Combined FEM and Green's function analysis of periodic SAW structure, application to the calculation of reflection and scattering parameters.

Because of more and more stringent requirements on SAW filter performances, it is important to compute, with very good accuracy, the SAW propagation characteristics, which include the calculation of reflection and scattering parameters. For that reason, the analysis of periodic structures on a semi-infinite piezoelectric substrate is one of the most important problems being investigated by SAW researchers. For infinite periodic grating modeling, we developed numerical mixed FEM/BEM (finite element method-boundary element method) models using an efficient interpolation basis function that takes into account the singularity at both edges of each electrode. In this paper, a review of the numerical program that has been developed during the past few years will be presented. For an infinite periodic grating, it is convenient to solve the propagation problem in the Fourier domain (wave number space and harmonic excitation), and important efforts have been spent to properly integrate the so-called periodic harmonic Green function. Using this numerical model together with the general P- matrix formalism, it is possible to compute all of the basic parameters with a very good accuracy. These consist of the single strip reflectivity, acoustic wave-phase velocity, and position offset between reflection and transduction centers. Simulations and comparisons with experiments are shown for each model.

Long-term outcome of idiopathic pulmonary hemosiderosis in children.

We retrospectively analyzed the long-term outcome of idiopathic pulmonary hemosiderosis (IPH) in 15 children. IPH started at a mean age of 5 years, and the mean duration of follow-up was 17.2 years (range, 10-36 yr). Four patients developed immune disorders, 3 cases of rheumatoid polyarthritis or rheumatoid polyarthritis-like diseases and 1 case of celiac disease. Respiratory outcome showed that 3 patients had severe symptoms: 2 patients developed severe pulmonary fibrosis resulting in major chronic respiratory insufficiency, and 1 patient had severe asthma. Twelve patients (80%) had mild or no respiratory problems and were able to lead a normal life. According to chest X-ray and pulmonary function test data, 4 patients had normal chest X-ray and no evidence of restrictive syndrome, 6 patients had an interstitial pattern on chest X-ray and evidence of restrictive pattern, 1 patient had an interstitial pattern but normal lung function, and 1 patient had a normal chest X-ray but evidence of mixed obstructive and restrictive pattern. Our results show that long-term survival is possible in patients with IPH. Factors of poor prognosis seem to be the presence of antineutrophil cytoplasm antibodies (ANCA) or other autoantibodies. No other clinical or biological predictive factors for prolonged survival were found.

Pharmacokinetic modelling of ifosfamide administered by continuous infusion on 5 days at the dose of 6 g/m2.

BACKGROUND: We aimed to create a model for Ifosfamide (IFX) pharmacokinetics for drug monitoring in order to improve protocol dose intensity. MATERIAL AND METHODS: We studied ifosfamide pharmacokinetics in 12 patients aged 8-19 years. Sixteen courses were modelled (6 g/m2, on 5 days). The auto-induction of ifosfamide was taken into account in the model. Ifosfamide measurement was performed on serum samples by gas chromatography with thermo-ionic detection. Two pharmacokinetic models were compared. The following parameters were estimated: volume of distribution (Vd), clearance at the beginning of the induction (CLi), clearance extrapolated to infinity (CLf), clearance at the end of infusion (CL120), a rate constant (Kc) indicating the clearance variation with time and the lag time (Lag) indicating the time elapsed between the start of infusion and the start of induction. The Wilcoxon test was used to investigate possible differences between models. We tested the hypothesis that Boddy's model is an acceptable simplification of Levy's model. RESULTS: Four of six parameters were significantly different between the two models (p = 0.05). The best curve fitting was obtained using the Levy's model which provided the following estimates, Cli = 2.46 +/- 0.94 L.h-1.m-2, CLf = 5.22 +/- 1.02 L.h-1.m-2, Kc = 0.024 +/- 0.014 h-1, Vd = 18.84 +/- 5.04 L and Lag = 4.86 +/- 6.61 h. The most important difference is found for the distribution volume. CONCLUSION: Levy's model is more accurate and takes into account the integration of clearance.

Expanding prostheses in conservative surgery for lower limb sarcoma.

Conservative resection of bone sarcoma in the lower limbs in children is very likely to be followed by a progressive problem of leg length inequality resulting from removal of the growth cartilage. To overcome this we have been using an expanding prosthesis and we report our experiences during the period 1985-1996. The prostheses are made of titanium and comprise 3 parts: an articular component, an expanding mechanism, and tibial and femoral stems. The degree of possible lengthening of the prostheses is virtually unlimited, and they can be inserted in children of 5 or more years of age. We report the use of 28 prostheses in patients aged from 5 to 18 years, of which 4 were tibial, 5 total femur, and 16 distal femur. There were 6 Ewing's sarcoma, 21 osteosarcoma, and 1 synovial sarcoma. The average follow-up was for 5 years. Five patients died from their disease, and 21 benefited from an average lengthening of 2.6 cm (range: 2 mm-120 mm). Using the Société Européenne des Tumeurs Osseouses (EMSOS) criteria, the functional results were excellent or very good in 16, fair in 7 and bad in 5. Five patients developed an infection; one required amputation and the others received a new expanding prosthesis. We conclude that an expanding prosthesis is an excellent alternative to amputation in young children. However, the risk of infection associated with repeat surgery has led us to develop a prosthesis which can be lengthened externally, without the need for reopening the wound.

Prognostic factors in patients with localized Ewing's sarcoma: the effect on survival of actual received drug dose intensity and of histologic response to induction therapy.

To bring to the fore the most important prognostic factors in Ewing's sarcoma (ES) with current protocols, we studied the classical prognostic factors, dose intensity (DI) of actual received drugs, age and histological response to induction therapy and their correlation in 39 patients with localized ES treated from 11/85 to 06/95 to identify eventual predictors of event-free survival (EFS). Inclusion criteria were age 35 yr or less, definitive local treatment by our team and chemotherapy including at least 4 drugs: vincristine (VCR), dactinomycin (DACT), doxorubicin (DOXO) cyclophosphamide (CPX). The endpoint was the absence of relapse. Parameters related to the status of patients were tested using the Chi square test or Fisher's exact test. The non parametric Kruskal-Wallis test was used for quantitative data. When necessary stratified analysis was done using the Mantel Cox test. With a median follow-up of 7 yr, overall survival (OS) and EFS were both 67% at 7 yr. According to univariate analysis, the significant predictors of survival were the DI of VCR and DACT, the histological response to preoperative chemotherapy (CT), the patient's age (< 18 yr DFS: 84%; > 18 yr DFS: 38%). The risk of metastases was almost tenfold higher in patients with low received DI of VCR (DFS 40% versus 95%) and of DACT (DFS 48% versus 94%). The prognostic value of primary tumor characteristics (tumoral volume or location) was erased by the comprehensive treatment. Following multivariate analysis, the actual received DI of VCR (p < 0.02) and DACT (p < 0.03) and the histological response to preoperative CT (p < 0.05) were retained as the only significant independent predictors of EFS. Taking into account the actual received DI of VCR and DACT, the prognostic value of age disappears. In conclusion, this study points out the main role of the drug DI in ES (particularly VCR and DACT) and of histological response to preoperative CT.

Possible monocytic origin of chondrosarcoma: in vitro transdifferentiation of HLA-DR blood monocyte-like cells from a patient with chondrosarcoma, into neo-fibroblasts and chondrocyte-like cells.

Nodules and multilayered areas composed of fibroblasts and chondrocyte-like cells embedded in an abundant extracellular matrix appeared spontaneously in in vitro culture of mononucleated blood cells taken from a patient with chondrosarcoma. Using specific antibodies it was demonstrated that the neo-fibroblasts which developed in the culture resulted from a direct transdifferentiation of monocytes expressing HLA-DR specificity. The experiment was carried out twice, once before surgery and then two years later. In both cases the spontaneous transdifferentiation of HLA-DR monocytes into neo-fibroblasts was observed. Previously it was shown that normal monocytes were also able to give rise in vitro to neo-fibroblasts. However, the latter are normally rapidly destroyed by cell-cell contact with T-cells. Normal T-cells adhere to normal neo-fibroblasts by which they are finally engulfed. As a result, the neo-fibroblasts lose their fibroblastic shape, no longer adhere to their support and die. Therefore the abnormal proliferation and persistence of neo-fibroblasts in pathological situations such as the present case may result either from an intrinsic defect in monocytes, T-cells or both. The question is whether or not this transdifferentiation process observed in vitro accounts for the development of chondrosarcoma in vivo. The present results suggest that in vivo chondrosarcoma may start in a necrotic zone (resulting for instance from trauma) and attract HLA-DR monocytes, where they accumulate and transdifferentiate into neo-fibroblasts and chondrocyte-like cells. The uncontrolled transdifferentiation of these HLA-DR monocytes resulting from a dysregulation of the immune system is probably linked to the malignant process which may have a retroviral origin. The question is raised regarding the embryologic origin of this special sub-population of blood monocytes in which pluripotential capabilities are retained; its origin may differ from that of the other circulating monocytes.

Influence of methotrexate dose intensity on outcome of patients with high grade osteogenic osteosarcoma. Analysis of the literature.

BACKGROUND: The authors surveyed the published clinical trial literature on the subject of localized high grade osteosarcoma in order to develop new hypotheses dealing with drug-dose combinations in the treatment of this disease. METHODS: A computerized literature search was conducted to identify all available published reports of the clinical trials using high dose methotrexate (MTX) in multidrug protocols treating osteosarcoma. Thirty studies, including discussion of high dose MTX (> 7.5 g/m2 per course) and precise quantification of 5-year disease free survival (DFS), fulfilled the inclusion criteria of this dose-intensity analysis. The total number of patients treated in eligible studies was 1909. Correlation among the planned total doses, the dose intensities of the drugs, and the 5-year DFS were tested by regression analysis. RESULTS: No correlation of any other drug dose or dose intensity with DFS appeared as important as the MTX finding. In multivariate analysis, the dose intensity of MTX was found to be the one most correlated with DFS. This correlation appeared to hold for adjuvant and neoadjuvant trials. CONCLUSIONS: The dose intensity of MTX seems to be a major factor in predicting the outcome of patients with localized high grade osteosarcoma.

Original method for measurement of optical mode fields.

We report on a new method for measurement of mode spot sizes of fibers or waveguides (Ti-diffused or proton-exchanged waveguides on LiNbO(3)) that uses neither camera nor optics and works at any wavelength with a 1-µm resolution. The measurements are in good agreement with a finite element simulation.

Dose escalation with pharmacokinetics monitoring in methotrexate chemotherapy of osteosarcoma.

This paper evaluates the influence of pharmacokinetics monitoring of HDMTX in the treatment of localized operable previously untreated high grade osteosarcoma. 44 patients (group 1) received a T10 protocol with dose adapted only to age. 27 other patients (group 2) had a pharmacokinetics monitored dose adaptation of MTX. The pharmacokinetics monitoring leads to higher dosage, higher area under the concentration/time curve and permits higher toxicity to be avoided. The higher dose intensity of MTX gave higher histologic response rate (66% compared to 45%) and higher 5 year disease free survival (92% compare to 76%). HDMTX treatment of osteosarcoma should be dose adapted to indivi-dual pharmacokinetics.

Characteristic parameters of surface acoustic waves in a periodic metal grating on a piezoelectric substrate.

The coupling problem between electrodes due to the propagation of acoustic waves in a periodic metal grating on a piezoelectric substrate is theoretically studied. A method for the determination of the mutual admittance between the grating electrodes is presented, and an analytical expression for the contribution of surface acoustic waves (SAWs) is proposed. The SAW characteristic parameters are determined with a numerical technique that is able to deal with a leaky SAW as well as a true SAW (conventional Rayleigh type or Bleustein-Gulyaev type). Using this technique, the SAWs' contribution to the mutual admittance can be removed, and the analysis of other contributions becomes possible. In particular, the amplitude decay rate of the residual mutual admittance with electrode separation gives information about the propagation of the surface skimming bulk waves (SSBWs). The method presented is applied to several currently used material-cut configurations.

Results of multidisciplinary limb salvage in 240 consecutive bone sarcomas.

From 1979 to 1989, 240 bone sarcomas of limbs were treated by a multidisciplinary limb salvage protocol. The tumors included 112 osteosarcomas, 71 chondrosarcomas, 3 fibrosarcomas, 10 malignant histiocytofibromas, 40 Ewing's sarcomas and 4 other rarer sarcomas. Patients mean age was 28.6 yr (range 4-91 yr). The average tumor size was 13.5 cm (3-43 cm). There were 2 grade IA, 21 IB, 1 IIA, 188 IIB, and 28 III B according to Enneking's classification. Extratumoral en bloc resection was performed in all cases (large in 113, marginal in 121, intrafocal in 6) by the same surgeon. In poor responders to preoperative chemotherapy with Ewing's sarcomas or osteosarcomas, 35 Grays postoperative radiotherapy was administered. Ewing's sarcomas and osteosarcomas received short preoperative and long postoperative chemotherapy. At last follow-up (median 60 months, range 6-120 months), 150 patients were disease-free; 4 were under treatment and had visible disease; 86 had died. Actuarial disease-free survival rate for patients seen with localized previously untreated disease was 83% at 2 yr and 77% at 3 yr. Fifteen local recurrences were observed (6%). Statistical analysis confirmed the poor prognosis factors of visible metastasis, proximal location and large tumor size, and pointed out the major prognostic value of therapeutic factors: the effectiveness of chemotherapy in Ewing's sarcoma and osteosarcomas, and the adequacy of surgery in all cases. Limb salvage can be performed by a well experienced multidisciplinary team in 96% of limb sarcomas without major risk of local recurrence. However, amputation is safer if the surgeon lacks experience.

Osteogenic osteosarcoma: a model of curable disease by multidisciplinary approach of treatment.

The authors review the mean steps for the treatment of osteogenic osteosarcoma from the 1970's: 1), demonstration of the effectiveness of HDMTX and possibility of weekly administration, dose-response effect, interest of other drugs (BCD, ADR, CDDP, IFX); 2), use of the primary as chemosensibility witness; 3), extent of conservative surgery. In order to optimize the good results obtained by Rosen (more than 80% DFS at 5y) the authors studied the HDMTX pharmacokinetics, the value of the seric peak at the end of infusion as an effective test and individualized the HDMTX treatment in each patient following his own pharmacokinetics. This individual approach allows us to obtain more than 90% actuarial event-free survival at 4 years in patients treated by conservative surgery.

Present trends in treatment of Ewing's sarcoma.

The prognosis of Ewing's sarcoma, the first malignant tumor in children under 10, has improved dramatically in the last 10 yrs. The authors review the signs and symptoms that permit diagnosis and analyse the improvement in treatment, based on multidrug's combination, neoadjuvant chemotherapy and surgical treatment of the primary. They point out the necessity of closed multidisciplinary co-operation to treat these patients. Under these conditions, disease free survival now reaches more than 90% at 3 years 1/2.

[Comparative study of 3 successive treatment protocols of osteogenic osteosarcoma in children, adolescents and young adults. Apropos of 100 cases]. / Etude comparative de trois protocoles successifs de traitement de l'ostéosarcome ostéogénique de l'enfant, de l'adolescent et de l'adulte jeune. A propos de 100 observations.

Three therapeutic protocols were used successively for the treatment of osteogenic osteosarcoma since 1978. The first protocol associated initial surgery and 12 months of chemotherapy and was applied to 41 patients with good results in adults but poor results in children. A protocol introducing adjuvant chemotherapy based on the association of adriamycin-cisplatinum gave very disappointing results first in children and then in adults. The protocol based on HD MTX gave much more encouraging results: the long version (3 months preoperative chemotherapy) was effective in good responders but did not influence the course of poor responders. The shortened version of this protocol, derived from the T 10 Rosen protocol (1 month preoperative chemotherapy conservative surgery and appropriate peri- and postoperative chemotherapy) seems to transform the prognosis of osteosarcoma. Our current results indicate a complete primary remission rate of 89% at one year, and 83% at 33 months.