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1.
PURPOSE: To study the intraocular pharmacokinetics of intravenously administered ciprofloxacin following eye trauma. METHODS: Twenty-three New Zealand albino rabbits and 12 Yorkshire pigs each received a surgically induced scleral injury to the right eye. Following repair, each rabbit received a single 30-mg intravenous infusion of ciprofloxacin. Each pig received either two 200-mg doses or two 400-mg doses of intravenous ciprofloxacin given 12 hours apart. Vitreous and serum samples were harvested at 0.5, 1, 4, 6, and 12 hours after antibiotic administration in rabbits and 1 hour after the second dose in pigs. Bioassays for ciprofloxacin were performed on each sample, and results were statistically compared by t test. The untraumatized left eye in each animal served as a control. RESULTS: The mean vitreous concentration of ciprofloxacin in traumatized rabbit eyes was 0.37 microgram/ml. This level was sustained above levels in control eyes (0.18 microgram/ml) for at least 4 hours following antibiotic administration. In control eyes, intravitreal levels peaked at 1 hour. Mean vitreous concentrations +/- SD in traumatized pig eyes were 0.091 +/- 0.017 microgram/ml in swine that had received 200-mg doses of ciprofloxacin vs 0.312 +/- 0.153 microgram/ml in swine that had received 400-mg doses (P = .02). Mean vitreous concentrations of ciprofloxacin in control eyes were not affected by increasing dosage. CONCLUSION: In both animal models, experimental surgical trauma increased intravitreal ciprofloxacin delivery. In addition, systemically administered ciprofloxacin achieved intravitreous levels exceeding minimum inhibitory concentrations for common ocular pathogens, suggesting a role for ciprofloxacin in the prophylaxis of posttraumatic endophthalmitis.  相似文献   

2.
Significantly higher (P < 0.05) thrombin-antithrombin III complex levels were found in the abdominal exudate of patients with peritonitis (median 5500 ng/ml) than in that of controls (median 89 ng/ml). In patients, peritoneal fluid concentrations of tissue and urokinase-type plasminogen activator were increased by factors of 65 and 10 respectively (P < 0.05). The concentration of plasminogen activator inhibitor (PAI) 1 was increased by a factor of about 800 (median 395 versus 0.5 ng/ml, P < 0.05). Despite markedly raised concentrations of PAI, peritoneal fluid displayed fibrinolytic activity as demonstrated by significantly increased (P < 0.05) concentrations of plasmin-alpha 2-antiplasmin complex (median 10,952 versus 57 ng/ml) and fibrin degradation products (median 40,360 versus 126 ng/ml). There was no correlation between plasma and peritoneal fluid concentrations. Intraabdominal coagulation and fibrinolysis are stimulated in the abdominal cavity of patients with bacterial peritonitis.  相似文献   

3.
A novel pH shock extraction procedure was used to measure nerve growth factor (NGF) levels in both normal and inflamed synovial fluids using a sensitive and specific two-site enzyme linked immunosorbant assay. To date no data is available on NGF levels in normal synovial fluids. Synovial fluids were taken from 5 normal volunteers, 12 patients with rheumatoid arthritis and 10 patients with other inflammatory arthropathies. The mean +/- SEM NGF concentration in normal synovial fluids was 95 +/- 33.2 pg/ml (range 39.1-143.1 pg/ml), whereas the mean NGF concentration in the synovial fluids taken from patients with rheumatoid arthritis was 532.5 +/- 123.8 pg/ml (range 152-1686 pg/ml). The mean NGF concentration in patients with other inflammatory arthropathies was also raised (430.6 +/- 90 pg/ml; range 89-1071 pg/ml). The NGF concentrations were significantly higher in the synovial fluids from both inflamed groups (ANOVA p < 0.05) compared to normals. Raised levels of NGF in synovial fluid may contribute directly to joint inflammation via activation of inflammatory cells.  相似文献   

4.
A method for the determination of inorganic sulphate based on high performance ion chromatography is presented. The separation was performed on an anion-exchange column with a 1.8 mmol/l sodium carbonate/ 1.7 mmol/l sodium hydrogen carbonate-buffer, pH 10.35. Conductivity of the eluate was monitored after suppression of the background conductivity caused by the eluent-buffer. Serum and synovial fluid samples were prepared by ultrafiltration through membranes with a molecular mass cutoff of M(r) 10,000. The viscosity of the synovial fluids was reduced by treatment with hyaluronate lyase before ultrafiltration. The method showed a linear response for sulphate concentrations between 0.5 and 1000 mumol/l. The limit of detection was 1 mumol/l for aqueous standards. For serum the coefficient of variation within-run was 2.3%-2.4%, the coefficient of variation between days 2.9%-3.1%. For synovial fluids the coefficient of variation within-run was 3.1%-3.4%, the coefficient of variation between days 4.6%-5.7%. Standard recovery experiments performed by spiking pools of human sera containing low sulphate concentrations with sulphate concentrations between 5 mumol/l and 40 mumol/l showed recoveries between 98.9% and 100.6%. The corresponding experiments with pools of synovial fluids showed recoveries of 98.3% to 100.9%. As determined from 127 serum samples the reference range for sulphate was 262 mumol/l-420 mumol/l, with a mean value of 314 mumol/l. No dependence on age or sex was observed. The sulphate concentration in 36 synovial fluids from knees affected by inflammatory processes showed a mean value of 424 mumol/l and a standard deviation of 70 mumol/l. In 41 synovial fluids from knees affected by chronic degeneration joint disease, the sulphate concentrations were statistically significantly lower, with a mean of 374 mumol/l and a standard deviation of 58 mumol/l. The concentrations of sulphate in the synovial fluids were statistically significantly higher than those in the serum samples used for determination of the reference range. Following the oral application of a subtoxic single dose of acetaminophen (32.5 mg/kg body weight-62.5 mg/kg body weight) to 4 healthy volunteers, there was a significant decrease in the concentration of sulphate in serum with a minimum at 4-5 h after application of the drug. The cumulative concentration decrease of sulphate in serum and the kinetic constant of the sulphate depletion were not correlated with the applied acetaminophen dose normalized for body weight.  相似文献   

5.
A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 microg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 microg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.  相似文献   

6.
To assess the possible role of intravenous (i.v.) infusion rate as a determinant of degree and rate of interstitial fluid penetration, six rabbits, each with four intraperitoneal implanted capsules, were studied by crossover design after a single dose of 1.7 mg of gentamicin per kg by either slow 2.5-min i.v. bolus or 30 min i.v. infusion. The mean serum peak antibiotic level after slow bolus was 17.4 mug/ml. After 30 min of infusion, mean serum peak was 8.3 mug/ml (P < 0.025). Mean capsule fluid antibiotic levels at 30 min, 1, and 2 h were 0.9 mug/ml, 1.6 mug/ml, and 1.8 mug/ml, respectively, after slow bolus and 0.6 mug/ml, 0.9 mug/ml, and 1.3 mug/ml after 30-min infusion (P < 0.05 at 30 min, P < 0.001 at 1 h, and P < 0.05 at 2 h). Comparison of capsule levels beyond 2 h revealed no significant differences, and peak capsular concentrations achieved by the two methods were similar. Slow 2.5-min i.v. bolus administration of gentamicin established higher interstitial fluid levels during the first 2 h of therapy and may be the preferred mode of delivery when rapid extravascular penetration is desired.  相似文献   

7.
We treated two cases of primary pulmonary cryptococcosis with fluconazole (FLCZ), the clinical usefulness of FLCZ was evaluated. FLCZ was administered orally in doses of 300 mg daily for about six months. Concentrations of FLCZ were measured in the serum of the two cases and in the bronchoalveolar lavage (BAL) fluid in one case. The following results were obtained: 1. Clinical cures were obtained in the two cases. 2. The serum levels of FLCZ was 15.1 microliters/ml, 13.6 micrograms/ml two hours after administration of 100 mg in case 1, that of levels were 11.1 micrograms/ml, 8.9 micrograms/ml one hour and 4.5 hours, respectively, after administration of 100 mg in case 2. BAL was performed 4.5 hours after administration of 100 mg in case 2, the BAL fluid level of FLCZ was 0.7 microgram/ml. 3. The minimal inhibitory concentration of FLCZ against one strain obtained from the cytology brush in case 1 was 4.0 micrograms/ml. 4. The cryptococcal antigen titer decreased with the improvement of clinical signs and the resolution of chest X-ray abnormalities within about six months, and there was no relapse. From these results, we consider that FLCZ is a useful antifungal agent for primary pulmonary cryptococcosis, and we therefore recommend a six month treatment.  相似文献   

8.
BACKGROUND: As abnormally high serum D-lactate levels may cause neurological impairment, we determined whether patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with lactate-containing fluids have increased serum D-lactate concentrations. METHODS: D- and L-lactate concentrations were determined in peritoneal dialysis fluids and in serum from control subjects (n = 10), haemodialysis patients (n = 10), and CAPD patients (n = 30) before and after 1 h of dialysis. RESULTS: We found the median D-lactate concentration in Dianeal CAPD fluid to be 26 mM (range 19-27), whereas it was less than 0.5 mM in DPCA2 fluid. Control, haemodialysis, and CAPD (DPCA2) patient median serum D-lactate concentrations were below 0.07 mM. However, CAPD (Dianeal) patient serum D-lactate concentrations were 4-fold higher than controls (P < 0.0001), at 0.28 mM, an hour after instillation of D-lactate-containing fluid. Three patients, whose serum D-lactate averaged 0.59 mM, were found to have D-lactate concentrations at 0.22 mM after overnight cessation of dialysis. CONCLUSION: We conclude that CAPD with D-lactate-containing fluids raises serum D-lactate to abnormal levels.  相似文献   

9.
In connection with a study on the prophylaxis of infectious diarrhea with specific egg yolk antibodies, the systemic availability of colostral bovine immunoglobulin G (bIgG) and chicken immunoglobulin Y (IgY) after feeding egg powder was investigated on 26 newborn calves from 23 different farms. Blood was sampled daily and at the same day time from these calves in the first 14 days of life. During the feeding of colostrum, the mean bIgG concentration was highest at day 1 post natum with a value of 9.3 mg/ml serum. Thereafter, the mean bIgG level was reduced continuously to a significant lower concentration of 4.9 mg/ml serum at day 12 post natum and remained nearly constant at 5.2 mg/ml till to the end of the observation period. Total protein concentrations in the serum did not change and plateaued at a mean value of 56.2 mg/ml (SD 11.2). The number of colostrum meals had no significant effect on the mean bIgG concentrations during that period. The individual variation of bIgG concentrations was very high on every day of the sampling period. The mean coefficient of variation was at 52.1 % (SD 5.7). After having described the individual bIgG concentration curves mathematically with a regression curve, two groups with significantly different bIgG elimination constants (k) could be obtained. Thus in one group (n = 10) with k-values of < -0.02 a mean half time of serum bIgG of 24.3 days (SD 4.6) was calculated. In the other group of calves (n = 16) with elimination constants of k > -0.02, a mean half time of 68.5 days (SD 36.7) could be calculated, possibly because these calves started earlier with their endogenous bIgG production. Additionally, to 18 of these calves 20 g egg powder with an IgY concentration of 15 mg/g was fed up to day 14. Calves had a maximal mean IgY concentration of 1.9 micrograms/ml serum if egg powder feeding started already during the first 12 hours of life. Starting at a later time resulted in a significant reduction of IgY levels. For example, the mean initial IgY concentration dropped to 0.035 micrograms/ml serum after having had the first egg powder application between 25 and 48 hours post natum. Using the individual IgY elimination constant derived from a regression analysis (r2 = 0.84) of the IgY concentration curve, a mean IgY half time of 5.0 days (SD 2.5) could be calculated. To prevent the absorption of heterologous antibodies and consecutively, also to prevent a possible systemic effect, egg powder for prophylactic purposes in newborn calves should be fed after the first 24, better 48 hour, post natum. Most important for the prophylactic effect of specific antibodies on infectious diarrhea is not their systemic but their high local intestinal availability.  相似文献   

10.
Rat peritoneal mast cells were incubated with serum from highly mite-sensitive patients. It was demonstrated that exposure of passive sensitized mast cells to allergen from mites Dermatophagoides farinae induced the release of histamine. Exposure of mast cells to 10 micrograms/ml and 50 micrograms/ml mite allergen resulted in an increase of histamine secretion to 48% of the basal level. The allergoid (formaldehyde-modified mite allergen) had poor histamine-releasing activity compared to allergen. The allergoid (50 micrograms/ml) induced a 2.5-fold decrease in histamine release. The allergen at the same concentrations and the same release as allergen in dose 0.1 microgram/ml.  相似文献   

11.
The pharmacokinetics of a single, oral dose of 750 mg of ciprofloxacin were studied in 35 subjects with various degrees of renal function (Group 1, Clcr > or = 80 ml/min; Group II, Clcr 50-79 ml/min; Group III, Clcr 10-49 ml/min) and on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Blood, urine and CAPD dialysate samples were collected over a period of 48 hours after dosing. Data were fitted using non-linear, least squares regression. The mean Cmax was 3.4 +/- 1.0 mg/l and tmax was 2.3 +/- 0.9 hours. The mean AUC in Group I was 14.7 mg.h/l, Group II was 33.7 (p < 0.001), Group III 63.8 (p < 0.001), HD 57.9 (p < 0.0001) and CAPD 44.3 (p < 0.001). Half-life in Group I was 4.6 h, and was shorter than Group III (11.1 h, p < 0.001), HD (13.4 h, p < 0.001) and CAPD (8.9 h, p < 0.001). Total body clearance and renal clearance demonstrated significant differences also. The dialysis clearance in CAPD patients was 0.53 +/- 0.39 l/h. Peritoneal effluent concentrations varied from 0.6 mg/l during the first exchange, to a peak of 2.2 mg/l during the second, to 0.13 mg/l in the 48 hour (9th) exchange. Dosage adjustments of ciprofloxacin in the presence of renal insufficiency are indicated for subjects with a Clcr < 20 ml/min/1.73m2.  相似文献   

12.
The pharmacokinetics of ceftazidime have been investigated in eight patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis. Each subject was given ceftazidime 1 g intravenously and 1 g intraperitoneally at an interval of 1 week. Ceftazidime was assayed by high-pressure liquid chromatography. After intravenous administration, the pharmacokinetic parameters of ceftazidime were: elimination plasma half-life (t1/2 beta) = 24.6 +/- 4.6 hours; apparent volume of distribution (V(area)): 0.37 +/- 0.09 1/kg, total plasma clearance (CL): 11.9 +/- 3.3 mL/minute, peritoneal clearance (CLp): 1.7 +/- 0.3 mL/minute. Over 72 hours, only 15.6 +/- 4.7% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftazidime appeared in the plasma rapidly, and the peak plasma concentration of 24.5 +/- 5.2 mg/L was achieved at the fourth hour; the elimination half-life (t1/2ke) was 20.8 +/- 1.7 hours. The absorption of ceftazidime from the peritoneal space was 74.1 +/- 7.4%. These data suggest that ceftazidime has bidirectional exchange characteristics through the peritoneal membrane. A single 1-g intraperitoneal dose led to serum and dialysate concentrations of ceftazidime above the minimum concentrations for susceptible pathogen germs for 24 hours.  相似文献   

13.
Toxicity of selected antibiotics in vitreous replacement fluid   总被引:1,自引:0,他引:1  
Experiments with rabbits demonstrated no toxic effects on the retina after vitrectomy when the infusion fluid contained either 20 microgram/ml chloramphenicol saline, 10 microgram/ml amikacin saline, 10 microgram/ml tobramycin saline, or 10 microgram/ml clindamycin saline. We found abnormal electroretinograms and abnormal histologic findings in eyes receiving vitreous replacement with these same drugs in higher concentrations.  相似文献   

14.
Pharmacokinetic and clinical studies on amikacin (AMK) by intravenous drip (i.v.d.) infusion were performed, and the following results were obtained. 1. Serum concentrations of AMK were determined in 4 patients with normal renal function after 1 hour i.v.d. infusion of 200 mg of AMK. The mean peak serum concentration was 14.20 +/- 0.88 micrograms/ml at the termination of i.v.d. infusion and declined to 2.30 +/- 0.79 micrograms/ml at 4 hours later. The half-life was 1.55 +/- 0.28 hours. 2. Twenty-three patients with severe pulmonary infection received 1 hour i.v.d. infusion of 200 mg of AMK 2 to 3 times a day. Clinical response was good in 17 cases, fair in 4 and poor in 2. Thus, 73.9% of the patients responded to AMK. 3. No adverse effects were observed with the exception of tinnitus and hearing loss in 1 case. Therefore, it is thought that the i.v.d. infusion of AMK will be useful for treatment of severe infectious patients with bleeding tendency and emaciation.  相似文献   

15.
We treated nine patients of mycoplasmal pneumonia with sparfloxacin (SPFX) the clinical efficacy, safety and usefulness of SPFX were evaluated. SPFX was administered orally at doses of 200 or 300 mg once daily, and we performed bronchoalveolar lavage (BAL) examinations in five patients. BAL was performed 5 hours after oral administration of 100 mg in one case, 19 hours after oral administration of 200 mg in four cases. Concentrations of SPFX and alubumine were measured in serum and in BALF (bronchoalveolar lavage fluid). The following results were obtained. 1. Nine patients were evaluated; eight patients judged as Good, one patient as Excellent. 2. The serum and BALF levels of SPFX was 0.79 microgram/ml, 0.107 microgram/ml 5 hours after single oral administration of 100 mg in one case and 19 hours after oral administration of 200 mg in four cases, those of levels of SPFX were 0.835 +/- 0.274 microgram/ml and 0.081 +/- 0.033 microgram/ml, respectively. 3. The ratio of SPFX/albumin in BALF was significantly higher than in the serum. From these results, we consider that SPFX is a useful antimicrobial agent for mycoplasmal pneumonia.  相似文献   

16.
Behavioral observations and hematological, serum biochemical and blood gas measurements were made on 8 naturally occurring twin calves during the first 48 hours of life. These values were compared to similar measurements collected from 30 single born calves, born under the same calving conditions. All calves survived to at least 3 weeks of age without physically detectable disease. Although the gestational age of the twins and singles were not different, the twins had a lower mean birth weight. Calving difficulty score, time interval to standing and time interval to nursing were not different between the 2 groups. Twin calves had significantly lower rectal temperatures, arterial oxygen tensions and blood glucose concentrations than the single calves through the first 12 hours of life. Hct, Hgb concentration, and RBC were lower in twin calves throughout the 48 hour period. The N:L ratio was lower in the twins at birth. Mean serum IgG1 concentrations were lower in twins only at 24 hours whereas IgM concentrations were lower at both 24 and 48 hours in twins. Serum chemistry value differences between twin and single calves were most numerous at 24 hours of age when serum proteins, urea nitrogen, total bilirubin, sodium, chloride, and total calcium concentrations were higher in the twins and serum phosphorus concentration was lower in the twins.  相似文献   

17.
18.
We developed an assay system for measuring free follistatin by using an anti-follistatin mouse monoclonal antibody and [125I]activin A. The sensitivity of this assay was 0.5 microgram/l and cross-reactivities with inhibin, luteinizing hormone, follicle-stimulating hormone and growth hormone were all less than 0.5%. The dose-response curves of human sera and follicular fluid were parallel to the standard curve, and the follicular fluid contained a large amount of follistatin (6.4 +/- 0.5 mg/l, mean +/- SEM; N = 13). The within- and between-assay coefficients of variation calculated from the analysis of serum samples of four different concentrations were 3.3-7.8% and 3.9-11.0%, respectively. The recovery rates of free follistatin at five different doses were 86.4 - 102.4%. When activin A was added to the same sample, free follistatin recovery rate declined dose-dependently. Gel filtration analyses of human serum and follicular fluid resulted in a single peak corresponding to authentic follistatin. Using this assay, free follistatin concentrations in sera were measured in normal, pregnant and diseased subjects. The free follistatin level in serum of normal adults was 3.5 +/- 0.2 micrograms/l (N = 60), which was significantly elevated in pregnant women (16.7 +/- 1.3 micrograms/l, N = 56), and in patients with chronic liver disease (8.1 +/- 1.1 micrograms/l, N = 20), chronic renal failure (6.7 +/- 0.9 micrograms/l, N = 42), advanced solid cancer (8.5 +/- 1.0 micrograms/l, N = 39) and hematological malignancies (6.8 +/- 1.0 micrograms/l, N = 18). These data indicated that the free follistatin concentration in serum is detectable and varies during pregnancy and in various diseased states.  相似文献   

19.
AIMS: The choice of a prophylactic antibiotic for cataract surgery is dependent on its antibacterial activity and tissue penetration. The influence of the route and timing of administration of cefuroxime on its intraocular concentrations was examined. METHODS: 120 patients were recruited before cataract surgery into a prospective trial to compare the anterior chamber concentration of cefuroxime at a fixed time after administration by three routes. In a further 110 patients, the interval before sampling was varied in order to permit an examination of the kinetics of penetration. In another 10 patients, cefuroxime was given topically at the completion of surgery to assess the effect of a corneal wound on aqueous penetration. Cefuroxime concentrations were measured by high performance liquid chromatography on 0.2 ml samples of aqueous aspirated from the anterior chamber. Mean aqueous concentrations of cefuroxime for each group were compared using Student's t test. RESULTS: After 25 mg cefuroxime, mean aqueous concentrations increased in the order forniceal (< 0.1 microgram/ml) < topical (0.18 microgram/ml) < subconjunctival (2.31 microgram/ml) when sampled 12-24 minutes after administration. Aqueous concentrations of cefuroxime reached a peak between 80 and 110 minutes after both forniceal and peribulbar injection but were still rising at this time after subconjunctival injection. Topical application of 12.5 mg cefuroxime to eyes with a 10 mm corneal wound resulted in a mean aqueous concentration of 9.34 micrograms/ml. CONCLUSION: In the intact eye, only sub-conjunctival injection resulted in clinically significant aqueous concentrations of cefuroxime (> 1 microgram/ml) between 12 and 24 minutes after administration. For all routes, maximal aqueous concentrations were delayed by at least 80 minutes from administration. In the presence of a corneal wound, high aqueous levels of cefuroxime were rapidly attained after topical application.  相似文献   

20.
Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was administered at a standard dose of 10 mg/kg once daily for 3 days to pediatric patients with bacterial infections. AZM was studied for its pharmacokinetic and clinical evaluation. 1. AZM possessed potent activity against Gram-positive bacteria and Gram-negative bacteria that had been clinically isolated. 2. Plasma samples were collected from two patients diagnosed as having pneumonia or enteritis, and urine samples were collected from one patient diagnosed as having pneumonia for drug level determination. The drug concentrations in plasma were 0.095 and 0.204 microgram/ml just before the end of treatment, and 0.017 and 0.096 microgram/ml at 48 hours post-treatment. The drug concentrations in urine were 5.16 micrograms/ml and 5.63 micrograms/ml during a period between 24 and 48 hours and between 48 and 72 hours after the start of treatment, respectively. 3. The drug was found effective in 37 of 38 cases with various pediatric infections. AZM treatment eradicated bacteria in 17 of 30 strains (56.7%). 4. One patient complained of mild vomiting, while abnormal laboratory test results indicating mild eosinophilia were reported in four cases.  相似文献   

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