Comparison of azithromycin leukocyte disposition in healthy volunteers and volunteers with AIDS

Azithromycin, has been proved to be effective in the treatment and prophylaxis of a wide variety of infections. While the penetration of azithromycin into a number of types of mammalian cells has been well characterized, the influence of HIV infection on the intracellular disposition of this agent has not been studied. We therefore studied the disposition of azithromycin in polymorphonuclear (PMN) and mononuclear (MONO) leukocytes from six healthy volunteers and six volunteers with AIDS. After oral administration of a single 1200-mg dose of azithromycin (two 600-mg tablets), blood samples were collected over 6 days and intracellular azithromycin concentrations in MONOs and PMNs were measured. Analysis of the intracellular pharmacokinetics revealed an apparent difference in the MONO and PMN profile; this profile was similar for both groups. Intracellular concentrations of azithromycin remained high throughout the study period. Furthermore, no statistically significant differences in the intracellular area under the curve (11309+/-2543 vs. 16650+/-6254 for PMN; 14180+/-3802 vs. 21211+/-10001 for MONO) were observed between the healthy and AIDS populations, respectively. Our data confirm the extensive uptake of azithromycin by white blood cells both in healthy volunteers and in AIDS patients.     

The development and validation of an occlusal site-specific plaque index to evaluate the effects of cleaning by tooth brushes and chewing gum

These studies sought to develop and validate an occlusal site-specific plaque index to be used to measure plaque removal by brushing or chewing gum. The index divides the occlusal surfaces into imaginary zones from which scores are apportioned on a 0-4 basis dependent on the perceived % plaque coverage of each zone. Examiner calibration was conducted over 2 studies assessing inter-examiner reproducibility and intra-examiner repeatibility, respectively. Study 1 involved 2 examiners who recorded scores from the same 3 groups of subjects who had suspended tooth cleaning for 4 days. Analyses for inter-examiner reproducibility showed no significant mean differences between examiners or no significant differences between variances of the 2 examiners scores. Study 2 involved the same 2 examiners individually scoring 3 groups of subjects 2 x (approximately 60 min apart) for occlusal plaque. Analysis for intra-examiner repeatability showed no significant mean differences between the 2 scorings of each examiner. Furthermore, there were no significant differences between the variances of each examiner's scores except for 1 examiner in the repeatability exercise for the 1st group of subjects. Study 3 involved groups of subjects at 2 separate clinical sites (Bristol, England and Berne, Switzerland) being scored for occlusal plaque before and after toothbrushing with water or after no toothbrushing. Data from individual examiners and examiners combined revealed a significant reduction in occlusal plaque with brushing compared to no brushing. Study 4 was the same as study 3 but occlusal plaque was scored before and after chewing gum or not chewing gum. The Bristol examiner recorded a significant reduction in plaque by chewing gum compared to not chewing gum but the Berne examiner did not. The latter may have resulted from a considerable disparity in the number of evaluable occlusal surfaces between the two study sites. The index could be employed as part of the overall assessment or oral hygiene or used in clinical trials to study mechanical and chemical plaque control agents.     

Determination of the enantiomer and positional isomer impurities in atomoxetine hydrochloride with liquid chromatography using polysaccharide chiral stationary phases

A normal-phase isocratic chiral liquid chromatographic method has been developed and validated for atomoxetine hydrochloride. In addition to the S-enantiomer of atomoxetine, the conditions separate both para and meta positional isomers and the phenyl des-methyl analog. Method development strategies included (a) evaluation of polysaccharide-based chiral stationary phases with nonaqueous mobile phases, (b) the use of an octyl stationary phase with a sulfated-beta-cyclodextrin mobile phase additive, and (c) capillary electrophoresis using a single isomer heptakis-6-sulfato-beta-cyclodextrin modifier. All three approaches yielded acceptable conditions for the separation of atomoxetine from related molecules with the former fully validated and the latter two held as alternatives if needed. The final method conditions employing a Chiralcel OD-H column and mobile phase of hexane/IPA/DEA/TFA (85/15/0.15/0.2, v/v/v/v) at 1.0 mL/min have been fully validated with acceptable specificity, linearity, accuracy, repeatability, intermediate precision and quantitation limit.     

Prophylactic laser treatment hastens choroidal neovascularization in unilateral age-related maculopathy: final results of the drusen laser study

PURPOSE: The Drusen Laser Study evaluated macular laser to prevent choroidal neovascularization (CNV) and vision loss in high-risk age-related maculopathy (ARM). DESIGN: Prospective, interventional, randomized, controlled clinical trial in five hospital centers. METHODS: Patients in the unilateral group had neovascular ARM and drusen in the study eye. Study eyes were randomized to laser-treated or no-laser groups. For patients in the bilateral drusen group, eyes were randomized to right eye, laser or no laser; and left eye, alternative. Laser treatment comprised 12 argon spots. Outcome was best-corrected visual acuity and CNV signs, which were monitored for 3 years. RESULTS: In the unilateral group, vision loss occurred in 21 (28.8%) of 73 patients in laser vs 13 (19.7%) of 66 no-laser patients (P=.214). Incidence of CNV was 27 (29.7%) of 91 in laser vs 15 (17.65%) of 85 no-laser patients (P=.061). CNV onset was approximately 6 months earlier in laser-treated compared with no-laser patients (P=.05). In the bilateral group, vision loss occurred in six (8.3%) of 72 laser-treated vs 10 (13.9%) of 72 fellow eyes (P=.3877). CNV incidence was 12 (11.6%) of 103 in laser-treated vs seven (6.8%) of 103 fellow eyes (P=.225). There was no difference in onset of CNV. CONCLUSIONS: Results do not support prophylactic laser of the fellow eye of patients with neovascular ARM. Its role in patients with bilateral drusen remains unclear.     

The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo androgen and antiandrogen responses. Phase 1: use of a potent agonist and a potent antagonist to test the standardized protocol

The Organisation for Economic Cooperation and Development (OECD) has completed phase 1 of the Hershberger validation intended to identify in vivo activity of suspected androgens and antiandrogens. Seventeen laboratories from 7 countries participated in phase 1, and results were collated and evaluated by the OECD with the support of an international committee of experts. Five androgen-responsive tissues (ventral prostate, paired seminal vesicles and coagulating glands, levator ani and bulbocavernosus muscles, glans penis, and paired Cowper's or bulbourethral glands) were evaluated. The standardized protocols used selected doses of a reference androgen, testosterone propionate (TP), and an antiandrogen, flutamide (FLU). All laboratories successfully detected TP-stimulated increases in androgen-responsive tissue weight and decreases in TP-stimulated tissue weights when FLU was co-administered. The standardized protocols performed well under a variety of conditions (e.g., strain, diet, housing protocol, bedding). There was good agreement among laboratories with regard to the TP doses inducing significant increases in tissue weights and the FLU doses decreasing TP-stimulated tissue weights. Several additional procedures (e.g., weighing of the dorsolateral prostate and fixation of tissues before weighing) and serum component measurements (e.g., luteinizing hormone) were also included by some laboratories to assess their potential utility. The results indicated that the OECD Hershberger protocol was robust, reproducible, and transferable across laboratories. Based on this phase 1 validation study, the protocols have been refined, and the next phase of the OECD validation program will test the protocol with selected doses of weak androgen agonists, androgen antagonists, a 5alpha-reductase inhibitor, and chemicals having no androgenic activity.     

Motorcycle-related hospitalizations in the United States, 2001

OBJECTIVES: To estimate the prevalence of motorcycle-related hospitalization in the United States in 2001 and to describe the demographic, clinical, hospital, and financial characteristics associated with these injuries. METHODS: Cross-sectional analysis of the 2001 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project was conducted in 2003. RESULTS: There were an estimated 30,505 (confidence interval=26,566-34,445) motorcycle-related hospital discharges in 2001. Approximately 62% of cases were aged > or =30 years, and males accounted for 89% of cases. The most common principal diagnoses were fractures of the lower limb (29.4%), fractures of the upper limb (13.1%), and intracranial injuries (12.3%). The mean length of stay was 5 days, the median hospital charge was $15,404, and the total estimated hospital charges were >$841 million. The majority of patients (56.5%) were admitted to large urban teaching hospitals, and these hospitals accounted for nearly 70% of all hospital charges. Approximately 26% of cases were self-pay or listed public insurance as the expected payer. CONCLUSIONS: These findings shed light on the substantial morbidity and financial impact of motorcycle-related injuries. Renewed and strengthened prevention efforts are warranted.