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M Le

Publications and source records attributed to M Le.

At least 55 records · Page 3Linked to original sources

[What is "mastopathy at risk" for the anatomopathologist?].

For the pathologist, the term "mastopathy at risk" comprises a double aspect. On one hand, a good definition of the boundary between benign lesions and cancer. The latter uses mainly, and still now, morphological signs, and no "markers" enable an infallible differentiation. Certainly certain criteria are useful observations to distinguish between intra-canal and intralobular epithelial hyperplasia of the carcinomas in situ, or to recognize between a tubular carcinoma and certain adenosis foci. But it is often the pathologist's experience which makes the difference. On the other hand, a good knowledge of the epidemiological studies associating, to each of the anatomopathological entities constituting the fibro-cystic mastopathy, a risk factor for breast cancer. Indeed, the pathologist must indicate, in his report, these various entities in order to help the clinician take his therapeutic decision. The results of the study of a population of 3,305 women who have been examined at the Gustave Roussy Institute between 1970 and 1973 for benign mammary lesions, 401 on whom a biopsy was carried out, will illustrate this observation, revealing the importance of multiple fibro-adenosis foci, small cysts and lobe hyperplasias. But the histological details of these benign mastopathies must imperatively be integrated to the epidemiological and clinical data on the patient in order to adapt the therapeutic protocol for the best.

Breast Diseases↗

Expansion of the bile acid pool changes the biliary transport characteristics of centrizonal hepatocytes.

We investigated whether acinar differences in taurocholate transport are responsible for the increased maximal secretory rate observed after expansion of the bile acid pool. The bile acid pool was expanded by cholate feeding for four days. Periportal and centrizonal hepatocytes were then probed by ante- and retrograde liver perfusion, respectively. In control animals, secretory rate constant (alpha 1) averaged 0.439 +/- 0.123 and 0.104 +/- 0.035 min-1 during ante- and retrograde perfusion, respectively, in the absence of exogenous taurocholate. These values did not significantly change when taurocholate was infused. In cholate-fed animals, alpha 1 was comparable during antegrade perfusion but was significantly reduced (0.038 +/- 0.035, p less than 0.05) during retrograde perfusion in the absence of exogenous taurocholate, presumably owing to induction of cytosolic bile acid binding proteins. During loading with exogenous taurocholate, by contrast, alpha 1 was significantly accelerated (0.252 +/- 0.026; p less than 0.01) in centrizonal hepatocytes from bile-acid fed rats. Expansion of the bile acid pool is able to change the bile salt secretory characteristics of centrizonal hepatocytes toward those of periportal ones.

Animals↗

Alterations in the functional expression of receptors on cirrhotic rat hepatocytes.

Reduced hepatic uptake and clearance of macromolecules in liver cirrhosis is due to two major factors: increased diffusional barriers, resulting primarily from the deposition of excessive connective tissue in the space of Disse, and hepatocellular dysfunction, manifested by receptor and/or postreceptor defects. To probe the mechanisms underlying hepatocellular dysfunction in liver cirrhosis, we have investigated receptor-ligand interactions for asialoorosomucoid, insulin and epidermal growth factor in hepatocytes isolated from the livers of rats chronically exposed to phenobarbital and carbon tetrachloride for up to 12 weeks. Viable cells were allowed to attach at 37 degrees C and the high-affinity cell surface binding sites for each ligand were assessed at 4 degrees C in the presence of [125I]-ligand. In parallel incubations, digitonin (0.055%) was added to the binding medium to assess total cellular binding sites. Results demonstrated that chronic treatment of rats with phenobarbital increased hepatocyte asialoorosomucoid surface receptor affinity (p less than 0.05) but had no affect on the number of asialoglycoprotein binding sites. Treatment with CCl4 and phenobarbital significantly reduced the number of surface binding sites for asialoorosomucoid (p less than 0.05) and epidermal growth factor (p less than 0.02), although this treatment had no effect on either the binding affinity or the number of binding sites for insulin. The decrease in cell surface binding sites for asialoorosomucoid and epidermal growth factor was not due to a redistribution of the surface sites to intracellular locations, since the total number of cellular binding sites also was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Poor esthetic results after conservative treatment of breast cancer. Technics of partial breast reconstruction].

A wide consensus exists today in favour of breast saving procedures for the surgical treatment of small breast cancers. The goal of conservative treatment is to preserve the shape of the breast and consequently to avoid the psychological consequences of the mutilation. In this respect, the final esthetic evaluation of conservative treatment is a major point to be considered after the oncological results. To evaluate these cosmetic results, 89 patients treated more than five years ago were analyzed on a standard picture protocol and rated according to a rigorous scale previously defined. In this group, 45% were rated as excellent, 34% as fair and 21% as poor. These results were compared to the cosmetic results of a second group of patients evaluated after the surgical stage of their conservative treatment in order to precise the morphological damage due to the surgical procedure. In the second group, 73% were rated as excellent, 20% as fair and 7% as poor. This study underlines the frequency of skin contractions (16%) and glandular defects (20%). Several rules are proposed to prevent such sequelae at the time of the tumorectomy. The difficulty of cosmetic improvement of the poor esthetic results is emphasized and the techniques of partial reconstructions are discussed in the light of our experience which includes 25 cases of partial reconstruction.

Breast↗

Uncoupling of the secretory pathways for IgA and secretory component by cholestasis.

Circulating polymeric immunoglobulin A (IgA) binds to secretory component (SC) on the surface of rat hepatocytes and is internalized and transported by vesicles to the canalicular membrane where the IgA-SC complex is secreted into bile. To further characterize this transport pathway, we examined the effects of bile flow reduction or transient bile duct obstruction on the secretion of IgA and SC into bile. In response to gradually increasing resistance to bile flow, the biliary concentration of IgA decreased as bile flow decreased, whereas total biliary protein concentration was little changed. After 2 h of bile duct clamping, the amount of IgA secreted into bile during the postclamp period was decreased to one-tenth of control values. Similarly, transport of biosynthetically labeled monoclonal IgA ([3H]MoIgA) during the postclamp period was reduced three-fold. In contrast to the impairment in IgA secretion, secretion of SC continued at nearly normal levels after resumption of bile flow. The reduced transport of IgA was not due to a failure of IgA to reach the hepatocyte, a functional alteration of the IgA, or a decrease in the number of hepatic IgA receptors. Our studies indicate that secretion of IgA is sensitive to bile flow and that the biliary secretory pathways for IgA and SC are dissociated after brief periods of cholestasis.

Animals↗

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

The effect of the calcium channel blocking agent, verapamil, on microcirculatory patterns and hepatic function was investigated in the perfused liver of cirrhotic rats. Compared with controls, cirrhotic livers had higher vascular resistance, increased intrahepatic shunting, and smaller extravascular albumin space and larger extravascular sucrose space, as determined by a multiple-indicator dilution technique. Hepatic function, estimated by determining propranolol and antipyrine extraction, was markedly reduced in cirrhotic livers. Portal pressure was then reduced 25% either pharmacologically by verapamil or hydrodynamically by lowering inflow. Verapamil decreased vascular resistance by 22%. This was associated with a 38% reduction in intrahepatic shunting and a 62% increase in extravascular albumin space. Hydrodynamically lowering pressure had no or adverse effects. The verapamil-induced improvement in microcirculatory characteristics was associated with a significant improvement in oxygen consumption (+21%) and antipyrine clearance (+20%). We conclude that the microvascular distortions of liver cirrhosis in the rat are partially reversible by vasodilators like verapamil.

Animals↗

Taurolithocholate increases heme catabolism and alters the clearance of antipyrine in the rat.

Taurolithocholate has been implicated in human cholestatic syndromes. Its action is believed to be due to an alteration in liver plasma membrane composition. To investigate whether other membranes are similarly affected, we studied the effect of taurolithocholate on hepatic heme turnover by means of a new 14CO breath test. Between 2 and 7 h after taurolithocholate administration, 14CO production was significantly increased, suggesting increased heme catabolism. This was substantiated by the finding of a 47% reduction of microsomal cytochrome P450 content 3 h after taurolithocholate administration. There was a reciprocal increase of 50% in heme oxygenase activity, the key enzyme in heme catabolism. To probe the biological significance of these findings, we measured plasma disappearance of propranolol and antipyrine. Clearance of neither propranolol nor antipyrine was altered by acute taurolithocholate administration. Prolonged administration of taurolithocholate, by contrast, decreased metabolic clearance rate of antipyrine by 48%. This was accompanied by a 25% decrease in microsomal cytochrome P450 content. Our findings suggest that taurolithocholate affects composition and function of the smooth endoplasmic reticulum, and that its action is not limited to the liver plasma membrane.

Animals↗

Characterization of calcium deprivation-induced cholestasis in the perfused rat liver.

To elucidate the role of calcium in regulation of canalicular bile flow, we studied biliary sucrose permeability and the transport kinetics of taurocholate in the in situ perfused rat liver. Calcium deprivation did not adversely affect viability or ultrastructural appearances of the liver. Removal of calcium led to initial choleresis followed by cholestasis dependent on external ionized calcium concentration. Biliary recovery of [14C]sucrose relative to that of tritiated water was determined by a biliary multiple-indicator dilution technique. Analysis in terms of irreversible thermodynamics suggested that biliary permeability to sucrose increased due to a change in the sieving coefficient from 0.135 to 0.435. Biliary recovery of taurocholate was significantly (P less than 0.001) reduced in low-calcium medium (from 79.6 +/- 6.5 to 17.6 +/- 11.8%). This was not due to a defect in hepatocellular uptake of taurocholate as determined in the perfused rat liver by a multiple-indicator dilution technique and in isolated hepatocytes. We conclude that calcium deprivation-induced cholestasis is characterized by an increased biliary permeability, a defect in cellular translocation and/or canalicular secretion of bile salts, and a defect in bile salt-independent bile flow.

Animals↗

Influence of common bile duct cannula size on maximal secretory rate of taurocholate in the rat.

The common bile duct of male Sprague-Dawley rats was cannulated with either PE 10 or PE 50 tubing. Maximal secretory rate of taurocholate averaged 389 +/- 67 (SD) and 657 +/- 115 nmoles X min-1 X g liver-1 in the PE 10 and PE 50 group, respectively (p less than 0.005). Maximal bile secretory pressure was significantly higher in the PE 10 group (240 +/- 28 vs 174 +/- 8 mm H20; p less than 0.005). When the maximal secretory rate was exceeded, bile flow decreased in both groups but this was accompanied with a decrease in maximal bile secretory pressure in the PE 10 group only. Maximal secretory rate of bile salts is markedly influenced by experimental technique. Use of small caliber common bile duct cannulae leads to partial obstruction and decreases the apparent maximal secretory rate for taurocholate.

Animals↗

Radical mastectomy versus radical mastectomy plus internal mammary dissection. Ten year results of an international cooperative trial in breast cancer.

A multicentric randomized trial evaluated the interest of internal mammary dissection on operable breast cancer patients. One thousand four hundred and fifty-three patients were included in the study and were followed for ten years. There is no difference in survival or in relapse-free survival between the two groups. There were significantly more local recurrences in the group without internal mammary dissection, but these recurrences occurred mainly on patients who developed metastases. A great difference between centers was observed in the number of nodes examined and there is therefore a difference in the prognostic value of the number of nodes invaded.

Breast Neoplasms↗

Taurocholate, but not taurodehydrocholate, increases biliary permeability to sucrose.

To determine whether bile salts alter the permeability of the biliary tree to inert solutes, we investigated the effects of taurocholate and taurodehydrocholate on [14C]sucrose bile-to-plasma ratio in the situ perfused rat liver. Sucrose bile-to-plasma ratio remained virtually constant over a 3-h period in untreated rats. Infusing increasing amounts of taurocholate produced the anticipated dose-dependent increase in bile flow and bile salt secretion up to a maximal secretory rate of 278 nmol X min-1 X g liver-1. When the secretory rate was exceeded, bile flow decreased by 22%. Even at doses below the maximal secretory rate, sucrose bile-to-plasma ratio increased in a dose-dependent fashion. To determine whether this was due to recruitment of more permeable centrizonal hepatocytes, the effect of equimolar amounts of taurodehydrocholate was determined. This nonmicelle-forming bile salt led to more marked choleresis than taurocholate but did not affect sucrose bile-to-plasma ratio. We conclude that taurocholate, but not taurodehydrocholate, leads to a dose-dependent increase in biliary permeability.

Animals↗

[Radical mastectomy and modified radical mastectomy in the treatment of breast cancer. Indications and results].

We studied first the long term results in a series of 1 139 immediately operable breast cancers, treated by a protocol which gave an important role to extended radical mastectomy (radical mastectomy with internal mammary node dissection). No difference in survival was noted according to the surgical procedure used, and the extended mastectomy does not seem to have demonstrated its superiority. Its value could be judged in a more rigorous manner thanks to the results of an international therapeutic trial, comparing radical mastectomy with extended radical mastectomy. Results were improved by the extended procedure in only one sub-group of patients, whose tumours was located in central or inner quadrants, T1 or T2, with positive axillary nodes: these patients represents 13 per cent of patients with immediately operable tumors. Taking these results into account a new protocol has been adopted at the Institut Gustave-Roussy: T1 cancers will be the object of a therapeutic trial between conservative treatment and modified radical mastectomy. T2 (internal or central) cancers, with axillary nodal involvement will be treated by extended radical mastectomy. T2 tumors (external) and all T3 tumors will be treated by a modified radical mastectomy.

Breast Neoplasms↗

Radical mastectomy versus radical mastectomy plus internal mammary dissection. Five-year results of an international cooperative study.

From 1963 to 1968, the international group collected 1580 cases of breast cancer, randomized into two therapeutic groups: radical mastectomy and extended mastectomy. The data were processed on the UNIVAC 1107 computer of the I.N.S.E.R.M. Computing Center. No significant difference was observed between the two groups in the overall five-year survival rate. However, a more detailed analysis, according to certain prognostic features, showed that extended mastectomy improved the results in one subgroup: cancers of inner or medial quadrants, axillary N+. Within this group the difference was highly significant for a smaller subgroup (190 patients) including only tumors T1 and T2. In conclusion, there is no indication for extended mastectomy in any cancers of the outer quadrants or in those of the inner or medial quadrants without axillary involvement. A limited indication for extended mastectomy may be provisionally retained for T1 and T2 cancers of the inner or medial quadrants with axillary involvement.

Breast Neoplasms↗

Decreased uptake of taurocholate and ouabain by hepatocytes isolated from cirrhotic rat liver.

To differentiate between the "intact" and "sick" cell hypothesis explaining decreased clearance of endo- and xenobiotics, we measured uptake of taurocholate and ouabain in hepatocytes isolated from cirrhotic rat liver. Cirrhosis was induced by chronic exposure of male Sprague-Dawley rats to phenobarbital and carbon tetrachloride. Uptake of [14C]taurocholate and [3H]ouabain was measured by a rapid filtration technique. Hepatocytes from cirrhotic liver were as viable as control hepatocytes--as judged by trypan blue exclusion and lactate dehydrogenase release--but consumed 28% less oxygen. Vmax of both taurocholate (3.16 +/- 0.95 vs. 0.40 +/- 0.35 nmoles X min-1 X 10(6) cells-1; p less than 0.001) and ouabain (2.16 +/- 0.78 vs. 0.83 +/- 0.26 nmoles X min-1 X 10(6) cells-1; p less than 0.005) was significantly reduced. These results are compatible with the "sick" cell hypothesis.

Animals↗