类风湿关节炎的治疗

应尽早控制类风湿关节炎患者的炎症 传统的改善病情抗风湿药以及新的生物制剂可以更有效地治疗类风湿关节炎 改善病情抗风湿药对类风湿关节炎患者的症状和体征控制有效，但是生物制剂对阻止骨质破坏的进展有更强的作用 初步数据显示：如果在类风湿关节炎起病时即开始生物制剂治疗，而且治疗持续足够的时间，则患者将来有完全停药的可能在新发关节炎患者的基层医疗和转诊后的专科诊治中均需要制定适当的方案[编者按]     

Intravesical oxybutynin: practicalities of clinical use.

Oral anticholinergic therapy, used for the treatment of detrusor overactivity (DO), is limited by systemic side-effects and because of failure to respond. Alternative routes of administration include the intravesical route. We reviewed 11 women who were treated with intravesical oxybutynin (IVO). All had idiopathic DO, their symptoms having been unsuccessfully controlled on oral agents. Seven patients had symptomatic improvement. Six out of the eight patients that completed their voiding diaries showed a reduction in voiding frequency. Five patients found the procedure too inconvenient. Seven patients suffered chemical irritation. One patient complained of voiding difficulties. No patient reported systemic side-effects. The mean duration of treatment was 4-5 weeks; two patients continue to use IVO. IVO can be used successfully in the treatment of DO, but its use is limited due to the inconvenience related to catheterisation. With the advent of Botox and oxybutynin patches, IVO probably has a limited role.     

Which issues concerning multiple pregnancies should be addressed during psychosocial counselling?

The global rise in multiple pregnancy rates due to assisted reproductive technology has led to the development of various strategies to diminish these rates without jeopardising pregnancy. Policies at treatment centres may include the option of fetal reduction, although each centre is subject to national laws and its own guidelines. However, personal opinions and goals may also influence practice. The development of clinical decisions, therefore, is complex and subject to change. Primary prevention is the best way to reduce multiple births. For preventative psychosocial counselling, some centres employ counsellors, but if not, this becomes the physician's task. An in-depth assessment is required to define how many embryos to transfer and what risk of multiple birth is acceptable to patients. Counselling should address the following: the relationship between pregnancy rate, multiple pregnancy rate and the number of embryos transferred; benefits and risks of multiple pregnancy; and possibilities for primary and secondary prevention. Patients should voice how they feel facing these issues; which issues are worrisome; how they anticipate these possibilities; and what psychosocial support exists that could be mobilized. In summary, psychosocial counselling reinforces the partnership between couples and the assisted reproductive technology team, allowing for primary prevention and informed consent on multiple pregnancy issues.     

Is there subclinical enthesitis in early psoriatic arthritis? A clinical comparison with power doppler ultrasound

Objective

Enthesitis is a recognized feature of spondylarthritides (SpA), including psoriatic arthritis (PsA). Previously, ultrasound imaging has highlighted the presence of subclinical enthesitis in established SpA, but there are little data on ultrasound findings in early PsA. The aim of our study was to compare ultrasound and clinical examination (CE) for the detection of entheseal abnormalities in an early PsA cohort.

Methods

Forty‐two patients with new‐onset PsA and 10 control subjects underwent CE of entheses for tenderness and swelling, as well as gray‐scale (GS) and power Doppler (PD) ultrasound of a standard set of entheses. Bilateral elbow lateral epicondyles, Achilles tendons, and plantar fascia were assessed by both CE and ultrasound, the latter scored using a semiquantitative (SQ) scale. Inferior patellar tendons were assessed by ultrasound alone. A GS SQ score of >1 and/or a PD score of >0 was used to describe significant ultrasound entheseal abnormality.

Results

A total of 24 (57.1%) of 42 patients in the PsA group and 0 (0%) of 10 controls had clinical evidence of at least 1 tender enthesis. In the PsA group, for sites assessed by both CE and ultrasound, 4% (7 of 177) of nontender entheses had a GS score >1 and/or a PD score >0 compared to 24% (9 of 37) of tender entheses. CE overestimated activity in 28 (13%) of 214 of entheses. All the nontender ultrasound‐abnormal entheses were in the lower extremity.

Conclusion

The prevalence of subclinical enthesitis in this early PsA cohort was low. CE may overestimate active enthesitis. The few subclinically inflamed entheses were in the lower extremity, where mechanical stress is likely to be more significant.     

Lipid metabolism in cachectic tumor‐bearing rats at different stages of tumor growth

Rates of lipogenesis and lipoprotein lipase (LPL) activity were measured in liver, adipose tissue, heart, and tumor at several stages during 10 days of palpable growth of a transplantable Leydig cell tumor in rats. This model showed the same characteristics as human cancer cachexia, including anorexia, weight loss, and muscle wasting. Comparison with pair‐fed controls showed that the rate of loss of body fat was greater than could be explained by anorexia alone.

The rate of lipogenesis tended to decrease during the later stages of tumor growth, particularly in the liver, where there was a statistically significant reduction on Days 5 and 10. This may be largely attributable to decreased availability of substrates caused by decreasing food intake and increasing glucose uptake by the tumor. There was a significant decrease in plasma glucose concentration by Day 10. In contrast, LPL activity in adipose tissue was depressed from the earliest stage of tumor growth, and this is likely to be a major cause of lipid depletion in cancer. There was no difference in adipose tissue LPL activity between the fed and postabsorptive states in the tumor‐bearing rats, indicating that the normal response to nutrient intake was impaired. Thus, treatment of cancer cachexia should concentrate on normalizing the metabolic response to nutrient ingestion.     

The problem of naming in SDAT: A relative deficit

Abstract

Research relating to language disorder in senile dementia of the Alzheimer type (SDAT) has focused primarily on naming impairment, formally termed anomia or nominal aphasia/dysphasia. Data resulting from this research have been insufficiently informed by a comparative linguistic framework in which performance on naming tasks is contrasted with performance on other forms of language tasks. The present study involves the comparison of 21 adults with SDAT and 18 demographically controlled normal elderly adults on the Test for Syntactic Complexity and fifteen subtests of the Western Aphasia Battery. Performance on naming is compared with performance on oral language variables of repetition, yes/no response, auditory word recognition, sequential commands, syntactic processing, as well as with performance on reading tasks and non-verbal tasks. Findings relating to oral language tasks show that structured syntactic processing requiring explicit interpretation and sequential commands are significantly more difficult for the SDAT sample than are three of four naming tasks. Further, significant SDAT performance variability is found across naming tasks. The generative categorical naming task is found to be significantly more difficult for the SDAT patient than are the other three naming tasks. It is concluded that the generative categorical naming task should be regarded as a meta-naming task. In sum, it is found that although language dysfunction in SDAT has anomic components, the essential character of the language disorder is not best conceptualized as a problem of naming.     

Factors influencing the acceleration of human factor XIa inactivation by antithrombin III

Controversy exists in the literature concerning the potentiating effect of heparin on the inactivation rate of factor XIa by antithrombin III (AT III) in both purified systems and in plasma. We have analyzed the factors that could influence this reaction and found that ionic strength of the medium, as well as the type and concentration of the heparin preparations accounted for the major discrepancies in the literature. At I = 0.43 N, a preparation of bovine lung heparin at 1 U/mL did not augment the inactivation rate of factor XIa by inhibitors in plasma or by purified AT III. However, when ionic strength was decreased, a progressive increase in the potentiating effect was observed, reaching 6.5-fold at I = 0.15 N. At saturating concentrations of heparin, which results in the formation of 100% AT III-heparin complex, (greater than ten-fold molar excess over AT III) in purified systems, all heparin preparations (porcine, bovine, low molecular weight [LMW], and high affinity) yielded an approximately 30-fold augmentation of the factor XIa inactivation rate. However, when heparin was less than saturating, we observed that various heparin preparations affected the AT III-induced inactivation of factor XIa to different degrees even though they exhibited the same inhibitory activity (1 U/mL) against thrombin. This variation resulted from differences in the number of AT III binding sites in each heparin preparation, despite a similar Kd for each. Addition of high molecular weight kininogen (HK) to AT III-heparin complexes did not enhance their ability to inhibit factor XIa, and high concentrations of HK decreased the inactivation rate. A high therapeutic dose of heparin only permits the formation of 2.5% to 16.5% of the AT III-heparin complexes that can be achieved at saturation. We observed that 1 U/mL heparin (bovine lung heparin) (high therapeutic concentration) in virtually undiluted plasma only accelerated the inactivation rate of factor XIa (in the absence of other active enzymes) less than two-fold. These new observations further support our previous conclusion that therapeutic levels of heparin have little to no influence on the inactivation rate of factor XIa in plasma.     

Genomic and Functional Assays Demonstrate Reduced Gammaretroviral Vector Genotoxicity Associated With Use of the cHS4 Chromatin Insulator

Interest in the use of recombinant retroviral vectors for clinical gene therapy has been tempered by evidence of vector-mediated genotoxicity involving the activation of cellular oncogenes flanking sites of vector integration. We report here that the rate of gammaretroviral vector genotoxicity can be significantly reduced by addition of the cHS4 chromatin insulator, based on two complementary approaches for assessing vector-mediated genotoxicity. One approach involves the direct, genomewide assessment of cellular gene dysregulation using panels of transduced cell clones and genomic microarrays, whereas the other involves the functional assessment of malignant transformation using a factor-dependent cell line. Both assays are robust and quantitative, and indicate the cHS4 chromatin insulator can reduce vector-mediated genotoxicity approximately sixfold (ranged three to eight fold). These approaches also provide a means for assessing various aspects of vector-mediated genotoxicity, including the overall rate of cellular gene dysregulation, the potential influence of vector provirus over large genomic distances, and the involvement of oncogenic pathways in vector-mediated malignant transformation.