Photocatalytic conversion of gaseous nitrogen trichloride into available chlorine--experimental and modeling study.

In water, chlorine reacts with nitrogen-containing compounds to produce disinfection byproducts such as nitrogen trichloride which induces ocular and respiratory irritations in swimming pool workers. A technical solution has been used to reduce NCl3 exposure to acceptable levels, by adding a stripping step to the water recycling loop. The pollutants extracted are currently rejected into the atmosphere without treatment. However, the physical properties of NCl3 could be harnessed to induce its controlled degradation by direct or indirect light. This paper describes the way to transform NCl3 into oxidizing chlorine by photocatalysis under laboratory conditions. Photocatalytic oxidation efficiently degrades gaseous nitrogen trichloride, producing compounds such as HClO. About 60% of NCl3 decomposed was converted into HClO which could be used as a disinfection compound. A kinetic model is proposed for the photocatalytic process based on a convection/diffusion model. The Langmuir-Hinshelwood model was applied to the chemical part of the mechanism. The apparent quantum yield was also estimated to assess the optimal irradiance for NCl3 transformation. The results show that photocatalysis performs much better than photolysis alone for NCl3 removal, i.e. at least 25 times more efficient.

[Precariousness, DRG's and health planning: pilot study at the Lariboisière hospital in Paris]. / Précarité, tarification à l'activité et planification sanitaire et sociale: étude pilote à l'hôpital Lariboisière de Paris.

OBJECTIVES: This paper considers the specific administrative procedures set up by managers of public healthcare establishments and those responsible for health and welfare policies to care for low-income pregnant women for whom 100% of the "price per act" (T2A) is refunded. What are the limitations and what improvements can be suggested? PATIENTS AND METHOD: The results are based on an analysis of data from semi-structured interviews, legislation and documents. RESULTS: The State, health insurance systems, public health establishments, local authorities, charities and outpatient services are involved in handling low-income parturients in different services and different establishments, both locally and regionally. A health and welfare policy comprising specific, coordinated actions and measures has been developed. The T2A "price per act" system may threaten its survival: the limited number of front-line facilities is often saturated and demand is increasing, treatment is often reduced to reactive management leading to unwanted readmissions, ethics are sometimes called into question and there is a risk of patient selection. DISCUSSION AND CONCLUSION: This pilot study provided some encouraging information but also indicated the limitations of the approach adopted. However, it was still of interest to see whether it was possible to use this approach, which did not require considerable resources, to reveal useful markers. This appeared to be the case. Regional Health Agencies (ARS) and local authorities could support the system. Additional funding is needed.

Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor.

Heterologous expression of the human neurotensin receptor type I (hNT1-R) has been achieved in the yeast Saccharomyces cerevisiae. Immunoanalysis of membranes prepared from cells expressing a c-myc-tagged version of hNT1-R revealed multiple c-myc cross-reacting polypeptides of high molecular mass, suggesting that hNT1-R was glycosylated in yeast. High-affinity binding sites for 125I-labeled-[monoiodo-Tyr3]neurotensin ([125I-Tyr3]NT) were detected on hNT1-R-expressing cells with Kd and Bmax values of 3.2 nM and of 500 receptors per cell, respectively. Competition binding studies of neurotensin with SR142948 and SR48692, two nonpeptidic antagonists of hNT1-R, indicated that the yeast-produced recombinant receptor displayed the same pharmacological properties as hNT1-R expressed in mammalian cells. Interestingly, neurotensin activated the pheromone pathway in hNT1-R-expressing cells in a dose-dependent fashion, as revealed by a beta-galactosidase activity assay with a pheromone-responsive Fus1:lacZ construct. Mutational inactivation of the SST2 and STE2 genes increased the level of beta-galactosidase activity in response to neurotensin by twofold. Recombinant hNT1-R-producing cells, which lacked the endogenous G-protein-coupled receptor for the alpha pheromone, mated with wild-type MATalpha haploid cells in response to neurotensin, leading to bona fide diploid zygote formation. This is the first report of a mammalian receptor that can replace the endogenous pheromone receptor when produced in yeast, by signaling a fully effective, agonist-induced, mating process.

[Intensive chemotherapy and autograft of hematopoietic stem cells in the treatment of metastatic cancer: results of the national protocol Pegase 04]. / Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques (CSH) dans le traitement des cancers du sein métastatiques: résultats du programme national Pegase 04.

UNLABELLED: We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients. PATIENTS AND METHODS: Inclusion criteria were: age < or = 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide: 120 mg/kg, Melphalan: 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled: 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response. RESULTS: The median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12). CONCLUSION: The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival.

Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

Molecular cloning of a levocabastine-sensitive neurotensin binding site.

A search for sequences homologous to the neurotensin receptor cDNA in a rat hypothalamic library has identified a novel neurotensin receptor (NTR-2). The 1539 bp cDNA encodes a 416 amino acid protein and shows highest homology to the previously cloned neurotensin receptor (NTR-1) (64% homology and 43% identity). Binding and pharmacological studies demonstrate that NTR-2 expressed in COS cells recognizes neurotensin (NT) with high affinity as well as several other agonists and antagonists. However, a fundamental difference was found; unlike NTR-1, NTR-2 recognizes, with high affinity, levocabastine, a histamine H1 receptor antagonist previously shown to compete with NT for low-affinity binding sites in brain.

Stabilization of the hydrophilic sphere of iobitridol, a new nonionic iodinated contrast agent.

The chemotoxicity of iodinated contrast agents is essentially related to the spatial accessibilty of lipophilic and polarizable iodine atoms. This accessibility was examined in iobitridol by HPLC and 1H- and 13C-NMR spectroscopy,taking into account both the static distribution of the hydrophilic groups around the triiodinated benzene ring and in particular the dynamic modulation of this distribution. The aim of this latter parameter is to prevent distortion of the hydrophilic sphere of nonionic agents when faced with a hydrophobic environment. Iobitridol is characterized by 2 tertiary carbamoyl substituents whose high rotation barriers (deltaG*353=27.6 kcal for E/Z-rotation and deltaG*345=17.3 kcal for syn/anti-rotation) stabilize the hydrophilic sphere. The 3rd dihydroxylated anilide substituent does not undergo SMILES rearrangement and provides iobitridol with its even hydrophilic distribution. Iobitridol presents remarkable chemical solubility (>140% m/v) and stability. The iobitridol molecule was specifically designed with the aim of stabilizing the hydrophilic sphere around the triiodinated benzene ring, therefore permanently masking access to the iodine atoms. This new concept represents a further step forward towards the synthesis of new iodinated contrast agents which should be totally inert vis-a-vis biological membranes and proteins.

[Cancer of the testis, sarcoidosis and neurinoma]. / Cancer du testicule, sarcoïdose et neurinome.

The association of testicular cancer, sarcoidosis and neuroma is reported. Review of the literature revealed the rarity of the association of testicular cancer and sarcoidosis which is probably a chance association, but which is important in the context of staging, as overstaging may lead to useless or even dangerous treatment.

[Advanced testicular seminoma: treatment of residual masses after chemotherapy. A review of 3 cases]. / Séminomes testiculaires évolués: traitement des masses résiduelles après chimiothérapie. Réflexions à partir de 3 observations.

Based on 3 cases of advanced testicular seminoma classified as stage IIC, the treatment of residual masses after chemotherapy is discussed. The excellent therapeutic response confirmed by histological study of the residual masses, which show a fibrotic or necrotic appearance, allows the adoption of a strategy using imaging techniques: either there is persistence of a gland mass syndrome and resection needs to be carried our or retroperitoneal fibrosis is visualised and careful follow up would appear to be sufficient.

[Exeresis of residual masses of germinal tumors of the testis after chemotherapy]. / L'exérèse des masses résiduelles des tumeurs germinales du testicule après chimiothérapie.

Between 1978 and 1988, amongst the 184 patients treated at the Hôpital du Val de Grâce for a testicular germ cell tumour, 47 patients underwent resection of residual masses after chemotherapy: 27 patients were classified as stage II and 20 were classified as stage III. The chemotherapy, administered for 3 to 6 cycles, used three types of protocols: VAB 6, PVeBV or BEP. Resection of residual masses was only undertaken after return to normal of the biological markers with persistently abnormal medical imaging. Histology of the testicular tumour revealed 3 seminomas and 44 non-seminomatous germ cell tumours. The histology of the residual masses after retroperitoneal lymphadenectomy (42 operations), thoracotomy (9 operations) or craniotomy (1 operation) revealed 22 cases of fibrosis or necrosis (47%), 10 cases of teratoma (21%), 8 cases of cancer (17%) and 7 normal cases (15%). The progression towards fibrosis, necrosis or nature teratoma is synonymous with cure, but the persistence of cancer cells corresponds to a very poor prognosis even after salvage treatment.

[Self assessment of the stages of sex maturation in male adolescents]. / Auto-estimation des stades de maturation pubertaire chez les adolescents de sexe masculin.

Self-assessment of sexual maturation was evaluated in 319 adolescent boys aged 10 to 18 years. Sexual maturation rates were defined by physicians based on physical examination and by adolescents on the basis of five standard photographs corresponding to Tanner's five sexual maturity ratings [5]. For genital development, the agreement between physician and boys is poor. It is good for pubic hair development. The assessments were age-dependent. The use of adolescent self-staging appears of value in studying puberty and adolescence.

Adiposity indices and clinical opinion.

The comparison of various adiposity indices in children and adolescents shows that there is a great similarity between the indices, and also between their ability to distinguish extreme groups. The adiposity indices used are highly correlated with weight and subscapular skinfold thickness, and are not generally independent of height. Differences in these correlations appear during the period of puberty. Discrimination of obese and non-obese subjects by the indices and by clinical opinion agrees in 65%-75% of instances, with no one index agreeing better than the others.

[Biological markers and germinal tumors of the testis. Value and limitations of the assay of chorionic gonadotrophin hormone and alpha-fetoprotein]. / Marqueurs biologiques et tumeurs germinales du testicule. Intérêts et limites du dosage de l'hormone chorionique gonadotrope (HCG) et de l'alpha-foeto-protéine (AFP).

Between 1978 and 1985, 128 patients with germinal tumors of the testes were treated at the Val-de-Grâce Hospital; biological market levels--beta HCG and AFP--were determined before and after orchidectomy in the peripheral blood and during orchidectomy in testicular blood in 76 patients. HCG levels were elevated in 13% of seminomas and HCG and/or AFP levels were elevated in 76% of non seminomas; the sensitivity of the determination was greater in testicular blood. However, in our study, there was no parallelism between marker levels before orchidectomy and tumor stage or prognosis. The change in HCG and/or AFP levels appears to an index of the response to therapy: 4 patients with high HCG and/or AFP levels during chemotherapy died. The diagnosis of recurrence is not always documented by elevated marker levels and monitoring must always documented by elevated marker levels and monitoring must always include both determination of marker levels and imaging.

Sister chromatid exchanges in patients with retinoblastoma.

Spontaneous and mitomycin C(MMC)-induced sister chromatid exchanges were studied in 11 patients with retinoblastoma and 7 normal controls. Spontaneous rates were similar in patients and in controls. The MMC-induced rate was found to be significantly higher in bilaterally affected patients than in controls. It is suggested that this increase may be due to a DNA repair deficiency. However, it is not possible to clarify whether this abnormality is associated with the retinoblastoma gene or with another factor acting on the degree of expressivity of the disease in gene carriers.

Segregation analysis in hereditary retinoblastoma.

Segregation analysis was performed in 211 nuclear families belonging to 166 pedigrees of hereditary retinoblastoma found in a number of series which have been gathered from the literature. Bilaterally affected carriers appear homogeneous. The segregation ratio in their offspring is 0.49 and the proportion of bilateral cases among affected offspring is 0.87. Both unilaterally affected and unaffected carriers appear heterogeneous. The very low segregation ratio (0.08) in the offspring of unilateral carriers who are not detected through an affected child, suggests the possibility of two types of carriers. "high" and "low transmitters." The proportions of "low transmitters" was estimated as 0.14 among all familial unilateral carriers and as 0.45 among all detected unaffected carriers. Unilateral and unaffected "high transmitters" give a significantly lower segregation ratio than bilaterally affected carriers. On the one hand, the existence of these two different types of carriers provides arguments in support of the hypothesis of delayed mutation. On the other hand, the differences in penetrance among "high transmitters." according to their phenotype, supports the hypothesis of host resistance. Under the two-mutation hypothesis, the possibility that the mutation rate is variable among individuals and partly genetically determined, is suggested.

Excess of cancer deaths in grandparents of patients with retinoblastoma.

An excess of cancer deaths was found in grandparents of 308 children with retinoblastoma. This excess was found in all types of retinoblastoma, unilateral and bilateral, sporadic and familial. We postulated that the excess could be the result of a factor of susceptibility to cancer, different from the retinoblastoma gene, which would increase the mutation rate in retinal and germ cells as well as in other tissues.

Mutation theory of carcinogenesis in retinoblastoma.

To test Knudson's hypothesis that two successive mutations are involved in retinoblastoma, we studied the data on 899 cases. Some of the findings appeared to differ from those that might be expected if Knudson's hypothesis were correct. Certain criticisms of Knudson's methodology and model were suggested. Alternative explanations proposed were 1) the role of the sequence in which mutations occur, and 2) the possibility of three mutational events.

[Poland's syndrome. Clinical and genetic studies; physiopathologic considerations]. / Le syndrome de Poland. Etudes clinique et génétique - considérations physiopathologiques

Study of malformations of the hand makes possible the definition of three forms of progressive severity in the Poland syndrome, in which there is unilateral symbrachydactylie associated with homolateral aplasia of the pectoralis major. The three forms share the predominance of involvement of the 2nd, 3rd and 4th fingers. The existence of alterations in palmar creases and dermatoglyphia of the involved side alone confirms the absence of any lesion, even infra-clinical, of the other hand. Genetic study favours a pluri-factorial inheritance. Topographical data and the comparative study of vascularisation suggest the possibility of hypoplasia of the proximal portion of the sub-clavian at the origin of this malformative association.