Evaluación del programa de diagnóstico y tratamiento rápido del cáncer de pulmón / Evaluation of the quick diagnosis and treatment program for lung cancer

Objetivo: Analizar la eficacia y el cumplimiento del programa de diagnóstico y tratamiento rápido (PDTR) del cáncer de pulmón. Adicionalmente se revisan datos epidemiológicos en los pacientes diagnosticados de cáncer de pulmón en el Hospital de la Santa Creu i Sant Pau. Material y métodos: Se incluyeron 58 pacientes diagnosticados de cáncer de pulmón. Veintinueve de ellos fueron incluidos en el programa PDTR desde octubre de 2005 hasta mayo de 2006, y el resto fueron seleccionados aleatoriamente de entre los pacientes diagnosticados de cáncer de pulmón durante el año anterior al inicio del programa (grupo control). Se compararon los intervalos de tiempo desde la primera visita al diagnóstico y al tratamiento, así como diferentes variables (edad, sexo, tipo histológico, estadificación TNM). Resultados: Se encontró una reducción de tiempo en el grupo PDTR (p<0,001) que mostró una media entre la primera visita y el inicio del tratamiento de 26,72 días (desviación típica [DT]=13,6), mientras que en el grupo control fue de 84 días (DT=53). La estadificación TNM fue inferior en el grupo PDTR, aunque sólo con significación estadística para la N (grado de afectación ganglionar) (p=0,007). Conclusión: Con el programa PDTR se ha conseguido reducir el tiempo desde la llegada del paciente al inicio del tratamiento a menos de 30 días en la mayoría de los pacientes, lo que representa una reducción significativa de éste. Su efecto sobre el pronóstico es controvertido y requerirá estudios a largo plazo (AU)

Objective: To analyze the efficiency of the program of quick diagnosis and treatment (PDTR, programa de diagnóstico y tratamiento rápido) of lung cancer established in the Hospital de la Santa Creu i Sant Pau of Barcelona to review the epidemiology of lung cancer. Methods and materials: Fifty-eight patients with lung cancer were studied. Twenty-nine of them were included in the program between October 2005 and May 2006, and the remaining were randomly selected among those diagnosed the year before (control group). Time between first visit, diagnosis and treatment and other variables (age, sex, histological type and TNM stage) were compared between groups. Results: Significant differences were found between the two groups. PDTR patients had a mean time between first visit and treatment of 26.7 days (Standard Deviation [SD]=13.6), whereas this was 84 days (SD=53) in the control group. The PDTR group had a lower TNM stage, but statistical significance was only found in N (lymph node involvement) (p=0.007). Conclusion: Most patients included in the PDTR program spend less than 30 days between first visit and treatment, which represents a significant reduction in time (p<0.001). The effect on prognosis is controversial and will need long term studies (AU)

[Evaluation of the quick diagnosis and treatment program for lung cancer]. / Evaluación del programa de diagnóstico y tratamiento rápido del cáncer de pulmón.

OBJECTIVE: To analyze the efficiency of the program of quick diagnosis and treatment (PDTR, programa de diagnóstico y tratamiento rápido) of lung cancer established in the Hospital de la Santa Creu i Sant Pau of Barcelona to review the epidemiology of lung cancer. METHODS AND MATERIALS: Fifty-eight patients with lung cancer were studied. Twenty-nine of them were included in the program between October 2005 and May 2006, and the remaining were randomly selected among those diagnosed the year before (control group). Time between first visit, diagnosis and treatment and other variables (age, sex, histological type and TNM stage) were compared between groups. RESULTS: Significant differences were found between the two groups. PDTR patients had a mean time between first visit and treatment of 26.7 days (Standard Deviation [SD]=13.6), whereas this was 84 days (SD=53) in the control group. The PDTR group had a lower TNM stage, but statistical significance was only found in N (lymph node involvement) (p=0.007). CONCLUSION: Most patients included in the PDTR program spend less than 30 days between first visit and treatment, which represents a significant reduction in time (p<0.001). The effect on prognosis is controversial and will need long term studies.

Réplica a “¿Hasta cuándo debemos soportar el dolor agudo en nuestros hospitales? / Reply. How much longer must we put up with acute pain in our hospitals?

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Factors influencing length of hospital stay in community-acquired pneumonia: a study in 27 community hospitals.

We did a retrospective study of 1920 episodes of community-acquired pneumonia (CAP) in 27 community hospitals and analysed inter-hospital variability in length of hospital stay (LOS), mortality and readmission rates. The overall adjusted LOS (mean+/-S.D.) was 10.0+/-9.8 days. LOS increased according to the Pneumonia Severity Index (PSI) risk class: 7.3 days for class I to 11.3 days for class V (P<0.001). In a multiple regression model, LOS increased (P<0.001) according to the hospital (inter-hospital variability), PSI risk class, complications during hospitalization, admission to ICU, need of oxygen and transfer to a nursing home. Hospitals with shorter LOS did not show an increased readmission rate (adjusted OR 1.02, 95% CI 0.51-2.03, P = 0.97) and post-discharge mortality (adjusted OR 1.20, 95% CI 0.70-2.05, P=0.51). There are significant inter-hospital variations in LOS in patients with CAP which are related to differences in clinical management. The reduction of these differences will further improve efficiency and quality of care.

SSU rRNA-based phylogenetic position of the genera Amoeba and Chaos (Lobosea, Gymnamoebia): the origin of gymnamoebae revisited.

Naked lobose amoebae (gymnamoebae) are among the most abundant group of protists present in all aquatic and terrestrial biotopes. Yet, because of lack of informative morphological characters, the origin and evolutionary history of gymnamoebae are poorly known. The first molecular studies revealed multiple origins for the amoeboid lineages and an extraordinary diversity of amoebae species. Molecular data, however, exist only for a few species of the numerous taxa belonging to this group. Here, we present the small-subunit (SSU) rDNA sequences of four species of typical large gymnamoebae: Amoeba proteus, Amoeba leningradensis, Chaos nobile, and Chaos carolinense. Sequence analysis suggests that the four species are closely related to the species of genera Saccamoeba, Leptomyxa, Rhizamoeba, Paraflabellula, Hartmannella, and Echinamoeba. All of them form a relatively well-supported clade, which corresponds to the subclass Gymnamoebia, in agreement with morphology-based taxonomy. The other gymnamoebae cluster in small groups or branch separately. Their relationships change depending on the type of analysis and the model of nucleotide substitution. All gymnamoebae branch together in Neighbor-Joining analysis with corrections for among-site rate heterogeneity and proportion of invariable sites. This clade, however, is not statistically supported by SSU rRNA gene sequences and further analysis of protein sequence data will be necessary to test the monophyly of gymnamoebae.

PTHrP inhibits adipocyte differentiation by down-regulating PPAR gamma activity via a MAPK-dependent pathway.

We examined the capacity of PTHrP to modulate the terminal differentiation of the preadipocytic cell line, 3T3-L1. These cells express endogenous PTHrP and its receptor, but expression levels were undetectable after differentiation into mature adipocytes. Cells stably overexpressing PTHrP failed to differentiate when induced to undergo adipogenesis and proliferated at a faster rate. MAPK activity was elevated in PTHrP-transfected 3T3-L1 cells, and treatment with the PKA inhibitor H-8 decreased this activity. Inhibition of MAPK kinase with PD098059 permitted terminal differentiation of PTHrP-transfected 3T3-L1 cells to proceed. Although PPAR gamma gene expression levels remained relatively constant in the PTHrP-transfected cells, PPAR gamma phosphorylation was enhanced. Furthermore, the capacity of PPAR gamma to stimulate transcription in the presence of troglitazone was diminished by PTHrP. Expression of the PPAR gamma-regulated adipocyte specific gene aP2 transiently rose and then fell in PTHrP-transfected cells. These results indicate that PTHrP can increase MAPK activity in 3T3-L1 cells via the PKA pathway, thereby enhancing PPAR gamma phosphorylation. This modification can inactivate the transcriptional enhancing activity of PPAR gamma and diminish the expression of adipocyte-specific genes. These studies therefore demonstrate that PTHrP may inhibit the terminal differentiation of preadipocytes and describe a molecular pathway by which this action can be achieved.

Role of activator protein 1 transcriptional activity in the regulation of gene expression by transforming growth factor beta1 and bone morphogenetic protein 2 in ROS 17/2.8 osteoblast-like cells.

In osteoblastic cells, transforming growth factor beta1 (TGF-beta1) has been found to regulate the expression of a variety of proto-oncogenes including c-fos, c-jun, and junB. The c-fos in particular has been implicated in the mitogenic effect of TGF-beta1. Here, we examined the role of these early response genes in the regulation of osteoblast (OB) gene expression by two members of the TGF-beta superfamily, TGF-beta1 and bone morphogenetic protein 2 (BMP-2). In ROS 17/2.8 cells, TGF-beta1 as well as BMP-2 up-regulated the expression of junB and c-fos messenger RNAs (mRNAs), and this increase was correlated in both cases with an increase in activator protein 1 (AP-1) DNA-binding activity involving JunB and c-Fos proteins. Protein kinase C (PKC)- and protein tyrosine kinase (PTK)-dependent pathways have been implicated in both TGF-beta1 signaling and AP-1 gene regulation. Therefore, using the kinase inhibitors chelerythrine chloride and genistein, we showed that PKC and PTK activities, respectively, participated in TGF-beta1- and BMP-2-induced increases in junB mRNA levels. Similarly, these kinase activities were involved in the stimulatory effect of BMP-2 on c-fos mRNA expression. Using a natural dominant negative for AP-1 transcriptional activity in ROS 17/2.8 cells, we then showed that AP-1 transcription factors mediated TGF-beta1- and BMP-2-regulated expression of the (alpha1) collagen I gene as well as TGF-beta1-regulated expression of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor. Our data emphasize the role of the AP-1 transcription factor in TGF-beta1 and BMP-2 signaling and highlight the importance of this transcription factor family in the expression of OB genes.

Evaluation of a portable respiratory recording device for detecting apnoeas and hypopnoeas in subjects from a general population.

This study was designed to validate a new home portable respiratory recording device (PRRD) to identify sleep apnoea and hypopnoea in a group of subjects (n=116), from a sample of the general population. Full night polysomnography (PSG) was used as the gold standard and simultaneously performed with PRRD. PRRD measurements included oronasal airflow (thermistry), chest wall impedance, oxygen saturation, snoring and body position. The sensors were unique for each recording system. Data obtained was blindly reviewed and analysed. A high level of agreement between both methods apnoea/hypopnoea index by PSG and the respiratory disturbance index (RDI) by PRRD was observed. Accuracy of the PRRD was evaluated in terms of sensitivity and specificity for different RDI-PRRD cut-off points with respect to AHI-PSG >10 and AHI-PSG >30. A logistic regression model was performed to estimate the chance per unit of RDI of apnoeas. A received operating characteristic (ROC) curve was drawn to obtain the sensitivity/specificity profile for each observed RDI value obtained. From the ROC curve the authors identified the better cut-off points, which represent a balanced sensitivity/specificity. Through a classification table defined by the cut-off point, the post-odds to exhibit the disease was calculated. For a full PSG cut-off point of 10 a PRRD of six showed a balanced sensitivity of 95% and a specificity of 92%. For a full PSG cut-off point of 30 a PRRD of 16 shows a balanced sensitivity/specificity (100% and 97%, respectively). Post odds of apnoea were calculated for each cut-off point. In conclusion, these data suggest that the portable respiratory recording device is an effective device to identify apnoeas and hypopnoeas in a general population and is therefore a suitable device to be used in epidemiological studies.

[Satisfaction with primary medical care: population determinants]. / Determinantes poblacionales de la satisfacción con el médico de atención primaria.

OBJECTIVES: To study the level of satisfaction with the family physician in the general population, and to evaluate the influence of characteristics of the individual and the available health care services. METHODS: Cross-sectional survey with a representative sample of 1,505 beneficiaries of the Social Security, older than one year, from the city of Matar¿o (Barcelona). A questionnaire, administered by home interview, examined the socio-demographic situation, health status, health care organizations and services used and the preferences and knowledge in relation to them. Satisfaction was measured on the scale of Hulka BS et al. developed at Andalusian primary care centres. RESULTS: Satisfaction with the family physician had, on a scale from 0 to 100, a mean score of 61.3 (standard deviation, 13.5) points. The main determinant of satisfaction was the model of primary care, users of non-reformed centres being less satisfied. It was followed by better knowledge of ambulatory services, age and better attitudes towards primary care, which were positively related to satisfaction. Indicators of health care accessibility and continuity, as well as the number of medical visits fulfilled, the subject's main activity and their level of health were also independent determinants of satisfaction. The explained satisfaction's variation was 38.98%. CONCLUSIONS: Satisfaction with family physician is a complex and multifactorial behaviour which is under constant change due to the interrelation of the individual with his social and health care environment.

Molecular evidence that Reticulomyxa filosa is a freshwater naked foraminifer.

Reticulomyxa filosa is a freshwater protist possessing fine granular, branching and anastomosing pseudopodia and therefore traditionally placed in the class Granuloreticulosea, order Athalamida, as a sister group to the order Foraminiferida. Recent studies have revealed remarkable similarities in pseudopodial motility and ultrastructure between R. filosa and foraminifera (e.g. Allogromia laticollaris), prompting us to conduct a molecular phylogenetic analysis of these seemingly disparate organisms. We sequenced the complete small-subunit of the ribosomal DNA of the cultured strain of R. filosa and compared it to the corresponding sequences of other protists including 12 species of foraminifera. We also sequenced and analyzed the actin coding genes from R. filosa and two species of foraminifera, Allogromia sp. and Ammonia sp. The analysis of both data sets clearly shows that R. filosa branches within the clade of foraminifera, suggesting that R. filosa is in fact a freshwater naked foraminiferan.

Extreme differences in rates of molecular evolution of foraminifera revealed by comparison of ribosomal DNA sequences and the fossil record.

Foraminifera have one of the best known fossil records among the unicellular eukaryotes. However, the origin and phylogenetic relationships of the extant foraminiferal lineages are poorly understood. To test the current paleontological hypotheses on evolution of foraminifera, we sequenced about 1,000 base pairs from the 3' end of the small subunit rRNA gene (SSU rDNA) in 22 species representing all major taxonomic groups. Phylogenies were derived using neighbor-joining, maximum-parsimony, and maximum-likelihood methods. All analyses confirm the monophyletic origin of foraminifera. Evolutionary relationships within foraminifera inferred from rDNA sequences, however, depend on the method of tree building and on the choice of analyzed sites. In particular, the position of planktonic foraminifera shows important variations. We have shown that these changes result from the extremely high rate of rDNA evolution in this group. By comparing the number of substitutions with the divergence times inferred from the fossil record, we have estimated that the rate of rDNA evolution in planktonic foraminifera is 50 to 100 times faster than in some benthic foraminifera. The use of the maximum-likelihood method and limitation of analyzed sites to the most conserved parts of the SSU rRNA molecule render molecular and paleontological data generally congruent.

Early origin of foraminifera suggested by SSU rRNA gene sequences.

Foraminifera are one of the largest groups of unicellular eukaryotes with probably the best known fossil record. However, the origin of foraminifera and their phylogenetic relationships with other eukaryotes are not well established. In particular, two recent reports, based on ribosomal RNA gene sequences, have reached strikingly different conclusions about foraminifera's evolutionary position within eukaryotes. Here, we present the complete small subunit (SSU) rRNA gene sequences of three species of foraminifera. Phylogenetic analysis of these sequences indicates that they branch very deeply in the eukaryotic evolutionary tree: later than those of the amitochondrial Archezoa, but earlier than those of the Euglenozoa and other mitochondria-bearing phyla. Foraminifera are clearly among the earliest eukaryotes with mitochondria, but because of the peculiar nature of their SSU genes we cannot be certain that they diverged first, as our data suggest.

Phylogenetic position of foraminifera inferred from LSU rRNA gene sequences.

A 5'-terminal region of 1600-1800 base pairs was amplified, cloned, and sequenced in the large subunit rDNA (LSU rDNA) of four species of foraminifera. These sequences were compared with the homologous regions of 16 eukaryotic taxa in order to establish the phylogenetic position of foraminifera. Analysis of 610 unambiguously aligned bases shows that foraminifera branch closely to plasmodial and cellular slime molds in the middle of the eukaryotic tree--that is, much earlier than suggested by the fossil record. These data, the first DNA sequences reported for foraminifera, will help analyze this class of protists and the early evolution of eukaryotes.

Structural requirements for the growth factor activity of the amino-terminal domain of urokinase.

High molecular weight urokinase-type plasminogen activator (uPA) in which proteolytic activity was inactivated (diisopropyl fluorophosphate (DFP)-uPA), its amino-terminal fragment (ATF, amino acids (aa) 1-143), and fucosylated and defucosylated growth factor domains (GFD, aa 4-43) were tested for growth-promoting effects and binding in human SaOS-2 osteosarcoma cells and U-937 lymphoma cells. DFP-uPA, ATF, and both the fucosylated and defucosylated GFD were capable of competing with 125I-ATF for binding to both SaOS-2 and U-937 cells. DFP-uPA, ATF, and fucosylated GFD were also mitogenic in SaOS-2 cells and increased cell numbers. However, defucosylated GFD was nonmitogenic in SaOS-2 cells and did not stimulate cell proliferation, even though it bound to these cells in a manner equivalent to the fucosylated GFD. A nonglycosylated high molecular weight uPA expressed and purified from Escherichia coli inhibited 125I-ATF binding to SaOS-2 cells but was also nonmitogenic. No mitogenic activity was observed in U-937 cells treated with the uPA forms capable of eliciting a mitogenic response in SaOS-2 cells. Proteolytically prepared kringle domain (aa 47-135) and low molecular weight uPA (aa 144-411) did not compete for 125I-ATF binding and did not elicit any mitogenic response in either of the cell lines tested. In addition, tissue plasminogen activator (tPA), which has been shown to be homologous to uPA in its growth factor domain and is also fucosylated, did not inhibit 125I-ATF binding nor elicit any mitogenic response. These results demonstrate that the GFD, implicated in binding to the uPA receptor, is also responsible for growth factor like activity in SaOS-2 cells and that the fucosylation at Thr18 within this domain may serve as a molecular trigger in eliciting this response.

Cellular localization of the SerH surface antigen in Tetrahymena thermophila.

We have purified the SerH surface antigen of T. thermophila by a novel and simple procedure and produced specific antisera against it. By the use of various immunochemical techniques, we have investigated the intracellular distribution of the antigen and shown that SerH is not only abundant in the cortex but also in the digestive apparatus of the ciliate. In each of these two localizations, SerH occupies a variety of compartments: in the cortex it can be found in the surface coat, the exocytotic mucocysts, the endocytotic parasomal sacs and as an integral protein of the membrane; in the digestive apparatus, SerH is found around ingested bacteria, in the cytoplasm surrounding the cytopharynx and the forming food vacuoles, and, seemingly, as a membrane-associated protein in young food vacuoles. Pulse-chase experiments have shown that feeding dramatically increases the global turnover of SerH. Besides these localizations, SerH is principally found in clumps around dense intracytoplasmic spheres, which could be mucocyst precursors. Indirect evidence is presented that SerH is routed to the peripheral or extracellular compartments via the mucocysts. The antigen is absent from alveolar, nuclear or mitochondrial membranes. We propose that SerH covers any membrane in contact or future contact with the extracellular medium.

Influence of calcium and 1,25-dihydroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells.

Exposure of quiescent bovine parathyroid cells to serum or a serum substitute caused an elevation in [3H] thymidine incorporation, followed by an increase in cell number. This was preceded by a rapid transient rise in c-myc and c-fos proto-oncogene mRNA levels. Alterations in the medium calcium concentration had no effect on the growth state of quiescent parathyroid cells. In addition, varying the medium calcium concentration did not influence either the time course or the degree of induction of proto-oncogene expression or the subsequent increase in [3H] thymidine uptake or proliferation of stimulated parathyroid cells. In contrast, when 1,25-dihydroxycholecalciferol was added with serum or serum substitute to quiescent parathyroid cells, no increase in c-myc mRNA levels was observed, and the expected increase in parathyroid cell number failed to occur. The augmentation in c-fos mRNA in response to serum was not, however, altered by 1,25-dihydroxycholecalciferol. These results indicate that 1,25-dihydroxyvitamin D, but not extracellular calcium, may directly modulate parathyroid cell proliferation by altering the expression of specific replication-associated oncogenes.

Immunological crossreactivity of Paramecium surface antigens: conformational differences account for cell surface specificity.

Surface antigens (i-Ags) G and D of Paramecium primaurelia, reported earlier to be completely unrelated on the basis of peptide mapping and immunological tests, were compared and found to be similar in molecular weight (Mr 235,000), isoelectric point (ca. 4.5), and amino acid composition. They are tightly folded proteins with more than 100 intramolecular disulfide bonds. Native i-Ags and their CNBr fragments were blotted onto nitrocellulose and labeled with a battery of homologous and heterologous antibodies fractionated on native and reduced i-Ag immunoadsorbents. It was found the i-Ags retained part of their antigenic structure upon cleavage and reduction. Analysis of labeling revealed that the two proteins share many of their antigenic sites, though they are completely distinct in their native conformation. Immunofluorescence and immunoadsorption on fixed cells confirmed these results. Antigenic crossreactivity also was found with surface antigens of a ciliate outside the Paramecium species complex. It is concluded that surface specificity of paramecia is due, in this case, to the expression of related proteins in different conformations.