The chronic liver disease in patients with short bowel syndrome: etiology and treatment.

Short bowel syndrome is a life threatening disease with a high mortality and morbidity. Since home parenteral nutrition (PN) has been established, there is an increasing number of patients surviving the acute loss of bowel function. But on the long-time these patients suffer from different complications of PN, with loss of central venous access, recurrent sepsis and finally the syndrome of progressive cholestatic liver disease. Both loss of central venous access and especially the progressive cholestatic liver disease are the limiting factor for the long-term survival of patients suffering from intestinal failure. Interestingly, the pathophysiologic mechanisms of PN induced intrahepatic cholestasis have not been dissolved yet and seem to be of multifactorial genesis. Cholestasis has shown to be associated with prematurity, recurrent sepsis, enteral and PN, especially with lipid emulsions. Enteral feeding and a well-controlled regime of PN lower the incidence of end-stage liver disease and, therefore, has to be optimized in the therapy of these patients.

Independent prognostic significance of cell cycle regulator proteins p16(INK4a) and pRb in advanced-stage ovarian carcinoma including optimally debulked patients: a translational research subprotocol of a randomised study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group.

The purpose of the study is to test the hypothesis that expression of cell cycle regulatory proteins p16(INK4a) and pRb is significantly associated with prognosis in ovarian carcinomas. We performed immunohistochemical analysis of p16(INK4a) and pRb expression and correlated with survival in a series of 300 patients with FIGO stage IIb-IV ovarian carcinoma which were enrolled in a randomized prospective trial evaluating two different platinum and paxlitaxel chemotherapy combinations after radical surgery. p16(INK4a) negative tumours (17/300; 6%) had a significantly worse prognosis (univariate analysis, P<0.001; multivariate analysis: odds ratio 2.41, P=0.009). Among p16(INK4a)-positive tumours (283 out of 300; 94%), survival was better for patients with intermediate expression as compared to low or high expression levels (P=0.001). High expression levels of pRb were associated with an incremental deterioration of prognosis (univariate analysis, P=0.004; multivariate analysis: odds ratio 2.98, P=0.002). This observation held also true in the subgroup of optimally debulked patients (n=82), in whom the most important established prognostic factor, postoperative residual tumour cannot be applied. In conclusion p16(INK4a) and pRb are independent prognostic factors in advanced-stage ovarian carcinomas after radical surgery and postoperative chemotherapy. High pRb expression is a significant prognosticator in optimally debulked patients and may hold potential for subgroup stratification in postoperative treatment.

[Molecular pathogenesis of cervical cancer and its first steps]. / Molekulare Pathogenese des Zervixkarzinoms und seiner Vorstufen.

Specific types of the human papillomaviruses (high risk human papillomaviruses) play an essential role in the pathogenesis of cervical cancer. Although infections by these viruses are very common in the general population, only few result in clinically relevant lesions. Continuous and deregulated expression of two viral oncoproteins E6 and E7 in basal or parabasal cells are required to induce and maintain neoplastic growth. In the course of an acute HPV-infection these genes are exclusively expressed in cell cycle arrested, terminally differentiated cells in the intermediate or superficial layers of the epithelium. Accidental activation of these genes in proliferating cells in the basal or parabasal cell layers results in interference with the cell cycle regulation, disturbances of the mitotic spindle apparatus and centrosome functions. This results in numerical and structural chromosome aberrations, chromosomal instability, increasing aneuploidy and initiates cervical carcinogenesis. The deregulated expression of the viral oncogene E7 is indicated by strong over-expression of the cellular p16(INK4a) gene product. This finding may have significant influence on novel strategies in cervical cancer diagnosis and screening. This review summarizes the basic molecular mechanisms of how papillomaviruses contribute to cellular transformation and how this can influence future diagnostic applications.

[The EMECAM project: the Spanish Multicenter Study on the Relationship between Air Pollution and Mortality. The background, participants, objectives and methodology]. / El proyecto EMECAM: Estudio Multicéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad. Antecedentes, participantes, objetivos y métodología.

In recent years, a growing number of studies suggests that increases in air pollution levels may have short-term impact on human health, even at pollution levels similar to or lower than those which have been considered to be safe to date. The different methodological approaches and the varying analysis techniques employed have made it difficult to make a direct comparison among all of the findings, preventing any clear conclusions from being drawn. This has led to multicenter projects such as the APHEA (Short-Term Impact of Air Pollution on Health. A European Approach) within a European Scope. The EMECAM Project falls within the context of the aforesaid multicenter studies and has a wide-ranging projection nationwide within Spain. Fourteen (14) cities throughout Spain were included in this Project (Barcelona, Metropolitan Area of Bilbao, Cartagena, Castellón, Gijón, Huelva, Madrid, Pamplona, Seville, Oviedo, Valencia, Vigo, Vitoria and Saragossa) representing different sociodemographic, climate and environmental situations, adding up to a total of nearly nine million inhabitants. The objective of the EMECAM project is that to asses the short-term impact of air pollution throughout all of the participating cities on the mortality for all causes, on the population and on individuals over age 70, for respiratory and cardiovascular design causes. For this purpose, with an ecological, the time series data analyzed taking the daily deaths, pollutants, temperature data and other factors taken from records kept by public institutions. The period of time throughout which this study was conducted, although not exactly the same for all of the cities involved, runs in all cases from 1990 to 1996. The degree of relationship measured by means of an autoregressive Poisson regression. In the future, the results of each city will be combined by means of a meta-analysis.

[The short-term effects of air pollution on mortality. The results of the EMECAM project in the city of Vigo, 1991-94. Estudio Multicéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad]. / Efectos a corto plazo de la contaminación atmosférica sobre la mortalidad. Resultados del proyecto EMECAM en la ciudad de Vigo, 1991-94.

BACKGROUND: In the Autonomous Region of Galicia, no study has been made of the impacts of air pollution on human health, despite the fact that several of its major cities have moderate levels of pollution. Therefore, we have considered the need of making this study in the city of Vigo. The main objective of this analysis is that of analyzing the short-term impact of air pollution on the daily death rate for all reasons in the city of Vigo throughout the 1991-1994 period, by using the procedure for analysis set out as part of the EMECAM Project. METHOD: The daily fluctuations in the number of deaths for all causes with the exception of the external ones are listed with the daily fluctuations of sulfur dioxide and particles using Poisson regression models. A non-parametric model is also used in order to better control the confusion variables. RESULTS: Using the Poisson regression model, no significant relationships have been found to exist between the pollutants and the death rate. In the non-parametric model, a relationship was found between the concentration of particles on the day immediately prior to the date of death and the death rate, an effect which remains unchanged on including the autoregressive terms. CONCLUSIONS: Particle-based air pollution is a health risk despite the average levels of this pollutant falling within the air quality guideline levels in the city of Vigo.

[The EMECAM project: a discussion of the results in the participating cities. Estudio Multicéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad]. / El proyecto EMECAM: discusión de los resultados en las ciudades participantes.

This article draws a comparison and provides a discussion of the findings resulting from the local analyses of the 14 cities participating in the EMECAM Project. An analysis is made of the time series related to mortality, pollutants (particles in suspension, SO2, NO2, O3 and CO), temperature and other factors taken from records of public institutions. By using Poisson autoregressive regression, an estimate has been made of the short-term relationship between the number of deaths and the air pollution indicators in each one of the following cities: Barcelona, metropolitan area of Bilbao, Cartagena, Castellón, Gijón, Huelva, Madrid, Pamplona, Seville, Oviedo, Valencia, Vigo, Vitoria and Saragossa. The findings reveal the air pollution figures in our country to be similar to those of other European cities. The levels of the different pollutants point toward road traffic as being the main source of most of this pollution. A relationship has been found between the mortality and different pollutants in most cities, although the results are not homogeneous among the cities and show variability in the different causes under study. In some cities, especially in those having smaller populations, there have been no findings providing any evidence of a relationship, or the findings themselves are not highly consistent. The meta-analysis will provide estimates for all of the cities as a whole and will allow the possibility of making a more clear-cut assessment of the time lag impact of air pollution on the mortality. Worthy of special mention is the participation in this project of public health officers as actively involved researchers.

Abdominal T-cell non-Hodgkin's lymphoma of the gamma/delta type in a patient with selective immunoglobulin A deficiency.

A 28-year-old man presented with selective immunoglobulin A deficiency and severe diarrhea responding to a gliadin-free diet. Biopsy samples of the small intestine showed dense T-cell infiltrations in the lamina propria and a slight increase of intraepithelial T-lymphocytes. No clonal rearrangement of the T-cell receptor c-beta chain genes was detectable by Southern blotting. Four years later, at the age of 32, the patient was hospitalized again with liver failure, abdominal lymphadenopathy, pancytopenia, and recurrent bacterial infections. Retrospective polymerase chain reaction analysis of formalin-fixed tissues of the intestinal biopsy samples obtained 4 years earlier showed monoclonal T-cell receptor gamma-chain gene rearrangement. Lymphoid cells of the peripheral blood showed an immunophenotype of CD3-positive gamma/delta T cells with a negativity for CD4 and CD8. A clonally rearranged T-cell receptor delta chain gene and a germline configuration of the c-beta chain genes was found by Southern blotting. Cytogenetics showed an abnormal karyotype with unbalanced translocations t(1;5) and t(9;13). The patient died of extensive lung infiltrations by gamma/delta T cells; autopsy showed a peripheral T-cell lymphoma of the gamma/delta type in the enlarged abdominal lymph nodes. This is the first report of an abdominal T-cell lymphoma of the gamma/delta type in a patient with selective immunoglobulin A deficiency.

[Oral health in Galician schoolchildren. 1995]. / La salud bucodental en los escolares gallegos. 1995.

BACKGROUND: To ascertain the condition of the oral hygiene of school children 6 and 12 years of age in Galicia and to assess the degree to which said condition meets the World Health Organization (WHO) oral hygiene objectives for the year 2000. METHODS: Observational cross-sectional study conducted in 1995 on a group of school children 6 and 12 years of age in Galicia selected by means of a multi-stage sampling by conglomerates, stratified by provinces and type of habitat. RESULTS: This study was conducted on 1,288 school age children, 643 in the 6-year-old group and 645 in the 12-year-old group. 46.7% of the 6 year-old children and 64.2% of the 12 year-olds were found to have cavities, which means an oc index of 1.84 and a AOC index of 1.60, respectively. CONCLUSIONS: A trend toward improvement in the oral hygiene of school-age children in Galicia has been found. The oral hygiene-related objectives recommended by the WHO for the year 2000 in the region of Europe have been accomplished, as a result of which further objectives are recommended.

Investigation of a phase transition in a single optically levitated microdroplet by Raman-Mie scattering.

Light-scattering measurements of optically levitated microdroplets containing three components, glycerin, water, and ammonium sulfate, are presented. Evaporation of the microdroplet is studied by means of morphology-dependent resonances observed in both Raman spectra as well as elastically scattered light and by the simultaneous measurement of the laser power. The phase transition from the liquid to the solid state of ammonium sulfate inside the microdroplet is observed by means of morphology-dependent resonances and Raman scattering.

Applications of the optical trapping technique to analyze chemical reactions in single emulsion particles.

The applicability of the single beam gradient force optical trap and the optical levitation technique to investigate dynamic processes in microparticles is examined. The device allows to follow chemical reactions, like the emulsion polymerization and the ester hydrolysis reaction, in single emulsion droplets. Furthermore the usability of optical traps to investigate living cells is demonstrated.

Chemical composition and reaction analysis of single aerosol particles.

In situ measurements of gas-liquid surface reactions of single aerosol microdroplets are presented. By means of optical levitation in combination with elastic (Mie) and inelastic (Raman) light scattering it is possible to get information on the chemistry of e.g. acid/base reactions as well as the physical behavior of single microparticles.

Somatic hypermutation in low-grade mucosa-associated lymphoid tissue-type B-cell lymphoma.

The origin of low-grade mucosa-associated lymphoid tissue (MALT)-type B-cell lymphoma is still unclear. Using a novel two-step procedure, we have sequenced the Ig VH genes expressed by cells from four patients with gastric low-grade MALT-type lymphoma. The nucleotide sequences of the complementarity determining region 3 (CDR3) of the genomic DNA were first amplified using consensus oligonucleotide primers, then sequenced. Based on the CDR3 sequence amplified from each MALT lymphoma, individual tumor-specific primers were synthesized and used directly in the polymerase chain reaction (PCR) to analyze the sequences of their Ig heavy-chain variable region. When compared with the germ-line sequence, many nucleotide substitutions, mainly in the CDRs, were found in the variable gene sequences of the four MALT lymphomas. The mutations showed a high replacement-to-silent ratio and were distributed in a way which suggested that the tumor cells had been positively selected through their antigen receptor. Our findings indicate that the MALT-type lymphoma B cells are hypermutated postgerminal center lymphocytes that have undergone antigen selection.