RESUMEN
Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Trastornos de la Coagulación Sanguínea , Humanos , Insuficiencia Hepática Crónica Agudizada/complicaciones , Trastornos de la Coagulación Sanguínea/complicaciones , Trastornos de la Coagulación Sanguínea/terapia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/terapia , Coagulación Sanguínea , HemostasisRESUMEN
Medullary thyroid cancer (MTC) is a rare disease from parafollicular C cells. Calcitonin has been suggested as a screening; its levels are proportional to the tumor size and predictive of metastatic disease. We present a case where an early action was taken with lower cut-off points. Male patient, 49 years old. Thyroid ultrasound (US) with a suspicious nodule. Fine Needle Aspiration Biopsy (FNAB) suggests MTC, with pre-operative serum calcitonin (CTN) of 591 pg/mL. Total thyroidectomy with central and bilateral dissection was performed. Biopsy: MTC in left nodule of 26 mm without lymph nodes (LN) metastases. Follow-up with undetectable CTN for six years. After that, CT was 4.7 pg/mL, and carcinoembryonic antigen (CEA) was 1.2 ng/mL. Neck US showed bilateral LN. FNAB of LN does not show recurrence. A progressive rise of markers with doubling time of CTN and CEA was 16 and 51.3 months, respectively. CTN raised until 112 pg/mL. Given the lack of cervical compromise, a neck and lung CT, liver MRI, and bone scintigraphy were ordered despite CTN levels < 150 pg/mL. MRI showed hypervascular hepatic lesions, contrasted with gadoxetic acid. PET Ga68-DOTATATE showed lesions with overexpression of somatostatin receptors in the liver. Surgery was done, and a biopsy confirmed metastases. Conclusions: The clinical guidelines may allow the management of cases; however, they should be used considering each case context. In our patient, if the guidelines had been strictly followed, it would not have been possible to detect liver metastases to achieve a surgical resection with curative intent.
Paciente masculino, 49 años. Ecografía tiroidea con nódulo sospechoso. Biopsia por aspiración con aguja fina (PAAF) sugiere cáncer medular de tiroides (CMT), calcitonina sérica preoperatoria (CTN) de 591 pg/mL. Se realizó tiroidectomía total con disección central y bilateral. Biopsia: CMT en nódulo tiroideo izquierdo de 2,6 cm sin metástasis en 29 ganglios linfáticos (GL). En el seguimiento, CTN sérica indetectable durante 6 años. Posteriormente CTN sérica de 4,7 pg/mL y antígeno carcinoembrionario (CEA) de 1,2 ng/mL. Ecografía cervical de control mostró GL subcentimétricos bilaterales en grupo IV. PAAF de GL sin evidencia de malignidad, con niveles de CTN indetectables en la muestra. El doblaje de CTN y CEA fue 16 y 51,3 meses respectivamente. Dado ausencia de compromiso cervical, se solicitó TC de cuello y tórax, RM hepática y gammagrafía ósea, a pesar de no presentar niveles de CTN > 150 pg/mL. La RM mostró 3 lesiones hepáticas hipervasculares; se complementa con un PET Ga-DOTATATE que mostró 2 lesiones focales con sobreexposición de receptores de somatostatina en el parénquima hepático, con SUVmáx de 6,8 y 7,3. Se realiza cirugía extirpando 5 lesiones; la biopsia confirmó metástasis de CMT. Conclusiones: Las guías clínicas pueden dar orientaciones generales y permitir el manejo de casos basados en la evidencia; sin embargo, siempre deben usarse considerando el contexto de cada caso en particular. Si se hubieran seguido estrictamente las pautas, no habría sido posible detectar las metástasis hepáticas dentro de la ventana de oportunidad para lograr una resección quirúrgica con intención curativa.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/diagnóstico por imagen , Tiroidectomía , Calcitonina/sangre , Antígeno Carcinoembrionario/sangre , Biomarcadores de Tumor/sangre , Guías de Práctica Clínica como Asunto , Biopsia con Aguja FinaRESUMEN
Medullary thyroid cancer (MTC) is a rare disease from parafollicular C cells. Calcitonin has been suggested as a screening; its levels are proportional to the tumor size and predictive of metastatic disease. We present a case where an early action was taken with lower cut-off points. Male patient, 49 years old. Thyroid ultrasound (US) with a suspicious nodule. Fine Needle Aspiration Biopsy (FNAB) suggests MTC, with pre-operative serum calcitonin (CTN) of 591 pg/mL. Total thyroidectomy with central and bilateral dissection was performed. Biopsy: MTC in left nodule of 26 mm without lymph nodes (LN) metastases. Follow-up with undetectable CTN for six years. After that, CT was 4.7 pg/mL, and carcinoembryonic antigen (CEA) was 1.2 ng/mL. Neck US showed bilateral LN. FNAB of LN does not show recurrence. A progressive rise of markers with doubling time of CTN and CEA was 16 and 51.3 months, respectively. CTN raised until 112 pg/mL. Given the lack of cervical compromise, a neck and lung CT, liver MRI, and bone scintigraphy were ordered despite CTN levels < 150 pg/mL. MRI showed hypervascular hepatic lesions, contrasted with gadoxetic acid. PET Ga68-DOTATATE showed lesions with overexpression of somatostatin receptors in the liver. Surgery was done, and a biopsy confirmed metastases. Conclusions: The clinical guidelines may allow the management of cases; however, they should be used considering each case context. In our patient, if the guidelines had been strictly followed, it would not have been possible to detect liver metastases to achieve a surgical resection with curative intent.
Asunto(s)
Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Masculino , Persona de Mediana Edad , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/diagnóstico por imagen , Tiroidectomía , Calcitonina/sangre , Biopsia con Aguja Fina , Antígeno Carcinoembrionario/sangre , Guías de Práctica Clínica como Asunto , Biomarcadores de Tumor/sangreRESUMEN
A recent paper by Beretta-Blanco and Carrasco-Letelier (2021) claims that agricultural eutrophication is not one of the main causes for cyanobacterial blooms in rivers and artificial reservoirs. By combining rivers of markedly different hydrological characteristics e.g., presence/absence and number of dams, river discharge and geological setting, the study speculates about the role of nutrients for modulating phytoplankton chlorophyll-a. Here, we identified serious flaws, from erratic and inaccurate data manipulation. The study did not define how erroneous original dataset values were treated, how the variables below the detection/quantification limit were numerically introduced, lack of mandatory variables for river studies such as flow and rainfall, arbitrary removal of pH > 7.5 values (which were not outliers), and finally how extreme values of other environmental variables were included. In addition, we identified conceptual and procedural mistakes such as biased construction/evaluation of model prediction capability. The study trained the model using pooled data from a short restricted lotic section of the (large) Uruguay River and from both lotic and reservoir domains of the Negro River, but then tested predictability within the (small) Cuareim River. Besides these methodological considerations, the article shows misinterpretations of the statistical correlation of cause and effect neglecting basic limnological knowledge of the ecology of harmful algal blooms (HABs) and international research on land use effects on freshwater quality. The argument that pH is a predictor variable for HABs neglects overwhelming basic paradigms of carbon fluxes and change in pH because of primary productivity. As a result, the article introduces the notion that HABs formation are not related to agricultural land use and water residence time and generate a great risk for the management of surface waterbodies. This reply also emphasizes the need for good practices of open data management, especially for public databases in view of external reproducibility.
Asunto(s)
Negro o Afroamericano , Ríos , Monitoreo del Ambiente , Eutrofización , Floraciones de Algas Nocivas , Humanos , Fósforo/análisis , Reproducibilidad de los Resultados , UruguayAsunto(s)
Adenocarcinoma/tratamiento farmacológico , Anafilaxia/prevención & control , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Bevacizumab/uso terapéutico , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/terapia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/complicaciones , Anafilaxia/etiología , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Bevacizumab/efectos adversos , Hipersensibilidad a las Drogas/complicaciones , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Considering that glycyrrhizic acid (GRA) has been shown to have in-vitro and in-vivo antiviral activity against a wide range of viruses as well as immunostimulating activity, a trial to evaluate its effects on the performance and the immune response against Newcastle disease of broiler chickens was carried out. The study was performed with one-day-old Ross x Ross broiler chickens. GRA was added to the drinking water throughout the 49-d production cycle at a dose of 0.03%. Sample size of the trial was established in a pilot assay. Results showed that broiler chickens treated with GRA presented better weight gain, final body weight, feed conversion ratio, and lower mortality rate than the non-treated controls. In addition, GRA-treated birds presented higher antibody titers against Newcastle disease virus and more efficient cellular immune response, as demonstrated by the late-hypersensitivity response test. Blood lymphocyte and thrombocyte counts also increased in this group. The histopathological examination of the bursa, spleen, and thymus revealed that only the thymus of the GRA-treated group had a clearly defined increase in cortex thickness on day 49. The bursa showed a higher number of lymphoid lesions in CG on days 21 and 49 compared with the GRA group. These results suggest that GRA has growth promotion properties, which are possibly linked to immune-based effects.
Asunto(s)
Animales , Biomarcadores/análisis , Pollos/crecimiento & desarrollo , Pollos/inmunología , Sistema Inmunológico/fisiología , Ácido Glicirrínico/análisis , Adyuvantes Inmunológicos/análisis , Antivirales/análisis , Enfermedad de Newcastle/fisiopatologíaRESUMEN
Considering that glycyrrhizic acid (GRA) has been shown to have in-vitro and in-vivo antiviral activity against a wide range of viruses as well as immunostimulating activity, a trial to evaluate its effects on the performance and the immune response against Newcastle disease of broiler chickens was carried out. The study was performed with one-day-old Ross x Ross broiler chickens. GRA was added to the drinking water throughout the 49-d production cycle at a dose of 0.03%. Sample size of the trial was established in a pilot assay. Results showed that broiler chickens treated with GRA presented better weight gain, final body weight, feed conversion ratio, and lower mortality rate than the non-treated controls. In addition, GRA-treated birds presented higher antibody titers against Newcastle disease virus and more efficient cellular immune response, as demonstrated by the late-hypersensitivity response test. Blood lymphocyte and thrombocyte counts also increased in this group. The histopathological examination of the bursa, spleen, and thymus revealed that only the thymus of the GRA-treated group had a clearly defined increase in cortex thickness on day 49. The bursa showed a higher number of lymphoid lesions in CG on days 21 and 49 compared with the GRA group. These results suggest that GRA has growth promotion properties, which are possibly linked to immune-based effects.(AU)
Asunto(s)
Animales , Ácido Glicirrínico/análisis , Biomarcadores/análisis , Sistema Inmunológico/fisiología , Pollos/inmunología , Pollos/crecimiento & desarrollo , Antivirales/análisis , Adyuvantes Inmunológicos/análisis , Enfermedad de Newcastle/fisiopatologíaRESUMEN
Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system, which preferentially attacks the optic nerve and spinal cord. It is associated with antibodies against aquaporin 4. Morbidity and mortality are higher than in multiple sclerosis and its treatment focuses on immunosuppressive drugs. Immunomodulators are contraindicated. We report a previously healthy 35-year-old man, presenting with NMO concomitantly with systemic lupus erythematosus. His evolution was torpid with three outbreaks in the 10 months after the diagnosis, requiring a first-line therapy with methylprednisolone and cyclophosphamide and then a second-line therapy with rituximab.
Asunto(s)
Humanos , Masculino , Adulto , Neuromielitis Óptica/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Paresia/complicaciones , Paresia/tratamiento farmacológico , Espasmo/complicaciones , Espasmo/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Neuromielitis Óptica/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Ciclofosfamida/uso terapéutico , Rituximab/uso terapéutico , Glucocorticoides/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system, which preferentially attacks the optic nerve and spinal cord. It is associated with antibodies against aquaporin 4. Morbidity and mortality are higher than in multiple sclerosis and its treatment focuses on immunosuppressive drugs. Immunomodulators are contraindicated. We report a previously healthy 35-year-old man, presenting with NMO concomitantly with systemic lupus erythematosus. His evolution was torpid with three outbreaks in the 10 months after the diagnosis, requiring a first-line therapy with methylprednisolone and cyclophosphamide and then a second-line therapy with rituximab.
Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Neuromielitis Óptica/complicaciones , Adulto , Antirreumáticos/uso terapéutico , Ciclofosfamida/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Metilprednisolona/uso terapéutico , Neuromielitis Óptica/tratamiento farmacológico , Paresia/complicaciones , Paresia/tratamiento farmacológico , Rituximab/uso terapéutico , Espasmo/complicaciones , Espasmo/tratamiento farmacológicoRESUMEN
OBJECTIVE: To determine the trend of high school students from Valparaíso Chile by means of an anthropometrical somatotype. MATERIAL AND METHODS: two samples of students during the years 1984-1985 (86 men and 71 women) and 2009-2010 (77 men and 86 women) between 15 and 18 years of age have been studied. Somatotype was estimated by the Heath-Carter anthropometric method. RESULTS: significant differences were found in all the variables of the somatotype during the periods studied (p < 0.01), except for height (p = 0.176) and humeral breadth in women (p = 0.067). Important distinctions were also found in the endomorphic, mesomorphic and ectomorphic components (p < 0.01). Men measurements registered remarkable differences in all the variables (p < 0.01), with the exception of weight (p = 0.156), calf breadth (p = 0.906) and arm breadth in contraction (p = 0.284). Measurement results of endomorphic (p < 0.01), ectomorphic (p < 0.01) and mesomorfic components (p < 0.05) revealed considerable differences. During the period 1984-1985, men classified as balanced mesomorph 2.7-4.8-3.1 which switched to mesomorph-endomorph 3.8-4.3-2.5 in the period 2009-2010. And the population of women in the 1984-1985 period is classified as mesomorph-endomorph 4.2-4.7-2.1 and changes to a mesomorphic-endomorph biotype 6.6-4.1-1.3 in the 2009-2010. CONCLUSIONS: the somatotype of the adolescent population, especially women in Valparaiso, Chile has changed to a predominant endomorphic biotype, and its mesomorphic component has decreased. A high relative adiposity contributes to increase the probability for these people to suffer non-transmissible chronic diseases and cardiovascular issues.
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Somatotipos/fisiología , Adiposidad/fisiología , Adolescente , Antropometría , Brazo/anatomía & histología , Estatura/fisiología , Peso Corporal/fisiología , Chile/epidemiología , Femenino , Humanos , Pierna/anatomía & histología , Masculino , Caracteres Sexuales , Grosor de los Pliegues Cutáneos , EstudiantesRESUMEN
AIM: To determine the accuracy of the perfusion/diffusion-weighted imaging (PWI/DWI) parameters [time to peak (TTP), mean time to peak (MTT), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) maps]; in the evaluation of acute versus hyperacute ischaemic stroke. MATERIALS AND METHODS: Fifty-five patients with symptomatic hyperacute (first 6h) or acute (7-24h) ischaemic stroke underwent diffusion and perfusion evaluation. Statistical analysis included Student's t-test, receiver operating characteristics (ROC) analysis of apparent diffusion coefficient (ADC), TTP, MTT, CBV, and CBF; correlation, linear, and logistic regression analysis. RESULTS: Area under receiver operating characteristics (AUROC) analysis identified the ADC cut-off value 385×10(-6)mm(2)/s, MTT at 109.5%, TTP at 3.05s, CBV at 129%, and CBF at 98.5% (the record of the time of onset was considered the reference standard). The best performance corresponded to TTP, which showed a sensitivity of 0.94 and specificity of 0.88 (p<0.001). CONCLUSIONS: Based on the present findings, hyperacute penumbra is reliably defined with a TTP >3s with no visible changes in diffusion. ADC, rCBF, and rCBV are not useful for discriminating between acute and hyperacute ischaemic stroke.
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Isquemia Encefálica/diagnóstico , Imagen de Difusión por Resonancia Magnética/métodos , Angiografía por Resonancia Magnética/métodos , Accidente Cerebrovascular/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo/fisiología , Volumen Sanguíneo/fisiología , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C(S0)) was 112.21 +/- 1.27 microg/mL and 201.43 +/- 1.56 microg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC(90)) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 +/- 2.26 microg/mL with 10 mg/kg SC and 72.14 +/- 3.04 microg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC(0-12)/MIC(90) ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC(0-12)/MIC(90) ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.
Asunto(s)
Antibacterianos/farmacocinética , Fosfomicina/administración & dosificación , Fosfomicina/farmacocinética , Animales , Antibacterianos/administración & dosificación , Antibacterianos/metabolismo , Área Bajo la Curva , Disponibilidad Biológica , Femenino , Fosfomicina/metabolismo , Semivida , Caballos , Inyecciones Intramusculares , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Tasa de Depuración Metabólica , Unión ProteicaRESUMEN
Pharmacokinetic variables of fosfomycin were determined after administration of buffered disodium-fosfomycin intravenously (IV), intramuscularly (IM), subcutaneously (SC) and orally (PO), in mongrel dogs, at 40 and 80 mg/kgday for three days. Renal integrity was also assessed by measuring key serum variables. Day 1, day 2 and day 3 plasma concentration vs. time profiles were undistinguishable, but there appears to be a lineal increase in serum concentrations vs. time with the dose. A non-accumulative kinetic behavior was observed after three days with both doses and most pharmacokinetic variables remain unaltered. Considering a MIC range from 1 mirog/mL to 16 microg/mL of fosfomycin in serum for sensitive bacteria, and a negligible plasma protein binding of fosfomycin (<0.5%), useful plasma concentrations can only be achieved after the SC injection of 80 mg/kg every 12h, having a C(max)=18.96+/-0.3 microg/mL; a T(1/2beta)=2.09+/-0.06 microg/mL and a bioavailability of 84-85%. No alterations were observed in serum variables of kidney-related biochemical values.
Asunto(s)
Antibacterianos/farmacocinética , Perros/metabolismo , Fosfomicina/farmacocinética , Animales , Antibacterianos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Vías de Administración de Medicamentos , Fosfomicina/administración & dosificación , Unión ProteicaRESUMEN
The aim of this trial was to assess the effect that calcium gluconate priming of 468 broilers has on the antibacterial activity of a standard dose of enrofloxacin. Hence, a series of oral pharmacokinetic studies were carried out in four groups of broilers medicated individually through an oral cannula as follows: group A, medicated only with enrofloxacin 10mg/kg; group B, receiving immediately one after the other, calcium gluconate (200mg/kg) and enrofloxacin 10mg/kg; group C, dosed first with calcium gluconate (200mg/kg) and 1h later enrofloxacin (10mg/kg); and group D, dosed first with calcium gluconate (200mg/kg) and 2h later enrofloxacin (10mg/kg). Broilers were bled at different times after the dose of enrofloxacin and antibacterial activity, measured as concentration of enrofloxacin, was measured by an agar diffusion assay. Results revealed that group D the greatest values of maximum serum concentration (Cs(max)), area under the concentration vs. time curve (AUC) and area under the moment curve (AUMC). These values were statistically higher than the corresponding ones derived from groups A, B and C (P<0.05). Taking Cs(max) and AUC values of group A as reference baseline, an increase of 24% and 50%, respectively, was obtained in group D. Group B had the lowest Cs(max), AUC, AUMC and elimination half life (T(1/2)beta) and these values were statistically different from groups A, C and D (P<0.05). The T(1/2)beta was statistically longer in groups C and D as compared with A and B, and the former groups were also different between each other (P<0.05). These results show that if calcium gluconate is first dosed to broilers and 2h later enrofloxacin is administered (as in group D), a more pronounced antibacterial activity of enrofloxacin can be obtained. A challenge of this sequential dosing scheme in a field trial may reveal its clinical value.
Asunto(s)
Antibacterianos/farmacocinética , Gluconato de Calcio/farmacología , Pollos/sangre , Fluoroquinolonas/farmacocinética , Animales , Antibacterianos/farmacología , Pollos/metabolismo , Interacciones Farmacológicas , Enrofloxacina , Fluoroquinolonas/farmacologíaRESUMEN
BACKGROUND: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood. AIM: To study atrophic gastritis among children from countries with high gastric cancer incidence. METHODS: Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum). RESULTS: One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p<0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years. CONCLUSION: Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia.
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Gastritis Atrófica , Infecciones por Helicobacter , Helicobacter pylori/aislamiento & purificación , Adolescente , Biopsia , Niño , Preescolar , Colombia , Femenino , Mucosa Gástrica/patología , Gastritis Atrófica/microbiología , Gastritis Atrófica/patología , Gastroscopía , Infecciones por Helicobacter/patología , Humanos , Corea (Geográfico) , Masculino , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Antro Pilórico/microbiología , Antro Pilórico/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: In the USA, atrophic gastritis and gastric cancer are rare, whereas gastro-oesophageal reflux disease (GERD) is common. Infection with Helicobacter pylori, especially a CagA positive strain, is unusual in patients with GERD/Barrett's oesophagus in the USA. AIM: To examine the relation between Barrett's oesophagus and CagA positive H pylori in Colombia, a country with a high prevalence of CagA positive H pylori associated atrophic gastritis and gastric cancer. METHODS: Helicobacter pylori and CagA status was determined among Colombian patients with long segment Barrett's oesophagus and a control group with simple H pylori gastritis. Helicobacter pylori status was determined using a triple stain and CagA status was determined by immunohistochemistry using a specific rabbit anti-CagA serum. RESULTS: Gastric and oesophageal mucosal biopsies were obtained from 51 patients--39 men (mean age, 57.8 years; SD, 13.1) and 12 women (mean age, 51.8 years; SD, 14.4)--with documented long segment Barrett's oesophagus. The results were compared with 24 Colombian patients with H pylori gastritis without oesophageal disease. Thirty two patients with Barrett's oesophagus had active H pylori infection. CagA status was evaluated in a subset of 23 H pylori infected patients with Barrett's oesophagus, and was positive in eight of these patients compared with 19 of 24 controls (p = 0.01). CONCLUSIONS: Although most Colombian patients with Barrett's oesophagus had H pylori infection, CagA positive infections were unusual. These data illustrate how consistent corpus inflammation reduces acid secretion, which prevents Barrett's oesophagus among those with abnormal gastro-oesophageal reflux barriers.
Asunto(s)
Antígenos Bacterianos/análisis , Proteínas Bacterianas/análisis , Esófago de Barrett/microbiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/química , Neoplasias Gástricas/microbiología , Adulto , Anciano , Animales , Esófago de Barrett/etnología , Esófago de Barrett/patología , Colombia/epidemiología , Femenino , Mucosa Gástrica/patología , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/clasificación , Humanos , Masculino , Metaplasia , Persona de Mediana Edad , Lesiones Precancerosas/etnología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Prevalencia , Conejos , Neoplasias Gástricas/etnología , Neoplasias Gástricas/patologíaRESUMEN
Heterogeneous enzymatic assays (HEA), where an enzyme in solution acts upon an immobilized substrate, are been increasingly used. Given their high throughput and versatility they hold great potential for developing massive enzyme inhibitor screening. However, current HEA lack, in general, rigorous quantitative use. This is in part due to technical problems as a multiplicity of suboptimal substrate populations achieved with traditional immobilization techniques but, more importantly, is due to a poor understanding of the particular kinetic behavior of these systems. This paper addresses the kinetic features of HEA that arise from the very low amount of solid-phase substrate and the resulting inalterability of the free enzyme concentration during the assay, which classify HEA as enzyme quasi-saturable systems (EQSS). We assessed the optimal enzyme concentration working range and time of reaction. We also considered certain attributes of HEA for evaluating isosteric inhibitors. These studies were done on the basis of a simplified model for the kinetics of EQSS and a formal splitting of the functional factor of the analytical sensitivity of an enzymatic assay into [E(o)]/K(m)-dependent and temporal components.
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Enzimas/análisis , Enzimas/química , Técnicas para Inmunoenzimas/métodos , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/análisis , Inhibidores Enzimáticos/farmacología , Enzimas/efectos de los fármacos , Cinética , Sensibilidad y EspecificidadRESUMEN
To define the impact that use of different levels of hard water has on the bioavailability of the antibacterial, enrofloxacin, in poultry, an oral bioavailability-pharmacokinetic study of the drug was carried out. Two hundred fifty clinically healthy broilers, divided into 5 groups, were individually dosed orally with 10 mg/kg of enrofloxacin diluted to 0.1%. The enrofloxacin was diluted with water of increasing hardness in accordance with an international grading system. After dosing, blood samples were obtained at predetermined times. Serum was recovered and quantified for enrofloxacin by means of an agar diffusion bacteriological method. The composite serum concentrations of enrofloxacin and metabolites vs. time relationships were analyzed using software for compartmental pharmacokinetics. Results show that there were statistically significant differences in the following pharmacokinetic variables: maximal serum concentrations (Csmax), area under the time vs. concentration curves, and half-lives of the elimination phases. The means of these values showed a linear decay of Csmax from one group to the next as water hardness increased. Chemical analysis of water calcium and magnesium ions revealed the formation of coordination groups. Lack of interference with the microbiological activity in vitro of enrofloxacin diluted in hard water indicated that diminished absorption may be partly responsible for reduction in bioavailability. These results stress the need for proper water supply when enrofloxacin is used and point out a factor that must be taken into account when clinical outcomes do not comply with expectations.
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Antibacterianos/farmacocinética , Pollos/sangre , Fluoroquinolonas/farmacocinética , Quinolonas/farmacocinética , Agua/efectos adversos , Agua/química , Animales , Disponibilidad Biológica , Calcio/análisis , Calcio/química , Enrofloxacina , Fluoroquinolonas/sangre , Magnesio/análisis , Magnesio/química , Espectroscopía de Resonancia Magnética , Quinolonas/sangreRESUMEN
With approximately 90 million cases annually, infection with Chlamydia trachomatis is the most prevalent sexually transmitted bacterial disease in the world. Considering that these infections are often asymptomatic and cause major complications like acute pelvic inflammatory disease, ectopic pregnancy, infertility or infant pneumonia, the estimated costs for diagnosis and treatment in the USA amounts to 2.2 million US dollars for each 500 cases. Therefore, there is a high need for correct, quick and cost-effective diagnosis and treatment of this urogenital tract infection. New innovative therapies provide good results with regard to efficacy and patients' compliance. The success rates of treatments are at least 95%. However, the occurrence of antibiotic resistance should not be ignored and new treatment schemes must be developed. The state-of-the-art of diagnosis and treatment of chlamydial infections as well as the pathophysiology is discussed in this review. In conclusion, infections with C. trachomatis is an important public health problem, especially in third world and developing countries, and more socio-economic studies linking secondary prevention of chlamydial infections, infertility and adverse pregnancy outcome are needed to understand more of its aetiology. In addition, diagnosis and treatment should be improved. Data in men revealed that past infections but not present infections are more related to male infertility. There is still controversial results. In future studies, function of the seminal vesicles and evaluation of the antioxidant capacity should be taken into account when role of C. trachomatis infection on male fertility is assessed.
Asunto(s)
Infecciones por Chlamydia/complicaciones , Chlamydia trachomatis , Infertilidad Masculina/microbiología , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/fisiopatología , Humanos , Infertilidad Masculina/epidemiología , Infertilidad Masculina/fisiopatología , MasculinoRESUMEN
To achieve a higher maximal serum concentration (Cs(max)) of enrofloxacin after oral administration of 10mg/kg/day of three commercial preparations of enrofloxacin to chickens, two concentrations of the drug were tested (0.1 and 0.2%), under controlled laboratory conditions. A single oral bolus dose was delivered directly into the proventriculus of each of 240 chickens, which were equally divided into six groups: three received the customary concentration (0.1%), and three received the higher concentration. A quantitative/qualitative microbiological analytical method to determine serum concentrations of enrofloxacin and a software program to obtain pharmacokinetic variables, revealed that time vs. concentration relationships best fitted double peak shape curves, Cs(max1) and Cs(max2). Statistically significant (P>0.01) increments were obtained when 0.2% enrofloxacin oral solutions from the three different commercial preparations were administered. The increments ranged from 175% to 338% for Cs(max1) and 69% to 342% for Cs(max2). Optimal bactericidal concentrations of enrofloxacin are usually twice the value of their minimal inhibitory concentration. Although clinical trials are now required, it would appear that increments in the serum concentration of enrofloxacin may reduce to the rate at which bacterial resistance occurs and so increase clinical efficacy without affecting the cost per treatment.