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1.
Nutr Metab Cardiovasc Dis ; 22(3): 237-43, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20708392

RESUMO

BACKGROUND AND AIMS: The assessment of oxidative stress may aid in the identification of subsequent metabolic risk in obese children. The objective of this study was to determine whether the plasma level of advanced oxidation protein products, analyzed with a recently proposed modified assay that involves a delipidation step (mAOPPs), was related to metabolic risk factors (MRFs) in severely obese children. METHODS AND RESULTS: The plasma levels of mAOPPs were determined by spectrophotometry in 54 severely obese and 44 healthy children. We also measured lipid peroxidation biomarkers (thiobarbituric acid-reactive substances, malondialdehyde, and 8-isoprotane F(2α)) and sulfhydryl groups, a marker of antioxidant defense. Protein oxidation and lipid peroxidation markers were higher and sulfhydryl levels were lower in obese children compared with controls. Taking metabolic risk into account, obese children were subdivided according to the cutoff point (53.2 µmol/L) obtained for their mAOPPs values from the ROC curve. Anthropometric measures and the existence of hypertension did not differ between groups. The presence of dyslipidemia and insulin resistance was significantly higher in the group with higher mAOPPs levels. The highest levels of mAOPPs were found in the children with ≥3 MRFs. The level of mAOPPs was positively correlated with triglycerides and negatively correlated with high-density lipoprotein cholesterol. There was no correlation of this marker of protein oxidation with biomarkers of lipid peroxidation. CONCLUSION: The determination of mAOPPs in delipidated plasma is an easy way to evaluate protein oxidation. It may be useful in severely obese children for better cardiovascular risk assessment.


Assuntos
Síndrome Metabólica/sangue , Obesidade/sangue , Estresse Oxidativo , Proteínas/metabolismo , Adolescente , Idade de Início , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Criança , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Resistência à Insulina , Modelos Lineares , Peroxidação de Lipídeos , Lipídeos/sangue , Masculino , Malondialdeído/sangue , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Obesidade/epidemiologia , Obesidade/fisiopatologia , Oxirredução , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Espectrofotometria , Compostos de Sulfidrila/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Regulação para Cima
2.
Eur J Clin Microbiol Infect Dis ; 28(3): 233-42, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18758831

RESUMO

The purpose of this paper is to determine the incidence of fungal colonization and infection in non-neutropenic critically ill patients and to identify factors favoring infection by Candida spp. A total of 1,655 consecutive patients (>18 years of age) admitted for > or = 7 days to 73 medical-surgical Spanish intensive care units (ICUs) participated in an observational prospective cohort study. Surveillance samples were obtained once a week. One or more fungi were isolated in different samples in 59.2% of patients, 94.2% of which were Candida spp. There were 864 (52.2%) patients with Candida spp. colonization and 92 (5.5%) with proven Candida infection. In the logistic regression analysis risk factors independently associated with Candida spp. infection were sepsis (odds ratio [OR] = 8.29, 95% confidence interval [CI] 5.07-13.6), multifocal colonization (OR = 3.49, 95% CI 1.74-7.00), surgery (OR = 2.04, 95% CI 1.27-3.30), and the use of total parenteral nutrition (OR = 4.37, 95% CI 2.16-8.33). Patients with Candida spp. infection showed significantly higher in-hospital and intra-ICU mortality rates than those colonized or non-colonized non-infected (P < 0.001). Fungal colonization, mainly due to Candida spp., was documented in nearly 60% of non-neutropenic critically ill patients admitted to the ICU for more than 7 days. Proven candidal infection was diagnosed in 5.5% of cases. Risk factors independently associated with Candida spp. infection were sepsis, multifocal colonization, surgery, and the use of total parenteral nutrition.


Assuntos
Estado Terminal , Fungos/isolamento & purificação , Micoses/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Fungos/classificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/mortalidade , Estudos Prospectivos , Fatores de Risco , Espanha
3.
Chem Commun (Camb) ; 55(7): 929-932, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30601480

RESUMO

A preloaded resin consisting of a thalidomide moiety and an ethylene-oxy linker allows the simple and fast formation of PROTACs. The feasibility of the procedure was illustrated by conjugating different protein kinase inhibitors. The biological functionality of an ibrutinib-like conjugate was then confirmed by a cellular experiment.

4.
Br J Pharmacol ; 173(17): 2645-56, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27390037

RESUMO

BACKGROUND AND PURPOSE: Cyclin-dependent kinase 5 (CDK5) has recently emerged as an attractive target in several tumour entities. Inhibition of CDK5 has been shown to have anti-angiogenic effects in vitro and in vivo. However, potent inhibitors of CDK5, which can be applied in vivo, are still scarce. We have recently developed a new series of 5-substituted 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3-d]pyrimidines that show a preference for inhibiting CDK5 and tested them in vitro and in vivo in a murine model of hepatocellular carcinoma. EXPERIMENTAL APPROACH: All compounds were initially examined for effects on proliferation of HUVECs. The most potent compounds were then tested on migration, and one of them, LGR2674, was selected for assessing effects on nuclear fragmentation, cell cycle, cell viability and metabolic activity. Furthermore, LGR2674 was tested in a tube formation assay and in vivo in a murine model of hepatocellular carcinoma, induced by s.c. injection of HUH7 cells (measurement of in vivo toxicity, tumour vascularization, tumour cell proliferation and tumour size). KEY RESULTS: LGR2674 showed an EC50 in the low nanomolar range in the proliferation and migration assays. Cytotoxic effects started at 50 nM, a concentration that did not influence the cell cycle. In vivo, LGR2674 was well tolerated and caused a clear reduction in vessel density in the tumours; also tumour cell proliferation was inhibited and tumour growth retarded. CONCLUSIONS AND IMPLICATIONS: Pyrazolo[4,3-d]pyrimidine is a novel scaffold for the development of potent CDK inhibitors with in vivo potential. Such structures are good candidates for broadening our pharmacological arsenal against various tumours.


Assuntos
Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Quinase 5 Dependente de Ciclina/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinas/farmacologia , Inibidores da Angiogênese/síntese química , Animais , Antineoplásicos/síntese química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
5.
Clin Infect Dis ; 41(12): 1709-16, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16288392

RESUMO

BACKGROUND: The purpose of our study was to analyze prognostic factors associated with mortality for patients with severe community-acquired pneumonia (CAP). METHODS: We conducted a prospective multicenter study including all patients with CAP admitted to the intensive care unit during a 15-month period in 33 Spanish hospitals. Admission data and data on the evolution of the disease were recorded. Multivariate analysis was performed using the SPSS statistical package (SPSS). RESULTS: A total of 529 patients with severe CAP were enrolled; the mean age (+/-SD) was 59.9+/-16.1 years, and the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/-SD) was 18.9+/-7.4. Overall mortality among patients in the intensive case unit was 27.9% (148 patients). The rate of adherence to Infectious Diseases Society of America (IDSA) guidelines was 57.8%. Significantly higher mortality was documented among patients with nonadherence to treatment (33.2% vs. 24.2%). Multivariate analysis identified age (odds ratio [OR], 1.7), APACHE II score (OR, 4.1), nonadherence to IDSA guidelines (OR, 1.6), and immunocompromise (OR, 1.9) as the variables present at admission to the intensive care unit that were independently associated with death in the intensive care unit. In 15 (75%) of 20 cases of Pseudomonas aeruginosa infection, the antimicrobial treatment at admission was inadequate (including 8 of 15 cases involving patients with adherence to IDSA guidelines). Chronic obstructive pulmonary disease (OR, 17.9), malignancy (OR, 11.0), previous antibiotic exposure (OR, 6.2), and radiographic findings demonstrating rapid spread of disease (OR, 3.9) were associated with P. aeruginosa pneumonia. CONCLUSIONS: Better adherence to IDSA guidelines would help to improve survival among patients with severe CAP. Pseudomonas coverage should be considered for patients with chronic obstructive pulmonary disease, malignancy, or recent antibiotic exposure.


Assuntos
Antibacterianos/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/mortalidade , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Estados Unidos
6.
Med Intensiva ; 29(1): 21-62, 2005 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-38620135

RESUMO

Community acquired pneumonia is still an important health problem. In Spain the year incidence is 162 cases per 100,000 inhabitants with 53,000 hospital admission costing 115 millions of euros per year. In the last years there have been significant advances in the knowledge of: aetiology, diagnostic tools, treatment alternatives and antibiotic resistance. The Spanish Societies of Intensive and Critical Care (SEMICYUC), Infectious Diseases and Clinical Microbiology (SEIMC) and Pulmonology and Thoracic Surgery (SEPAR) have produced these evidence-based Guidelines for the management of community acquired pneumonia in Adults. The main objective is to help physicians to make decisions about this disease. The different points that have been developed are: aetiology, diagnosis, treatment and prevention.

7.
Pediatr Obes ; 10(6): 448-53, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25559237

RESUMO

BACKGROUND: Some optic nerve diseases are silent and insidious. Recently, reduced thickness of retinal nerve fibre layer (RNFL) has been associated with increasing body mass index in adults. OBJECTIVES: To investigate the association of childhood obesity with RNFL measured by optical coherence tomography imaging. METHODS: Ninety-seven children aged 5-14 years classified according to standard deviation score of body mass index (SDS-BMI) were included. Parameters of metabolic risk, adipocytokines (leptin, adiponectin) and interleukin-6 were analyzed. All subjects underwent a comprehensive ophthalmologic examination with direct ophthalmoscopy. Evaluation of RNFL with optical coherence tomography of the head of the nerve was performed. RESULTS: RNFL thickness on the average and inferior, superior and nasal quadrants were decreased in severely obese children (SDS-BMI > 4) with respect to the other groups. However, no statistically significant association was found between the different groups of children and RNFL thickness in the temporal quadrant. There was a significant inverse correlation of RNFL thickness with adiposity indices (P = 0.016), leptin (P = 0.029) and interleukin-6 (P = 0.030) in overweight and obese children. CONCLUSIONS: These findings suggest that adiposity and obesity-related inflammatory factors may be associated with the loss of retinal ganglion cells in children.


Assuntos
Fibras Nervosas/patologia , Obesidade Mórbida/patologia , Obesidade Infantil/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Adiponectina/sangue , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Interleucina-6/sangue , Leptina/sangue , Masculino , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Infantil/sangue , Obesidade Infantil/complicações , Estudos Prospectivos
8.
Intensive Care Med ; 19(7): 377-82, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8270716

RESUMO

OBJECTIVES: To demonstrate that blind insertion of the protected telescoping catheter (PTC-NB) through the orotracheal tube can provide reliable pulmonary samples for the diagnosis of nosocomial pneumonia (NP) in ventilated patients. DESIGN: We performed a random comparison between the protected telescoping catheter introduced through a bronchofiberscope (PTC-B) and the PTC-NB to diagnose NP. SETTING: A general intensive care unit of a University Hospital. PATIENTS: 40 consecutive patients on mechanical ventilation and with suspicion of NP. The diagnosis of NP was suspected by clinical and chest X-ray findings. MEASUREMENTS AND RESULTS: NP was confirmed microbiologically in 26 (65%) patients and maintained in 8 patients by clinical and radiological criteria. PTC-NB confirmed the microbiological diagnosis of PN in 21 (80%) patients. The use of antibiotics prior taking respiratory samples reduced the sensitivity of PTC-NB and PTC-B from 100-74% and from 94-70% (p = 0.001). Both techniques agreed in 24 of 33 (73%) patients but such agreement was better when PN was on the right lung. Two patients developed a self-limiting hemoptysis after the PTC-B procedure. CONCLUSIONS: PTC-NB is as sensitive as specific as PTC-B for diagnosing PN in mechanically ventilated patients, being a much easier technique to use.


Assuntos
Infecção Hospitalar/diagnóstico , Infecção Hospitalar/etiologia , Pneumonia/diagnóstico , Pneumonia/etiologia , Respiração Artificial/efeitos adversos , Adolescente , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia/métodos , Infecção Hospitalar/microbiologia , Feminino , Tecnologia de Fibra Óptica , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumonia/microbiologia , Estudos Prospectivos , Pseudomonas aeruginosa/isolamento & purificação , Distribuição Aleatória , Staphylococcus aureus/isolamento & purificação
9.
JPEN J Parenter Enteral Nutr ; 16(5): 419-22, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1433774

RESUMO

The incidence of gastroesophageal reflux (GER) in critically ill patients as well as the effect of a nasogastric tube (NGT) and body position as risk factors for GER were determined. Seventy patients with orotracheal intubation receiving enteral nutrition through a NGT for more than 48 hours were prospectively studied with two randomly assigned body positions: supine or semirecumbent. Detection of GER was achieved by scintigraphy after labeling gastric contents with 500 microCi of technetium-99m sulfur colloid administered through the NGT. In 50 patients scintigraphy was performed after subjects had remained in the randomized position for 2 hours with the NGT pinched. Twenty additional patients were studied after the NGT had been removed. In 50 patients with NGT, GER was present in 74% (37 of 50) and was higher in the supine position (81%, 21 of 26) than in the semirecumbent position (67%, 16 of 24), but this difference was not statistically significant (p = .26). In 20 patients without NGT, the incidence of GER was 35% (7 of 20) and it was also higher in the supine (50%, 6 of 12) than in the semirecumbent position (12%, 1 of 8, p = .16). There was a statistically significant difference between GER in patients with and without NGT (74% vs 35%, p = .0002). These data show that there is a high incidence of GER in patients with orotracheal intubation and NGT. The presence of a NGT is a risk factor for GER. Semirecumbency does not prevent GER, but there is less incidence than in the supine position.


Assuntos
Nutrição Enteral , Refluxo Gastroesofágico/etiologia , Intubação Gastrointestinal , Postura , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Decúbito Dorsal
10.
JPEN J Parenter Enteral Nutr ; 24(2): 103-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10772190

RESUMO

BACKGROUND: Use of a large-bore nasogastric tube (NGT) and patient position are considered key factors in promoting gastroesophageal reflux (GER) and pulmonary aspiration in critically ill patients. The objective of this study was to determine the incidence of GER and pulmonary aspiration of gastric contents in mechanically ventilated (MV) patients using small-bore NGTs. METHODS: We studied 30 patients on mechanical ventilation for acute respiratory failure who tolerated enteral nutrition through a small-bore NGT. Patients were randomly assigned to a group with (n = 16) or without (n = 14) a small-bore NGT and were maintained in a semirecumbent position during the study. GER and aspiration of gastric contents were assessed by a radioisotopic technique. Scans were done 24 hours after technetium-99m administration (n = 30). In 9 patients a dynamic scintigraphy was performed immediately after colloid administration, and samples of blood and tracheal and oropharyngeal secretions were obtained basally, 30 minutes, and 24 hours after technetium administration and analyzed for radioactivity using a gamma counter. RESULTS: Both groups were similar in age, underlying diagnosis, number of days of mechanical ventilation at the day of study, and mortality. There were no GER reaching the oropharynx and aspiration of gastric contents in both groups. CONCLUSIONS: GER and aspiration of gastric contents were not detected in MV patients using small-bore NGTs and may be a simple measure to prevent ventilator-associated pneumonia.


Assuntos
Refluxo Gastroesofágico/etiologia , Intubação Gastrointestinal/efeitos adversos , Pneumonia Aspirativa/etiologia , Respiração Artificial , Feminino , Refluxo Gastroesofágico/epidemiologia , Humanos , Incidência , Unidades de Terapia Intensiva , Intubação Gastrointestinal/instrumentação , Masculino , Pessoa de Meia-Idade , Pneumonia Aspirativa/epidemiologia , Postura , Síndrome do Desconforto Respiratório/terapia , Fatores de Risco
11.
Int J Clin Pharmacol Ther ; 33(8): 449-52, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8556224

RESUMO

The serum protein binding of itraconazole and fluconazole, new azole antifungal agents, has been investigated in vitro, in serum from healthy volunteers and from patients with cancer. Protein binding was determined by ultrafiltration. Concentrations of both alpha 1-acid glycoprotein (AAG) and albumin (HSA) were measured in all serum samples. The serum protein binding of itraconazole was reduced in patients (96.02 +/- 1.41% vs 97.25 +/- 0.54%; p < 0.01) with respect to healthy volunteers. In contrast, fluconazole protein binding was increased in the same group of patients (22.96 +/- 3.60% vs 13.30 +/- 2.58%; p < 0.01). HSA levels in cancer patients were significantly decreased (p < 0.01) and AAG levels were found to be significantly elevated in patients with respect to control subjects (p < 0.05). A significant linear relationship between the bound/unbound concentration ratio of itraconazole and HSA (r2 = 0.3340; p < 0.01) was found. Similarly, a significant relation was established between the bound/unbound concentration ratio of fluconazole and AAG levels (r2 = 0.2235; p < 0.05). Thus, a weak association between the binding of these drugs and serum protein levels has been observed. It is concluded that both antifungal drugs show different protein binding behaviour in cancer patients.


Assuntos
Antifúngicos/sangue , Proteínas Sanguíneas/metabolismo , Fluconazol/sangue , Itraconazol/sangue , Neoplasias/sangue , Adulto , Idoso , Antifúngicos/farmacocinética , Neoplasias da Mama/sangue , Neoplasias do Colo/sangue , Neoplasias Esofágicas/sangue , Feminino , Humanos , Modelos Lineares , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Ligação Proteica , Albumina Sérica/análise , Albumina Sérica/metabolismo
12.
Int J Clin Pharmacol Ther ; 32(7): 361-4, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7952798

RESUMO

The serum protein binding of itraconazole and fluconazole, new triazole antifungal agents, has been investigated in vitro in the serum of healthy volunteers and in patients with chronic renal failure (predialysis). Protein binding was determined by ultrafiltration. Concentrations of both alpha 1-acid glycoprotein (AAG) and albumin were measured in all serum samples. The protein binding of itraconazole showed no significant changes in patients with chronic renal failure when compared to healthy volunteers (96.64 +/- 0.99% vs. 96.85 +/- 0.33%). In contrast, fluconazole protein binding was significantly increased in the same patients (22.91 +/- 6.15% vs. 12.51 +/- 2.37%; p < 0.001). In addition, whereas albumin levels in the latter patients were significantly decreased (p < 0.001), their AAG levels were found to be significantly elevated with respect to control subjects (p < 0.001). While no correlation was established between itraconazole protein binding and albumin or AAG concentrations, a significant correlation was found between fluconazole protein binding and AAG levels (r = 0.72; p < 0.001). Fluconazole protein binding was found to be independent of albumin concentrations. In vitro carbamylation of serum protein with potassium cyanate caused no changes in the protein binding of fluconazole or itraconazole. We conclude that the binding of itraconazole by serum proteins is not altered in diseases involving changes of AAG or albumin concentrations. However, fluconazole protein binding may be altered in disease states associated with increased AAG concentrations.


Assuntos
Fluconazol/metabolismo , Itraconazol/metabolismo , Falência Renal Crônica/metabolismo , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Orosomucoide/metabolismo , Ligação Proteica , Albumina Sérica/metabolismo , Ultrafiltração
13.
J Pharm Pharmacol ; 42(3): 164-6, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1974610

RESUMO

Penbutolol is a beta-adrenoceptor antagonist that is extensively bound to alpha 1-acid glycoprotein (alpha 1-AGP), a protein that increases in inflammatory diseases thereby binding more drug in such conditions. Changes in serum binding can lead to modifications in the pharmacokinetics and pharmacodynamics of a drug, therefore, the central effect (as the anticonvulsant response) and brain uptake of penbutolol given intravenously to mice with experimental inflammation have been measured. A significant decrease of the central effect of penbutolol and its brain uptake was seen in diseased when compared with control animals (P less than 0.01). A parallel decrease in free fraction of penbutolol in diseased vs normal animals was detected. These results suggest that there is an increase in serum binding of basic drugs related to increments in alpha 1-AGP concentration, which reduces their central pharmacological effect.


Assuntos
Pembutolol/farmacologia , Propanolaminas/farmacologia , Animais , Proteínas Sanguíneas/metabolismo , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Eletrochoque , Inflamação/metabolismo , Injeções Intravenosas , Masculino , Camundongos , Orosomucoide/análise , Pembutolol/sangue , Pembutolol/farmacocinética , Ligação Proteica , Convulsões/prevenção & controle , Albumina Sérica/metabolismo
14.
Int J Clin Pharmacol Res ; 10(5): 271-6, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2079384

RESUMO

The plasma protein binding of ketoconazole, an oral antifungal agent of a weak basic nature, was measured after the addition of the drug (10 micrograms.ml-1) to serum from 35 healthy individuals, ten patients with chronic renal disease and seven patients with hepatic cirrhosis. The percentage of free ketoconazole was markedly increased in patients with chronic renal disease and in patients with hepatic cirrhosis, when it was compared with the group of healthy volunteers (7.33 +/- 0.11 in renal patients; 6.12 +/- 1.43 in hepatic patients compared with 2.93 +/- 0.12 in healthy individuals). The binding ratio of ketoconazole in health and disease was significantly related to plasma albumin concentration, but not to plasma alpha 1-acid glycoprotein (AAG) concentration. Moreover, ketoconazole binds to isolated human serum albumin in a greater proportion but does not bind to isolated AAG indicating that human serum albumin is the major binding protein for this drug in plasma.


Assuntos
Cetoconazol/sangue , Adulto , Proteínas Sanguíneas/metabolismo , Feminino , Humanos , Cetoconazol/farmacocinética , Falência Renal Crônica/metabolismo , Cirrose Hepática/metabolismo , Masculino , Orosomucoide/metabolismo , Ligação Proteica , Valores de Referência
15.
Methods Find Exp Clin Pharmacol ; 13(10): 693-6, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1770832

RESUMO

The in vitro effect of the halothane metabolite, trifluoroacetic acid, on the protein binding of three different benzodiazepines (diazepam, lorazepam and midazolam) has been investigated. Furthermore, protein binding of these drugs was studied in serum from patients under the effect of halothane anesthesia (1-2.5%; 2.5 h). Trifluoroacetic acid, 4 mmol/l, displaced diazepam and midazolam from serum and produced a marked increase in the free percentage, but did not influence lorazepam binding. Moreover, 48 h after the end of halothane anesthesia, there were changes in protein binding of diazepam (3.9 +/- 0.3% at 48 h vs. 3.3 +/- 0.3% before halothane anesthesia; p less than 0.05). It can be concluded that halothane anesthesia (1-2.5%; 2.5 h) may temporarily potentiate the pharmacological effect of diazepam in the postoperative period following anesthetic procedures.


Assuntos
Diazepam/metabolismo , Halotano/farmacologia , Lorazepam/metabolismo , Midazolam/metabolismo , Ácido Trifluoracético/farmacologia , Adulto , Anestesia por Inalação , Ligação Competitiva , Diazepam/sangue , Interações Medicamentosas , Humanos , Midazolam/sangue , Pessoa de Meia-Idade , Medicação Pré-Anestésica , Ligação Proteica/efeitos dos fármacos , Ácido Trifluoracético/sangue
16.
Med Clin (Barc) ; 75(6): 250-3, 1980 Oct 10.
Artigo em Espanhol | MEDLINE | ID: mdl-7421360

RESUMO

The incidence and clinical course of urinary tract infections in postmenopausal diabetic patients in comparison to non-diabetic women have been evaluated. All cases with former history of urinary instrumentation or underlying conditions favoring urinary infections were rejected. Urinary tract infection was present in 14.9 percent of postmenopausal diabetics versus 10.5 percent in the non-diabetics. The incidence of urinary tract infection in premenopausal women was 12.5 percent. Urinary pathogenes showed similar incidence rate in both groups: E. coli (41 versus 57 percent), P. mirabilis (20 versus 28 percent) and Klebsiella (11 versus 20 percent). Diabetic women showed a higher rate of sepsis and infection recurrence than non-diabetic (10.7 and 17.8 percent versus 2.6 and 2.6 percent, respectively). Severe impairment of renal function (plasma creatinine clearance > 2 mg/100 ml) was registered in 12.5 percent of postmenopausal patients with diabetes mellitus, but none of the non-diabetics suffered renal damage (p < 0.01).


Assuntos
Nefropatias Diabéticas/epidemiologia , Menopausa , Infecções Urinárias/epidemiologia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Espanha
17.
Med Clin (Barc) ; 102(14): 527-31, 1994 Apr 16.
Artigo em Espanhol | MEDLINE | ID: mdl-8208021

RESUMO

BACKGROUND: The evaluation of the prognosis of critically ill patients by the APACHE II method is common in intensive care units (ICU). The aim of the present was to analyze the possible factors associated to errors in prediction. METHODS: A prospective study of 564 consecutive admissions in a department of intensive medical care was carried out. Prediction errors were studied by the calculation of the probability of death established after the first 24 hours of admission by means of APACHE II. The factors analyzed in relation to the prediction errors were: the diagnosis or cause of admission to the ICU, the length of the stay in the ICU, the time until possible death, the possible relation of the death with the cause of admission and the treatment given to the patients during the first 24 hours. Statistical analysis was performed with the SPSS software package with significance being determined at p < 0.05. RESULTS: Mortality was of 20.6% (116 cases) with three cut off points being chosen for probability of death (50, 70, and 90%). Accuracy of precision was 83.5%, 82.8% and 80.1%. There were 64 false survivors (mortality lower than 50%, 13.25%-64/483) and 29 false deaths (survival greater than 50%, 35.8%-29/81). Upon analysis of the cause of admission of these patients in whom there were prediction errors it was found that there were no differences among the false survivors and the false deaths. Significant differences were only detected upon comparison of the false survivors with the verified survivors, however these disappeared when the 136 cases admitted due to myocardial infarction were excluded. Neither did the length of stay in the ICU demonstrate any significant difference except among the verified and false deaths in that the stay was longer in the latter. CONCLUSIONS: The factors analyzed did not demonstrate that they may influence or be associated with errors in prediction of the prognosis of patients admitted to an intensive care unit, with these errors probably being due to errors in the system used.


Assuntos
Estado Terminal/mortalidade , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos
18.
Med Clin (Barc) ; 111(17): 650-4, 1998 Nov 21.
Artigo em Espanhol | MEDLINE | ID: mdl-9881346

RESUMO

OBJECTIVE: To determine the techniques used for the etiological diagnosis of community-acquired pneumonia in patients admitted to the intensive care unit (ICU) and to describe the predominant causative organisms as well as prognostic factors of ICU mortality. PATIENTS AND METHODS: A total of 262 patients with community-acquired pneumonia admitted to 26 ICUs between 1 November of 1991 and 31 October of 1992 were included in a prospective, open, multicenter study. RESULTS: The diagnostic techniques most frequently used were blood culture (243 cases) and simple tracheal aspirate (166 cases). Simple tracheal aspirate (58.4%), bronchoalveolar lavage (47.7%), and protected-specimen brush (44.2%) were the techniques that showed the highest diagnostic reliability. In 220 cases, techniques considered of high diagnostic probability were employed. With the use of these procedures, the most frequent causative pathogens were Streptococcus pneumoniae (13.6%) and Legionella pneumophila (9.5%). In 100 cases (45.5%), no pathogen was isolated. A total of 88 patients (33.6%) died during the ICU stay. Predictive variables of poor outcome selected by means of a multivariate analysis were as follows: multisystemic failure (OR = 28.6; 95% CI: 12.8-65.1; p = 0.0001), APACHE II at the time of ICU admission (OR = 5.3; 95% CI: 2.5-11.3; p = 0.0001), progression and/or spread of lung infection (OR = 4.5; 95% CI: 2.4-8.4; p = 0.0001), and shock on admission (OR = 8.48; 95% CI: 4.5-15.9; p = 0.0001). CONCLUSIONS: In 45.5% of patients with community-acquired pneumonia admitted to ICU, no causative pathogen was identified. The prognosis of these patients was influenced by the severity of disease assessed by APACHE II score and presence of multisystemic failure and shock at the time of ICU admission.


Assuntos
Pneumonia Bacteriana/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Prognóstico , Estudos Prospectivos
19.
An Med Interna ; 15(8): 433-5, 1998 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-9780426

RESUMO

A 44 year-old man with a type I Neurofibromatosis (NFI) and an intercostal mass is presented. By means of percutaneous fine needle aspiration punction under CT control, this tumor could be diagnosed of neurofibroma. It is important to remark not only the role of helical CT with anatomical reconstruction in the diagnosis of intercostal tumors, but also that intercostal location of neurofibromas has been rarely reported in the literature. Because of frequent association between NFI and neoplasms, it is always necessary to perform histological study of every new tumor that appears in the course of this entity.


Assuntos
Músculos Intercostais , Espectroscopia de Ressonância Magnética , Neurofibroma/diagnóstico , Neurofibromatose 1 , Adulto , Humanos , Masculino , Neurofibroma/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
Cir Pediatr ; 8(4): 158-60, 1995 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-8679392

RESUMO

Ureterocele is a congenital cystic dilatation of the intravesical segment of the ureter. As a consequence, the proximal ureter and renal pelvis become dilated and that results in renal-parenchymal pathological involvement. Management of this anomaly is still controversial. Among the therapeutical options there is a place for endoscopic punction. Our experience with 11 patients undergoing this treatment modality is reported. In all these cases endoscopic punction was the initial treatment. In 7 patients this technique was all that was needed. The technique of intravesical punction is described and its results are specified.


Assuntos
Punções , Ureterocele/terapia , Ureteroscopia , Criança , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Rim/anormalidades , Rim/diagnóstico por imagem , Masculino , Ultrassonografia , Ureterocele/diagnóstico , Ureterocele/diagnóstico por imagem , Urografia
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