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Biomedical subjects

B Dousset

Publications and source records attributed to B Dousset.

At least 19 recordsLinked to original sources
PubMed2006

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.

BACKGROUND: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. PATIENTS AND METHODS: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. RESULTS: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. CONCLUSION: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.

Adult↗
PubMed2005

Myocardial collagen turnover in normotensive obese patients: relation to insulin resistance.

OBJECTIVES: The present study was undertaken to assess the differential impact of insulin resistance, leptin and body composition on myocardial mass and serum markers of cardiac fibrosis in obese subjects, within a small range of elevated BMI (30-40 kg/m(2)), without pulmonary disease, cardiovascular disease, hypertension, cardiac hypertrophy or other cardiovascular disease. BACKGROUND: Obesity is an independent predictor of left ventricular mass (LVM) and is associated with disturbances in cardiac structure. The extent of the interstitial fibrosis in obese patients is not known, especially in the absence of cardiac hypertrophy. METHODS AND RESULTS: We included 160 obese subjects. The LVM was obtained using the Devereux formula. Body composition was estimated from a total body scan. Insulin sensitivity was assessed by homeostasis model assessment (HOMA), and cardiac collagen turnover by measurement of procollagen type III aminopeptide (PIIINP). PIIINP was correlated to the E/A ratio (r=0.24; P=0.012), a marker of ventricular function. PIIINP was independently correlated with glucose concentration (r=0.27; P=0.004), indexes of insulin resistance (HOMA (r=0.27; P=0.003), insulin (r=0.24; P=0.008)), and parameters associated with the insulin-resistance syndrome (HDL-cholesterol r=-0.27; P=0.004) and fat trunk/fat leg ratio (r=0.24; P=0.053)). The variable most correlated with PIIINP was HDL-cholesterol, followed by HOMA (r (2)=0.13). When HOMA was substituted for blood glucose concentration and insulinemia (Model 2), HDL-cholesterol was strongly related to lower PIIINP levels, followed by higher glucose concentration (r (2)=0.21). Regression analyses showed that LVM had the strongest independent positive correlation with fat-free mass (FFM) (r=0.39; P=0.0002), followed by systolic blood pressure (r=0.19; P=0.034). Neither adipose mass nor height independently added information to multivariate models. The ratio leptin/fat mass was correlated with LVM (r=-0.27; P=0.004), but not independently of the FFM. Markers for fibrosis were not significantly correlated with LVM. As a result, FFM was the most predictive factor of LVM in obese subjects. CONCLUSION: We found that serum levels of markers of cardiac collagen synthesis were significantly associated with insulin resistance in normotensive, nondiabetic obese subjects, and not related to the LVM. As a result, PIIINP could be a very early marker of ventricular dysfunction in these patients. Furthermore, we suggest that, for better detection of left ventricle hypertrophy in obese subjects, LVM should be indexed to FFM rather than to body surface area, or height.

Adult↗
PubMed2004

Accuracy of rectal endoscopic ultrasonography and magnetic resonance imaging in the diagnosis of rectal involvement for patients presenting with deeply infiltrating endometriosis.

OBJECTIVE: To compare the accuracy of rectal endoscopic ultrasonography (REU) and magnetic resonance imaging (MRI) for predicting rectal wall involvement in patients presenting histologically proven deeply infiltrating endometriosis (DIE). METHODS: This was a retrospective study of a continuous series of 81 patients presenting histologically proven DIE who underwent preoperative investigations using both REU and MRI. The sonographer and the radiologist, who were unaware of the clinical findings and patient history, but knew that DIE was suspected, were asked whether there was involvement of the digestive wall. RESULTS: Rectal DIE was confirmed histologically in 34 of the 81 (42%) patients. For the diagnosis of rectal involvement, sensitivity, specificity and positive and negative predictive value for REU were 97.1%, 89.4%, 86.8% and 97.7% and for MRI they were 76.5%, 97.9%, 96.3% and 85.2%. CONCLUSION: The sensitivity and negative predictive value of REU were higher than those of MRI suggesting that REU performs better than MRI in the diagnosis of rectal involvement for patients presenting with DIE. Prospective studies with a large number of patients are needed in order to validate these preliminary results.

Adult↗
PubMed2004

Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.

BACKGROUND: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. PATIENTS AND METHODS: A large series of surgically resected liver metastases (n=153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (alpha-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. RESULTS: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. CONCLUSIONS: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.

Adenocarcinoma↗
PubMed2004

Predictive value of preoperative transthoracic echocardiography in patients undergoing adrenalectomy for pheochromocytoma.

BACKGROUND: Adrenalectomy for pheochromocytoma is a life-threatening procedure. Few echocardiographic assessments have been reported in patients undergoing adrenalectomy for pheochromocytoma. METHODS: Sixty-three consecutive patients undergoing adrenalectomy for pheochromocytoma underwent routine preoperative M-mode and two-dimensional echocardiography, and Doppler examination. Abnormal echocardiographic findings were defined as left ventricular dilatation or dysfunction (left ventricular percentage fractional shortening < 30%), and/or left ventricular wall motion abnormalities, and/or left ventricular hypertrophy (left ventricular mass index > 110 g m(-2) in women and >134 g m(-2) in men) and/or valvular abnormalities. Physical characteristics, daily urinary metanephrine and normetanephrine excretions, preoperative functional limitation, pre-existing congestive heart failure, type and duration of surgery, and haemodynamic instability in the intra and postoperative periods were compared in patients with normal and abnormal echocardiographic findings. RESULTS: Twenty-four out of 63 patients were found to have abnormal preoperative echocardiography. There was no difference between patients with normal and abnormal preoperative echocardiography as regards to the investigated criteria, except for pre-existing self-reported functional limitation and chest pain suggesting coronary artery disease. CONCLUSIONS: The relevance of routine preoperative echocardiographic examination in patients scheduled for adrenalectomy for pheochromocytoma, who have no cardiac symptoms or clinical evidence of cardiac involvement, is questionable.

Adrenal Gland Neoplasms↗
PubMed2003

Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification.

BACKGROUND: Deeply infiltrating endometriosis (DIE) is recognized as a specific entity responsible for pain. The distribution of locations and their contribution to surgical management has not been previously studied. METHODS: Medical, operative and pathological reports of 241 consecutive patients with histologically proven DIE were analysed. DIE lesions were classified as: (i). bladder, defined as infiltration of the muscularis propria; (ii). uterosacral ligaments (USL), as DIE of the USL alone; (iii). vagina, as DIE of the anterior rectovaginal pouch, the posterior vaginal fornix and the retroperitoneal area in between, and (iv). intestine, as DIE of the muscularis propria. RESULTS: A total of 241 patients presented 344 DIE lesions: USL (69.2%; 238); vaginal (14.5%; 50); bladder (6.4%; 22); intestinal (9.9%; 34). The proportion of isolated lesions differed significantly according to the DIE location: 83.2% (198) for USL DIE; 56.0% (28) for vaginal DIE; 59.0% (13) for bladder DIE; 29.4% (10) for intestinal DIE (P < 0.0001). The total number of DIE lesions varied significantly according to the location (P < 0.0001). In 39.1% of cases (9/23) intestinal lesions were multifocal. Only 20.6% (seven cases) of intestinal DIE were isolated and unifocal. CONCLUSIONS: Multifocality must be considered during the pre-operative work-up and surgical treatment of DIE. We propose a surgical classification based on the locations of DIE. Operative laparoscopy is efficient for bladder, USL and vaginal DIE. However, indications for laparotomy still exist, notably for bowel lesions.

Adnexal Diseases↗
PubMed2003

Somatostatin receptors 2 and 5 are the major somatostatin receptors in insulinomas: an in vivo and in vitro study.

Somatostatin (SRIF) receptors (sst) are present on normal pancreatic endocrine beta-cells. However, the use of SRIF analogs in the scintigraphic imaging of insulinomas and in the medical management of these tumors seems to be restricted to a subgroup of patients. The aim of this study was to determine the prevalence of sst expression in vitro and characterize sst subtype binding in insulinomas and its correlation with in vivo sst receptor scintigraphy (SRS). In vitro studies were performed on 27 insulinomas from 25 patients: 22 with benign and three with malignant tumors. Semiquantitative RT-PCR of sst mRNAs was performed for 20 of these insulinomas. Sst2 and sst5 were expressed in 70%, sst1 in 50%, and sst3 and sst4 subtypes only in 15-20% of the tumors. (125)I-Tyr(0)DTrp(8)SRIF(14) binding was assessed by quantitative autoradiography in 18 insulinomas, and competition experiments were performed with SRIF(14) and L797-591, L779-976, L796-778, L803-087, L817-818, selective agonists of the five sst subtypes, and BIM23244, a selective agonist of sst2 and sst5. Significant specific binding was observed in 72% of the insulinomas. Displacement experiments with ligands of higher affinity for each of the sst receptors revealed significant binding with the sst2 and sst5 ligands in 72%, sst3 in 44%, sst1 in 44%, and sst4 in 28% of cases. All insulinomas displaying sst2 binding were also sst5 sensitive. However, the ratio of sst5/sst2 displacement was variable and only equal to that for SRIF(14) in experiments with the sst2/sst5 agonist BIM23244. SRS was performed 10 times in nine patients; it detected 60% of the tumors, including metastases of a malignant insulinoma. All the tumors detected by SRS displayed high levels of (125)I-Tyr(0)DTrp(8)SRIF(14) binding. The mechanisms underlying the loss of expression of sst2/sst5 in a third of insulinomas remains to be determined, but this loss of expression may be involved in beta-cell dysfunction.

Adult↗
PubMed2002

The allergenicity of soybean-based products is modified by food technologies.

BACKGROUND: Numerous products based on soybean are available and various food technologies are applied for their production. The allergenicity of natural soybean may be modified by these treatments. OBJECTIVES: To compare the allergenicity of native soybean proteins with those of soy milk and texturized protein products. To show additional allergens. METHODS: Three commercial products and two infant formulas were studied: Soybean flour, soy milk, texturized soy proteins, two infant formulas; the first containing total proteins and the second containing a soy protein hydrolysate. Sera from 9 patients allergic to soy protein were tested by immunoblotting (IB). IB inhibition was achieved by incubating sera with protein extract from soybean flour. RESULTS: The SDS-PAGE profile of soybean flour protein and soy milk showed a difference in the proportions of the various protein fractions, with a higher concentration of 37-kD protein in flour and 33-kD protein in milk. Infant formula 1 contained proteins with a molecular weight below 28 kD. The texturized extract contained high proportions of 31- to 34- and 38-kD proteins. Immunoblotting revealed a lack of allergenicity in infant formula. Sera recognizing the 38- and 50-kD proteins in texturized soy protein also recognized the 37- and 49-kD proteins in soybean flour and in soy milk, suggesting a protein glycation by texturization processes. The 30- to 34-kD band in texturized proteins was devoid of any allergenicity. This study seems to indicate that the 30-kD allergen (Gly m Bd 30) disappears during the production of texturized soy protein. CONCLUSION: All technologies applied to soybean-based products induce striking variation in the protein profile and allergenicity. Texturized protein could lack the major allergen Gly m Bd 30. Further studies or texturization might generate modified technologies in order to create hypoallergenic texturized proteins.

Adolescent↗
PubMed2002

Action of boron at the molecular level: effects on transcription and translation in an acellular system.

It has been shown that boric acid has well-defined biological effects such as stimulation of wound healing in vivo, release of growth factors and cytokines, and increase of the extracellular matrice turnover. We examined its action at the molecular level, using cell-free systems of transcription (isolated placenta nuclei) and translation (wheat germ extract). We found that 10 mM boric acid greatly increased RNA synthesis, measured by absorbance at 260 nm (x 6.4) or by [3H]-UTP uptake (x 11). Full-length functional mRNA was produced because proteins of 14-80 kDa were translated. Among these proteins, factors involved in angiogenesis and, subsequently, in wound healing (VEGF and TGFbeta) were identified by slot blot, whereas growth factors such as FGF1 and TNFalpha were not detected. These results demonstrate that boron may contribute to biological cell activities at both the transcription and translation levels. However, the mechanism of action is still not known.

Autoradiography↗
PubMed2002

[Diagnostic and therapeutic strategy for an incidental finding of an adrenal mass].

The incidental finding of an unsuspected adrenal mass ranges from 0.5% to 5% in abdominal CT series. The optimal diagnostic approach to such masses is to diagnose malignant or secretory tumors requiring excision and to otherwise avoid unnecessary surgery. Physical examination generally contributes little. A standard biochemical evaluation should include the measurement of 24 hour urinary catecholamines and metanephrine, urinary free cortisol and plasma cortisol levels at 8 a.m. and 8 p.m. combined with an overnight low-dose dexamethasone suppression test, serum potassium assay, and determination of upright plasma aldosterone to plasma renin activity. These tests will serve to screen for pheochromocytoma, subclinical Cushing's syndrome, and primary hyperaldosteronism respectively. Imaging characteristics suggestive of malignancy include: size greater than 4 cm., heterogeneous lesion and/or density greater than 20 Hounsfield Units on CT scan, slow enhancement with delayed washout after intravenous contrast injection on CT scan, and slightly decreased signal intensity in out of phase (fat suppressed) MR acquisition. Fine-needle aspiration biopsy should be performed only if metastatic disease is suspected. Adrenal scintigraphy with iodocholesterol may be useful where adenoma with subclinical Cushing's syndrome or solid tumor is suspected. In summary, the following strategy is recommended for the management of adrenal incidentalomas : mass lesions larger than 4 cm. and hormone-secreting tumors should be removed. All non-secreting adrenal incidentalomas smaller than 4 cm. in diameter should be followed by serial imaging at regular intervals (6, 12, and 36 months) and by endocrine reevaluation at one year.

Adrenal Cortex Function Tests↗
PubMed2001

Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis.

Diabetes mellitus, a common complication of chronic pancreatitis, can disturb the metabolism of zinc, copper, and selenium. We analyzed the effects of hyperglycemia, malabsorption, and dietary intake on these factors in 35 men with alcohol-induced chronic pancreatitis complicated by insulin-treated diabetes mellitus (CP-D), 12 men with chronic pancreatitis but no diabetes (nondiabetic CP), 25 men with type 1 diabetes mellitus (type 1 DM), and 20 control subjects. Diabetes due to chronic pancreatitis was associated with decreased plasma zinc and selenium concentrations and with increased urinary copper excretion. Of the chronic pancreatitis patients, 17% had low plasma zinc, and 41% of them had low plasma selenium. None of the type 1 diabetic patients had low plasma concentrations of zinc, but 12% of them had a low selenium concentration. Hyperglycemia, as assessed by fasting plasma glucose and by plasma HbAlc, was responsible for the increased zinc excretion and the decreased superoxide dismutase activity. The perturbations of the copper, selenium, and zinc metabolism were particularly pronounced in subjects with chronic pancreatitis plus diabetes mellitus. We have yet to determine whether the differences in trace-element status contribute to the clinical expression of the disease.

Adult↗
PubMed2001

Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship.

Cardiac extracellular matrix undergoes extensive and continuous turnover involved in the lesion-reparation process, such as in cardiac remodeling, in hypertensive cardiac hypertrophy, in dilated cardiomyopathy, after myocardial infarction in the transition to heart failure, and during the progression of left ventricular dysfunction. Cardiac fibrosis is a major determinant of diastolic dysfunction and pumping capacity, and it may provide the structural substrate for arrhythmogenicity, thus potentially contributing the to progression of heart failure and sudden death. Aldosterone was shown to promote cardiac fibrosis in various experimental models. It was demonstrated that spironolactone may oppose the effect of aldosterone in promoting cardiac fibrosis. Measurement of cardiac collagen turnover by use of serological markers is a useful tool for monitoring cardiac tissue repair and fibrosis in experimental models or clinical conditions. We found that high serum levels of a marker of collagen turnover (procollagen type III N-terminal peptide ) in patients with chronic heart failure receiving conventional therapy, including ACE inhibitors, was associated with high mortality and hospitalization rates. In RALES (Randomized Aldactone Evaluation Study), in patients randomized to placebo, markers continued to increase or remained unchanged after 6-month follow-up. On the contrary, adding spironolactone 25 mg daily significantly decreased the levels of these serum markers during the same period. Most importantly, the spironolactone-related morbidity and mortality benefit was most predominant in subgroups with highest baseline levels of serum markers. These results suggest that limitation of the aldosterone-related excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with chronic heart failure.

Aldosterone↗