Pharmacokinetics of clinafloxacin enantiomers in humans

The pharmacokinetics of R-clinafloxacin and S-clinafloxacin enantiomers of the broad-spectrum fluoroquinolone antibiotic, clinafloxacin, were characterized in selected volunteer subjects and patients after the administration of oral and intravenous doses of racemic drug. The absorption of each enantiomer was rapid and nearly complete after a single, oral 400 mg racemic dose. The mean (+/- SD) bioavailability of R-clinafloxacin was 87.5% +/- 4.8% compared to 86.2% +/- 5.8% for S-clinafloxacin. The mean Cmax of each enantiomer was 1.19 micrograms/mL, with plasma concentrations of each enantiomer remaining above 0.1 microgram/mL for at least 12 hours. No notable differences in the disposition of R-clinafloxacin and S-clinafloxacin were observed. After a single 400 mg intravenous dose of racemic drug, mean (+/- SD) t1/2 was 5.6 +/- 0.3 hours and 5.7 +/- 0.4 hours, plasma Cl was 329 +/- 49 mL/min and 314 +/- 45 mL/min, and Vdss was 138 +/- 18 L and 134 +/- 16 L for R- and S-clinafloxacin, respectively. Two healthy volunteers each received a single 400 mg oral dose of racemic clinafloxacin (alone) and with oral administration of 1 gm probenecid separated by a 1-week washout period between treatments. With probenecid coadministration, the increase in AUC0-infinity was 75% and 83% for R-clinafloxacin and was 71% and 75% for S-clinafloxacin in each subject, respectively. Probenecid increased the total exposure (AUC) of both R-clinafloxacin and S-clinafloxacin, although it had no stereo-selective effects on the disposition of either enantiomer. The antimicrobial potency of the isomers was also evaluated. In vitro susceptibility testing showed that the two compounds were comparable in their inhibitory activities, as all MICs were within twofold for each organism tested. These results demonstrate that in addition to their similar antimicrobial potency, R- and S-clinafloxacin have nearly identical disposition characteristics and are eliminated by similar mechanisms that display no apparent enantioselectivity in man.     

Children's use of CROS hearing aids

Ten children with unilateral hearing loss, aged 7 to 17 years, who were fit with contralateral routing of signal (CROS) hearing aids were followed up for three years to assess the suitability of this type of hearing aid fitting on children. The determination of the success of the fitting was based on follow-up visits, chart review, and response to a questionnaire sent to the parents. The fitting was considered to be successful if the child accepted the aid and if parents and teachers observed substantial improvement in academic performance and/or social behavior. Seven children were considered to be successful users of their CROS aids; one was unavailable for follow-up; one did better with a BICROS aid; and one did not do well with amplification. Our experience suggests that children with unilateral hearing loss can benefit from CROS amplification.     

Medullary carcinoma of the thyroid gland.

Out of the discovery of concurrent multiple endocrine neoplasms has evolved the concept of multiple endocrine adenomatosis (MEA1 and MEA2). Medullary carcinoma of the thyroid gland is the most constant facet of MEA2 and is derived from C-cells of the neural crest. These cells, resembling parafollicular cells of lower animals, elaborate calcitonin which acts as a sensitive signal of the presence of the tumor. Ninety per cent of MCT occurs sporadically; in 10% the tumor presents as an atuosomal dominant trait. Other endocrinopathies, especially pheochromocytomas, are present in 70% of cases. The lesions are "cold" on iodine radioisotope scan. On microscopic examination, the appearance of amyloid is characteristic. Regional lymph node metastasis occurs early. The tumor deserves appropriate aggressive management. Surgical therapy should begin early and vigorously with the minimum procedure being total thyroidectomy. Frequent lymph node metastasis speaks for the need for regional neck dissection extended into the superior mediastinum. The search for, and the treatment of, the frequently associated endocrinopathies is essential. Pheochromocytoma must be suspected and eradicated before treatment of the thyroid tumor. A genetic workup should be included.     

Health of retired workers: survival status and Medicare service use

Data from the Social Security Administration's 1982 New Beneficiary Survey and Master Beneficiary Record were matched with 1984 data from the Medicare Automated Data Retrieval System to study the effects of self-reported health on subsequent health service usage and survival. Proportionately, more new retired workers who reported poorer health in 1982 were decreased by December 1984. Functionally dependent beneficiaries as determined by the Functional Capacity Limitation Index had death rates four to five times greater than those who reported no limitations. The health status of retired workers who received Social Security benefits before age 65 was no better than beneficiaries 65 or over. Decedents were more likely than survivors to incur Medicare charges, and to have substantially higher median charges--$8,834 compared with $285.     

A comparison of scintigraphy, thermography, ultrasound and phlebography in grading of clinical varicocele

Varicocele, a varicosity of the pampiniform plexus, usually on the left side, is a common urologic problem. It may be associated with symptoms of local discomfort or abnormal spermatogenesis. Internal spermatic vein phlebography is the "gold standard" investigative technique, but it is invasive. Noninvasive studies include: labeled blood-pool scintigraphy, thermography and ultrasound. Two hundred sixty-three patients were investigated with various combinations of these modalities. The degree of abnormality for each modality was graded semiquantitatively and the results compared. In addition, the results of semen analysis were correlated to imaging results. Ninety-six patients were investigated with all four tests (scintigraphy, thermography, ultrasound and phlebography). The correlation of positive phlebography to positive scintigraphy was 98%, to thermography 100% and to ultrasound 98%. The concordance (grade for grade) was 71% for scintigraphy, 68% for thermography and 62% for ultrasound. There was no obvious correlation between abnormalities of semen analysis and grading of varicocele. We conclude that the diagnostic accuracy and grading of severity by noninvasive techniques (including scintigraphy) compare very favorably with that of phlebography. Moreover, scintigraphy allows the noninvasive evaluation of reflux through the internal spermatic vein, which may be useful in planning therapy.     

Inability to demonstrate hydroxylation of tyrosine by murine melanoma "tyrosinase" (L-DOPA oxidase), using the tritiated water assay technique.

Validity of the tritiated water assay technique for tyrosine hydroxylase activity as a qualitative method was demonstrated with mushroom tyrosinase. Using this method, isolated murine melanoma "tyrosinase" (L-dopa oxidase) showed no tyrosine hydroxylase activity. This finding supports previous studies in our laboratory which used a variety of histochemical and biochemical methods. The nonenzymatic production of tritiated water caused by tritium exchange with hydrogen peroxide complicates the use of the tritiated water assay technique with crude systems, since hydrogen peroxide is generated by a variety of oxidase reactions. For this reason, previous studies using the tritiated water assay technique with crude systems are ambiguous.     

Clinical and radiographic "reankylosis" following hip surgery in ankylosing spondylitis.

Eleven patients with ankylosing spondylitis underwent reconstructive hip surgery (21 hips). In 10 of these hips multiple surgical procedures had been performed. The final procedure included total hip arthroplasties (16 hips), femoral cup arthroplasties (four hips) and an Austin-Moore prosthetic replacement (one hip). A clinical and radiographic evaluation in the postoperative period revealed a high incidence of decreased joint motion and heterotopic ossification. Clinically moderate to severe restriction of motion was noted in 12 hips, and in six of these "reankylosis" was present. Radiographically moderate to severe new bone formation was seen in 11 hips, and in nine of these "reankylosis" was suggested. An association of excessive ossification and multiple surgical procedures was evident. It would appear that when the prime indication for hip surgery in patients with ankylosing spondylitis is restricted motion, the operation may not be beneficial.     

A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate

BACKGROUND: Renal insufficiency is characterized by lipoprotein abnormalities including elevated triglyceride levels. PATIENTS AND METHODS: The safety and efficacy of micronized fenofibrate as a treatment for dyslipidemia in patients with progressive renal insufficiency was evaluated in a randomized, placebo-controlled double-blind study comparing fenofibrate and dietary modification to dietary modification alone. Patients were evaluated following a 3-month pre-randomization period of dietary counseling. Twenty-eight patients with moderate renal insufficiency and triglyceride levels 2.3 mmol/l or LDL/HDL ratio 5 were randomized to placebo (n = 12) or fenofibrate (n = 16) therapy. Treatment and dietary counseling continued for 6 months. RESULTS: Ten of 16 patients (63%) treated with fenofibrate achieved a 30% reduction in triglyceride levels or LDL/HDL ratio reduction < 5 compared to 2 of 17% in the placebo group (p = 0.015). Triglyceride levels were significantly reduced in the fenofibrate group (-31%) versus placebo (+1.3%, p = 0.003). In compliant patients (n = 25) there was also a significantly greater increase in HDL cholesterol levels in the fenofibrate group (+19.9%) compared to placebo (-4.7%, p = 0.001). Changes in measured creatinine clearance were not significantly different between the groups and there were no serious adverse effects of treatment. CONCLUSION: Fenofibrate therapy combined with dietary modification effectively reduced triglyceride levels in renal insufficiency patients without serious adverse effects.