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Biomedical subjects

Marc Froissart

Publications and source records attributed to Marc Froissart.

14 recordsLinked to original sources

Sentinel lymph node biopsy improves staging in early cervical cancer.

OBJECTIVES: The main study objective was to describe the distribution of sentinel lymph nodes (SLNs) and the prevalence of SLN micrometastases in patients with early cervical cancer. The secondary objective was to confirm the SLN detection rate and negative predictive value found in our preliminary study. PATIENTS AND METHODS: We prospectively included 25 patients with early cervical cancer, each of whom received an injection of 120 MBq of technetium-99m for preoperative lymphoscintigraphy and intraoperative node detection using an endoscopic gamma probe. Patent blue dye was injected intraoperatively. SLNs were sought in the pelvic and para-aortic drainage areas. Radical iliac dissection was performed routinely at the end of the procedure. SLNs were examined after hematoxylin-eosin-saffron staining; negative specimens were assessed using immunohistochemistry. RESULTS: Most (85%) of the SLNs were in the inter-iliac territory. Para-aortic or parametrial SLNs were found respectively in 2 patients and common iliac SLNs in 5 patients. Thus 9/25 patients had additional information due to SLN detection. One metastasis and one micrometastasis were detected in SLNs. No patients had positive non-sentinel nodes with negative SLNs. CONCLUSION: SLN detection ensures the identification of SLNs in unusual locations in 36% of patients. SLN disease was found in 8% of our patients. Thus, SLN biopsy improves staging in patients with early cervical cancer. Studies in larger patient populations are needed to evaluate the clinical impact of SLN biopsy.

Adenocarcinoma↗

Gated blood pool tomoscintigraphy with 4-dimensional optical flow motion analysis quantifies left ventricular mechanical activation and synchronization.

BACKGROUND: Gated blood pool tomoscintigraphy has the unique capacity to accurately assess myocardial motion in paced patients. Our goal was to develop a precise radionuclide angiography analysis of cardiac dynamics to evaluate ventricular synchronization in patients undergoing biventricular pacing. METHODS AND RESULTS: On the basis of a 4-dimensional deformable motion estimation algorithm, we developed a protocol allowing estimation of motion fields after gated blood pool tomoscintigraphy. We measured the mechanical activation times for 17 left ventricular (LV) segments and determined the main types of contraction pattern in 10 normal subjects, 17 patients with dilated cardiomyopathy, and 12 resynchronized patients. We analyzed intra-LV dyssynchrony: apex to base, septum to lateral wall, and anterior wall to inferior wall. Three-dimensional measurements of intra-LV activation time (r > .80, P < .001) and LV ejection fraction (r > 0.90, P < .0001) are linearly correlated to 2-dimensional values. LV contraction follows the electrical activation pattern. In normal subjects the anteroseptal and anterior segments are first activated, followed by the apex and inferolateral segments. In resynchronized patients contraction begins with the lateral and apicoseptal segments in correspondence to the LV and right ventricular lead implantation. CONCLUSIONS: By measuring mechanical activation times, this technique allows for the analysis of the regional synchronous contraction. This may help to assess the variation of the activation pattern according to the cardiomyopathy type and the role of septal resynchronization in ventricular functional recovery.

Aged↗

Role of anemia in progression of chronic kidney disease.

Anemia is a well-known consequence of chronic kidney disease (CKD), and its prevalence progressively increases when the estimated glomerular filtration rate decreases to less than 60 mL/min/1.73 m2. However, analyses of the consequences of anemia and of the mechanisms of progression of CKD suggest that anemia also could contribute to the deterioration of kidney function. This hypothesis is based mostly on experimental data that imply that hypoxia of tubular cells plays an important role in tubulointerstitial damage associated with CKD and, thus, in the progression of renal failure. It also is supported by the fact that red blood cells represent a major antioxidant component of blood and that oxidative stress appears to contribute to glomerulosclerosis and tubulointerstitial damage. In humans, post hoc analysis of the Reduction of End points in non insulin-dependent diabetes mellitus (NIDDM) with the Angiotensin II Antagonist Losartan study and analyses of smaller prospective cohorts of CKD patients have shown that anemia is an independent risk factor for progression of CKD. In addition, 3 small randomized studies have suggested that anemia correction could slow the progression of CKD. Thus, the existence of a relationship between anemia and progression of CKD is not only plausible biologically, but also is supported by observational studies and by small intervention studies. However, only a large, randomized, prospective trial will be able to establish if anemia correction can slow the progression of CKD effectively.

Anemia↗

[How to improve estimation of renal function in the elderly].

Kidney function is defined by the glomerular filtration rate (GFR). It has been clearly established that serum creatinine should not be used alone to estimate GFR, and that estimated GFR should be calculated using formulas that take into account various parameters including serum creatinine. In adults, two formulas are mostly used to estimate GFR: the Cockcroft-Gault formula and the MDRD formula. In elderly, GFR should only be estimated using the MDRD formula, since the Cockcroft-Gault formula systematically underestimates GFR. GFR tends to decrease with age, but it should be 60 mL/min/1,73 m2 or higher in all subjects who do not suffer from kidney disease, regardless of age.

Aged↗

Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function.

Recent recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients with chronic kidney disease. The most widely used equations are the Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulas. However, they still need to be validated in large samples of subjects, including large non-U.S. cohorts. Renal clearance of (51)Cr-EDTA was compared with GFR estimated using either the CG equation or the MDRD formula in a cohort of 2095 adult Europeans (863 female and 1232 male; median age, 53.2 yr; median measured GFR, 59.8 ml/min per 1.73 m(2)). When the entire study population was considered, the CG and MDRD equations showed very limited bias. They overestimated measured GFR by 1.94 ml/min per 1.73 m(2) and underestimated it by 0.99 ml/min per 1.73 m(2), respectively. However, analysis of subgroups defined by age, gender, body mass index, and GFR level showed that the biases of the two formulas could be much larger in selected populations. Furthermore, analysis of the SD of the mean difference between estimated and measured GFR showed that both formulas lacked precision; the CG formula was less precise than the MDRD one in most cases. In the whole study population, the SD was 15.1 and 13.5 ml/min per 1.73 m(2) for the CG and MDRD formulas, respectively. Finally, 29.2 and 32.4% of subjects were misclassified when the CG and MDRD formulas were used to categorize subjects according to the Kidney Disease Outcomes Quality Initiative chronic kidney disease classification, respectively.

Adult↗

Anemia management and chronic renal failure progression.

Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.

Anemia↗

[Sentinel lymph node biopsy in cervical and endometrial cancers: a feasibility study].

The sentinel lymph node (SLN) biopsy has been proposed for the cancers of the uterus in order to optimize the diagnosis of lymphatic metastases and micrometastases in early stage tumors. Patients with early invasive cervical (n = 8) or endometrial (n = 15) cancers were enrolled. A lymphoscintigraphy was carried out before the intervention. Intraoperative SLN identification was performed with blue dye combined to a handheld gamma probe detection. Non-sentinel pelvic nodes were separately cleared out. SLNs were examined with frozen sections, permanent sections with hematoxylin-eosin staining and further serial sections with immunohistochemistry if negative. Six cervical cancer patients and 13 endometrial cancer patients had a positive lymphoscintigraphy, showing in 5 patients extra-iliac SLN(s). The intraoperative detection was successful in 6 cervical cancer patients and 14 endometrial cancer patients. The higher detection rate was obtained with the isotopic method. Most of the SLNs were ilio-obturator. Four endometrial cancer patients had a lymphatic spread, only involving the SLN in each case. No false negative SLN has been noted. SLN biopsy appears feasible in cervical and endometrial cancers. This procedure could improve the lymphatic evaluation of these cancers.

Adult↗

Differentiated thick ascending limb (TAL) cultured cells derived from SV40 transgenic mice express functional apical NHE2 isoform: effect of nitric oxide.

Studying the apical Na/H exchanger NHE2 is difficult in the intact thick ascending limb (TAL) because of its weak expression and transport activity compared with the co-expressed NHE3. From a mouse transgenic for a recombinant plasmid adeno-SV(40) (PK4), we developed an immortalized TAL cell line, referred to as MKTAL, which selectively expresses NHE2 protein and activity. The immortalized cells retain the main properties of TAL cells. They have a stable homogeneous epithelial-like phenotype, express SV(40) T antigen and exhibit polarity with an apical domain bearing few microvilli and separated from lateral domains by typical epithelial-type junctional complexes expressing ZO1 protein. Tamm-Horsfall protein is present on the apical membrane. MKTAL cells express NHE2 and NHE1 proteins but not NHE3 and NHE4, whereby NHE2 protein is expressed selectively in the apical domain of the plasma membrane. NHE2 contributed about half of the total Na/H exchange activity. mRNAs for the Na-K-2Cl cotransporter-2 (NKCC2) and the anion exchangers AE2 and AE3 were also present. While acute exposure to NO donors did not alter NHE2 activity, chronic exposure inhibited NHE2 activity selectively and down-regulated NHE2 mRNA abundance. In conclusion, MKTAL cells retain structural and functional properties of their in vivo TAL counterparts and express functional NHE2 protein in the apical membrane, which may be inhibited by NO. Thus, MKTAL cells may be an appropriate model for studying the cellular mechanisms of NHE2 regulation.

Animals↗

Basal asynchrony and resynchronization with biventricular pacing predict long-term improvement of LV function in heart failure patients.

Biventricular pacing (BiV) is emerging for patients with dilated cardiomyopathy (DCM) and asynchrony. We measured basal asynchrony and early resynchronization by radionuclide angioscintigraphy (RNA) in order to predict long-term evolution of ventricular function after BiV. Thirty-four patients (NYHA Class III-IV,65.4 +/- 11 years) with large QRS(179 +/- 18 ms)were implanted with BiV and studied by RNA before (D0), at day 8 (D8), and during follow-up(20 +/- 7 months). We calculated left and right ejection fractions, the interventricular dyssynchrony (TRVLV), and the apicobasal dyssynchrony (Tab). LVEF improved from 20.2 +/- 8.1%(D0) to27.1%+/- 12.6%(follow-up,P < 0.003 vs D0) and RVEF from 28.6%+/- 13%(D0) to 34.3 +/- 11.5%(follow-up,P < 0.03 vs D0). Inter- (DeltaTRVLV) and intraventricular resynchronization was immediate and remained stable: TRVLV decreased from 68.3 +/- 38 ms(D0) to 13.4 +/- 48.5 ms(D8) and1.8 +/- 39.2 ms(follow-up,P < 0.0001 vs D0); and Tab from 45.8 +/- 64.1 msto-18 +/- 68(D8) and-28.3 +/- 53.6 ms(follow-up,P < 0.0001 vs D0). Early inter- and intraventricular resynchronization (DeltaTab) at D8 were related to late LVEF and RVEF improvement. Together, an LVEF > 15% and a significant interventricular dyssynchrony (TRVLV > 60 ms) at D0 have a sensitivity of 79% and a positive predictive value of 83% to predict an improvement of LVEF superior to 5% at follow-up. In DCM patients, BiV resynchronizes ventricles early and in the long-term, while RVEF and LVEF improve progressively. Patients with large electromechanical dyssynchrony benefit most from BiV.

Aged↗

Ventricular coupling of electrical and mechanical dyssynchronization in heart failure patients.

We studied the relationships of electrical and mechanical synchronization in patients with heart failure (CHF) and various degree of ventricular conduction delays. Ninety-two CHF patients (60 +/- 13 years old, LVEF < 45%), NYHA II-III-IV, and 35 age-matched control subjects were studied with angioscintigraphic phase analysis. We measured ejection fractions (LVEF, RVEF) and calculated the total activation time for the left (TtLV) and right ventricle (TtRV), and the synchronization time between right and left ventricle (TRVLV), and between LV apex and base (Tab). Patients were divided into three groups according to QRS duration: group 1 < 120 ms (n = 28), group 2 < 150 ms (n = 23), group 3 > or = 150 ms (n = 41). In group 1: LVEF = 31.1 +/- 10.9%, RVEF = 30.1 +/- 12.6%, TtLV = 204 +/- 70 ms, TtRV = 183 +/- 61 ms, TRVLV = 7 +/- 33 ms, Tab = 29 +/- 23 ms. In group 2, these were: 27.8 +/- 9.1%, 27.8 +/- 8.8%, 227 +/- 95 ms, 248 +/- 137 ms, 35 +/- 42 ms*, and 39 +/- 53 ms respectively. In group 3: LVEF = 20.5 +/- 9.5%t, RVEF = 28.4 +/- 16.1%, TtLV = 304 +/- 155 mst, TtRV = 234 +/- 106 mst, TRVLV = 64 +/- 42 mst, and Tab = 67 +/- 48 ms*, all P < 0.001 versus controls *P < 0.05 versus G1, tP < or = 0.01 versus G1. A significant relation links QRS to both inter- and intraventricular asynchrony (TRVLV: r = 0.65; TtLL: r = 0.70, Tab: r = 0.60), and to LV function (r = 0.72); while LVEF relates more closely to intraventricular asynchrony: TtLV (r = 0.52), TtLL (r = 0.67), than to interventricular asynchrony: TRVLV (r = 0.48); P < 0.01, P < or = 0.001. In CHF patients, electromechanical and contractile alterations are coupled; regional activation may be an early parameter allowing the detection of ventricular dyssynchronization.

Bundle-Branch Block↗

Split renal function outcome after renal angioplasty in patients with unilateral renal artery stenosis.

The general use of bilateral rather than separate renal function evaluation has led to the publication of conflicting results concerning the effect of percutaneous transluminal renal angioplasty (PTRA) on renal function, especially in patients with atherosclerotic renal artery stenosis. The aim of this study was to evaluate prospectively, in standardized conditions, split renal function (SRF) and GFR outcome after successful PTRA, by measuring single kidney GFR with synchronous inulin or (51)Cr-ethylenediaminetetraacetic acid clearance and (99m)Tc-diethylenetriamine pentaacetic acid scintigraphy, in a well-defined population of patients with unilateral renal artery stenosis. Thirty-two consecutive hypertensive patients (18 with atherosclerotic and 14 with dysplastic disease) with significant unilateral stenosis of the main native renal artery (> or = 60%) and normal renal function were included in the study. Renal and angiographic follow-up evaluations were performed 6 mo after PTRA. PTRA alone or combined with stenting (n = 2) was technically successful in all patients. Repeat PTRA was necessary in two patients, evaluated 6 mo after the second PTRA. Six mo after PTRA, total GFR had increased slightly but significantly in the 29 patients with positive lateralization indices. SRF and single-kidney GFR of the stenotic kidney increased significantly, whereas concurrently the GFR and SRF of the nonstenotic kidney decreased significantly. Six mo after successful PTRA reducing renal ischemia, a reversal of both the hypoperfusion of the stenotic side and the hyperperfusion of the nonstenotic side was observed, which was accompanied by a slight increase in total GFR.

Adult↗