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Biomedical subjects

A Roche

Publications and source records attributed to A Roche.

At least 19 recordsLinked to original sources

Dynamic assessment of antiangiogenic therapy by monitoring both tumoral vascularization and tissue degeneration.

Tumor growth is dependent both on endothelial and tumor cells. The aim of this study was to investigate dynamically whether changes in tumor vasculature implicate tumor tissue degeneration during antiangiogenic therapies. In order to quantify intra-tumor vascularization and necrosis, we have used ultrasound technology. This study has identified essential parameters needed to quantify specifically and sensitively the number of microvessels and the extent of necrosis in xenografted human carcinomas during natural tumor evolution, using contrast-enhanced high-frequency ultrasonography with (HFCDUS) or without (HFUS) color Doppler. We showed that quantification of intra-tumor microvessels between HFCDUS and immunohistochemistry is correlated using an anti-CD31 antibody. Furthermore, quantification of tumor necrosis with HFUS was confirmed by histological examination of hematoxylin-eosin-saffranin-stained sections over the observation period. Subsequently, for the assessment of novel angiogenic inhibitors, HFCDUS and HFUS were used to elucidate the underlying dynamics linking vessel inhibition and tumor eradication. We describe a novel application for HFCDUS/HFUS that constitutes an effective, convenient, and non-invasive method for clinical assessment of angiogenic inhibitors. In conclusion, we showed that tumor cells abruptly became necrotic following an antivascular therapy, whereas untreated tumors were protected from degeneration by a significant blood supply.

Adenoviridae↗

[Anaesthetic considerations for interventional radiology].

OBJECTIVE: To describe the new procedures applied for interventional radiology leading to specific anaesthetic care and organization. DATA SOURCE: Record of references from national and international journals in Medline. STUDY SELECTION: All types of articles were selected including prospective studies, practice guidelines, reviews and case reports. DATA SYNTHESIS: During interventional radiology, anaesthesia should be adapted to the duration of the procedure, the pain induced by the radiologist, the position of the patient and its medical status. General anaesthesia would be preferred for long procedures, requiring total immobility. Locoregional anaesthesia can be proposed for some cases. Sedation associating hypnotics (propofol, midazolam, sevoflurane) and opioids (alfentanil, remifentanil) is commonly used according to different schemes, as discontinuous boluses, continuous infusion, target controlled intravenous sedation or patient controlled sedation. Monitoring of temperature and diuresis may be useful for long procedures. Haemodynamic monitoring (arterial catheter, central venous pressure) and haemostatic monitoring may be necessary for interventional neuroradiology and endovascular stenting. Radiofrequency and laser procedures are often painful, requiring the choice of adequate analgesic regimen. Hydratation associated with acetylcysteine seems to be able to prevent contrast induced nephropathy in patients with risk factors for chronic renal insufficiency. CONCLUSION: As advances in interventional radiology are obvious, general organisation as well as anaesthetic procedures should be adapted to these specific techniques.

Analgesia↗

Hyperselective intra-arterial preoperative chemotherapy in patients with squamous cell carcinoma of the oral cavity: preliminary results.

OBJECTIVES: To investigate radiological response and findings after Intra Arterial Chemotherapy (IAC) for patients with Squamous Cell Carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS: Patients received 1-2 cycles of IAC. Radiological assessment was performed on day 7 and day 21 after each cycle using CT scan and MRI. RESULTS: Six patients (median age: 52, ranging 46-60; male/female: 5/1) received 10 cycles (4 patients received 2 cycles). Primary tumors were floor of the mouth (4 patients) and oral tongue (2 patients). TNM classification was T2N0-2b in 3 patients and T4N0-1 in 3 patients. All patients had good locoregional/systemic tolerance and 3 showed clinical objective response (OR). Four patients were evaluable on both CT and MRI, 1 patient on MRI only and 1 patient did not tolerate imaging. Three patients showed OR both on CT and MRI, 1 patient showed stable disease (SD) on CT and OR on MRI and 1 patient showed SD on MRI. Contrast-enhancement of hemiperfused tongue was reported in all evaluable patients. Two patients presented intratumoral necrosis and 5 patients displayed local edema (MRI). One patient had modification of the sternocleidomastoid muscle after IAC. CONCLUSION: Radiological modifications were observed in the infused area and correlated well with clinical response. This study is ongoing.

Antineoplastic Agents↗

Portal vein stenosis and occlusion stenting after liver transplantation in two adults.

We report two cases of percutaneous transhepatic stenting of the portal vein to treat stenosis and occlusion disclosed 5 and 18 months, respectively, after orthotopic liver transplantation in two adult patients. If long-term patency is satisfactory, this technique should allow long-term management of portal vein stenosis and occlusion without the use of thrombolysis.

Constriction, Pathologic↗

Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases.

BACKGROUND: The aim of this study was to prospectively evaluate the use of Doppler ultrasonography with perfusion software and contrast agent injection (DUPC) during isolated limb perfusion (ILP) with high-dose chemotherapy and TNF-alpha(biochemotherapy) in patients with locally advanced extremity soft tissue sarcoma (STS). PATIENTS AND METHODS: Fifty-two patients were prospectively included in this monocentric imaging trial. Three were excluded because the study was incomplete in two patients and one tumour did not exhibit any contrast uptake. DUPC was performed before ILP and on days 1, 7, 15, 30 and 60 after ILP. A total of 292 DUPC were performed on 55 target lesions in 49 evaluable patients. The percentage of contrast uptake was evaluated at each tumour site by two radiologists. The criterion tested was a decrease of more than 50% in intra-tumour contrast uptake compared to the pre-ILP examination. Results were compared with both MRI and histological analysis after resection of residual disease. RESULTS: According to MRI and the histological analysis, 25 (51%) patients were good responders (no difference between the four treatment arms) with tumour necrosis exceeding 90% and 24 (49%) were poor responders. As of day +1, the accuracy of DUPC in predicting tumour response was 82% (18/25 good responders and 22/24 poor responders) increasing to 91% at day +7, 95% at day +15 and 96% at day +30. At day +15, DUPC was predictive of a good response in 100% of the cases. CONCLUSION: DUPC is a simple technique, allowing early prediction of tumour response after ILP. A new treatment planning scheme can be proposed based on the results of this study.

Adolescent↗

Role of contrast-enhanced color Doppler ultrasonography and dynamic flow in the evaluation of hepatic tumors treated with radiofrequency.

The contribution of contrast-enhanced color Doppler ultrasonography (CDUS) and dynamic flow (DF) (Toshiba) in the evaluation following treatment of hepatic tumors with radiofrequency (RF) is discussed. Twenty-seven patients with 34 hepatic tumors were included in this prospective study. The treated tumors measured 10-58 mm in diameter (mean diameter 29 mm). Two tumors were treated twice and one three times, comprising a total of 38 target lesions treated with RF and evaluated by 127 contrast-enhanced CDUS. The results of CDUS follow-up were compared to those of the dynamic MRI at 2 months, 4 months, 6 months and 1 year. Before RF, the injection of Levovist raised the number of vascularized lesions seen with unenhanced Doppler from 44% to 79%. All the non-vascularized lesions were metastases. Twenty-four hours after RF, four tumors presented an enhancement with Levovist, in which two were insufficiently treated lesions. Twenty-one treated tumors have been followed-up jointly by CDUS and MRI at the same time at 2 months, 20 at 4 months, 12 at 6 months and nine at 1 year. Compared to the MRI and the evolution, the CDUS presented a sensitivity of 100% and a specificity of 90% for the detection of progressive recurrence. The preliminary results show that the CDUS is useful to confirm the absence of detectable vascularity after treatment with RF ablation, whereas the presence of enhancement must be confirmed by MRI.

Adult↗

[Validation of a new methodology for characterizing ultrasound contrast agents (UCA)].

PURPOSE: Validation of an experimental ultrasound system on erythrocyte suspensions with variable levels of aggregation and application to the echogenicity quantification of UCA under quasi-physiologic flow conditions. MATERIALS AND METHODS. The system is constituted with a Couette cell with variable applied shear rates, an ultrasound emitter/receiver and a digital scope for radio-frequency signal acquisition. Ultrasound indices (UI) were defined for the two experimental established protocols based on the gold standard laser methodology. Washed red cells with or without variable Dextran 70 kD concentrations were used to simulate a wide particle size range. A preliminary application to UCA was conducted with Levovist for calibration of the system. RESULTS: For each protocol, applied ten times on identical whole blood samples, a student t-test revealed no significant variation for all UI. Results on washed red cells were in good agreement with Rayleigh's theory of ultrasound backscattering. Significant correlations were obtained between laser and UI for washed red cells with different Dextran concentrations. An elevation of 12.13 dB in backscattered intensity was obtained after addition of Levovist. CONCLUSION: The constituted Couette system allowed reproducible and accurate echogenicity quantification of small scatterers such as UCA in quasi-physiologic blood flow conditions.

Contrast Media↗

[The Munchausen syndrome: a diagnosis not to be forgotten in urology].

INTRODUCTION: Among the manifestations of Münchausen's syndrome, "neurological" forms may exist. OBSERVATION: We present the case of a patient presenting with urinary retention following treatment for urinary incontinence. The patient had injected himself with infected urine collected from his catheter, in order to create septicemia. COMMENTS: Nephritic colitis, false gall stones, addition of fecal matter or of food and saliva in the urine or the bladder, neurogenic bladder and urinary infections have all been reported as possible manifestations of Münchausen's syndrome. Diagnosis of this syndrome is often delayed and laborious, after repeated hospitalisations, examinations and often aggressive treatment. Its therapeutic management is difficult. Patients, despite proof, deny their deceit and refuse psychiatric care.

Diagnosis, Differential↗

Percutaneous radiofrequency thermoablation as an alternative to surgery for treatment of liver tumour recurrence after hepatectomy.

BACKGROUND: Radiofrequency (RF) current, converted into heat through ion agitation and friction, can destroy liver tumours by means of coagulation necrosis. This study assessed whether percutaneous RF ablation is a useful and safe technique for the treatment of liver tumour recurrence after hepatectomy. METHODS: Forty-seven patients presenting with local recurrence after hepatectomy for malignant tumours (29 with colorectal secondaries) were treated with percutaneous RF ablation instead of repeat hepatectomy. RF thermal ablation was performed under image guidance for 12-15 min. This group represented 63 per cent of 75 patients treated with curative intent for liver recurrence in the same time interval. The other 28 patients underwent repeat hepatectomy. RESULTS: The mean(s.d.) number of liver metastases destroyed was 1.4(0.7) (range 1-3) and their diameter was 21(8) (range 9-35) mm. Twenty-six patients presented with liver recurrence at least once but up to three times after the initial RF application. Incomplete local RF treatment was observed in six of 47 patients. Fifteen patients developed extrahepatic recurrence. The mean(s.d.) interval between RF ablation and the last follow-up visit was 14.4(10.1) (range 5.5-40) months. One death and three major complications occurred. Survival rates at 1 and 2 years were 88 and 55 per cent respectively. A retrospective study of the authors' database over two similar consecutive periods showed that RF ablation increased the percentage of curative local treatments for liver recurrence after hepatectomy from 17 to 26 per cent and decreased the proportion of repeat hepatectomies from 100 to to 39 per cent. CONCLUSION: Percutaneous RF treatment increases the number of patients eligible for curative treatment. It should be preferred to repeat hepatectomy when feasible and safe because it is less invasive. Repeat hepatectomy is indicated only when percutaneous RF ablation is contraindicated or fails.

Adolescent↗

What is the best similarity measure for motion correction in fMRI time series?

It has been shown that the difference of squares cost function used by standard realignment packages (SPM and AIR) can lead to the detection of spurious activations, because the motion parameter estimations are biased by the activated areas. Therefore, this paper describes several experiments aiming at selecting a better similarity measure to drive functional magnetic resonance image registration. The behaviors of the Geman-McClure (GM) estimator, of the correlation ratio, and of the mutual information (MI) relative to activated areas are studied using simulated time series and actual data stemming from a 3T magnet. It is shown that these methods are more robust than the usual difference of squares measure. The results suggest also that the measures built from robust metrics like the GM estimator may be the best choice, while MI is also an interesting solution. Some more work, however, is required to compare the various robust metrics proposed in the literature.

Algorithms↗

Percutaneous radiofrequency ablation of hepatic tumors during temporary venous occlusion.

OBJECTIVE: We evaluated the feasibility, tolerance, and efficacy of percutaneous hepatic vein or segmental portal branch balloon occlusion during radiofrequency ablation of hepatic malignancies. SUBJECTS AND METHODS: Ten tumors were treated by percutaneous radiofrequency ablation during balloon occlusion of a hepatic vein (n = 8) or a segmental portal branch (n = 2). Venous occlusion was undertaken because the tumor was in contact with a hepatic vein (n = 3) or a portal branch (n = 1); because the tumor exceeded 35 mm in width (mean, 44 mm), which was considered the maximum size amenable to ablation in a single session (n = 2); or because of both large size and contact with a hepatic vein (n = 3) or a portal branch (n = 1). RESULTS: Vascular occlusion was always technically possible. Radiofrequency was delivered to one to three locations (mean, 1.9 locations) with a cluster electrode. The largest axis of radiofrequency-induced lesions after ablation with the cluster needle-between 42 and 51 mm (mean, 49 mm)-was always larger than the targeted tumor. These sizes were statistically larger than in a matched control group of patients who underwent radiofrequency ablation without vascular occlusion (p < 0.0003). After a mean follow-up of 12.6 months, CT and MR imaging revealed complete destruction of nine tumors after a single radiofrequency ablation treatment; one tumor required three treatments to achieve ablation. Five patients are tumor-free 12-18 months (mean, 14.4 months) after the first radiofrequency ablation treatment, and five developed new liver metastases. CONCLUSION: Temporary hepatic vein or portal branch occlusion during radiofrequency ablation can safely facilitate the treatment of large tumors or tumors in contact with the walls of large vessels.

Adult↗

Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET).

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.

Aged↗

Radio-frequency tissue ablation of the liver: effects of vascular occlusion on lesion diameter and biliary and portal damages in a pig model.

The aim of this study was to assess the effect of vascular occlusion on radio-frequency (RF) lesion size and on potential associated biliary and portal lesions. Radio-frequency lesions using a 1-cm exposed-tip cooled electrode were created in pig liver. Liver perfusion was modified by arterial embolization (n=2), left portal clamping (n=2), and both (n=2). Two pigs were used as controls. Two weeks after, control portography was performed, animals were killed, and ex-vivo cholangiography was carried out. Pathological studies evaluated the lesion surface and associated portal and biliary damages. A mathematical regression model showed that portal occlusion increased by 43 mm2 (+40%) the surface of RF lesions, arterial occlusion by 135 mm2 (+126%), and associated occlusion by 466 mm2 (+435%). Biliary stenoses were found in 4 cases (two arterial occlusions, one portal occlusion, and one associated occlusion). One case of partial portal vein thrombosis was found in one case of portal occlusion and resolved at 2 weeks. Ischemic damages adjacent to RF lesions were found in cases of combined occlusions. The reduction of liver perfusion increases significantly the size of RF lesions but is associated with a risk of biliary, portal, or parenchymal complications.

Animals↗

Evaluation of contrast-enhanced color Doppler ultrasound for the quantification of angiogenesis in vivo.

RATIONALE AND OBJECTIVES: To evaluate contrast-enhanced color Doppler ultrasonography (CDUS) aimed at quantifying angiogenesis in vivo. METHODS: Eight colon tumors xenografted into mice were studied with CDUS both without and after injection of SHU 508A. The number of intratumor vessels and pedicles visualized with CDUS and the value of the acoustic intensity quantified by computer were compared with the evaluation of angiogenesis by study of digitized histological slides. RESULTS: SHU 508A increased the number of intratumor vessels and pedicles depicted by CDUS, which could also be quantified by acoustic intensity. The comparison of CDUS and digitized histological slide studies showed that the detection threshold after SHU 508A administration allowed visualization of small vessels (40 microm in diameter). The "hot spots" seen on histology were superimposable onto vessels seen with CDUS. Regions in which no vessels were detected by CDUS corresponded to regions in which vascularization was absent by histological analysis. CONCLUSION: Injection of SHU 508A significantly increased vessel detection with CDUS.

Animals↗

Antigen 43, the major phase-variable protein of the Escherichia coli outer membrane, can exist as a family of proteins encoded by multiple alleles.

agn43 encodes a major phase-variable outer-membrane protein, antigen 43 (Ag43), involved in autoaggregation of Escherichia coli cells. The gene is present in single copy on the chromosome of E. coli K-12. In contrast, Southern hybridization and gene inactivation studies demonstrate that control producer strain E. coli ML308-225 possesses duplicate copies of agn43 (agn43A and agn43B). Construction and analyses of single and double knockout mutants clearly show that both alleles are capable of expressing antigen in a phase-variable manner, with observed differences in the ON<-->OFF switch frequencies appearing to favour expression of Ag43B under conditions of normal laboratory growth. Comparative analysis of agn43A and agn43B gene sequences revealed 98% identity at the nucleotide and predicted protein levels, with differences in the protein sequence of the surface-expressed alpha(43) subunit altering the surface probability of one of the predicted epitopes. Analysis of a panel of enteropathogenic E. coli strains by Southern hybridization using agn43-specific gene probes provided strong evidence for the presence of varying numbers of agn43 alleles within clinical isolates. Taken together, the results indicate the presence of a family of distinct Ag43 proteins encoded by multiple chromosomal alleles.

Adhesins, Bacterial↗