Outcome of pregnancy in patients with autoimmune rheumatic disease before the disease onset.

The outcomes of 419 pregnancies of 154 unselected patients with various auto-immune diseases, including 390 pregnancies before the disease onset, were studied retrospectively. The patients comprised 40 with systemic lupus erythematosus (SLE), 72 with rheumatoid arthritis, 21 with primary Sjögren''s syndrome (1 degree SS), 14 with progressive systemic sclerosis (PSS), and seven with mixed connective tissue disease. The histories of 267 pregnancies of 98 healthy, age matched women served as controls. Our data indicate that compared with healthy controls autoimmune patients do not experience a higher incidence of fetal loss. The incidence of fetal loss before disease onset in the various groups of autoimmune patients (as well as after disease onset in patients with SLE and RA) was not significantly different from that of controls. Spontaneous abortions in patients with 1 degree SS and PSS before disease onset occurred significantly more frequently (p less than 0.05) than in controls. Nevertheless, it should be noted that this was not the case when the incidence per woman was considered. On the other hand, patients with SLE, both before and after disease onset, experienced a higher incidence of premature deliveries (p less than 0.05). Finally, the analysis of autoantibody profiles, including antibodies to nuclear antigens, to Ro(SSA) cellular antigen, to double stranded DNA, and to cardiolipin, could not demonstrate any association of autoantibodies with any particular pregnancy outcome.     

Distribution of cells bearing "rheumatic" antigens in peripheral blood of patients with rheumatic fever/rheumatic heart disease

Cell surfaces of some peripheral blood cells from individuals with a history of rheumatic fever/rheumatic heart disease (RHD) have been demonstrated by the use of monoclonal antibodies to be antigenically distinct from the majority of the population. Our study examines the distribution of cells bearing these "rheumatic" antigens in 23 subjects with rheumatic fever/RHD of Maori, Polynesian and Caucasian ancestry and 182 members of their families (rheumatic fever/RHD families) as well as in 46 members of families in which no member had been demonstrated to have had rheumatic fever/RHD (control families). Mononuclear cells from the blood of all cooperating family members were prepared and non-T cells isolated by sheep red blood cell rosette depletion. The binding of monoclonal antibodies 83S19.23 and D8103 to non-T cells was measured using an immunoperoxidase technique. Subjects with rheumatic fever/RHD had a significantly higher proportion of cells binding the antibodies than the unaffected members of all families. Unaffected members of rheumatic fever/RHD families had significantly higher levels of such rheumatic cells than control families. An increase in the proportion of rheumatic cells with age was noted in unaffected members of rheumatic fever/RHD families but not in rheumatic fever/RHD subjects of control families. A level of 13% 83S19.23 positive non-T cells optimally discriminated between rheumatic and nonrheumatic individuals. The relative risk for rheumatic fever/RHD with 13% or greater positive cells was 9.48. The negative predictive value of having less than 13% positive cells was 98.3%. In the population studied, 83S19.23 seems especially capable of identifying those with low risk for rheumatic fever/RHD.     

Anaesthesiological aspects of pregnancy in patients with rheumatic diseases

The anaesthesiologist facing a pregnant woman with rheumatic disease is caught between a rock (the problems of general anaesthesia, i.e., the difficult airway and/or the cardiopulmonary dysfunctions that can worsen the response to general anaesthetics or to mechanical ventilation) and a hard place (the problems of loco-regional anaesthesia, i.e., intrinsic or iatrogenic haemostatic dysfunctions, potentially causing spinal haematoma, the most threatening complication). However, the term lupus anticoagulant is a misnomer and in the absence of an underlying coagulation deficit or anticoagulant therapy, the anaesthesiologist can usually guarantee epidural analgesia for vaginal delivery to parturients affected by rheumatic diseases (so contributing to the decrease of the caesarean section rate) and, in case of a caesarean section for medical or obstetrical indications, often he can perform a loco-regional anaesthesia, which determines a substantially lower maternal mortality rate. It is very important to adopt a multidisciplinary approach comprising an antepartum team evaluation (to be performed at 36th gestational week) of the basal condition of the parturient: together, the obstetrician, the rheumatologist and the anaesthesiologist should define the type of delivery. We will also try to define the haemostatic safety criteria to be fulfilled for administration of an epidural analgesia to a parturient affected by rheumatic disease.     

Psychologic aspects of pregnancy in patients with rheumatic diseases

Under normal conditions, pregnancy constitutes a developmental crisis. In high-risk pregnancies, the stages of adaptation and attachment to the developing fetus may be delayed. Prior miscarriage or loss of a more fully developed baby, which is common in SLE, may further challenge the bonding process. In deciding whether or not to have a baby, couples need current medical information provided by an internist/rheumatologist, in close coordination with the obstetrician.     

风湿性心脏病合并冠心病的临床研究

目的了解我国风湿性心脏病患者的冠心病并发情况及临床特征。方法对本院自1993年～1997年7月40岁以上的已行瓣膜置换手术治疗的风湿性心脏病患者81例的冠状动脉造影及临床情况进行对比研究，男性48例，女性33例，年龄41～69岁，平均55．09±5．85岁。二尖瓣病变者19例，主动脉瓣病变者7例，联合瓣膜病变者55例。结果81例风湿性心脏病患者中有11例的冠状动脉有单支或多支≥50％的狭窄病变，发生率为13．58％，男女之比为2．67：1，多因素回归分析表明风湿性心脏病合并冠心病的发生与瓣膜病变的部位无明显相关性，但与冠心病的危险因素如吸烟，血脂升高，血糖升高等有一定的相关性。结论40岁以上风湿性心脏病患者应常规开展冠心病的危险因素的防治，若出现典型的胸痛，有多种冠心病易患因素存在则高度提示合并冠心病的存在，但由于部分病人为无症状性心肌缺血，因此40岁以上患者术前应常规做冠脉造影检查。     

Neonatal outcome in patients with rheumatic disease

Rheumatic autoimmune diseases have a higher prevalence in women, particularly during their childbearing age. Due to improved management, an increasing number of patients plan and carry out one or more pregnancies. Therefore, a growing interest is being paid to the possible consequences of maternal disease and associated treatment on the fetus and newborn infant. If maternal disease is characterized by the presence of IgG isotype autoantibodies, these can cross the placenta with possible antibody-mediated damage to the fetus. This is typically the case of the so called neonatal lupus erythematosus (NLE); a similar mechanism has been shown in infants of patients with immune thrombocytopenic purpura (ITP) and, less frequently, in those from mothers with antiphospholipid syndrome (APS). Indeed, this last condition is often responsible for placental, rather than neonatal, pathology. In addition, immunosuppressive and other drugs administered to the mothers during pregnancy and lactation might affect the fetal and neonatal immune system development. Finally, mothers disease and/or treatment could be related to neuropsychological alteration reported in some of their children.     

The determination of the prognosis of pregnancy in rheumatic heart disease

In determining the prognosis in pregnancy of 142 women with rheumatic heart disease, the following factors were considered: duration of rheumatic fever, age, functional capacity, history of previous failure, type of valvular damage, size of heart, nature of earlier rheumatic manifestations, and parity. It was found that the important signs were those which helped prognosticate congestive failure. That failure is the governing feature in prognosis is supported by the observations (1) that it is the most common cause of death in pregnancy complicated by rheumatic heart disease and (2) that the infant mortality rate for our group of patients with congestive heart failure was three times as high as for patients who had heart disease without failure and four times as high as for normal pregnant women delivered on the same obstetrical service.The factors found to be important in prognosticating failure and in estimating the risk involved in pregnancy form integral parts of a basic principle, which consists of establishing the patient's position in the natural course of her rheumatic heart disease. This principle gains validity when data collected under wellcontrolled conditions indicate that pregnancy per se does not alter the course of this disease. The application of this principle for determining prognosis led to interruption (per vagina) of only eleven of 142 pregnancies. No hysterotomies were performed after the patient was permitted to pass through the first trimester of pregnancy. There were no deaths from congestive heart failure among the 129 patients who remained under our care through pregnancy and parturition.     

Safety of biologic therapies during pregnancy in women with rheumatic disease

Inflammatory rheumatic diseases frequently affect women of childbearing age. Biologic therapy during pregnancy is an important topic that is yet unresolved. The majority of documented experiences are in case series, case reports, or registries. Tumor necrosis factor (TNF) inhibitors are now better known. Some evidence suggests that it is possible that differences between drugs regarding safety are associated with the structure and capacity to cross the placenta, but we are not aware of any study that supports unequivocally this statement. Most of the monoclonal antibodies are actively transferred to fetal circulation using the neonatal Fc receptor. Although this transfer does not appear to be associated with the risk of miscarriage, stillbirth, or congenital abnormality, the rate of premature births and lower birth weight may be increased. During fetal development, the neonatal period, and childhood, the immune system is constantly maturing. The ability to produce cytokines in response to infectious stimulus remains low for years, but is similar to that of an adult around the age of 3 years owing to the adaptive nature of the newborn’s immune system as a result of exposure to microbes. Therefore, exposure to TNF inhibitors may have serious consequences on the newborn, such as severe infections or allergic reactions. Regarding the former, an anecdotal case report described a fatal case of disseminated bacillus Calmette-Guérin (BCG) infection in an infant born to a mother taking infliximab for Crohn’s disease. Although the baby was born and progressed well initially, he died at 4.5 mo after he was vaccinated with BCG. Fortunately, serious infections do not appear to be frequent in newborns exposed to in utero biologic therapy. However, very limited short-term experiences are available regarding complications in an exposed fetus, and no data are available about long-term implications on the child’s developing immune system. Therefore, we must be aware of potential complications in later years. Although the clinical data to date are promising, no firm conclusions can be drawn about the safety of biologic drugs during pregnancy, and, without further evidence, guidelines that suggest these drugs should be avoided at the time of conception cannot yet be changed.     

The influence of adrenoreactive preparations on clinical and haemodynamic parameters in patients with ischaemic heart disease.

The influence of anaprilin, oxprenolol, nonachlazine, prazosin and levodopa on the clinical course and haemodynamics was investigated in 138 patients with ischaemic heart disease in whom selective coronary angiography had revealed an up to 50 percent stenosis of one of coronary arteries. The clinical picture of IHD patients with a high tolerance of physical exercise was characterized by a preponderance of spontaneous angina pectoris accompanied by painless myocardial ischaemia. A certain role in the genesis of these disturbances is played by the relative increase in the activity of alpha 1-adrenoreceptors and decrease in beta-adrenoreceptor activity. Prazosin and nonachlazine in monotherapy reduced the number of anginal attacks and episodes of painless myocardial ischaemia.     

Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum

OBJECTIVE: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). METHODS: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon gamma (IFNgamma), interleukin (IL) 1beta, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. RESULTS: Low levels of IL10 were found sporadically, whereas IFNgamma and IL1beta were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. CONCLUSIONS: IFNgamma and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity.     

Morphometric analysis of peripheral blood and synovial fluid lymphocytes of patients with rheumatic disease

A morphometric analysis of lymphocytes from the peripheral blood and the synovial fluid (SF) of patients with rheumatoid arthritis (RA) was based on a determination of the nuclear contour index (NCI = perimeter divided by the square root of the area of the nucleus). Use of this method showed that a particular type of lymphocyte, the cerebriform mononuclear cell (CMC), occurred in higher percentages in the SF than in the peripheral blood of patients with RA. The mean NCI of the lymphocytes (non-CMC) was also higher in the SF. These findings indicate that lymphocytes in the inflammatory compartment are morphologically altered, compared to the corresponding cells in the peripheral blood of the same patients, the change probably expressing an alteration in functional status.     

风湿病相关性间质性肺病临床特点及治疗分析

目的分析呼吸内科收治的风湿病（RD）相关间质性肺病（ILD）临床特点。方法回顾分析2003年1月至2006年12月之间北京大学人民医院呼吸内科收治的RD相关ILD患者资料。结果呼吸内科收治RI）相关ILD患者44例（占同期住院ILD33％），原发病多为干燥综合征，共23例（占52％）。所有患者行胸部高分辨CT（HRCT）检查，均显示肺间质病变，其中10例肺功能正常。20例长期口服糖皮质激素，12例复查胸部HRCT，共9例ILD吸收，其中7例支气管肺泡灌洗液（BALF）淋巴细胞增高，经糖皮质激素治疗肺部病变均吸收；4例胸部HRCT蜂窝不明显而无BALF结果，经糖皮质激素治疗2例吸收。结论RD是引起ILD常见病因，常以肺部病变为首诊原因。胸部HRCT诊断ILD优于肺功能。BALF淋巴细胞增高和（或）胸部HRCT蜂窝不明显者经糖皮质激素治疗ILD可吸收。     

Sub-optimal pain control in patients with rheumatic disease

The visual analog scale (VAS) of pain is a ubiquitous clinical and research tool with widespread application in the rheumatic diseases. The objectives of this study were to assess if patients report pain differently to doctors or nurses, to determine reproducibility of this test for diagnosis, age, gender, and treatment, and to ascertain the level of pain in patients attending general rheumatology clinics. Using a standardized line of exactly 100 mm and instructions with identical wording, consecutive patients attending general rheumatology clinics were asked to score their perceived level of pain in the preceding week. Two assessments were carried out, one before and one after the clinic visit, and each patient was questioned by both a doctor and a nurse. Differences between the first and second VAS scores (VAS1 and VAS2) were recorded. One hundred and eight patients completed the study (69 female). VAS1 and VAS2 scores were administered by a similar number of doctors and nurses. There was no significant difference between mean VAS1 and VAS2 scores (41.1 vs. 41.4 mm, p = 0.78). VAS1 and VAS2 differed by <4 mm in 59% of patients. Age, gender, or diagnosis did not influence VAS1 or VAS2. Differences in scores were independent of which health professional administered the scale (p = 0.19). Patients taking painkillers had higher mean VAS scores (49 mm) compared with those not on analgesia (27 mm; p < 0.001). Anti-rheumatic treatment did not influence pain scores (p = 0.13). The VAS is a reliable and effective method of pain assessment. Results are independent of which health professional administers the scale. Patients with rheumatic disease report their pain similarly regardless of diagnosis. However, pain control is sub-optimal in patients taking analgesia. Specific assessment of pain is, thus, important in patients attending rheumatology clinics.     

失眠对高血压患者血压的影响

目的 研究失眠对高血压患者血压的影响及睡眠改善后患者血压的变化.方法 高血压失眠患者271例 ,随机分为治疗组(137例)和对照组(134例),分别采用艾司唑仑和安慰剂治疗,观察患者第4、8、15天血压的变 化:袖带坐位收缩压谷值和舒张压谷值与基线血压的变化、目标血压达标率,同时对患者进行睡眠障碍量表(sleep dys-funtion rating scale,SDRS)和汉密尔顿焦虑量表(Hamilton anxiety rating scale,HAMA)评价.结果 在 治疗第8、15天,治疗组患者的收缩压谷值和舒张压谷值显著下降,而对照组下降不明显;治疗组目标血压的达标率也明 显高于对照组(P<0.01).同时在治疗第8、15天,治疗组的SDRS和HAMA评分也较基线总分有显著下降;治疗组治疗失眠的总有效率为67.2%,对照组总有效率为16.4%,治疗组优于对照组(P<0.01).结论 艾司唑仑治 疗高血压失眠患者有显著疗效.失眠可严重影响高血压患者的血压变化,改善睡眠有利于改善患者的血压状态.     

低分子肝素对老年冠心病患者凝血机制的影响

目的　探讨老年冠心病患者使用低分子肝素的安全性。方法　观察24例老年冠心病成功进行PTCA术后及51例对照组使用低分子肝素(速避凝)10000ICUAXa,每日2次共10d后出血情况及凝血机制改变。结果　用药后两组出血情况、其它脏器合并症及凝血时间测定等均无明显差异,老年组血浆纤维蛋白原(FBI)较对照组明显增高(4.69±1.36,3.95±1.01,P＜0.05),对照组治疗后FBI较治疗前明显降低(3.95±1.01,3.33±0.41,P＜0.05)。结论　老年人应用较大剂量低分子肝素具有相对好的安全性。     

Aquatic therapy for patients with rheumatic disease

Aquatic therapy is justifiably a rapidly expanding, beneficial form of patient treatment. The goals established at the initial and subsequent evaluations usually are met as quickly and as sensibly as possible. Understanding the theory of water techniques is essential in implementing an aquatic therapy program. The success of the program, however, will always depend on the pleasure and benefits achieved by the patients. Remember, rheumatic patients most likely will need to modify their previous daily functioning. Patients need to be aware of the long-term ramifications of the disease process and understand how treatment and care may be altered during various stages of exacerbation and remission. Patient education is critical in ensuring individual responsibility for the changes that must be made when not supervised by a professional. Aquatic therapy is a step in molding a positive lifestyle change for the patient. The patient can be encouraged to be fitness oriented and, at the same time, exercise in a manner that is safe, effective, and biomechanically and physiologically sound. The environment, hopefully, also will be conductive to family and social interaction that ultimately encourages the compliance of long-term exercise programs.     

Prevention of cardiovascular disease in patients with rheumatic diseases

Cardiovascular disease (CVD), the leading cause of death in the USA, has emerged as an important comorbidity in the rheumatic diseases. As disease-modifying therapies have resulted in better disease control and decreases in disease-associated mortality, it is now apparent that the prevalence of CVD and cardiovascular (CV) events is significantly increased in a number of rheumatic disorders when compared with age and gender-matched subjects from the general population. Investigations into the mechanisms of CVD in the general population have provided insights into potential mechanisms in rheumatic disease patients and possible aetiologies for their increased risk. Although there are no evidence-based guidelines for CV risk factor screening and interventions specific to patients with rheumatic disease, the best current approach utilizes evidence-based recommendations for the general population (and higher-risk subgroups) modified by what is known of CV risk factor and event prevalence in these patients.