Biomedical subjects

R Seligsohn

Publications and source records attributed to R Seligsohn.

8 recordsLinked to original sources

PubMed1991

Pharmacokinetics of intravenous metronidazole at different dosages in healthy subjects.

Metronidazole is effective in the treatment of trichomoniasis and serious anaerobic infections. Individual doses given clinically ranged from 250 mg to 2.0 gm. Most of the available pharmacokinetic data were obtained when the drug was administered at the low end of the dosage range. Several other studies were done using assays that were subject to interference by metabolites. We therefore conducted this investigation to evaluate the pharmacokinetics of metronidazole at different dosage levels in normal subjects in a crossover manner using a specific HPLC assay. Nine male normal volunteers were each administered 250 mg, 1.0 gm and 2.0 gm of intravenous metronidazole in a crossover manner. Serial blood samples were obtained immediately before and at 0, 15, 30, 60, 90 minutes, 2, 4, 6, 10, 24 and 32 hours after the dose. Serum concentrations of metronidazole and its metabolites were determined by HPLC. The half-lives, elimination rate constants, volumes of distribution and areas under the concentration-time curve were calculated. Analysis of variance revealed a statistically significant difference between the low dose (250 mg) and the high dose (1.0 gm and 2.0 gm) effect on the calculated pharmacokinetic parameters. In addition, the production and the elimination of the metronidazole hydroxy metabolite were also found to be reduced when higher doses of the drug were administered. These findings revealed that the pharmacokinetics of metronidazole and its hydroxy metabolite are altered when higher doses of the drug are given; the metabolic transformation of the parent drug is also expected to be reduced.

Adult↗

PubMed1987

Pharmacokinetics of metronidazole in patients with alcoholic liver disease.

The pharmacokinetics of metronidazole was evaluated in eight patients with alcoholic liver disease. Metronidazole (7.5 mg/kg) was administered to each patient intravenously. Serial blood samples were obtained after the dose. Serum metronidazole concentrations were determined by high-performance liquid chromatography. The following pharmacokinetic parameters (mean +/- standard deviations) were obtained: half-life, 18.31 +/- 6.06 h; elimination rate constant, 0.042 +/- 0.013 h-1; volume of distribution, 0.77 +/- 0.16 liters/kg; and total body clearance, 0.51 +/- 0.11 ml/min per kg. Compared with subjects with normal liver function, patients with liver disease showed a reduction in drug elimination rate and total body clearance. The half-life of metronizadole in serum and volume of distribution were increased. Large variations of these parameters were also observed among the patients. On the basis of these observations, a reduced dose of metronidazole should be given to patients with alcoholic liver disease to avoid accumulation of metronidazole and its metabolites. Monitoring of drug concentration in serum may also be necessary to optimize therapy.

Adult↗

PubMed1986

Comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin.

Fifty-four patients treated with gentamicin and 52 patients treated with amikacin were evaluated for nephrotoxicity and ototoxicity in a prospective, randomized, blinded comparative trail. According to our definition of nephrotoxicity (an increase in serum creatinine levels to at least 50 percent and 0.5 mg/dl above the baseline value), nephrotoxicity occurred in eight (15 percent) of the patients who were treated with gentamicin and none of the patients who were treated with amikacin (p = 0.006). Using several other definitions of nephrotoxicity, the differences in incidence between the treatment arms were not significant. Nephrotoxicity appeared to be associated with impaired baseline renal function, greater age, and the presence of bacteremia. Ototoxicity occurred in six (11 percent) of the 54 gentamicin-treated patients; auditory toxicity occurred in three patients, and toxic changes were observed in three of the 33 patients who could also be evaluated for vestibular toxicity. Similarly, ototoxicity was observed in seven (13 percent) of the 52 amikacin-treated patients; auditory toxicity occurred in four patients, and of the 34 patients who could also be evaluated for vestibular toxicity, three exhibited vestibular toxicity without auditory toxicity are one experienced vestibular effects in addition to those affecting the cochlea. We observed a modest association of ototoxicity with nephrotoxicity and with an elevated mean trough aminoglycoside serum level. The results of this study indicate that amikacin may be less nephrotoxic than gentamicin in humans; however, the broad applicability of this finding to other patient populations is uncertain.

Adolescent↗

PubMed1978

Simplified radioenzymatic assay for chloramphenicol.

A simplified radioenzymatic assay for chloramphenicol was developed by eliminating the need for cumbersome extraction procedures. After the acetylation of chloramphenicol with [(14)C]acetyl coenzyme A in the presence of chloramphenicol acetyltransferase, the reaction mixture was added to a toluene-based scintillation fluid. Since (14)C-acetylated chloramphenicol is more soluble than [(14)C]acetyl coenzyme A in toluene, the radioactive product could be counted directly. The rapidity of this assay, as well as its accuracy, precision, and specificity, makes it particularly suitable for clinical use. In contrast to previous reports of enzymatic assays for chloramphenicol, we have found that results of the assay of standards prepared in serum were up to 25% higher than those of standards prepared in saline, cerebrospinal fluid, or urine.

Acetyl Coenzyme A↗

PubMed1978

Effects of radiopharmaceuticals on radioenzymatic assays of aminoglycoside antibiotics: interference by gallium-67 and its elimination.

Radionuclides currently used in clinical medicine were evaluated for their possible interference with radioenzymatic assays of aminoglycoside antibiotics. Of the radiopharmaceuticals tested, only (67)Ga citrate interfered with the radioenzymatic assay of gentamicin. Radioenzymatic assay of serum samples obtained from patients receiving (67)Ga yielded gentamicin concentrations falsely elevated by more than 1 mug/ml for approximately 1 week after (67)Ga administration. A procedure was developed to eliminate (67)Ga interference with radioenzymatic assays of aminoglycoside antibiotics. After (67)Ga citrate was spotted onto phosphocellulose filter disks, the filters were immersed in 7.2 N HCl, and radioactivity was removed by successive extractions of the acid phase with diisopropyl ether. After three extractions, less than 0.1% of the original radioactivity remained. Similar extraction of disks containing (14)C-adenylylated gentamicin or tobramycin or (14)C-acetylated amikacin had no effect on (14)C radioactivity. The concentrations of aminoglycosides in serum standards supplemented with (67)Ga citrate were determined accurately by radioenzymatic assays followed by extraction with diisopropyl ether. Concentrations of gentamicin in six serum samples from patients injected with (67)Ga during gentamicin therapy, as determined by radioenzymatic assay and extraction, were within 9% of the results obtained by reassay of the same samples after the decay of (67)Ga.

Aminoglycosides↗

PubMed1977

Comparative clinical studies of ototoxicity and nephrotoxicity of amikacin and gentamicin.

A comparative study of the oto- and nephrotoxicity of amikacin and gentamicin was carried out prospectively. Twenty-six gentamicin-treated patients and 27 amikacin-treated patients were monitored for changes in auditory and renal function during and after therapy. Thirteen of those treated with gentamicin and 20 of those treated with amikacin underwent vestibular caloric testing which could be evaluated for evidence of toxicity. In four (15.4%) of the gentamicin-treated patients, nephrotoxicity developed; no such toxicity was seen in the amikacin-treated patients. This difference may have been due to a fortuitously higher incidence of pretreatment renal impairment in the gentamicin-treated group. In two gentamicin-treated patients (7.7%), ototoxicity developed (one auditory, one vestibular), and in two amikacin-treated patients (7.4%), auditory toxicity developed. Statistical analysis of oto- and nephrotoxicity and their risk factors was not attempted because of the small numbers of patients who could be evaluated. Additional patients are being studied.

Adult↗

PubMed1977

Aspergillus terreus osteomyelitis.

Aspergillus terreus infection limited to the L1-2 disk space and first and second lumbar vertebrae developed in a patient not predisposed to invasive aspergillosis. The observation of morphologically distinct secondary spores (aleuriospores) on microscopic examination of open biopsy specimens permitted a preliminary identification of A terreus, which was confirmed by culture. The infection was eradicated with amphotericin B in a total dose of 3 gm. Aspergillus terreus is usually a saprophyte. The present case and four others collected from the literature establish this species as an invasive pathogen.

Adult↗

PubMedDate not supplied

Ganglion cell counts in the cochleae of patients with normal audiograms.

Spiral ganglion cells were counted in the right cochleae of 16 patients with normal audiograms and without a history of hearing deficit or other auditory symptoms. Total counts ranged from 29 802 to 38 352, with a mean of 33 623. There was no relationship between total counts and patient age or between total counts and length of either the cochlea or the spiral ganglion.

Adolescent↗