CT diagnosis of perihepatic endometriosis complicated by malignant transformation.

Endometriosis is a condition in which endometrial tissue becomes implanted on extrauterine sites, most commonly within the pelvis. Malignant transformation of endometriotic foci is rare, but has been frequently reported. We describe a patient with a CT scan demonstrating pathologically proven perihepatic endometriosis, including malignant transformation. Endometrioses should be considered in the differential diagnosis of perihepatic masses.

The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in two large American Midwest metropolitan hospital populations.

OBJECTIVE: There are no published large-scale studies of the overall prevalence of diffuse idiopathic skeletal hyperostosis (DISH) and it has been proposed that the prevalence is greater than previously reported. We thus decided to review chest radiographs in a population of patients over 50 years of age seen at two large but differing metropolitan hospitals in a major American Mid-west city. DESIGN AND PATIENTS: The posterior-anterior and lateral chest radiographs of 1363 patients were reviewed for evidence of DISH at the University of Minnesota Hospital and Clinic. There were 500 consecutive inpatient admissions, 540 consecutive patients who attended the outpatient clinics and 326 patients collected from our film archive. A population of 1001 patients seen at Hennepin County Medical Center was also studied. It was possible to subclassify this latter group with respect to race. RESULTS AND CONCLUSION: Using strict criteria, i.e., four or more levels involved, the overall prevalence of DISH in the male population over age 50 years was 25% and in the female population over age 50 years was 15%. This prevalence climbed to 28% in males over 80 years and to over 35% in males over age 70 years. In females over 80 years, the prevalence was found to be 26%. Although our population base was small, DISH was found to be less common in the black, Native-American and Asian populations. The prevalence of DISH was also found to be far lower in a similar white population with osteoporosis. The overall prevalence of DISH was higher than expected in a predominantly white population over age 50 years with a lesser incidence in the black, Native-American and Asian populations, suggesting a genetic origin of the condition.

Hyperfunctioning and nonhyperfunctioning benign adrenal cortical lesions: characterization and comparison with MR imaging.

The authors evaluated the potential of magnetic resonance (MR) imaging at 0.35 T to permit differentiation of nine hyperfunctioning adrenal cortical lesions from 21 nonhyperfunctioning adrenal cortical adenomas. Both qualitative data (visual assessment) and quantitative data (signal intensity ratios, T1, and T2) were used for tissue characterization. With a 2,000/56-100 sequence (repetition time msec/echo time msec), the majority of lesions were visually isointense to liver. Of 34 quantitative measures, only lesion-liver and lesion-kidney intensity ratios at 2,000/150 showed statistically significant differences among nonhyperfunctioning adenomas, aldosterone-producing lesions, and corticosteroid-producing lesions; however, the authors question the significance of these differences because of the abundant noise associated with the 2,000/150 sequence. The results suggest that nonhyperfunctioning adrenal cortical adenomas cannot be distinguished from benign hyperfunctioning cortical lesions with use of MR imaging at 0.35 T.

Ceftriaxone pharmacokinetics following multiple intramuscular dosing.

The steady-state pharmacokinetics and tolerance of ceftriaxone after multiple i.m. doses of 0.5 and 1 g q12 h for 3.5 days were investigated in 12 healthy, adult volunteers. Ceftriaxone was rapidly absorbed after i.m. administration with mean peak times ranging from 1.3 to 1.9 h. Steady-state plasma concentrations were apparent after the third dose of both dosage regimens, with trough plasma concentrations of 24 +/- 6 and 39 +/- 8 micrograms/ml (mean +/- SD) after the 0.5 and 1 g q12 h regimens, respectively. Multiple i.m. administrations of ceftriaxone did not alter its elimination half-life; however, small increases were observed in the plasma clearance and volume of distribution at the 1-g regimen. These increases were attributed to the non-linear binding of ceftriaxone to human plasma proteins, and are therapeutically unimportant. Ceftriaxone was well tolerated and serious or lasting adverse reactions were not encountered in the study.

Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment.

The effects of renal impairment on the pharmacokinetics of ceftriaxone in humans were examined after intravenous infusion of a 1-g dose over 15 min to 30 renally impaired patients. The study included 12 dialysis patients and 18 patients with severe, moderate, or mild renal impairment. Plasma and, where appropriate, urine and dialysate samples were collected at predetermined times and analyzed for ceftriaxone by high-pressure liquid chromatography. The elimination half-life (group mean ranged from 11.7 to 17.3 h) and plasma clearance (group mean ranged from 529 to 705 ml/h) did not correlate linearly with creatinine clearance. The renal clearance and fraction of dose excreted unchanged in urine were related linearly, however weakly, with creatinine clearance. Ceftriaxone was not removed from plasma to a significant extent during hemodialysis. The half-life was prolonged twofold, the plasma clearance was lowered less than 50%, and the volume of distribution was relatively unchanged in renally impaired patients compared with young or elderly healthy subjects with normal renal function at an equivalent dose. Since these changes are moderate, adjustment in the dosage regimen of ceftriaxone for patients with impaired renal function should not be necessary when ceftriaxone dosage is 2 g or less per day (2 g every 24 h or 1 g every 12 h). It was reported that the elimination half-life of ceftriaxone is substantially prolonged in a small percentage of patients with end-stage renal disease maintained on hemodialysis. Therefore, plasma concentrations of ceftriaxone should be monitored in dialysis patients to determine whether dosage adjustments are necessary.

Clinical pharmacology of ceftriaxone in patients with neoplastic disease.

Pharmacological studies of ceftriaxone, a new semisynthetic cephalosporin, were conducted in 35 cancer patients. This antibiotic was administered in a variety of doses and schedules with no observed toxicity. Intramuscular administration of 500 mg of ceftriaxone to seven patients produced mean peak serum concentrations of 32.9 mug/ml 2.0 h after administration. The terminal serum half-life was 10.9 h. Intravenous infusion of 500 mg of ceftriaxone over 5 min to the same group of seven patients produced a mean peak concentration of the drug in serum of 83 mug/ml at the end of administration which decreased to 16.8 mug/ml at 8 h. A dose of 1 g of ceftriaxone given in identical fashion to the same group of seven patients produced mean peak concentrations in serum of 130 mug/ml at the end of administration and 17.3 mug/ml at 12 h. The mean percentages of drug recovered in urine 12 h after single intravenous doses of 500 mg and 1 g were 30 and 20%, respectively. A 1-g dose of ceftriaxone was administered every 8 h to 10 patients, and a 2-g dose was administered every 12 hours to 9 patients. Drug concentrations in serum were measured for each patient after drug administration on day 1, day 3 or 4, and day 7 or 8. The 1-g dose produced an observed mean peak concentration of 154 mug/ml and a mean terminal-phase half-life of 5.6 h on day 3 or 4. The 2-g dose produced a mean peak concentration in serum of 262 mug/ml and a terminal-phase serum half-life of 6.3 h on day 3 or 4. Continuous infusion studies were performed in nine neutropenic patients for up to 8 days by using a loading dose of 1 g over 30 min, followed by 2 g every 8 h. Mean concentrations in serum were maintained at about 135 mug/ml during the infusion period.

Pharmacokinetics of ceftriaxone in pediatric patients with meningitis.

Pharmacokinetics of ceftriaxone after a single dose of 50 or 75 mg/kg were determined in 30 pediatric patients with bacterial meningitis. Data for doses of 50 and 75 mg/kg, respectively, were as follows (mean +/- standard deviation): maximum plasma concentrations, 230 +/- 64 and 295 +/- 76 mug/ml; elimination rate constant, 0.14 +/- 0.06 and 0.14 +/- 0.04 h(-1); harmonic elimination half-life, 5.8 +/- 2.8 and 5.4 +/- 2.1 h; plasma clearance, 51 +/- 24 and 55 +/- 18 ml/h per kg; volume of distribution, 382 +/- 129 and 387 +/- 56 ml/kg; mean concentration in cerebrospinal fluid 1 to 6 h after infusion, 5.4 and 6.4 mug/ml. A dosage schedule of 50 mg/kg every 12 h for bacterial meningitis caused by susceptible organisms is suggested for pediatric patients over 7 days of age.

Single-dose ceftriaxone pharmacokinetics in pediatric patients with central nervous system infections.

Ceftriaxone has greater in vitro and in vivo efficacy against many common bacteria than other third-generation cephalosporins. Single-dose ceftriaxone pharmacokinetics were studied in 17 patients, aged 0.6 to 52 months, with infections of the central nervous system. Patients received a randomized dose of 50 or 75 mg/kg ceftriaxone intravenously over 5 minutes on the second to fifth day of illness. Serial blood samples were collected over 24 hours in all patients, and cerebrospinal fluid (CSF) was obtained 1 to 4.5 hours after injection. Ceftriaxone mean peak plasma concentrations, determined by high-power liquid chromatography, were 267 and 184 microgram/ml for the 75 and 50 mg/kg dosage groups, respectively. The harmonic mean elimination half-life was 4.2 hours, and the mean percent drug penetrance into CSF was 4.8 +/- 3.5%. Of CSF studies evaluated, the glucose concentration was correlated most closely (inversely) with CSF penetration of ceftriaxone. Individual CSF concentrations of ceftriaxone exceeded the minimal inhibitory concentrations of the respective bacteria causing infection by 480 to 5,600 times. Ceftriaxone may be useful in the treatment of serious pediatric infections, including meningitis.

Pharmacokinetics and tolerance of ceftriaxone in humans after single-dose intramuscular administration in water and lidocaine diluents.

The effects of 1% lidocaine as a diluent on the pharmacokinetics and tolerance of ceftriaxone administered intramuscularly were investigated in 12 adult volunteers. Each subject received two 0.5-g doses of ceftriaxone (one in water and the other in 1% lidocaine) at least 1 week apart in a randomized crossover fashion. Plasma and urine samples were collected serially and assayed for ceftriaxone content by high-performance liquid chromatography. The mean peak plasma concentration, time to attain the peak, area under the plasma curve from time zero to infinity, and elimination half-life were 45 micrograms/ml, 2.5 h, 578 micrograms . h/ml, and 7.1 h, respectively, after intramuscular administration of ceftriaxone in water diluent. The corresponding mean values in 1% lidocaine diluent were 42 micrograms/ml, 3 h, 577 micrograms . h/ml, and 7.0 h. The pharmacokinetic data suggested that 1% lidocaine does not alter either the elimination parameters or the bioavailability of intramuscularly administered ceftriaxone. The intensity and frequency of pain at the injection site were reduced considerably by the coadministered lidocaine.

Clinical bioavailability evaluation of a controlled release formulation of diazepam.

A controlled release formulation of diazepam was compared to equal daily dose of the trade tablet under single day and steady-state conditions. Virtually no differences were found in the mean steady-state concentrations of diazepam or its metabolites, N-desmethyldiazepam, when the subjects received the 5 mg trade table three times daily or the 15 mg controlled release formulation once daily. Similarly, there was no difference in mean diazepam or N-desmethyldiazepam plasma concentrations when single doses of the controlled release formulation were give to fed or fasted volunteers. These data indicate that the controlled release formulation produces plasma concentrations of diazepam and N-desmethyldiazepam comparable to those achieved with the same daily dose of the trade product given three times daily, suggesting that these regimens can be used interchangeably.

Determination of the major urinary metabolite of flurazepam in man by high-performance liquid chromatography.

A high performance liquid chromatographic method for the determination of N-1-hydroxyethylflurazepam, the major urinary metabolite of flurazepam, in human urine is described. Urine specimens were incubated enzymatically to deconjugate N-1-hydroxyethylflurazepam glucuronide (metabolite) and were then extracted at pH 9.0 to extract the metabolite. The extracts were chromatographed on a microparticulate silica gel column using automatic sample injection, isocratic elution at ambient temperature and UV monitoring at 254 nm. The internal standard was 7 chloro-5(2'-chlorophenyl) 1,3-dihydro-1-2-dimethylaminoethyl-2H-1,4-benzodiazepine-2-one. The recovery from urine, in the 0.5-25.0 microgram/ml range, was 96.5 +/- 11.5% (S.D.), and the sensitivity limit was 0.5 microgram/ml. The method was found to be specific for N-1-hydroxyethylflurazepam in the presence of intact flurazepam and other possible urinary metabolites of flurazepam. The method was successfully applied to urine specimens collected from human subjects following the administration of 30-mg single oral doses of flurazepam dihydrochloride.

Simultaneous automated determination of free and total sulfisoxazole and sulfamethoxazole in plasma and urine.

A fully automated method for the determination of sulfisoxazole, N4-acetylsulfisoxazole, sulfamethoxazole, and N4-acetylsulfamethoxazole in human plasma and urine was developed. Untreated plasma is analyzed by automation of dialysis, hydrolysis, color development, and quantitation. The method has a sensitivyt limit of 2 microgram/ml of plasma and has been used successfully to determine sulfonamide levels following administration of sulfoxazole and a combination drug product containing sulfamethoxazole and trimethoprim in humans. Samples are processed at the rate of 40 per hour, with a minimum of sample handling, data reduction, and materials.

Determination of trimethoprim in biological fluids by high-performance liquid chromatography.

A rapid, sensitive, and specific high-performance liquid chromatographic assay was developed for the determination of trimethoprim in blood, plasma, and urine using normalphase (adsorption) chromatography on a microparticulate silica column and UV monitoring at 280 nm. Trimethoprim is selectively extracted from the biological sample matrix at alkaline pH with chloroform, providng nearly quantitative extraction (greater than 95%) and a sensitivity limit of 0.01 to 0.02 microgram/ml blood or plasma, without interference from sulfonamides.

Pharmacokinetics of flunitrazepam following single- and multiple-dose oral administration to healthy human subjects.

Healthy human subjects received single and multiple oral doses of flunitrazepam. Absorption and disposition were first order and reproducible from administration. The oral doses were virtually completely available to the liver, and elimination from the body occurred entirely via metabolism. Assuming the liver to be the sole eliminating organ, hepatic blood clearance and extraction ratio were approximately 0.235 liter/hr/kg and 0.154, respectively. Steady-state blood volume of distribution averaged 3.76 liters/kg in the single-dose studies. Terminal exponential half-lives from the single- and multiple-dose studies (different subjects) averaged 13.5 and 19.2 hr, respectively; these differences were not due to clearance changes but were entirely attributable to variations in volumes of distribution.

Rapid determination of diazepam and nordiazepam in plasma by electron capture gas--liquid chromatography. Application in clinical pharmacokinetic studies.

A rapid method was developed for the determination of diazepam and nordiazepam (N-desmethyldiazepam) in human plasma using electron capture gas--liquid chromatography (GLC--ECE). The concentration of diazepam and nordiazepam is determined using 0.5 ml of plasma extracted with 1.0 ml of benzene containing 25 ng/ml of methylnitrazepam as the internal standard. The benzene extract is removed and an aliquot is subjected to automated GLC-ECD analysis. The method has a sensitivity limit of 5 ng diazepam and 10ng nordiazepam per milliliter of plasma. The method was used to determine the plasma levels in man following the first 5-mg diazepam dose, as well as during chronic oral administration of 5 mg diazepam three times daily and 15 mg diazepam once a day.