A controlled trial of plasmapheresis therapy in severe lupus nephritis. The Lupus Nephritis Collaborative Study Group.

BACKGROUND. The prognosis of patients with systemic lupus erythematosus who have glomerulonephritis is poor, despite treatment with immunosuppressive therapy. Plasmapheresis therapy has been used, but there have been few controlled clinical observations of its efficacy. METHODS. We carried out a randomized, controlled trial comparing a standard-therapy regimen of prednisone and cyclophosphamide (standard therapy) with a regimen of standard therapy plus plasmapheresis in 86 patients with severe lupus nephritis in 14 medical centers. The patients underwent plasmapheresis three times weekly for four weeks. Drug therapy was standardized, with strict adherence to nine detailed medical-management protocols. RESULTS. Forty-six patients received standard therapy, and 40 patients received standard therapy plus plasmapheresis. The mean follow-up was 136 weeks. Six patients (13 percent) in the standard-therapy group and eight patients (20 percent) in the plasmapheresis group died. Renal failure developed in 8 patients (17 percent) in the standard-therapy group, as compared with 10 (25 percent) in the plasmapheresis group. Thirty patients (35 percent) reached stopping points--14 (30 percent) in the standard-therapy group and 16 (40 percent) in the plasmapheresis group. A similar number of patients in each group had a decrease in both the serum creatinine concentration and urinary protein excretion to approximately normal values. Patients treated with plasmapheresis had a significantly more rapid reduction of serum concentrations of antibodies against double-stranded DNA and cryoglobulins. CONCLUSIONS. Treatment with plasmapheresis plus a standard regimen of prednisone and cyclophosphamide therapy does not improve the clinical outcome in patients with systemic lupus erythematosus and severe nephritis, as compared with the standard regimen alone.     

A randomized trial of prednisolone in patients with severe alcoholic hepatitis.

BACKGROUND. Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta-analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease. METHODS. We conducted a randomized, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty-seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months. RESULTS. One patient was lost to follow-up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional-hazards model. CONCLUSIONS. Treatment with prednisolone improves the short-term survival of patients with severe biopsy-proved alcoholic hepatitis.     

TNF检测在环磷酰胺治疗狼疮性肾炎中的价值

目的 探讨肿瘤坏死因子（ＴＮＦ）检测在大剂量环磷酰胺静脉冲击治疗狼疮性肾炎（ＬＮ）中的价值。方法 用ＥＬＩＳＡ双抗体夹心法检测５１例ＬＮ患者环磷酰胺静脉冲击治疗（ＩＶ－ＣＴＸ）前后血清和尿ＴＮＦ水平。结果 活动期ＬＮ患者血清和尿ＴＮＦ水平显著高于稳定性（Ｐ〈０．００１）。血甭ＴＮＦ水平与血沉呈显著正相关（ｎ＝５１,ｒ＝０．３８６,Ｐ〈０．０５）。轻度肾功不全患者血清ＴＮＦ显著高于肾功正常（Ｐ,０．     

A randomized, controlled trial of vitamin A in children with severe measles

BACKGROUND. Measles kills about 2 million children annually, and there is no specific therapy for the disease. It has been suggested that vitamin A may be of benefit in the treatment of measles. METHODS. We conducted a randomized, double-blind trial involving 189 children who were hospitalized at a regional center in South Africa because of measles complicated by pneumonia, diarrhea, or croup. The children (median age, 10 months) were assigned to receive either vitamin A (total dose, 400,000 IU of retinyl palmitate, given orally; n = 92) or placebo (n = 97), beginning within five days of the onset of the rash. At base line, the characteristics of the two groups were similar. RESULTS. Although clinically apparent vitamin A deficiency is rare in this population, the children's serum retinol levels were markedly depressed (mean [+/- SEM], 0.405 +/- 0.021 mumols per liter [11.6 +/- 0.6 micrograms per deciliter]), and 92 percent of them had hyporetinemia (serum retinol level less than 0.7 mumols per liter [20 micrograms per deciliter]). Serum concentrations of retinol-binding protein (mean, 30.1 +/- 2.0 mg per liter) and albumin (mean, 33.4 +/- 0.5 g per liter) were also low. As compared with the placebo group, the children who received vitamin A recovered more rapidly from pneumonia (mean, 6.3 vs. 12.4 days, respectively; P less than 0.001) and diarrhea (mean, 5.6 vs. 8.5 days; P less than 0.001), had less croup (13 vs. 27 cases; P = 0.03), and spent fewer days in the hospital (mean, 10.6 vs. 14.8 days; P = 0.01). Of the 12 children who died, 10 were among those given placebo (P = 0.05). For the group treated with vitamin A, the risk of death or a major complication during the hospital stay was half that of the control group (relative risk, 0.51; 95 percent confidence interval, 0.35 to 0.74). CONCLUSIONS. Treatment with vitamin A reduces morbidity and mortality in measles, and all children with severe measles should be given vitamin A supplements, whether or not they are thought to have a nutritional deficiency.     

Acupuncture in severe, stable angina pectoris: a randomized trial

Twenty-six patients with stable angina pectoris, resistant to medical treatment, were randomized to either active or sham acupuncture in a single-blind design. Sham acupuncture was defined as the insertion of needles in a point within the same spinal segments as the active acupuncture, but outside the Chinese meridian system. The effect was evaluated from anginal attack rate, nitroglycerin consumption and exercise tests. Compared to patients receiving sham acupuncture the patients receiving active acupuncture increased cardiac work capacity significantly, expressed as dPRP (difference in pressure-rate-product between rest and maximum exercise) and maximal PRP during exercise (p less than 0.001). None of the other variables showed any significant difference between the two groups. Concerning exercise tolerance the median difference was 138 Wmin (95% confidence limits - 12.5 to 325 Wmin), concerning anginal attack rate the median difference was 29.5% (95% confidence limits 55% to -11%) and with regard to nitroglycerin consumption the median difference was 5% (95% confidence limits +67% to -44%). No significant effect of sham treatment was observed, no adverse effect was observed. We suggest that acupuncture may improve cardiac work capacity in patients with angina pectoris, refractory to medical treatment.     

Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus

Severe systemic lupus erythematosus affecting the kidney or central nervous system may lead to organ failure or death despite treatment with high doses of corticosteroids. To evaluate the clinical and immunologic effects of intravenous cyclophosphamide in this setting, we treated nine patients with monthly intravenous infusions of cyclophosphamide for six months. A comparison of characteristics at entry and follow-up revealed improvements (by paired t-test) in creatinine clearance (66 vs. 96 ml per minute, P less than 0.001); 24-hour urinary protein level (4.11 vs. 0.90 g, P less than 0.05), Farr anti-DNA titer (43 vs. 8.5 percent, P less than 0.01); complement components C3 (894 vs. 1150 mg per liter, P less than 0.05), C4 (154 vs. 222 mg per liter, P less than 0.05), and total complement activity (CH50) (88.7 vs. 113.4 IU, P less than 0.05); and Westergren erythrocyte sedimentation rate (60.2 vs. 34.4 mm per hour, P less than 0.0005). Other manifestations of lupus improved markedly in most cases, despite a reduction in the mean daily dose of prednisone, from 45 mg at entry to 17 mg at follow-up (P less than 0.01). The numbers of lymphocytes positive for T3, T4, T8, and B1 declined progressively during treatment. At follow-up, persistent decreases were observed in the T-lymphocyte subsets, whereas the absolute number of B lymphocytes had returned to levels near base line. T-cell proliferative responses at follow-up were not significantly different from entry values, except that the response to mitogenic anti-T11 (CD2) antibodies was decreased (P less than 0.01). Our data indicate that monthly intravenous administration of cyclophosphamide was associated with a substantial amelioration of severe systemic lupus, in conjunction with discrete changes in T-lymphocyte markers and T-cell function. This was a preliminary, uncontrolled study, but the results warrant further investigation of this form of treatment.     

An open randomized controlled trial of desmopressin and pulse dexamethasone as adjunct therapy in patients with pulmonary involvement associated with severe leptospirosis

Pulmonary involvement in leptospirosis is emerging as a common complication of severe leptospirosis. A prospective randomized controlled trial of desmopressin or high-dose (pulse) dexamethasone as adjunctive therapy in 68 patients with pulmonary involvement associated with severe leptospirosis was conducted between July 2003 and October 2006 at five hospitals in Thailand. There were 23 patients in the desmopressin group, 22 in the pulse dexamethasone group, and 23 in a control group who received standard critical care alone. The diagnosis of leptospirosis was confirmed in 52 patients (77%). There were 15 deaths (22%), of which eight patients received desmopressin, four patients received pulse dexamethasone, and three patients received critical care alone (p 0.19). Eight patients with confirmed leptospirosis died (five patients in the desmopressin group, one in the pulse dexamethasone group and two in the control group). The mortality was not significantly different in the desmopressin group or pulse dexamethasone group compared to the control group in both intention-to-treat patients, and in patients with confirmed leptospirosis. There were no serious events associated with desmopressin treatment, although pulse dexamethasone treatment was associated with a significant increase in nosocomial infection. The results of logistic regression analysis revealed that serum bilirubin level was the only significant risk factor associated with mortality (OR 0.759, 95% CI 0.598–0.965, p 0.024). The results obtained in the present study do not support the use of either pulse dexamethasone or desmopressin as adjunct therapy for pulmonary involvement associated with severe leptospirosis.     

环磷酰胺冲击疗法对狼疮性肾炎血清IL—6的影响

目的探讨白介素-6(IL-6)在狼疮性肾炎(LN)发病中的作用及大剂量环磷酰胺静脉给药(IV-CTX)对IL-6产生的影响.方法应用ELISA双抗体夹心法对IV-CTX治疗前后LN患者血清IL-6水平进行检测.结果活动期LN血清IL-6水平显著高于非活动期及健康人(P＜0.001),血清IL-6水平与血沉呈显著正相关(n=22,r=0.570,P＜0.01);抗ds-DNA抗体阳性且血清IgG＞16g/L的LN患者有更高的血清IL-6水平(P＜0.05);活动期LN治疗4w后血清IL-6水平显著下降(P＜0.001).结论LN的B细胞过度活化和自身抗体产生可能与IL-6分泌过量有关.IV-CTX可能通过抑制IL-6的产生而减轻免疫损伤,血清IL-6检测有助于监视狼疮活动和免疫抑制剂疗效.     

Three cases of childhood-onset male systemic lupus erythematosus (SLE) successfully treated with a combination of pulse methylprednisolone and pulse cyclophosphamide]

We reported three cases of childhood-onset male systemic lupus erythematosus (SLE), all of whom successfully treated with a combination of pulse methylprednisolone (mPSL) and pulse cyclophosphamide (IVCY). All of them had severe lupus nephritis and were complicated with other collagen diseases. Two cases were complicated with Sj?gren syndrome (SS) and the other was complicated with both SS and anti-phospholipid syndrome (APS). After a combination of pulse mPSL and IVCY for a year, followed by oral predonisolone (PSL) and azathioprine (AZA), following up renal biopsy were performed in all cases, which showed histological improvement in glomerulonephritis. One case had flares a year later, but no flares were observed either in clinical symptoms or in laboratory examinations in the others. Their autoantibodies except anti-nuclear antibody (ANA) were eliminated. We suggest a combination of pulse mPSL and IVCY is effective for the patients who are suffering with severe lupus nephritis complicated with the other collagen diseases.     

Effect of interval training programme on pulse pressure in the management of hypertension: a randomized controlled trial

Background

Pulse pressure (PP), might be a stronger determinants of cardiovascular risk.

Objective

To investigate the effect of interval training program on PP in subjects with hypertension.

Methods

Two hundred and forty five male patients with mild to moderate (Systolic Blood Pressure [SBP] between 140–179 & Diastolic Blood Pressure [DBP] between 90–109 mmHg) essential hypertension were age-matched and grouped into exercise and control groups. The exercise (work: rest ratio of 1:1) groups involved in an 8-weeks interval training programs of between 45–60 minutes, at intensities of 60–79% of HR max (maximum heart rate), while the control group remained sedentary during this period. SBP, DBP, VO₂max and PP were assessed.

Results

Findings of the study revealed significant correlation between PP and blood pressure; correlation of PP with SBP was much stronger (95% variance). Also, there was significant effect of the exercise training program on SBP, DBP and PP. Changes in VO₂max also negatively correlated with changes in PP (r= −.285) at p<0.05.

Conclusion

Moderate intensity interval training programs is effective in the non-pharmacological management of hypertension and may prevent cardiovascular event through the down regulation of PP in hypertension.     

A randomized, controlled trial of theophylline in patients with severe chronic obstructive pulmonary disease

To assess the effects of theophylline in chronic obstructive pulmonary disease, we conducted a randomized, placebo-controlled, double-blind, crossover trial in 60 patients with severe but stable disease. The patients (mean age, 61 years) were studied before and after two months of placebo and two months of treatment with a sustained-release preparation of theophylline (10 mg per kilogram of body weight per day), administered orally. The two treatments were administered in a random order and separated by an eight-day washout period. After taking theophylline for two months (mean plasma concentration, 14.8 mg per liter), as compared with the two months of placebo, the patients had significant improvements in dyspnea, pulmonary gas exchange (partial pressure of arterial oxygen, 66 vs. 61 mm Hg [P less than 0.0001]; partial pressure of arterial carbon dioxide, 44 vs. 49 mm Hg [P less than 0.0001]), vital capacity (63 percent vs. 58 percent of the predicted value [P less than 0.0001]), and forced expiratory volume in one second (36 percent vs. 32 percent of the predicted value [P less than 0.0001]), with no significant change in airway resistance or functional residual capacity. Minute ventilation increased by a mean of 18 percent (P less than 0.0001) in the patients taking theophylline because of increased tidal volume, with no change in respiratory frequency. The respiratory-muscle performance of the patients taking theophylline improved by approximately 29 percent (P less than 0.0001), as indicated by a decline in the ratio of inspiratory pleural pressure during quiet breathing to maximal pleural pressure. We conclude that theophylline improves respiratory function and dyspnea in patients with severe chronic obstructive pulmonary disease and that these improvements are probably due to better respiratory-muscle performance.     

A randomized controlled trial of cognitive-behavioral treatment for posttraumatic stress disorder in severe mental illness

A cognitive-behavioral therapy (CBT) program for posttraumatic stress disorder (PTSD) was developed to address its high prevalence in persons with severe mental illness receiving treatment at community mental health centers. CBT was compared with treatment as usual (TAU) in a randomized controlled trial with 108 clients with PTSD and either major mood disorder (85%) or schizophrenia or schizoaffective disorder (15%), of whom 25% also had borderline personality disorder. Eighty-one percent of clients assigned to CBT participated in the program. Intent-to-treat analyses showed that CBT clients improved significantly more than did clients in TAU at blinded posttreatment and 3- and 6-month follow-up assessments in PTSD symptoms, other symptoms, perceived health, negative trauma-related beliefs, knowledge about PTSD, and case manager working alliance. The effects of CBT on PTSD were strongest in clients with severe PTSD. Homework completion in CBT predicted greater reductions in symptoms. Changes in trauma-related beliefs in CBT mediated improvements in PTSD. The findings suggest that clients with severe mental illness and PTSD can benefit from CBT, despite severe symptoms, suicidal thinking, psychosis, and vulnerability to hospitalizations.     

Metabolic alkalosis induced by plasmapheresis in a patient with systemic lupus erythematosus.

We report a patient with systemic lupus erythematosus (SLE), who had developed metabolic alkalosis during plasmapheresis. The metabolic alkalosis could be promptly corrected by reducing the amount of citrate load. The development of metabolic alkalosis can be explained by the citrate load during plasmapheresis. Careful monitoring of acid base status is mandatory in patients with limited renal function and the reduction of citrate load may be advisable in plasmapheresis.     

Use of plasmapheresis in therapy of systemic lupus erythematosus: a controlled study

The effectivity of a combination of various plasma exchange regimens in combination with immunosuppressive medication consisting of corticosteroids and cyclophosphamide was tested in patients with severe systemic lupus erythematosus (SLE) the symptoms of which were found to be refractory to conventional immunosuppressive treatment administered orally. The patients were then submitted in a controlled manner to the following treatment modalities: 1. consecutive plasmapheresis (plasma exchanges every 2 to 3 days during a period of 2 to 3 weeks) with a continuation of immunosuppressive therapy administered orally; 2. chronic intermittent treatment (once per week) with parallel immunosuppression; 3. 2 plasmaphereses followed by an i.v. cyclophosphamide bolus. Only the third approach resulted in a stable and persistent clinical and serological improvement of disease activity.     

Successful treatment of intravenous cyclophosphamide pulse therapy for lupus myelitis with urinary disturbance and acute confusional state]

A 18-year-old female had low grade fever, butterfly rush, proteinuria, leukocytopenia and hypocomplimentemia in 1988, and she was diagnosed as systemic lupus erythematosus (SLE) with lupus nephritis (WHOIIb). Treatments with prednisolone and mizoribine resulted in the remission for three years. In May 2001, she presented neurosis and polakisuria despite of the increase of prednisolone to 20 mg/day. Finally, she admitted in our hospital because of manic and repressive state and disorientaion. A brain MRI revealed high intensity lesions in bilateral basal ganglia in T2 weighted images, and cerebrospinal fluid showed elevated protein and IFN-alpha (421 IU/ml). In addition, she manifested neurogenic bladder, muscle weakness and hyperactive deep tendon reflex of bilateral lower limbs due to both supranuclear disorder and hypesthesia under the Th 10 level. Spinal MRI revealed marked atrophy and high intensity signals at the middle to lower thoracic spinal cord in T2 weighted images, indicating complication of lupus myelitis as well as cerebral involvement. Although the symptoms of CNS lupus did not respond to prednisolone, twelve monthly cyclophosphamide pulse therapy (IV-CY) has resolved urinary disturbance, muscle weakness and sensory loss, along with the improvement of both cerebral and spinal MRI images. Lupus myelitis and neurogenic bladder are the rare, but very refractory manifestation among CNS involvement of SLE. We here propose IV-CY as an invaluable choice for the treatment of not only active lupus myelitis but also neurogenic bladder resisted for steroid.     

Behavioral treatment of hypertensive heart disease in African Americans: rationale and design of a randomized controlled trial.

African Americans experience higher morbidity and mortality than Whites do as a result of hypertension and associated cardiovascular disease. Chronic psychosocial stress has been considered an important contributing factor to these high rates. The authors describe the rationale and design for a planned randomized controlled trial comparing Transcendental Meditation, a stress-reduction technique, with lifestyle education in the treatment of hypertension and hypertensive heart disease in urban African Americans. They pretested 170 men and women aged 20 to 70 years over a 3-session baseline period, with posttests at 6 months. Outcomes included clinic and ambulatory blood pressure, quality of life, left ventricular mass measured by M-mode echocardiography, left ventricular diastolic function measured by Doppler, and carotid atherosclerosis measured by beta-mode ultrasound. This trial was designed to evaluate the hypothesis that a selected stress reduction technique is effective in reducing hypertension and hypertensive heart disease in African Americans.