Ceftriaxone therapy of chronic inflammatory arthritis. A double-blind placebo controlled trial

To determine whether chronic inflammatory arthritis may respond to antibiotic therapy (implying a bacterial origin), we conducted a placebo-controlled, double-blind study. Sixty patients with inflammatory arthritis and antibody titers to Borrelia burgdorferi 1:64 or more were randomized to receive placebo (n = 20) or 2 g/d of ceftriaxone intravenously (n = 40) for 2 weeks. Two of 20 placebo- and 19 of 40 antibiotic-treated patients improved. At 1 month, the placebo-treated patients could elect to receive ceftriaxone. Altogether, 58 patients were treated with ceftriaxone and followed up for 13 to 24 months. Improvement was noted in 27 of the 58 antibiotic-treated patients. Patients with a wide diversity of inflammatory arthritis were studied. Response to ceftriaxone was seen in all groups, including 5 of 12 with rheumatoid arthritis, 5 of 8 with psoriatic arthritis, 3 of 5 with vasculitis, and 14 of 33 with less well-differentiated chronic inflammatory arthritis. In 16 of the 27 who responded to the antibiotic, the arthritis worsened 6 to 18 months after the initial response to ceftriaxone. Previous improvement of arthritis after oral antibiotic was a better predictor of response to ceftriaxone than either duration of disease or Lyme antibody titer. Side effects to ceftriaxone were frequent and included diarrhea (29/60) and acute allergic reactions (9/58). We conclude that some patients may have an occult bacterial infection underlying their chronic inflammatory arthritis, and may respond to antibiotic therapy. The response to ceftriaxone in patients with even weakly reactive Lyme titers encourages further prospective placebo-controlled studies of antibiotics in various subsets of chronic arthritis.     

Digoxin and xamoterol in patients with moderate chronic heart failure. A double-blind,randomized, controlled study

Summary Xamoterol is a partial beta₁ adrenoceptor agonist with positive inotropic properties. Treatment with xamoterol and digoxin was compared in 19 patients with cardiac failure (NYHA class II–III). The study consisted of a short-term and a long-term phase. The former was a randomized, doubleblind, crossover study with 6-week treatment periods. In the 15 patients who completed this phase, there was no significant difference between exercise duration on digoxin and on xamoterol. Exercise duration increased on digoxin by 27% and on xamoterol by 17% relative to baseline. Comparing digoxin and xamoterol, maximum exercise heart rate (p<0.001), blood pressure (p<0.01), and the pressure-rate product during maximum exercise were significantly lower on xamoterol treatment. The systolic time interval was shorter on digoxin than on xamoterol (p<0.001). No changes occurred in the echocardiographic parameters. After the short-term study, 13 patients were followed 3–6 months on the drug to which they had responded best (digoxin 7, xamoterol 6). The results of the short-term study were maintained during this period. In conclusion, we found that xamoterol may be an alternative to digoxin in patients with mild to moderate heart failure.     

Effect of oral 1,25 dihydroxycholecalciferol on calcium and phosphate malabsorption in primary biliary cirrhosis.

Changes in calcium and phosphate absorption in response to treatment with small doses of oral 1,25 (OH)2D3 were studied in 10 patients with primary biliary cirrhosis by means of a combined radio-isotope technique. There was a marked improvement in the fractional rates of absorption of calcium (P less than 0.01) and phosphate (0.05 P less than 0.1) after treatment. This implies than there is no end organ unresponsiveness to the action of active Vitamin D metabolites at the intestinal level in primary biliary cirrhosis.     

Acupuncture treatment for irritable bowel syndrome. A double-blind controlled study.

BACKGROUND/AIM: Irritable bowel syndrome is one of the most common gastrointestinal disorders in Western society, affecting around 15% of the population, especially young adults. The cause(s) of irritable bowel syndrome and effective treatment(s) have remained elusive. This study aimed at exploring the therapeutic value of acupuncture by comparing the responses of irritable bowel syndrome sufferers to true acupuncture versus sham acupuncture in a controlled double-blind study. METHODS: Twenty-five patients who fulfilled the Rome criteria (irritable bowel syndrome symptoms persisting for more than 1 year) comprised the final study population. They were recruited through a 'call for' bulletin sent to gastroenterologists practicing in the region of our medical center. True acupuncture was performed at LI-4 (colonic meridian, needle only) and sham acupuncture at BL-60 (urinary vesicle meridian, needle only). Patient assignment to one of the two groups was random. RESULTS: The effect of the first true acupuncture on overall symptoms and abdominal pain was a clear and significant improvement (p = 0.05). No comparable effect was seen in the second session. CONCLUSIONS: Although the true acupuncture results were consistently better, no difference was found between the two groups in the overall statistical analysis. We could not show a therapeutic benefit of this treatment modality in irritable bowel syndrome.     

Comparative efficacy and side effects of ursodeoxycholic and chenodeoxycholic acids in dissolving gallstones. A double-blind controlled study

In a double-blind controlled study of ursodeoxycholic acid (400 and 800 mg/day) and chenodeoxycholic acid (375 and 750 mg/day), in comparison with placebo, ursodeoxycholic acid was significantly more effective than chenodeoxycholic acid in dissolving gallstones after 12 mo of treatment. Although there continued to be better dissolution during ursodeoxycholic acid treatment (dissolution complete in 30% and partial in another 30% of the patients) than during chenodeoxycholic acid treatment (dissolution complete in 7% and partial in 40%) at 24 mo, this difference between the treatment groups was no longer statistically significant. The incidence of floating stones was significantly higher in the patients who dissolved their stones than in those who did not (p less than 0.001). The three failures of dissolution of floating stones during bile acid treatment were associated with chenodeoxycholic acid therapy--two of them with the 750-mg and the third with the 375-mg doses. Gallstone dissolution with ursodeoxycholic acid occurred in spite of a rise in biliary cholesterol saturation, which was consistent with a nonmicellar mechanism of cholelitholysis. Furthermore, more than threefold serum elevations of L-alanine aminotransferase were observed only during chenodeoxycholic acid therapy. They occurred in 2 patients treated with 375 and 750 mg/day, respectively. The enzyme levels normalized after discontinuation of chenodeoxycholic acid and have remained normal for 13 and 8 mo, respectively, after the institution of treatment with 800 mg/day of ursodeoxycholic acid. There was no correlation between the liver tests and biliary levels of lithocholic acid. Of all the symptoms studied, only constipation showed changes that approached statistical significance (p = 0.0681). There was a significant improvement of constipation in the combined chenodeoxycholic acid groups when they were compared with the combined ursodeoxycholic acid groups. The total bile acid pool expanded significantly in both the chenodeoxycholic acid and in the 800-mg ursodeoxycholic acid treatment groups. The marked increases of biliary ursodeoxycholic acid and chenodeoxycholic acid, respectively, indicated compliance with the treatment in all but 1 bile acid-treated patient. Neither serum triglycerides nor serum cholesterol showed significant changes in any of the treatment groups. The study shows that ursodeoxycholic acid dissolves gallstones faster and with fewer side effects than chenodeoxycholic acid. The results of the study are also consistent with the view that ursodeoxycholic acid is cholelitholytic at a lower dose than is chenodeoxycholic acid.     

Doxium 500 in chronic venous insufficiency: a double-blind placebo controlled multicentre study

The aim of this double-blind placebo-controlled study was to evaluate the therapeutic efficacy of Doxium in chronic venous insufficiency (CVI). 225 patients were treated randomly for 4 weeks with 1.5 g (3 capsules/day) of Doxium or placebo. The evolution of the leg oedema was determined by measuring calf and ankle circumferences. Pain and discomfort were assessed by visual analogue scale. The results show that at the end of the trial, all the examined parameters (leg oedema, pain, day and night cramps, discomfort, heavy legs, paresthesia and restless legs) were significantly more improved in the Doxium group than in the placebo group: the leg volume was diminished by 3.8% in the Doxium group compared to 1.2% in the placebo (p less than 0.005). The overall assessment by the physicians showed an improvement in 82% of the Doxium-treated patients compared to 42% of the placebo group (p less than 0.0001). The tolerance of the treatment was comparable in both groups.     

Twice daily dosage of bacampicillin in chronic bronchitis. A double-blind study.

Three groups of patients (total 48) with acute exacerbations of chronic bronchitis were treated orally for 10 days, in a double-blind clinical trial, with bacampicillin (an ampicillin ester) 1600 mg twice daily, 800 mg three times daily and oral ampicillin 1000 mg three times daily. Most exacerbations were caused by Haemophilus influenzae or Streptococcus pneumoniae. Clinical and bacteriological results were significantly more favourable in the two bacampicillin-treated groups. Both drugs were generally well tolerated. Serum and sputum ampicillin assays after the first dose showed higher and earlier peak levels after bacampicillin. Only after bacampicillin did the sputum levels regularly exceed the ampicillin M.I.C. for the Haemophilus influenzae strains. After the 1600 mg and 800 mg dose these levels averaged 0.85 and 0.41 mg/l respectively. One third of the Haemophilus influenzae strains studied required more than 0.25 mg/l ampicillin for inhibition of growth. Bacampicillin 1600 mg twice daily appears to be an effective and safe treatment for most episodes of acute exacerbations of chronic bronchitis.     

Sulpiride improves functional dyspepsia: A double-blind controlled study

A 4-week placebo-controlled trial was performed to study the efficacy of sulpiride, a hypothalamic non-sedative neuroleptic and dopamine antagonist, in the treatment of 100 patients with functional dyspepsia, defined as dyspeptic symptoms despite normal endoscopy and cholecystography. Two patients on sulpiride were withdrawn because of sleepiness; no other undue side effects were recorded. At the end of 4 weeks, significantly (P < 0.02) more patients on sulpiride had improvement of nausea and belching (78%, 54% respectively) than patients on placebo (45%, 17% respectively). Pain and vomiting disappeared in approximately 50% and 70% of patients, respectively. In the overall assessment, 72% and 39% of the patients on sulpiride and placebo respectively had satisfactory improvement or became symptom-free (P < 0.001). Response to treatment was not related to personal and environmental factors. It was concluded that sulpiride was effective in improving symptoms of dyspepsia, particularly nausea and belching.     

Nifedipine inhibits hypoxic pulmonary vasoconstriction during rest and exercise in patients with chronic obstructive pulmonary disease. A controlled double-blind study

To determine whether nifedipine reduces pulmonary artery pressure and pulmonary vascular resistance index during rest and exercise in patients with hypoxic pulmonary hypertension, we studied 6 clinically stable patients using a randomized, double-blind, crossover design. While patients were hypoxic, nifedipine significantly lowered mean pulmonary artery pressure during rest from (mean +/- SEM) 38 +/- 2 mmHg with placebo to 35 +/- 3 mmHg with nifedipine (p less than 0.01) and during exercise from 63 +/- 4 mmHg with placebo to 51 +/- 3 with nifedipine (p less than 0.01). During hypoxia nifedipine reduced pulmonary vascular resistance index during rest by 27% from 7.84 +/- 0.5 units with placebo to 5.71 +/- 0.6 units with nifedipine (p less than 0.02) and during exercise by 44% from 7.84 +/- 1 units with placebo to 4.37 +/- 1 units with nifedipine (p less than 0.001). Nifedipine when added to low flow oxygen reduced pulmonary vascular resistance index during rest by 16% from 6.15 +/- 0.8 units with oxygen to 5.14 +/- 0.5 units with oxygen plus nifedipine (p less than 0.007) and during exercise by 27% from 5.9 +/- 0.9 units with oxygen to 4.3 +/- 0.7 units with oxygen plus nifedipine (p less than 0.005). On room air nifedipine decreased PaO2 during rest by only 4 +/- 1 mmHg and did not decrease exercise PaO2. During oxygen therapy nifedipine decreased PaO2 during rest by 12 +/- 4 mmHg and during exercise by 8 +/- 3 mmHg. Nifedipine therapy, however, substantially increased oxygen delivery during rest and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of duodenal ulcer with antacid and sulpiride. A double-blind controlled study.

The effect of aluminum-magnesium hydroxide tablets (800 mg seven times per day) and that of sulpiride, a hypothalamic neurolaptic, were studied in 101 patients with duodenal ulcer in a double-blind controlled 4-wk trial. Significantly more of the patients treated with antacid, sulpiride, or antacid-sulpiride combination showed a greater than 50% reduction in ulcer size than did the patients treated with placebo. However, only in the antacid- and antacid-sulpiride-treated groups did the ulcer, with and without residual inflammation, disappear statistically more often than in the placebo-treated group. Furthermore, only in the antacid-sulpiride-treated group did complete healing, with no trace of inflammation, occur statistically more often than in the placebo-treated group. Disappearance of ulcer pain was likewise statistically more frequent in the antacid-sulpiride group than in the placebo-treated group. Antacid therapy with aluminum-magnesium hydroxide tablets appears to accelerate the rate of ulcer healing. Sulpiride appears to have a minor but definite synergism with antacids. Cigarette smoking affected ulcer healing adversely; on the other hand, factors favorable to healing were the early onset age of ulcer symptoms and acid hypersecretion. Male patients also healed more favorably than females.     

Angioscintigraphic assessment of hemodynamic effects of penbutolol in cirrhotics with portal hypertension. A double-blind, randomized, controlled study

This randomized double-blind controlled study analyzed the hemodynamic effects of penbutolol, a new levorotatory beta-blocker, using radionuclide angiography. Twenty cirrhotics with esophageal varices were randomized to two groups: 10 received 40 mg/day of penbutolol orally and the others placebo. Angioscintigraphy was performed before and after an 8-day treatment period. Three cases in the penbutolol group were lost due to software damage, hence the data of 17 patients were analyzed. The two groups were matched for age, sex, etiology of cirrhosis and hepatic function. The index of portal perfusion decreased significantly (-29%; p = 0.018) and the hepatic artery index increased significantly (+23%; p = 0.018), while no changes were observed after placebo. The heart rate decreased significantly after penbutolol (-9%; p = 0.028), while neither penbutolol nor placebo modified the ejection fraction. In conclusion, penbutolol decreased portal perfusion index (the compensatory increase in the hepatic artery index confirmed this change) without major modification of total hepatic blood flow or systemic hemodynamics. Angioscintigraphy is reasonably accurate, reproducible, safe and can be considered suitable for routine use in the assessment of liver hemodynamics.     

Evaluation of D-penicillamine in juvenile chronic arthritis. A double-blind, multicenter study

Seventy-four children with juvenile chronic arthritis were entered into a 6-month, multicenter, comparative double-blind study of the efficacy of D-penicillamine versus placebo. The results were evaluated in 70 patients, 55 of whom completed 6 months of the study. Improvement was observed in the total number of stiff joints, total number of painful joints, and total severity index measuring joint pain. There was also a significant reduction in the concurrent use of nonsteroidal anti-inflammatory drugs. D-penicillamine was well-tolerated in all but 2 patients. Some children in the placebo group exhibited definite improvement; however, relapses that were observed were mainly in that group. These results confirm the efficacy of D-penicillamine for the treatment of joint involvement in juvenile chronic arthritis.     

A comparison of cyclobenzaprine and placebo in the management of fibrositis. A double-blind controlled study

The efficacy of cyclobenzaprine (Flexeril), as compared with placebo, was tested in a 12-week, double-blind, controlled trial of 120 patients with fibrositis. Of the patients who received placebo, 52% dropped out due to lack of efficacy of the drug, compared with 16% of patients taking cyclobenzaprine. The dropout rate due to adverse reactions was similar in the 2 groups. Patients taking cyclobenzaprine experienced a significant decrease in the severity of pain and a significant increase in the quality of sleep. There was a trend toward improvement in the symptoms of fatigue, but morning stiffness was not alleviated. These improvements in symptoms were associated with a significant reduction in the total number of tender points and in muscle tightness. Our findings indicate that cyclobenzaprine is a useful adjunct in treating patients with the fibrositis syndrome.     

A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B

BACKGROUND: Emtricitabine is a nucleoside analogue approved for treatment of human immunodeficiency virus 1 with clinical activity against hepatitis B virus (HBV). METHODS: To compare the safety and efficacy of emtricitabine with placebo in patients with HBV, we conducted a randomized (2:1), double-blind study at 34 sites in North America, Asia, and Europe that enrolled adults between November 2000 and July 2002 who had chronic HBV infection but had never been exposed to nucleoside or nucleotide treatment. Each patient received either 200 mg of emtricitabine (n=167) or placebo (n=81) once daily for 48 weeks and underwent a pretreatment and end-of-treatment liver biopsy. Histologic improvement was defined as a 2-point reduction in Knodell necroinflammatory score with no worsening in fibrosis. RESULTS: At the end of treatment, 103 (62%) of 167 patients receiving active treatment had improved liver histologic findings vs 20 (25%) of 81 receiving placebo (P<.001), with significance demonstrated in subgroups positive (P<.001) and negative (P=.002) for hepatitis Be (HBe) antigen. Serum HBV DNA readings showed less than 400 copies/mL in 91 (54%) of 167 patients in the emtricitabine group vs 2 (2%) of 81 in the placebo group (P<.001); alanine aminotransferase levels were normal in 65% (109/167) vs 25% (20/81), respectively (P<.001). At week 48, 20 (13%) of 159 patients in the emtricitabine group with HBV DNA measured at the end of treatment had detectable virus with resistance mutations (95% confidence interval, 8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss were not different between arms. The safety profile of emtricitabine during treatment was similar to that of placebo. Posttreatment exacerbation of HBV infection developed in 23% of emtricitabine-treated patients. CONCLUSION: In patients with chronic HBV, both positive and negative for HBe antigen, 48 weeks of emtricitabine treatment resulted in significant histologic, virologic, and biochemical improvement.     

Electrophysiologic effects of the calcium antagonist isradipine, a double-blind placebo controlled study

The electrophysiologic effects of the calcium channel antagonist isradipine (0.5 mg) in comparison to placebo were evaluated in a double blind study with nine patients in two groups. The patient groups were not different in respect to the underlying cardiac disease, electrophysiologic parameters at the baseline study, or in blood pressure. Isradipine significantly decreased the systolic (p less than 0.01) and diastolic (p less than 0.05) blood pressure, while sinus cycle length decreased significantly (p less than 0.05) in the placebo group and the isradipine group with no difference between the two study groups. The influence on sinus node recovery time, effective refractory period of the av-node, intranodal conduction time, and PR interval were not significant. In conclusion, isradipine significantly decreased systolic and diastolic blood pressure. The decrease in sinus cycle length after intravenous isradipine was not significantly different from the decrease seen in the placebo group. Atrioventricular conduction was not significantly affected.     

曲昔派特治疗慢性胃炎的多中心随机双盲对照研究

[目的]观察曲昔派特治疗慢性胃炎的疗效。[方法]将慢性胃炎患者随机分为治疗组与对照组,各60例。治疗组用曲昔派特(100mg/次,tid,餐后服用),对照组用迪乐(110mg/次,qid,餐前及睡前服用),2组疗程均为4周。分别于治疗4周及治疗结束后1周评估2组临床症状及内镜下胃黏膜病变改善率。[结果]:治疗组临床症状缓解率为90.0%,高于对照组(66.7%),2组比较差异有统计学意义(P0.01);治疗组内镜下黏膜病变缓解率为75.0%,与对照组(68.3%)比较,差异无统计学意义(P0.05)。[结论]曲昔派特对缓解慢性胃炎主要临床症状的疗效优于迪乐。     

Oxerutins (Venoruton): efficacy in chronic venous insufficiency--a double-blind,randomized, controlled study

The aim of this study was to confirm the clinical efficacy of oxerutins by evaluation of venous parietal tone and microvascular perfusion in a double-blind, randomized, placebo-controlled study. The study included 60 patients. Venous tone was evaluated by air-plethysmography (APG) in patients with venous insufficiency (CVI). Forty patients were treated with oxerutins and 20 with placebo for 4 weeks. The dose of the first 2 weeks was higher than that of the following 2 weeks. The age range was between 18 and 65 years. Randomized patients received treatment (oxerutins or placebo) according to the grade of CVI. Patients with grade I CVI received 2 g/day in the first 2 weeks of treatment and 1 g/day in the following weeks. Patients with grade II CVI received 3 g/day in the first 2 weeks and 2 g/day in the following 2 weeks. Visits were scheduled at baseline time (visit 1), at 2 weeks (visit 2) and at 4 weeks (visit 3). They were assessed with the following: (1) APG; (2) light reflection rheography (LRR); (3) capillaroscopy; (4) liquid crystals thermography. CVI signs/symptoms--heavy legs, edema, paresthesia, and cramps--were evaluated following a 4-point rating scale (0 = no symptom; 3 = severe symptoms). At visit 3 a final opinion on efficacy was provided by both patients and investigators, based on a 4-point scale (none, fairly good, good, excellent). The two groups were homogeneous for age, sex, and clinical distribution. The changes in venous capacity, were significant (p<0.01) in the oxerutins group at visits 2 and 3; values in the placebo group remained unchanged. The changes in LRR were significant in the treatment group at visits 2 (p<0.05) and 3 (p<0.01); values in the placebo group remained unchanged. Changes in temperature were significant in the oxerutins group at visits 2 (p<0.05) and 3 (p<0.01); changes in the placebo group were not significant at the end of the study. Capillaroscopy showed an improvement in patients treated with oxerutins. The results of the analysis of signs/symptoms favored active treatment. The overall effects of oxerutins were significantly better than the effects of placebo. Considering both noninvasive tests and clinical evaluation, oxerutins is effective in controlling chronic venous hypertension, without side effect, and with good tolerability.