Pharmacokinetics of ofloxacin in healthy subjects and patients with varying degrees of renal impairment.

The pharmacokinetics of the new fluoroquinolone antimicrobial ofloxacin were studied in 18 subjects with normal renal function or varying degrees of renal impairment, including patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis. Apparent total body and renal clearances declined and elimination half-life increased with decreasing creatinine clearance. CAPD and haemodialysis removed clinically insignificant fractions of ofloxacin body burden over the study period (6-15% and 9-11% of the dose, respectively). The apparent volume of distribution, peak concentration, time to peak concentration, and non-renal clearance were not altered significantly by renal insufficiency. An extended dosing interval of 24-48 h is recommended, depending upon the degree of renal impairment, when creatinine clearance falls below 50 mL/min. In addition, supplemental doses would not appear to be necessary during CAPD and following haemodialysis.     

Radiographic assessment of asymmetry of the mandible.

PURPOSETo assess the relationship between mandibular asymmetry and disorders of the temporomandibular joint.METHODSWe used advanced imaging of the temporomandibular joint to distinguish different causes of mandibular asymmetry. MR imaging and arthrography were applied to the temporomandibular joints of 11 patients presenting with mandibular asymmetry.RESULTSCondyle hyperplasia was identified as the cause of the asymmetry in 5 patients. In the other 6 patients the mandibular condyle was normal on the long side, but the short side of the face demonstrated a small condyle head, short condyle neck associated with disk displacement, internal derangement, and degenerative joint disease of the temporomandibular joint.CONCLUSIONSThese observations suggest that both condyle hyperplasia on the long side of the mandible and disk displacement and degenerative joint disease of the temporomandibular joint on the short side can cause mandibular asymmetry. It was concluded that MR imaging or arthrography can be valuable for understanding the cause of mandibular asymmetry and be effective in treatment planning.     

A rapid half-cell technique for the pre-screening of polymer fuel cell catalysts

Four platinum-based catalysts with different catalytic activity for the oxygen reduction reaction have been prepared and tested in polymer fuel cells (PFCs) and in half-cells with H₂SO₄ and HF electrolytes. The activity results of PFCs at 0.9 V versus RHE (reversible hydrogen electrode) can be mimicked in parallel by the results obtained in HF electrolyte but not by the results obtained in H₂SO₄ electrolyte. This paper concludes that the pre-screening of a huge number of Pt-based catalysts for the selection of potential catalysts for the PFCs can be carried out by a rapid half-cell technique with a non-adsorbing electrolyte such as HF.     

Contextual modulation of synchronization to random dots in the cat visual cortex

Synchronization of neuronal activity has been proposed as a binding mechanism for integration of image properties into one coherent percept. In the present study, we investigated the contextual modulation of synchronization to random dot patterns. Coherent motion of random dots evoked well synchronized responses in area 17 of anaesthetized cats when the stimulus was presented in the compound receptive field of recorded sites. Gradually changing the directional coherence of random dots in the surround while maintaining fully coherent motion of the stimulus in the receptive field significantly suppressed synchronization of neuronal activity for some stimulus conditions. However, usually one or two peaks of increased synchronization were found in the surround coherence tuning curves with low (8–12%) and/or moderate (25–50%) coherence in the surround. At the population level, synchronization was significantly depressed with incoherent motion in the receptive field and when both the surround and the receptive field were jointly stimulated with 0% coherence. The intriguing finding was the discovery of two distinct groups of cells with opposite synchronization changes dependent on the presence or absence of significant synchronization in their spontaneous activity. The latter group of neurons showed peaks of increased synchronization with lower surround coherence, thus probably being more sensitive to the direction of the surround motion. Overall, our findings support the notion that binding of stimulus properties can be achieved by synchronized activity of cortical cells. However, our findings go further than the original hypothesis of feature binding by synchrony to show that synchronization of cortical activity may be directly related to the decision making processes, which in turn are related to the threshold of perception of coherent motion.     

Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET 012

BACKGROUND: The HIVNET 012 trial in Uganda demonstrated that single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. NVP resistance (NVPR) mutations were detected in 25% of women 6 to 8 weeks after NVP, with a higher rate of NVPR in women with subtype D than A. This study examined emergence and fading of specific NVPR mutations in women with these subtypes. METHODS: Plasma HIV-1 was analyzed with the ViroSeq genotyping system (Celera Diagnostics, Alameda, CA). Genotypes were obtained from paired samples collected 7 days and 6 to 8 weeks after NVP from 140 women, 83 with subtype A and 57 with subtype D. RESULTS: The rate of NVPR was similar in women with subtype A vs. D at 7 days but was higher in subtype D than A at 6 to 8 weeks. The higher rate of NVPR in subtype D was explained by at least 2 factors: Y181C faded from detection at a greater rate in women with subtype A (odds ratio = 3.06; 95% CI, 1.04, 8.90) and K103N accumulated at a greater rate in women with subtype D (odds ratio = 1.74; 95% CI, 0.62, 4.87). CONCLUSIONS: HIV-1 subtype influences selection and fading of HIV-1 variants with specific drug resistance mutations after antiretroviral drug exposure.     

Formulary management of macrolide antibiotics

Selection of macrolide antibiotics for formulary addition can be a difficult task, with the increasing availability of new agents as well as the numerous differences in pharmacokinetic and pharmacodynamic properties of available agents. Nonetheless, appropriate evaluation of the important characteristics of macrolide antibiotics should allow selection of the most cost-effective agents for formulary addition. Most importantly, differences in antimicrobial activity and efficacy, product formulation, tolerability and cost should be carefully considered when making formulary decisions. Notably, evidence from in vitro studies and clinical trials indicate differences between the macrolide antibiotics, especially in the management of a variety of opportunistic infections in immunocompromised patients. For selected clinical situations, it may be important to select an effective agent available in both oral and intravenous formulations, especially in severe pneumonia caused by Legionella spp. In addition, the availability of generic formulations should be considered for its potential to reduce cost. Comparative drug costs, as well as costs associated with noncompliance, should also be evaluated carefully. Dosage regimens should also be considered, as shorter durations of therapy and less frequent dose administration may lead to increased compliance and thereby improved effectiveness and economic efficiency.     

Preparation and protein conjugation of a divinyl sulphone derivatized bifunctional chelating agent

A new bifunctional chelating agent with a novel linking arm, 2-[p-?N-benzyl-N-(2-vinylsulfoethyl)?- (aminobenzyl)?-1,3-propane-diamine-N,N,N',N'-tetraacetic acid (VS-PDTA) was synthesized and was conjugated to protein for the purpose of attaching radiometals to monoclonal antibodies (MAbs). The effect of various parameters such as ligand concentration, protein concentration, pH, temperature and reaction period on the conjugation have been examined using chromatographic (SE and TLC) analysis after labeling with 111In. The parameters and chemical variables studied have significant effects on the efficiency and rate of protein conjugation.     

Residual curarization in the neonate after Caesarean section

The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d-tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)