Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning ...subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC.
Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients.
Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status.
Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.
The clinical consequences of immune antibodies generated to abciximab (ReoPro) and infliximab (Remicade) are described. Abciximab, a chimaeric Fab fragment that binds to the beta3 integrin of the ...GPIIb/IIIa and alphavbeta3 receptors on human platelets, is approved in the US and Europe for use in percutaneous coronary intervention (PCI) to prevent cardiac ischaemic complications. The effects of induced antibodies upon the safety and efficacy of repeat administration of abciximab have been evaluated in the ReoPro Re-administration Registry Study, in which 5.7% of patients were HACA positive before re-treatment. An interim evaluation of 1000 patients has indicated that re-administration of abciximab can be accomplished in the setting of PCI with an acceptable safety and efficacy profile. Infliximab is a chimaeric IgG1 antibody specific for human TNFalpha, and is approved in the US and Europe for the acute treatment of the signs and symptoms of Crohn's disease and for the chronic treatment of rheumatoid arthritis (RA). The incidence of antibodies to infliximab is reported to be approximately 10%; however, an inverse dose-immunogenicity relationship was observed, indicating that higher doses of infliximab (> or = 3 to 10 mg/kg) could reduce the incidence of immune antibodies. The induction of immune antibodies could also be reduced by concomitant administration of low-dose methotrexate and other immunosuppressant agents. Although antibodies to infliximab appeared to be associated with lower serum infliximab concentrations and a slightly higher incidence of infusion reactions, these immune antibodies were generally not associated with a reduction in clinical efficacy. In addition, the antibodies induced to infliximab are specific for infliximab, and do not cross-react with other currently available therapeutic antibodies.
Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a ...preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies. Currently, only a few biomarkers are available for monitoring or predicting HBV disease progression and treatment response. As new therapies become available, new biomarkers to monitor viral and host responses are urgently needed. In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) held a virtual and interactive workshop on HBV biomarkers endorsed by the International HBV Meeting. Various stakeholders from academia, clinical practice and the pharmaceutical industry, with complementary expertise, presented and participated in panel discussions. The clinical utility of both classic and emerging viral and immunological serum biomarkers with respect to the course of infection, disease progression, and response to current and emerging treatments was appraised. The latest advances were discussed, and knowledge gaps in understanding and interpretation of HBV biomarkers were identified. This Roadmap summarizes the strengths, weaknesses, opportunities and challenges of HBV biomarkers.
Radioiodine has been in use for over
60
years
as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects ...and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic
I
131
administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate,
T
eff
and target mass. The dose was converted to normalized total dose delivered at
2
Gy
per fraction
(
NTD
2
)
. Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The
TD
50
and
m
parameters of the NTCP model approach were then estimated using the likelihood method. The
TD
50
, expressed as
NTD
2
, resulted in
60
Gy
(95% C.I.:
45
–
75
Gy
) and
96
Gy
(95% C.I.:
86
–
109
Gy
) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves’ disease should be characterized by more radiosensitive cells compared to autonomous nodules. The
m
parameter for all patients was 0.27 (95% C.I.: 0.22–0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.
Radionuclide therapy with bone seeking radiopharmaceuticals is one of the oldest interventions in nuclear medicine and has been now in use for many years as an effective method of palliating painful ...bone metastases. Clinical indications have slowly but progressively increased starting from end-stage prostate cancer with diffuse painful bone metastases to earlier stages of several cancers with only microinvolvement of the skeleton. Several newer bone seeking agents for therapeutic applications have been developed during the last 10 years. A large body of specific literature is now available, but only a few well designed clinical trials can be selected to obtain evidence-based guidelines. This study summarizes the therapeutic effects of the three commercially available radiopharmaceuticals, the current indication for their use as supported by the most rigorous literature studies and the original contributions of the "Regina Elena" ten-year experience. Innovative strategies and future research questions are also breafly addressed.
The aim of the paper is to calculate the dose to bone surface and bone volume using a Monte Carlo particle transport model and to give quantitative arguments for activity prescription.
This study ...simulates the dose delivery process to skeletal metastases by bone surface- and bone volume-seeking radiopharmaceuticals. Dose distributions for three radiopharmaceuticals, 186Re-HEDP, 153Sm-EDTMP and 89SrCl2, frequently used for pain palliation therapies, were calculated using the EGSnrc Monte Carlo code. The model simulates a cylindrical geometry with regions of different constant density compositions and radioactivity distribution consistent with known biodistribution features of the three radiopharmaceuticals: superficial for phosphonates (186Re-HEDP and 153Sm-EDTMP) and volumetric for 89SrCl2. After 3D dose distribution calculation, dose-volume histogram reduction was carried out using the "preferred Lyman" method, which yields effective uniform dose (D(eff)) equivalent to the inhomogeneous dose distributions to the reference region (volume and surface).
Our simulations showed that to obtain a delivered dose to bone surface equivalent to that obtained from 89SrCl2, the administered activities of 153Sm-EDTMP and 186Re-HEDP should be increased by 37% and 48%, respectively, in comparison with those usually administered.
These results prove theoretically the empirical results from clinical observations and show that improvement in bone pain palliation by means of radiopharmaceutical therapy should be expected for dose-guided prescription.
We have demonstrated a stable expansion of CD8+ T cells in the peripheral blood of a child with chronic arthritis. The expanded TCRBV family (TCRBV14) was enriched for CD57hiCD28– T cells. Sequencing ...of the TCRBV14 amplification products showed a TCR sequence which contributed 32% of the total TCR in the CD8+TCRBV14 population. Using the modified heteroduplex technique, the CD8+TCRBV14 cells showed a clonal pattern and these bands were restricted to the CD28– population. This method also detected multiple other clones within the CD8+ population but few in the CD4+ cells. The dominant TCRBV14+ clone was not detectable in synovial fluid T cells from two inflamed joints by CDR3 length analysis or heteroduplex probing, suggesting that this long-lived clone is excluded from inflammatory sites. Synovial fluid T cells showed an unexpected discordance of the CD28 and CD57 phenotype compared to peripheral blood mononuclear cells. T cells from both inflamed joints both showed marked oligoclonality in all TCR families and had almost identical heteroduplex patterns. Taken together these data suggest that some clones are actively excluded from inflamed sites in juvenile chronic arthritis, yet the pattern of restricted T cell expansion is shared between sites of inflammation.
Polydimethylsiloxane (PDMS) is an organic silicone with a viscoelastic behavior suitable for use in engineering. This material presents substantial changes in its properties depending on the ...temperature and the flow rate: at high temperatures or high flow rates, it behaves as a viscous liquid; whereas, at low temperatures or low flow rates, it behaves as an elastic solid. The lack of accurate information about the modifications in PDMS under thermal changes affects the design of transducers (both sensors and actuators) based on this material and also their calibration. In this study, 10:1 base-agent mixing ratio was analyzed in a 20 °C to 50 °C temperature range to assess the ultrasonic P-wave properties (velocity, attenuation, and variation of both with the frequency) and hence complex elastic modulii of this material under a temperature dependent environment. P-wave velocity and attenuation were extracted for every temperature step in a 3–7 MHz frequency range which is the typical range for medical applications. Acoustic dispersion of PDMS properties such as velocity and attenuation in a pulse-echo set up were analyzed to also compute attenuation coefficient, temperature and frequency dependent models and complex modulus.
•Temperature affects PDMS p-wave velocity with a slope of 3.2 m/s/°C at 5 MHz.•Temperature affects PDMS p-wave attenuation with a slope of 1 m−1/°C at 5 MHz.•The dispersion in PDMS is small, with less than 2% variation in p-wave velocity.•Models of velocity and attenuation including frequency and temperature are proposed.•Complex modulus considering frequency and temperature are calculated.
Measurement of gas diffusivity in heavy oils Zhang, Y.P.; Hyndman, C.L.; Maini, B.B.
Journal of petroleum science & engineering,
2000, 2000-1-00, Letnik:
25, Številka:
1
Journal Article
Odprti dostop
Molecular diffusion of gases in oil plays a role in several heavy oil recovery processes. In solution gas drive, the gas diffusion coefficient has a direct impact on the amount of gas that is ...released and the level of supersaturation that exists during pressure depletion. In the Vapex process, molecular diffusion controls the rate at which the solvent vapour is absorbed by the oil. Molecular diffusion is also important in supercritical fluid extraction of heavy oils and in recovery of residual oil by miscible displacement. Unfortunately experimental data on gas diffusion coefficient in heavy oils are relatively scarce due to the tedious nature of diffusivity measurements. The main objective of this work was to develop a simple experimental technique for measuring gas diffusion coefficients in heavy oils. Diffusion coefficients of carbon dioxide and methane were measured by measuring the rate of gas absorption in a high-pressure windowed cell. The diffusion equation, coupled with the gas material balance equation, was used to history match the gas absorption data using the diffusion coefficient as an adjustable parameter. The diffusion coefficients calculated by this history match technique are compared with the reported values of diffusion coefficients in similar systems.
Absence seizures represent a complex group of epilepsy, characterized by lapse of consciousness with staring. Bilateral, synchronous, and symmetric bursts of 3-Hz spike-and-wave discharges are ...observed on the electroencephalogram, whereas interictal background activity is normal. This kind of epilepsy has to be differentiated from other generalized epilepsies such as juvenile absence epilepsy and juvenile myoclonic epilepsy. Moreover, absence seizures, together with generalized spike-and-wave discharges, may coexist with other types of epilepsy such as frontal lobe epilepsy, temporal lobe epilepsy, benign epilepsy with centrotemporal spikes, and childhood epilepsy with occipital paroxysms. We have carried out ictal single photon emission computed tomography (SPECT) in 10 patients with clinical evidence of absence seizures with the aim to better understand and to distinguish this kind of seizure as primarily or secondarily generalized to a specific area and to obtain more information on the neuronal mechanisms involved in the different types of seizures, usually not identifiable at the first appearance. During the long follow-up period (9 months to 14 years), 7 of the 10 examined patients underwent interictal SPECT when they became seizure free. Our data permitted, in two patients, the diagnosis of childhood absence seizures; in three patients, they suggested the possibility of later appearance of other seizure types, on the basis of focal hyperperfusion indicating a possible focal firing. In three of the examined patients, the diagnosis of idiopathic localization-related epilepsies mimicking childhood absence seizures could be performed. In the last two patients, the hypothesis of a coexistence of absences with partial and generalized seizures was considered. From our results, it can be presumed that ictal SPECT findings may contribute to the physiopathologic classification of the different types of epilepsies. Moreover, anticonvulsant treatment more appropriate to the different forms of seizures can be used. (J Child Neurol 2001;16:339-344).
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