Neoplasias primarias malignas múltiples en pacientes con cáncer gástrico en el área sanitaria de León / Multiple malignant primary neoplasms in patients with gastric neoplasms in the health district of León

Objetivos: analizar las características de los pacientes con tumores gástricos diagnosticados de una neoplasia primaria maligna múltiple (NPMM) en el área sanitaria de León. Pacientes y método: utilizando los datos del Registro de Tumores del Hospital de León se han seleccionado aquellos pacientes con tumores gástricos diagnosticados entre 1993 y 2002. Se realizó un seguimiento hasta el 31 de diciembre de 2004 analizando las características de los pacientes diagnosticados de una segunda neoplasia durante el periodo de seguimiento. Resultados: la prevalencia de NPMM fue del 1,96%. El 56% de los pacientes tenían antecedentes oncológicos en familiares de primer grado. Las segundas neoplasias más frecuentes fueron las digestivas (26%) y las urológicas (21%). El 87% de los pacientes fueron diagnosticados del segundo tumor en los primeros dos años. No se observaron diferencias respecto a la supervivencia entre los pacientes con NPMM sincrónicas y metacrónicas. Conclusiones: las NPMM en los pacientes con cáncer gástrico son un problema relevante. Aunque los agentes carcinógenos externos puedan actuar como promotores en el desarrollo de una segunda neoplasia, en estos pacientes parece existir una base genética que favorece el desarrollo del una NPMM. La prevención secundaria es la mejor medida para evitar el desarrollo de una NPMM

Objectives: we analyzed the characteristics of patients with gastric tumors diagnosed with multiple malignant primary neoplasm (MMPN) in the Health District of León. Material and methods: using the information in the Tumor Registry at León Hospital patients selected were those with gastric neoplasms diagnosed between 1993 and 2002. A follow-up was performed until December 31, 2004, and the characteristics of patients diagnosed with a second neoplasm were analyzed. Results: MMPN prevalence was 1,96%; 56% of patients had a history of cancer in first-degree relatives. The most frequent second neoplasms were digestive (26%) and urologic (21%); 87% of patients were diagnosed with a second neoplasm within the first two years. No significative differences in survival were observed among patients with synchronous or metachronous MMPN. Conclusions: MMPN in patients with gastric neoplasms is a relevant problem. While external carcinogenic agents could act as promoters in the development of second neoplasms, these patients seem to have a genetic background favoring the development of MMPN. Secondary prevention is the best measure to avoid MMPN development

[Analysis of the characteristics of patients with bladder cancer diagnosed of multiple neoplasms in the health district of León (Spain)]. / Análisis de las características de los pacientes con cáncer vesical diagnosticados de neoplasias múltiples en el área sanitaria de León.

OBJECTIVE: We analyzed the characteristics of the patients with bladder neoplasms who developed a multiple malignant primary neoplasm (MMPN) in the health district of León, the impact on survival and the prognostic variables. MATERIAL AND METHODS: We have used the data from the Tumor Registry of the Hospital of León and selected all those patients who were diagnosed of a bladder tumor between 1993 and 2002. They were classified into two groups: the first with 71 patients with MMPN and a second group with 159 patients with single bladder tumors diagnosed between 1996 and 1997. RESULTS: Incidence of MMPN was of 7.1 percent. More than half of the patients had familial oncologic background. The second most frequently diagnosed neoplasms were urologic, followed by gastrointestinal and respiratory. Survival of patients with MMPN was 21 percent lower than single neoplasms. Variables with prognosis significance were the stage of the second neoplasm, diagnosis of a second urologic neoplasm and surgery treatment for the second tumor. CONCLUSIONS: MMPN in patients with bladder tumors are frequent in our geographic area. The high frequency of familial oncologic antecedents in these patients suggest a genetic background. Prognosis of MMPN patients is worse than single tumors patients, but no differences were observed regarding prognosis in patients with synchronous or metachronous MMPN.

Cáncer colo-rectal multicéntrico (CCRM) en el área sanitaria de León / Multicentric colo-rectal cancer (MSCC) in the health district of León

Objetivos: Analizar las características de los pacientes diagnosticados de CCRM en el área sanitariade León, el impacto sobre la supervivencia y las posibles variables pronósticas.Material y métodos: Utilizando los datos del Registro de Tumores del Hospital de León se hananalizado las características de aquellos pacientes con tumores colo-rectales diagnosticados entre 1993y 2002, clasificándolos dos grupos: el primero constituido por 74 pacientes diagnosticados de CCRMy el segundo formado por 1342 pacientes con tumores únicos diagnosticados en el bienio 1996-1997.Resultados: La frecuencia de CCRM fue del 2,7%. La edad de los pacientes con CCRM fue 2años mayor con respecto a la de los pacientes con neoplasias únicas, con una elevada proporción(38%) de antecedentes familiares oncológicos en familiares de primer grado. No se observaron diferenciassignificativas en cuanto a la localización y el estadio del primer tumor colo-rectal con respectoal grupo de tumores únicos. La supervivencia de los pacientes con CCRM metacrónico fue netamenteinferior, posiblemente en relación con un mayor número de segundas neoplasias diagnosticadas en estadiostempranos en los pacientes con CCRM sincrónico. Las variables que influyeron en el pronósticofueron la edad, el sexo, y el padecimiento de un CCRM sincrónico o metacrónico.Conclusiones: El CCRM es una entidad frecuente en nuestro medio. La tasa de antecedentes familiaresoncológicos en estos pacientes es muy elevada. No se encontraron diferencias significativasen cuanto al pronóstico de estos pacientes respecto al de los pacientes con neoplasias únicas

Purpose: We analyze the characteristics of patients with multicentric colo-rectal cancer (MCRC)in the health district of León, the impact on survival, and the prognostic variables.Material and methods: : Using the data from the Hospital de León Tumour Registry, weanalyzed the characteristics of all the patients diagnosed of having colo-rectal tumours between 1993and 2002. The patients were classified in two groups: one of them composed by 74 patients with MCRC,and the other formed by 1342 patients diagnosed in 1996 and 1997 of having single colo-rectal tumours.Results: The observed frequency of MCRC corresponded to 2.7 percent of the whole cases. Theage of the MCRC patients was 2 years higher than that of the patients with single neoplasms, andshowed a higher familial oncologic history, that was present in 38 percent of the cases. No differenceswere observed for location and stage of the first appeared colo-rectal neoplasm. The survival of thepatients developing metachronous MCRC was lower than for those with synchronous disease,possibly due to the higher number of the second neoplasms appearing in these patients at early stages.Prognostic values were age, sex, and metachronous or synchronous type of disease.Conclusions: MCRC is a frequent entity. The frequency of familial oncologic history is veryhigh. No significant differences were seen in relation to prognosis between single and multiple colorectalcancer

Multiple malignant primary neoplasms in patients with gatric neoplasms in the health district of León.

OBJECTIVES: We analyzed the characteristics of patients with gastric tumors diagnosed with multiple malignant primary neoplasm (MMPN) in the Health District of León. MATERIAL AND METHODS: Using the information in the Tumor Registry at León Hospital patients selected were those with gastric neoplasms diagnosed between 1993 and 2002. A follow-up was performed until December 31, 2004, and the characteristics of patients diagnosed with a second neoplasm were analyzed. RESULTS: MMPN prevalence was 1,96%; 56% of patients had a history of cancer in first-degree relatives. The most frequent second neoplasms were digestive (26%) and urologic (21%); 87% of patients were diagnosed with a second neoplasm within the first two years. No significative differences in survival were observed among patients with synchronous or metachronous MMPN. CONCLUSIONS: MMPN in patients with gastric neoplasms is a relevant problem. While external carcinogenic agents could act as promoters in the development of second neoplasms, these patients seem to have a genetic background favoring the development of MMPN. Secondary prevention is the best measure to avoid MMPN development.

Effect of pimobendan in patients with chronic heart failure.

OBJECTIVE: To assess the effects of a calcium sensitizer, pimobendan, in patients with mild to moderate chronic heart failure. PATIENTS AND METHODS: Pimobendan was administered at a dose of 2.5 mg/day for 12 months to 34 patients with chronic heart failure (New York Heart Association functional class IIm to III) after treatment with diuretics and angiotensin-converting enzyme inhibitors. The etiologies of heart failure were dilated cardiomyopathy (DCM), old myocardial infarction (OMI) and other heart disease (Others). The effects of pimobendan were assessed by echocardiography, blood pool scintigraphy, Holter monitoring, (123)I-meta-iodobenzylguanidine (MIBG) imaging and (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) imaging. RESULTS: Pimobendan produced improvement of symptoms in the majority of patients. Improvement was more common in the DCM group than in the OMI group. Left ventricular internal diameter measured by echocardiography was significantly decreased. Left ventricular ejection fraction was significantly increased in the DCM and Others groups. The heart to mediastinum ratio on MIBG imaging was significantly increased in the DCM and Others groups, and the heart to mediastinum ratio on BMIPP imaging was significantly increased in the DCM group. CONCLUSIONS: Pimobendan is effective in patients with chronic heart failure but is less effective in patients with OMI than in patients with DCM or other heart diseases.

[Incidence of digestive tumors in the health district of Leon, Spain in 1993-1997: high incidence of colorectal carcinoma]. / Incidencia de los tumores digestivos en el Area de Salud de León en el quinquenio 1993-1997: alta incidencia del carcinoma colorrectal.

AIM: To determine the incidence of various digestive tumors in the health district of Leon. PATIENTS AND METHODS: All digestive tumors registered in the Hospital Tumor Registry in Leon from 1993-1997 were included. Unadjusted and adjusted incidence rates of each kind of tumor, using the ICD-9 classification, were calculated. RESULTS: A total of 9,913 cancer cases were included. Diagnosis was confirmed by the Department of Pathology in 93.4%. Of these, 25.38% originated primarily in the digestive system, which represents an unadjusted incidence of 151.73 new cases per 100,000 inhabitants/year. A total of 58.07% were male and 41.93% female. Colon cancer was the most frequent (31.5%), followed by gastric cancer (25.7%) and rectal cancer (20.3%). The highest incidence, both unadjusted and adjusted, was in colon cancer (52.8 and 25.9) followed by gastric cancer (47.4 and 24.3) and rectal cancer (36.1 and 18.3, all they 10(5)/year. CONCLUSIONS: Incidence of digestive cancer in Leon is very high and that of colorectal cancer is higher than in any other region in Spain. This is only partly due to the marked aging of our population.

Cellular regulation of ribosomal DNA transcription:both rat and Xenopus UBF1 stimulate rDNA transcription in 3T3 fibroblasts.

A novel RNA polymerase I (RPI) driven reporter gene has been used to investigate the in vivo role of the architectural ribosomal transcription factor UBF in gene activation and species specificity. It is shown that the level of UBF overexpression in NIH3T3 cells leads to a proportionate increase in the activities of both reporter and endogenous ribosomal genes. Further, co-expression of UBF antisense RNA suppresses reporter gene expression. Thus, UBF is limiting for ribosomal transcription in vivo and represents a potential endogenous ribosomal gene regulator. In contrast to some in vitro studies, in vivo, the mammalian and Xenopus forms of UBF1 show an equal ability to activate a mouse RPI promoter. This activity is severely impaired in mutants compromised for either dimerization or DNA binding. Similarly, the natural UBF2 splice variant shows a severely impaired capacity to activate RPI transcription. The data strongly suggest that UBF predominantly regulates ribosomal transcription by binding to and activating the ribosomal genes, but does not eliminate a possible secondary role in titrating ribosomal gene repressors such as Rb. Consistent with the DNA folding ability and cellular abundance of the UBF, we suggest that the protein may regulate a structural transition between the potentially active and active chromatin states.

Affinity purification of mammalian RNA polymerase I. Identification of an associated kinase.

Overlapping cDNA clones encoding the two largest subunits of rat RNA polymerase I, designated A194 and A127, were isolated from a Reuber hepatoma cDNA library. Analyses of the deduced amino acid sequences revealed that A194 and A127 are the homologues of yeast A190 and A135 and have homology to the beta' and beta subunits of Escherichia coli RNA polymerase I. Antibodies raised against the recombinant A194 and A127 proteins recognized single proteins of approximately 190 and 120 kDa on Western blots of total cellular proteins of mammalian origin. N1S1 cell lines expressing recombinant His-tagged A194 and FLAG-tagged A127 proteins were isolated. These proteins were incorporated into functional RNA polymerase I complexes, and active enzyme, containing FLAG-tagged A127, could be immunopurified to approximately 80% homogeneity in a single chromatographic step over an anti-FLAG affinity column. Immunoprecipitation of A194 from 32P metabolically labeled cells with anti-A194 antiserum demonstrated that this subunit is a phosphoprotein. Incubation of the FLAG affinity-purified RNA polymerase I complex with [gamma-32P]ATP resulted in autophosphorylation of the A194 subunit of RPI, indicating the presence of associated kinase(s). One of these kinases was demonstrated to be CK2, a serine/threonine protein kinase implicated in the regulation of cell growth and proliferation.

[Effects of oral amezinium metilsulfate in patients with sick sinus syndrome].

The effects of amezinium metilsulfate (Risumic) were studied in patients with sick sinus syndrome. Four males and 11 females with clinical symptoms were treated with 0.5 mg/kg for 1 to 40 weeks. In all patients, the length of sinus pause observed during 24-hour Holter monitoring was longer than 2.0 sec, and/or the sinus node recovery time in the electrophysiologic study was longer than 2.0 sec. The effects were evaluated by Holter monitoring and standard electrocardiography. The total number of heart beats every 24 hours by Holter monitoring were significantly increased from 78,917 +/- 15,983 (mean +/- SD) to 85,753 +/- 17,849 beats after the treatment. The length of the sinus pause was significantly decreased from 3.89 +/- 1.24 to 2.36 +/- 1.45 sec. Patients with sinus node recovery time of less than 5.0 sec showed the effects especially clearly. The total number of premature ventricular contractions was decreased from 530 +/- 767 to 123 +/- 182 beats. The PQ, QRS and QTc intervals did not change. Only diastolic pressure was slightly increased. Clinical symptoms disappeared in almost all patients and the clinical courses were favorable. Amezinium metilsulfate, which stimulates the intrinsic sympathetic nervous system, increased total heart beat and shortened sinus pause in patients with sick sinus syndrome. Few side effects, such as arrhythmogenecity or increase of blood pressure were observed. These results show that amezinium metilsulfate is useful in the treatment of patients with sick sinus syndrome, if the disease is not so severe as to require implantation of a cardiac pacemaker.

Growth factor for cardiac hypertrophy.

Cardiac size can be regulated by the balance in activity between cardiac growth factors and inhibiting factors, chalones. This study was undertaken to verify the role of the cardiac growth factor and its purification from hypertrophied hearts. For this propose the hypertrophied hearts of renovascular hypertensive rats were used. The purification was made by using an isoelectric focusing chromatography and the HPLC method. We examined the cardiac growth effect of the isolated fractions with cultured chicken embryonic cardiac myocytes. Simultaneously, the influence of these fractions on the cardiac cell cycle was examined by DNA analysis with the flow cytometric method. If the hearts were overloaded due to hypertension, the growth of the cardiac size could be induced by increased the level of five proteins with different molecular weight and with an isoelectric point of 8.3. The significant growth activities were observed at these five proteins compared to the absence of the fractions. For the appearance of these growth effect, it is necessary that the structure of the protein is there fundamentally as a form with a molecular weight of 27 k dalton. After addition of these isolated fractions, BrdU content is S and G2 phases by flow cytometry was increased. This change indicates that the cardiac myocytes are stimulated in form DNA synthesis.

Abnormalities of ADP/ATP carrier protein in J-2-N cardiomyopathic hamsters.

ADP/ATP carrier protein (AAC) is located in the mitochondrial inner membrane and has an important function in mitochondrial energy supply. This protein transports ATP to the cytoplasm and counter transports ADP into the mitochondria. J-2-N cardiomyopathic hamsters were investigated to determine the AAC content in cardiac mitochondria. After recording an electrocardiogram and collecting blood, the cardiac mitochondria were isolated. The mitochondrial membranes were labelled with eosin-5-maleimide (EMA) and separated on SDS polyacrylamide gels. The position of the AAC component was identified by exposing the gel under UV light, and the AAC content was determined by densitometry after staining with Coomassie blue. The AAC content ratio was significantly decreased in both 10-week-old and 1-year survived J-2-N hamsters when compared to control Golden hamster. Among 10-week-old J-2-N hamsters, the decrease in the AAC content ratio was more marked for the animals with more severe myocardial damage. The H(+)-ATPase activities of mitochondrial membrane were higher in 10-week-old J-2-N hamsters than in control hamsters. These results suggest that the decrease of AAC in J-2-N hamster plays an important role in the pathogenesis of cardiomyopathy in J-2-N hamsters.

Myocardial contractility and ventricular myosin isoenzymes as influenced by cardiac hypertrophy and its regression.

Changes in myocardial contractility and ventricular myosin isoenzymes were examined during pressure-overloaded cardiac hypertrophy in rats. Effects of regression of cardiac hypertrophy were also examined. Cardiac hypertrophy was induced by abdominal aortic constriction in 7-week-old male Wistar rats. Regression of cardiac hypertrophy was obtained by opening the aortic band. Myocardial contractility was estimated by measuring isometrically developed tension and maximum rate of tension rise (+dT/dtmax) in isolated left-ventricular papillary muscles perfused with Tyrode solution (32 degrees C, pH 7.4, bubbled with 95% O2.5% CO2, stimulation frequency: 0.2 Hz). Left-ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis and the isoenzyme pattern was determined by densitometry. Isometrically developed tension (T) in hypertrophic myocardium remained unchanged, but +/-dT/dtmax decreased as compared with hearts of normal rats. Decreased +/-dT/dtmax recovered near to the level in normal rats by regression of cardiac hypertrophy. Left-ventricular myosin isoenzyme pattern shifted towards VM-3 in hypertrophied myocardium and shifted again toward VM-1 by regression of cardiac hypertrophy. In conclusion, myocardial contractility and ventricular myosin isoenzymes were changed in pressure-overloaded hypertrophy in rats and these changes were reversible to a normal level by regression of cardiac hypertrophy.

Effects of regression of cardiac hypertrophy on myocardial contractility and ventricular myosin isoenzymes.

The effects of regression of cardiac hypertrophy on myocardial contractility and ventricular myosin isoenzymes were investigated in rats with renovascular hypertension. Six-week-old male Wistar rats were made hypertensive by constriction of one renal artery with a silver clip. Regression of cardiac hypertrophy was induced following the lowering of blood pressure by nephrectomy on the affected side 5-6 weeks after constriction of the renal artery and was maintained for 5-6 weeks. In contrast, myocardial hypertrophy was induced by 10-11 weeks of the hypertensive state. Isometric developed tension of isolated left ventricular papillary muscles was measured, while they were being perfused with Tyrode solution. Left ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis. The ventricular to body weight ratio of the nephrectomized group was significantly lower than that of the hypertensive group, although it was greater than that of age-matched normal control rats. There were no significant differences in the isometric developed tension among three groups, the nephrectomized, hypertensive, and normal control rats. However, dT/dtmax tended to decrease in the hypertensive rats and recovered to normal in the nephrectomized rats. The left ventricular myosin isoenzyme pattern was shifted toward VM-3 in hypertensive rats and was shifted back toward VM-1 again in nephrectomized rats.

[A histopathological study of the hepatic changes induced by parenteral nutrition in the rat]. / Estudio histopatológico de las alteraciones hepáticas inducidas por la nutrición parenteral en la rata.

Total parenteral nutrition is associated with hepatic metabolic and morphologic changes. Histological alterations induced by administration of glucose plus amino acids (group A) or glucose plus amino acids and lipids (group B) have been investigated in the rat. Parenteral nutrition provided 187 kcal/kg/day in both groups of animals. Rats in group B received 30% of nonprotein calories as lipids (Intralipid). In group A the most frequent histopathological findings were inflammation, portal edema and microesteatosis. Those alterations did not disappear by lipid addition, being frequent the existence of congestive phenomenons and esteatosis together with occasional pigment deposits in Kupffer cells. Those data suggest that supplementation of solutions with LCT-base lipid emulsions does not compensate for the histopathological alterations induced by parenteral nutrition.