Can tissue drug concentrations be monitored by microdialysis during or after isolated limb perfusion for melanoma treatment?

Isolated limb perfusion (ILP) with melphalan is used to treat recurrent melanoma. This study aimed to develop a microdialysis technique for melphalan tissue concentration measurement during ILP. The effects of melphalan concentration (50-600 mu g/ml), microdialysis flow rate (0.55-17.5 mu l/min), probe length (5-50 mm) and temperature (25-41.5 degrees C) on in vitro recovery were studied. In addition, in vivo recovery was measured in rat hindlimbs perfused with melphalan using 50 mm microdialysis probes implanted subcutaneously and into muscle. Both dialysate and tissue sample melphalan concentrations were determined by high performance liquid chromatography. The in vitro recovery of melphalan was not affected by melphalan concentration or temperature, but increased with probe length and decreased with flow rate. The melphalan concentrations in subcutaneous and muscle dialysates were not significantly different. A linear relationship was found between tissue dialysate concentrations and actual tissue concentrations of melphalan (r(2) = 0.97). Microdialysis is a potential method for tissue drug monitoring which may assist in the efficacious use of cytotoxics in human ILP. (C) 2000 Lippincott Williams & Wilkins.

Mothers' mental illness and child behavior problems: Cause-effect association or observation bias

Objective: A number, of studies have consistently found that a mother's mental health (particularly her level of depression) is a strong predictor of mental health problems experienced by her child(ren). However, the validity of this finding is in doubt because the majority of these studies have relied on maternal reports as indicators of children's behavior. Method: This prospective, longitudinal study examines data an the mental health of the mother from prior to the birth of her child to when the child reaches 14 years of age. Child behavior is measured at 14 years of age using reports from mother and child. Mother and child responses are compared to provide an indication of the possible magnitude of maternal observation bias in the reporting of child behavior problems. Results: Anxious and/or depressed mothers tend to report more cases of child behavior problems than do their mentally healthy counterparts or children themselves. Differences between mothers and youths In reporting behavior problems appear to be related to the mothers' mental health. Conclusions: Current maternal mental health impairment appears to have a substantial effect on the reporting of child behavior problems by the mother, thereby raising questions about the validity of reports of child behavior by persons who are currently emotionally distressed.

Evaluation of a new bioelectrical impedance instrument for the prediction of body cell mass independently of height or weight

The objective of the present study was to evaluate the performance of a new bioelectrical impedance instrument, the Soft Tissue Analyzer (STA), which predicts a subject's body composition. A cross-sectional population study in which the impedance of 205 healthy adult subjects was measured using the STA. Extracellular water (ECW) volume (as a percentage of total body water, TBW) and fat-free mass (FFM) were predicted by both the STA and a compartmental model, and compared according to correlation and limits of agreement analysis, with the equivalent data obtained by independent reference methods of measurement (TBW measured by D2O dilution, and FFM measured by dual-energy X-ray absorptiometry). There was a small (2.0 kg) but significant (P < 0.02) difference in mean FFM predicted by the STA, compared with the reference technique in the males, but not in the females (-0.4 kg) or in the combined group (0.8 kg). Both methods were highly correlated. Similarly, small but significant differences for predicted mean ECW volume were observed. The limits of agreement for FFM and ECW were -7.5-9.9 and -4.1-3.0 kg, respectively. Both FFM and ECW (as a percentage of TBW) are well predicted by the STA on a population basis, but the magnitude of the limits of agreement with reference methods may preclude its usefulness for predicting body composition in an individual. In addition, the theoretical basis of an impedance method that does not include a measure of conductor length requires further validation. (C) Elsevier Science Inc. 2000.

Feed intake and liveweight responses to nitrogen and/or protein supplements by steers of Bos taurus, Bos indicus and Bos taurus x Bos indicus breed types offered a low quality grass hay

Thirty steers were used in two pen experiments (Expts 1 and 2). and 27 of these in a third (Expt 3), to quantify their responses of hay intake, rumen ammonia nitrogen (RAN) concentrations, and liveweight to inputs of rumen soluble nitrogen (urea) and rumen undegradable protein (formaldehyde-treated casein; F-casein) when added to a basal diet of low quality hays. The hays were made From unimproved native pastures typical of those grazed by cattle in the subtropics of Australia and contained 7.8 g N/kg dry matter (DM) with coefficient of organic matter digestibility of 0.503 in Expts 1 and 2, and 5.2 g N/kg DM with a digestibility range from 0.385 to 0.448 in Expt 3. The steers (15 months old) were either Brahman (B), Hereford (H) or the F-1 Brahman x Hereford (BH) cross. Steers were offered supplementary minerals with the hays in each experiment. In Expt 1 (35 days) urea was sprayed on part of the hay, allowing for daily urea intakes (g/steer) of either 0, 5, 11, 16 or 26. In Expt 2 (42 days), F-casein was offered daily (g/steer) at either 0, 75, 150, 225 or 300 and in Expt 3 (56 days) discrete offerings were made of soluble casein (225 g/day), of urea (18 g/day) + F-casein (225 g/day) or of nil. There were significant linear effects of urea intake upon hay intake and liveweight change of steers. However, B steers had smaller increases in intake and liveweight change than did H steers, and B steers did not have a linear increase in RAN concentrations with increasing urea intake as did H and SH steers. In Expt 2 there were significant linear effects of F-casein supplements on hay intake and liveweight change of steers and a significant improvement in their feed conversion ratio (i.e. DM intake:liveweight change). The B steers did not differ from H and BH steers in liveweight change but had significantly lower hay intakes and non-significantly smaller increases in RAN with increasing F-casein intake. In Expt 3, hay intake of the steers increased with soluble casein (by 16.8 %) and with urea + F-casein (24.5 %). Only steers given urea + F-casein had a high RAN concentration (94 mg/l) and a high liveweight gain. The B steers had a liveweight loss and a lower hay intake than H or BH steers in Expt 3 but a higher RAN concentration. These studies have indicated the importance of the form and quantity of additional N required by cattle of differing breed types to optimize their feed intake and liveweight gain when offered low-N, low-digestible hays.

Self-reported needs for care among persons who have suicidal ideation or who have attempted suicide

This study examined the self-reported needs of suicidal users of mental health services and the extent to which needs were met. Data on 10,641 adults were available from the Australian National Survey of Mental Health and Well-being. In the year before the survey, 245 persons with suicidal ideation used services, 37 of whom had attempted suicide. Suicidal persons reported a range of needs, especially for counseling, medication, and information. More than half of those with suicidal ideation and those who had attempted suicide who reported any needs felt that their needs had not been fully met. Suicidal persons were significantly more likely to perceive that they had needs.

Compact stellar systems in the Fornax Cluster: Super-massive star clusters or extremely compact dwarf galaxies?

We describe a population of compact objects in the centre of the Fornax Cluster which were discovered as part of our 2dF Fornax Spectroscopic Survey. These objects have spectra typical of old stellar systems, but are unresolved on photographic sky survey plates. They have absolute magnitudes - 13 < M-B

Modelling socially optimal land allocations for sugar cane growing in North Queensland: a linked mathematical programming and choice modelling study

A modelling framework is developed to determine the joint economic and environmental net benefits of alternative land allocation strategies. Estimates of community preferences for preservation of natural land, derived from a choice modelling study, are used as input to a model of agricultural production in an optimisation framework. The trade-offs between agricultural production and environmental protection are analysed using the sugar industry of the Herbert River district of north Queensland as an example. Spatially-differentiated resource attributes and the opportunity costs of natural land determine the optimal tradeoffs between production and conservation for a range of sugar prices.

Adolescent depressive symptomatology: Improve schools or help students?

Despite the increasing interest in programs designed to improve the social ecology of schools, surprisingly little is known about whether differences between schools influence student mental health. This 3-year prospective, naturalistic study examines the school effect on adolescent depressive symptomatology (measured by the Center for Epidemiological Studies Depression Scale, CES-D) among 2,489 students from 25 Australian high schools. Multilevel modelling techniques (HLM) formed the basis of the statistical analyses, There were statistically significant school effects on students' depressive symptomatology; however, these were much smaller than expected. Nearly all of the variation in CES-D depression scores was found to be at the student level, indicating that the potential mental health gains from reducing risk factors in school social environments may be extremely limited and have little effect on student depressive symptomatology.

The VITATOPS (vitamins to prevent stroke) Trial: Rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke

Background: Epidemiological studies suggest that raised plasma concentrations of total homocysteine (tHcy) may be a common, causal and treatable risk factor for atherothromboembolic ischaemic stroke. Although tHcy can be lowered effectively with small doses of folic acid, vitamin B-12 and vitamin B-6, it is not known whether lowering tHcy, by means of multivitamin therapy, can prevent stroke and other major atherothromboembolic vascular events. Purpose: To determine whether vitamin supplements (folic acid 2 mg, B-6 25 Mg, B-12 500 mug) reduce the risk of stroke, and other serious vascular events, in patients with recent stroke or transient ischaemic attacks of the brain or eye (TIA). Methods: An international, multi-centre, randomised, double-blind, placebo-controlled clinical trial. Results: As of November 2001, more than 1,400 patients have been randomised from 10 countries in four continents. Conclusion: VITATOPS aims to recruit and follow up 8,000 patients between 2000 and 2004, and provide a reliable estimate of the safety and effectiveness of dietary supplementation with folic acid, vitamin B-12, and vitamin B-6 in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke. Copyright (C) 2002 S. Karger AG, Basel.

Scope for further analytical solutions for constant flux infiltration into a semi-infinite soil profile or redistribution in a finite soil profile

[1] We attempt to generate new solutions for the moisture content form of the one-dimensional Richards' [1931] equation using the Lisle [1992] equivalence mapping. This mapping is used as no more general set of transformations exists for mapping the one-dimensional Richards' equation into itself. Starting from a given solution, the mapping has the potential to generate an infinite number of new solutions for a series of nonlinear diffusivity and hydraulic conductivity functions. We first seek new analytical solutions satisfying Richards' equation subject to a constant flux surface boundary condition for a semi-infinite dry soil, starting with the Burgers model. The first iteration produces an existing solution, while subsequent iterations are shown to endlessly reproduce this same solution. Next, we briefly consider the problem of redistribution in a finite-length soil. In this case, Lisle's equivalence mapping is generalized to account for arbitrary initial conditions. As was the case for infiltration, however, it is found that new analytical solutions are not generated using the equivalence mapping, although existing solutions are recovered.

To fix or not to fix: The role of 2-phenoxyethanol in rabbit, Oryctolagus cuniculus, chin gland secretion

The European rabbit (Oryctolagus cuniculus) uses the secretion of the chin gland to maintain dominance hierarchies in the wild. Recent work has investigated changes in the secretion when social status is manipulated in the rabbit. When a rabbit becomes dominant, a new compound appears in his secretion, 2-phenoxyethanol. This compound is used as a fixative in the perfume industry. This study investigates whether the compound performs a similar function in the secretion of the rabbit. 2-Phenoxyethanol is not detected olfactorially by rabbits, and slows the release rate of some of the compounds that occur naturally in rabbit chin gland secretion. We suggest that when a rabbit becomes dominant, he adds a fixative to his secretion so that his scent will persist in the environment and not dissipate. He will thus come to dominate the olfactory environment, in much the same way as he does the physical environment.

Virus or not? Phylogenetics of polydnaviruses and their wasp carriers

Our current, still limited, understanding of the comparative biology and evolution of polydnaviruses (PDVs) is reviewed, especially in the context of the possible origins of these parasitoid viruses and of their coevolution with carrier wasps. A hypothetical scenario of evolution of PDVs from ascovirus (or ascovirus-like) ancestors is presented, with examples of apparent extant transitional forms. PDVs appear, in the case of bracoviruses, to show phylogenetic relationships that mirror those of their wasp carriers: with ichno-viruses, the picture is less clear. Ongoing sequencing studies of entire PDV genomes from diverse wasp species are likely to greatly contribute to our understanding of PDV evolution. (C) 2003 Elsevier Science Ltd. All rights reserved.

Molecular diversity through sugar scaffolds

Monosaccharides provide an excellent platform to tailor molecular diversity by appending desired substituents at selected positions around the sugar scaffold. The presence of five functionalized and stereo-controlled centres on the sugar scaffolds gives the chemist plenty of scope to custom design molecules to a pharmacophore model. This review focuses on the peptidomimetic developments in this area, as well as the concept of tailoring structural and functional diversity in a library using carbohydrate scaffolds and how this can lead to increased hit rates and rapid identification of leads, which has promising prospects for drug development.