RESUMEN
Pathological studies have revealed that one of the main features encountered in the pulmonary vasculature of patients with pulmonary hypertension is the presence of thrombotic lesions. Open pilot studies have indicated that aerosolized iloprost may have beneficial effects in patients with pulmonary hypertension. The effects of aerosolized iloprost on platelet function and plasma cyclic adenosine monophosphate (cAMP) were studied. Platelet aggregation and plasma cAMP were measured at baseline, 30 min, 4 and 6 h after inhalation of 15 microg iloprost in 10 healthy volunteers. Maximal platelet aggregation in response to adenosine diphosphate (ADP) (2 and 6 micromol x L(-1)), collagen (2.5 and 5 microg x mL(-1)), epinephrine (1.25 and 5 micromol x L(-1)) and arachidonic acid (0.5 mg x mL(-1)) was measured. Platelet aggregation was significantly inhibited at 30 min in response to ADP (2 and 6 micromol x L(-1), epinephrine (1.25 and 5 micromol x L(-1)) and collagen (2.5 microg x mL(-1)). It was still inhibited at 4 h in response to the same agents, but normalized at 6 h. cAMP increased at 30 min, from 27.3+/-1.2 to 31.8+/-1.2 nmol x L(-1), remained increased at 4 h (29.2+/-1.3 nmol x L(-1)) and normalized at 6 h (27.4+/-1.1 nmol x L(-1)). Aerosolized iloprost induced a mild but sustained inhibition of platelet aggregation. Platelet aggregation inhibition may be one of the mechanisms which explains the beneficial effect of repeated inhalation of iloprost in pulmonary hypertension.
Asunto(s)
AMP Cíclico/análisis , Iloprost/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Administración por Inhalación , Adulto , Análisis de Varianza , Determinación de la Presión Sanguínea , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Plaquetaria , Probabilidad , Valores de ReferenciaRESUMEN
To assess the diagnostic value of procalcitonin (PCT), interleukin (IL)-6, IL-8, and standard measurements in identifying critically ill patients with sepsis, we performed prospective measurements in 78 consecutive patients admitted with acute systemic inflammatory response syndrome (SIRS) and suspected infection. We estimated the relevance of the different parameters by using multivariable regression modeling, likelihood-ratio tests, and area under the receiver operating characteristic curves (AUC). The final diagnosis was SIRS in 18 patients, sepsis in 14, severe sepsis in 21, and septic shock in 25. PCT yielded the highest discriminative value, with an AUC of 0.92 (CI, 0.85 to 1.0), followed by IL-6 (0.75; CI, 0.63 to 0.87), and IL-8 (0.71; CI, 0.59 to 0.83; p < 0.001). At a cutoff of 1.1 ng/ml, PCT yielded a sensitivity of 97% and a specificity of 78% to differentiate patients with SIRS from those with sepsis-related conditions. Median PCT concentrations on admission (ng/ ml, range) were 0.6 (0 to 5.3) for SIRS; 3.5 (0.4 to 6.7) for sepsis; 6.2 (2.2 to 85) for severe sepsis; and 21.3 (1.2 to 654) for septic shock (p < 0.001). The addition of PCT to a model based solely on standard indicators improved the predictive power of detecting sepsis (likelihood ratio test; p = 0.001) and increased the AUC value for the routine value-based model from 0.77 (CI, 0.64 to 0.89) to 0.94 (CI, 0.89 to 0.99; p = 0.002). In contrast, no additive effect was seen for IL-6 (p = 0.56) or IL-8 (p = 0.14). Elevated PCT concentrations appear to be a promising indicator of sepsis in newly admitted, critically ill patients capable of complementing clinical signs and routine laboratory parameters suggestive of severe infection.
Asunto(s)
Biomarcadores/análisis , Calcitonina/análisis , Interleucina-6/análisis , Interleucina-8/análisis , Precursores de Proteínas/análisis , Sepsis/diagnóstico , Adulto , Área Bajo la Curva , Péptido Relacionado con Gen de Calcitonina , Cuidados Críticos , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Regresión , Sensibilidad y Especificidad , Sepsis/fisiopatologíaRESUMEN
BACKGROUND/AIMS: The clinical features of peritonitis are usually absent in cirrhotic patients with an ascitic fluid infection, raising the interest for specific biological markers of inflammation. METHODOLOGY: We prospectively measured the plasma and ascitic fluid levels of procalcitonin, an innovative infection parameter, interleukin-6, and C-reactive protein in 20 cirrhotics with or without spontaneous bacterial peritonitis. The patient's condition was followed-up for 12 weeks after paracentesis. RESULTS: None of the 10 patients with spontaneous bacterial peritonitis presented with severe systemic signs of infection. Procalcitonin level in plasma, but not in ascites, was significantly higher in patients with spontaneous bacterial peritonitis compared to controls (0.74 +/- 0.6 vs. 0.2 +/- 0.1 ng/mL, P < 0.05). Interleukin-6 levels in ascites were similar between groups. C-reactive protein concentrations were higher both in plasma and in ascitic fluid in patients with spontaneous bacterial peritonitis compared to controls (85.3 +/- 63 vs. 18.6 +/- 19 mg/dL, 24.6 +/- 25 vs. 4.5 +/- 4 mg/dL, P < 0.05, respectively). Three patients with spontaneous bacterial peritonitis died, but the outcome was not related to the concentrations of biological markers. CONCLUSIONS: In spontaneous bacterial peritonitis, procalcitonin measurement is not an accurate diagnostic test, possibly due to the absence of systemic inflammatory response syndrome in this condition. In addition, the diagnostic value of C-reactive protein is limited by the wide overlap between values.
Asunto(s)
Calcitonina/sangre , Cirrosis Hepática/sangre , Peritonitis/sangre , Precursores de Proteínas/sangre , Adulto , Anciano , Líquido Ascítico/química , Biomarcadores , Proteína C-Reactiva/análisis , Péptido Relacionado con Gen de Calcitonina , Femenino , Humanos , Interleucina-6/sangre , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Peritonitis/complicaciones , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
BACKGROUND: Urinary tract infection (UTI) is a common problem in children. Because clinical findings and commonly used blood indices are nonspecific, the distinction between lower and upper urinary tract infection cannot be made easily in this population. However, this distinction is important because renal infection can induce parenchymal scarring. The objective of this study was to determine the accuracy of procalcitonin (PCT) compared with C-reactive protein (CRP) rapid tests to predict renal involvement in children with febrile UTI. METHODS: PCT and CRP were measured in the blood of children admitted to the emergency room with fever, signs and symptoms of urinary tract infection and/or a positive urine dipstick analysis. Renal parenchymal involvement was assessed by a 99mTc-labeled dimercaptosuccinic acid renal scan in the acute phase of infection in all children. Sensitivity, specificity and likelihood ratios were determined for both tests. RESULTS: Fifty-four children with a proven urinary tract infection were enrolled: 63% had renal involvement; and 37% had infection restricted to the lower urinary tract. No difference was found for age, sex and total white blood cell count between the groups. The calculated likelihood ratios of procalcitonin and C-reactive protein rapid tests were between 3.8 and 7 and 1.5 and 2.8, respectively. A positive PCT value predicted renal involvement in 87 to 92% of children with febrile UTI, compared with 44 to 83% using CRP values. CONCLUSIONS: A rapid determination of procalcitonin concentration could be useful for the management of children with febrile UTI in the emergency room.
Asunto(s)
Proteína C-Reactiva/orina , Calcitonina/sangre , Fiebre/complicaciones , Precursores de Proteínas/sangre , Infecciones Urinarias/diagnóstico , Adolescente , Péptido Relacionado con Gen de Calcitonina , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Factores de Tiempo , Infecciones Urinarias/complicacionesRESUMEN
UNLABELLED: Fever without localising signs in very young children remains a diagnostic problem. Until present, a clinical scoring system combined with leucocyte count, urine analysis and determination of CRP are recognised as being helpful to identify patients at risk of serious bacterial illness. In this study we asked the question whether the determination of procalcitonin (PCT), interleukin (IL)-6, IL-8 and interleukin-1 receptor antagonist (IL- Ra) was superior to these commonly used markers for the prediction of a serious bacterial infection (SBI). Children, 7 days to 36 months of age, with a rectal temperature above 38 degrees C and without localising signs of infection were prospectively enrolled. For each infant, we performed a physical examination, a clinical score according to McCarthy, a complete white cell count, an urine analysis and a determination of CRP. We further determined PCT, IL-6, IL-8, and IL-1Ra concentrations and compared their predictive value with those of the usual management of fever without localising signs. Each infant at risk of SBI had blood culture, urine and cerebrospinal fluid cultures when indicated, and received antibiotics until culture results were available. A total of 124 children were included of whom 28 (23%) had SBI. Concentrations of PCT, CRP and IL-6 were significantly higher in the group of children with SBI but IL-8 and IL-1Ra were comparable between both groups. PCT showed a sensitivity of 93% and a specificity of 78% for detection of SBI and CRP had a sensitivity of 89% and a specificity of 75%. CONCLUSION: Compared to commonly used screening methods such as the McCarthy score, leucocyte count and other inflammatory markers such as interleukin-6, interleukin-8 and interleukin- receptor antagonist, procalcitonin and C-reactive protein offer a better sensitivity and specificity in predicting serious bacterial infection in children with fever without localising signs.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Proteína C-Reactiva/metabolismo , Calcitonina/metabolismo , Interleucinas/metabolismo , Precursores de Proteínas/metabolismo , Índice de Severidad de la Enfermedad , Bacteriemia/diagnóstico , Bacteriemia/metabolismo , Infecciones Bacterianas/metabolismo , Biomarcadores , Péptido Relacionado con Gen de Calcitonina , Humanos , Lactante , Recién Nacido , Interleucina-1/agonistas , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Modelos Logísticos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Recent research in iron metabolism has revealed the existence of iron-responding elements in the 5'UTR of the mRNA of ferritin. Binding of these structures with iron-regulatory proteins regulates ferritin synthesis within the cell, according to the intracellular iron level. Several mutations of the iron-responding elements located at the 5'UTR of the L-ferritin subunit, which lead to the hereditary hyperferritinaemia cataract syndrome, an autosomal dominant hereditary disease, have been described. Patients with congenital bilateral nuclear cataract present high serum ferritin (360-2264 micrograms/l) in the absence of iron overload. The purpose of our study was to look for this syndrome in Switzerland and in particular in the Geneva population. About 3000 cases of cataract operated on during a 4-year period (1995-1998) in the University Clinic of Ophthalmology were screened. We found 135 patients operated on before the age of 51 years. However, only 19 had bilateral nuclear cataract. 15 patients agreed to undergo iron screening. In 2 of them, a slight elevation of ferritin (267 micrograms/l in a female, 416 micrograms/l in a male) was found in the absence of iron overload. In both cases there is a positive family history of cataract. DNA sequencing analysis in these patients showed a normal nucleotide sequence of the whole iron-responding elements region. One of them (male) was found to present the codon 63 mutation at HFE gene in the heterozygous state. Our local study indicates that hereditary hyperferritinaemia cataract syndrome is extremely rare in Switzerland. However, similar studies should be carried out in other regions of the country. Iron status evaluation and ferritin level monitoring should become routine examinations in all new cases presenting with bilateral nuclear cataract before the age of 50 years.
Asunto(s)
Catarata/genética , Ferritinas/genética , Trastornos del Metabolismo del Hierro/genética , Regiones no Traducidas 5' , Secuencia de Bases , Catarata/epidemiología , Extracción de Catarata , Femenino , Humanos , Trastornos del Metabolismo del Hierro/epidemiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Suiza/epidemiología , SíndromeRESUMEN
AIMS: This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations. METHODS: Nineteen obese patients with impaired glucose tolerance (IGT) were treated with either metformin or placebo in a randomized, double-blind, placebo-controlled, cross-over study. Insulin secretion and insulin resistance were quantified using the homeostasis model assessment (HOMA) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose (SSPG). RESULTS: The average benefit of metformin was 0.6 mmol/l for glucose (95% confidence interval (CI) 0.2-0.9 P = 0.002), 2.8 pmol/l for insulin (95% CI 0.2-5.4, P = 0.019). Insulin resistance, as quantified by HOMA, was improved by 1.1 (95% CI 0.2-2.0, P = 0.004), without any change in insulin secretion. Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period, as was the SSPG concentration. However, both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo. CONCLUSIONS: These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure. In contrast, neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia.
Asunto(s)
Glucemia/metabolismo , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/farmacología , Metformina/uso terapéutico , Obesidad/sangre , Obesidad/tratamiento farmacológico , Glucemia/efectos de los fármacos , Péptido C/sangre , Método Doble Ciego , Femenino , Fructosamina/sangre , Intolerancia a la Glucosa/complicaciones , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Masculino , Obesidad/complicaciones , PlacebosRESUMEN
BACKGROUND: Elderly persons who have osteoporotic hip fracture are often undernourished, particularly with respect to protein. Protein malnutrition may contribute to the occurrence and outcome of hip fracture. OBJECTIVE: To investigate whether oral protein supplements benefit bone metabolism in patients with recent hip fracture. DESIGN: 6-month, randomized, double-blind, placebo-controlled trial with a 6-month post-treatment follow-up. SETTING: University orthopedic ward. PATIENTS: 82 patients (mean age, 80.7 +/- 7.4 years) with recent osteoporotic hip fracture. Patients received calcium supplementation, 550 mg/d, and one dose of vitamin D, 200,000 IU (at baseline). INTERVENTION: Protein supplementation, 20 g/d, or isocaloric placebo (among controls). MEASUREMENTS: Bone mineral density, biochemical markers of bone remodeling, calciotropic hormone levels, biochemically evaluated nutritional and immunologic status, and muscle strength were measured every 6 months. RESULTS: Compared with controls, patients who received protein supplements had significantly greater increases in serum levels of insulin-like growth factor-I (85.6% +/- 14.8% and 34.1% +/- 7.2% at 6 months; difference, 51.5 percentage points [95% CI, 18.6 to 84.4 percentage points]; P = 0.003) and an attenuation of the decrease in proximal femur bone mineral density (-2.29% +/- 0.75% and -4.71% +/- 0.77% at 12 months; difference, 2.42 percentage points [CI, 0.26 to 4.59 percentage points]; P = 0.029). Seven and 13 new vertebral deformities were found among patients who received protein supplements and controls, respectively (P > 0.2). Median stay in rehabilitation wards was shorter for patients who received protein supplements than for controls (33 days [CI, 29 to 56 days] and 54 days [CI, 44 to 62 days]; difference, 21 days [CI, 4 to 25 days]; P = 0.018). CONCLUSION: Protein repletion after hip fracture was associated with increased serum levels of insulin-like growth factor-I, attenuation of proximal femur bone loss, and shorter stay in rehabilitation hospitals.
Asunto(s)
Densidad Ósea , Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Fémur/metabolismo , Fracturas de Cadera/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Osteoporosis/complicaciones , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Estudios de Seguimiento , Fracturas de Cadera/etiología , Fracturas de Cadera/terapia , Humanos , Inmunoglobulina M/sangre , Tiempo de Internación , Masculino , Placebos , Prealbúmina/metabolismo , Deficiencia de Proteína/prevención & control , Albúmina Sérica/metabolismoRESUMEN
We describe the application of a stable isotope dilution assay (IDA) to determine precise insulin, C-peptide, and proinsulin levels in blood by extraction from serum and quantitation by mass spectrometry using analogues of each target protein labeled with stable isotopes. Insulin and C-peptide levels were also determined by immunoassay, which gave consistently higher results than by IDA, the relative difference being larger at low concentrations. Insulin, C-peptide, and proinsulin levels were all shown by IDA to be higher in type II diabetics than in non-diabetics, with mean values rising from 22 (+/- 2) to 92 (+/- 8), 335 (+/- 11) to 821 (+/- 24), and 6 (+/- 1) to 37 (+/- 3) pM, respectively. Interestingly, the ratio between IDA and immunoassay values for insulin levels increased from 1.3 in non-diabetics to 1.7 in type II diabetics. The ratio between proinsulin and insulin levels by IDA increased from 0.24 in non-diabetics to 0.36 in type II diabetics, whereas the ratio between C-peptide and insulin levels by IDA decreased from 17.6 to 10.7. This disproportionate change in protein levels between different types of individuals has implications for the metabolism of insulin in the diabetics studied (type II) and suggests that C-peptide levels are not always a reliable guide as to pancreatic insulin secretion. In addition, levels of the 33-residue C-peptide (partially trimmed form) were shown to be less than 10% that of the fully trimmed 31-residue C-peptide levels, and we tested IDA in a clinical context by two post-pancreatic graft studies. IDA was shown to give direct, positive identification of the target protein with unrivaled accuracy, avoiding many of the problems associated with present methodology for protein determination.
Asunto(s)
Péptido C/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Insulina/sangre , Proinsulina/sangre , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Trasplante de PáncreasRESUMEN
Insulin levels in humans were measured by a new assay, the isotope dilution assay (IDA), based on stable isotope dilution mass spectrometry. A known amount of a deuterated analog of insulin was used as an internal standard and added to the serum samples before sample processing. After isolation by immunoaffinity chromatography and solid phase extraction, followed by a purification step on reversed-phase microbore high-performance liquid chromatography (HPLC), the insulin-containing fraction was analyzed by mass spectrometry. The relative intensity of the signals due to insulin and its deuterated analog in the mass spectrum was used to determine the concentration of insulin in the sample. Using serum samples of 0.5-2.0 ml, we were able to measure insulin levels in the range of 3-1700 pmol/l in several clinical samples from type II diabetic patients. The basal level of endogenous insulin was also determined in two normal subjects and found to be approximately 20 pmol/l. Insulin secretion was followed after the ingestion of 75 g glucose in one healthy volunteer. Finally, the determination of the insulin level of one hemolyzed post-mortem blood sample, for which immunoassays gave inconsistent results, was performed to help forensic investigations. Our results showed a good correlation with standard immunoassay data, except in six samples where much lower values were obtained by our stable isotope dilution assay, suggesting an overestimation of insulin levels by immunoassay in some cases. As it is not subject to immunological interferences by insulin-related compounds, this new assay has a major clinical advantage in that it avoids confusions related to hyperinsulinemia.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus/sangre , Insulina/sangre , Insulina/metabolismo , Obesidad , Adulto , Animales , Cromatografía de Afinidad/métodos , Cromatografía Líquida de Alta Presión/métodos , Deuterio , Sobredosis de Droga , Glucosa/farmacología , Prueba de Tolerancia a la Glucosa , Humanos , Hiperinsulinismo , Inmunoensayo/métodos , Insulina/envenenamiento , Secreción de Insulina , Marcaje Isotópico/métodos , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Valores de Referencia , Sensibilidad y Especificidad , PorcinosRESUMEN
We evaluated the effects of enalapril [angiotensin converting enzyme (ACE) inhibitor] in comparison with atenolol (beta-blocker) on insulin sensitivity and serum lipoprotein concentration in obese hypertensive dyslipidemic patients. Twenty-eight hypertensive [mean blood pressure (MAP) 152 +/- 3/103 +/- 1 mm Hgl], obese [mean body mass index (BMI) 30 + 1 kg/m2A], dyslipidemic [total triglycerides 2.0 +/- 0.2 mM and/or high density lipoprotein (HDL) cholesterol 1.1 +/- 0.1 mM and low density lipoprotein (LDL) cholesterol 4.5 +/- 0.2 mM] outpatients were randomized in two groups receiving enalapril or atenolol for 12 weeks, in an investigator-blinded, parallel, comparative two-center trial. Insulin sensitivity was assessed by a modified insulin suppression test. Blood pressure (BP), insulin sensitivity, and serum lipoprotein concentrations were compared before and after each treatment and between the two treated groups. BP decreased significantly and comparably during enalapril and atenolol treatment (p < or = 0.01). The sensitivity to insulin improved by 15% (p = 0.03) in the enalapril group and worsened by 17% (p < or = 0.01) in the atenolol group. Serum lipoprotein concentrations were not modified by any treatment. The improvement in insulin sensitivity caused by enalapril treatment appears to be an advantage as compared with atenolol treatment in hypertensive obese and dyslipidemic patients, whereas the BP-lowering efficacy of the two drugs is similar. Because this effect has been reported with other ACE inhibitors, it appears to be characteristic of the entire class of ACE inhibitors.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Enalapril/uso terapéutico , Hiperlipidemias/fisiopatología , Hipertensión/tratamiento farmacológico , Insulina/farmacología , Obesidad/fisiopatología , Glucemia/análisis , Femenino , Humanos , Hiperlipidemias/sangre , Insulina/sangre , Lipoproteínas/sangre , Masculino , Obesidad/sangreRESUMEN
Primary hyperparathyroidism is the most frequent cause of hypercalcemia in outpatients. In contrast, this electrolyte disorder is very often associated with cancer when detected in hospital, particularly in the frame of tumors of breast, lung or lympho-hematopoietic system. Hypercalcemia results from an imbalance between the fluxes of calcium entering and leaving the extracellular space. Theses fluxes, mainly those at the levels of bone and kidney, are the main regulators of calcium homeostasis. Depending on the etiology, increases in either bone resorption or renal tubular calcium reabsorption can predominate as the cause of elevated calcemia. Thus, an increment of renal tubular reabsorption of calcium plays a prominent role in hypercalcemia resulting from increased serum concentrations of parathyroid hormone, but can also be detected in 50% of malignant hypercalcemias. The ectopic production of authentic parathyroid hormone has convincingly been demonstrated in very few cases. The syndrome of pseudohyperparathyrodism encountered in malignant hypercalcemia can be accounted for by the tumoral secretion of an analog of parathyroid hormone, parathyroid hormone-related protein. Both proteins, which are produced by different genes located on different chromosomes, interact with the same cell membrane receptors and display identical spectrum of actions. Since they are immunologically quite distinct, there is no cross-reactivity in the various competitive or radiometric immunoassays actually available. The determination of circulating levels of parathyroid hormone is an essential step in the differential diagnosis of hypercalcemias, provided the assays offer adequate sensitivity and specificity. Nowadays, this appears to be generally the case.
Asunto(s)
Hipercalcemia/diagnóstico , Hormona Paratiroidea/sangre , Calcio/sangre , Diagnóstico Diferencial , Humanos , Hipercalcemia/sangre , Modelos LinealesRESUMEN
Cyclosporine (CyA) is eliminated from the body via biliary excretion at a rate directly proportional to bile production and the functional status of the liver. Previous reports demonstrated that disturbances in the hepatic excretory function with a rise in the plasma bilirubin level are positively correlated with high blood concentrations of CyA and CyA plus metabolites (CyA + M). Less information is available about the blood concentrations of the CyA parental substance or CyA metabolites in the case of liver dysfunction when there was no elevation of serum bilirubin content. To answer this question, we compared the pharmacokinetic profile of CyA in a cholestatic and in a ischemic model in pigs. Our results show that in pigs receiving a single dose of CyA after liver ischemia, the blood concentrations of CyA and CyA + M are significantly increased independently of the serum bilirubin concentration, probably through a slow down of CyA metabolism by impairment of cytochrome P450 III A.
Asunto(s)
Ciclosporina/farmacocinética , Hígado/efectos de los fármacos , Alanina Transaminasa/sangre , Fosfatasa Alcalina , Animales , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Biotransformación , Ciclosporina/sangre , Ciclosporina/toxicidad , Hígado/fisiopatología , Pruebas de Función Hepática , Modelos Animales , Tiempo de Protrombina , PorcinosRESUMEN
Patients with malignant hypercalcemia can display not only an increase in bone resorption, but also changes in the renal tubular reabsorption of calcium and phosphate similar to those found in primary hyperparathyroidism. A protein of tumoral origin likely responsible for this syndrome has been described. Even if produced by another gene than parathyroid hormone, it shares a homology in the aminoterminus and seems to exert a similar spectrum of action. Besides its role in malignant hypercalcemia, this analogue may be involved in physiological regulatory processes.
Asunto(s)
Hipercalcemia/fisiopatología , Neoplasias/fisiopatología , Hormona Paratiroidea/fisiología , Proteínas/fisiología , Humanos , Hipercalcemia/etiología , Hipercalcemia/metabolismo , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/metabolismo , Neoplasias/complicaciones , Neoplasias/metabolismo , Hormona Paratiroidea/genética , Hormona Paratiroidea/metabolismo , Proteína Relacionada con la Hormona Paratiroidea , Proteínas/genética , Proteínas/metabolismoRESUMEN
We have analyzed genomic DNA sequences from 125 prospectively collected single unilateral primary breast carcinoma samples for the presence of alterations of c-myc, c-erbB-1, c-erbB-2, c-Ki-ras and c-Ha-ras protooncogenes. Amplification of the c-myc gene was found in 18% of the samples, and in one sample a non-germ line c-myc related DNA fragment or rearrangement was detected. We have found a significant association (P = 0.0010) between amplified c-myc gene and inflammatory carcinoma, a particularly aggressive breast cancer. The c-erbB-2 gene was amplified in 22% of the tumor samples and a rearrangement was observed once. Alteration of the c-erbB-2 gene was significantly linked to histological grade III tumors (P = 0.005) and the absence of estrogen and progesterone receptors (P = 0.036). No amplifications were observed for c-erbB-1, c-Ki-ras, and c-Ha-ras genes. About 40% of breast carcinomas contain either amplified c-myc or c-erbB-2 protooncogenes, whereas simultaneous amplification of both was seen in only one sample, suggesting the involvement of two distinct molecular mechanisms in breast cancer. Comparison of DNA from peripheral blood and tumor samples indicated loss of one c-Ha-ras allele in 29% of patients heterozygous for this polymorphism. A significant correlation (P = 0.016) between c-Ha-ras locus (11p14) allele loss and patient survival was found. These data suggest that 11p14 allelic loss plays a role in the evolution of human breast cancer, amplification of c-erbB-2 gene is associated with increasing stage of malignancy, and alteration of the c-myc gene in inflammatory breast carcinoma may contribute to the rapid progression of this human tumor subtype.
Asunto(s)
Neoplasias de la Mama/genética , Genes ras , Proteínas Proto-Oncogénicas/genética , Proto-Oncogenes , Southern Blotting , ADN de Neoplasias/genética , Femenino , Amplificación de Genes , Reordenamiento Génico , Humanos , Metástasis Linfática , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-myc , Receptor ErbB-2RESUMEN
Undetectable serum TSH values measured by immunoradiometric methods are highly suggestive of hyperthyroidism. However, serum TSH levels can also be very low in severely ill patients and in this case thyroid disease can be ruled out by thyroid hormone measurements. The authors have determined the frequency of low thyroid hormone values and of low serum TSH measurements in hospitalized patients. They investigated 276 euthyroid patients, 21 of whom were found to have decreased values for serum total T4 and free T4 index (FTI). Serum TSH was below the lower limit of detection (less than 0.2 mU/l) in 4 of these 21 patients (19%) and normal in 17 others. Serum TSH measurements are therefore considered more reliable than thyroid hormone measurements in ruling out primary hypothyroidism. Interestingly, serum TSH was also found to be unmeasurable in 7 of 248 patients with normal total serum T4 and FTI (3%). An unmeasurable TSH value is therefore not synonymous with low T4 in sick patients, which indicates that both measurements are needed in this category of patients. Data are also included on 7 patients with high serum total T4 and FTI but still normal serum T3, in whom as measurable serum TSH concentration rules out hyperthyroidism.
Asunto(s)
Enfermedad Aguda , Hormonas Tiroideas/sangre , Tirotropina/sangre , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Hipertiroidismo/sangre , Hipotiroidismo/sangre , Masculino , Persona de Mediana Edad , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
Complete enteral nutrition preparations include blenderised formulas based on natural foods with some fibre content and also low-residue polymeric formulas. This study examines the effect of the different fibre content of two commercial formulas (6.4 g/l and 0.25 g/l) on glycaemic and insulin response and hydrogen production in the colon during constant rate administration in 11 normal subjects. No difference in serum glucose and insulin levels was found. No rise in hydrogen production was detected with either formula suggesting no carbohydrate malabsorption. The quantity or nature of fibre present in blenderised formulas does not modify the pattern of carbohydrate absorption compared to a low-residue polymeric formula. However, this does not preclude other possible physiological effects of fibre content upon gastrointestinal motility and function.
RESUMEN
GDPmannose dehydrogenase (EC 1.1.1.132) in a mucoid strain of Pseudomonas aeruginosa isolated from a patient with cystic fibrosis was identified by demonstrating the NAD-linked formation of GDPmannuronate from GDPmannose mediated by a cell extract of the organism. Nonmucoid mutant strains did not contain GDPmannose dehydrogenase, which suggests that the enzyme is involved in the biosynthesis of alginate-like polysaccharide by P. aeruginosa.