细胞免疫功能有所改善.结论 硒和VA有协同作用,补充硒或同时加VA,作为辅助治疗支原体肺炎的方法,安全、有效.     

Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension

The renin-angiotensin system is involved in control of blood pressure and salt and fluid homeostasis. Genes for components of this system have been of major focus in research on the causation of the common, complex, polygenic trait, essential hypertension (HT). Association of an A→C variant at nucleotide 1166 of the angiotensin II type 1 receptor (AT₁R) gene with HT, but an absence of linkage of this locus with this disease, has been reported recently. Since confirmation in a different setting is imperative, we performed a cross-sectional case-control study of the A1166C variant in a well-characterized group of 108 Caucasian HT subjects with a strong family history (two affected parents) and early onset disease. Genotyping was by mismatch polymerase chain reaction/ Bfr I restriction fragment length polymorphism analysis. Frequency of the C¹¹⁶⁶allele was 0.40 in HTs and 0.29 in normotensives. The difference in genotype (χ²= 13, P = 0.0015) and allele (χ²= 5.3, P = 0.02) frequencies between the two groups was significant (odds ratio for CC vs AA+AC = 7.3 [95% CI, 1.9–31.9). The present results implicate the AT₁R gene, or a locus in linkage disequilibrium with the variant tested, in the causation of essential HT.     

Utilization of care in haemophilia: a resource-based method for cost analysis from the Haemophilia Utilization Group Study (HUGS)

Summary.  The Haemophilia Utilization Group Study (HUGS) was created 10 years ago to examine the annual utilization and cost of haemophilia-related healthcare services. Retrospective chart reviews for 336 patients with haemophilia A receiving treatment in one of five comprehensive haemophilia treatment centres (HTCs) during 1995 were completed through interview of the provider. This method provided adequate collection of data from patient charts without the abstractor having direct access to patient health information. Utilization data were used to impute the costs of different components of care (e.g. physician visits, factor VIII concentrate, emergency room, hospitalization). The total annual cost of care was $139 102 (SD $304 033). Factor VIII concentrate costs comprised the largest proportion of these costs; mean factor VIII concentrate use was 128 517 units per patient per year. Unbilled physician utilization accounted for 7.8% of the mean total physician costs per annum, while mean allied healthcare costs accounted for 33.5% of the total annual allied healthcare costs per patient. In the ordinary least-squares regression model, higher costs were associated with severe factor VIII deficiency, arthropathy, more comorbid conditions, an inhibitor to factor VIII concentrate, infusing through a port and prophylaxis. Although factor VIII concentrate is the most costly component, the treatment of haemophilia uses many healthcare resources. HUGS has demonstrated that patient clinical characteristics and physician practices predominantly drive the costs of haemophilia care. Specifically, patients with more severe arthropathy had greater healthcare costs. As future funding decisions are made, it is important to provide for all components of care.