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PubMed2000

A Tensorial Formalism Adapted to the Rovibronic Couplings in the Colored Hexafluorides: Application to the nu(5)(F(2g)) and nu(3)(F(1u)) Modes.

A tensorial formalism adapted to the case of transition-metal hexafluorides in a degenerate electronic state has been developed on the basis of preceding works about spherical-top molecules in a nondegenerate electronic state. We have introduced electronic operators constructed using group theory features and some physical considerations. Vibronic couplings (Jahn-Teller effect, etc.) have been reviewed for the triply degenerate vibrational modes nu(5)(F(2g)) and nu(3)(F(1u)) leading to the identification of the main vibronic parameters. For the first time, an effective rovibronic Hamiltonian as well as the effective transition moment operators (dipole moment and polarizability) for rovibronic transitions have been studied qualitatively thanks to the tensorial algebra properties. Copyright 2000 Academic Press.

Journal Article↗

PubMed1996

Curative chemotherapy for acute myeloid leukemia: the development of high-dose ara-C from the laboratory to bedside.

In the bench to bedside development of drugs to treat patients with cancer, the common guide to dose and schedule selection is toxicity to normal organs patterned after the preclinical profile of the drug. An understanding of the cellular pharmacology of the drug and specifically the cellular targets linked to the drug's effect is of substantial value in assisting the clinical investigator in selecting the proper dose and schedule of drug administration. The clinical development of ara-C for the treatment of acute myeloid leukemia (AML) provides a useful paradigm for the study of this process. An understanding of the cellular pharmacology, cytokinetics and pharmacokinetics of ara-C in leukemic mice showed substantial schedule-dependency. Exposure to high doses for a short duration (C x t) resulted in a palliative therapeutic outcome. In marked contrast, exposure to lower doses for a protracted period (c x T) was curative. Clinical use of ara-C in patients with AML patterned after the murine experience, c x T approach, has been of limited benefit in terms of long-term disease-free survival. Studies with human leukemia blasts from patients have shown that for the majority of patients, the initial rate-limiting step is membrane transport, the characteristics of which are substantially affected by extracellular drug concentration (dose). This pharmacologic impediment is eliminated with the blood levels attained during the infusion of gram doses (1-3 gm/m2) of the drug (high-dose ara-C, HiDaC) for shorter periods of time, a C x t approach. Clinical confirmation of these pharmacologic observations is evident in the therapeutic efficacy of HiDaC in patients with relapsed or SDaC-refractory acute leukemia. This is further emphasized by the significantly improved leukemia-free survival of patients with AML treated with HiDaC intensification during remission compared to those patients treated with milligram doses typical of SDaC protocols. Thus, the identification and monitoring of important parameters of drug action in tumors during the course of a clinical trial can be of substantial assistance in optimizing drug dose and schedule so as to attain the best therapeutic index.

Acute Disease↗

PubMed1982

High-dose methotrexate: a clinical and pharmacokinetic evaluation. Treatment of advanced squamous cell carcinoma of the head and neck using a prospective mathematical model and pharmacokinetic surveillance.

Some of 66 patients with head and neck tumors were treated with high-dose methotrexate monochemotherapy. The use of a prospective mathematical model with pharmacokinetic surveillance proved to be reliable, practical, and useful. By this means chemotherapy could be individualized, with a resultant marked reduction in the frequency and severity of toxicity. The onset of clinical toxic manifestations was significantly correlated with a poor therapeutic response and poor prognosis. The patients were classified in to three groups according to poor, intermediate, and good pharmacokinetic parameters calculated after an intravenous identification dose of methotrexate. These group allocations had a very high prognostic value with regard to toxicity, and especially to the quality of therapeutic response to high-dose methotrexate. They are suggested as useful guidelines in the prescription of high-dose methotrexate chemotherapy.

Adult↗

PubMed2003

Assessment of brain perfusion with MRI: methodology and application to acute stroke.

We review the methodology of brain perfusion measurements with MRI and their application to acute stroke, with particular emphasis on the work awarded by the 6th Lucien Appel Prize for Neuroradiology. The application of the indicator dilution theory to the dynamic susceptibility-weighted bolus-tracking method is explained, as is the approach to obtaining quantitative measurements of cerebral blood flow (CBF) and volume (CBV). Our contribution to methodological developments, such as CBV measurement with the frequency-shifted burst sequence, development of the PRESTO sequence, comparison of different deconvolution methods and of spin- and gradient-echo sequences, and the validation of MRI measurements against positron emission tomography is summarised. The pathophysiology of brain ischaemia and the role of neuroimaging in the setting of acute stroke are reviewed, with an introduction to the concepts of ischaemic penumbra and diffusion/perfusion mismatch. Our work on the determination of absolute CBF and CBV thresholds for predicting the area of infarct growth, identification of the best perfusion parameters (relative or absolute) for predicting the area of infarct growth and the role of MR angiography is also summarised. We conclude that MRI is a very powerful way to assess brain perfusion and that its use might help in selecting patients who will benefit most from treatment such as thrombolysis.

Acute Disease↗

PubMed2004

Dual-phase 18F-fluoro-2-deoxy-D-glucose positron emission tomography as a prognostic parameter in patients with pancreatic cancer.

PURPOSE: Recently, dual-phase 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) was shown to be useful in the differentiation between malignant and benign pancreatic lesions. The aim of this prospective study was to evaluate the value of dual-phase FDG-PET as a prognostic parameter in patients with pancreatic cancer. METHODS: Sixty-five consecutive patients with pancreatic cancer underwent dual-phase FDG-PET. Standardised uptake values at 1 h (SUV1) and 2 h (SUV2) following the injection of FDG were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1. The prognostic value of SUV1, SUV2 and RI was analysed, along with the various clinical and biochemical parameters. RESULTS: Multivariate analysis showed that only three factors had an independent association with longer patient survival: female gender (p<0.01), TNM stage I-III (p<0.05) and RI>10% (p<0.01). Neither SUV1 nor SUV2 showed any prognostic significance. Combination of tumour stage and RI allowed more accurate prognostic evaluation. Patients at stage I-III with RI>10% survived longer than did patients at the same stage with RI<10% (15.3 vs 11.5 months, p<0.01). Patients at stage IV with RI>10% had an intermediate prognosis, with a median survival of 9.5 months; patients at stage IV with RI<10% showed the worst prognosis, with a median survival of 4.9 months (p<0.05). CONCLUSION: RI calculated with dual-phase FDG-PET can be used not only as a tool for initial diagnosis and staging of pancreatic cancer but also as a strong independent prognostic parameter that can allow accurate identification of those patients who will benefit from intensive anticancer treatment at different stages of the disease.

Female↗

PubMed1999

A weakly nonlinear analysis of a model of avascular solid tumour growth.

In this paper we study a mathematical model that describes the growth of an avascular solid tumour. Our analysis concentrates on the stability of steady, radially-symmetric model solutions with respect to perturbations taken from the class of spherical harmonics. Using weakly nonlinear analysis, previous results are extended to show how the amplitudes of the asymmetric modes interact. Attention focuses on a special case for which the model equations simplify. Analysis of the simplified model equations leads to the identification of a two-parameter family of asymmetric steady solutions, the dimensions of whose stable and unstable manifolds depend on the system parameters. The asymmetric steady solutions limit the basin of attraction of the radially-symmetric steady state when it is linearly stable. On the basis of these numerical and analytical results we postulate the existence of fully nonlinear steady solutions which are stable with respect to time-dependent perturbations.

Cell Division↗

PubMed1980

Effects of tumbling and lateral diffusion on phosphatidylcholine model membrane 31P-NMR lineshapes.

Two factors determining the isotropic motional averaging of NMR spectra obtained from lipids in model and biological membranes systems are particle tumbling and lateral diffusion. The influence of these motions (of which the magnitudes are detemined by the medium viscosity and temperature) on the 31P-NMR spectra arising from unilamellar dioleoyl phosphatidylcholine vesicles of a defined size are examined. It is shown that the lineshapes obtained are in good agreement with those predicted by the theory of motional narrowing. These results are discussed with regard to order parameter determinations and polymorphic phase identifications as obtained by NMR techniques.

Diffusion↗

PubMed1995

Role of plantar fascia in the load bearing capacity of the human foot.

Plantar fascia release is an accepted and widely used surgical way to reduce heel pain, however its effect of the load bearing characteristics of the foot is not well studied. A simple biomechanical model is developed here to analyze load bearing mechanism of the foot during the stance phase of the gait cycle. Quasilinearization is used for the system identification, and all model's parameters are determined from the in vivo tests. The model is used to compare the load bearing mechanism of different pathological situations. The results of the study suggest that the plantar fascia carries as much as 14% of the total load on the foot. Its surgical release decreases dynamic loading on the ankle by only 10%. It is also found that the lowering of the arch degenerates the load bearing capacity of the foot. Thus, the plantar fascia plays an important part in the load bearing by the foot and its surgical release should be carefully considered.

Adolescent↗

PubMed1996

A model of wound-healing angiogenesis in soft tissue.

Angiogenesis, or blood vessel growth, is a critical step in the wound-healing process, involving the chemotactic response of blood vessel endothelial cells to macrophage-derived factors produced in the wound space. In this article, we formulate a system of partial differential equations that model the evolution of the capillary-tip endothelial cells, macrophage-derived chemoattractants, and the new blood vessels during the tissue repair process. Chemotaxis is incorporated as a dominant feature of the model, driving the wave-like ingrowth of the wound-healing unit. The resulting model admits traveling wave solutions that exhibit many of the features characteristic of wound healing in soft tissue. The steady propagation of the healing unit through the wound space, the development of a dense band of fine, tipped capillaries near the leading edge of the wound-healing unit (the brush-border effect), and an elevated vessel density associated with newly healed wounds, prior to vascular remodeling, are all discernible from numerical simulations of the full model. Numerical simulations mimic not only the normal progression of wound healing but also the potential for some wounds to fail to heal. Through the development and analysis of a simplified model, insight is gained into how the balance between chemotaxis, tip proliferation, and tip death affects the structure and speed of propagation of the healing unit. Further, expressions defining the healed vessel density and the wavespeed in terms of known parameters lead naturally to the identification of a maximum wavespeed for the wound-healing process and to bounds on the healed vessel density. The implications of these results for wound-healing management are also discussed.

Animals↗

PubMed2004

PM10-bound polycyclic aromatic hydrocarbons (PAHs) in the Greater Area of Athens, Greece.

Polycyclic aromatic hydrocarbons (PAHs) associated to ambient PM10 were determined at four sites within the Greater Athens Area (GAA), Greece, during the period May 2001-June 2002. Daily average PM10 samples were collected using reference samplers installed in two urban locations (Maroussi, MAR and Aristotelous, ARI), a mixed urban-industrial location (Elefsina, ELE), and a background location (Thracomacedones, THR). Spatial and temporal variation of ambient PAH levels and possible relationships with conventional air pollutants and meteorological parameters were investigated. Moreover, source identification was attempted using diagnostic ratios. The PAH concentrations observed in this study, even in downtown Athens, were towards the lowest end of the range of values reported for other European urban locations. The mean concentration of the well known carcinogen B[alpha]Py was at all four sites below the proposed value of 1 ng m-3 (annual average assessment threshold). Automobile traffic was identified as the major PAH source in the GAA exhibiting greatest contribution in the urban sites.

Air Pollutants↗

PubMed2006

Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies.

Angiogenesis, the growth of a network of blood vessels, is a crucial component of solid tumour growth, linking the relatively harmless avascular growth phase and the potentially fatal vascular growth phase. As a process, angiogenesis is a well-orchestrated sequence of events involving endothelial cell migration, proliferation; degradation of tissue; new capillary vessel (sprout) formation; loop formation (anastomosis) and, crucially, blood flow through the network. Once there is blood flow associated with the nascent network, the subsequent growth of the network evolves both temporally and spatially in response to the combined effects of angiogenic factors, migratory cues via the extracellular matrix and perfusion-related haemodynamic forces in a manner that may be described as both adaptive and dynamic. In this paper we present a mathematical model which simultaneously couples vessel growth with blood flow through the vessels--dynamic adaptive tumour-induced angiogenesis (DATIA). This new mathematical model presents a theoretical and computational investigation of the process and highlights a number of important new targets for therapeutic intervention. In contrast to earlier flow models, where the effects of perfusion (blood flow) were essentially evaluated a posteriori, i.e. after generating a hollow network, blood flow in the model described in this paper has a direct impact during capillary growth, with radial adaptations and network remodelling occurring as immediate consequences of primary anastomoses. Capillary network architectures resulting from the dynamically adaptive model are found to differ radically from those obtained using earlier models. The DATIA model is used to examine the effects of changing various physical and biological model parameters on the developing vascular architecture and the delivery of chemotherapeutic drugs to the tumour. Subsequent simulations of chemotherapeutic treatments under different parameter regimes lead to the identification of a number of new therapeutic targets for tumour management.

Animals↗

PubMed2005

Quality assurance in the EORTC phase III randomised 'boost vs. no boost' trial for breast conserving therapy: comparison of the results of two individual case reviews performed early and late during the accrual period.

BACKGROUND AND PURPOSE: To evaluate the impact of quality assurance on treatment compliance, we compared the outcome of the two individual case reviews (ICR) conducted early and late during the accrual period of a large prospective multi-centre trial. PATIENTS AND METHODS: At the onset of the trial, medical files of five patients from each participating centre were evaluated for the compliance to the protocol for eligibility, surgery, pathology and radiotherapy and for the quality of reporting of the data on the case report forms. In nine major centres, this procedure was repeated near the end of the trial. RESULTS: Both in the early and the late ICR, we found a very limited number of deviations from the guidelines for eligibility, staging, surgery, and pathology. Compliance to radiotherapy requirements was good with the exception of a too low minimal dose in 30% and the lack of target volume delineation in the majority of the evaluated patients. The comparison of the late with the early ICR demonstrated an improvement of the quality of data reporting by 6% and of target volume delineation from 33 to 53%. CONCLUSIONS: The initial ICR has lead to the identification of a number of parameters, which needed a clarification in the protocol. These items have been corrected and the individual institutions have been made aware of the necessary adaptations. The evaluation at the end of the trial period showed that there was an improvement but also showed that continuous monitoring is necessary, especially for institutions which have the most deviations in the first ICR.

Breast Neoplasms↗

PubMed2006

Description of HLA class I- and CD8-deficient patients: Insights into the function of cytotoxic T lymphocytes and NK cells in host defense.

Over the last few years, several patients with defects in the HLA class I presentation pathway have been described. Analysis of their clinical symptoms and immunological parameters have led to the identification of several unexpected findings which are of importance to understand the role of HLA class I-dependent immune responses in host defense. Here, we will describe and compare clinical manifestations and immunological findings of patients with defects in the peptide transporter proteins (TAP complex), tapasin and CD8 molecules.

Animals↗

PubMed2005

Equine fetal gender determination from mid- to advanced-gestation by ultrasound.

Equine fetal gender can be easily determined by ultrasound between Days 120 and 210. A combination of transrectal and transabdominal ultrasound examinations can visualise fetal sex organs up to 8 months of gestation. Early equine fetal sexing techniques, performed between approximately Days 58 and 70, are aimed at identifying the position of the genital tubercle. A wider diagnostic window, a diagnosis based on several parameters, and the ease of identification of fully developed fetal primary sex organs make gender diagnosis in mid- to advanced-gestation a preferable technique.

Animals↗

PubMed2003

A method for quantifying reflex responses from intra-muscular and surface electromyogram.

Measuring human reflex responses from electromyogram (EMG) traces in an accurate, repeatable and reliable way with a high degree of specificity has traditionally been a difficult task. This paper describes a new method that can be used to quantify reflex responses from both surface and intra-muscular EMG. This technique extends the classical cumulative sum (CUSUM) calculations by defining precise points for the calculation of latencies, durations and strengths to facilitate automatic reflex detection and permit the strength of a reflex to be defined in absolute units. The effect of varying the pre-stimulus time, the number of trials averaged and the amount of filtering used on the identification and classification of reflex parameters are also investigated. Furthermore, the effect of noise on these values, and how to remove it, is discussed. The new method, which is an expansion of the CUSUM analysis, is compared and contrasted with the more common threshold-crossing method in two different muscles: masseter and first dorsal interosseous (FDI), in experiments utilizing both mechanical and electrical stimulation. There are a number of advantages to using the new method; not only does the modified CUSUM method detect reflexes earlier than threshold-crossing methods but also the strength and duration are less susceptible to averaging and filtering parameters while giving a better indication of the reflex size. The data suggests that a pre-stimulus analysis period of at least 100 ms be used to correctly identify the variability inherent in EMG traces. It is also concluded that for subtle reflexes, 50 stimuli should be the minimum number used when spike trigger averaging is employed as lower numbers are associated with much greater pre-stimulus variability. Zero-phase filtering the rectified averaged EMG traces is recommended as this makes it easier to identify significant changes in the electrical activity of the muscle in question. In addition, noise estimation and removal from averaged rectified EMG recordings yields results that are a more accurate representation of the synaptic activity of the motor units in question.

Action Potentials↗

PubMed1986

Etiopathogenesis of uric acid and ammonium urate uroliths in non-Dalmatian dogs.

The etiopathogenesis of uric acid, sodium acid urate, and ammonium acid urate uroliths in non-Dalmatian dogs appears to be a complex phenomenon. It may involve one or more pathologic and/or physiologic processes acting independently or in concert to increase urinary concentration of lithogenic substances that result in initiation, growth, and retention of urate uroliths. Increased urine uric acid concentration and/or urinary excretion of uric acid appear to be primary predisposing factors in urate lithogenesis. Specific disorders resulting in hyperuricuria may involve abnormalities of increased synthesis, diminished biodegradation, and/or enhance excretion of uric acid. In addition, ammonium ion, hydrogen ion, and other organic and inorganic urine constituents appear to have major influences on urate urolith formation. Unfortunately, many specific disorders of uric acid metabolism and other factors promoting or inhibiting urate urolith formation remain poorly characterized in the majority of non-Dalmatian dogs with urate urolithiasis. Growing awareness of the significance of urate uroliths in non-Dalmatian dogs should encourage further investigation into the identification, characterization, and quantitation of parameters influencing urate lithogenesis. Results of such studies are required for development of practical and effective strategies for treatment and prevention of canine urate urolithiasis.

Animals↗

PubMed1998

Evaluation of infection control parameters according to the 1994 Centers for Disease Control and Prevention Tuberculosis guidelines: a 2-year experience.

BACKGROUND: Because of classification as a high-risk institution for potential Mycobacterium tuberculosis exposure and an employee purified protein derivative conversion rate of 2.7%, a large university-affiliated county hospital enhanced administrative and engineering controls, as recommended by its tuberculosis task force in early 1994. METHODS: For 1994 and 1995 the medical records of all patients with culture-confirmed M. tuberculosis were reviewed according to the 1994 Centers for Disease Control and Prevention guidelines for case surveillance and risk assessment (infection control parameters). The chi 2-test was used to compare 1994 and 1995 infection control parameters for statistical significance (p < or = 0.05). RESULTS: In 1994 and 1995 there were 253 patients with tuberculosis, 85% of whom (214/253) had pulmonary-site tuberculosis. The "representative" patient with pulmonary tuberculosis was profiled, along with institution-specific surveillance data on diagnostics, medication regimens, and airborne isolation practices. Between 1994 and 1995 there was a trend toward increased numbers of homeless patients with tuberculosis, from 8.2% to 17% (p = 0.07). Decreases in the numbers of HIV seropositive patients with tuberculosis from 35% in 1994 to 24% in 1995 (p = 0.2) and of jailed patients with tuberculosis from 9.8% to 5% (p = 0.5) were not significant. Drug-resistance patterns increased from 13% to 24%, with borderline significance (p = 0.06). The employee purified protein derivative testing compliance rate increased from 49% in 1994 to 74% in 1995, with the purified protein derivative conversion rate also increasing from 2.7% to 3.5%. CONCLUSION: The infection control parameter data were beneficial in identification of institution-specific risk factors for our population with tuberculosis. Although labor-intensive, the annual tuberculosis reports supported requests for administrative and engineering controls; however, efficacy of the 1994 tuberculosis control plan was difficult to assess from purified protein derivative conversion rates alone, because the testing compliance rate also increased.

Adult↗

PubMed2003

Bioremediation of diesel oil-contaminated soil by composting with biowaste.

Soil spiked with diesel oil was mixed with biowaste (vegetable, fruit and garden waste) at a 1:10 ratio (fresh weight) and composted in a monitored composting bin system for 12 weeks. Pure biowaste was composted in parallel. In order to discern the temperature effect from the additional biowaste effect on diesel degradation, one recipient with contaminated soil was hold at room temperature, while another was kept at the actual composting temperature. Measurements of composting parameters together with enumerations and identifications of microorganisms demonstrate that the addition of the contaminated soil had a minor impact on the composting process. The first-order rate constant of diesel degradation in the biowaste mixture was four times higher than in the soil at room temperature, and 1.2 times higher than in the soil at composting temperature.

Biodegradation, Environmental↗