Femoral capital osteonecrosis: MR finding of diffuse marrow abnormalities without focal lesions

Six painful hips in five patients were examined with magnetic resonance (MR) imaging and were found to have diffuse signal abnormalities in the marrow of the femoral head and neck, which extended into the intertrochanteric area in five cases. The abnormal regions were low in signal intensity on images obtained with a short repetition time (TR) and a short echo time (TE) and were isointense or hyperintense on long TR/TE images--findings that have been attributed by others to bone marrow edema. Edema was also seen in marrow just above the acetabulum in two cases. No focal abnormalities characteristic of osteonecrosis were seen. Osteonecrosis was subsequently shown to be present in all six femoral heads at core biopsy (three cases) or by subsequent development of focal MR abnormalities reported to be highly specific for osteonecrosis (three cases). The affected hips had been radiographically normal or subtly osteopenic and had shown intense radionuclide uptake in the femoral head at scintigraphy, with lesser abnormality in the neck and intertrochanteric region. Follow-up MR examinations of five of the six femoral heads showed the diffuse abnormalities to have been transient. Although diffuse MR abnormalities in the proximal femur are not specific, they may indicate the presence of osteonecrosis of the femoral head.     

力竭运动大鼠心室肌蛋白质组表达特征

目的:采用蛋白质组学技术,建立安静和递增运动负荷训练后力竭大鼠心室肌蛋白质组的差异性表达谱,初步筛选出心室肌对力竭运动产生反应的目标蛋白质。方法:实验于2007-03在湖南师范大学生命科学学院蛋白质化学与蛋白质组学国家教育部重点实验室和省级运动人体科学实验室完成。①实验分组:10只SD雄性大鼠随机分为对照组和运动组,每组5只。②实验方法:运动组经过7周的大强度递增运动负荷训练后(最后一次力竭),对两组心室肌组织的全蛋白进行双向凝胶电泳分离。结果:经图像分析,在运动组的电泳图谱上共展现蛋白质点(338±17)个,对照组展现蛋白质点(352±17)个。运动后差异表达的蛋白质点共有99个。对其中差异表达的9个蛋白质点进行质谱鉴定,共鉴定出7个蛋白质,Stress-70protein,NADH-ubiquinone oxidoreductase Mr75000subnunit,Long-chain specific acyl-CoA dehydrogenase,Tropomyosin-1alphachain在运动后"缺失",Nitrilase family,member2在运动后表达上调在5倍以上,一个相对分子质量为21000的未知蛋白在运动后表达下调在5倍以上,另外有两个点经鉴定均为Myosin-6,在运动后表达量相反。这些蛋白质属于收缩蛋白、能量代谢酶、分子伴侣等。结论:递增运动负荷训练后力竭时,大鼠心室肌蛋白质组明显地发生了反应。运动后"缺失"和下调的蛋白质点与心肌收缩的调控和能量代谢的方式转变以及细胞的应激反应有关,其中,成功筛选出6种在运动医学领域尚未涉足的、具有运动应激特点的目标蛋白质。     

肺源性心脏病急性发作期免疫功能的改变

目的:观察肺源性心脏病(简称肺心病)急性发作期患者免疫功能的变化。方法:选择南华大学附属第一医院2004-11/2006-01收治慢性肺心病急性发作期患者60例为肺心病组,于急性加重期入院第2天7:00,空腹抽取静脉血,采用流式细胞仪检测T细胞亚群CD3 、CD4 、CD8 及自然杀伤细胞活性,免疫浊度法检测体液免疫指标(IgG,IgM,IgA及补体C3)。以同期60例健康体检者为对照。结果:120例是否受试者均进入结果分析。①T细胞亚群:肺心病组CD3 ,CD4 水平低于对照组(0.52±0.06,0.62±0.04;0.32±0.06,0.41±0.06;P均<0.05),CD4 /CD8 高于对照组(1.96±0.26,1.84±0.78,P<0.05)。②免疫血清指标:肺心病组IgA、补体C3及自然杀伤细胞活性低于对照组[(1.26±0.74),(2.45±0.85)g/L;(6200±217),(9960±302)mg/L;0.34±0.08,0.57±0.07;P均<0.05]。结论:肺源性心脏病急性发作期患者的细胞免疫和体液免疫功能均受损,尤以细胞免疫功能受损更突出,且与病情呈平行关系。     

Histamine levels in stored platelet concentrates. Relationship to white cell content

The histamine levels in samples from platelet concentrates (PC) were measured at various storage times by a radioenzymatic assay. Elevated histamine levels were detected in 5 of 14 PC after 3 days of storage (range, less than 1 to 13.3 ng/ml) and in 9 of 14 PC after 5 days (range, less than 1 to 22.2 ng/ml). A very good linear correlation (r = 0.913) was found between the initial white cell content of the PC and the histamine level at 5 days of storage. The rise in histamine content was not influenced by the type of plastic container. The results indicate a process of histamine release by the white cells during storage. Although histamine is metabolized rapidly in vivo, a critical histamine threshold could be reached in man by the rapid infusion of stored PC containing high levels of histamine. This could explain some unexpected transfusion reactions in patients receiving PC.     

Markers of HIV infection in the Concorde trial. Concorde Co-ordinating Committee

The Concorde trial compared immediate (Imm) with deferred (Def) AZT monotherapy in asymptomatic HIV-positive participants. Haematological and immunological markers and weight were measured throughout, and correlated with clinical endpoints. Markers associated with disease progression (CD4 lymphocyte count and percentage, platelets, p24 antigen and beta 2 microglobulin favoured Imm: those associated with toxicity (haemoglobin, neutrophils and white cell count) favoured Def. CD8 and total lymphocyte count did not differ significantly between groups. In multivariate analysis, the combination of baseline CD4, p24 antigen and beta 2m was the best baseline predictor of disease. Including change in CD4 and beta 2m at 12 weeks, or changes over follow- up in these markers significantly improved the fit. Markers were also incorporated into the definition of 'clinical' endpoints. Hazard ratio estimates from end-points that included CD4 < 50 and CD4 < 25 were closest to those for AIDS or death alone, but added very few extra events. Use of other landmark CD4 counts (100 or greater) or relative decreases in counts (25% or more) increased the number of events, but overestimated the effect of immediate AZT. Although AZT had a beneficial effect on the surrogate markers of efficacy evaluated, these changes did not predict clinical outcome, nor could the markers be usefully incorporated into an endpoint definition.      

Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1

Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = ?0.81); most patients with low-medium (39–55) repeat numbers survived until the end of reproductive age. The number of CAG repeats expands in meiosis, particularly in paternal transmissions; the average total increase in intergenerational transmissions in our cohort was estimated at 1.6 CAG repeats. The fertility rates of heterozygous carriers of 39–55 CAG repeats in women were no different from those of the general Sakha population. Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels. The low (0.19) Crow’s index of total selection intensity in our SCA1 cohort implies that this mutation is unlikely to be eliminated through natural selection alone.     

Aggression on inpatient units: Clinical characteristics and consequences

Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient–staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression–rule breaking, aggression–medication, and aggression–containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression–containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation.     

Functional characterization of alpha1-adrenoceptor subtypes in human subcutaneous resistance arteries

The functional characteristics of the alpha1-adrenoceptor subtypes in human resistance arteries are still not clear. We recently reported that the alpha1A-adrenoceptor predominantly mediates contraction to norepinephrine in human skeletal muscle resistance arteries. In this study we extended these investigations to human subcutaneous resistance arteries. Arterial segments were isolated from the inguinal subcutaneous fat and mounted on a small vessel wire myograph. Potencies of agonists and antagonists were examined. N-[5-(4,5-dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulphonamide (A-61603) was found to be 10- and 54-fold more potent than norepinephrine and phenylephrine, respectively. Brimonidine (UK 14304) evoked significantly smaller contractile responses than norepinephrine and phenylephrine, showing the presence of a small population of alpha2-adrenoceptors in these arteries, and this was confirmed by the studies with selective alpha1- and alpha2-adrenoceptor antagonists prazosin and (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13a-decahydro-3-methoxyl-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]-naphthyridine (RS 79948). Prazosin, 5-methyl-urapidil, and 2-[2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB 4101) shifted the potency of norepinephrine concentration dependently giving pA2 values of 9.4, 8.9, and 10.1, respectively, showing the presence of the alpha1A-subtype in these arteries. Pretreatment with 1 and 10 microM chloroethylclonidine did not affect the potency of and maximum responses to norepinephrine, ruling out the presence of the alpha1B-subtype in these arteries. 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378, 10 and 100 nM) did not affect the potency of norepinephrine but a small shift was observed by 1 microM BMY 7378, giving a pK(B) value of 7.1, much less than that reported for the alpha1D-subtype. These results suggest the predominant involvement of alpha1A-adrenoceptor in the contractile responses to norepinephrine in these arteries. The physiological role of this subtype in the maintenance of peripheral arterial resistance is yet to be confirmed.     

Bladder cancer biomarkers and their role in surveillance and screening

Early detection of bladder cancer and its recurrences is essential for improved prognosis and long-term survival. The detection and follow-up of these patients is currently based on cystoscopy, which is expensive and invasive, and, in most cases, cytology, which is non-invasive but not very sensitive. During recent years, many urine-based tests have been developed and tested in different patient populations. In this review we discuss new developments for biomarkers in bladder cancer that have potential use in surveillance and screening. In almost all publications authors compare sensitivity of the test with a concomitantly executed cystoscopy, for example, determine cross-sectional sensitivity. However, it has also been shown that false positive test results may be followed by a positive cystoscopy in the near future, showing that cystoscopy itself does not provide 100% sensitivity. This suggests that for a proper evaluation of urine-based tests, longitudinal studies should be carried out and the results communicated to the urologist.