[Evaluation of the efficacy and safety of HIVEC intravesical thermochemotherapy with intermediate-risk and high-risk non-muscle-invasive bladder cancer]. / Évaluation de l'efficacité et de la tolérance de la thermo-chimiothérapie intravésicale HIVEC pour les tumeurs de vessie non infiltrant la musculeuse de risque intermédiaire et de haut risque.

INTRODUCTION: Non-muscle-infiltrating cancers (NMIBC) represent 75% of bladder tumors. The objective of our study is to report a single-center experience of the efficacy and tolerability of HIVEC on intermediate- and high-risk NMIBC in adjuvant therapy. MATERIAL AND METHOD: Between December 2016 and October 2020, patients with intermediate-risk or high-risk NMIBC were included. They were all treated with HIVEC as an adjuvant therapy to bladder resection. Efficacy was assessed by endoscopic follow-up and tolerance by a standardized questionnaire. RESULTS: A total of 50 patients were included. The median age was 70years (34-88). The median follow-up time was 31 months (4-48). Forty-nine patients had cystoscopy as part of the follow-up. Nine recurred. One patient progressed to Cis. The 24-month recurrence-free survival was 86.6%. There were no severe adverse events (grade 3 or 4). The ratio of delivered instillations to planned instillations was 93%. CONCLUSION: HIVEC with the COMBAT system is well tolerated in adjuvant treatment. However, it is not better than standard treatments, especially for intermediate-risk NMIBC. While waiting for recommendations, it cannot be proposed as an alternative to standard treatment.

[Preoperative endorectal MRI in prostate cancer: a monocentric retrospective cohort]. / Place de l'IRM prostatique avant prostatectomie radicale. Cohorte monocentrique rétrospective.

INTRODUCTION: The aim of the study was to assess the added value of a prostatic MRI performed in a non-expert center before radical prostatectomy for prostate cancer. PATIENTS AND METHODS: All patients considered for a radical prostatectomy for a clinically localised prostate cancer in our institution between June 2006 and April 2011 were analysed. They underwent a systematic endorectal 1.5 T MRI [eMRI] (T2 and diffusion-weighted imaging). The procedure was performed at least 8 weeks after transrectal ultrasound guided prostate biopsies. They were analyzed by a single experimented genitourinary radiologist. The preoperative characteristics and biopsy data were collected, as the eMRI interpretation using a systematic scale. Correlation between eMRI and final histopathology has been analyzed (standardized pathological report using the Stanford procedure). We considered the following points: extracapsular extension, seminal vesicle invasion and cancer localisation. Cancer localization was analyzed both by halves (left/right) and on sextant-basis (base, middle, apex, left and right respectively). For each data, sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were calculated. Finally, we compared the results with those from the Partin's table and the Kattan's nomogram for T stage. RESULTS: Two hundred and fifteen patients underwent a radical prostatectomy, having a mean age of 63 ± 6 years, a mean PSA: 7.8 ± 3.8 ng/mL. One hundred and fifty-nine patients had organ confined disease. Fifty-six had pT3 disease (50 pT3a and 6 pT3b). Sensibilities and specificities were the following: for extracapsular extension 26% and 96%; for seminal vesicle invasion 17% and 98%; for cancer localisation 64% and 74%; for prediction of left or right side 81% and 48%. DISCUSSION: MRI showed equal performances compared to the Partin's table and the Kattan's nomogram for T stage. It showed lower performance compared to biopsy results for cancer localization (sensitivity 88%, specificity 70%). Literature provides wide ranges of results for eMRI. The results of this study were at the low limit of these ranges but reflect everyday practice. When performed, as it was in our study, eMRI did not seem to be accurate for staging. It had at best a very limited added value compared to the existing tools.

Evaluation of IPPSE, an alternative method for sequential population PKPD analysis.

The aim of this study is to present and evaluate an alternative sequential method to perform population pharmacokinetic-pharmacodynamic (PKPD) analysis. Simultaneous PKPD analysis (SIM) is generally considered the reference method but may be computationally burdensome and time consuming. Evaluation of alternative approaches aims at speeding up the computation time and stabilizing the estimation of the models, while estimating the model parameters with good enough precision. The IPPSE method presented here uses the individual PK parameter estimates and their uncertainty (SE) to propagate the PK information to the PD estimation step, while the IPP method uses the individual PK parameters only and the PPP&D method utilizes the PK data. Data sets (n = 200) with various study designs were simulated according to a one-compartment PK model and a direct Emax PD model. The study design of each dataset was randomly selected. The same PK and PD models were fitted to the simulated observations using the SIM, IPP, PPP&D and IPPSE methods. The performances of the methods were compared with respect to estimation precision and bias, and computation time. Estimated precision and bias for the IPPSE method were similar to that of SIM and PPP&D, while IPP had higher bias and imprecision. Compared with the SIM method, IPPSE saved more computation time (61%) than PPP&D (39%), while IPP remained the fastest method (86% run time saved). The IPPSE method is a promising alternative for PKPD analysis, combining the advantages of the SIM (higher precision and lower bias of parameter estimates) and the IPP (shorter run time) methods.

[Prone and supine position for percutaneous nephrolithotomy: is it necessary to change the operative technique?]. / Néphrolithotomie percutanée : faut-il passer du décubitus ventral au décubitus dorsal ?

PURPOSE: To assess the safety and effectiveness of percutaneous nephrolithotomy performed in the supine position. To investigate whether the change in operative technique, between prone and supine position, is easy. METHOD: Thirty patients who underwent percutaneous nephrolithotomy, by one surgeon in one hospital, were studied retrospectively. The eight first cases were performed in prone position, and the following 22 patients were operated in supine position according to Valdivia's operative technique. Data were analyzed with t-test. We considered P<0.05 as significant. RESULTS: Surgical complication rate, transfusion rate and fever rate were the same for both groups. Success rate was 72% in supine position group and 63% in prone position group (P>0.05). These results were comparable with the data of the literature. Only operative time was shorter in supine position group with significant statistical difference (P=0.02). CONCLUSION: In our experience, percutaneous nephrolithotomy in the supine position was safe and efficient, and outcomes were similar to that in the prone position. Learning curve was easy and fast.

Expression analysis of loci associated with type 2 diabetes in human tissues.

AIMS/HYPOTHESIS: Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues. METHODS: We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n = 50), colon (n = 195) and liver (n = 50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. RESULTS: Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. CONCLUSIONS/INTERPRETATION: This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.

[Do broader indications for partial nephrectomy result in excess morbidity?]. / Elargir les indications de la néphrectomie partielle induit-il un surcroît de morbidité? Une étude multicentrique française.

OBJECTIVE: To evaluate the morbidity of partial nephrectomy (PN) according to tumour size and the type of indication based on a multicentre retrospective study. MATERIALS AND METHODS: Seven French teaching hospitals participated in this study. Data concerning tumour size, indication for PN (elective or necessity), age, gender, TNM stage, histological type, Fuhrman grade, ASA score and performance status (ECOG) were analysed. Medical and surgical complications, intraoperative blood loss, blood transfusion rate and length of hospital stay were also studied. Statistical analysis of qualitative and quantitative variables was performed with Chi-square test (Fisher's test) and Student t-test. RESULTS: Six hundred and ninety one patients were included. The median tumour diameter was 3cm (0.4-18). Tumours measuring less or equal to 4cm and incidental tumours represented 77.7 and 80.7% of cases, respectively. Clear cell carcinomas represented 75.1% of malignant tumours. Some 89.1% of tumours were T1, 1.6% were N+ and 2.3% were M+. In the 486 elective indications: the operating time (p = 0.03), mean blood loss (p = 0.04), and urinary fistula rate (p = 0.01) were significantly higher in tumours greater than 4cm. These differences were not associated with an increase in the medical (p = 0.7) or surgical complication rate (p = 0.2), or the length of hospital stay (p = 0.4). CONCLUSION: Broader indications for elective PN is associated with an increased morbidity but which remains acceptable. This is an important point for patient information and to guide the choice of surgical strategy, particularly in elderly, frail patients or patients with major comorbidities.

[What is the clinical practice of partial nephrectomy in France?]. / Quelle pratique de la néphrectomie partielle en France ?

OBJECTIVE: To describe the practice of partial nephrectomy (PN) in France and assess its results in terms of morbidity and cancer control. MATERIAL AND METHOD: Seven French University Hospitals in which nephron sparing surgery represents at least 30% of the total number of nephrectomies for renal tumour, participated in this study. All centres included, as exhaustively as possible, all their PN cases. For each patient, 70 variables were harvested in order to characterize the patient population, the indications, the operative technique, the per- and postoperative course and complications, the tumor specificities, the carcinologic control and renal function follow-up. RESULTS: Seven hundred and forty-one PN, of which 579 for malignant tumours were analysed. The mean tumour size was 3.4+/-2.1 cm (0.1-18) and 20.8% of the tumours were larger than 4 cm. In 30.1% of cases, the indication was imperative. Among the PN, 12.2% were performed laparoscopically. The mean operating time was 151+/-54.2 min (55-420). The medical and surgical complications rates were respectively 15.2 and 14.7%. At a mean 38 months follow-up, the local recurrence rate was 3.5% and the specific death rate was 4.5%. CONCLUSION: PN is nowadays getting a more and more widely used technique in France. This expansion is completely justified by its results and urologists must consider nephron sparing surgery as the gold standard treatment for renal tumours measuring less than 4 cm.

The nanostructure of porous cobalt coatings deposited by magnetron sputtering in helium atmosphere.

In this work, (scanning) transmission electron microscopy has been used to study the nanostructure of porous cobalt coatings obtained by magnetron sputtering using helium as process gas. This nanostructure consists of closed pores of different nanometric size (about 4-20 nm) that are distributed all over a nanocrystalline Co matrix and filled with the deposition gas. Spatially resolved electron energy-loss spectroscopy analysis was applied to measure and map, with high lateral resolution, the relevant physical properties (density, pressure and He-K edge shift) of helium trapped inside these individual nanopores, in order to provide new insights about the growth mechanism involved in such systems. In particular, a coefficient of proportionality, C = 0.039 eV nm3, between the blue shift of the He K-edge and the He density has been found. In addition, very high He densities (10-100 at./nm3) and pressures in the gigapascal range (0.05-5.0 GPa) have been measured. The linear dependence of these parameters as a function of the inverse radii obeying to the Laplace-Young law for most of the pores suggests that their formation during the coating's growth takes place in regime of elastic deformation of the Co matrix.

Engineering of III-Nitride Semiconductors on Low Temperature Co-fired Ceramics.

This work presents results in the field of advanced substrate solutions in order to achieve high crystalline quality group-III nitrides based heterostructures for high frequency and power devices or for sensor applications. With that objective, Low Temperature Co-fired Ceramics has been used, as a non-crystalline substrate. Structures like these have never been developed before, and for economic reasons will represent a groundbreaking material in these fields of Electronic. In this sense, the report presents the characterization through various techniques of three series of specimens where GaN was deposited on this ceramic composite, using different buffer layers, and a singular metal-organic chemical vapor deposition related technique for low temperature deposition. Other single crystalline ceramic-based templates were also utilized as substrate materials, for comparison purposes.

Induced Responses in Phenolic Metabolism in Two Norway Spruce Clones after Wounding and Inoculations with Ophiostoma polonicum, a Bark Beetle-Associated Fungus.

Two Norway spruce (Picea abies Karst.) clones, one resistant and the other susceptible to mass inoculation with Ophiostoma polonicum Siem., were compared with regard to their phenolic compositions and chalcone synthase (CHS) and stilbene synthase activities of their phloem before and at 6 and 12 d after artificial inoculation with sterile malt agar or O. polonicum. In unwounded phloem, the resistant clone differed from the susceptible clone by the presence of taxifolin glycoside, lower concentrations of stilbene glycosides, and higher CHS activity. After inoculation, (+)-catechin concentration and CHS activity dramatically increased around the wound, particularly in the resistant clone. Stilbene synthase activity also increased, but more slowly and to a lower level, whereas the concentrations of stilbenes remained stable. Tanning ability decreased in the susceptible clone, whereas it remained stable in the resistant one. It is proposed that the induced phenolic response of Norway spruce phloem consists of an activation of the phenolic pathway, finally leading to tannins and insoluble polymers. It is suggested that resistance to O. polonicum depends on the ability of the tree to easily activate the flavonoid pathway.

Quantitative analysis of cholesterol and cholesteryl esters in human atherosclerotic plaques using near-infrared Raman spectroscopy.

Raman spectroscopy is a non-destructive analytical technique and previous results have shown that qualitative analysis of the lipid component of human atheromatous arteries is feasible. In this paper, we describe a quantitative analytical method for cholesterol and cholesteryl esters in human atherosclerotic plaques, combined with Raman spectroscopic results, using partial least-squares (PLS) regression, a statistical multivariate method based on factorial analysis. Twenty-nine human atherosclerotic pooled samples were studied and the results of Raman spectroscopy coupled with the PLS method were compared to biochemical results. The standard error of prediction was 16.1, 13.6, 1.9, 3.3 and 3.4 mg/g for total cholesterol, free cholesterol, palmitate cholesteryl, oleate cholesteryl and linoleate cholesteryl, respectively. The repeatability of Raman spectroscopy was found to be excellent. Our results show that Raman spectroscopy is a promising technique to obtain a consistent and non-destructive quantitative analysis of cholesterol and cholesteryl esters in human atherosclerotic lesions. In situ and in vivo analysis is a possibility in the near future.

Metabolism of apolipoproteins AI and AII in subjects carrying similar apoAI mutations, apoAI Milano and apoAI Paris.

ApoAI Milano (AI(M)) and apoAI Paris (AI(P)) are mutant forms of apoAI in which cysteine is substituted for arginine at residues 173 and 151 respectively leading to the formation of homodimers and heterodimers with apoAII. Heterozygous subjects with these mutants are characterized by low levels of plasma HDL cholesterol and apoAI. The present study analyzed the metabolism of the different complexes of apoAI in three subjects, two AI(M) and one AI(P), using a primed-constant infusion of trideuterated leucine. In AI(M) carriers, the mutant form was almost equally distributed in AI(M) dimer, AI(M):AII heterodimer and the monomer, whereas, in the AI(P) subject, the mutant apoAI was essentially in the apoAI(P):AII complex. Normal apoAI was low in the AI(M) subjects (20 and 16 mg/dl) but very low in the AI(P) subject (0.3 mg/dl). In the AI(M) subjects, the low levels of apoAI were due to a rapid catabolism with a normal synthetic rate. However, the apoAI kinetics were heterogeneous with a rapid catabolism of the AI(M):AII complex (FCR of 0.430 and 0.401 day(-1)) and the AI(M) monomer (FCR of 0.570 and 0.406 day(-1)) whereas the AI(M) dimer was catabolized slowly (FCR of 0.114 and 0. 118 day(-1)). In contrast, AI(P) was catabolized relatively slowly with a FCR of 0.263, 0.182 and 0.258 day(-1) for AI(P) homodimer, apoAI(P):AII heterodimer and AI(P) monomer. In the three subjects, normal apoAI was catabolized quickly, with an FCR of 0.805 and 0.601 day(-1) in AI(M) carriers and 0.526 day(-1) in the AI(P) carrier. Therefore, the low level of apoAI in the AI(P) carrier is caused by a low production rate of apoAI, particularly of normal apoAI. In conclusion, apoAI is kinetically heterogeneous in AI(M) and in AI(P) subjects. Moreover, the two mutations lead to significant differences in the kinetic behavior of mutant apoAI depending on its inclusion in its complexes.

Fish-eye disease: structural and in vivo metabolic abnormalities of high-density lipoproteins.

Fish-eye disease (FED) in humans is characterized by corneal opacities and markedly decreased plasma concentrations of high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) AI, and apo All, but no tendency to precocious atherosclerosis is present. To elucidate this paradox, the structure of HDL, the potential of serum to promote cholesterol efflux from cultured cells, and the in vivo metabolism of HDL were examined in a 53-year-old woman with a FED syndrome in association with a markedly decreased lecithin:cholesterol acyltransferase (LCAT) activity in HDL due to a mutation of the LCAT gene (Arg158 --> Cys). HDLs isolated by ultracentrifugation were small and enriched in unesterified cholesterol and phospholipids at the expense of cholesteryl esters and proteins. The apolipoprotein content showed an enrichment in apo E and apo AIV, whereas apo AI and apo All were dramatically reduced. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting using specific antibodies showed that the apo E was free or covalently bound to apo All. These particles analyzed by electron microscopy were small and round lipoproteins with a size similar to the smallest fraction of normal HDL3. The potential capacity of the serum to promote efflux from the cells was approximately 40% of control serum levels, but FED HDLs were as efficient as control HDLs in promoting cholesterol efflux from cells. To assess the metabolism of HDL apolipoproteins, in vivo apolipoprotein kinetic studies were performed using endogenous labeling techniques in the patient with FED and three control subjects. All subjects were administered D3-labeled leucine by primed constant infusion for up to 10 hours. The fractional synthetic rates (FSRs) of apo AI and apo All in the patient were 0.674 and 0.594 per day, clearly higher than in controls, 0.210 +/- 0.053 and 0.148 +/- 0.014 per day for apo AI and apo All, respectively. Apo AI and apo All production rates in the patient with FED were normal, 11.32 and 2.62 mg/kg x d, respectively, as compared with those in normal subjects, 11.45 +/- 1.23 and 2.68 +/- 0.17 mg/kg x d. These data established that hypoalphalipoproteinemia in FED was caused by marked hypercatabolism of apo AI and apo All. This hypercatabolism could be the consequence of structural abnormalities due to the selective LCAT deficiency. In conclusion, two steps of reverse cholesterol transport, cholesterol efflux and apo-HDL metabolism, appeared particularly efficient. This efficiency could participate in the absence of premature atherosclerosis in FED patients as regards the low HDL level.

Haemostasis in relation to dietary fat as estimated by erythrocyte fatty acid composition: the prime study.

We investigated whether haemostatic variables were related with dietary fatty acid composition as estimated by the fatty acid content of erythrocytes. Subjects were a subsample (n=283) of the participants in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study. Factor VII, fibrinogen, tissue-type plasminogen activator antigen (tPA-ag), plasminogen activator inhibitor type 1 (PAI-1), D-dimer and von Willebrand factor (vWf) were measured and the fatty acid composition was determined in the phospholipids of total erythrocytes by gas chromatography. Statistical analyses were performed using multiple linear regression analyses with adjustment for age, center and body mass index. tPA-ag was significantly related to the n-3 fatty acids derived from fish. This was reflected in an inverse association of all n-3 fatty acids combined with tPA-ag (beta=-0.37 ng/ml/%, 95% confidence intervals: -0.45, -0.29, P<.01). Positive and significant associations of D-dimer with arachidic and eicosamonoenoic acid were observed (P<.01). No relationships were found between fatty acids and fibrinogen, vWf, PAI-1 or factor VII. The results of this study suggest that consumption of n-3 fatty acids derived from fish may favourably influence tPA-ag.

Fatty acid abnormalities in chronic pancreatitis: effect of concomitant diabetes mellitus.

OBJECTIVE: Patients with chronic pancreatitis suffer from malabsorption and nutritional deficiencies. However there is little data available concerning the fatty acid profile in chronic pancreatitis. Diabetes mellitus, a common complication of this disease, could interfere with the metabolism of fatty acids. SUBJECTS: We therefore compared the fatty acid composition of LDL from four groups of male patients with (a) chronic pancreatitis without diabetes (ND-CP; n=12), (b) diabetes secondary to chronic pancreatitis and insulin-treated (CP-D; n=35); (c) type 1 diabetes (n=25); and (d) controls (n=20). RESULTS: The patients in both groups of chronic pancreatitis (ND-CP and CP-D) had lower mean values for linoleic acid than that seen in the type 1 DM and control groups, whereas monounsaturated fatty acids (MUFA; 18 : 1(n-9) and (16 : 1(n-7)) were significantly increased in these two groups (ND-CP and CP-D). Docosa-hexaenoic-acid (22 : 6(n-3)) was significantly decreased in the CP-D group (P>0.05), a response that could be explained by the effects of diabetes mellitus and by selenium deficiency. In this way, diabetes was associated with a decrease in the docosa-hexaenoic-acid (22 : 6(n-3); r=0.30, P=0.005), and selenium was correlated with DHA (r=0.28, P=0.029) and with the 22 : 6(n-3)/20 : 5(n-3) ratio (evaluating the delta 4 desaturation); r=0.31, P=0.022), independently of the diabetes effect. Selenium was negatively correlated with 20 : 4(n-6)/20 : 3(n-6) ratio (evaluating the delta 5 desaturase; r=-0.30; P=0.025). These results suggest that these two factors may have a role in the regulation of the desaturation process. If we consider that a ratio of 16 : 1(n-7)/18 : 2(n-6) greater than 0.086 in plasma indicates an EFAn-6 deficiency, 40% of our CP patients, 57.6% of CP-D patients and 13.6% of type 1 DM patients were involved. CONCLUSIONS: The consequences of these deficiencies are not evaluated in this disease. However, correction of the fundamental deficiencies in essential fatty acids and in selenium seems desirable in chronic pancreatitis.

XeCl laser in biliary calculus fragmentation: fluence threshold and ablation products.

The in vitro action of a xenon-chlorine (XeCl) excimer laser on biliary calculi is reported: fluence threshold and rate for ablation process are given. An analysis of gaseous products evolved during irradiation of gallstones, performed through an infrared spectrophotometric technique is also reported. Based on the different results, we discuss the mechanism of destruction.

Longitudinal distribution of brush border hydrolases and morphological maturation in the intestine of the preterm infant.

The morphological maturation and the distribution of brush border hydrolase activities were studied in the small intestine and the colon in newborn babies of 28-38 weeks gestational age. Lactase and sucrase activities were higher at term with maximal activity in the proximal intestine. In contrast, aminopeptidase and glucoamylase exhibited maximum activity in the distal part of the small bowel. Glucoamylase activity was already significant in the small intestine and in the colon of the preterm newborn. Sucrase activity present in the proximal colon of the preterm dropped to a negligible amount at term, whereas aminopeptidase activity increased, reaching values found in the small intestine. The enzymic changes occurring in the intestinal tract were related to the morphological maturation of the mucosa from fetal to adult type during late gestation. Accelerated morphological and functional maturation was observed in one preterm infant nourished intravenously for 12 days, these processes being independent of the presence of nutrients in the intestine. At term, the distal part of the intestine seems to have increased digestive capacities for peptides and polysaccharides. We present evidence that full-term, and to a lesser extent preterm infants are able to hydrolyse glucose polymers.

Early human hand morphology: an estimation of fetal age.

Fetal hand morphogenesis was studied between 6 and 14 weeks of gestation by scanning electron microscopy. Detailed observations of surface features allowed three individualized phases of hand development to be distinguished, related to the shape (6 to 10 weeks), to the appearance of creases (10 to 13 weeks) and of ridges (13 weeks onwards).

Maturation of brush border hydrolases in human fetal intestine maintained in organ culture.

This investigation was undertaken to study the effects of hormones, sugars and amniotic fluid on the maturation of brush border enzymes in the human fetal intestine, at early stages of gestation. Intestinal explants from 8-13-weeks fetuses were maintained in organ culture for 3 days in the presence of the agents to be tested. The data show that the explanation of human fetal gut in a serum free culture medium elicits a significant maturation (2-4-fold increase above preculture levels) of lactase and aminopeptidase whatever the gestational stage studied and of sucrase and alkaline phosphatase at specific stages of development. To be expressed, the overall maturation needs the presence of sugar (in particular glucose) in the culture medium. The addition of dexamethasone, insulin or amniotic fluid to the medium did not further enhance brush border enzyme activities except for lactase whose levels were doubled by the dexamethasone. The present data suggest that in addition to the differences which exist among mammalian species in the timing of enzyme development, there may be a species specificity in the factors involved in fetal enzymatic maturation.

Developmental pattern of brush border enzymes in the human fetal colon. Correlation with some morphogenetic events.

The present study is concerned with a multilevel approach to human colon organogenesis, involving scanning and transmission electron microscopy together with brush border enzymology. The results emphasize the particular developmental pattern of sucrase activity which appears towards 11 weeks, increases at 14 weeks, begins to decrease around 28 weeks and disappears totally at term. In contrast, other enzymes like aminopeptidase and alkaline phosphatase persist in the adult colon. The correlation, in the fetal large bowel, of enzyme activities and villus structures similar to those found in the small intestine is discussed.