Seroprevalence canine survey for selected vector-borne pathogens and its relationship with poverty in metropolitan Pereira, Colombia, 2020.

Background: Tick-borne diseases (TBD) and dirofilariosis are currently not under surveillance in most Latin American countries. In addition, there is a significant lack of studies describing the current situation in most endemic areas, including Colombia. Therefore, seroprevalence studies are crucial for understanding the epidemiology of these vector-borne diseases. Methods: A serosurvey for TBD and dirofilariosis among 100 dogs was carried out in the municipality of Pereira, located in the Coffee-Triangle region, Colombia. Samples were tested using a rapid assay test system (SNAP® 4Dx®); based on an enzyme immunoassay technique' screening for antibodies to Anaplasma phagocytophilum/platys (sensitivity 99.1%)' Borrelia burgdorferi s.l. (98.8%), and Ehrlichia canis/ewingii (96.2%) by using specific antigens and checking for Dirofilaria immitis antigen based on specific antibodies (99.2%). Bivariate analyses were performed on Stata®14, significant p < 0.05. Findings: Global seroprevalence to the selected vector-borne pathogens was 74% (95%CI 65-83%). The highest seroprevalence was found for E. canis/ewingii (74%), followed by A. phagocytophilum/platys (16%). Seropositivity for Borrelia spp. and Dirofilaria spp. was 0%. All Anaplasma spp. seropositive dogs showed co-detection of Ehrlichia spp. (16%). Seroprevalence was significantly higher among dogs from families of lower socioeconomic status/level (I, 86%), followed by level II (74%), and III (36%) (p = 0.001). All dogs exhibiting anorexia (12%) were invariably seropositive (100%) (p = 0.029). Seroprevalence was higher among those showing mucocutaneous paleness (95%) compared to those without paleness (68%) (p = 0.013) (OR = 9.3; 95%CI 1.18-72.9). There was high variability in seroprevalence through the studied areas, ranging from 0% (La Libertad Park) up to Combia, Cesar Nader, Las Brisas and Saturno localities (100%) (p = 0.033). Interpretation: Given the high seroprevalence obtained in an area with documented ticks, there is a potential risk of zoonotic transmission to humans. Further seroprevalence studies in humans are needed to assess the prevalence of infections. Poverty is highly associated with these tick-borne pathogens in Pereira, as shown in the present study.

Randomized clinical trial between polyacrylate-polyalcohol copolymer (PPC) and dextranomer-hyaluronic acid copolymer (Dx/HA) as bulking agents for endoscopic treatment of primary vesicoureteral reflux (VUR).

OBJECTIVE: To compare the radiological and clinical outcomes of endoscopic treatment of primary VUR using polyacrylate-polyalcohol copolymer (PPC-Vantris®) or dextranomer-hyaluronic acid copolymer (Dx/HA-Deflux®). MATERIALS AND METHODS: From October 2014 to April 2017, patients with primary VUR grade III to V that needed endoscopic treatment (ET) were eligible for this randomized clinical trial. We excluded toilet-trained patients with lower urinary tract symptoms. Patients were randomized and allocated into two groups: PPC group and Dx/HA group. After endoscopic treatment a voiding cystourethrography (VCUG) was performed at 6 months; if VUR was still present a second ET was performed. Radiological success was considered if postoperative VUR grade was 0 and clinical success rate was considered if no more fUTI appeared during follow-up. RESULTS: Forty-six patients were eligible but 2 did not accept the trial. Forty-four patients with 73 refluxing ureters were included. PPC: 34 refluxing ureters; and Dx/HA: 39 refluxing ureters. Both groups were statistically homogeneous and comparable. Mean follow-up was 27.6 months. Radiological success rate (82.2%) and clinical success rate (92.3%) were similar in both groups (p > 0.05). The volume of bulking agent used in those successfully treated was greater in Dx/HA group (p < 0.05). Distal ureter was excise in all cases of ureteral reimplantation after PPC treatment; however, distal ureter was preserved in all ureters reimplanted after Dx/HA injection. CONCLUSION: PPC and Dx/HA had similar outcomes, but we must warn that ureteral reimplantation after endoscopic treatment with PPC is difficult because of the periureteral fibrosis.

Valoración de riesgo de los hallazgos clínico-quirúrgicos y de anatomía patológica en neonatos con enterocolitis necrotizante que han recibido tratamiento quirúrgico / Evaluation of the risk of the clinical-surgical and pathology study findings in newborns with necrotizing enterocolitis who have received surgical treatment

Introducción. A pesar de los avances en cuidados neonatales entre el 20 y 63% de los niños con enterocolitis necrotizante (ECN) necesitan cirugía. El objeto fue buscar una correlación y factores de riesgo de los neonatos con ECN “IIB/IIIA/IIIB” de Bell y los hallazgos clínicos, quirúrgicos y de anatomía patológica. Material y métodos. Se analizaron neonatos con diagnóstico de ECN que recibieron cirugía y se analizó las variables: clínico- quirúrgicas y de anatomía patológica. Estudiamos dos grupos: control (n= 5)y grupo ECN (n= 12). Se realizaron comparaciones entre los grupos mediante la U-Mann-Whitney y el coeficiente de Sperman (r). Para valorar el riesgo de morbilidad/mortalidad asociada a la extensión de (..) (AU)

Introduction. Despite advances in neonatal care between 20% and63% of children with necrotizing enterocolitis (NEC) require surgery. The aim was correlation the risk factors of infants with NEC “IIB / IIIA/ IIIB” Bell and the clinical, surgical and pathological findings. Method. In the children with diagnosis of NEC surgically treated, were analyzed of variables: clinical, surgical and pathological findings. We studied two groups: control (n= 5) and NEC group (n= 12). Comparisons were made between groups using the Mann-Whitney U- and the Spearman coefficient (r). To assess the risk of morbidity / mortality associated with the extent of intestinal resection we applied the Cox (..) (AU)

[Evaluation of the risk of the clinical-surgical and pathology study findings in newborns with necrotizing enterocolitis who have received surgical treatment]. / Valoración de riesgo de los hallazgos clínico-quirúrgicos y de anatomía patológica en neonatos con enterocolitis necrotizante que han recibido tratamiento quirúrgico.

INTRODUCTION: Despite advances in neonatal care between 20% and 63% of children with necrotizing enterocolitis (NEC) require surgery. The aim was correlation the risk factors of infants with NEC "IIB / IIIA / IIIB" Bell and the clinical, surgical and pathological findings. METHOD: In the children with diagnosis of NEC surgically treated, were analyzed of variables: clinical, surgical and pathological findings. We studied two groups: control (n=5) and NEC group (n=12). Comparisons were made between groups using the Mann-Whitney U- and the Spearman coefficient (r). To assess the risk of morbidity / mortality associated with the extent of intestinal resection we applied the Cox regression. RESULT: We found differences (p < 0.05) between control group and the NEC group regarding Bell, the mean height of villi, Chiu and the number of goblet cells. In the NEC group we find correlations (p < 0.05) from Bell, regarding Chiu (r = 0.761), resection of the colon (r = 0.687), pneumatosis / perforation (r = 1) and the mean height of villi (r = -0.878). The gut reseccion was at 26 cm (3-107). We observed a risk of 1.04 in the neonatal period (p > 0.05) of mortality or consequence post-enterocolitis associated with the extent of bowel resection. CONCLUSION: The decrease in the average height of villi, the highest level of microscopic intestinal injury and reduced goblet cell population contributes to a greater extent of intestinal resection, which favors the risk of death or developing consequence post-enterocolitis.

Digestive alpha-amylases from Tecia solanivora larvae (Lepidoptera: Gelechiidae): response to pH, temperature and plant amylase inhibitors.

The biochemical properties of the digestive alpha-amylase from Tecia solanivora larvae, an important and invasive insect pest of potato (Solanum tuberosum), were studied. This insect has three major digestive alpha-amylases with isoelectric points 5.30, 5.70 and 5.98, respectively, which were separated using native and isoelectric focusing gels. The alpha-amylase activity has an optimum pH between 7.0 and 10.0 with a peak at pH 9.0. The enzymes are stable when heated to 50 degrees C and were inhibited by proteinaceous inhibitors from Phaseolus coccineus (70% inhibition) and P. vulgaris cv. Radical (87% inhibition) at pH 6.0. The inhibitors present in an amaranth hybrid inhibited 80% of the activity at pH 9.0. The results show that the alpha-amylase inhibitor from amaranth seeds may be a better candidate to make genetically-modified potatoes resistant to this insect than inhibitors from common bean seeds.

Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer.

PURPOSE: Recent studies suggest that HER-2/neu specifically promotes the invasive capacity of tumor cells by up-regulating secretion of the proteolytic enzyme, urokinase-type plasminogen activator (uPA), or its inhibitor, plasminogen activator inhibitor-1 (PAI-1), in colon and gastric cancer. It was the purpose of this study to: (a) evaluate the association between HER-2/neu and uPA and PAI-1 expression in a large primary breast cancer cohort; (b) perform the first multivariate analysis, including HER-2/neu, uPA, and PAI-1 in breast cancer; and (c) define the effect of HER-2/neu overexpression on uPA and PAI-1 expression in breast cancer cells. EXPERIMENTAL DESIGN: HER-2/neu, uPA, and PAI-1 were measured as continuous variables by ELISA in primary breast cancer tissue extracts from 587 patients with clinical follow-up and analyzed for correlations with clinical outcome. Furthermore, a full-length human HER-2/neu cDNA was introduced into five human breast cancer cell lines to define the effects of HER-2/neu overexpression on uPA and PAI-1 expression. In addition, we tested whether HER-2/neu antibodies could reverse any given alteration of uPA and PAI-1 levels. RESULTS: Our findings indicate a weak positive association between HER-2/neu and uPA (r = 0.147; P < 0.001) and no association between HER-2/neu and PAI-1 (r = 0.07; P = 0.085). HER-2/neu overexpression (> or =400 fmol/mg) and high levels of uPA/PAI-1 (> or =5.5 ng/mg and/or > or =14 ng/mg, respectively) were significantly associated with shorter disease-free survival (DFS; P < 0.001 and P = 0.003) and metastasis-free survival (MFS; P = 0.015 and P < 0.001). Multivariate analysis revealed prognostic independence between HER-2/neu and the uPA/PAI-1 axis for DFS and MFS. Both uPA and PAI-1 had no significant discriminatory effect among HER-2/neu-positive patients for DFS. The prognostic value of HER-2/neu overexpression for MFS, however, was significantly enhanced by elevated uPA expression (P = 0.053). Stable transfection of the HER-2/neu gene into multiple human breast cancer cell lines resulted in consistent down-regulation of uPA or PAI-1 expression. In addition, anti-HER-2/neu antibodies did not significantly affect uPA or PAI-1 expression in human cancer cell lines naturally overexpressing HER-2/neu. CONCLUSIONS: The present findings suggest that the invasive phenotype elicited by HER-2/neu overexpression in breast cancer is not a direct effect of uPA or PAI-1 expression. HER-2/neu and the uPA/PAI-1 axis have been shown to affect the invasive capacity of breast cancer independently. Determination of uPA can provide significant additional prognostic information for MFS in HER-2/neu-positive and -negative patients.

A protease inhibitor associated with the surface of Toxoplasma gondii.

Toxoplasma gondii has a broad host-range including man and a variety of warm-blooded animals. The ability to infect and survive in this wide spectrum of hosts suggests highly evolved mechanisms to handle the harsh environments encountered. Here we show that extracellular tachyzoites are resistant to milligram levels of trypsin and describe the presence of an inhibitor of trypsin associated with the surface of T. gondii, TgTI. TgTI has an estimated molecular mass of 37000 dalton and is encoded by the TgTI-gene which is found at low abundance as an expressed sequence tag (EST) in both the bradyzoite and tachyzoite stages. The inhibitory binding region was found to be in the N-terminus of TgTI where aminoacid-alignment to earlier described protease inhibitors demonstrates 75% similarity. In functional analysis, recombinant TgTI-protein inhibits the activity of trypsin approximately 10 times more efficiently than an inhibitor isolated from soybean. In contrast to other known trypsin inhibitors, TgTI also possesses a predicted membrane-binding region. Polyclonal antibodies raised against recombinant TgTI bind to the surface of the tachyzoite stage as seen both by immunofluorescence and immunoprecipitation of surface labelled parasite proteins. The high survival rate of the parasite in the upper gastrointestinal tract may be enhanced by the presence of the TgTI-molecule.

[Analysis of complex segregation in a large family with hereditary cerebrovascular disease in Antioquia, Colombia]. / Análisis de segregación compleja de una familia numerosa con enfermedad cerebrovascular hereditaria en Antioquia (Colombia).

INTRODUCTION: Among different kinds of cerebrovascular diseases, few of them are caused by genetic disturbances, such as CADASIL (caused by Notch3 mutations), CARASIL, mitochondrial encephalopathy, MELAS and dementia typed Binswanger. However, to describe these type of cerebrovascular diseases related with genetic mutations could permit to determinate the causes of both hereditary and sporadic cerebrovascular diseases and then lead solutions. OBJECTIVE: To describe the genetic, environmental and cohort factors that determinate the presence of many affected people by a several cerebrovascular diseases in the pedigree of a large family from Antioquia (Colombia). PATIENTS AND METHODS: We performed one pedigree (268 individuals), through singular recruit and then complex segregation analysis with POINTER program. RESULTS: The model that more close to data is autosomal dominant mayor locus without influence of environmental factors. Frequency of allele of susceptibility to develop stroke or subcortical vascular dementia was 0.0006. Mayor gene is over epistatic effects or interactions with other gene. CONCLUSIONS: Described an autosomal dominant hereditary model through complex segregation analysis in a pedigree of patients with hereditary cerebral vascular diseases characterized by recurrent strokes, early onset subcortical dementia, hearing loss, antecedent of migraine and MRI signal abnormalities, subcortical infarcts and leukoencephalopathy. In this family the parameter calculated, autosomal dominant model, and clinical feature strongly support the diagnostic of CADASIL, linkage analysis and sequentiation will be performed to determinate if mutant gene is Notch3.

Demencia vascular hereditaria tipo CADASIL en Colombia.III. Análisis de ligamiento a Notch3 / Vascular hereditary dementia cadasil type in Colombia. III. Linkage analysis to Notch3 gene

Objetivo. Realizar el análisis de ligamiento entre los marcadores microsatélites D19S923, D19S929 y D19S22, los cuales flanquean el gen Notch3, para contrastar la hipótesis de que el fenotipo enfermedad vascular hereditaria detectado en una extensa familia de Colombia es una arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). Somos conscientes de que técnicas como el SSCP (Single Strand Conformational Polymorphisms) pueden dilucidar si hay mutaciones sobre Notch3, pero no darían información si existen alteraciones intrónicas. Introducción. El fenotipo CADASIL es causado por una mutación en el gen Notch3. El espectro clínico de esta enfermedad familiar consiste en episodios de infartos cerebrovasculares recurrentes, historia de migraña, isquemia cerebral transitoria, cambios de comportamiento y demencia. Material y métodos. Los análisis de ligamiento fueron llevados a cabo mediante el uso de métodos paramétricos y no paramétricos. El análisis paramétrico se realizó de acuerdo con el modelo general de Elston-Stewart. El análisis de ligamiento no paramétrico se efectuó mediante el método de sib pair (pares de hermanos). Se realizaron simulaciones variando el fenotipo de afección de la enfermedad, incluyendo y no incluyendo individuos afectados de migraña, los valores de penetrancia, las frecuencias genéticas de los alelos de los loci marcadores y del locus enfermo, para determinar el efecto de estos cambios sobre los valores de LOD (logarithm of odds) score obtenidos. Resultados. Los resultados de LOD score máximos unipunto se presentaron cuando se consideró un valor de penetrancia cercana a 1 (2,04). El análisis de ligamiento multipunto cartografió el gen causante de la demencia vascular hereditaria en esta familia a 0,11 cM de D19S23, distancia a la cual se encuentra Notch3. Ello significa que existe una probabilidad mayor de 100 veces de que exista ligamiento a Notch3 frente a que éste no exista y que, por ende, el gen causante de la demencia vascular hereditaria en este grupo familiar colombiano es, con una probabilidad muy alta, el Notch3. Los resultados de los análisis de ligamiento no paramétricos fueron similares a los resultados paramétricos. Estos valores de LOD score no se sostuvieron cuando se consideró la migraña como una forma de afección con baja penetrancia.Conclusiones. Los resultados del análisis de ligamiento confirman que la forma de demencia vascular hereditaria que presenta esta familia colombiana es CADASIL, ocasionado por polimorfismos sobre Notch3.Del mismo modo, sugieren que el fenotipo migraña representa una entidad independiente del fenotipo CADASIL. Finalmente, los resultados plantean la necesidad de realizar secuenciamiento de los exones en los que se han descrito conglomerados de mutaciones que causan CADASIL. Dichos resultados permitirán comparar, diagnosticar, realizar seguimiento y definir por qué existe tan alta variabilidad en el comportamiento familiar de la enfermedad (AU)

[Lung infection by Mycobacterium terrae]. / Infección pulmonar por Mycobacterium terrae.

Mycobacterium terrae complex encompasses three species of microbacteria that are usually saprophytic and that may occasionally cause disease in humans, particularly in joints and synovial fluid. The literature includes slightly over a dozen cases of pulmonary infection, although none has been described in Spain. We report a case of infection by M. terrae in an immunodepressed patient with no other risk factor. Microbial identification by culture was unexpected and clinical management was difficult due to the absence of an established treatment protocol.

Análisis de segregación compleja de una familia numerosa con enfermedad cerebrovascular hereditaria en Antioquia (Colombia) / Segregation analysis of hereditary cerebrovascular disease in a large family from antioquia (Colombia)

Introducción. Entre las diferentes formas de enfermedad cerebrovascular que existen, pocas son causadas por anomalías genéticas, tal es el caso del CADASIL (causado por mutaciones en el gen Notch3), el CARASIL, la encefalopatía mitocondrial MELAS y la demencia tipo Binswanger. Sin embargo, describir estas formas de enfermedades vasculares cerebrales asociadas a alteraciones genéticas permitirá discriminar las causas de las formas hereditarias y esporádicas de la enfermedad cerebrovascular y, consecuentemente, acercarnos a soluciones. Objetivos. Discriminar los componentes genéticos, ambientales y de cohorte que determinan la existencia de un gran número de afectados por una forma de enfermedad vascular cerebral hereditaria en la genealogía de una extensa familia proveniente de Antioquia (Colombia). Pacientes y métodos. Reconstrucción de la genealogía (268 individuos) mediante reclutamiento singular y posterior realización de análisis de segregación compleja usando el programa POINTER. Resultados. El modelo que mejor ajusta los datos es el de un locus mayor autosómico dominante sin la existencia de efectos ambientales. La frecuencia del alelo de susceptibilidad para desarrollar trombosis cerebral o demencia vascular subcortical es de 0,0006.El gen mayor detectado está sometido a efectos epistáticos o interacciones con otros genes. Conclusiones. Describimos un patrón de herencia autosómico dominante a través de un análisis de segregación compleja en una genealogía de pacientes con enfermedad cerebrovascular hereditaria caracterizada por episodios de trombosis cerebral recurrente, demencia subcortical precoz, hipoacusia, historia de migraña y alteraciones de tipo leucoencefalopatía e infartos subcorticales en la resonancia magnética de cráneo. En esta familia, los parámetros estimados, el modelo autosómico dominante y la correlación con la clínica sugieren fuertemente el diagnóstico de CADASIL; se realizarán estudios posteriores de ligamiento y secuenciación para determinar si el gen mutado es Notch3 (AU)

Infección pulmonar por Mycobacterium terrae / Lung infection by Mycobacterium terrae

Mycobacterium terrae complex comprende tres especies de micobacterias habitualmente saprofitas y que muy raramente causan enfermedad en humanos, sobre todo de localización articular y sinovial. En la bibliografía mundial se recoge algo más de una docena de casos de infección pulmonar, aunque ninguno de ellos en nuestro país. Presentamos un caso de infección por M. terrae en un paciente sin inmunodepresión ni otros factores de riesgo. Su identificación en los cultivos representó una sorpresa y su abordaje clínico ha planteado dificultades por la ausencia de pautas terapéuticas definidas. (AU)

Caracterización clínica de una familia numerosacon enfermedad vascular cerebral hereditaria en Colombia / Clinical characterization of hereditary cerebrovascular disease in a large family from colombia

Introducción. La arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) es causada por una mutación en el gen Notch3, cromosoma 19p13.1, y se caracteriza por alteración de las arterias cerebrales pequeñas. La presentación clínica consiste en migraña, infartos cerebrales recurrentes, cambios de comportamiento y demencia. Objetivo. Describir el fenotipo clínico de una familia colombiana con diagnóstico probable de CADASIL. Pacientes y métodos. Elaboramos una genealogía con 268 individuos, evaluación neurológica a 57 individuos y resonancia magnética craneal (RMN) a 25 de ellos. Resultados. El análisis clínico apoya fuertemente el diagnóstico de CADASIL ya que 12 individuos presentaron trombosis cerebral (TC) de repetición, que en cinco de ellos conllevó demencia subcortical. Dos pacientes presentaban demencia sin historia previa de TC. Todos los afectados por TC o demencia a los que se realizó RMN (nueve casos) tienen hiperintensidades de la sustancia blanca e infartos subcorticales. Otros siete individuos presentan anomalías típicas de CADASIL en la RMN, de los cuales cuatro son asintomáticos, uno tuvo episodios de isquemia cerebral transitoria y dos padecen migraña. Otros 22 pacientes presentan sólo migraña. Llama la atención la alta frecuencia de lesión del cuerpo calloso, encontrada en cinco individuos con TC o demencia, el paciente con isquemia cerebral transitoria y uno de los asintomáticos; además, resaltamos la presencia de hipoacusia en siete individuos con TC o demencia. Conclusiones. Describimos una familia con enfermedad vascular cerebral hereditaria caracterizada por episodios de TC, demencia vascular precoz, hipoacusia, migraña y leucoencefalopatía, infartos subcorticales y alteraciones del cuerpo calloso evidenciadas en la RMN. El análisis clínico apoya fuertemente el diagnóstico de CADASIL (AU)

[Clinical characteristics of hereditary cerebrovascular disease in a large family from Colombia]. / Caracterización clínica de una familia numerosa con enfermedad vascular cerebral hereditaria en Colombia.

INTRODUCTION: The cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the Notch3 gene in the chromosome 19p13.1. and is characterized by small-vessel disease of the cerebral. The clinical feature consists of migraine, recurrent strokes, mood changes and dementia. OBJECTIVE: To describe the clinical phenotype of a Colombian family with hereditary cerebrovascular disease. PATIENTS AND METHODS: We performed one pedigree with 268 individuals, neurologic examination to 57 members and magnetic resonance imaging (MRI) to 25 of them. RESULTS: Clinical analysis strongly support the diagnosis of CADASIL because 12 individuals had suffered recurrent stroke, five of them later developed subcortical dementia. Two patients developed dementia without preceding stroke. All affected individuals by stroke or dementia whom were tested with MRI had white matter hyperintensities and subcortical infarcts (nine cases). Others seven individuals have MRI signal abnormalities like CADASIL, four of them are asymptomatic, one had suffered ischemic transient attacks and two had suffered migraine. Other 22 individuals had only migraine. We outstand the high frequency of MRI signal abnormalities in corpus callosum that we found in five individuals with stroke or dementia, the patient with ischemic transient attack and one asymptomatic patient, either the presence of hearing loss in seven individuals with stroke or dementia. CONCLUSIONS: We describe one large family with hereditary cerebrovascular disease characterized by recurrent strokes, subcortical dementia, hearing loss, migraine, and MRI signal abnormalities typed leukoencephalopathy, subcortical infarcts and alterations in corpus callosum. Clinical analysis strongly support the diagnosis of CADASIL.

Prediction on admission of in-hospital mortality in patients older than 70 years with acute myocardial infarction.

STUDY OBJECTIVE: To identify the differential characteristics regarding risk factors, presentation, and clinical status on hospital admission in patients aged 70 years or older with acute myocardial infarction (MI) of less than 24 h of evolution, compared with patients younger than 70 years, and to analyze possible factors that could affect mortality on admission in the group of patients older than 70 years. STUDY DESIGN: Of 1,289 patients admitted in the coronary care unit with acute MI during the period 1988 to 1991, with a delay from onset of symptoms of less than 24 h, we defined two groups according to age: younger than 70 years (group 1) and 70 years or older (group 2) in order to analyze the possible predictive factors for mortality on hospital admission in patients older than 70 years (n = 322). By means of univariate analysis, we studied clinical variables that were present on admission; age; sex; medical history of diabetes, cerebrovascular accident, stable angina, previous MI, cardiac failure, right bundle branch block, and atrial fibrillation; previous treatment with digoxin, calcium antagonists, angiotensin-converting enzyme inhibitors (ACEI), antiaggregants or beta-blockers; location and extension of the acute MI, and thrombolysis. The association between mortality, as the dependent variable, and all other variables, as independent variables, was evaluated using a stepwise logistical regression procedure. RESULTS: In patients older than 70 years of age, the model included the following as independent predictors of mortality: female sex (odds ratio [OR], 2.59); complete right bundle branch block (CRBBB) (OR, 4.88); Q-wave MI (OR, 0.35 for non-Q-wave MI); and Forrester grade 2 to 3 (OR, 6.36) and 4 (OR, 80.14). CONCLUSIONS: In patients with acute MI and older than 70 years at the time of admission to the coronary care unit, together with the variables indicating the degree of hemodynamic involvement and the extension of the acute MI, factors such as female sex and CRBBB stand out as independent predictors of mortality.

HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells.

Growth of human breast cells is closely regulated by steroid hormone as well as peptide hormone receptors. Members of both receptor classes are important prognostic factors in human breast cancer. Clinical data indicate that overexpression of the HER-2 gene is associated with an estrogen receptor-negative phenotype. In this study, we demonstrate that introduction of a HER-2 cDNA, converting non-overexpressing breast cancer cells to those which overexpress this receptor, results in development of estrogen-independent growth which is insensitive to both estrogen and the antiestrogen, tamoxifen. Moreover, activation of the HER-2 receptor in breast cancer cells by the peptide growth factor, heregulin, leads to direct and rapid phosphorylation of ER on tyrosine residues. This is followed by interaction between ER and the estrogen-response elements in the nucleus and production of an estrogen-induced protein, progesterone receptor. In addition, overexpression of HER-2 receptor in estrogen-dependent tumor cells promotes ligand-independent down-regulation of ER and a delayed autoregulatory suppression of ER transcripts. These data demonstrate a direct link between these two receptor pathways and suggest one mechanism for development of endocrine resistance in human breast cancers.

[Neurological manifestations of fat embolism syndrome]. / Manifestaciones neurológicas del síndrome de embolia grasa.

Fat embolism is a frequent complication of long bone trauma. Although neurological signs are key elements in the diagnosis of this syndrome, little attention to them has been paid in the spanish literature. We present a retrospective study of 13 patients with fat embolism syndrome in which we focused on neurological manifestations and alterations in computerized tomography (CT) of the head. The most frequent symptom was impairment of consciousness of varying degrees. Three patients out of the 13 also presented focal signs (hemiparesis and partial seizures). CT revealed edema (4/7) and multiple low density foci (1/7). All but one patient recovered without sequelae. Our study does not allow us to establish either the physiopathology of fat embolism syndrome or the most effective treatment.

Correlation of the survival of ovarian cancer patients with mRNA expression of the 60-kD heat-shock protein HSP-60.

PURPOSE: Ovarian carcinomas express the 60-kD heat-shock protein HSP-60 at widely varying levels in different tumors. The aim of this study was to determine whether there was a relationship between expression of HSP-60 and survival in patients with ovarian carcinoma. MATERIALS AND METHODS: Total RNA and DNA were prepared from 51 epithelial ovarian cancer tissue samples. The expression and structure of the HSP-60 gene were examined by Northern and Southern blot analyses using the carboxyl-terminal portion of this gene as a probe (0.89 kilobases [kb]). HSP-60 expression was correlated with overall survival by the Kaplan-Meier method. RESULTS: The 2.3-kb HSP-60 message was detected in all samples, but there was marked variation from tumor to tumor. Patients were classified into two groups on the basis of HSP-60 expression: group 1 (n = 25) included patients with low expression, and group 2 (n = 26) consisted of patients with high expression. There were no significant differences between the groups with respect to age, cell type, pathologic grade, clinical stage, and previous treatment. After a median follow-up period of 17 months, Kaplan-Meier plots demonstrated a much better survival for group 1 (median, 46.8 months; 41% at 4 years) than group 2 (median, 22.1 months; 16% at 3.9 years), a difference that was highly significant by the Mantel-Haenszel test (P = .00183). Southern blot analysis of these samples showed no amplification or rearrangement of the gene. CONCLUSION: The level of HSP-60 mRNA expression is a valuable prognostic factor in epithelial ovarian cancer. Variation in the level of expression is not due to amplification of this gene.