Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children.

BACKGROUND: Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5-10 microg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. OBJECTIVE: To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIV-infected children. METHODS: A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. RESULTS: Median (25th-75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5-1.5) microg/ml, 1.94 (1.4-2.2) microg/ml and 7.68 (6.1-7.8) microg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4-8.8) microg/ml and 9.25 (8.2-10.3) microg/ml respectively. CONCLUSION: Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children.     

Ofloxacin pharmacokinetics in patients on continuous ambulatory peritoneal dialysis

Pharmacokinetics of ofloxacin (OFX) was studied in patients on continuous ambulatory peritoneal dialysis (CAPD) carrying out three exchanges per day. In 11 patients given 300 mg of OFX orally, serum OFX concentration peaked at 2.44 mg/l 3.7 hours after administration and the mean elimination half-life of OFX was 25 hours. OFX concentrations in peritoneal fluid underwent cyclical changes with each change of solutions, reaching beyond 0.5 mg/l after 2 hours of equilibration. There was a highly significant correlation between corresponding serum and peritoneal fluid concentrations of OFX after an 8 h equilibration (r = 0.85, p less than 0.001). In 5 patients given a 400 mg loading dose followed by 200 mg of OFX per day for 7 days, trough serum OFX concentrations ranged from 1.35 to 7.00 mg/l and no adverse effects were noticed. CAPD per exchange removed less than 2% of the total dose of OFX given.     

Plasma concentrations of fluconazole after a single oral dose and administration in drinking water in cockatiels (Nymphicus hollandicus)

Candidiasis frequently affects the oropharynx, esophagus, and crop of juvenile birds with immature immune systems and adult birds that have received long-term antibiotic treatment. Fluconazole is used extensively in human medicine to treat mucosal and invasive candidiasis and has been used in birds; however, there have been few pharmacokinetic studies in avian species to guide safe and effective treatment. The purpose of the present study was to investigate the disposition of fluconazole in cockatiels (Nymphicus hollandicus) after single oral dose administration and to determine if therapeutic plasma concentrations could be safely achieved by providing medicated water. Twenty-eight cockatiels were placed into 7 groups and were orally administered a 10 mg/kg fluconazole suspension. Blood samples were collected from each group for plasma fluconazole assay at serial time points. Fluconazole-medicated drinking water was prepared daily and offered to 15 cockatiels at a concentration of 100 mg/L for 8 days. Blood was collected for plasma fluconazole assay at 2 time points on days 3 and 7. When using naive averaged data in the single-dose study, pharmacokinetic parameters were similar for both compartmental and noncompartmental analyses. The elimination half-life of fluconazole was 19.01 hours, maximum plasma concentration was 4.94 microg/mL, time until maximal concentration was 3.42 hours, and the area under the plasma concentration versus time curve (AUC) was 149.28 h x microg/mL. Computer-simulated trough and peak plasma concentrations at steady-state after multiple doses of fluconazole at 10 mg/kg every 24 hours, 10 mg/kg every 48 hours, and 5 mg/kg every 24 hours were approximately 4.1-8.5 microg/mL, 1.2-6.0 microg/mL, and 2.0-4.3 microg/mL, respectively. Mean +/- SD plasma fluconazole concentrations for the 100 mg/L medicated water study at 0800 and 1600 hours on day 3 were 3.69 +/- 1.22 microg/mL (range, 1.73-5.26 microg/mL) and 4.17 +/- 1.96 microg/mL (range, 3.58-7.49 microg/mL), respectively, and at 0800 and 1600 hours on day 7 were 4.78 +/- 0.91 microg/mL (range, 2.62-6.11 microg/mL) and 6.61 +/- 1.67 microg/mL (range, 3.76-8.78 microg/ mL), respectively. Treatment with fluconazole administered orally at a dosage of 5 mg/kg once daily or 10 mg/kg every 48 hours or fluconazole administered in the drinking water at a concentration of 100 mg/L is predicted to maintain plasma concentrations in most cockatiels that exceed the minimum inhibitory concentration of 90% or therapeutic AUC:MIC of most strains of Candida albicans (by using susceptibility data from humans). The compounded oral suspension was stable for 14 days when stored at 5 degrees C (41 degree sF) and protected from light.     

An evaluation of the perioperative efficacy of selective beta 1-blockade in coronary surgery. Studies with a late preoperative dose of metoprolol

The plasma concentration of metoprolol was measured hourly following an oral dose on two consecutive days--the day before, and the day of, coronary surgery. No significant difference was found between the two sampling days, though there was a tendency to lower concentrations during and after extracorporeal circulation. After a median dose of 50 mg the peak concentration (reached on average after 1.5 h) was 545 +/- 70 nmol/l on the first day and 388 +/- 57 on the day of surgery. The respective elimination rates from plasma, expressed as half-life, were 3.4 +/- 0.21 and 3.5 +/- 0.19 hours (NS). On the day of surgery the heart rate rose during the second half of the observation period, peaking above 130 beats/min. Heart rate was inversely correlated to metoprolol concentration in plasma with coefficient -0.68 before induction of anesthesia and -0.77 two hours after termination of extracorporeal circulation. The perioperative efficacy of beta-blockade following a late preoperative oral dose of the agent thus appeared to be reduced and inadequate.     

Pharmacokinetics of mycophenolate mofetil in patients with end-stage renal failure

BACKGROUND: Mycophenolate mofetil (MMF) acts as a prodrug for the immunosuppressive drug mycophenolic acid (MPA). It is rapidly converted to MPA following oral ingestion. MPA is metabolized to MPA glucuronide (MPAG), which is renally excreted. This study examines the pharmacokinetics of MPA and MPAG in patients with end-stage renal failure who were on hemodialysis (N = 10) or peritoneal dialysis (N = 10) treatment. METHODS: After an overnight fast, a single oral dose of 1 g MMF was given. Plasma concentrations of MPA and MPAG were measured from 0 (predose) to 36 hours after administration, using high-performance liquid chromatography (HPLC). The area under the concentration time curve (AUC) from 0 to 36 hours was calculated using the trapezoidal rule. RESULTS: Mean (+/- SD) AUC for MPA was 55.7 +/- 32.6 mg/L.h for hemodialysis patients and 44.7 +/- 14.7 mg/L.h for peritoneal dialysis patients, which is similar to expected values for subjects with normal renal function. The mean (+/- SD) maximum plasma concentration (Cmax) for MPA was lower than would be expected for subjects with normal renal function (16.01 +/- 10.61 mg/L for hemodialysis, 11.48 +/- 4.98 mg/L for peritoneal dialysis). MPAG clearance was prolonged with AUC approximately five times what would be expected in subjects with normal renal function (1565 +/- 596 mg/L.h for hemodialysis, 1386 +/- 410 mg/L.h for peritoneal dialysis). There was no significant difference for any of the pharmacokinetic parameters between subjects on hemodialysis and those on peritoneal dialysis. Plasma concentrations of MPA and MPAG did not fall significantly during hemodialysis. No MPA was detectable in hemodialysis or peritoneal dialysis fluid, but small amounts of MPAG were detected in hemodialysis fluid in 1 out of 10 subjects and in peritoneal dialysis fluid in 3 out of 10 subjects. CONCLUSIONS: The accumulation of MPAG may be responsible for the poor gastrointestinal tolerance of this drug in dialysis patients and probably limits the maximum dose of MMF that can be tolerated.     

Once weekly intraperitoneal therapy for gram-positive peritonitis

The pharmacokinetics and clinical outcome following a 30 mg/kg/2 L intraperitoneal (IP) dose of vancomycin, which was administered once a week for 3 weeks, was studied in ten continuous ambulatory peritoneal dialysis patients with peritonitis. Vancomycin was 91% absorbed following the first dose and rapidly achieved therapeutic serum concentrations, 19 +/- 8 mcg/mL at 1 hour and a peak of 37 +/- 8 mcg/mL at 6 hours. Vancomycin was eliminated slowly with a mean total clearance of 7 +/- 3 mL/min/70 kg and a distribution volume of 1.2 +/- 0.3 L/kg. The resultant mean serum t1/2 over the first week was 184 hours and the mean serum concentration at 168 hours was 10 +/- 4 mcg/mL. Based on the positive clinical outcome (100% cure) among patients with uncomplicated gram-positive peritonitis, the potential use of this alternative vancomycin dosing regimen is proposed.     

Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents

Summary The effect of equivalent oral doses of vitamin D3 600 IU/day, 4200 IU/week and 18,000 IU/month on vitamin D status was compared in a randomized clinical trial in nursing home residents. A daily dose was more effective than a weekly dose, and a monthly dose was the least effective. Introduction It is assumed that equivalent daily, weekly or monthly doses of vitamin D3 equally influence vitamin D status. This was investigated in a randomized clinical trial in nursing home residents. Methods The study was performed in ten nursing homes including 338 subjects (76 male and 262 female), with a mean age of 84 (± SD 6.3 years). They received oral vitamin D3 either 600 IU/day, or 4200 IU/week, or 18,000 IU/month or placebo. After 4 months, calcium was added during 2 weeks, 320 mg/day or 640 mg/day or placebo. Outcome: serum levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone turnover markers. Statistical approach: linear multilevel analysis. Results At baseline, mean serum 25(OH)D was 25.0 nmol/L (SD 10.9), and in 98%, it was lower than 50 nmol/L. After 4 months, mean serum 25(OH)D levels increased to 62.5 nmol/L (after daily vitamin D3 69.9 nmol/L, weekly 67.2 nmol/L and monthly 53.1 nmol/L, P < 0.001 between groups). Median serum PTH levels decreased by 23% (p < 0.001). Bone turnover markers did not decrease. Calcium supplementation had no effect on serum PTH and bone turnover. Conclusion Daily vitamin D was more effective than weekly, and monthly administration was the least effective.     

Intraperitoneal penetration of pefloxacin in patients on continuous ambulatory peritoneal dialysis

Summary: Six patients with continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis were treated with oral pefloxacin 400 mg twice a day. the concentration of pefloxacin was assayed in 20 sets of serum and peritoneal dialysate samples taken from these patients. With a mean starting serum level of 7.6 mg/L, pefloxacin was detected in all peritoneal dialysates within 15 min and attained a mean concentration of 4.2 mg/L within 2 h. the percentage penetration of pefloxacin into peritoneal fluid was 72.9% (SD 19.4%). the results showed that the administration of oral pefloxacin 400 mg b.d. could result in peritoneal drug levels that should be adequate for the treatment of peritonitis caused by common pathogens like Enterobacteriaceae species and Staphylococcus aureus. However, it may be necessary to give the drug parenterally on the first day of treatment before steady-state plasma concentrations are achieved and, in empirical therapy, combination antibiotics may be required when infection by more resistant pathogens is suspected.     

Pharmacokinetics of modified slow-release oral testosterone over 9 days in normal men with experimental hypogonadism

Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 μg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P < .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency.     

Corticosteroids in acute severe asthma: effectiveness of low doses.

BACKGROUND: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known. METHODS: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days. RESULTS: The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose. CONCLUSIONS: Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone.     

Clinical comparison of cefadroxil, new oral cephalosporin, and cephalexin in uncomplicated urinary tract infection.

Efficacy and safety of cefadroxil, a new oral cephalosporin, were compared with that of cephalexin in the treatment of 28 women with acute urinary tract infections. According to a randomized double-blind design, each patient received cefadroxil 1,000 mg. twice daily or cephalexin 500 mg. four times a day for ten days. Cures based on urine culture five to nine days post-treatment were obtained for all but 1 patient receiving cefadroxil; reinfection after eradication of the original pathogen was recorded for only 1 patient in each treatment group. No drug-related side effects or significant clinical laboratory abnormalities were observed during the study. Cefadroxil 1,000 mg. given twice daily was as effective and as well tolerated as cephalexin 500 mg. given four times daily. The significance of this dosage schedule advantage is discussed.     

Pharmacokinetics of intravenous cefuroxime during intermittent and continuous arteriovenous hemofiltration

The pharmacokinetics of cefuroxime were determined in ten patients during intermittent hemofiltration (IHF) and in three patients during continuous arteriovenous hemofiltration (CAVH). All patients received a bolus dose of 1.5 g of cefuroxime intravenously and the concentrations of cefuroxime in serum and ultrafiltrate were followed during the hemofiltration period and up to 16 hours after injection of cefuroxime. During IHF the mean terminal half-life of cefuroxime was 1.6 +/- 0.3 hours compared with a terminal half-life of 21.7 +/- 5 hours after treatment. The total cefuroxime clearance was 120 +/- 22 ml/min. The hemofiltration clearance represented 86% of the total clearance and the hemofiltration process removed in average 63% of the dose. During CAVH the terminal half-life of cefuroxime was 7.9 +/- 2.2 hours. The total plasma clearance for cefuroxime was 32 +/- 7.5 ml/min where the CAVH-treatment represented only 34% of the total clearance. From these data we suggest that a full loading dose (1.5 g of cefuroxime) should be given after each intermittent hemofiltration treatment when performed every second day. In CAVH, where nonrenal clearance will influence the dosage scheme significantly, we suggest an initial dose of 1.5 g of cefuroxime to be followed by a supplementary dose of 750 mg every 20-24 h.     

The effect of dosing strategy on kidney cortical accumulation of aminoglycosides in rats

The influence of three different dosage schedules on kidney cortical accumulation of aminoglycosides was studied in rats. A daily dose of 10 mg/kg of gentamicin or tobramycin or 33.3 mg/kg of amikacin were given, either in single injections, three injections eight hours apart, or by continuous infusion. Kidney cortical levels of aminoglycosides were examined at regular intervals up to eight days. The pattern for cortical accumulation under different dose regimens was drug-dependent. Continuous infusion of gentamicin resulted in remarkably higher cortical concentrations than after intermittent administrations. In contrast, cortical levels of tobramycin were independent of the regimen used. For amikacin, higher accumulation resulted from continuous administration from the second day. However, the differences in tissue levels after one or the other dose regimen were less striking than for gentamicin. These observations were explained by differences in cortical uptake kinetics for aminoglycosides previously reported. Elevations in serum concentrations of gentamicin were associated with nonlinear uptake. Accordingly, uptake of gentamicin is more "efficient" at low serum concentrations. Uptake of tobramycin was linearly related to increases in serum levels. Amikacin showed a mixed kinetics pattern, saturation at low serum levels, and linear kinetics at high serum concentrations. This explains the higher cortical levels reached with continuous infusion of amikacin compared with intermittent administration. Uptake kinetics play an essential role in cortical aminoglycoside concentrations achieved after different dosing strategies. The design of regimens minimizing cortical uptake may decrease the risk of nephrotoxicity.     

Systemic absorption of oral vancomycin in patients with renal insufficiency and antibiotic-associated colitis

The systemic absorption of orally administered vancomycin was evaluated in five patients (six occasions) with moderate to severe renal insufficiency and documented antibiotic-associated colitis. The patients' ages ranged from 28 to 63 years and weights varied from 50.0 to 76.2 kg. Vancomycin doses were 125 mg (one case), 250 mg (three cases), and 500 mg (two cases) every six hours. Multiple serum concentrations were obtained (range four to 19) during the seven- to 28-day courses of vancomycin therapy. Vancomycin serum concentrations were detectable in five of the six cases as soon as two hours after the first dose, and plateaued within four days. A linear relationship between daily dose and the vancomycin serum concentration was observed (r = .8575, P less than .01). Routine monitoring of vancomycin serum concentrations in adult patients may not be necessary unless high dose (greater than 2 g/d) or prolonged therapy (greater than ten days) is required.     

Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis

Kinetics of fosfomycin were investigated in six patients undergoing continuous ambulatory peritoneal dialysis. Each subject received both an i.v. and an i.p. 1 g dose of fosfomycin with a one week washout between doses. Fosfomycin was assayed by a microbiological diffusion technique. After intravenous injection the fosfomycin serum kinetic parameters were as followed: elimination half-life (t1/2 beta) 38.4 +/- 8.7 h; volume of distribution 0.32 +/- 0.02 l/kg; total plasma clearance 7.0 +/- 1.4 ml/min and peritoneal clearance 3.2 +/- 0.2 ml/min. Dialyzate fosfomycin concentrations reached a maximum mean value of 32.2 +/- 2.8 micrograms/ml at 4 h post-injection and fosfomycin was detectable in dialyzate samples for up to 72 hours post-dosing. After intraperitoneal instillation, fosfomycin appeared in the serum rapidly and the mean peak plasma concentration was 36.2 +/- 2.8 micrograms/ml at the 4th h. The absorption rate (ka) was 0.580 +/- 0.039 h-1 and the absorption of fosfomycin from peritoneal space was 68.4 +/- 6.0%. These data suggest a bidirectional exchange through the peritoneal membrane. Intraperitoneal administration of 1 g either 48 h apart for anephric patients or 36 h apart for patients with residual renal function may achieve therapeutic serum concentrations.     

Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients

BACKGROUND: The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. METHODS: 29 HD patients were randomized into two groups: 15 patients were treated orally with 400 mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical--TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. RESULTS: Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23+/-11.94 vs. 11.41+/-1.94 mIU/L, p<0.001; CRP: 5.20+/-3.50 vs. 3.40+/-3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. CONCLUSION: Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.     

Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients

OBJECTIVE: To determine the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) concentration after pediatric cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, clinical cohort study. SETTING: A fifteen-bed tertiary-care pediatric intensive care unit. PATIENTS: Fourteen pediatric patients admitted for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Serum PCT and CRP were measured before cardiopulmonary bypass (CPB); after CPB; and on the first, second, and third days after surgery by means of immunoluminometry and nephelometry, respectively. Reference values for systemic inflammatory response syndrome are 0.5 to 2.0 ng/mL for PCT and <5 mg/L for CRP. Baseline serum PCT and CRP concentrations were 0.24 +/- 0.13 ng/mL and 4.06 +/- 3.60 mg/L (median 25th percentile-75th percentile), respectively. PCT concentrations increased progressively from the end of CPB (0.62 +/- 0.30 ng/mL), peaked at 24 hours postoperatively (POD1) (0.77 +/- 0.49 ng/mL), and began to decrease at 48 hours or POD2 (0.35 +/- 0.21 ng/mL). CRP increased just after CPB (58.82 +/- 42.23 mg/L) and decreased after 72 hours (7.09 +/- 9.81 mg/L). CONCLUSION: An increment of both PCT and CRP was observed just after CPB. However, PCT values remained within reference values, whereas CRP concentrations increased significantly after CPB until the third day. These preliminary results suggest that PCT was more effective than CRP to monitor patients with SIRS and a favorable outcome.     

川芎嗪对慢性腹膜透析大鼠腹膜功能及间皮细胞形态的影响

目的 探讨不同剂量的川芎嗪对高糖透析液作用下慢性大鼠腹膜透析（腹透）模型腹膜间皮细胞的形态和功能的影响及它们之间的关系。方法 ４０只ＳＤ大鼠随机分为４．２５％腹透液（ＨＧ组）、４．２５％腹透液＋４０ｍｇ／Ｌ川芎嗪（ＨＧＬ组）、４．２５％腹透液＋１６０ｍｇ／Ｌ川芎嗪（ＨＧＨ组）、对照组。除对照组外,余３组每天分别腹腔内注入２０ｍｌ含不同剂量川芎嗪的４．２５％透析液［０（ＨＧ）、４０ｍｇ／Ｌ（ＨＧＬ）     

Trimethoprim-sulphamethoxazole and metronidazole as prophylaxis in colorectal surgery: a study of bioavailability after an oral single dose.

OBJECTIVE: To evaluate oral single dose prophylaxis in colorectal surgery. DESIGN: Prospective study. SETTING: University hospital, Sweden. SUBJECTS: 24 patients (13 women; 11 men; mean age 57 years, range 27-81) listed for elective colorectal operations. INTERVENTION: At 0630 on the day of the operation all patients were given an oral dose of trimethoprim-sulphamethoxazole (TMP 160 mg and SMZ 800 mg) and metronidazole (2 g). The serum concentrations of TMP and SMZ were analysed in venous samples taken at the start and end of each operation. RESULTS: The earliest operation started at 0830 and the last finished at 1700. The median (range) serum concentrations of TMP were 1.4 (0.7-2.6) mg/L (start) and 1.3 (1.0-2.8) mg/L (end), and of SMZ 35 (15-65) mg/L (start) and 33 mg (13-70) mg/L (end). The individual values were above or equal to the minimal inhibitory concentration (TMP 0.8 mg/L; SMZ 15.2 mg/L) for relevant gram-negative species. CONCLUSION: Oral TMP/SMZ in the morning gives satisfactory serum concentrations independently of when the operation is done during the day. The regimen is simple and has the potential for being an effective alternative to intravenous prophylaxis.     

Mizoribine oral pulse therapy for patients with disease flare of lupus nephritis

AIM: Mizoribine (MZR) is a newly developed immunosuppressive agent in Japan. To relieve disease flare of lupus nephritis, a prospective pilot study of oral MZR pulse therapy (a phase II trial) is conducted as an alternative therapy to dose up of corticosteroids. METHODS: Six Japanese patients with biopsy-proven lupus nephritis who experienced disease flare were prospectively evaluated. MZR at a dose of 5 - 10 mg/kg per day (up to 500 mg) in 1 or 2 divided daily doses was orally administered twice a week for 3 months. At the time of disease flare, 4 patients had refused to take dose up of corticosteroids, and the other 2 had complained of opportunistic infection. RESULTS: At presentation, urine protein excretion, serum hemolytic complement activity (CH50) and serum anti-dsDNA antibody were 1.9 +/- 0.6 g/day, 15.7 +/- 5.8 U/ml (normal 23 - 46 U/ml) and 164.8 +/- 184.0 IU/ml (normal < 12.0 IU/ml), respectively. Urine protein excretion and serum anti-dsDNA antibody decreased significantly following MZR oral pulse therapy (0.2 +/- 0.1 g/day and 29.7 +/- 23.4 IU/ml (p < 0.05), respectively), and serum CH50 recovered to normal (35.1 +/- 10.4 U/ml, p < 0.05). Moreover, a significant histologic improvement was observed in a patient who received repeat renal biopsies at pre- and post-treatment. Reported peak serum MZR levels enough to inhibit human mixed-lymphocyte reaction (3.0 - 6.0 microg/ml) were achieved in all patients. No serious adverse effects were observed. CONCLUSION: Although we had no control subjects in this series, MZR oral pulse therapy may be of benefit to a proportion of patients with disease flare of lupus nephritis as an alternative therapy to dose up of corticosteroids.