Development,validity and responsiveness of the Clinical COPD Questionnaire

Background  

The new Global Obstructive Lung Disease (GOLD) guidelines advice to focus treatment in Chronic Obstructive Pulmonary Disease (COPD) on improvement of functional state, prevention of disease progression and minimization of symptoms. So far no validated questionnaires are available to measure symptom and functional state in daily clinical practice. The aim of this study was to develop and validate the Clinical COPD Questionnaire (CCQ).     

Identification of a self-association region within the SCA1 gene product, ataxin-1

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine tract within the SCA1 gene product, ataxin-1. Expansion of this tract is believed to result in a gain of function by the mutant protein, perhaps through altered self-associations or interactions with other cellular proteins. We have used the yeast two hybrid system to determine if ataxin-1 is capable of multimerization. This analysis revealed that ataxin-1 does have the ability to self-associate, however, this association does not appear to be influenced by expansion of the polyglutamine tract. Consistent with this finding, deletion analysis excluded the involvement of the polyglutamine tract in ataxin- 1 self-association, and instead localized the multimerization region to amino acids 495-605 of the wild type protein. These results, while identifying an ataxin-1 self-interaction region, fail to support a proposed model of polar-zipper mediated multimerization involving the ataxin-1 polyglutamine tract.      

吸收度线性组合法测定乳糖干扰下扑尔敏含量

本文通过乳糖干扰下扑尔敏的含量测定,主要探讨及考察了非专属的一般操作误差对方法的正确评价和比较的影响,提出了检查一般操作误差大小的方法,进一步确认了吸收度线性组合法的优越性。同时讨论了吸收度线性组合法的组合精度与组合点数之间的关系,以及主组分吸收度过小对测定精度的影响,考察了吸收度比值在确定组合方式中的重要性。     

Evaluation of a new mineral and trace metal supplement for use with synthetic diets

In an earlier study (Alexander et al., 1974) it was shown that the mineral mixture used in association with a synthetic diet was deficient in zinc, copper, iron, and manganese. A new mixture containing appropriately increased amounts of these trace metals has now been evaluated by means of metabolic balance studies carried out on children with phenylketonuria. This new mixture was shown to be satisfactory for zinc, copper, and iron, but minor changes have been recommended for manganese.     

输液管内发生化学配伍禁忌反应的调查报告

1　临床资料1.1　病例报告　患者 ,男 ,2 4岁 .因患感冒来我院内二科门诊治疗 .医师处方用 :穿琥宁注射液 2 0 m L+5 0 g· L- 1葡萄糖注射液 2 5 0 m L ,静脉滴注 ,1次 / d;硫酸妥布霉素注射液 16万 U+9g· L- 1氯化钠注射液 2 5 0 m L,静脉滴注 ,1次 / d.从处方上看 ,上述用药方案是可行的 .但在护理操作过程中 ,却出现了不同液体瓶里的两种药液在输液管内相遇时 ,发生了化学反应 ,生成了白色絮状沉淀[1 ] .幸好护理人员及时发现 ,中止输液 ,避免了一场事故的发生 .1.2　调查报告　我们对本院门诊和内二科病房作了一次调查 .1999— 0 6…     

Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone)

The M-2 protocol (vincristine, cyclophosphamide, BCNU, melphalan, and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia. Complete remission (absence of all clinical and bone marrow evidence of leukemia) and partial response (greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 x 10(6)/liter) were achieved in 17% and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, RR, or no response were 73+, 40, and 14 mo respectively. The median survival time from onset of treatment for stages II, III, and IV disease were 47, 20 and 19 mo, respectively, which was not statistically different from historical controls. However, when untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (p = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although complete remissions in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced wih acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol will be needed to eradicate the disease.     

An explanation for nonimmunologic adsorption of proteins onto red blood cells: Schiff's base reactions

During a phase I evaluation of diglycoaldehyde (INOX), an intravenous chemotherapeutic agent used to treat children with malignancies, all of eight patients tested developed a positive direct antiglobulin test (DAT) in vivo. The DAT became positive within one to seven days after the first administration of the drug and remained positive for up to 12 days following the last dose. The indirect antiglobulin tests were negative. None of the patients showed clinical or laboratory evidence of hemolysis at the time the DAT became positive or during follow-up. Eluates made from the red cells of two of the eight patients were both negative by indirect antihuman globulin testing. In vitro studies with INOX and glutaraldehyde, both dialdehyde compounds, showed nonimmunologic adsorption of protein onto red cells, probably by the condensation of aldehyde groups of these compounds to form Schiff's bases with amino acids of serum proteins and red cell membrane proteins. This reaction provides an explanation for the globulin detected on the red cells of patients treated with INOX.     

Depotentiation of intact rat cardiac muscle unmasks an Epac‐dependent increase in myofilament Ca2+ sensitivity

Recently, a family of guanine nucleotide exchange factors have been identified in many cell types as important effectors of cyclic adenosine 3′,5′‐monophospahte (cAMP) signalling that is independent of protein kinase A (PKA). In the heart, investigation of exchange protein directly activated by cAMP (Epac) has yielded conflicting results. Since cAMP is an important regulator of cardiac contractility, this study aimed to examine whether Epac activation modulates excitation–contraction coupling in ventricular preparations from rat hearts. The study used 8‐(4‐chlorophenylthio)‐2′‐O‐methyladenosine‐3′, 5′‐cyclic monophosphate (cpTOME), an analogue of cAMP that activates Epac, but not PKA. In isolated myocytes, cpTOME increased Ca²⁺ spark frequency from about 7 to 32/100 μm³/s (n = 10), P = 0.05 with a reduction in the peak amplitude of the sparks. Simultaneous measurements of intracellular Ca²⁺ and isometric force in multicellular trabeculae (n = 7, 1.5 mmol/L [Ca²⁺]_o) revealed no effect of Epac activation on either the amplitude of Ca²⁺ transients (Control 0.7 ± 0.1 vs cpTOME 0.7 ± 0.1; 340/380 fura‐2 ratio, P = 0.35) or on peak stress (Control 24 ± 5 mN/mm² vs cpTOME 23 ± 5 mN/mm², P = 0.20). However, an effect of Epac in trabeculae was unmasked by lowering extracellular [Ca²⁺]_o. In these depotentiated trabeculae, activation of the Epac pathway increased myofilament Ca²⁺ sensitivity, an effect that was blocked by addition of KN‐93, a Ca²⁺/calmodulin‐dependent protein kinase II (CaMK‐II) inhibitor. This study suggests that Epac activation may be a useful therapeutic target to increase the strength of contraction during low inotropic states.