RESUMEN
PURPOSE: Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. METHODS: PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. RESULTS: This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. CONCLUSION: The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.
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Neoplasias Colorrectales/patología , Oncología Médica/métodos , Células Neoplásicas Circulantes/patología , Medicina de Precisión/métodos , Neoplasias Colorrectales/sangre , Humanos , Biopsia Líquida , España , Transferencia de TecnologíaRESUMEN
BACKGROUND/OBJECTIVES: The apparent widespread extent of zinc (Zn) deficiency in developing countries and the efficacy of oral Zn supplements as an adjunct to oral rehydration therapy make oral Zn supplementation an increasingly important modality in clinical medicine and public health. In this study we aimed to compare the relative bioavailability of oral doses of 30 mg of Zn in two dosing forms. SUBJECTS/METHODS: In total, 10 healthy male volunteers ingested oral Zn doses with 200 ml plain water at about 0830 hours in the fasting state on two occasions, once as 30 mg of Zn in an aqueous solution of reagent grade zinc sulfate (ZnSO(4)) and another time as 1.5 NutriSet Zn tablets (Nutriset, Malaunay, France); on a third occasion, only plain water was consumed. Venous blood specimens were collected at baseline, 60, 120, 180 and 240 min after ingestion and the plasma Zn was measured for each sample. RESULTS: The relative bioavailability of oral Zn from a commonly used, tableted (NutriSet) form is only about half of that of a reference dose of aqueous ZnSO(4) as indicated by the area under the curve of serial plasma Zn excursion and maximal change in circulating Zn. CONCLUSIONS: Reduced or absent functional outcomes in Zn intervention trials may derive, in part, from a lower than anticipated intestinal uptake of the Zn in the tableted form.
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Suplementos Dietéticos , Sulfato de Zinc/administración & dosificación , Sulfato de Zinc/farmacocinética , Zinc/administración & dosificación , Zinc/farmacocinética , Administración Oral , Adolescente , Adulto , Disponibilidad Biológica , Países en Desarrollo , Relación Dosis-Respuesta a Droga , Ayuno , Guatemala , Humanos , Masculino , Persona de Mediana Edad , Comprimidos/administración & dosificación , Adulto Joven , Zinc/sangreRESUMEN
Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis.
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Neoplasias Endometriales/etiología , Neoplasias Endometriales/patología , Moléculas de Adhesión Celular/fisiología , Neoplasias Endometriales/genética , Femenino , Expresión Génica , Humanos , Invasividad NeoplásicaRESUMEN
OBJECTIVE: Combating iron deficiency in toddlers with iron-fortified food has proved difficult in countries with phytate-rich diets. For this purpose, a new haem iron preparation was developed. The study compared changes in iron status after administration of refried beans with beans fortified with a haem iron preparation or ferrous sulphate (FeSO4). DESIGN: In a masked, stratified-randomised intervention trial, children received five 156-g cans of refried black beans per week for 10 consecutive weeks. The beans-only (control), FeSO4 and haem iron groups were offered a cumulative dose of 155 mg, 1625 mg and 1700 mg of iron from the bean intervention, respectively. Haemoglobin (Hb) and ferritin concentrations were determined at baseline and after 5 and 10 weeks. Compliance was examined weekly. SETTING: A low-income community in Guatemala City. SUBJECTS: One hundred and ten children aged 12-36 months with initial Hb values between 100 and 115 g l(-1). RESULTS: The cumulative intake of beans was approximately 80% of that offered, signifying an additional approximately 1300 mg of either haem or inorganic iron in the corresponding treatment groups over 10 weeks. Hb concentrations increased by the order of 7.3-11.4 g l(-1) during the intervention, but without significant differences across treatments. Average ferritin concentrations were unaffected by treatment assignment. However, post hoc analysis by subgroups of initial high ferritin and initial low ferritin found the Hb increments after 10 weeks in the haem iron group (13.1+/-7.7 g l(-1)) to be significantly greater than the respective increases (6.8+/-11.2 and 6.4+/-8.5 g l(-1)) in the inorganic iron and beans-only groups. CONCLUSIONS: Canned refried beans are a candidate vehicle for fortificant iron. Given the improved colour and organoleptic properties imparted by haem iron added to refried beans, its additional potential for benefiting the iron status of consumers with iron deficiency may recommend it over FeSO4.
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Anemia Ferropénica/dietoterapia , Alimentos Fortificados , Hierro de la Dieta/uso terapéutico , Anemia Ferropénica/sangre , Preescolar , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Fabaceae , Femenino , Ferritinas/análisis , Compuestos Ferrosos/administración & dosificación , Compuestos Ferrosos/uso terapéutico , Guatemala/epidemiología , Hemoglobinas/análisis , Humanos , Lactante , Hierro de la Dieta/administración & dosificación , Masculino , Cooperación del Paciente , Resultado del TratamientoRESUMEN
The primary goal of this phase II study was to determine the efficacy of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil in patients with pancreatic cancer. Eligibility criteria included nonresectable locally advanced or metastatic pancreatic adenocarcinoma and measurable disease. Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every 4 weeks. Twenty nine patients were enrolled. The overall response rate was 21% (95% confidence interval: 8% to 40%), consisting of one complete response and five partial responses; 16 patients (55%) had stable disease. Median survival was 8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was generally of short duration. No thrombocytopenia or evidence of cumulative myelosuppression was observed. The only significant nonhematologic events were grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is active and well tolerated compared with results reported for each of these single agents. Thus, this combination justifies future comparative clinical trials. Semin Oncol 28 (suppl 10):44-49.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Análisis de Supervivencia , GemcitabinaRESUMEN
Coffee is commonly given daily to toddlers in Guatemala. Possible negative effects of coffee ingestion on cognitive development and sleep patterns were assessed in 132 children 12-24 months of age who had received coffee for > 2 months and were iron deficient on at least one indicator. Children were stratified by initial hemoglobin (A= anemic, Hgb < 10.5 g/dl; NA = 'non-anemic', Hgb > or = 10.5 g/dl) and were randomly assigned to an experimental group (S = substitute consisting of sugar and coloring), and a control group (C = continuation of coffee) (42 C-NA; 53 S-NA; 18 C-A; and 19 S-A). Anemic children were provided Fe supplements for 2-3 months. Compliance was assessed every 2 weeks. After 5 months, testers masked to treatment group and anemia evaluated children with the Bayley Scales of Infant Development II in a central location. Scores were the Mental Development Index (MDI), the Psychomotor Development Index (PDI), and scales from the Behavior Rating Scale (BRS). The child's sleep in the previous 24 h was assessed with a set of standardized sleep questions to the care giver on the first visit and every 2 weeks thereafter. No significant effects of treatment on test scores or BRS ratings were found. In the 24 h period reported on at the final visit, children in the Substitute group slept more during the night and overall (night plus naps) than children in the Coffee group, a difference not found at the first visit. No differences were found in sleep difficulty or number of times waking at night. Women's reported coffee intake per day during pregnancy was associated with lower BRS ratings, even after controlling for SES and child age. The effects of postnatal coffee ingestion in Guatemala were seen for sleep duration, but not for cognitive development. Prenatal coffee ingestion was negatively associated with Behavior Rating Scales and should be investigated further.
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Anemia Ferropénica/fisiopatología , Cafeína/administración & dosificación , Café , Cognición , Deficiencias de Hierro , Sueño , Anemia Ferropénica/tratamiento farmacológico , Femenino , Guatemala , Hemoglobinas/análisis , Humanos , Lactante , Hierro/uso terapéutico , Embarazo , Efectos Tardíos de la Exposición PrenatalRESUMEN
BACKGROUND: Deuterated retinol dilution (DRD) gives quantitative estimates of total body stores of vitamin A. OBJECTIVES: In elderly people, we studied 1) the time when an oral dose of deuterated vitamin A equilibrates with body stores, 2) whether serum ratios of deuterated to nondeuterated retinol (D:H) at 3 or 6 d postdosing predicted body stores, and 3) the ability of DRD to detect changes in the size of the body vitamin A pool. DESIGN: A 10-mg oral dose of [2H4]retinyl acetate was administered to 60-81-y-old Guatemalans (n = 47); percentage enrichment of serum retinol with deuterated retinol was determined at 1-3 time points per subject at 3, 6, 7, 14, 20, 21, and 54 d. In subjects from whom blood was obtained at 3 and 21 d (n = 15) and at 6 and 20 d (n = 9), total body stores were calculated by using the formula of Furr et al (Am J Clin Nutr 1989;49:713-6) with 21- or 20-d data and correlated with serum D:H at 3 or 6 d postdosing. Nine subjects received diets containing 982+/-20 microg RE (x+/-SEM) plus 800 microg RE as retinyl acetate supplements for 32 d. DRD, serum retinol, and relative dose response were used to assess vitamin A status before and after the intervention. RESULTS: Deuterated retinol equilibrated with the body pool by 20 d postdosing. Vitamin A supplementation for 32 d increased body stores, although unexplained exaggerated increases were seen in some subjects. An inverse linear relation was found between estimates of body stores and serum D:H at 3 d postdosing (r = -0.75, P = 0.002); at 6 d postdosing, the correlation was weaker. CONCLUSIONS: DRD can detect changes in total body stores of vitamin A, although factors affecting serum D:H need to be elucidated. Serum D:H 3 d postdosing might be used as an early indicator of total body stores of vitamin A, although a predictive equation will need to be developed.
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Técnicas de Dilución del Indicador , Vitamina A/análisis , Administración Oral , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Deuterio , Suplementos Dietéticos , Diterpenos , Femenino , Guatemala , Humanos , Masculino , Persona de Mediana Edad , Ésteres de Retinilo , Vitamina A/administración & dosificación , Vitamina A/análogos & derivados , Vitamina A/sangreRESUMEN
This study investigated the structure and environment of 31 street food vendors in an urban park in the downtown area of Guatemala City. Vendors were interviewed and observed in order to assess the quality, safety, and accessibility of street food. The street food vending in the park consisted of five types: whole meal, snack, beverage, fruits, and carts. A great variety of typical Guatemalan meals, as well as ready-to-eat fruits and hot dog chapin (hot dog with cabbage and avocado cream), were found in the park. The food preparation and handling revealed inadequacies concerning the hygiene. Circumstances, such as the lack of portable water near the vending site and unhygienic sanitary facilities, supported the transmission of pathogens. The clientele was of all ages, and included female as well as the male purchasers. Typical clients came from the surrounding area, i.e. the employees of civil and private offices, commercial businesses, and the non-food vendors of the park. Comparing the economy of street food with the definition of very poor in Guatemala, the prices on the street were often above the daily money needed for a basic food basket. However, a special clientele were the very poor, such as the street children and handicapped people, who earned their meals by helping out at the vending sites. Mainly female street food vendors were found at the whole meal, snack, and refreshment sites whereas men sold predominantly at the carts. For all of the vendors, it was the main source of income and for many families the only one.
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Seguridad de Productos para el Consumidor , Manipulación de Alimentos , Alimentos , Higiene , Población Urbana , Niño , Femenino , Contaminación de Alimentos , Guatemala , Humanos , Masculino , Pobreza , Control de CalidadRESUMEN
Coffee is one of the first liquids given to infants in Guatemala. To evaluate whether this practice has an adverse effect on iron status, 160 children 12-24 mo of age who had received coffee for > or = 2 mo and had at least one indicator of iron deficiency were stratified by initial hemoglobin concentration (anemic, or nonanemic, ie, hemoglobin > or = 105 g/L) and randomly assigned to a control (continuation of coffee; coffee) or intervention (provided with a substitute consisting of sugar and coloring; substitute) group for 5 mo. Anemic children were provided with iron supplements for 2-3 mo. Hematologic and anthropometric measurements were made before and after the intervention and dietary and morbidity data were collected every 2 wk. A total of 139 children completed the study: 45 coffee, nonanemic; 56 substitute, nonanemic; 19 coffee, anemic; and 19 substitute, anemic. Compliance with the procedures was good: median coffee intake was 891 mL/wk in the coffee group compared with 18 mL/wk in the substitute group (P = 0.0001). There was no significant effect of discontinuing coffee consumption on changes in hemoglobin, hematocrit, ratio of zinc protoporphyrin to heme or plasma iron, zinc or copper in either nonanemic or anemic children, or plasma ferritin in children who did not take iron supplements. In children who took iron supplements, change in plasma ferritin was significantly greater in the substitute group than in the coffee group (106% compared with 1%, P < 0.05). This implies that coffee interferes with the utilization of supplemental iron. It is likely that the amount and strength of coffee consumed by Guatemalan toddlers are too low to significantly affect the other indexes of iron status.
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Anemia/inducido químicamente , Café/efectos adversos , Alimentos Infantiles/efectos adversos , Deficiencias de Hierro , Anemia/sangre , Antropometría , Preescolar , Femenino , Alimentos Formulados , Guatemala , Hematócrito , Pruebas Hematológicas , Hemoglobinas , Humanos , Lactante , Hierro/metabolismo , Masculino , Zinc/sangreRESUMEN
Coffee is widely consumed by children in Guatemala. To evaluate whether coffee has an adverse effect on growth or morbidity, 160 children 12-24 mo of age who had received coffee for > or = 2 mo and had at least one indicator of iron deficiency were stratified by initial hemoglobin (Hb) (A = anemic vs. NA = "nonanemic", i.e., Hb > or = 105 g/L) and randomly assigned to a control (C = continuation of coffee) or intervention group (S = provided with a substitute consisting of sugar and coloring) for 5 mo. Anemic children were provided iron supplements for 2-3 mo. Hematological and anthropometric measurements were made before and after the intervention, and dietary and morbidity data were collected every 2 wk. A total of 139 children completed the intervention: 45 C-NA, 56 S-NA, 19 C-A and 19 S-A. Compliance with the intervention was good: median coffee intake was 127 mL/d in group C vs. 3 mL/d in group S (P = 0.0001). There were no significant differences between C vs. S groups in food intake before or after the intervention. In the total sample, there was no effect of the intervention on weight or length gain. However, in children initially consuming more than 100 mL/d of coffee (n = 96), length gain was 22% greater in the S vs. the C group (P = 0.07), and weight gain was 46% greater in the S-A vs. the C-A group (P < 0.05; NS in the NA groups). Total illness prevalence (particularly respiratory illness) was significantly lower in the S-NA vs. the C-NA group (P < 0.05), but somewhat higher in the S-A vs. the C-A group (P = 0.09). Morbidity differences did not explain the effect of the intervention on growth. These results indicate a modest increase in growth associated with discontinuation of coffee consumption by toddlers with initial intakes >100 mL/d.
PIP: Coffee intake has been associated with several adverse nutritional consequences in both animal models and human studies. Accordingly, in North America, coffee is not thought to be an appropriate beverage for children. In contrast, coffee is widely consumed among children in Guatemala and is even one of the first liquids given to infants, beginning as early as 2 months of age. A study investigated whether coffee has an adverse effect upon child growth or morbidity. 160 children of age 12-24 months who had received coffee for 2 or more months and had at least one indicator of iron deficiency were stratified by initial hemoglobin and randomly assigned to the control or intervention group for 5 months. Children in the control group continued to receive coffee, while children in the intervention group were instead given a substitute consisting of sugar and coloring. Anemic children were provided iron supplements for 2-3 months. Hematological and anthropometric measurements were made at baseline and after the intervention, while dietary and morbidity data were collected every 2 weeks. 139 children completed the intervention and compliance was high. No significant difference was found between the control and intervention groups in food intake before or after the intervention. Overall, the intervention had no effect upon weight or length gain. However, a modest increase in growth was associated with the discontinuation of coffee consumption by toddlers with initial intakes of more than 100 ml/day.
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Anemia Ferropénica/complicaciones , Café/efectos adversos , Crecimiento , Proteína C-Reactiva/análisis , Diarrea/epidemiología , Ingestión de Líquidos , Ingestión de Alimentos , Femenino , Guatemala/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lactante , Infecciones/epidemiología , Masculino , Morbilidad , Prevalencia , Enfermedades Respiratorias/epidemiología , Aumento de PesoRESUMEN
Plasma retinol and beta-carotene levels were measured in 502 preschool Guatemalan children from five rural hamlets. Their ages ranged from 6 to 78 months (mean: 42.9 +/- 19.2 months); 45% males and 55% females. The mean retinol value in the whole group was 0.9 +/- 0.4 mumol/l (range: 0.1 to 8.4 mumol/l). There was no significant difference between sexes in retinol mean values nor in the incidence of retinol values less than 0.7 mumol/l (22% in males, 18% in females). When grouped by age and community, significant low retinol mean values were found in two hamlets in the youngest age group (12 to 23 months) as compared to the other age-groups (p < 0.05). In the other two hamlets, there were no significant differences among retinol means by age-group. The highest prevalence of deficient retinol values by age-group was in the 12 to 23 months group (40%), and decreased as age increased. The mean value for beta-carotene in the whole group was 0.13 +/- 0.18 mumol/l (range: 0.01 to 2.23 mumol/l). There were no significant differences in beta-carotene means between sexes in the whole group. Stratifying the beta-carotene data by age-groups and community, values were significantly higher in the 48-59 months and 72-83 months groups, as compared with the other age groups in two of the communities (p < 0.05). Significant differences across communities for beta-carotene were found only in the 12 to 23 months group.
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Carotenoides/sangre , Salud Rural , Vitamina A/sangre , Factores de Edad , Carotenoides/deficiencia , Niño , Preescolar , Femenino , Guatemala/epidemiología , Humanos , Incidencia , Lactante , Masculino , Prevalencia , Tamaño de la Muestra , Factores Sexuales , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/epidemiología , beta CarotenoRESUMEN
Patterns of genetic subdivision in parasite populations can provide important insights into transmission processes and complement information obtained using traditional epidemiological techniques. We describe mitochondrial sequence variation in 265 Ascaris collected from 62 individual hosts (humans and pigs) from 35 households in 3 Guatemalan locations. Restriction mapping of individual worms revealed 42 distinct mitochondrial genotypes. We ask whether the mitochondrial genotypes found in worms from individual hosts, from families of hosts and from villages represent random samples from the total Ascaris population. Patterns of genetic subdivision were quantified using F-statistics, while deviations from the null hypothesis of randomness were evaluated by a simple resampling procedure. The analysis revealed significant deviations from panmixia. Parasite populations were strongly structured at the level of the individual host in both humans and pigs: parasites bearing the same mitochondrial genotype were found more frequently than would be expected by chance within hosts. Significant heterogeneity was also observed among populations from different villages, but not from different families within a village. The clustering of related parasites within hosts suggests a similar clustering of related infective stages in the environment and may explain why sex ratios in Ascaris are female-biased. We discuss aspects of Ascaris biology which may lead to the observed patterns.
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Ascariasis/epidemiología , ADN de Helmintos/genética , ADN Mitocondrial/genética , Animales , Ascariasis/genética , Ascaris/clasificación , Transmisión de Enfermedad Infecciosa , Guatemala/epidemiología , Haplotipos , Humanos , Modelos Genéticos , Mapeo Restrictivo , Población Rural , Porcinos/parasitologíaRESUMEN
The levels of plasmatic lipids and fat liposoluble vitamins were measured in 107 elderlies (29% males, 71% females) who were residents of a poor periurban neighborhood of Guatemala City. The age ranged between 60-103 years (means +/- sd 69 +/- 8). The mean and sd for the plasmatic levels of lipids and vitamins were (ranges in parenthesis): cholesterol 220 +/- 42 mg/dl (128 to 428); triglycerides: 189 +/- 92 mg/dl (54 to 513); retinol 50 +/- 16 ug/dl (4.5 to 103); beta-carotene 17 +/- 12 ug/dl (12 to 60), tocopherol 1.32 +/- 0.36 mg/dl (0.54 to 2.46). A significant correlation was found in both sexes between cholesterol and retinol (r = 0.3, p < 0.05) and cholesterol and tocopherol (r = 0.4, p < 0.05), triglycerides and retinol (r = 0.3, p < 0.05). Cholesterol and beta-carotene was also significant in women (r = 0.5, p < 0.05). The correlation between triglycerides and beta-carotene by gender was not significant.
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Lípidos/sangre , Vitaminas/sangre , Anciano , Anciano de 80 o más Años , Carotenoides/sangre , Colesterol/sangre , Estudios Transversales , Femenino , Guatemala , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , Población Urbana , Vitamina A/sangre , Vitamina E/sangreRESUMEN
In Guatemalan villages people commonly rear pigs, and both hosts may be infected with Ascaris. This study was designed to ask whether both humans and pigs are potential hosts in a single parasite transmission cycle in such villages, or alternatively, if there are two separate transmission cycles, one involving pigs and one involving human hosts. Parasites were collected from both host species from locations in the north and south of Guatemala. Allelic variation in the nuclear genome of Ascaris was measured using enzyme electrophoresis, while mitochondrial DNA (mtDNA) sequence variation was quantified using restriction mapping. Low levels of enzyme polymorphism were found in Ascaris, but allele frequencies at two loci, mannose phosphate isomerase and esterase, suggest that there is little gene exchange between parasite populations from humans and pigs. MtDNA haplotypes fall into two distinct clusters which differ in sequence by 3-4%; the two clusters broadly correspond to worms collected from humans and those collected from pigs. However, some parasites collected from humans have mtDNA characteristic of the 'pig Ascaris' haplotype cluster, while some parasites collected from pigs have mtDNA characteristic of the 'human Ascaris' haplotype cluster. These shared haplotypes are unlikely to represent contemporary cross-infection events. Patterns of phylogenetic similarity and geographical distribution of these haplotypes suggest, instead, that they are the result of two historical introgressions of mtDNA between the two host-associated Ascaris populations. The results clearly demonstrate that Ascaris from humans and pigs are involved in separate transmission cycles in Guatemala.