Cox regression with doubly truncated responses and time-dependent covariates: the impact of innovation on firm survival.

The creation of new firms is an important incentive for the economic growth of a country, since it generates employment, it encourages the competition, and promotes innovation. In this work, we investigate the survival of Spanish firms which were created since 2001 and closed down between 2004 and 2012. The information was gathered from Technological Innovation Panel (PITEC), a survey with a focus the technological innovation in Spanish firms. In particular, a Cox regression model with time-dependent covariates was used in order to identify and quantify the determinants of the risk of exit for the firm. The selection bias due to the interval sampling for the firms was corrected by using methods for doubly truncated lifetimes. Interestingly, it is seen how the correction for the selection bias changes both the size and the statistical significance of the effects provided by standard Cox regression.

Direct promoter induction of p19Arf by Pit-1 explains the dependence receptor RET/Pit-1/p53-induced apoptosis in the pituitary somatotroph cells.

Somatotrophs produce growth hormone (GH) and are the most abundant secretory cells of the pituitary. Somatotrophs express the transcription factor Pit-1 and the dependence receptor RET, its co-receptor GFRa1 and ligand GDNF. Pit-1 is a transcription factor essential for somatotroph proliferation and differentiation and for GH expression. GDNF represses excess Pit-1 expression preventing excess GH. In the absence of GDNF, RET behaves as a dependence receptor, becomes intracellularly processed and induces strong Pit-1 expression leading to p53 accumulation and apoptosis. How accumulation of Pit-1 leads to p53 expression is unknown. We have unveiled the relationship of Pit-1 with the p19Arf gene. There is a parallel correlation of RET processing, Pit-1 increase and ARF protein and mRNA expression. Interfering the pathway with RET, Pit-1 or p19Arf siRNA blocked apoptosis. We have found a Pit-1 DNA-binding element within the ARF promoter. Pit-1 directly regulates the CDKN2A locus and binds to the p19Arft promoter inducing p19Arf gene expression. The Pit-1-binding element is conserved in rodents and humans. RET/Pit-1 induces p19Arf/p53 and apoptosis not only in a somatotroph cell line but also in primary cultures of pituitary somatotrophs, where ARF siRNA interference also blocks p53 and apoptosis. Analyses of the somatotrophs in whole pituitaries supported the above findings. Thus Pit-1, a differentiation factor, activates the oncogene-induced apoptosis (OIA) pathway as oncogenes exerting a tight control in somatotrophs to prevent the disease due to excess of GH (insulin-resistance, metabolic disease, acromegaly).

Lesiones purpúricas acrolocalizadas y fiebre

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Hiperplasia endotelial papilíferaintravascular en el seno de un granulomapiógeno / Intravascular papillary endotelial hiperplasia developped in a pyogenic granuloma

La hiperplasia endotelial papilífera intravascular (HEPIV) representa un proceso vascular benigno de aspecto clínico inespecífico. Histopatológicamente se caracteriza por proliferación papilar de células endoteliales, habitualmente asociada con material trombótico. Puede presentarse en un vaso normal dilatado, o en asociación con diversas lesiones vasculares proliferativas. La importancia de su conocimiento reside principalmente en su diferenciación del hemangiosarcoma. Aportamos un nuevo caso de HEPIV desarrollada en el seno de un granuloma piógeno. Se discuten los aspectos clínicos, histológicos y etiopatogénicos de esta peculiar lesión (AU)

Selenio y carcinogénesis mamaria / Selenium and breast carcinogenesis

La relación entre el selenio (Se) y el cáncer comenzó a plantearse en 1943 y desde entonces, aunque algunos estudios epidemiológicos han mostrado un incremento del riego del cáncer de mama ante estados deficitarios de Se, otra proporción similar de trabajos no han encontrado tal asociación. En estu dios experimentales el Se se mostró muy eficaz para inhibir la carcinogénesis mamaria inducida por diferentes noxas en diversos modelos animales. Se cuestiona la utilidad del Se sérico en las enfermas de cáncer de mama como un marcador tumoral.De acuerdo con los datos de la bibliografía revisada y de los hallazgos de nuestro grupo, la disminución del Se sérico en las enfermas con cáncer de mama estaría relacionada con la actividad biológica del tumor, siendo un fenómeno posterior a la aparición del cáncer. También se apuntan nuevas líneas de investigación. (AU)

Increased serum IgE in acute type A, B and delta hepatitis.

Serum IgE levels have been documented in patients of acute type B hepatitis. There are very few studies on serum IgE in acute type A hepatitis and, to our knowledge, there are no data on serum IgE in acute delta hepatitis patients. The purpose of this study was to measure total IgE levels in 38 patients with acute A, B and delta hepatitis and in 181 controls in order to determine the possible existence of changes in this parameter in the course of these infections. Our results showed a relevant increase in IgE levels in the three groups (hepatitis A, B and delta) with respect to the control group. Moreover, the hepatitis B group showed increased total serum IgE levels with respect to the hepatitis delta group.

Plasmatic fibronectin in malignancies.

Plasmatic fibronectin has been studied in tumor patients on the basis of the role that unspecific opsonin may play in tumor growth and spreading. Alterations in fibronectin levels might be used as a biological marker and our purpose has been to evaluate the significance of this test in the biological diagnosis of cancer. When comparing the levels found in the control group (22.86 +/- 1.40 mg/dl) and in tumor patients (23.80 +/- 1.90 mg/dl), we observed no difference in the overall group. However, in relation to the localization of tumors, a significant increase was found in breast cancer (31.83 +/- 3.83 mg/dl) and a significant decrease in squamous cell carcinoma of the head and neck (9.56 +/- 1.68 mg/dl). These results suggest that plasmatic fibronectin could be useful as a biomarker in some types of tumors. Our conclusion was confirmed by analysis of ROC curves related to every one of the studied tumors.

[Ceruloplasmin levels in patients with chronic obstructive bronchopneumopathy]. / Niveles de ceruloplasmina en enfermos con bronconeumopatía crónica obstructiva.

The seric levels of ceruloplasmin in a group of 20 patients suffering of chronic obstructive lung disease were studied. Levels in this group of patients (51.42 +/- 11.15 mg/dl) (p less than 0.005) were significantly higher than those of the control group (36.59 +/- 13.37 mg/dl). There was no correlation between ceruloplasmin levels and PaO2, PaCO2, SaO2, HCO3- measurements. Results show a possible oxidation reaction; owing to the fact that ceruloplasmin is a general oxidase which, combined with an antioxidant stimulus of patients with chronic respiratory insufficiency, can produce this reaction.

[Contribution to the study of the epidemiology of rheumatic diseases in our country and their occupational impact]. / Contribución al estudio de la epidemiología de las enfermedades reumáticas en nuestro medio y su repercusión laboral.

In a workforce of 8,149 workers, we reviewed the sick leave certificates issued over a period of 1 year. Amongst the absenteeism resulting from common diseases, 9.28% were of rheumatic nature (the second cause being respiratory viral infections). Furthermore, these rheumatic complaints were responsible for 14.66% days absenteeism from work, with a mean duration of 38.17 days, which was longer than for any of the other causes. In respect of accidents in the work place, 16.17% were influenced by rheumatic problems. These resulted in 18.77% days absenteeism with a mean duration of 33.94 days, which was greater than that relating to all other accidents. The total cost was close to 1.600 million pesetas.

[Effect of cimetidine on free fatty acid liberation]. / Influencia de la cimetidina en la liberación de ácidos grasos libres.

Certain studies have brought to light the relationship between the administration of cimetidine and alterations of the lipidic metabolism. The changes in cholesterol levels observed after cimetidine administration have not yet been satisfactorily explained, at least in certain aspects. This paper studies free fatty acid behavior in a group of healthy volunteers who were given a 600 mg infusion of cimetidine. A significant drop (p less than 0.05) in fatty acids was found in these subjects in comparison with isolated physiological saline solution infusion. Our results imply that this fatty acid process may be involved in the lipid metabolism changes brought on by cimetidine administration.

[Results of the functional tests using calcitonin in patients with chronic diffuse hepatopathy]. / Resultados de la prueba funcional con calcitonina en pacientes con hepatopatía crónica difusa.

A group of ten patients suffering cirrhosis who were treated with 100 U/l of calcitonin was studied with the aim of knowing whether in patients with cirrhosis the calcitonin is able to provoke the usual characteristic biologic modifications on the basis of the knowledge of their hormonal high levels accompanied of oesteopenia. Regarding their baseline determinations, no statistically significant modifications have been observed in calcium, phosphorous, alkaline phosphatase or its thermostable and thermolabile fractions, magnesium, uric acid and creatinine plasma concentrations respectively. This absence of a biological response to calcitonin could be due either to a numeric or functional damage of the hormone receptors or a diminished biodisponibility, although there are facts suggesting a lesser hormone biopotenciality in these patients.

[Changes in the activity of plasma renin and aldosterone induced by a pattern of increasing administration of zinc sulphate in normotensive individuals]. / Modificaciones en la actividad de renina plasmática y aldosterona provocadas por una pauta de administración creciente de sulfato de cinc en individuous normotensos.

The behavior of the renin-angiotensin-aldosterone system was evaluated in response to an increasing zinc intake. This oligoelement can modify the activity of the angiotensin I converting enzyme (ACE). Six healthy normotensive volunteers received 30 mg of zinc sulphate orally for 4 days and 600 mg for 4 additional days. On the first, fifth and ninth days plasma renin activity (PRA) and serum aldosterone were measured, and the possible changes in blood pressure were evaluated. PRA and aldosterone showed significant increases, with a stepwise distribution throughout the zinc overload. On the first day, PRA was 0.40 +/- 0.08 ng/ml/h; on the fifth day it was 0.80 +/- 0.21 ng/ml/h, and on the ninth day 1.39 +/- 0.34 ng/ml/h (1st-5th day; p less than 0.05; 1st-9th day: p less than 0.02). On the first day, the aldosterone levels were 81 +/- 17 pg/ml, on the fifth day they were 119 +/- 26 pg/ml, and on the ninth day 164 +/- 30 pg/ml (1st-5th day: nonsignificant difference; 1st-9th day: p less than 0.02). The values of arterial pressure did not change significantly after zinc overload. It is concluded that zinc overload can modify PRA and aldosterone levels, and that these changes are dose-related.

Changing patterns of gastric cancer mortality in Spain.

Time trends and the geographical variation of mortality from gastric cancer in Spain are analysed. The national (1961-1980) and the provincial (1975-1980) crude death rates as well as the age adjusted death rates were calculated using the population census (years 1960 and 1970) and the figures for national and provincial mortality. Mortality increased until 1963-1965 and then decreased significantly (P less than 0.01). Analysis of the geographic distribution reveals that the mortality rate is significantly higher in the interior than in the coastal provinces of the country, and higher in the provinces over 600 m above sea level.

ROC analysis of diagnostic performance utilizing serum antiproteases in cancer patients.

Assessment of the accuracy of diagnostic procedures is made independent of diagnostic criteria by means of a receiver-operating-characteristics (ROC) curve. We performed ROC analysis for the major serum antiproteases: alpha-1-antitrypsin (A1AT) and alpha-2-macroglobulin (A2M), in 99 cancer patients compared with 71 normal individuals. A1AT and A2M were significantly higher in cancer patients (p less than 0.0005). By comparing true positive and false positive rates for different serum levels, ROC analysis showed that serum A1AT quantification seems more useful in clinical practice than serum A2M.

Biological changes in serum antiproteases as related to tumor progression.

The two major antiproteases (alpha-1-antitrypsin and alpha-2-macroglobulin) were studied in the serum of cancer patients (273 and 103 subjects, respectively) and in a control group. In cancer patients, the values were stratified by clinical stage (local, loco-regional and metastatic disease). Serum alpha-1-antitrypsin was different in normal people (341 +/- 110.7 mg/dl) than in every cancer group (p less than 0.0005). The behavior of alpha-2-macroglobulin was similar, with significant differences (p less than 0.0005) between normal people (317.6 +/- 105.4 mg/dl) and the cancer groups. Serum alpha-1-antitrypsin was different in local, loco-regional and metastatic disease; however, alpha-2-macroglobulin did not show these differences. In metastatic disease, sensitivity was 96.66% for alpha-1-antitrypsin and 94.79% for alpha-2-macroglobulin.