Danthron, an Anthraquinone Isolated from a Marine Fungus, Is a New Inhibitor of Angiogenesis Exhibiting Interesting Antitumor and Antioxidant Properties.

The role played by a sustained angiogenesis in cancer and other diseases stimulates the interest in the search for new antiangiogenic drugs. In this manuscript, we provide evidence that 1,8- dihydroxy-9,10-anthraquinone (danthron), isolated from the fermentation broth of the marine fungus Chromolaenicola sp. (HL-114-33-R04), is a new inhibitor of angiogenesis. The results obtained with the in vivo CAM assay indicate that danthron is a potent antiangiogenic compound. In vitro studies with human umbilical endothelial cells (HUVEC) reveal that this anthraquinone inhibits certain key functions of activated endothelial cells, including proliferation, proteolytic and invasive capabilities and tube formation. In vitro studies with human breast carcinoma MDA-MB231 and fibrosarcoma HT1080 cell lines suggest a moderate antitumor and antimetastatic activity of this compound. Antioxidant properties of danthron are evidenced by the observation that it reduces the intracellular reactive oxygen species production and increases the amount of intracellular sulfhydryl groups in endothelial and tumor cells. These results support a putative role of danthron as a new antiangiogenic drug with potential application in the treatment and angioprevention of cancer and other angiogenesis-dependent diseases.

Characterization of the activity and the mechanism of action of a new toluquinol derivative with improved potential as an antiangiogenic drug.

The inhibition of sustained angiogenesis is an attractive approach for the treatment of cancer, blindness and other angiogenesis-dependent diseases. Encouraged by our previous finding that toluquinol, a methyl hydroquinone isolated from a marine fungus, exhibited an interesting antiangiogenic activity, we further explored structural modifications of this natural compound in order to develop improved drug candidates. Our results indicate that although the methyl group plays a relevant role in the cytotoxic activity of toluquinol, some derivatives in which this methyl was replaced by another substituent, could keep the antiangiogenic activity, whereas exhibiting a lower cytotoxicity in vitro. This is the case of (E)- 2-(3-methoxyprop-1-en-1-yl) benzene-1,4-diol, which exhibits a decreased toxicity, whereas maintaining or even improving the antiangiogenic activity of toluquinol, as demonstrated by a number of in vitro (endothelial cells proliferation, migration and tube formation) and in vivo (chick embryo chrorioallantoic membrane vascularization and murine corneal neovascularization) experimental approaches. Our results point to a mechanism of action that could be related to an induction of apoptosis, as well as to an increase in the reactive oxygen species levels, a reduction of the redox capacity and the inhibition of the VEGFR2, Akt and ERK phosphorylation in VEGF-activated endothelial cells. The biological activity of this new angiogenesis inhibitor, along with its lower undesired toxicity, suggests that it is a promising drug candidate with improved potential for the treatment of angiogenesis-related diseases.

A course-based undergraduate research experience to illustrate the early stages of the drug discovery process.

We have implemented at the University of Málaga (Spain) a new course-based undergraduate research experience (CURE) to involve undergraduate students of Science in a real-world scientific problem. Within the topic "Let's find acetylcholinesterase inhibitors as new drug candidates for the treatment of Alzheimer's", students have been engaged into the early stages of the drug discovery process. Working in groups of 4-5 persons, they have searched information in databases, proposed solutions to the driving question and designed protocols to carry them out in vitro and in silico. Overall, the implementation of this experience has been very satisfactory in terms of academic performance and students' perception. This article reports a session from the virtual international 2021 IUBMB/ASBMB workshop, "Teaching Science on Big Data".

Angioprevention of Urologic Cancers by Plant-Derived Foods.

The number of cancer cases worldwide keeps growing unstoppably, despite the undeniable advances achieved by basic research and clinical practice. Urologic tumors, including some as prevalent as prostate, bladder or kidney tumors, are no exceptions to this rule. Moreover, the fact that many of these tumors are detected in early stages lengthens the duration of their treatment, with a significant increase in health care costs. In this scenario, prevention offers the most cost-effective long-term strategy for the global control of these diseases. Although specialized diets are not the only way to decrease the chances to develop cancer, epidemiological evidence support the role of certain plant-derived foods in the prevention of urologic cancer. In many cases, these plants are rich in antiangiogenic phytochemicals, which could be responsible for their protective or angiopreventive properties. Angiogenesis inhibition may contribute to slow down the progression of the tumor at very different stages and, for this reason, angiopreventive strategies could be implemented at different levels of chemoprevention, depending on the targeted population. In this review, epidemiological evidence supporting the role of certain plant-derived foods in urologic cancer prevention are presented, with particular emphasis on their content in bioactive phytochemicals that could be used in the angioprevention of cancer.

Non-targeted metabolomics characterization of Annona muricata leaf extracts with anti-angiogenic activity.

The tropical plant Annona muricata has been widely used for traditional ethnobotanic and pharmacologic applications. Extracts from different parts of this plant have been shown to have a wide range of biological activities. In the present study, we carry out a metabolomic study of both aqueous and DMSO extracts from Annona muricata leaves that has allowed us to identify 33 bioactive compounds. Furthermore, we have shown that aqueous extracts are able to inhibit endothelial cell migration and both aqueous and DMSO extracts inhibit the formation of tubule-like structures by endothelial cells cultured on Matrigel. We conclude that extracts of Annona muricata leaves have great potential as anti-angiogenic natural combinations of bioactive compounds.

The Mediterranean Diet, a Rich Source of Angiopreventive Compounds in Cancer.

Diet-based chemoprevention of cancer has emerged as an interesting approach to evade the disease or even target its early phases, reducing its incidence or slowing down tumor progression. In its basis in the essential role of angiogenesis for tumor growth and metastasis, angioprevention proposes the use of inhibitors of angiogenesis in cancer prevention. The anti-angiogenic potential exhibited by many natural compounds contained in many Mediterranean diet constituents makes this dietary pattern especially interesting as a source of chemopreventive agents, defined within the angioprevention strategy. In this review, we focus on natural bioactive compounds derived from the main foods included in the Mediterranean diet that display anti-angiogenic activity, as well as their possible use as angiopreventive agents.

Leishmaniasis in the major endemic region of Plurinational State of Bolivia: Species identification, phylogeography and drug susceptibility implications.

The Plurinational State of Bolivia is one of the Latin American countries with the highest prevalence of leishmaniasis, highlighting the lowlands of the Department of La Paz where about 50% of the total cases were reported. The control of the disease can be seriously compromised by the intrinsic variability of the circulating species that may limit the efficacy of treatment while favoring the emergence of resistance. Fifty-five isolates of Leishmania from cutaneous and mucocutaneous lesions from patients living in different provinces of the Department of La Paz were tested. Molecular characterization of isolates was carried out by 3 classical markers: the rRNA internal transcribed spacer 1 (ITS-1), the heat shock protein 70 (HSP70) and the mitochondrial cytochrome b (Cyt-b). These markers were amplified by PCR and their products digested by the restriction endonuclease enzymes AseI and HaeIII followed by subsequent sequencing of Cyt-b gene and ITS-1 region for subsequent phylogenetic analysis. The combined use of these 3 markers allowed us to assign 36 isolates (65.5%) to the complex Leishmania (Viannia) braziliensis, 4 isolates (7, 27%) to L. (Viannia) lainsoni. and the remaining 15 isolates (23.7%) to a local variant of L. (Leishmania) mexicana. Concerning in vitro drug susceptibility the amastigotes from all isolates where highly sensitive to Fungizone® (mean IC50 between 0.23 and 0.5µg/mL) whereas against Glucantime® the sensitivity was moderate (mean IC50 ranging from 50.84µg/mL for L. (V.) braziliensis to 18.23µg/mL for L. (L.) mexicana. L. (V.) lainsoni was not sensitive to Glucantime®. The susceptibility to miltefosine was highly variable among species isolates, being L. (L.) mexicana the most sensitive, followed by L. (V.) braziliensis and L. (V.) lainsoni (mean IC50 of 8.24µg/mL, 17.85µg/mL and 23.28µg/mL, respectively).

Early- versus late-onset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients.

Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤ 30 years (early onset), age between 31 and 59 years (standard onset), and age ≥ 60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients.

Misión "Manuela Espejo", paradigma de la solidaridad convertida en política de Estado en Ecuador / Mission "Manuela Espejo", paradigm of solidarity turned into a state policy in Ecuador

A partir de los últimos foros internacionales de evaluación sobre la eficacia de la Ayuda Oficial al Desarrollo, se ha intensificado el debate en torno a las modalidades de cooperación Sur-Sur. En dicho debate, aunque presentes parcialmente, las experiencias internacionalistas impulsadas desde los países del ALBA, no están siendo adecuadamente ponderadas en su total dimensión. El propósito de este trabajo es analizar las principales características de la Misión "Manuela Espejo" e identificar las experiencias más importantes para contribuir con este conocimiento sistematizado a su implementación en otros países. Realizamos revisión de documentación bibliográfica e institucional del ALBA, Vicepresidencia de la República del Ecuador, Ministerio de Salud Pública del Ecuador, informes públicos de resultados de la misión y entrevistas semiestructuradas a su personal, y consulta a expertos en cooperación internacional Sur-Sur. La misión se implementó en Ecuador en el 2009 a través de cuatro etapas de intervención: diagnóstico, respuesta, prevención e inclusión. A través del diagnóstico se logró georeferenciar a toda la población discapacitada, en la de respuesta se distribuyeron ayudas técnicas y elementos que mejoraron las condiciones de vida de esta población. Posteriormente, se implementaron campañas de tamizaje con carácter preventivo, así como diversas actividades de sensibilización y promoción de los derechos de los discapacitados. Actualmente la Misión "Manuela Espejo" representa un modelo de atención integral para la población discapacitada, así como un nuevo paradigma de cooperación internacional Sur-Sur. Ha posibilitado que la población con discapacidad del Ecuador sea visibilizada y reconocida en sus derechos y el ejercicio pleno de su ciudadanía.

Since the last international assessment forums on the effectiveness of Official Development Assistance (ODA), the debate on the modalities of South-South cooperation has become more intensive. In this debate, experiences promoted by ALBA countries, though partially present, are not being properly weighted in its full dimension.The purpose of this papaer is to analyze in detail the main features of the "Manuela Espejo" Mission, in order to identify the most important lessons learned from this experience and to contribute with this systematic knowledge its implementation in other countries. We made review of published bibliographic and institutional documents from ALBA, the vice-presidency of the Republic of Ecuador, the Ministry of Public Health of Ecuador, from public reports of results of the Mission, semi-structured interviews to the Mission staff and consultation to experts in the international South-South cooperation. Since 2009, "Manuela Espejo" Mission in Ecuador has been implemented through four main stages of intervention: diagnosis, response, prevention and inclusion. Through diagnosis it was managed to geo-reference the whole disabled population, and then the response phase implemented the distribution of technical aids and elements that substantially improved the living conditions of this population. Later campaigns were implemented as a preventive screening and awareness raising events and promotion of the rights of the disabled. Currently, this mission has become a model of integrated care for the disabled population, as well as a new paradigm of South-South international cooperation. It has made possible that the rights and the full exercise of citizenship of the disabled population be visualized and recognized.

Proton pump inhibitors in gastroesophageal reflux disease: "a custom-tailored therapeutic regimen".

The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage) and extraesophageal syndromes (with acid established association and proposed association). In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence) has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs.Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses.

"Diseñando un traje a la medida": los inhibidores de la bomba de protones en la enfermedad por reflujo gastroesofágico / Proton pump inhibitors in gastroesophageal reflux disease: "a custom-tailored therapeutic regimen"

La Clasificación de Montreal divide la enfermedad por reflujo gastro-esofágico (ERGE) en síndromes esofágicos sintomáticos y con daño a la mucosa y en síndromes extraesofágicos con asociación establecida al ácido y asociación propuesta. En síntomas ERGE típicos el tratamiento con inhibidores de la bomba de protones (IBP) es satisfactorio (> 90%) a 8 semanas en la mayoría de los casos. Las tasas de respuesta a los IBP en la ERGE son muy variables; ya que también dependen de un adecuado diagnóstico clínico de la enfermedad; la endoscopia diferencia el fenotipo macroscópico de la ERGE. La variedad no erosiva (prevalencia 50-70%) tiene una tasa de respuesta sintomática diferente ya que el ácido no es causa suficiente para explicar los síntomas. Las posibles explicaciones a la falla al tratamiento son el apego al tratamiento, alteraciones en el metabolismo y características de IBP y diagnóstico inadecuado. Los síntomas refractarios se relacionan con neutralización del contenido por el uso crónico de IBP. Las manifestaciones extraesofágicas se asocian con otros mecanismos fisiopatológicos como la disfunción del sistema nervioso autónomo. En estas entidades es necesario establecer la relación o no con el ácido para determinar el uso con IBP o considerar otros fármacos. Es decir, necesitamos responder a las preguntas en quien, para qué, cómo y por cuánto tiempo, para diseñar un "traje a la medida". Por último, la seguridad y la tolerabilidad a IBP son factores a considerar en pacientes de edad avanzada que requieren su uso crónico y que generalmente tienen enfermedades crónicas concomitantes (AU)

The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage) and extraesophageal syndromes (with acid established association and proposed association). In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence) has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs. Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses (AU)

Equidad e inversión en salud pública de la República del Perú / Equity and investment in the public health system of the Republic of Peru

Introducción La inversión pública del Estado peruano en salud se ha incrementado significativamente en los últimos cinco años. Sin embargo, persisten serios problemas de inequidad en la asignación de los recursos, en la concepción del sistema de inversión y en su gestión. Objetivo Reflexionar entorno a la lógica de la inversión pública en salud que permita brindar oportuna asesoría al Ministerio de Salud del Perú en un intento de lograr la optimización en el uso de los recursos disponibles y un mayor impacto en los principales indicadores sanitarios. Métodos Revisión de documentación institucional del Ministerio de Salud del Perú, de informes de seguimiento y evaluación de proyectos de inversión implementados, entrevistas estructuradas al personal del Ministerio de Salud del Perú y consulta a expertos en inversión pública, políticas sociales y salud pública. Resultados Varias regiones peruanas, entre ellas, Huancavelica y Puno, tienen mayor porcentaje de desnutrición crónica en niños menores de cinco años y mayores tasas de mortalidad infantil, respectivamente, y sin embargo, no son precisamente las que invierten más en salud, a pesar de que en la mayor parte de estas regiones se desarrollan actividades mineras a cargo de empresas transnacionales. Se detectó falta de capacidad de gestión presupuestal y operativa en el personal a cargo del trabajo sobre inversión pública en salud. El Sistema Nacional de Inversión Pública tiene problemas estructurales, entre ellos, desarticulación de la perspectiva sistémica integral, insuficiencia de mecanismos de planificación, seguimiento y evaluación y poca participación de la población destinataria. Conclusiones Para optimizar la inversión pública en salud y alcanzar mejores resultados sanitarios es necesario llevar a cabo una reestructuración técnica y conceptual del Sistema Nacional de Inversión Pública, incorporándole indispensables componentes de eficiencia social, calidad y solidaridad.

Introduction The public investment of the Peruvian state in health care has significantly increased in the last five years. However, there are still serious problems of inequality in terms of allocation of resources, conception of the investment system and management. Objective To make reflections on the logics of the Peruvian public investments in health care that will allow providing adequate advice to the Ministry of Health of Peru, in an attempt to optimize the use of available resources and to have bigger impact on the main health indicators. Methods Review of documents from the Ministry of Health of Peru, of follow-up reports and of the evaluation of implemented investment projects; structured interviews to the staff of that ministry and consultation to experts in public investment, social policies and public health. Results Several Peruvian regions like Huancavelica and Puno have high percentages of chronic malnutrition in under 5 years-old children and higher rates of infant mortality respectively. However, they do not have large investments in the field of health care, despite the mining activities that are developed in these regions in charge of transnational companies. Lack of budget management and operational capacity was detected in the staff responsible for the public investments in health. The National System of Public Investment has structural problems such as breaking up of integrated systemic perspectives, inadequacy of planning, follow-up and evaluation mechanisms, low level of participation of the recipient population and shortage of cross-sectional approaches to investment. Conclusions For the purpose of optimizing the public investments in health and to achieve better results, it is required to carry out technical and conceptual rearrangement of the National Public Investment System by adding indispensable elements of social efficiency, quality and solidarity.

Effect of body weight and esophageal damage on the severity of gastroesophageal reflux symptoms. Mexican GERD working group.

BACKGROUND AND AIMS: Several studies have demonstrated overweight and obesity are strong independent risk factors of GERD symptoms and esophageal erosions. Our aim was to analyze the joint effect of BMI with the grade of esophageal damage over symptoms' intensity of GERD. METHODS: We used a questionnaire with a Likert scale for severity of symptoms related to GERD. The distal portion of the esophagus was evaluated to determine the presence of mucosal injury, classified by Los Angeles criteria (LA). RESULTS: We included 917 subjects (53.76% females) with average age 36.8+/-7 years. Males had higher BMI than females (26.8+/-3.5 vs. 25.2+/-4.5, p<0.001). Severe damage (C-D ulcers) was associated with overweight (BMI 25-30), severity of heartburn,retching, halitosis, regurgitation, and chest oppression. BMI >30 had high score for heartburn and retching, but low score for nausea, compared with lower weight. The model with interaction showed a non-linear association between BMI and LA. Overweight (but not obese) patients with damage scored C-D had the highest score for intensity of heartburn and retching. CONCLUSIONS: BMI and LA do not have additive effects on the severity of symptoms of GERD. Those with BMI between 25 and 30 had severe symptoms score, but those with BMI >30 showed lower scores. These findings could explain controversial results found in other studies.

[Patients with type III obesity given sibutramine 15 mg/day lose weight in amounts proportional to those in types I and II, but waist circumferences does not decrease proportionally]. / El grado de obesidad modifica la respuesta de disminución de circunferencia de cintura en pacientes que reciben 15 mg diarios de sibutramina. Estudio abierto sobre tolerancia y efectividad de la sibutramina.

OBJECTIVE: The etiology, comorbidity, metabolism, and treatment response vary among overweight and obesity types I, II and III individuals. We assessed the association between obesity type with body mass index, waist circumference and tolerance to a daily dose of 15 mg of sibutramine. MATERIALS AND METHODS: A sample of 701 individuals recruited from 47 health centers was analyzed. All subjects received 15 mg of sibutramine daily for 8 weeks. Weight, height, and waist circumference were measured at day 0 and weeks 4 and 8. RESULTS: Patients in all obesity types lost proportional amounts of weight (p=0.86), but those in type IIl obesity had a smaller reduction in waist circumference than those in types I and 1 (p=0.003). Side effects of sibutramine were rarely observed. Subjects with type III obesity exhibited even fewer side effects. CONCLUSIONS: The lack of association between weight reduction and decreased waist circumference across obesity types could be related to differences in the sympathetic nervous system or to sibutramine biodistribution. Subjects with body mass index greater than 40 Kg/ m(2) required a higher dose of sibutramine in order to loose the same proportion of abdominal fat as those in other types of obesity.

El grado de obesidad modifica la respuesta de disminución de circunferencia de cintura en pacientes que reciben 15 mg diarios de sibutramina: estudio abierto sobre tolerancia y efectividad de la sibutramina / Patients with type III obesity given sibutramine 15 mg/day lose weight in amounts proportional to those in types I and II, but waist circumferences does not decrease proportionally

Objetivo. Los pacientes con sobrepeso y las clases de obesidad I, II, III presentan diferente etiología, comorbilidad, efectos metabólicos y diferente respuesta terapéutica. En este análisis evaluamos el efecto del grado de obesidad sobre la disminución del índice de masa corporal (IMC) y la circunferencia de cintura (CC) eficacia y tolerancia de sibutramina 15mg al día. Material y métodos. Se analizó una base de datos de una muestra de 701 sujetos colectados de 47 clínicas. Los sujetos recibieron tratamiento con 15 mg de sibutramina al día. Se registró el peso, estatura y la CC en las visitas basal, 4 y 8 semanas. Resultados. Los pacientes con diferentes grados de obesidad disminuyeron proporcionalmente el IMC (p = 0.86), pero los sujetos con obesidad clase III mostraron menor disminución de la CC (p = 0.003) que los otros grupos. Los eventos adversos fueron pocos, y de menor frecuencia con grados mayores de obesidad. Discusión. La disociación de disminución de IMC y la CC puede estar relacionada al control ejercido por el sistema simpático de acuerdo con el grado de obesidad, además de la biodistribución de sibutramina. Los sujetos con IMC mayor de 40 necesitan mayor dosis para alcanzar proporcionalmente la pérdida de grasa abdominal de los otros grupos de obesos.

OBJECTIVE: The etiology, comorbidity, metabolism, and treatment response vary among overweight and obesity types I, II and III individuals. We assessed the association between obesity type with body mass index, waist circumference and tolerance to a daily dose of 15 mg of sibutramine. MATERIALS AND METHODS: A sample of 701 individuals recruited from 47 health centers was analyzed. All subjects received 15 mg of sibutramine daily for 8 weeks. Weight, height, and waist circumference were measured at day 0 and weeks 4 and 8. RESULTS: Patients in all obesity types lost proportional amounts of weight (p=0.86), but those in type IIl obesity had a smaller reduction in waist circumference than those in types I and 1 (p=0.003). Side effects of sibutramine were rarely observed. Subjects with type III obesity exhibited even fewer side effects. CONCLUSIONS: The lack of association between weight reduction and decreased waist circumference across obesity types could be related to differences in the sympathetic nervous system or to sibutramine biodistribution. Subjects with body mass index greater than 40 Kg/ m(2) required a higher dose of sibutramine in order to loose the same proportion of abdominal fat as those in other types of obesity.

Results of the national survey of borderline ovarian tumors in Spain.

MATERIAL AND METHODS: Retrospective multi-center analysis of women diagnosed with borderline ovarian tumor and treated between January 1990 and December 1997. A national survey was conducted, in which 457 patients from 27 centers corresponding to ten of Spain's autonomous communities were analyzed. RESULTS: Four hundred fifty-seven women with borderline ovarian tumor were analyzed. The mean age of patients was 45.5+/-16.9 years. Of these, 390 patients (85.3%) were at stage I, 8 (1.8%) were at stage II and 36 (7.9%) at stage III. A bilateral tumor was observed in 63 women (13.8%). The mean tumor size was 14.2 cm and in 88 cases (19.3%) the tumor was on the surface of the ovary. Microinvasion was observed in 25 (5.5%) cases, and 29 women (6.3%) showed a micropapillary pattern. Study of the factors related to the appearance of peritoneal implants revealed positive tumor markers (OR 15.02: 1.9-32.9) and a tumor on the ovarian surface (OR 8.0: 1.8-127) to be independent risk factors. With respect to recurrence, the presence of peritoneal implants at the time of initial surgery (OR 3.4: 1.1-10.4) and signs of microinvasion in the anatomicopathological study (OR 5.5: 1.5-17.8) were found to be independent risk factors. The overall survival rate in our series was 97% with a mean follow-up of 88.3 months. The survival rate by stage was 97% for stage I, 100% for stage II and 97% for stage III. CONCLUSIONS: Although borderline ovarian tumors have an excellent prognosis, they are not exempt from a risk of recurrence. Characterization of patients with borderline ovarian tumor is essential in order to prevent their evolution. Likewise, the taking on board of risk factors will enable more selective treatments to be offered in each case.

[Is endoscopy necessary to initiate medical treatment in primary-level medical care patients with not investigated dyspepsia?]. / Es necesaria la endoscopia para iniciar el tratamiento médico en pacientes en el primer nivel de atención médica con dispepsia no investigada?

INTRODUCTION: Approximately 2 to 5% of primary care consultations are patients with dyspepsia. One of the most controversial points among primary-care physicians and gastroenterologists is the diagnostic-therapeutic approach of the uninvestigated dyspeptic patient. AIMS AND METHODS: Our aim was to investigate prevalence of organic disease and Helicobacter pylori (Hp) status in uninvestigated dyspeptic out-patients at a primary-care level. Two hundred two adult out-patients (130 F/72 M), > or = 18 and < 75 years, mean age 36 years (range 18-73 years), were recruited and sent for upper gastrointestinal endoscopy and gastric biopsies for CLO-test due to dyspeptic symptoms according to Rome II criteria. Patients were excluded if they had previously been investigated by any means, had a background of NSAIDs or corticoesteroids intake, irritable bowel syndrome (IBS) or any alarm sign or symptom. All endoscopic findings were reported to primary care physicians who decided on patient management. RESULTS: A total of 86.14% (174/202 patients) showed no endoscopic lesions and only 13.86% (28/202) [95% CI = 9.1-18.6] showed evidence of non-malignant organic lesions. By age group, prevalence of organic diseases was 10.81% (16/148) [95% CI = 6.3-16.9] in patients < 45 years and 22.22% (12/54) [95% CI = 12.04-35.6] in patients > 45 years, OR = 0.424. [95% CI = 0.186-0.968]. CONCLUSIONS: Prevalence of upper gastrointestinal tract organic disease in dyspeptic out-patients selected according to Rome II criterion at a primary-care level is low, with no malignancies detected. These findings show that patients < 45 years of age with uninvestigated dyspepsia may empirically and safely receive symptom-guided antisecretory therapy.