Ofloxacin efficacy in the prophylaxis and treatment of experimental plague due to antigen complete and defective strains of the pathogen]

Strains of the plague microbe, antigen complete and defective by fraction I and mouse toxin had the same in vitro susceptibility to ofloxacin (MIC 0.08 mg/L). The drug was superior in its activity to pefloxacin and especially nalidixic acid. In the experiments with albino mice (prophylaxis, 5 days) the ofloxacin efficacy was lower when the infection was due to the plague microbe strains deprived of the ability to produce fraction I and mouse toxin, evident from a statistically significant increase of the drug ED50 and a decrease of the animal survival percentage. When used in the doses corresponding to the human average daily doses, ofloxacin provided effective animal protection (80 to 100 per cent survival) after the prophylaxis for 7 days and the treatment of the plague infection irrespective of the strains, complete or antigen changed. However, when the infection is due to the antigen changed strain, ofloxacin should be used in the maximum daily doses at least for 7 days.     

The augmentin (amoxicillin/clavulanate) prophylaxis of postoperative infectious complications in patients with acute surgical diseases of the abdominal cavity organs]

Augmentin was used prophylactically in 25 patients with an account of the infectious complication risk according to 4 regimens: ultrashort-term (1.2 g intravenously with initial narcosis), short-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg in 8 and 16 hours), middle-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg every 8 hours for 2 days) and long-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg every 8 hours for 3 days). One complication episode as wound suppuration was recorded. The routine approach to the use of antibiotics in emergency abdominal surgery, when antibiotics are administered every day for several days after the operation, should be revised.     

The experimental validation of the advantages of combined emergency (fluoroquinolones) and specific (EV Nalr) prevention of plague versus their sequential use]

Mice immunization with reference vaccine at the early stage of plague infection provided animals survival and prolonged mean survival period up to 2-5 days. Ciprofloxacin, ofloxacin and pefloxacin prevents development of post vaccine immunity at white mice, immunized by reference vaccine strain EV. Nalidixic acid and norfloxacin effect on post vaccine immunity was lower. Use of immunogenic strain EV Nafr (resistant to nalidixic acid and fluoroquinolones) provided antiplague immunity formation at the background of fluoroquinolones prophylaxis. Ciprofloxacin, ofloxacin and pefloxacin used for plague prophylaxis at white mice infected with Yersinia pestis (about 1000 LD50) inhibited postinfective immunity development. Nalidixic acid and norfloxacin didn't demonstrate such effect. Urgent (fluoroquinolones) and specific (EV Nalr) combined prophylaxis was evaluated as more effective for a 5-day period and provided the development of antiplague immunity.     

A trial of using augmentin (amoxicillin/clavulanate) in surgical practice]

The experience with the use of augmentin (amoxycillin/clavulane) in abdominal surgery for prophylaxis of postoperative purulent complications was analyzed. The drug was used in 44 patients after relatively pure operations, 37 of them having various risk factors. In 2 patients (4.5 per cent) of that group postoperative pyoinflammatory complications were recorded. For comparison the results of the prophylactic use of cefoperazone, cefamandole or ceftazidime in the group of 78 patients after relatively pure operations on the abdominal cavity organs were analyzed. Postoperative complications in the latter group amounted to 7.4 per cent (4 patients). The results of the treatment of patients in two groups after contaminated operations were also compared. The patients of one group (41 patients) were treated prophylactically with augmentin in a dose of 1200 mg intraoperatively followed by the drug use in a dose of 600 mg thrice daily for 1 to 2 days after the operation. Postoperative pyoinflammatory complications were recorded in 4 patients of that group (9.7 per cent). 78 patients of the other group were treated prophylactically with ceftazidime or cefoperazone in a dose of 2 g and metronidazole intraoperatively or cefoperazone in a dose of 2 g twice daily and metronidazole in a dose of 500 mg twice daily for 1 to 2 days after the operation. Postoperative infectious complications were recorded in 8 patients of that group (10 per cent). In the group of patients with acute cholecystitis treated with ciprofloxacin in a dose of 400 mg in combination, with metronidazole before the operation and for 1 to 2 days after the operation postoperative complications were recorded in 4 patients (17 per cent).     

Gatifloxacin Versus Ofloxacin for the Treatment of Uncomplicated Enteric Fever in Nepal: An Open-Label,Randomized, Controlled Trial

Background

Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A.

Methodology and Principal Findings

Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9–23) years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median time to fever clearance was 4.70 days (IQR 2.98–5.90) in the ofloxacin group versus 3.31 days (IQR 2.29–4.75) in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and all randomized patients were comparable.

Conclusion

Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. Trial registration: ISRCTN 63006567 (www.controlled-trials.com).     

Carminomycin study in breast cancer]

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.     

Famciclovir as antiviral prophylaxis in laser resurfacing procedures

Latent herpes simplex virus (HSV types I and II) may be reactivated by laser resurfacing procedures, presenting serious postoperative complications in approximately 9 percent of patients. Perioperative prophylactic administration of nucleoside analog antiviral agents has been shown to decrease the duration and severity of postsurgical herpes infection and to prevent recurrence. This study was conducted to assess the efficacy of famciclovir in preventing orofacial herpes virus reactivation and primary infection in patients undergoing laser resurfacing. HSV history was obtained from a total of 121 patients undergoing the procedure. Antiviral prophylaxis with famciclovir was begun 1 to 2 days before surgery and continued for 5 days after surgery. Patients with no history of orofacial herpes (n = 94) received 125 mg of famciclovir twice daily. Those with a history of orofacial herpes (n = 27) received 250 mg of famciclovir twice daily. Postsurgical HSV infection rates in patients receiving famciclovir prophylaxis were compared with those from a similar historical control group of HSV-positive patients (n = 127) who received no prophylaxis. In patients receiving famciclovir prophylaxis, one patient (1.1 percent) in the HSV-negative history group and no patients in the HSV-positive history group had postsurgical herpes infection. Famciclovir significantly reduced postsurgical herpes infection when compared with the 9.4 percent rate of herpes reactivation in patients who received no prophylaxis (p = 0.003). This study suggests that twice-daily famciclovir prophylaxis markedly reduces orofacial herpes virus infection in patients undergoing laser resurfacing.     

Single dose cefotaxime plus metronidazole versus three dose cefuroxime plus metronidazole as prophylaxis against wound infection in colorectal surgery: multicentre prospective randomised study.

OBJECTIVE--To establish whether a single preoperative dose of cefotaxime plus metronidazole was as effective as a standard three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery. DESIGN--Prospective randomised allocation to one of two prophylactic antibiotic regimens in a parallel group trial. Group sequential analyses of each 250 patients were performed. SETTING--14 District general and teaching hospitals. PATIENTS--1018 Adults having colorectal operations were randomised, of whom 943 were evaluated. Demographic features, conditions requiring surgery, and operative procedures were similar in the two groups. Most patients had surgery for carcinoma of the colon or rectum. INTERVENTIONS--Group 1 received cefotaxime 1 g intravenously plus metronidazole 500 mg intravenously preoperatively. Group 2 received cefuroxime 1.5 g intravenously plus metronidazole 500 mg intravenously preoperatively, followed by cefuroxime 750 mg intravenously plus metronidazole 500 mg intravenously eight hours and 16 hours postoperatively. MAIN OUTCOME MEASURES--Development of surgical wound infection (as evidenced by the presence of pus), death, or discharge from hospital. RESULTS--Wound condition was scored on a five point scale on alternate days until discharge or for up to 20 days postoperatively. Wound infection rates were: group 1, 32/453 (7.1%; 95% confidence interval 4.7% to 9.4%); group 2, 33/454 (7.3%; 95% confidence interval 4.9% to 9.6%). Death rates (group 1: 26/470 (5.5%); group 2: 31/471 (6.6%], the incidence of postoperative complications, the median duration of hospital stay (12 days), and antibiotic tolerance were all similar in the two groups. Pooled data from groups 1 and 2 showed that wound infections were more frequent when minor faecal contamination had occurred at operation and when the duration of operation exceeded 90 minutes (greater than 90 min 11.2% of cases; less than 90 min 4.8%) and were associated with an extended hospital stay. CONCLUSIONS--A single preoperative dose of cefotaxime plus metronidazole is an efficacious as a three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery and has practical advantages in eliminating the need for postoperative antibiotics.     

The use of augmentin (amoxicillin/clavulanate) in the postoperative period in patients with infectious-inflammatory diseases of the ENT organs]

Augmentin (SmithKline Beecham) was used in the treatment of 24 patients after operations on the otorhinolaryngologic organs. The drug was administered orally, intravenously or applied locally. After a radical operation on the maxillary sinus the use of augmentin resulted in a marked decrease of the wound secretion and soft tissue edema on the 6th-7th days. After tonsillectomy cleaning of the tonsil niche from the fibrin patches and the epithelialization started on the 4th-5th days. After operations on the temporal bone cleaning of the postoperative cavity and beginning of the epithelialization were observed on the 9th-10th days. On the whole, the use of augmentin accelerated the cure which was recorded 3-4 days earlier.     

Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

OBJECTIVE--To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN--Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING--The medical wards of University and City Hospitals, Nottingham. SUBJECTS--1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES--Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS--Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS--Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena.     

Ciprofloxacin in the treatment of infections in oncology patients

Treatment of infectious complications with ciprofloxacin in 65 patients provided good and satisfactory results in 67.7 and 20.0 per cent of the cases, respectively. The drug was efficient in sepsis, urogenital infections, respiratory infections and postoperative purulent complications. Ciprofloxacin showed a broad antibacterial spectrum. 96.3 per cent of the isolates belonging to aerobic organisms causing purulent inflammatory processes, including those with high antibiotic resistance levels, such as Pseudomonas spp., Proteus spp., Klebsiella tribe and Staphylococcus aureus were sensitive to the drug. In its antibacterial spectrum ciprofloxacin was similar to ofloxacin. The advantage of ciprofloxacin is its possible use not only orally but also intravenously. Adverse reactions to ciprofloxacin were observed in 5 (7.7 per cent) out of the 65 patients. In two cases discontinuation of the drug use was required. The use of ciprofloxacin in treatment of infectious complications in oncological patients is promising.     

On fluoroquinolones treatment safety in children (clinical, morphological and catamnesis data)]

Results of prospective comparative investigation of monofluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin) arthropathy are presented. The trial was performed at 144 children with mucoviscidosis (aged 0.5-16) and at 37 children with aplastic anemia (aged 1.75-15). Two groups differ by necessary antibacterials regimes and hence by different abilities for arthropathy development: patients with mucoviscidosis were treated with fluoroquinolones followed by repeated short courses in combination with other antibacterials; patients with aplastic anemia--were treated permanently for a long time with low doses as monotherapy for autoinfection prophylaxis. Analysis was performed on the base of catamnesis, year growth rate, postmortal morphological investigation of the right knee joint. It was shown that quinolone arthropathy development didn't depend on treatment duration, as it developed during the first three weeks of the fluoroquinolone use, but depended on the drug, patient age and nosology. Arthropathy has favourable prognosis and was fully resolved at the period from 7 days to 3 month according to the arthropathy form (arthrologic, arthritic). Quinolones arthropathy at the children has specific features, the main one is absence of cartilage damage confirmed by morphological analysis.     

Open, randomized multicenter comparative trial of rabeprazole, ofloxacin and amoxicillin therapy for Helicobacter pylori eradication: 7 vs. 14 day treatment

BACKGROUND: Because of the increasing resistance to clarithromycin and metronidazole, two of the antibiotics used for the eradication of Helicobacter pylori, new therapeutic alternatives are needed. The aim of this study was to determine the efficacy of a randomized, comparative trial of 7 vs. 14-day triple treatment with rabeprazole, ofloxacin and amoxicillin for H. pylori eradication. MATERIAL AND METHODS: The present authors studied 76 dyspeptic patients infected with H. pylori diagnosed by both histology and a rapid urease test. Patients were randomized to receive rabeprazole (20 mg b.i.d.), plus ofloxacin (400 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 7 days (group 1) vs. 14 days (group 2) and were followed by 6 weeks. Eradication was assessed 4 weeks after completing the course of study treatment by the (14)C-urea breath test. Per protocol and intention-to-treat eradication rates were determined. RESULTS: For the intention to treat analysis, the eradication rate was 62.2% for group 1 and 92.3% for group 2 (p =.004). For the per protocol analysis, eradication rate for group 1 was 63.9% and for group 2 was 97.3% (p =.001). CONCLUSIONS: Triple therapy with rabeprazole, amoxicillin and ofloxacin by 14 days was efficient for H. pylori eradication and therefore deserves further study. The same regimen prescribed for 7 days had a significantly lower and unacceptable cure rate and should not be used.     

Characterization of fumonisin toxicity in orally and intravenously dosed swine

Fumonisin B₁ (FB₁), a recently identified mycotoxin produced by Fusarium moniliforme in corn, has been shown to cause death in swine due to pulmonary edema, an apparently species specific effect, and to interfere with sphingolipid metabolism in vitro. Here we characterize the toxicity of fumonisins, using female cross-bred swine weighing 6 to 13 kg, and present a hypothesis regarding the mechanism of fumonisin-induced pulmonary edema in swine. FB₁ was given daily intravenously (IV) to pig 1 for 9 days for a total of 72 mg (7.9 mg/kg) and to pig 2 for 4 days for a total of 67 mg (4.6 mg/kg). Pig 3 (control) was given saline IV for 9 days. Corn screenings naturally contaminated with FB₁ (166 ppm) and FB₂ (48 ppm) were fed to pigs 4, 5, and 6, and ground corn was fed to pigs 7 and 8 (controls). Pigs 4 and 7 were killed on day 5; pig 5 was found dead on day 6; and pigs 6 and 8 were killed on day 15. Pigs 4 and 5 had ingested 187 and 176 mg total fumonisins, respectively, while pig 6 had ingested 645 mg. Feed consumption had decreased in pigs fed corn screenings, with an additional sharp decrease prior to onset of clinical signs. Increases in serum liver enzymes, total bilirubin, and cholesterol were present, but electrocardiograms, heart rate, and body temperature were unaffected. Pigs dosed IV with FB₁, developed mild intermittent respiratory abnormalities, while those fed screenings developed respiratory distress within 5 days. Mild interstitial pulmonary edema was observed in pig 1. Severe interstitial pulmonary edema, pleural effusion, and increased lung wet/dry weight ratio were observed in pigs 4 and 5. All pigs given fumonisin (either IV or orally) had hepatic changes characterized by hepatocyte disorganization and necrosis; pancreatic acinar cell degeneration was also observed. Ultrastructural changes in orally dosed swine included loss of sinusoidal hepatocyte microvilli; membranous material in hepatic sinusoids; and multilamellar bodies in hepatocytes, Kupffer cells, pancreatic acinar cells and pulmonary macrophages. Pulmonary intravascular macrophages (PIMs) contained large amounts of membranous material. Thus, the target organs of fumonisin in the pig are the lung, liver, and pancreas. At lower doses, slowly progressive hepatic disease is the most prominent feature, while at higher doses, acute pulmonary edema is superimposed on hepatic injury and may cause death. We hypothesize that altered sphingolipid metabolism causes hepatocellular damage resulting in release of membranous material into the circulation. This material is phagocytosed by the PIMs thus triggering the release of mediators which ultimately results in pulmonary edema.Presented in part at the 1991 Annual Meeting of the Society of Toxicology. The Toxicologist 11: 143 (A499).     

氧氟沙星对小鼠生殖毒性和致畸性的研究

目的研究氧氟沙星对昆明系小鼠胚胎和胎鼠发育的影响,确定其是否存在生殖毒性和致畸性。方法①雄鼠分别灌服各剂量氧氟沙星,连续10d,末次给药24h后与母鼠合笼,在妊娠第三天取胚胎,记录各剂量组胚胎发育率。②孕鼠妊娠零天给药,分别经口灌服高、中、低剂量[36、72和360mg(kg.bw)]氧氟沙星溶液,连续给药3d,在妊娠第三天收集胚胎,记录胚胎发育率。③孕鼠妊娠零天给药,分别经口灌服各剂量氧氟沙星溶液,连续给药10d,在妊娠第16天取出胎鼠,记录胎鼠体重、胎盘重、活胎数、胎鼠外观畸形和内脏畸形等指标。结果给药组与对照组相比,雄鼠服用高剂量组360mg(kg.bw)氧氟沙星对着床前胚胎发育影响显著(P<0.05),而中等剂量和低剂量组对着床前胚胎发育的影响不显著(P>0.05)。雌鼠服用不同剂量氧氟沙星对着床前胚胎发育影响不显著(P>0.05)。氧氟沙星对受孕鼠的活胎数和吸收胎数均无明显影响,给药组的活鼠体重、胎盘重均未见明显差异(P>0.05);药物组和对照组均未出现外观畸形和内脏畸形,也不存在剂量和效应关系。结论孕鼠服用不同剂氧氟沙星对昆明系小鼠胚胎和胎鼠发育无明显的影响,表明氧氟沙星对雌性鼠不具有明显的生殖毒性和致畸性;但雄鼠服用高剂量氧氟沙星对着床前胚胎发育影响显著。     

The efficacy of cefepime (Maxipime) in the treatment of abdominal sepsis in surgical patients]

The efficacy of cefepime in the treatment of 46 patients operated for general peritonitis of various genesis and severity (APACHE II not greater than 35) was studied. Cefepime was used in a dose of 2 g administered every 12 hours as slow intravenous infusions in 0.9 per cent sodium chloride solution in combination with metronidazole administered intravenously in a dose of 7.5 mg/kg body weight. The treatment course was 4 to 15 days. 45 patients were given diflucan for the prophylaxis of fungal superinfection, 3 patients were given aminoglycoside antibiotics (netilmicin or amikacin) and 2 patients were given vancomycin per os. The favourable clinical effect of the cefepime therapy was stated in 38 patients (82.6 per cent) including 4 out of 10 patients with initial APACHE II > 15. 101 isolates of aerobic gram-negative and gram-positive microbes from 38 patients treated with cefepime in combination with metronidazole were tested to estimate the bacteriological efficacy of the therapy and it was shown that only 5.9 per cent of them was resistant. The pathogen eradication was stated in 84.2 per cent of the patients.     

Treatment of Colorectal Cancer Using a Combination of Liposomal Irinotecan (Irinophore C?) and 5-Fluorouracil

Purpose

To investigate the use of liposomal irinotecan (Irinophore C™) plus or minus 5-fluorouracil (5-FU) for the treatment of colorectal cancer.

Experimental Design

The effect of irinotecan (IRI) and/or 5-FU exposure times on cytotoxicity was assessed in vitro against HT-29 or LS174T human colon carcinoma cells. The pharmacokinetics and biodistribution of Irinophore C™ (IrC™) and 5-FU, administered alone or in combination, were compared in vivo. A subcutaneous model of HT-29 human colorectal cancer in Rag2-M mice was utilized to assess the efficacy of IrC™ alone, and in combination with 5-FU.

Results

The cytotoxicity of IRI and 5-FU were strongly dependent on exposure time. Synergistic interactions were observed following prolonged exposure to IRI/5-FU combinations. Pharmacokinetics/biodistribution studies demonstrated that the 5-FU elimination rate was decreased significantly when 5-FU was co-administered intravenously with IrC™, versus alone. Significant decreases in 5-FU elimination were also observed in plasma, with an associated increase of 5-FU in some tissues when 5-FU was given by intraperitoneal injection and IrC™ was given intravenously. The elimination of IrC™ was not significantly different when administered alone or in combination with 5-FU. Therapeutic studies demonstrated that single agent IrC™ was significantly more effective than the combination of IRI/5-FU; surprisingly, IrC™/5-FU combinations were no more effective than IrC™ alone. The administration of combinations of 5-FU (16 mg/kg) and IrC™ (60 mg IRI/kg) showed increased toxicity when compared to IrC™ alone. Treatment with IrC™ alone (60 mg IRI/kg) delayed the time required for a 5-fold increase in initial tumor volume to day 49, compared to day 23 for controls. When IrC™ (40 mg IRI/kg) was used in combination with 5-FU (16 mg/kg), the time to increase tumor volume 5-fold was 43 days, which was comparable to that achieved when using IrC™ alone (40 mg IRI/kg).

Conclusions

Single agent IrC™ was well tolerated and has significant therapeutic potential. IrC™ may be a suitable replacement for IRI treatment, but its use with free 5-FU is complicated by IrC™-engendered changes in 5-FU pharmacokinetics/biodistribution which are associated with increased toxicity when using the combination.     

Short and long courses of ofloxacin therapy of Klebsiella pneumoniae sepsis following irradiation.

Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The optimal length of therapy of such infection is not established. The effect of short and long courses of oral therapy with the quinolone ofloxacin for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy of bilateral radiation from 60Co. A dose of 10(8) organisms was given orally 4 days after irradiation, and therapy was started 1 day later. Cultures of the ileum 7 days after irradiation showed the recovery of K. pneumoniae in 7 of 10 untreated mice and in 3 of 20 treated with ofloxacin. However, 14 days after irradiation K. pneumoniae was isolated in 5 of 6 untreated mice, in 7 of 9 that received the short course of therapy, and in one of those that received the long course of therapy (P less than 0.05). At Day 7, K. pneumoniae was isolated from the livers of 6 of 10 untreated mice, and from none of those receiving ofloxacin (P less than 0.05). At 14 days, K. pneumoniae was isolated in 4 of 6 untreated animals, in 4 of 9 that received the short course of therapy, and in none of the mice that received the long course of therapy (P less than 0.05). Only 3 of 20 (15%) untreated mice survived for 30 days as compared to 11 of 20 (55%) mice treated for 7 days with ofloxacin and 18 of 20 (90%) mice treated for 21 days with ofloxacin (P less than 0.05). These survival data illustrate the efficacy of a 21-day course over a 7-day course of ofloxacin therapy for orally acquired K. pneumoniae infection in irradiated hosts.     

Short term treatment with St. John's wort, hypericin or hyperforin fails to induce CYP450 isoforms in the Swiss Webster mouse

This investigation was designed to determine whether St. John's wort (SJW)(435 mg/kg/d), a readily available antidepressant, or its purported active constituents hypericin (1 mg/kg/d) and hyperforin (10 mg/kg/d) were able to induce various hepatic cytochrome P450 (CYP450) isoforms. SJW, hypericin and hyperforin were administered to male Swiss Webster mice for four consecutive days and hepatic microsomes were prepared on day 5. None of the three treatments resulted in a statistical change in total hepatic CYP450 (SJW treated 0.95 +/- 0.09 nmol/mg vs control 1.09 +/- 0.14 nmol/mg). Furthermore, the catalytic activities of CYP1A2. CYP2E1 and CYP3A were unchanged from control following all three treatments as determined by ethoxyresorufin O-deethylation, p-nitrophenol hydroxylation and erythromycin N-demethylation respectively. Additionally, western immunoblotting demonstrated that there was no significant change in the polypeptide levels of any of the three isoforms. These results indicate that four days of treatment with moderate to high doses of SJW, hyperforin or hypericin fails to induce these CYP450 isoforms in the male Swiss Webster mouse.     

Safety and efficacy of intravenous sodium valproate in the treatment of acute migraine

This multicenter study investigated the safety and efficacy of intravenous valproate in acute migraine attacks and the possible impact of prophylactic valproate pre-treatment. Thirty-six patients established on migraine prophylaxis were administered 500 mg sodium valproate intravenously against acute migraine attacks. Pain development was assessed by visual analogue scale up to a 24 hours follow up interview to detect e.g. possible relapse symptoms. A subgroup analysis examined whether prophylactic treatment with valproate affected its acute anti-migraine efficacy. A meaningful headache reduction within two hours was achieved in all 12 patients with and in 20 out of 24 patients without valproate prophylaxis. Headache-associated signs and symptoms were substantially reduced. No serious side-effects were reported. The results confirm the therapeutic value of intravenous valproate in acute migraine attacks described in literature and show a beneficial effect on all investigated efficacy parameters with a trend to even better response in patients receiving valproate prophylaxis.