Aziridinylbenzoquinone (AZQ) in the treatment of recurrent pediatric brain and other malignant solid tumors

Summary To assess the response rates and toxicity of AZQ in children with recurrent brain and other malignant solid tumors, a phase II study was implemented by the Pediatric Oncology Group. Eligible patients received AZQ 18 mg/M²/week i.v. for 4 doses followed by a 2 week rest period. Each dose was given over four hours (1/3 over the initial 20 minutes). After the first year, the dosage was reduced to 13 mg/M² due to myelotoxicity resulting in treatment delays. No objective responses were observed in 73 evaluable children with various noncentral nervous system tumors. Of the 91 patients with brain tumors, there were 4 CR's and 2 PR's in patients with astrocytoma, ependymoma, glioblastoma multiforme, oligodendroglioma, brain stem glioma and intracranial yolk sac tumor (median duration, 10 months; range, 2–20+ months). Three of 4 CR's were achieved with a dosage of 18 mg/M²/week. An additional 13 children with brain tumors experienced stable or improved disease (duration, 2–36 + months; median 7.5 months). The principal toxicity was myelosuppression which was cumulative but there were also 3 allergic reactions to AZQ. We conclude that for selected brain tumors, the rates of objective response and stable disease plus the duration of responses support further assessment of AZQ in combination with other agents. Furthermore, the 18 mg/M² dosage may provide better responses. Address for offprints: Pediatric Oncology Group, Operations Office, 4949 West Pine Boulevard, St. Louis, MO 63108, USA     

Phase II Trial of SarCNU in Malignant Glioma: Unexpected Pulmonary Toxicity with a Novel Nitrosourea

Summary Purpose: A multi-centre phase II study of SarCNU—a novel chloroethylnitrosourea (CNU)—in patients with recurrent malignant glioma to assess response rate, survival and effects of treatment. Patients and methods: Ten patients with histologically proven malignant glioma (seven with glioblastoma multiforme (GBM) and three with anaplastic astrocytoma) received SarCNU (860 mg/m²) orally on days 1, 5 and 9 on a 6 week schedule. Results: A total of ten patients were treated on protocol before accrual was suspended for a high rate of pulmonary toxicity. Of eight evaluable patients, five demonstrated at least one grade deterioration in DLCO from baseline. This necessitated premature closure of the trial. Stable disease was seen in five of seven evaluable patients (median duration 4.8 months; range 0.8–9.2) with progressive disease in the remainder. Conclusion: Despite promising preclinical data, SarCNU caused pulmonary toxicity in patients with recurrent malignant glioma and we plan no further studies in this indication. Supported by a grant from the Canadian Cancer Society via the National Cancer Institute of Canada     

Ethanol-induced advance in the onset of puberty is prevented by the GABAA antagonist bicuculline in female rats

OBJECTIVE: The use of alcohol during lactation produces an advance in the onset of puberty in female rats. This research studied the possible participation of GABAA activity in this phenomenon. METHOD: Female Wistar rats were exposed to one of three different treatments from 13 to 18 days of postnatal age: (1) ethanol (2.5 g/kg PO) twice a day and isotonic saline (10 ml/kg IP) four times a day (AS group), (2) ethanol (2.5 g/kg PO) twice a day and bicuculline (2.5 mg/kg IP) four times a day (ABic group), (3) water (25 ml/kg PO) twice a day and bicuculline (2.5 mg/kg IP) four times a day (WBic group). A fourth group (control) did not receive any drug. RESULTS: The advance in the age at vaginal opening and at the first vaginal estrous seen in females of the AS group was completely prevented in the ABic group when bicuculline was added to alcohol treatment. The age at first behavioral estrous, however, was not different between groups. The age at vaginal opening, first vaginal estrous and first behavioral estrous was not significantly different in control, ABic and WBic groups. Body weight at vaginal opening was lower in the AS group than in the other three groups. Gestational period was longer in the AS group, but the number of pups per litter was lower in females of the ABic and WBic groups. CONCLUSIONS: The results reported here support a significant role for GABAA activity in the effects of alcohol at the onset of puberty.     

Balsalazide: a review of its therapeutic use in mild-to-moderate ulcerative colitis

The aminosalicylate balsalazide is a prodrug which is metabolised by bacterial azo reductases in the colon to release its therapeutically active moiety mesalazine [mesalamine (US) or 5-aminosalicylic acid] and an inert carrier molecule. The systemic absorption of balsalazide and its metabolites is not required for the therapeutic efficacy of the drug, and has been demonstrated to be limited. Data from well designed trials with a duration of 8 to 12 weeks show that oral balsalazide 6.75 g/day is as effective as (two trials) or more effective than (one trial) oral delayed-release (pH-dependent) mesalazine 2.4 g/day and appears to be as effective as oral sulfasalazine 3 g/day in the treatment of active mild-to-moderate ulcerative colitis. In addition, balsalazide appears to have a faster onset of action than mesalazine. Furthermore, balsalazide was as effective as delayed-release mesalazine (dosages used were 1.2 and 1.5 g/day, where 1.6 g/day is recommended) and oral sulfasalazine 2 g/day (recommended dosage) in the prevention of relapse in ulcerative colitis in remission after 6 to 12 months of treatment; the balsalazide dosage was 3 g/day versus mesalazine and 2 g/day versus sulfasalazine. Although not well established, additional benefits may be achieved with balsalazide dosages up to 6 g/day. Data from well designed, 2- to 12-month trials show that balsalazide is well tolerated by patients with ulcerative colitis in both acute and maintenance indications, and is better tolerated than standard formulations of sulfasalazine at therapeutically relevant dosages. CONCLUSION: Balsalazide is a well tolerated and effective first-line therapeutic option for patients with ulcerative colitis, both for the treatment of active mild-to-moderate disease and as maintenance therapy to prevent disease relapse.     

Oral delayed-release mesalazine: a review of its use in ulcerative colitis and Crohn's disease

Oral delayed-release mesalazine is an enteric-coated formulation which releases mesalazine in the terminal ileum and colon. Up to 74% of patients with mild to moderately active ulcerative colitis experience endoscopic or symptomatic improvement (including remission) or both when treated with oral delayed-release mesalazine 2.4 to 4.8 g/day. There is a trend towards a better response in patients receiving higher daily dosages of oral delayed-release mesalazine, especially in patients with active distal disease. In patients with left-sided ulcerative colitis, oral balsalazide 6.75 g/day appears to be more effective than oral delayed-release mesalazine 2.4 g/day, but a higher dosage of oral delayed-release mesalazine 4.8 g/day may provide additional benefit in these patients. Oral delayed-release mesalazine 0.8 to 4.4 g/day appears to be as effective as sulfasalazine 2 to 4 g/day, prolonged-release mesalazine 1.5 g/day or balsalazide 3 g/day in maintaining remission in patients with ulcerative colitis. The optimal dosage of oral delayed-release mesalazine for the maintenance of remission is unclear. However, oral delayed-release mesalazine 1.6 g/day with rectal mesalazine 4g, administered twice weekly, was more effective than oral drug alone in maintaining remission in patients at high risk of relapse. In patients with left-sided or distal disease oral olsalazine 1 g/day appeared to be superior to oral delayed-release mesalazine 1.2 g/day for maintenance of symptomatic remission. Limited data in patients with Crohn's disease have shown oral delayed-release mesalazine 0.4 to 4.8 g/day to be an effective therapy for active disease (remission in up to 45% of patients) and for quiescent disease (relapse in 34% of recipients over a duration of up to 12 months). Preliminary data indicate that oral delayed-release mesalazine 2.4 g/day is effective in preventing postoperative recurrence of Crohn's disease. Oral delayed-release mesalazine is effective and well tolerated in sulfasalazine-intolerant patients with ulcerative colitis or Crohn's disease. CONCLUSIONS: Oral delayed-release mesalazine is effective in patients with mild to moderately active or quiescent ulcerative colitis. Available data suggest that patients with left-sided or distal ulcerative colitis are likely to require higher daily dosages of oral delayed-release mesalazine or supplementation with rectal mesalazine. Oral delayed-release mesalazine also appears to be effective in active and quiescent Crohn's disease. The drug is well tolerated and it appears to be effective in sulfasalazine-intolerant patients.     

No clinically relevant drug interaction between paracetamol and phenprocoumon based on a pharmacoepidemiological cohort study in medical inpatients

OBJECTIVE: A recent case control study suggests that paracetamol at a dosage above 1300 mg/day increases the anticoagulant effects of warfarin. In many European countries, phenprocoumon and not warfarin is used as an anticoagulant. However, the effects of paracetamol on the anticoagulant effects of phenprocoumon have so far not been evaluated. METHODS: This study is based on the data recorded prospectively between 1996 and 1998 in two Swiss teaching hospitals in the pharmacoepidemiological database of the SAS/CHDM project. As a first step, all phenprocoumon-treated patients with at least one international normalized ratio (INR) determination at least 4 days after cohort entry were selected and evaluated concerning paracetamol co-administration. The "paracetamol group" included only patients receiving at least 1300 mg/day paracetamol on the 3 days preceding the INR determination, whereas the comparison group contained only patients without paracetamol exposure during hospital stay. Thereafter, INR values of the paracetamol and the comparison groups were compared. RESULTS: The paracetamol and the comparison groups included 54 and 180 patients, respectively. Patients' characteristics in both groups were comparable. Patients in the paracetamol group received on average 2220 +/- 651 mg/day paracetamol. The median duration of paracetamol exposure was 5 days. The median difference in INR values between the paracetamol and the comparison groups was -0.3 (with a 99% confidence interval of -0.6, 0.1). CONCLUSIONS: These results suggest that paracetamol co-administration at a dosage of 2000-2500 mg/day for 3 days has no clinically relevant effects on the anticoagulant effects of phenprocoumon.     

静脉丙种球蛋白治疗川崎病疗效观察

目的探讨不同用法静脉输注丙种球蛋白(IVIG)治疗小儿川崎病的临床疗效。方法对298例川崎病(KD)患儿采用3种不同治疗方案:A组为IVIG 1g/kg单次静脉输注;B组为IVIG 2.0g/kg单次静脉输注,C组为IVIG 0.4g/(kg·d),连用4～5d,对比3组治疗后冠状动脉病变(CAD)发生率和急性期临床症状消失时间。结果川崎病发病10d内IVIG 1g/kg与IVIG 2.0g/kg和0.4g/(kg·d),连用4～5d,均能有效预防CAD的发生;急性期临床症状缓解方面:IVIG 1g/kg组和IVIG 2.0g/kg明显优于IVIG 0.4g/(kg·d)组,差异有显著性,但是A组与C组无显著差异。结论 IVIG 1g/kg单次静脉输注为治疗小儿川崎病经济方便和有效的方法。     

Gd-DTPA对胶质瘤磁共振波谱分析的影响研究

目的 探讨对比剂Gd-DTPA对颅脑胶质瘤氢质子磁共振波谱的影响.方法 28例脑胶质瘤患者（Ⅲ级间变型星形细胞瘤13例、Ⅳ级胶质母细胞瘤15例）,先行MRI平扫,包括T1WI轴位和矢状位扫描、T2WI轴位扫描、T2WI轴位FLAIR扫描.在FLAIR序列上选取肿瘤最大层面,设置感兴趣区进行三位多体素或者单体素氢质子波谱扫描.经肘静脉团注15 ml磁共振对比剂Gd-DTPA后行增强扫描,在肿瘤强化明显后再次行1H-MRS,位置及扫描参数与平扫 MRS完全一致.采用Philips波谱分析软件,比较注射对比剂前后胶质瘤强化区代谢产物NAA、Cr、Cho、NAA/Cr、ChdCr、NAA/Cho值.结果 胶质瘤平扫与增强MRS的瘤体强化区代谢产物NAA、Cr、Cho、NAA/Cr、Cho/Cr、NAA/Cho值分别为（0.20±0.08、0.19±0.09）、（0.24±0.15、0.23±0.15）、（0.51±0.16、0.53±0.17）、（1.02±0.69、0.99±0.63）、（2.76±1.46、2.79±1.51）、（0.41±0.20、0.38±0.17）,差异无显著性（P〉0.05）.结论 Gd-DTPA对波谱图像无影响,1H-MRS宜在增强扫描后进行,更准确地反映病变区域的代谢物情况.     

Retrospective analysis of the dosage of amphotericin B lipid complex for the treatment of invasive fungal infections.

STUDY OBJECTIVE: To understand the relationship between dosage and therapeutic response of amphotericin B lipid complex (ABLC) by analyzing underlying diseases, types of infections, and therapeutic outcomes with different dosages as second-line antifungal therapy. DESIGN: Retrospective analysis of low-dose (initial dose < or = 3 mg/kg) ABLC from three open-label, clinical, second-line treatment studies. SETTING: Centers in the United States (204), Canada (3), Australia (1), Mexico (1), and The Netherlands (1). PATIENTS: Five hundred fifty-one patients (5 enrolled twice) with invasive fungal infections, of whom 289 failed and 267 were intolerant to conventional antifungal therapy. INTERVENTIONS: Patients were to receive the recommended dosage of ABLC 5 mg/kg/day, with dosage reduction for markedly increased serum creatinine. The duration of treatment was 4 weeks; therapy could be extended if the investigator considered additional treatment necessary. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients (13%) received ABLC 3 mg/kg/day (low dosage) instead of the protocol-recommended 5 mg/kg/day Response was 65% and 56%, respectively. Logistic regression analysis revealed that the following patients are most likely to start therapy at the lower dosage: those with candidiasis and other yeast infections, patients with nephrotoxicity due to prior amphotericin B, and those with underlying conditions other than hematologic malignancy. CONCLUSION: These results suggest that ABLC 3 mg/kg/day may be effective in treating patients with candidiasis who do not have hematologic malignancy.     

Clinical experience with argatroban for heparin-induced thrombocytopenia in a large teaching hospital

Background:

Argatroban is a direct thrombin inhibitor approved for the prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). The product monograph does not guide clinicians beyond specifying the initial dose of 2 μg/kg per minute (or 0.5 μg/kg per minute for patients with hepatic impairment). Some authors have suggested that in the intensive care unit (ICU) and for patients with acute cardiac disease and those with renal or hepatic dysfunction, this dose may result in a supratherapeutic activated partial thromboplastin time (aPTT).

Objectives:

To evaluate the efficacy and safety of argatroban in adult patients with suspected HIT in a large teaching hospital, and to review dosing for patients in the ICU, patients with acute cardiac disease, and patients with renal or hepatic dysfunction.

Methods:

Charts of patients with suspected HIT who had received argatroban for at least 24 h between October 1, 2005, and October 1, 2007, at the Foothills Medical Centre, Calgary, Alberta, were examined retrospectively.

Results:

Thirty patients met the inclusion criteria, with charts available for review. Of these, 21 (70%) patients had an initial argatroban dose of 2 μg/kg per minute and 4 (13%) had an initial dose of 0.5 μg/kg per minute. The median duration of therapy was 6 days, and the mean dose was 2.14 μg/kg per minute. There were 122 dosage adjustments, the most common change being 0.5 μg/kg per minute, followed by adjustments of 1 and 0.1 μg/kg per minute. Six patients had supratherapeutic aPTT values (above 100 s), and none experienced major bleeding.

Conclusions:

The results of this study suggest that an initial argatroban dose of 2 μg/kg per minute is appropriate for patients with no hepatic dysfunction. Patients with acute cardiac disease and critically ill patients may require lower doses of argatroban; however no dosage adjustments are required for patients with renal dysfunction.     

Influence of N-Hexane on Embryo and Fetal Development in Mice

Pregnant outbred albino mice (CD-1) received n-hexane once daily by gavage at doses up to 2.20 g/kg/day on days 6–15 of gestation. Other pregnant mice received higher hexane doses (up to 9.90 g/kg/day), employing a three times a day injection schedule. At the lower, once-daily doses only one dam died and no teratogenic effects occurred. Higher hexane doses (t.i.d.) were toxic: 2 of 25 dams treated with 2.83 g/kg/day, 3 of 34 treated with 7.92 g/kg/day and 5 of 33 treated with 9.90 g/kg/day died. At the 7.92 and 9.90 g/kg/day doses, the average fetal weight was significantly (p<0.05) reduced, but the incidence of malformations in treated and vehicle (cottonseed oil) control groups did not differ significantly. Thus, n-hexane was not teratogenic even at doses toxic to the dam.     

Pharmacokinetic/pharmacodynamic and time-to-event models of ribavirin-induced anaemia in chronic hepatitis C

BACKGROUND: Interferon (IFN)-alpha and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C. However, ribavirin induces anaemia, especially by haemolysis, an adverse effect that is dose-limiting. OBJECTIVES: The aim of this study was to determine the relationships between ribavirin exposure and haemoglobin time-course, the time-to-anaemia and the covariates influencing these relationships in a population of patients treated for chronic hepatitis C. In addition, we also intended to establish a simple rule defining the need for dosage adjustment, using data obtained during the first month of treatment. METHODS: A retrospective analysis of 99 patients treated with IFNalpha plus ribavirin, with known dosage administration history, liver biopsy, demographic data, red blood cell counts, haemoglobin level (1037 measurements, median 10 per patient, range 2-31) and serum creatinine during the entire treatment period (178 days, range 53-382 days) was conducted. The data were analysed by a pharmacokinetic/pharmacodynamic population model and Weibull time-to-anaemia model. The rule defining the need for dosage adjustment was as follows: adjustment was needed if haemoglobin at steady state (H(ss)), estimated by the Bayesian method based on data obtained during the first month of treatment, was <12 g/dL for men or <11 g/dL for women. RESULTS: In both models, anaemia was related to the exposure of erythrocytes to ribavirin at time t (RT in mg/kg/day) by a maximum effect model, with RT(50) (dosage administration rate at which half the maximal effect is reached) approximately 12 mg/kg/day, and the significant covariates were initial haemoglobin level and bodyweight. Performances of a Bayesian prediction of H(ss) based on two early haemoglobin level measurements were encouraging (mean prediction error 0.12 g/dL, precision 0.85 g/dL). The proposed rule for the need of dosage adjustment was able to predict the actual evolution of the dosage regimen in 76% of non-adapted patients and 69% of adapted patients. CONCLUSION: The current guidelines for ribavirin dosage administration, based on bodyweight, are adequate, at least in the 45-105 kg range. Results indicate that Bayesian therapeutic monitoring could be helpful in controlling ribavirin-induced anaemia.     

The prevalence, clinical features and association of HLA-B27 in sacroiliitis associated with established Crohn's disease

Background Sacroiliitis is a recognized complication of Crohn's disease and may occur distinct from progressive ankylosing spondylitis (AS).
Aim To estimate prospectively the prevalence of sacroiliitis in patients with established Crohn's disease, to characterize the clinical features and to correlate these with the presence of HLA-B27.
Methods All Crohn's disease patients under active follow-up of between 5 and 12 years duration were invited to participate. Patients underwent a clinical evaluation including symptom questionnaire, rheumatological examination and underwent HLA genotyping. Patients then underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The clinical and radiological factors were correlated with HLA-B27 status.
Results 56 patients underwent initial assessment and 44 had MRI scans. Seventeen of 44 (39%) patients had MRI evidence of sacroiliitis, of whom 5 fulfilled the criteria for AS. Symptoms of low back pain were elicited in a majority of these patients – 11/17 (65%) compared to 3 of 27 (11%) patients with normal scans ( P  = 0.003). There were no differences in functional indices with the exception of patients with AS. HLA-B27 was present in seven patients, and all seven had MRI evidence of sacroiliitis, five had AS.
Conclusions Sacroiliitis is common in patients with established Crohn's disease and in the majority of cases, patients have symptoms of inflammatory low back pain if questioned carefully. HLA-B27 is not associated with isolated sacroiliitis, but is associated with AS. However, possession of HLA-B27 appears to convey a very high risk of developing axial inflammation in Crohn's disease.     

不同剂量丙种球蛋白治疗川崎病的疗效及对患儿冠脉病变的影响

目的：分析不同剂量丙种球蛋白（IVIG）在川崎病（KD）临床治疗中的应用价值。方法：回顾性分析2012年1月～2014年1月我院儿科收治确诊为川崎病48例患儿的临床资料,根据IVIG治疗剂量进行分组,给予IVIG 1g/kg剂量治疗24例为观察组,给予IVIG 2g/kg剂量治疗24例为对照组,观察比较两组治疗效果及随访患儿冠脉病变（CAL）影响。结果：观察组平均黏膜充血时间少于对照组,差异具有统计学意义（P<0.05）,而两组患儿热退、手足肿胀消退、淋巴结肿大消退时间比较均无显著差异（P>0.05）;观察组CAL发生率虽然略高于对照组,但差异无统计学意义（P>0.05）。结论：1g/kg剂量IVIG治疗川崎病不仅能达到常规2g/kg剂量的治疗及降低患儿CAL发生率的效果,而且相对经济、安全,值得临床推广。     

Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results

BACKGROUND: Anti-tumour necrosis factor-alpha antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor-alpha suppressive properties. AIM: To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. METHODS: Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5-2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. RESULTS: Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). CONCLUSIONS: Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension.     

万古霉素治疗葡萄球菌肺炎的疗效与肾毒性评价

目的:评价万古霉素治疗葡萄球菌肺炎的疗效及肾毒性。方法:回顾性分析浙江省中医院加强监护病房(ICU)应用万古霉素治疗 67例葡萄球菌感染病人的临床资料。根据病人肌酐清除率,决定每日万古霉素剂量,每日剂量 (30±s10 )mg·kg-1,疗程 7~14d,疗程剂量(22±13)g。结果:临床有效率为 88 %,细菌清除率 88 % (59 /67),毒性发生率为 16 % (11 /67 ),在发生肾毒性的病人中,23 %肾功能可以恢复正常。Logistic回归分析表明APACHEⅡ评分及万古霉素治疗前感染持续时间是临床疗效相关因素,肾毒性的发生与APACHEⅡ评分、万古霉素剂量及其他药物密切相关。结论:万古霉素治疗葡萄球菌肺炎疗效明显,肾毒性低,是安全可靠的抗生素。     

Effect of aztreonam on bacterial flora in human feces

Aztreonam (AZT), a new injectable monobactam antibiotic, was administered to 7 healthy male volunteers, aged 21-28 years (23 years, on average) and weighing 60.5-87.0 kg, (69.5 kg, on average) by one shot intravenous injection of 1,000 mg twice a day for 5 days. The effect of AZT on the fecal flora was studied 3 days before administration, on the day of the initiation, 3 and 5 days (end of the administration course) after the initiation, and 3, 5 and 10 days after the end of the administration. Fecal concentration of AZT was also studied. Also, fecal concentration and recovery rate of AZT in 4 healthy male volunteers aged 23-31 years (26 years, on average), weighing 59.5-70.5 kg (65.6 kg, on average) were measured by injecting 1,000 mg of AZT by intravenous injection only one time. Susceptibility of the bacteria isolated from the 7 cases receiving consecutive dosage to AZT, cefmetazole (CMZ), latamoxef (LMOX), cefoperazone (CPZ) and ceftazidime (CAZ) as well as side effect and laboratory values were examined with the following results. In the fecal flora, the population of Enterobacteriaceae on average was 10(7) cells/g feces on the day of the initiation and decreased by 2 logarithms to 10(5) cells/g 3 days after the initiation, 10(5) cells/g feces 5 days after the initiation with no bacterial isolation in 2 cases, 10(7) cells/g feces on 3 and 5 days after the end of administration respectively with recovery of the population to the average population on the day of the initiation. However, it increased 10 days after the end of administration with the population of 10(9) cells/g feces due to the isolation of one 10(10) cells/g feces, which was an increase by 2 logarithms as compared with average population before the administration. It was also higher than the average population 3 days before the initiation of administration. Temporal decrease or disappearance of the bacteria were noted by the administration of AZT. As to other cases of Gram-negative bacilli, Pseudomonas sp. was detected from only 2 cases 3 days before the initiation of administration and on the day of the initiation, but there was an increase to 4 and 5 cases 3 and 5 days after the initiation respectively. Number of isolation returned to 2 cases, 3, 5 and 10 days after the end of administration respectively and it was same as the number before the initiation of administration.(ABSTRACT TRUNCATED AT 400 WORDS)     

Lansoprazole in children: pharmacokinetics and efficacy in reflux oesophagitis

BACKGROUND: Data on the proton pump inhibitor lansoprazole in paediatric patients are limited. AIM: To investigate the pharmacokinetics, optimal dosage and efficacy of lansoprazole in paediatric patients. METHODS: A 24-h gastric pH recording and a pharmacokinetic study were performed after 7 days of lansoprazole, 17 mg/m2, in 23 patients with reflux oesophagitis (median age, 3.5 years). Response was defined as pH > 3 for > 65% of the recording. The dosage was doubled in non-responders. Patients with no response on day 14 were excluded. Responders underwent endoscopy after 4 weeks on the response-inducing dosage; abnormal findings led to a repeat endoscopy after four additional weeks. RESULTS: Nine patients responded to 17 mg/m2 and six to 30.3 mg/m2. On day 7, time with pH > 3 was significantly correlated with the area under the plasma concentration-time curve (P=0.003). The area under the plasma concentration-time curve was significantly greater in the nine responders to 17 mg/m2 than in the 14 other patients. Pharmacokinetic parameters were similar in responders and non-responders to the higher dose. After 4 weeks, oesophagitis was healed in 80% of responders. Adverse events occurred in three patients and required treatment discontinuation in one. CONCLUSIONS: Lansoprazole is effective and safe in children. The optimal starting dosage is 30 mg/m2 or 1.4 mg/kg.     

Effect of Kalmegh extract on rat liver and serum enzymes

Oral administration of Kalmegh extract under acute (single dosage) and sub-acute (for 7 and 15 consecutive days) conditions at a dosage of 0.5 g dry leaf/kg/day to adult rats produced no change in the activities of glutamate oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase (GPT) in liver and rerum. Administration of ethyl alcohol at a dosage of 0.2 g/kg/day (oral) for 7 and 15 consecutive days produced an appreciable increase in liver GOT and GPT activities. No appreciable change in serum GOT and GPT activities was observed under similar condition of treatment. Oral administration of a high dosage of ethyl alcohol (3 g/kg/day) produced significant increase in the activities of serum enzymes only. This alcohol-induced increase in serum transaminase activity became normal with pre- and post-treatment of Kalmegh extract (0.5 g/kg/day). This result suggests that Kalmegh extract protects alcohol-induced toxic-effect in liver tissue.     

Prolonged-release mesalazine: a review of its therapeutic potential in ulcerative colitis and Crohn's disease

Prolonged-release mesalazine (Pentasa) consists of ethylcellulose-coated microgranules from which mesalazine (known in the US as mesalamine) is released in the small and large intestine in a diffusion-dependent manner. Dose-dependent improvements in clinical and endoscopic parameters have been reported with prolonged-release mesalazine 2 and 4 g/day in clinical trials in patients with mild to moderately active ulcerative colitis. Induction of clinical and endoscopic remission was achieved in more patients receiving a daily dosage of 4 g/day than in those receiving placebo. In patients with ulcerative colitis in remission, prolonged-release mesalazine is effective in reducing the rate of relapse. Higher dosages tend to be more effective, and a 12-month remission rate of 64% has been reported for patients treated with a 4 g daily dosage of this formulation. Comparative data indicate that prolonged-release mesalazine has similar efficacy in maintaining remission to molar equivalent doses of sulfasalazine. Data from a study in patients with mild to moderately active Crohn's disease indicates that higher dosages (4 g/day) of prolonged-release mesalazine are more effective than placebo in reducing disease activity. After 16 weeks' treatment, 64% of patients receiving a 4 g/day dosage experienced clinical improvement and 43% attained remission. In studies of patients in remission of Crohn's disease, the formulation appears to be more effective in preventing relapse in patients with isolated small bowel disease than in those with colonic involvement. The tolerability profile of oral prolonged-release mesalazine is similar to that of placebo and the incidence of adverse events does not appear to be dose-related. Nausea/vomiting, diarrhoea, abdominal pain and dyspepsia occur most frequently, although their incidence is low. Reports of nephrotoxicity during prolonged-release mesalazine treatment are rare. Conclusions: Oral prolonged-release mesalazine is effective for maintenance and induction of remission of mild to moderately active colitis, both in patients with distal disease and in those with pancolitis. The formulation has similar efficacy to that of equimolar concentrations of sulfasalazine. Prolonged-release mesalazine also appears to be effective in the treatment of Crohn's disease, and maintenance therapy is of particular value in patients with isolated small bowel involvement. Evidence suggests that higher dosages (3 to 4 g/day) of prolonged-release mesalazine have additional therapeutic benefits over lower dosages in patients with inflammatory bowel disease without increasing the incidence of adverse events.