Is pathological complete response after a trimodality therapy, a predictive factor of long-term survival in locally-advanced esophageal cancer? Results of a retrospective monocentric study.

OBJECTIVE: To evaluate long-term (5- and 10-year) survival and recurrence rates on the basis of the pathological complete response (pCR) in the specimens of patients with esophageal carcinoma, treated with trimodality therapy. METHODS: Between 1993 and 2014, all consecutives patients with esophageal locally-advanced non-metastatic squamous cell carcinoma (SCC) or adenocarcinoma (ADC) who received trimodality therapy were reviewed. According to histopathological analysis, patients were divided in two groups with pCR and with pathological residual tumor (pRT). The primary endpoint was overall survival (OS). The secondary endpoints included the disease-free survival (DFS), the recurrence rate, and the predictive factors of overall survival and recurrence. RESULTS: One hundred and three patients were included: 49 patients with pCR and 54 patients with pRT. The median OS was significantly longer in pCR group than in pRT group (132±22.3 vs. 25.5±4 months), with both 5- and 10-years OS rates of 75.2% vs. 29.1%, and 51.1% vs. 13.6%, respectively (P<0.001). Also, pRT, major postoperative complications (Dindo-Clavien grade>IIIb) and recurrence were the 3 independent predictive factors for worse OS. CONCLUSIONS: Patients with locally-advanced oesophageal carcinoma, who responded to trimodality therapy with a pCR, could be achieved a 10-year survival rate of 51%.

Genetic heterogeneity of glycogen storage disease type Ia in France: a study of 48 patients.

Forty-eight patients with glycogen storage disease type Ia (GSD Ia) were studied. Using a combination of single-strand conformation polymorphism (SSCP) analysis, restriction enzyme digestion and direct sequencing, we were able to identify 93/96 mutant alleles, comprising 23 different mutations in the glucose-6-phosphatase gene (G6PC). Among these, 7 are novel mutations of G6PC: M5R, T111I, A241T, C270R, F322L, and two deletions, 793delG and 872delC, resulting in the same mutation at the amino acid level, fs300Ter (300X).

Simultaneous determination of hemoglobin and coproporphyrin by second derivative differential spectrophotometry: application to the diagnosis of meconium aspiration.

We describe a simple, fast method for simultaneous measurement of hemoglobin and coproporphyrin in urine and amniotic fluid, by second-derivative differential spectrophotometry. Both pigments were determined in biological samples without prior extraction. Despite the slightly overlapping spectra, the method permitted satisfactory resolution and avoided interspectral interference. Its sensitivity, sufficiently good, allowed to detect hemoglobin and coproporphyrin in slightly pathological urine and amniotic fluid as an aid to the diagnosis of meconium aspiration.

Changes in phospholipid composition of tracheal aspirates from newborns with hyaline membrane disease or transient tachypnoea.

Phospholipid analysis of tracheal aspirates obtained from 37 newborn infants, all intubated for respiratory diseases, was performed in order to compare infants having hyaline membrane disease (HMD) (n = 11), to those presenting with transient tachypnoea (TT) (n = 16) or another respiratory disorder (n = 10) and to determine if distinguishing features could be discovered for HMD or TT. In the HMD group, a significantly lower amount (about 20%) of recoverable phospholipid material was observed. Furthermore, the groups differed in their phospholipid profile: infants with HMD presented with a deficiency in saturated phosphatidylcholine, but had a related increase in unsaturated phosphatidylcholine, and an increased proportion of phosphatidylethanolamine (about 2.5 times more) as compared with both other groups. In infants suffering HMD and TT, phosphatidylglycerol was lower and phosphatidylinositol was higher than in infants with other diseases. This change was the only one displayed in infants with TT. We speculate that the observed changes reflect changes in amount and composition of surfactant and are involved in the etiology of HMD and TT.

Lactate dehydrogenase isoenzyme activity in malignant haematological diseases.

The isoenzymes 1 and 2 (LDH1 and LDH2) of lactic dehydrogenase (LDH) were studied in the serum of 32 patients with malignant haematological diseases. In non-Hodgkin lymphoma (NHL) a diminution in LDH1 and an increase in LDH2 was a sign of evolution towards a more aggressive phase of the disease, or the absence of clinical remission, even when no significant variation of total LDH can be observed in the serum. In acute lymphoblastic leukaemia (ALL), the isoenzymatic variations are not an early indication of relapse. No significant variations in serum LDH or of these isoenzymes was observed in chronic lymphocytic leukaemia (CLL) or Hodgkin's disease (HD). Only in NHL did the variations of LDH1 and LDH2 appear to be a biochemical marker of the tumour process and of cellular differentiation.

Implication of apolipoprotein E and the L-arginine-nitric oxide system in preeclampsia.

OBJECTIVE: During pregnancy, Apolipoprotein (Apo) E is synthesized in the placenta to facilitate the uptake of maternal lipoproteins. Preeclampsia is associated with an abnormal lipid profile. Apo E levels may affect the production of nitric oxide. We investigated whether Apo E variations could be related to the high lipid levels and nitric oxide secretion in preeclamptic women. METHODS: Blood samples from 15 normotensive women and 12 mild and 23 severe cases of preeclampsia were assayed for standard lipid profile, Apo E, and nitrate. Urine samples were analyzed for nitrate and cyclic GMP. RESULTS: In women with mild preeclampsia, the triglyceride concentration was significantly higher (p < 0.05) than in normotensive women (3.30 +/- 1.38 versus 2.31 +/- 0.92 g/L) and associated with a higher (p < 0.01) triglyceride/Apo E ratio (0.71; range = 0.40-1.70). In women with severe preeclampsia, the triglyceride/Apo E ratio was similar to normotensive women [0.39 (range = 0.18-1.19) versus 0.41 (range = 0.18-0.79)] associated with a normal triglyceride level and a twofold higher serum nitrate level [36 (range = 1-63 mumol/L) versus 14 (range = 1-37 mumol/L)]. CONCLUSION: The triglyceride/Apo E ratio is significantly higher in mild preeclampsia. In the severe form, this ratio is similar to that of normotensive pregnant women, probably due to a better uptake of triglyceride. Moreover, in the severe form, it is associated with a twofold normal serum nitrate level. Thus, Apo E and the nitric oxide status may be implicated in preeclampsia.

Urinary cGMP levels during pregnancy with and without uterine contractions.

OBJECTIVE: The purpose of this study was to investigate the nitric oxide-cGMP (NO-cGMP) system by urinary cGMP level determinations in pregnant women with and without uterine contractions. DESIGN AND SUBJECTS: cGMP expressed in nmol/mmol of creatinine was performed by radio immuno-assay (Amersham UK) in urine samples obtained from 94 pregnant women with non-complicated pregnancies. Population A without contractions (n = 62) was divided into three groups according to the gestational age (group I, < or = 15 weeks; group II, 16-33 weeks; group III, > 33 weeks). The group III from A population was compared to B population (of the same gestational age) presenting uterine contractions (n = 32). RESULTS: In A population, no significant urinary cGMP level differences were observed whatever the gestational age. Nevertheless, the comparison between patients with or without uterine contractions (A III and B populations) showed a significant difference by a variance analysis (P < 0.05). Lower levels of cGMP were seen when uterine contractions occurred. CONCLUSION: Urinary cGMP levels are significantly decreased in pregnant women with uterine contractions, without any difference from early to late pregnancy. These results, completed by more precise investigations, could suggest that the NO-cGMP system might be implicated in uterine quiescence.

[Enzymatic determination of sodium, potassium and chloride in plasma]. / Le dosage enzymatique du sodium, du potassium et du chlorure dans le plasma.

The Boehringer enzymatic reagents for Na, K and Cl determination on a Hitachi 717 automatic analyser at 37 degrees C were evaluated. Except for Na, the within-run and between-run precision assays gave CV within the SFBC ranges but were higher than those of the comparison analysers: Ektachem 500 Kokak, Dimension Ars Du Pont-De-Nemours and flame photometry. The linear ranges were larger than the usual clinical results. Accuracy, estimated from human controls, was 99 to 103% for Na and K, and 105% for Cl. Comparison of plasma from 102 to 152 patients showed a good concordance for sodium with the Dimension ARS (y = 1x + 0). On the contrary, with Ektachem Kodak, differences appeared, particularly for high values (y = 0.91x + 13.6). For potassium, the concordance was good with flame photometry (y = 1x + 0.1) and Ektachem Kodak (y = 0.94x - 0.16). For chloride, comparison was satisfactory except for high values which were underestimated by the enzymatic method: Dimension ARS (y = 1.03x - 4.8), Ektachem Kodak (y = 0.91x + 9.8). The enzymatic methods were very easy to perform and can be adapted on any autoanalyser at 37 degrees C. We conclude that they are suitable for routine clinical determination. Urinary assays are currently being developed.

[Development of a rapid method of immunoassay of C reactive protein by polarization of fluorescence]. / Evaluation d'une méthode rapide d'immunodosage de la protéine C réactive par polarisation de fluorescence.

Increased level of C reactive protein in the serum of neonates indicates the presence of infection, whereas the classic signs (hyperthermia, neutrophilia...) may often fail. So the determination of C reactive protein is useful and has to be rapidly performed on a small quantity of blood. The authors evaluate a fluorescence-polarization immunoassay (TDX Abbott System), and compare this method to the radial immunodiffusion (RID) and the laser immunonephelemetry. Sensitivity (detection limit = 10 mg/l), reproducibility (cv less than 5 p. cent), linearity (until 243 mg/l), are satisfactory. The assay correlates well with RID (r = 0.98, p less than 0.001) and laser immunonephelometry (r = 0.93, p less than 0.001). The proposed method is rapid (10 minutes), requires small quantities of blood (less than 100 microliters), and is not influenced by important amounts of haemoglobin, bilirubin or triglycerides. Thus, this method provides a good means for C reactive protein determination, especially in neonates.

[Biochemical aspects of amniotic fluid aspiration]. / Aspects biochimiques de l'inhalation amniotique.

The authors propose a simple, quick and reliable biochemical method for diagnosis of amniotic aspiration in the newborn infant. The optical density of the infant's first urine is determined at 420, 390 and 405 nm. A urinary meconial index (IMU) is computed from these values. A meconial amniotic inhalation must be suspected if this index is greater than one. The presence of coproporphyrins identified in urine of infants having inhaled meconial amniotic fluid seems to be at the origin of the spectral characteristics of pathological urines.

[Refinement and role of the diagnosis of Gilbert disease with molecular biology]. / Mise au point et intérêt du diagnostic de la maladie de Gilbert par biologie moléculaire.

Gilbert syndrome (GS), characterized by mild, chronic and isolated unconjugated hyperbilirubinemia is due to a partial deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1). Recently, the genetic basis of GS has been identified in caucasian populations : it is related to the insertion of a dinucleotide (TA) in the promoter region of the UGT1A1 gene. In Asian populations, GS is due to missense mutations (either homozygous or heterozygous) in the coding sequence. The aim of this study was to develop a simple and rapid method to detect both genetic polymorphisms and mutations. This technique was performed (1) to explore unrelated unconjugated hyperbilirubinemia; (2) to evaluate the frequency of GS in a population of 97 healthy caucasian volunteers: 17% of them were homozygous for the TA7/TA7 polymorphism; (3) to determine the incidence of this syndrome in a population of 105 neonates with unconjugated hyperbilirubinemia. The incidence of GS (15%) was not significantly higher than it was in the control group. A correlation between GS genotype and neonatal jaundice was not established; (4) to seek a relationship between GS and preeclampsia with or without Hellp syndrome. The incidence in the Hellp syndrome group (n = 19) was 26%, two fold higher than in preeclampsia group (n = 22) and control group (n = 50) with only 14% and 13% respectively, (5) to start a study regarding the toxicity of irinotecan treatment in a population of homozygous children for the UGT1A1 polymorphism.

[Carbimazole and leukocytoclastic vasculitis: apropos of a case]. / Carbimazole et vascularite leucocytoclasique: à propos d'un cas.

INTRODUCTION: The authors describe the case of biopsy-proven cutaneous leukocytoclastic vasculitis secondary to treatment with carbimazole. EXEGESIS: A 78-year-old white female developed erythematous macules on the lower limbs which cleared after discontinuation of her current treatment and implementation of oral steroid therapy. Causal explorations (lack of systemic disorder or infectious disease) remain negative, except for positive immune complexes. This case clearly differs from the two cases of microvasculitis (myositis and nephritis) secondary to treatment with carbimazole previously mentioned in the literature. CONCLUSION: To our knowledge this is the first report of biopsy-proven cutaneous leukocytoclastic vasculitis associated with this antithyroid agent. Its widespread use makes awareness of the side-effect important.

[Phosphatidylglycerol in amniotic fluid. Value of rapid determination using an immunologic technic]. / Le phosphatidylglycérol dans le liquide amniotique. Intérêt de son évaluation rapide à l'aide d'un test immunologique.

We have studied 55 samples of amniotic fluid taken by amniocentesis from 32 women, most of whom had arterial hypertension, with or without intra-uterine growth retardation; with or without uncertainty as to their dates. Fetal pulmonary maturity was estimated by determining the lecithin/sphingomyelin (L/S) ratio and the levels of phosphatidylglycerol (PG) in 55 samples. The semi-quantitative levels of PG were worked out using a simple and rapid immunological method. Our results show that there is a good correlation between the two tests. The level of PG is, however, more specific than the L/S ratio, for which we found some false negatives. In particular, there were 7 samples looked at 48 hours before delivery which showed an L/S ratio lower than 2 and a PG at or above 2 micrograms/ml. None of these 7 had hyaline membrane disease. Furthermore the simplicity and speed of this test make it possible to use it routinely.

[Fast determination of pulmonary surfactant in amniotic fluid using fluorescent polarization (FLM test Abbott)]. / Détermination rapide du surfactant pulmonaire dans le liquide amniotique par polarisation de fluorescence (FLM test Abbott).

A study of 60 amniotic fluids obtained by amniocentesis shows that the measurement of total surfactant phospholipids by the TDX Fetal Lung Maturity assay makes it possible to predict accurately fetal lung maturity. A sensitivity of 100% is similar to that of other tests currently used but with a higher specificity (93% instead of 65% for the L/S ratio and 55% for the phosphatidylglycerol). The phospholipid/albumin ratio is carried out automatically by means of a fluorescence polarization method with the TDX Abbott apparatus. A cut off value of 50 mg/g should be considered as a good fetal lung maturity indicator. The population studied was composed of women with an arterial hypertension (n = 6), diabetes (n = 9) preterm premature rupture of the membranes (n = 8), gemellary pregnancy (n = 5) or with a risk of premature outcome (n = 10). In all cases delivery occurred within 24 hours after the amniocentesis. The average gestational age was 36 weeks. Seven newborns (11%) presented hyaline membrane disease. In conclusion, this simple and rapid test seems to be adequate to evaluate with accuracy the fetal lung maturity in abnormal pregnancies. It must however, be associated with the determination of phosphatidylglycerol, when the fluid is contaminated by blood or meconium.

[Gestational age and fetal lung maturity]. / Age gestationnel et maturité pulmonaire foetale.

In order to assess the lung maturity of the fetus, a biochemical analysis using two reliable, simple and rapid methods (FLM-TDX Abbott and determination of phosphatidylglycerol (PG) have been carried out on 166 amniotic fluids taken by amniocentesis. The patients were particularly pregnant women presenting disorders such as diabetes (n = 41), premature rupture of the membranes (n = 30), hypertension (n = 20), intra uterine growth retardation (n = 13) and gemellar pregnancies (n = 27). The lung maturity of the fetus has been considered as mature (no risk of any hyaline membrane disease: HMD) when the phospholipid rate is higher than 50 mg/g albumin (FLM-TDX Abbott), associated or not with the presence of PG (PG positive). The latter phospholipid was present only in women whose pregnancy was about 35 weeks. Besides, our results show a very large disparity of the phospholipid rates (FLM-TDX) in the amniotic samples for an identical gestational age. Values from 9 to 124 for pregnancies with term of 31 weeks, and from 21 to higher than 160 for those of 38 weeks. In infants born not later than 48 hours after the amniotic punction (n = 30), four of them presented an HMD. The FLM-TDX values were less than 30 for three cases and equal to 52 for the fourth. The term of these newborns was 37 weeks or more for three of them, and 31 weeks for the last one. Our study confirm that the TDX-FLM Abbott is useful to assess the fetal lung maturity and does not correlate with the gestational age.

[A study of fetal pulmonary maturity using amniotic fluid obtained from the vagina after premature rupture of membranes]. / Etude de la maturité pulmonaire foetale dans le liquide amniotique prélevé par voie vaginale aprés rupture prématurée des membranes.

Amniotic fluid was obtained from the vagina not more than 24 hours before delivery in 100 patients who had premature rupture of the membranes. Thirty per cent of these cases had contamination with blood or with meconium. Phosphatidylglycerol (PG) estimate the degree of lung maturity using an immunological method (AMNIOSTAT-FLM test). In the 22 cases where the gestational age was 35 weeks or less there were two cases of hyaline membrane disease. In 68% of the 22 cases, the PG was negative, intermediate in 14% and positive in 18%. One of the cases of hyaline membrane disease was accompanied by fluid that was not infected and that was negative for PG; the other case had infection with S. faecalis and the PG was intermediate. On the other hand in the 78 cases when the pregnancies had lasted longer than 35 weeks there were no children who had hyaline membrane disease. The PG reaction was positive in only 57% of these cases. Search for bacteria showed infection in 10 cases (three with alpha-haemolytic streptococci, four with group B beta-haemolytic streptococci and three with E. coli). Determination of PG on the supernatant of reference strain cultures showed positive results for S. faecalis and E. coli. In conclusion, the poor specificity of the test (48%) and the possibility that when there was bacterial contamination false positive results were obtained shows that looking for fetal maturity by testing amniotic fluid from the vagina is unreliable and is contra-indicated.

[Clinical, haemodynamic and genetic features of familial pulmonary arterial hypertension]. / Caractéristiques cliniques, hémodynamiques et génétiques de l'hypertension artérielle pulmonaire familiale.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is defined by a raised pressure in the pulmonary arterial circulation associated with small vessel narrowing due to proliferation of the endothelium and vascular smooth muscle. Idiopathic PAH should be distinguished from PAH associated with a causal disease. One familial type (familial PAH), gathered from one family, has recently been linked to a mutation of the BMPR 2 (bone morphogenetic protein receptor 2) gene. It seems important to compare the idiopathic form of PAH with these familial forms to confirm that the same diagnostic and therapeutic principles can be applied to familial PAH. MATERIAL AND METHODS: The demographic, clinical, haemodynamic and prognostic data from 34 cases of familial PAH were compared with those of 451 cases of idiopathic PAH. The genetic characteristics of the familial forms were also defined. RESULTS: Familial PAH presented at a younger age than idiopathic PH (31 +/- 15 vs. 45 +/- 18 years p=0.002) without any other demographic difference (sex-ratio 2.09/1 et 1.42/1 p=NS). There was no difference in exercises tolerance (6 minute walking test 341 +/- 98 and 289 +/- 135 metres p=NS), in haemodynamic parameters (mean PAP 65 +/- 12 and 62 +/- 15 mmHg, p=NS), or in prognosis, with the exception of an absence of a vasodilator response in the familial group to nitric oxide challenge. We found the BMPR 2 gene mutation to be quantitatively and qualitatively comparable to previously published data. CONCLUSION: The only difference between these two forms of this illness were of a younger age at presentation and an absent vasodilator response in the familial PAH group. We do not propose that familial PAH should be treated any differently from the idiopathic form. Genetic counselling will need to be developed in line with the progress being made in the understanding of this condition.