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.     

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

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.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

A locus for autosomal dominant anterior polar cataract on chromosome 17p

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.      

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.