系统性硬化症的心脏受累

系统性硬化症(SSc)患者常伴有心脏受累,尽管大多数的心脏病变都呈隐匿性进展,但是当患者出现明显的临床心血管疾病症状时,常提示预后不良.SSc可以影响心脏各个部位,最终导致心肌缺血、心脏循环障碍、心律失常,心包积液以及瓣膜损伤.在目前众多的检测方法中,超声心动图,特别是组织多普勒成像、心脏磁共振成像以及PET扫描等对早期筛选SSc相关心脏病具较高敏感性.钙通道阻断剂和血管紧张素转换酶抑制剂的使用可以改善SSc心肌灌注和心脏功能,更重要的是,对SSc心脏受累进行早期的筛查和治疗,将对其预后改善产生重要影响.     

系统性红斑狼疮的心脏损害

目的分析系统性红斑狼疮(SLE)的心脏损害情况.方法回顾分析300例SLE患者超声心动图(UCG)、心电图(ECG)的检测结果,比较SLE活动期与非活动期心脏损害的发生率.结果 300例SLE患者UCG异常阳性率 71.67%(2 15/300).活动性SLE UCG异常阳性率为85.77%(205/239), 包括心包积液56.90%(136/239),瓣膜病变40.17%(96/239) ,心肌异常20.50%(49/239);非活动性SLE UCG异常阳性率为16. 39%(10/61),两者相比有显著性差异(P＜0.01).ECG异常阳性率 40.67%(122/300),活动性SLE ECG异常阳性率为47.28%(1 13/239),以窦性心动过速和ST-T改变多见;非活动性SLE为14.75%( 9/61),显著低于活动性SLE患者(P＜0.01).结论 SLE心脏损害多发生于狼疮活动期.     

Possible involvement of serotonin receptors in anxiety disorders

An overview of the behavioral, electrophysiological and neurochemical data found in the literature concerning the involvement of serotonin (5-HT) receptors in the regulation of anxiety was presented on the basis of animal models. At present, 5-HT receptors are classified into 7 families including at least 14 subtypes. Among these 5-HT receptors, it is conceivable that 5-HT1A-receptor-mediated effects are the most important part of the mechanism of anxiety. The demonstrated efficacy of 5-HT1A-receptor partial agonists in anxiety disorders has emphasized the importance of these receptors. Enhanced anxiety was observed in mutant mice lacking 5-HT1A receptors. In 5-HT1B receptors knockout mice, on the other hand, aggressive behavior was increased. Some of the selective antagonists acting on 5-HT2 and 5-HT3 receptors have shown the anxiolytic effects in various animal models. Inactivation of mRNA encoding 5-HT6 receptors using antisense oligonucleotide produced decreases in cortical 5-HT release enhanced by anxiety. These observations lead to the suggestion that different mechanisms, mediated by various 5-HT receptors, are involved in the pathogenesis of anxiety.     

Neuropsychiatric involvement in systemic lupus erythematosus: current therapeutic approach

The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their usefulness in the treatment of neuropsychiatric SLE. This article reviews the clinical approach to therapy in patients with SLE and neuropsychiatric involvement.     

Absence of mast cell involvement in active systemic anaphylaxis in rats

This study investigates the role of mast cells in the hypotension induced by antigen-mediated anaphylaxis, compound 48/80 and dextran in mast cell-deficient white spotting (Ws/Ws) and normal wild type (+/+) rats. Rats were sensitized with 10 μg of intraperitoneal ovalbumin in saline or saline alone (sham-sensitized). Sensitized rats, both Ws/Ws and +/+ but not sham-sensitized rats, challenged intravenously with ovalbumin exhibited hypotensive responses. There was no evidence of mast cell activation in rat mesentery 20 min after intravenous antigen challenge in sensitized +/+ rats. Hypotension induced by intravenous injection of dextran (Dextran-162, 6%, 2 ml kg⁻¹) or compound 48/80 (1 mg kg⁻¹) occurred in +/+ rats, but not in Ws/Ws rats, and was inhibited by pretreatment with a combination of chlorpheniramine and cimetidine. Taken together, these data indicate that the hypotensive response induced by antigen-mediated anaphylaxis is independent of mast cell activation, whereas mast cell amines play the main role in the hypotensive response induced by dextran or compound 48/80.     

系统性红斑狼疮患者心脏受累的超声心动图分析

目的 应用多普勒超声心动图（ＤＥ）分析２３例系统性红斑狼疮患者心脏受累情况。方法 用ＤＥ测量患者组与健康人对照组心脏各房、室腔的内径、室壁厚度、左室舒张功能并观察心瓣膜与心包有无病变。结果 ＳＬＥ组的主动脉及左室内径和室壁厚度均较对照组为大（Ｐ〈０．０１）,心室肥厚和（或）扩张者占４７％;左室舒张功能异常;瓣膜病变、心包积液和肺动脉高压分别占１７％、３９％和８．６％,总的结构异常率为６０．８％。结     

硬皮病消化系统累及的评估和治疗

消化系统是系统性硬化症除皮肤外最常见的受累器官,从口腔到直肠肛门均可受累,范围非常广泛.系统性硬化症患者消化系统受累症状不一,但消化系统受累的危害却不容小觑,症状明显者严重影响患者的生存质量.本文对硬皮病消化系统受累的临床表现,评估方法和治疗进行详细综述,以帮助风湿科、消化科或其他科室医生能早期识别硬皮病消化道受累的表现,能够让患者早诊断、早治疗,改善生存质量.     

Nasal mucosal involvement in systemic lupus erythematosus: histopathologic and immunopathologic study

The aim of this study was to investigate the pattern of nasal mucosal involvement in patients with Systemic Lupus Erythematosus (SLE). The authors selected patients affected by SLE with a symptomatology based on bad nasal breathing, in absence of anatomical deformities of the nose. Specimens representing eighteen histological sections of nasal mucosa were examined under the light microscope to establish a set of histopathologic and immunophahologic features. A number of significant alterations were identified. The authors indicate the possible physiopathogenetic relationship between nasal mucosal involvement and systemic disease.     

系统脱敏法治疗功能性胃肠病的疗效

目的探讨功能性胃肠病患者实施系统脱敏法治疗的临床效果。方法选取2015年7月～2018年6月我院消化内科及门诊收治的功能性胃肠病患者共105例为研究对象,根据患者入院时间先后顺序进行分组,包括对照组52例,观察组53例。对照组患者临床治疗中开展常规药物疗法,观察组患者给予常规药物疗法基础上行系统脱敏法治疗,两组患者治疗前后均行焦虑自评量表(SAS)、抑郁自评量表(SDS)、临床症状自评量表(Scl-90)检测,以评定两组患者负性情绪和临床症状改善效果。结果治疗前两组患者SAS、SDS及Scl-90评分数据差异无统计学意义(P 0.05),治疗后两组患者SAS、SDS及Scl-90评分相比同组治疗前均有显著下降,其中观察组下降趋势更为理想,经比较差异有统计学意义(P 0.05)。结论功能性胃肠病患者实施系统脱敏法治疗效果理想,可有效改善患者负面情绪,促进其临床症状改善,对患者的康复具有积极影响,因此该种治疗方法值得在临床中进行推广。     

Non-invasive diagnostic and functional evaluation of cardiac and pulmonary involvement in systemic sclerosis

BACKGROUND: The aim of the present study was to evaluate the role of non-invasive methods in the early detection of pulmonary and cardiac involvement in Systemic sclerosis (SSc) and to identify clinical and/or instrumental patterns of prognostic value. PATIENTS AND METHODS: Twenty female patients affected by SSc (8 with diffuse cutaneous SSc and 12 with limited cutaneous SSc) were enrolled in our study. Cardiac and pulmonary involvement (respiratory function tests and carbon monoxide lung diffusion [DLCO], chest radiography, high resolution computed tomography [HRCT] and lung perfusion magnetic resonance) were evaluated. RESULTS: All 18 patients studied with respiratory function tests showed a significant reduction of DLCO. HRCT was considerably more sensitive than traditional chest radiography (59% versus 28%; p<0.05). Lung perfusion MRI revealed normal findings in 15 patients. Abnormal lung perfusion MRI results were found only in 3 patients. Angina pectoris with electrocardiographic and scintigraphic ischemic changes, severe regional wall motion abnormalities and complex arrhythmias seemed to be associated with poor prognosis. CONCLUSION: Taken together these results indicate that a pulmonary involvement occurs both in limited and in diffuse cutaneous SSc patients and develops, in 83% of the cases, without any regional lung perfusion abnormality. Furthermore, cardiac involvement is detected in 65% of the cases as a consequence of a range of noxious events including myocardial ischemia, fibrosis and pressure overload which may result in ventricular dysfunction and arrhythmias. Lung perfusion MRI should be considered as a complementary diagnostic method for the functional evaluation of these symptoms in systemic sclerosis.     

Oesophageal mucosal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy

AIM: To assess the prevalence of oesophagitis, Barrett's oesophagus (BE) and other oesophageal mucosal abnormalities in patients with systemic sclerosis (SSc) without prior selection on digestive clinical presentation. We also investigated the association between oesophageal endoscopic and manometric data with clinical manifestations of SSc. METHODS: Oesophageal endoscopy and manometry were performed in 133 consecutive patients with SSc, receiving proton pump inhibitor (PPI) therapy since SSc diagnosis. RESULTS: Endoscopy revealed oesophagitis in 43 patients (32.3%), BE in 9 patients (6.8%), candidiasis in 7 patients (5.3%) and hyperplastic polyp arising in ectopic gastric mucosa in 1 patient. Patients with severe oesophageal motor impairment further exhibited a higher prevalence of interstitial lung disease (ILD) when compared with those without. CONCLUSION: Our study underlines the high frequency of oesophageal mucosal abnormalities in unselected SSc patients receiving long-term PPI therapy. A relationship between oesophagitis/BE and severe manometric motor disturbances was established; these patients may require a higher regimen of PPI. Finally, our series indicates a correlation between severe oesophageal motor disturbances and evidence for ILD in patients, suggesting that gastro-oesophageal reflux may be one of the contributing factors of ILD in SSc; this subgroup of patients may require close monitoring of lung parameters.     

Histamine involvement in the local and systemic microvascular effects produced by intradermal substance P

The cutaneous microvascular changes produced by intradermal substance P were quantitatively evaluated in both substance P-injected and contralateral, saline-injected guinea pig ears. Substance P evoked a dose-dependent increase in cutaneous microvascular permeability in both treated and untreated ears which was reduced, but not abolished, by a mepyramine-cimetidine combination. This indicates that the local effect of substance P on microvascular permeability and the effect on the contralateral ear (presumably the result of systemic substance P absorption) are both partially mediated by histamine. A cutaneous vasodilator response was also observed in substance P treated and contralateral ears, but a bell-shaped dose-response relationship was apparent. Unlike microvascular permeability, pretreatment with mepyramine and cimetidine failed to consistently attenuate the vasodilator response to substance P. Thus, a direct cutaneous vasodilator effect appears to predominate in both substance P-injected and saline-injected ears.     

Circling behavior following systemic d-amphetamine administration: Potential noradrenergic and dopaminergic involvement

Systemic treatment with d-amphetamine produced a dose-dependent increase in the circling behavior of normal mice. Treatment with both -methyl-p-tyrosine (-MpT) and FLA-63 antagonized the amphetamine-induced circling behavior. Similarly, blockade of B-adrenergic receptors by propranolol and dopamine receptors by haloperidol reversed the circling response elicited by amphetamine. In contrast to -MpT and haloperidol, however, neither FLA-63 nor propranolol attenuated the locomotor excitation engendered by amphetamine. Following repeated d-amphetamine injections the circling ordinarily induced by a single injection was abolished, whereas the locomotor effects of amphetamine remained unaltered. These findings are consistent with earlier work suggesting that tolerance may occur in those behaviors that involve a noradrenergic component.     

Targeting B lymphocyte stimulator in systemic lupus erythematosus and other autoimmune rheumatic disorders

B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression of BLyS in mice can lead to systemic lupus erythematosus (SLE)-like disease and to Sjögren’s syndrome (SS)-like disease. Treatment of mice with established SLE with BLyS antagonists ameliorates disease progression and enhances survival. Moreover, similar treatment of mice with inflammatory arthritis ameliorates the ongoing inflammation and subsequent joint destruction. In humans, BLyS overexpression is common in patients with SLE, rheumatoid arthritis or SS. Results from a Phase I clinical trial with a BLyS antagonist in human SLE have shown the antagonist to be biologically active and safe. These features collectively point to BLyS as an attractive therapeutic target in human disease.     

Targeting B lymphocyte stimulator in systemic lupus erythematosus and other autoimmune rheumatic disorders

B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression of BLyS in mice can lead to systemic lupus erythematosus (SLE)-like disease and to Sj?gren's syndrome (SS)-like disease. Treatment of mice with established SLE with BLyS antagonists ameliorates disease progression and enhances survival. Moreover, similar treatment of mice with inflammatory arthritis ameliorates the ongoing inflammation and subsequent joint destruction. In humans, BLyS overexpression is common in patients with SLE, rheumatoid arthritis or SS. Results from a Phase I clinical trial with a BLyS antagonist in human SLE have shown the antagonist to be biologically active and safe. These features collectively point to BLyS as an attractive therapeutic target in human disease.     

Review article: oral ulcers and its relevance to systemic disorders

Oral ulceration is a common problem, and is sometimes a marker of gastroenterological disease. Patients with signs or symptoms of oral ulcers are sometimes referred to gastroenterology clinics, however, in most instances the ulcers does not reflect gastrointestinal disease. Indeed, a spectrum of disorders other than those of the gut can give rise to oral mucosal ulcers ranging from minor local trauma to significant local disease such as malignancy or systemic illness. This present article reviews aspects of the aetiology, diagnosis and management of common ulcerative disorders of the oral mucosa.     

Psychiatric disorders,acne and systemic retinoids: comparison of risks

Background: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids.

Materials and methods: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest.

Results: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin.

Conclusion: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.