Double blind trial of pulse methylprednisolone versus conventional oral prednisolone in lupus nephritis

A double blinded clinical trial was conducted in which the efficacy and safety of pulse methylprednisolone (400 mg/day) was compared with oral prednisolone (50 mg/day), a control drug for a period of 3 months. One-hundred and two (102) patients were enrolled in the study, of which 91 patients were determined as eligible for analysis of efficacy. Patients on pulse methylprednisolone had more favorable response to therapy with regard to laboratory value changes from baseline such as CH50 and anti-DNA antibody titers. In terms of anti-DNA antibodies, a significant difference was detected at one week after treatment. With regard to time course changes in laboratory values, CH50 at one and two weeks after treatment showed a significantly higher elevation in the pulse methylprednisolone group than in the control group. There was no significant difference noted in incidence of adverse reactions between both treatment groups. No serious adverse reaction was encountered in the pulse methylprednisolone group. The physician's assessment of final global improvement significantly favored the pulse methylprednisolone-treated group. The above results suggest that the pulse therapy with methylprednisolone leads to more rapid onset of drug effect than the conventional oral prednisolone in the treatment of lupus nephritis.     

A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis

OBJECTIVE: To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG). METHODS: Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/day) and a 0.7-gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first-line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued. RESULTS: Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P < 0.05). The incidence of Pneumocystis carinii pneumonia was higher in oral CYC-treated patients (30.4%) than in pulse CYC-treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) (P = 0.02). CONCLUSION: Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.     

Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study

OBJECTIVE: There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (i.v.) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: The efficacy and toxicity of i.v. pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvement. RESULTS: The cumulative CYC dose was reduced by 57% in patients with i.v. pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups. However, the rate of leukopenia (P < 0.01) and severe infections (P < 0.05 by 1-tailed test) was significantly reduced in the i.v. pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the i.v. pulse group, as indicated by significantly lower levels of follicle-stimulating hormone. CONCLUSION: This randomized study shows that i.v. CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis and renal involvement.     

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide

OBJECTIVE: Pulmonary fibrosis is a common feature of systemic sclerosis (SSc) and a major cause of morbidity and mortality. Since alveolitis may be an essential step in the development of pulmonary fibrosis, we investigated the use of immunosuppressive drug therapy to improve pulmonary function in patients with SSc. METHODS: Eighteen patients with progressive pulmonary dysfunction, diminished vital capacity (VC), and/or decreased static lung compliance (Cst) were treated with cyclophosphamide and corticosteroids for 1 year. Eight patients had diffuse cutaneous SSc and 10 had limited cutaneous SSc. The median disease duration was 2.5 years (range 0.5-17 years). RESULTS: VC increased in 14 of 18 patients and the median VC rose from 74% to 80% of predicted. Cst improved in 8 of 12 patients and the median Cst increased from 59% to 66% of predicted. Pulmonary nonfibrotic opacities disappeared in 9 of 12 patients. The erythrocyte sedimentation rate (ESR) and serum concentrations of orosomucoid, C-reactive protein, and aminopropeptide type III collagen all improved. The patients were divided into 2 groups based on the presence or absence of elevations in acute-phase protein levels and ESR before therapy. Among the 12 patients with biochemical signs of inflammation, VC increased in 11, and Cst improved or was unchanged in 7 of the 8 who were tested. The median VC in this subgroup increased from 73% to 80% of predicted and the median Cst increased from 57% to 60% of predicted. In the group of 18 patients overall, the skin score decreased, while esophageal and renal function remained stable. CONCLUSION: Cyclophosphamide may have a beneficial effect on pulmonary fibrosis in patients with SSc and elevated levels of acute-phase proteins. Controlled trials of cyclophosphamide in pulmonary SSc should be performed and should focus on such patients.     

Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis

BACKGROUND & AIMS: Antibiotic prophylaxis in severe pancreatitis has recently yielded promising clinical results, with imipenem significantly reducing the incidence of infected necrosis compared with an untreated control group. On the bases of pefloxacin's spectrum of action and pancreatic penetration, we investigated whether such drugs represent a valid alternative to imipenem. METHODS: In a multicenter study, 60 patients with severe acute pancreatitis with necrosis affecting at least 50% of the pancreas were randomly allocated to receive intravenous treatment for 2 weeks with pefloxacin, 400 mg twice daily (30 patients), or imipenem, 500 mg three times daily (30 patients), within 120 hours of onset of symptoms. Age, sex, body weight, Ranson and Apache II scores, C-reactive protein, etiology, and time from onset of symptoms to treatment were well matched in the two groups. RESULTS: The incidences of infected necrosis and extrapancreatic infections were 34% and 44%, respectively, in the pefloxacin group and 10% and 20% in the imipenem group. Imipenem proved significantly more effective in prevention of pancreatic infections (P 相似文献   

Intravenous pulse cyclophosphamide in the treatment of interstitial lung disease due to collagen vascular diseases

OBJECTIVE: Substantial toxicity limits the use of daily oral cyclophosphamide (CYC) for the treatment of interstitial lung disease (ILD) due to collagen vascular diseases. We examined whether intravenous (i.v.) pulse CYC can be substituted for daily oral therapy. METHODS: Six patients with rapidly progressive ILD due to polymyositis, systemic sclerosis, systemic lupus erythematosus, or primary Sj?gren's syndrome received 6-9 cycles of i.v. pulse CYC (0.5 gm/m2 of body surface area), together with an initial course of 50 mg of prednisolone, which was tapered to a maintenance dosage of 5-7.5 mg/day, and their response was measured clinically, by high-resolution computed tomography (HRCT) and by assessment of the bronchoalveolar lavage (BAL) cell profile. RESULTS: All patients showed significant improvement in exercise tolerance and lung function. Elevated BAL neutrophils dropped substantially, whereas the response of BAL lymphocytes was inconsistent. Low-attenuation opacities in the HRCT regressed in 4 patients and remained unchanged in 2, but reticular infiltrates remained largely unaffected. Remission was maintained with hydroxychloroquine, azathioprine, or cyclosporin A. CONCLUSION: I.v. pulse CYC proved to be an effective and well-tolerated treatment in these patients. Since it appears to target mainly the inflammatory component of the disease, it should be reserved for progressive ILD featuring indices of high inflammatory activity.     

Topical clindamycin versus systemic tetracycline in the treatment of hidradenitis suppurativa

BACKGROUND: Antibiotics are often used to treat hidradenitis, but only topical clindamycin has been shown to be effective in a randomized controlled trial. The paucity of these trials may be the result of difficulties in disease assessment. OBJECTIVE: We compare topical clindamycin with systemic tetracycline in the treatment of hidradenitis suppurativa, and study clinical disease assessment. METHODS: A total of 46 patients with stage 1 or 2 hidradenitis suppurativa were treated in a double-blind, double dummy controlled trial. RESULTS: No significant difference was found between the two types of treatment. Patients' global assessment of disease was significantly worse than physician's assessment in 3 of 5 evaluations (P = .0096 to .015), but the correlation between patients' and physicians' assessments was satisfactory after only one visit (rs = .761 to .895). Soreness was the key factor in patients' overall assessment of the disease. CONCLUSION: Systemic therapy with tetracyclines did not show better results than topical therapy with clindamycin. Subjective factors, particularly soreness, appear to be a key factor in patients' assessment of the disease and should, therefore, be included as an outcome variable in future therapy studies.     

Controlled trial of penfluridol and thiothixene in the maintenance treatment of chronic schizophrenic syndromes

In a controlled trial of penfluridol and thiothixene as maintenance drugs in patients with chronic schizophrenic syndromes, some improvement over previous neuroleptics was seen with both drugs. This improvement was mainly evident in variables concerned with participation in social activities as assessed with the S-scale and by ward behaviour. The drug dosages necessary were very low and gave few and easily manageable side-effects. There was no significant difference between penfluridol and thiothixene. Penfluridol has the clear practical advantage of being the only long-acting drug for oral administration so far available.     

Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial

We report the results of a randomized controlled multicentre study on interferon-gamma (IFN-gamma) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty-four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty-nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN-gamma treated patients with normalized skin sclerosis scores >/=1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN-gamma treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN-gamma treatment but not in the control group, whereas N-terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza-like adverse events during IFN-gamma treatment. Only four of nine drop-out patients, however, experienced symptoms most probably associated with IFN-gamma treatment. We conclude that IFN-gamma therapy has mild beneficial effects on skin sclerosis and disease-associated symptoms in type I and II scleroderma. IFN-gamma treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.     

Prospective randomized trial of meropenem versus cefotaxime and metronidazole in the treatment of intraabdominal infections

BACKGROUND: The empiric antibiotic treatment of intraabdominal infections is in constant evolution. Monotherapy appears to be a desirable goal because of the simplicity of its administration, lack of toxic effects and wide spectrum. PATIENTS AND METHODS: A multicentre, prospective, randomized, open study was carried out to compare two antibiotic regimens in the treatment of intraabdominal infections in patients undergoing surgery. Ninety-eight consecutive patients were randomly allocated into two groups. One group (GM, n = 51) received meropenem (1 g/8 h) and the other (GCM, n = 47) a combination of cefotaxime (2 g/8 h) plus metronidazol (0.5 g/8 h). Clinical and bacteriological responses were assessed at the end of treatment and at 2-4 weeks. RESULTS: The severity of patients as assessed by the APACHE II score was similar in both groups (GM: 7.2 and GCM: 8.1). Three patients in each group could not be evaluated due to premature interruption of treatment or deviation from the protocol. The mean duration of treatment was 7.4 days in GM and 7.9 days in GCM. A satisfactory clinical response was obtained in 95% of patients in both groups. 31 patients (61%) in GM and 26 patients (55%) in GCM were bacteriologically evaluable. Bacteriological erradication was achieved in 94% of patients in GM and in 92% of patients in GCM. CONCLUSION: Meropenem is a good alternative for single antibiotic therapy in intraabdominal infections of moderate severity.     

Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism

Since the first reports in the late 1950's, a large amount of data have been collected. The analysis of the main evidence from the major randomized trials will be analyzed in this paper according to preoperative, postoperative and chemoradiation approaches. Fifteen randomized preoperative trials were reported; they have been grouped according to the fractionation schedule. In the hypofractionation group (5 Gy for fraction), all five studies that delivered 3-5 doses in one week had a significant improvement in local control and one of them also showed improvement in survival. Operative mortality was higher in the radiotherapy arm if inadequate techniques had been applied. In 3 out of 8 studies with conventional fractionation there was a significant improvement in local control, but no impact in survival was detected. No studies with total dose lower than 34 Gy had an improvement in local control. None of the six randomized postoperative studies showed an improvement in local control or survival. In all trials the local control rate was uniform; ranging from 76% to 84%. Toxicity was higher in the radiotherapy arm. One preoperative and five postoperative randomized studies that used chemoradiation were analyzed. One postoperative chemoradiation study showed a significant improvement in survival in comparison to the surgery arm, and another showed the same advantage compared to the postoperative arm. Protracted infusional administration of 5FU concomitant to radiotherapy showed better survival than bolus administration. No advantages were shown in using MeCCNU or Levamisole in two studies. Toxicity was high and related to the dose and the modality of administration of the drugs in order to adequately treat the different stages of rectal cancer, patients must be carefully selected in order to prescribe the most effective and the least toxic treatment for the individual stage; organ preservation should be an essential goal for its impact on quality of life, and the cost estimates should be taken into account.     

Damage occurs early in systemic vasculitis and is an index of outcome

The use of products containing PCB in buildings resulted in indoor air contaminations. The search for appropriate measures is hampered by several different uncertainties in the regulatory toxicological process. These refer to problems in exposure assessment including measurement approaches, the toxicological evaluation of health risks including the derivation of a tolerable intake and the use of TCDD toxicity equivalency factors and finally the legal consequences of health risk evaluation. Since no consensus on these aspects has been achieved, the regulatory consequences vary considerably from one German state government to the other. FAO/WHO have not been able to arrive at a satisfactory supranational recommendation of a tolerable intake for PCB.     

The effect of prednisolone on the systemic response and wound healing after colonic surgery

To study the effect of preoperative treatment with a single high-dose of glucocorticoid on the systemic and immunological response, wound healing, and convalescence after colonic surgery, thirty patients were double-blind randomized to receive either methylprednisolone 30 mg/kg intravenously 90 minutes prior to induction of anaesthesia (group 1, n = 12), or to receive placebo (group 2, n = 12). Six patients were excluded from the study. Assessments of pain, pulmonary function, convalescence, various injury and wound-healing factors were done until 10 days after surgery. Conventional reduction in pulmonary function and mobilization was improved in group 1. Interleukin-6 and C-reactive protein levels increased significantly less in group 1, as delayed-type hypersensitivity was abolished in group 1. Plasma cascade system activation was significantly less pronounced in group 1. Reduction of collagen turnover was observed in group 1, but without detrimental effect on collagen accumulation. It is concluded that treatment with a single high dose of glucocorticoid before colonic surgery may improve postoperative pulmonary function and mobilization and reduce plasma cascade system activations, the inflammatory response, and immunofunction, but without detrimental effects on wound healing.