Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin

A randomized double-blind study was carried out in patients with unresolving antibiotic-associated colitis due to Clostridium difficile, to compare the effect of bacitracin (80,000 U/day) with vancomycin (500 mg/day) on the resolution of symptoms, clearance of organism, and prevention of relapse. Forty-two patients with colitis, 9 of whom had a pseudomembrane, were randomized, 21 patients to each treatment group. The two groups were comparable in age, disease severity, and antibiotic exposure. For a 50% reduction in stool frequency the mean times (+/- SE) were 4.1 +/- 0.4 days for bacitracin and 4.2 +/- 0.4 days for vancomycin. Sixteen patients (76%) had symptom resolution after 7 days of treatment with bacitracin, compared with 18 patients (86%) given vancomycin. Patients who failed to respond were crossed over (blind) to the alternative antibiotic, but tended to be refractory to the alternative medication as well. Vancomycin-treated patients had negative toxin (83% vs. 53%, p = 0.04) and negative stool cultures (81% vs. 52%, p = 0.02) more frequently than did those patients given bacitracin. Similar numbers of patients in each group had symptomatic relapse during 1 mo of follow-up, but most of them relapsed yet again after blinded crossover therapy. Although bacitracin was significantly less effective than vancomycin in clearing C. difficile from the stools, both were of similar value in the control of symptoms in a group of patients with predominantly nonpseudomembranous colitis. In view of its low cost, bacitracin is a reasonable first-line alternative to vancomycin in the treatment of antibiotic-associated colitis.     

Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial

The efficacy of ciprofloxacin was compared with that of trimethoprim-sulfamethoxazole in a placebo-controlled trial of the 5-day treatment of acute diarrhea among 181 adults recently arrived in Guadalajara, Mexico. Both antimicrobial agents were significantly (p less than 0.0001) more efficacious than placebo in the treatment of diarrhea, with the average duration of diarrhea being 29, 20, and 81 hours, respectively, in the ciprofloxacin, trimethoprim-sulfamethoxazole, and placebo treatment groups. The antimicrobial agents were also more efficacious than placebo in treating diarrhea caused by enterotoxigenic Escherichia coli, invasive enteropathogens, and unknown pathogens. Both antimicrobials were effective in treating mild-to-moderate and moderate-to-severe disease, and both were well tolerated. Ciprofloxacin appears to be a logical alternative to trimethoprim-sulfamethoxazole in the initial treatment of acute travelers' diarrhea.     

A double-blind trial of Dextran-haemodilution vs. placebo in claudicants.

Haemodilution is often recommended for peripheral arterial disease, yet little data is available to support its clinical efficacy. This study was designed to prove or disprove the effectiveness of Dextran-haemodilution in intermittent claudication. Twenty claudicants with long, well-collateralized arterial occlusions were randomized into groups 1 and 2. Group 1 received isovolemic haemodilution with Dextran 40 (500 ml per session) during 3 weeks, which was followed by a wash-out period, followed by placebo treatments for 3 weeks. In group 2 this sequence was reversed. Pain-free and maximal walking distances were measured by standardized treadmill tests along with plethysmographic blood flow, Doppler pressures, haematocrit, blood and plasma viscosity as well as fibrinogen. Walking distances increased significantly by about 50% during haemodilution in both groups. This was paralleled by a fall in haematocrit and blood viscosity. All other variables remained constant. During placebo treatments there were no significant changes of any variable. The treatment was tolerated without complications. Thus Dextran-haemodilution seems safe and effective in selected peripheral occlusive arterial disease (POAD) patients. Potential responders might be identifiable before the start of therapy by angiographic investigations. The clinical effectiveness of Dextran 40 is comparable to that of hydroxyethyl starch 200 as reported in the literature.     

Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of vancomycin and metronidazole for eradication of asymptomatic Clostridium difficile fecal excretion as a means of controlling nosocomial outbreaks of C. difficile diarrhea. DESIGN: Randomized, placebo-controlled, non-blinded trial. SETTING: Six hundred-bed regional referral Veterans Affairs Medical Center. PATIENTS: Thirty patients excreting C. difficile without diarrhea or abdominal symptoms. INTERVENTIONS: All patients were randomized to receive 10 days of oral vancomycin, 125 mg four times daily; metronidazole, 500 mg twice daily; or placebo, three times daily. MEASUREMENTS: Stool cultures were obtained during treatment and for 2 months after treatment. All C. difficile isolates were typed by restriction endonuclease analysis (REA). RESULTS: Clostridium difficile organisms were not detected during and immediately after treatment in 9 of 10 patients treated with vancomycin compared with 3 of 10 patients treated with metronidazole (P = 0.02) and 2 of 10 patients in the placebo group (P = 0.005). The fecal vancomycin concentration was 1406 +/- 1164 micrograms/g feces, but metronidazole was not detectable in 9 of 10 patients. Eight of the nine evaluable patients who had negative stool cultures after treatment with vancomycin began to excrete C. difficile again 20 +/- 8 days after completing treatment. Three of these patients received additional antibiotics before C. difficile excretion recurred, and five acquired new C. difficile REA strains. Four of six patients who received only vancomycin before C. difficile excretion recurred were culture-positive at the end of the study compared with one of nine patients who received only placebo (P = 0.047). CONCLUSIONS: Asymptomatic fecal excretion of C. difficile is transient in most patients, and treatment with metronidazole is not effective. Although treatment with vancomycin is temporarily effective, it is associated with a significantly higher rate of C. difficile carriage 2 months after treatment and is not recommended.     

Oral type II collagen treatment in early rheumatoid arthritis. A double-blind,placebo-controlled,randomized trial

Objective. To investigate the efficacy of oral type II collagen in the treatment of early rheumatoid arthritis (RA). Methods. Ninety patients with RA (disease duration ⩽3 years) were treated for 12 weeks with oral bovine type II collagen at 1 mg/day (n = 30) or 10 mg/day (n = 30) or with placebo (n = 30), in a double-blind randomized study. Results. There was no significant difference between the 3 groups in terms of response to treatment. However, we observed a higher prevalence of responders in the type II collagen-treated groups: 7 responders in the 10-mg type II collagen group and 6 in the 1-mg group, versus 4 in the placebo group. Furthermore, 3 patients in the 10-mg type II collagen group and 1 patient in the 1-mg type II collagen group, but no patients in the placebo group, had very good response. A total of 14 patients had to be withdrawn from the study: 2 because of side effects (nausea) and 12 because of lack of efficacy. Conclusion. Only a minority of patients responded to treatment with oral type II collagen. These results justify further efforts to identify which patients will have a good response to such therapy.     

Treatment of cirrhosis with colchicine. A double-blind randomized trial.

As part of a double-blind, randomized, controlled trial to evaluate the effect of colchicine on liver cirrhosis, 43 cirrhotic patients were assigned to either a placebo (20 patients) or a colchicine (23 patients) treatment group. Colchicine 1 mg and an indistinguishable placebo were administered orally on a daily dose 5 days a week. In the colchicine group, 12 were males and 11 females, while in the control group 13 were males and 7 females. The time elapsed between diagnosis and inclusion in the study was 14.1 mo for the controls and 14.5 mo for the patients on colchicine. Mortality related to the liver disease occurred in 4 patients on colchicine and 8 patients on placebo. Although the probability of surviving in the colchicine group was greater than that of the placebo, the difference did not reach statistically significant levels. Of the colchicine-treated patients, in three a remarkable decrease in liver fibrosis was observed in serial biopsies. In two other patients, carcinoma of the liver developed. Six of the survivors on colchicine have improved clinically, noticing disappearance of ascites and edema, as well as a decrease in the size of the spleen. All the survivors on placebo continue to show clinical deterioration. In contrast to the usual drop of serum albumin seen in the cirrhotic patients, those receiving colchicine increased and maintained their serum albumin levels throughout the study. Serum proline values were elevated only in the alcohol cirrhotic patients. Serum alkaline phosphatase increased only in those patients receiving colchicine. The results indicate that in some cases, liver fibrosis could be modified by treatment with antifibrotic drugs. The use of colchicine at present should remain within controlled studies.     

三孔法与经典腹腔镜胆囊切除术的对比研究

目的比较“三孔法”与经典腹腔镜胆囊切除术（LC）的效果：方法采用“双肓随机对照”将400例慢性结石性胆囊炎择期于术患者分成2组，分别行三孔法LC与经典LC，比较2组手术时间、成功率、术后不同部位及整体疼痛程度、止痛剂使用情况、并发症、术后平均住院时间以及切口美容效果。结果2组在手术时间、成功率、并发症以及术后平均住院时间方面无明显差异；三孔LC组右肋缘下疼痛程度比经典LC组轻，而2组在剑下疼痛、擎体疼痛程度以及止痛剂使用情况无明显差别；三孔LC组切口美容效果好于经典LC组。结论和经典LC相比，三孔LC并没有因为戳孔的减少而增加手术的难度，同时具有良好的安全性，切口局部疼痛程度轻，美容效果更好，值得推广。     

Tapering of corticosteroid therapy following exacerbation of asthma. A randomized, double-blind, placebo-controlled trial

Systemic corticosteroids are effective in the treatment of acute asthma, but the optimal schedule for steroid withdrawal following an asthma exacerbation has not been determined. This study was designed to test the hypothesis that tapering the corticosteroid dosage over a longer period of time reduces the number of reexacerbations. Non-steroid-dependent adult men hospitalized for asthma exacerbations during a one-year period (n = 43) were randomly assigned to corticosteroid tapering regimens of one or seven weeks, following an eight-day course of high-dose corticosteroid therapy. There were no significant differences between the long-taper and short-taper groups in rate of reexacerbation (41% vs 52%) or readmission (22% vs 21%) during the 12-week study period. Patients who did not have a reexacerbation during the 12 weeks were evaluated with spirometry, with no significant differences occurring between the two groups. More patients in the long-taper group reported corticosteroid side effects (41% vs 14%). Patients who required mechanical ventilation during the initial hospitalization (n = 7), or who reported more than two days of worse than usual dyspnea in the 12-week period (n = 20), had high rates of reexacerbation (86% and 80%, respectively). These results provide reasonable certainty (90%) that a long taper does not result in a large reduction (50% or more) in reexacerbations compared with a short taper. We conclude that the relapse rate is high in this population regardless of the corticosteroid tapering regimen used, and that a long taper does not appear to provide enough benefit to justify its routine use.     

Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial

OBJECTIVE: Although hypomagnesemia reduces insulin sensitivity, benefits of magnesium supplementation to non-diabetic insulin resistant subjects has not been established. Our purpose was to determine whether oral magnesium supplementation with magnesium chloride (MgCl2) 2.5 g daily modify insulin sensitivity in non-diabetic subjects. MATERIAL AND METHODS: This study was a 3 months randomized double-blind placebo-controlled trial. Apparently healthy subjects were eligible to participate if they had insulin resistance (HOMA-IR index equal or greater than 3.0) and hypomagnesemia (Serum magnesium levels equal or lower than 0.74 mmol/l). Subjects were randomized to receive either, MgCl2 2.5 g daily or placebo by 3-months. RESULTS: At baseline there were not significant anthropometric or laboratory differences between both groups. At ending of the study, magnesium-supplemented subjects significantly increased their serum magnesium levels (0.61 +/- 0.08 to 0.81 +/- 0.08 mmol/l, p<0.0001) and reduced HOMA-IR index (4.6 +/- 2.8 to 2.6 +/- 1.1, p<0.0001), whereas control subjects did not (0.62 +/- 0.08 to 0.61 +/- 0.08 mmol/l, p=0.063 and 5.2 +/- 1.9 to 5.3 +/- 2.9, p=0.087). CONCLUSIONS: Oral magnesium supplementation improves insulin sensitivity in hypomagnesemic non-diabetic subjects. Clinical implications of this finding have to be established.     

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.     

Levamisole therapy in chronic type B hepatitis. Results of a double-blind randomized trial

A double-blind, randomized, controlled trial has been undertaken to evaluate treatment of chronic hepatitis type B with levamisole. Ten patients received levamisole (150 mg/day, 3 days/wk) and 10 received placebo until seroconversion to antibody to hepatitis B e antigen eventually occurred, or for a maximum of 18 mo. Final evaluation at 24 mo after starting treatment revealed that 60% of the patients in the levamisole group had become hepatitis B e antigen negative, 90% were hepatitis B virus-deoxyribonucleic acid negative in serum, and 8 of 9 (89%) patients had cleared hepatitis B core antigen from the liver. On the other hand, in the placebo group only 4 of the 10 subjects (40%) were hepatitis B e antigen and hepatitis B virus-deoxyribonucleic acid negative in serum and 3 of 8 (37.5%) of them became hepatitis B core antigen free in the liver. Moreover, in 8 patients of the treated group and in 4 of the control cases aminotransferase activities fell into the normal range. A liver biopsy specimen was obtained after treatment in 17 patients and 7 of 9 levamisole recipients showed marked improvement in hepatic histology, compared with 3 of 8 placebo recipients. These data show that patients treated with long-term levamisole therapy have a tendency toward normalization of aminotransferase activities and suppression of hepatitis B virus replication, suggesting that the drug may be of benefit in chronic hepatitis B e antigen-positive hepatitis.     

Low-dose antacid therapy in the treatment of duodenal ulcer--a multicentre double-blind trial vs. misoprostol.

We conducted a 4-week double-blind randomized controlled multicentre trial to compare low-dose-antacid (AA) therapy (225 meq total neutralizing capacity per day) with therapy using the prostaglandin E1-analogue, misoprostol (MS) (400 micrograms bid), on ulcer healing and relief of symptoms in 100 outpatients with endoscopically proven duodenal ulcer (DU, 49 patients on AA, 51 patients on MS). Of the 100 patients enrolled in the study 96 could be evaluated; 49 received AA, 47 MS. Endoscopies were performed before treatment, 2 and 4 weeks after initiation of treatment. Healing rates of AA- and MS-treatment were 36.7% vs. 25.5% (2 weeks) and 79.6% vs. 74.4% (4 weeks) and did not differ as much as relief of pain during the daytime. Rates of relief of nighttime pain were significantly higher on AA-treatment after 2 weeks of treatment (81.1% vs. 48.6%; p less than 0.05), but not during the later course of treatment. Thus, it can be concluded that low-dose AA-treatment using an aluminum/magnesium hydroxide preparation in tablet form represents an effective and safe therapy for duodenal ulcer.     

A randomized trial of oral vs. topical diltiazem for chronic anal fissures

INTRODUCTION: Chemical sphincterotomy has proved effective in treating chronic anal fissure. Glyceryl trinitrate is the most widely used agent, and topical 0.2 percent glyceryl trinitrate ointment heals up to two thirds of chronic anal fissures. Unfortunately, however, many patients experience troublesome headaches as a side effect of this treatment. This study assessed the effectiveness of oral and topical diltiazem in healing chronic fissures. METHODS: Fifty consecutive patients with chronic anal fissures were randomly assigned to receive oral (60 mg) or topical (2 percent gel) diltiazem twice daily for up to eight weeks. Anal manometry was performed before and after the first dose, and blood pressure was recorded at 15-minute intervals. Patients were reviewed fortnightly, pain was expressed with a visual linear analog scale, blood pressure was recorded, fissure healing was assessed, and side effects were noted. RESULTS: Twenty-four patients received oral diltiazem, and 26 received topical diltiazem. Mean (± standard error of the mean) maximum resting anal pressures fell by 15 and 23 percent from 95±4 to 81±4 and from 102±5 to 79±5 cm H₂O in the two groups, respectively. There was no significant reduction in blood pressure during the study or at follow-up in either group. Fissure healing was complete in 9 patients (38 percent) receiving oral diltiazem and 15 (65 percent) on topical treatment by eight weeks. Oral diltiazem caused side effects in eight patients (rash, two; headaches, two; nausea or vomiting, three; reduced smell and taste, one), whereas no side effects were seen in those receiving topical therapy (P=0.001). CONCLUSION: Oral and topical diltiazem heal chronic anal fissures. Topical diltiazem is more effective, achieving healing rates comparable to those reported with topical nitrates, with significantly fewer side effects.Supported by a Royal College of Surgeons of England Research Fellowship.Presented at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, June 24 to 29, 2000.