An alternative non-macrolide, non-imidazole treatment regimen for curing Helicobacter pylori and duodenal ulcers: ranitidine bismuth citrate plus amoxicillin. The RBC H. pylori Study Group. A comparative trial of low dose cefaclor and macrocrystalline nitrofurantoin in the prevention of recurrent urinary tract infection. Three-day therapy of lower urinary tract infections with nitrofurantoin macrocrystals: a randomized clinical trial. The course of neuropathy after cessation of cisplatin treatment, combined with Org 2766 or placebo. Efficacy of 28-day and 40-day regimens of sodium stibogluconate (Pentostam) in the treatment of mucosal leishmaniasis. Short and long term outcome of Helicobacter pylori positive resistant duodenal ulcers treated with colloidal bismuth subcitrate plus antibiotics or sucralfate alone. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. A new six-drug antiblastic regimen (R 14) at low doses (micropolychemotherapy) compared to CMF in the treatment of metastatic breast cancer: phase III study. Triple therapy for the eradication of Helicobacter pylori and reduction of duodenal ulcer relapse: comparison of 1 week and 2 week regimens and recrudescence rates over 12 months.
Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second-line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse.
                Two identically designed randomized, double-blind, double-dummy studies were conducted in patients with an H. pylori-associated duodenal ulcer. Patients were treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2 weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4 weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment were eligible for entry into a 24-week observation phase for the assessment of H. pylori status (culture, histology, and CLOtest) and ulcer relapse.
                A total of 229 patients with confirmed H. pylori infection at baseline were evaluated. Of these, 132 whose ulcers had healed entered the 24-week posttreatment observation phase. The combination of RBC plus amoxicillin resulted in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than did either treatment alone. All treatment were well tolerated.
                The combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori infection in more than half of the patients treated. This treatment regimen shows promise as the basis for future non-macrolide, non-imidazole triple therapy regimens for curing H. pylori infection. Such regimens may be appropriate second-line treatment for patients who are resistant to or who are unable to tolerate macrolide- or imidazole-containing therapies. One hundred and twenty women, aged between 18 and 90 years, with a history of at least four episodes of symptomatic urinary tract infection in the preceding 12 months, were randomized in an open, prospective study to prophylactic treatment with cefaclor 250 mg at bedtime or macrocrystalline nitrofurantoin 50 mg at bedtime for 12 months. Ninety-seven (49 taking cefaclor, 48 taking macrocrystalline nitrofurantoin) were assessed for efficacy; 80% of these were symptomatically improved and remained abacteriuric during the period of prophylaxis. Symptomatic attacks while patients were taking prophylaxis occurred at least five times less often than before prophylaxis had started. Seventy percent of the patients continued in an improved condition after having stopped prophylaxis. All 120 patients were assessed for adverse events; these were twice as frequent in patients taking macrocrystalline nitrofurantoin (20% vs. 10%), but only 11 patients (three taking cefaclor, eight taking macrocrystalline nitrofurantoin) withdrew from the study. Due to the small numbers of patients experiencing adverse events, these differences are not statistically significant. No significant changes in haematological or biochemical parameters were found during or after the end of the 12-month course. The 22 patients assessable for efficacy who had a non-obstructive radiological abnormality responded as well to prophylaxis as those with no detectable abnormality. Long-term, low-dose prophylaxis with a suitable antimicrobial agent is highly effective management for patients with recurrent urinary tract infections, and can appropriately be provided by the family doctor. Prophylaxis given for 1 year gives better results than when given for 6 months. Forty-nine girls between the ages of 2 and 18 years with a symptomatic urinary tract infection documented by two clean-catch urine cultures completed a double-blind study comparing the effectiveness of three days versus ten days of nitrofurantoin macrocrystal therapy. Localization of the infection to the lower urinary tract was presumed on the basis of clinical presentation. All patients had sterile urine on day two or three of therapy. In the ten-day group, two of 23 patients (8.7%) experienced a single relapse, and seven patients (30%) had 12 episodes of reinfection during a six-month follow-up. In the three-day group, two of 26 patients (7.7%) had a single relapse, and six patients (23%) had 12 episodes of reinfection. The rates of relapse and reinfection in the compared groups were not statistically significantly different (P greater than 0.05). Three days of treatment with nitrofurantoin macrocrystals is an effective regimen for symptomatic girls presumed to have uncomplicated lower urinary tract infections. Peripheral neuropathy is an important and disabling side-effect of cisplatin treatment. A new drug, Org 2766, has been found to prevent this neuropathy up to 1 month after treatment. A group of 18 patients with ovarian cancer, who participated in an earlier randomized study with placebo or Org 2766, together with cisplatin and cyclophophamide, were thereafter prospectively followed up to 2 years after discontinuation of treatment to monitor the development of neurological signs and symptoms and vibration perception threshold (VPT). Exploratory, descriptive data analysis shows that between 1 and 4 months after the last cycle the average sum score for neurological signs and symptoms and VPT had deteriorated compared with 1 month after treatment. Thereafter a gradual but incomplete improvement was seen between 4-12 and 12-24 months after treatment. These changes were seen in all patients regardless of previous treatment with Org 2766 or placebo, but deterioration was less pronounced in patients previously treated with Org 2766. These results suggests that treatment with Org 2766 to prevent a cisplatin-induced neuropathy should possibly be continued up to 4 months after the last cycle of cisplatin. The efficacy and toxicity of two regimens of antimony, 28 and 40 days of 20 mg of antimony/kg/day, were compared in the treatment of culture-positive mucosal leishmaniasis involving more than one anatomic site. Forty consecutive eligible Peruvians with infiltrative or ulcerative mucosal disease of the lips, nose, palate-uvula-pharynx, or larynx-epiglottis were randomized to receive either 28 days (P28) or 40 days (P40) of sodium stibogluconate (Pentostam). Treatment was prematurely terminated due to thrombocytopenia in three patients and two patients did not complete six months of follow-up. At one month post-treatment, 13% (2 of 16) of the P28 patients and 16% (3 of 19) of the P40 patients no longer had infiltrates or ulcers and were initially considered cured. During a further 11 months of follow-up, infiltrated lesions healed in eight more P28 patients and in 10 more P40 patients. The cure rate after 12 months of follow-up was therefore 63% for both groups (10 of 16 in the P28 group and 12 of 19 in the P40 group). The total of 13 patients who had infiltrates or ulcers at the 9-12-month follow-up were considered failures. All seven patients (three in the P28 group and four in the P40 group) whose lesions were culture-positive for Leishmania at some point in the 12 months after treatment, and who were thereby parasitologic failures, were also clinical failures.(ABSTRACT TRUNCATED AT 250 WORDS) Thirty two patients with Helicobacter pylori positive duodenal ulcers resistant to treatment were randomly assigned to 4 weeks' treatment with sucralphate 4 g/day or colloidal bismuth subcitrate 480 mg/day plus amoxycillin from days 1 to 7 and tinidazole from days 8 to 14. After 4 weeks, patients with unhealed ulcers were crossed over to the other form of treatment for a further 4 week period. Patients with healed ulcers were followed up for 1 year without maintenance therapy with clinical and endoscopic investigations 3, 6, and 12 months after healing. Complete healing rates at 4 weeks were 88% (15 of 17) in the colloidal bismuth subcitrate plus antibiotics group and 40% (six of 15) in the sucralphate group (p < 0.05). After cross over, overall healing rates were 88% (22 of 25) and 47% (eight of 17), respectively (p < 0.05). H pylori eradication occurred in 83% of patients treated with the triple therapy. Cumulative relapse rates at 12 months were 12% (two of 17) in patients in whom H pylori had been eradicated and 100% (10 of 10) in those with persistent infection after short term therapy (p < 0.05). These results show that a colloidal bismuth subcitrate plus antibiotics regimen is highly effective in the short term treatment of resistant duodenal ulcers and that H pylori eradication can change the natural tendency to early recurrence of these ulcers. Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost.
                This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency.
                This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection.
                Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30.
                In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment. Two groups of 23 patients each, having advanced breast cancer, entered this prospective and randomized study. One group was treated with the conventional schedule of CMF (cyclophosphamide 100 mg/m2/po from the first to the 14th day, methotrexate 40 mg/m2/iv the first and the 8th day, 5-fluorouracil 600 mg/m2/iv the first and the 8th day), and the other was treated with a new six-drug regimen, administered at low doses (R 14: cyclophosphamide 2 mg/kg/iv, vincristine 0.01 mg/kg/iv, vinblastine 0.1 mg/kg/iv, the first day and 5-fluorouracil 5 mg/kg/iv, methotrexate 0.7 mg/kg/iv, adriamycin 0.5 mg/kg/iv the 2nd day every 21 days). The remission rate was 35% (8/23) and 39% (9/23) for CMF and R 14 respectively. The median duration of objective remission was 6 months for CMF and 5 months for R 14 regimen. The median survival time of responding patients was 18 months for CMF and 14 months for R 14. This study shows that the new six-drug regimen at low doses is effective (regarding subjective, objective response and survival rate), and its toxicity is no higher than that of CMF (the incidence of leukopenia was significantly lower during the first course). Therefore, R 14 should be considered an alternative regimen to CMF in the treatment of advanced and, possibly, early breast cancer. The advantages for using R 14 are: 1) it is less toxic (a single dose is a very small amount of medicine compared to what is usually administered), 2) an iv administration always follows a therapeutic program (while in a CMF schedule cyclophosphamide is self-administered by the patient). The aim of this study is to assess the relationship between Helicobacter pylori and the relapse of duodenal ulcer, and also to evaluate the differences in efficacy and side effects between 1 week and 2 week triple therapy. Sixty-two patients with active duodenal ulcer, which healed within 8 weeks of nizatidine treatment, were randomly allocated to one of two groups. Group 1 (n = 29) received no drugs, Group II (n = 33) received triple therapy for 1 week (IIa, n = 16) or 2 weeks (IIb, n = 17). Eleven patients whose ulcer did not heal after an 8 week nizatidine treatment period were randomly assigned into Group IIa (n = 5) and IIb (n = 6). Seven patients whose ulcer recurred after discontinuation of nizatidine were allocated to receive 2 weeks of triple therapy. All patients received endoscopy 6 weeks after entry, and again at 3, 6 and 12 months unless both ulcer recurrence and H. pylori infection were found. The frequency of ulcer relapse 6 weeks after the active duodenal ulcer had healed was 83% (24/29 in Group I, 13% in Group 11a and 14% in Group IIb. The cumulative rate of recurrence was significantly higher in Group I than in Group II (90 vs 30% at 12 months, P < 0.01). Ulcer relapse was associated with persistence of H. pylori infection (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.