Loop electrosurgical excision procedure for conization of the uterine cervix

Fluconazole is a novel azole antifungal agent with low lipophilicity and high metabolic stability which has been investigated pharmacokinetically in six animal species and in man. The pharmacokinetic parameters of this drug have been compared across species and allometric relationships for fluconazole have been established. The volume of distribution was an 'invariant' parameter. When expressed in units corrected for bodyweight, the volume of distribution was constant across species, in keeping with being distributed throughout body water. Allometric relationships were obtained for total and renal clearance parameters. The closeness of the allometric exponents was in keeping with renal elimination accounting for most of the clearance in all species investigated. It also follows from the invariant characteristics of the volume of distribution term that an allometric relationship for plasma elimination half-life (t1/2) was also evident. Fluconazole thus possesses pharmacokinetic properties which are predictable for all terrestrial mammals. More detailed analysis of renal clearance (CLR) with regard to its relationship with glomerular filtration rate (GFR) has also been carried out. The data suggest that CLR is a direct function of GFR, involves only passive diffusion phenomena and that the extent of tubular re-absorption (approx. 80%) is constant across species. These observations are in keeping with the moderate lipophilicity and plasma protein binding of fluconazole and the incomplete re-absorption of the drug from the kidney tubules. It follows from these investigations that a knowledge of GFR in patients with altered renal function should allow a mechanistically based prediction of elimination characteristics of fluconazole.     

Changes in the impulse activity of neurons of the human thalamic ventrolateral nucleus during voluntary movement

Functional differences were revealed in evoked activity of two types (A and B) of units of the human thalamic ventro-lateral nucleus (VL). Collective activities of these polyfunctional neurons were selectively related to triggering and execution phases of movement. Common character of dynamics of the responses seems to be due to similar polyfunctional nature as well as to the functional role of these two complementary elements in the motor signal transmission. The collective activities reflect in the VL the integrative processes related to processing and programming of generalised parameters of motor signals, but unrelated to performance of a concrete motor act.     

The lifestyle assessment questionnaire: an instrument to measure the impact of disability on the lives of children with cerebral palsy and their families

Suitable measures of health and morbidity are less readily available for children than they are for adults. We present a measure, which is used to describe the impact of impairment and disability on the lives of children with cerebral palsy and their families. The development of this measure involved data collected from 691 children with cerebral palsy contained within the North-East England Cerebral Palsy Register and born between 1960 and 1985. Uniquely, multidimensional scaling techniques were used to derive dimensions analogous with those described in the International Classification of Impairments, Disabilities, and Handicaps. We present the analyses undertaken to test the properties of the tool, which show that it is a reliable and valid measure of the disadvantages experienced by children with cerebral palsy.     

Spatial integration in human smooth pursuit

When viewing a moving object, details may appear blurred if the object's motion is not compensated for by the eyes. Smooth pursuit is a voluntary eye movement that is used to stabilize a moving object. Most studies of smooth pursuit have used small, foveal targets as stimuli (e.g. Lisberger SG and Westbrook LE. J Neurosci 1985;5:1662-1673.). However, in the laboratory, smooth pursuit is poorer when a small object is tracked across a background, presumably due to a conflict between the primitive optokinetic reflex and smooth pursuit. Functionally, this could occur if the motion signal arising from the target and its surroundings were averaged, resulting in a smaller net motion signal. We asked if the smooth pursuit system could spatially summate coherent motion, i.e. if its response would improve when motion in the peripheral retina was in the same direction as motion in the fovea. Observers tracked random-dot cinematograms (RDC) which were devoid of consistent position cues to isolate the motion response. Either the height or the density of the display was systematically varied. Eye speed at the end of the open-loop period was greater for cinematograms than for a single spot. In addition, eye acceleration increased and latency decreased as the size of the aperture increased. Changes in the density produced similar but smaller effects on both acceleration and latency. The improved pursuit for larger motion stimuli suggests that neuronal mechanisms subserving smooth pursuit spatially average motion information to obtain a stronger motion signal.     

Current status of trade in cultured shrimps

Shrimp culture is an attractive sector of aquaculture business, in view of the high profits and quick turnover. The vast majority of cultured shrimp production occurs in Asian countries. The author details the levels of production, consumption and trade of cultured shrimps since 1991 in and between the major producing countries. A decline in production has been registered in some countries in recent years, due to mass mortality caused by a number of diseases (particularly 'white spot' disease). Efforts to overcome these problems have met with only partial success.     

Reduced COX-2 protein in colorectal cancer with defective mismatch repair

Most colorectal adenomas and carcinomas arise in the setting of chromosomal instability characterized by progressive loss of heterozygosity. In contrast, approximately 15-20% of colorectal neoplasms arise through a distinct genetic pathway characterized by microsatellite instability (MSI) associated with frequent loss of expression of one of the DNA mismatch repair enzymes, most often hMLH1 or hMSH2. These distinct genetic pathways are reflected by differences in tumor histopathology, distribution in the colon, prognosis, and dwell time required for progression from adenoma to carcinoma. To determine whether these two groups of tumors differ in their expression of cyclooxygenase-2 (COX-2), a putative chemopreventative target, immunostaining for this protein was performed in colorectal cancers categorized by the presence (n = 41) and absence (n = 66) of defective mismatch repair. Defective mismatch repair was defined by the presence of tumor microsatellite instability (MSI-H, > or =40% of markers demonstrating instability) and by the absence of protein expression for either hMLH1 or hMSH2. Overall, our results showed that low or absent COX-2 staining was significantly more common among tumors with defective mismatch repair (P = 0.001). Other features predictive of low COX-2 staining included marked tumor infiltrating lymphocytosis, and solid/cribiform or signet ring histological patterns. These observations indicate that colorectal cancers with molecular and phenotypic characteristics of defective DNA mismatch repair express lower levels of COX-2. The clinical implications of this biological distinction remain unknown but should be considered when assessing the efficacy of COX-2 inhibitors for chemoprevention in patients whose tumors may arise in the setting of defective DNA mismatch repair.