Three-point boundary value problems for second-order, ordinary, differential equations

We establish existence results for solutions to three-point boundary value problems for nonlinear, second-order, ordinary differential equations with nonlinear boundary conditions. (C) 2001 Elsevier Science Ltd. All rights reserved.

Topological methods for some boundary value problems

We establish existence of solutions for a finite difference approximation to y = f(x, y, y ') on [0, 1], subject to nonlinear two-point Sturm-Liouville boundary conditions of the form g(i)(y(i),y ' (i)) = 0, i = 0, 1, assuming S satisfies one-sided growth bounds with respect to y '. (C) 2001 Elsevier Science Ltd. All rights reserved.

Long-term risk stratification for survivors of acute coronary syndromes - Results from the long-term intervention with pravastatin in ischemic disease (LIPID) study

OBJECTIVES We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS). BACKGROUND Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting. METHODS Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes. RESULTS In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% fur those assigned placebo. CONCLUSIONS Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy. CT Am Coil Cardiol 2001;38:56-63) (C) 2001 by the American College of Cardiology.

Saturable dose-response relationships for melphalan in melanoma treatment by isolated limb infusion in the nude rat

Nude rats bearing melanomas on their hindlimbs were treated by isolated limb infusion (ILI) with increasing doses (7.5-400 mug/ml) of melphalan. The response of tumours to treatment at the end of the observation period was graded, according to diameter, as complete response (CR), partial response (PR), no change (NC) or progressive disease (PD). No linear relationship between the dose of melphalan and the tumour response was observed. All doses above a threshold of 15 mug/ml achieved a PR or CR. The achievement of CR was not related to increased dose. Two major implications arise from this work. Firstly, the typically two-to three-fold increase in cytotoxic drug concentration given in high dose chemotherapy compared with standard drug concentration may not be sufficient to produce the expected increase in tumour response and possibly survival, and the controversial results of high dose chemotherapy in different studies may thus be explained. Secondly, since an increase in melphalan dose above a certain threshold does not greatly increase tumour response, the use of combination therapies would seem to be more likely to be effective than increased chemotherapeutic drug doses in achieving better tumour responses.

Pharmacokinetics and pharmacodynamics of melphalan in isolated limb infusion for recurrent localized limb malignancy

Isolated limb infusion (ILI) is an attractive, less complex alternative to Isolated limb perfusion (ILP). It has a lower morbidity in treating localized recurrences and in transit metastases of the limb for tumours such as melanoma, Merkel cell tumour and Kaposi's sarcoma, allowing administration of high concentrations of cytotoxic agent to the affected limb under hypoxic conditions. Melphalan is the preferred cytotoxic agent for the treatment of melanoma by ILP or ILI. We report pharmacokinetic data from 12 patients treated by ILI for tumours of the limb in Brisbane. The kinetics of drug distribution in the limb was calculated using a two-compartment vascular model, where both tissue and infusate act as well-stirred compartments. Analysis of melphalan concentrations in the perfusate during ILI showed good agreement between the values measured and the concentrations predicted by the model. Recirculation and wash-out flow rates, tissue concentrations and the permeability surface area product (PS) were calculated. Correlations between the PS value and the drug concentrations In the perfusate and tissue were supported by the results. These data contribute to a better understanding of the distribution of melphalan during ILI in the limb, and offer the opportunity to optimize the drug regimen for patients undergoing ILI. (C) 2001 Lippincott Williams & Wilkins.

Microdialysis and response during regional chemotherapy by isolated limb infusion of melphalan for limb malignancies

This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chemotherapy by Isolated Limb Infusion (ILI). 19 patients undergoing ILI for treatment of various limb malignancies were monitored for intra-operative melphalan concentrations in plasma and, using microdialysis, in subcutaneous and tumour tissues. Peak and mean concentrations of melphalan were significantly higher in plasma than in subcutaneous or tumour microdialysate. There was no significant difference between drug peak and mean concentrations in interstitial and tumour tissue, indicating that there was no preferential uptake of melphalan into the tumours. The time course of melphalan in the microdialysate could be described by a pharmacokinetic model which assumed melphalan distributed from the plasma into the interstitial space. The model also accounted for the vascular dispersion of melphalan in the limb. Tumour response in the whole group to treatment was partial response: 53.8% (n = 7); complete response: 33.3% (n = 5); no responses 6.7% (n = 1). There was a significant association between tumour response and melphalan concentrations measured over time in subcutaneous microdialysate (P < 0.01). No significant relationship existed between the severity of toxic reactions in the limb or peak plasma creatine phosphokinase levels and peak melphalan microdialysate or plasma concentrations. It is concluded that microdialysis is a technique well suited for measuring concentrations of cytotoxic drug during ILI. The possibility of predicting actual concentrations of cytotoxic drug in the limb during ILI using our model opens an opportunity for improved drug dose calculation. The combination of predicting tissue concentrations and monitoring in microdialysate of subcutaneous tissue could help optimise ILI with regard to post-operative limb morbidity and tumour response. (C) 2001 Cancer Research Campaign http:,//www.bjcancer.com.

Comparison between Eysenck's and Gray's models of personality in the prediction of motivational work criteria

Impulsivity based on Gray's [Gray, J. A. (1982) The neuropsychology of anxiety: an enquiry into the function of the septo-hippocampal system. New York: Oxford University Press: (1991). The neurophysiology of temperament. In J. Strelau & A. Angleitner. Explorations in temperament: international perspectives on theory and measurement. London. Plenum Press]. physiological model of personality was hypothesised to be more predictive of goal oriented criteria within the workplace than scales derived From Eysenck's [Eysenck. H.J. (1967). The biological basis of personality. Springfield, IL: Charles C. Thompson.] physiological model of personality. Results confirmed the hypothesis and also showed that Gray's scale of Impulsivity was generally a better predictor than attributional style and interest in money. Results were interpreted as providing support for Gray's Behavioural Activation System which moderates response to reward. (C) 2001 Elsevier Science Ltd. All rights reserved.

Movement and stock structure of narrow-barred Spanish mackerel as indicated by parasites

Data from permanent parasites (juvenile trypanorhynchs and anisakids) indicated that Spanish mackerel Scomberomorus commerson from four sites on the west coast of Australia, Abrolhos, Shark Bay, Exmouth and Onslow, intermingled and were probably all drawn from the same stock. Fish from Broome, Kupang (Indonesia), Groote Eylandt-Torres Strait and the cast coast of Australia had distinct faunas of permanent parasites and probably each belonged to a different stock. There was evidence of movement of fish between Broome and the west coast. Abundances of temporary parasites (gill copepods and monogeneans) suggested that males and females on the west coast migrated separately because in several cases the parasite fauna of one sex was more similar to that of fish in an adjacent area than to the opposite sex in the same area. (C) 2001 The Fisheries Society of the British Isles.

Responses of sugarcane, maize, and soybean to phosphorus and vesicular-arbuscular mycorrhizal fungi

The presence of vesicular-arbuscular mycorrhizal (VAM) fungi in long-term cane-growing fields associated with yield decline led to the supposition that VAM fungi may be responsible for the poor yields. A glasshouse trial was established to test the effectiveness of a species of VAM fungi, Glomus clarum, extracted from one of these North Queensland fields on the growth of sugarcane (Saccharum interspecific hybrid), maize (Zea mays), and soybean (Glycine max) for 6 phosphorus (P) rates (0, 2.7, 8.2, 25, 74, 222 mg/kg). For maize and soybean plants that received VAM (+ VAM), root colonisation was associated with enhanced P uptake, improved dry weight (DW) production, and higher index tissue-P concentrations than those without VAM (-VAM). By comparing DW responses of maize and soybean for different P rates, savings in fertiliser P of up to 160 and 213 kg/ha, respectively, were realised. Sugarcane plants were generally less responsive. Apart from a 30% DW increase with VAM when 2.7 mg P/kg was added, DW of +VAM plants was equivalent to, or worse than in the case of 222 mg P/kg, DW of -VAM plants. For all 3 host species, colonisation was least at the highest P application, presumably from excessive P within the plant tissue. Critical P concentrations for the 3 host species were below those reported elsewhere, and for soybean and sugarcane, the critical concentration for +VAM plants was lower than that of -VAM plants. There are 3 implications that arise from this study. First, VAM fungi present in cane-growing soils can promote the growth of maize and soybean, which are potential rotation crops, over a range of P levels. Second, the mycorrhizal strain taken from this site did not generally contribute to a yield decline in sugarcane plants. Third, application of P fertiliser is not necessary for sugarcane when acid-extractable P is

Induction of immune tolerance by dendritic cells: implications for preventative and therapeutic immunotherapy of autoimmune disease

Dendritic cells (DC) have a key role in controlling the immune response, by determining the outcome of antigen presentation to T cells. Through costimulatory molecules and other factors, DC are involved in the maintenance of peripheral tolerance through modulation of the immune response. This modulation occurs both constitutively, and in inflammation, in order to prevent autoimmunity and to control established immune responses. Dendritic cell control of immune responses may be mediated through cytokine or cell-contact dependent mechanisms. The molecular and cellular basis of these controls is being understood at an increasingly more complex level. This understanding is reaching a level at which DC-based therapies for the induction of immune regulation in autoimmunity can be tested in vivo. This review outlines the current state of knowledge of DC in immune tolerance, and proposes how DC might control both T cell responses, and themselves, to prevent autoimmunity and maintain peripheral tolerance.

Nuclear RelB(+) cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions

Differentiated dendritic cells (DC) have been identified by the presence of nuclear RelB (nRelB) and HLA-DR, and the absence of CD20 or high levels of CD68, in lymph nodes and active rheumatoid arthritis synovial tissue. The current studies aimed to identify conditions in which nRelB is expressed in human tissues, by single and double immunohistochemistry of formalin-fixed peripheral and lymphoid tissue. Normal peripheral tissue did not contain nRelB(+) cells. nRelB(+) DC were located only in T- or B-cell areas of lymphoid tissue associated with normal organs or peripheral tissues, including tonsil, colon, spleen and thymus, or in association with T cells in inflamed peripheral tissue. Inflamed sites included skin delayed-type hypersensitivity reaction, and a wide range of tissues affected by autoimmune disease. Nuclear RelB(+) -HLA-DR- follicular DC were located in B-cell follicles in lymphoid organs and in lymphoid-like follicles of some tissues affected by autoimmune disease. Lymphoid tissue T-cell areas also contained nRelB(-) -HLA-DR+ cells, some of which expressed CD123 and/or CD68. Nuclear RelB(+) cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions.