RESUMO
The purpose of this study was to investigate the clonal structure, antimicrobial resistance phenotypes and their determinants among early vancomycin-resistant Enterococcus faecium (VREm) isolates in Poland. Two hundred and eighty-one VREm isolates collected between 1997 and 2005 were studied. VREm isolates were characterised by multilocus sequence typing (MLST). The presence of antimicrobial resistance determinants, transposon-specific genes, IS16 and esp Efm was checked by polymerase chain reaction (PCR). Ciprofloxacin and ampicillin resistance determinants were investigated by sequencing. Two hundred and twenty-two (79 %) and 59 (21 %) VREm isolates were vanA- and vanB-positive, respectively. Among 135 representative isolates, MLST yielded 33 different sequence types (STs), of which 29 were characteristic of hospital-associated E. faecium; 128 (94.8 %) and 123 (91.1 %) isolates harboured the IS16 and esp Efm genes, and all 135 isolates were resistant to ciprofloxacin and ampicillin. Resistance to tetracycline (71.1 % isolates) was mostly associated with tetM (75.0 %) and the concomitant presence of the Tn916 integrase gene. High-level resistance to streptomycin (93.3 % of isolates) and high-level resistance to gentamicin (94.1 % of isolates) were due to ant(6')-Ia and aac(6')-Ie-aph(2â³) genes, respectively, the latter of which is known to be located on various Tn4001-type transposons. Fifteen combinations of mutations in the quinolone-determining regions of GyrA and ParC were identified, including changes not previously reported, such as S83F and A84P in GyrA. Twenty-three variants of the penicillin-binding protein PBP5 occurred in the studied group, and novel insertions at amino acid positions 433 and 568 were identified. This analysis revealed the predominance of hospital-associated strains of E. faecium, carrying an abundant and divergent range of resistance determinants among early VREm isolates in Poland.
Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/genética , Resistência a Vancomicina/genética , Resistência a Ampicilina/genética , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , DNA Girase/genética , DNA Topoisomerase IV/genética , Elementos de DNA Transponíveis/genética , Enterococcus faecium/isolamento & purificação , Gentamicinas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Polônia , Estreptomicina/farmacologia , Tetraciclina/farmacologia , Vancomicina/farmacologiaRESUMO
The objective of this investigation was to evaluate, in a placebo-controlled manner, the developing mouse liver after antenatal exposure either to a single dose or to a multidose of betamethasone. Ninety gravid CD-1 mice were randomly divided into three groups (n = 30/group) to receive either saline (0.25 mL s.c.) or betamethasone (0.10 mg s.c.) as a single dose on gestational day (GD) 14 of a 19-day gestation or as a 0.10 mg dose given twice daily on GD 14 and on GD 15 (4 doses). GD 0 is defined by the presence of a copulatory plug. These exposures of betamethasone cause fetal mouse lung maturation as would be observed in premature humans at 24-34 weeks of gestation. The livers were removed either from the fetuses on GD 16.5 or from the offspring on postnatal day 1, 3, 5, and 120. Special stains were used to evaluate hepatocyte architecture, glycoprotein and glycogen content, extramedullary hematopoiesis and iron storage. Hepatocyte intranuclear DNA content, cell size, and cell shape were measured by image analysis (CAS 200). At GD 16.5, betamethasone produced a significant decrease in the liver/body weight ratio that, when compared with the placebo group, was greater with the multidose (p < 0.01) than with the single dose (p < 0.05). 16.5 GD single dose hepatocytes were smaller in size as compared to placebo without impact on intranuclear DNA (p < 0.01). Single dose PND 1 hepatocytes demonstrated an increase in intranuclear DNA as compared to placebo but without change in cell size (p < 0.001). The prenatal reduced liver weight recovered in the newborn period. No difference in microscopic architecture of the hepatocytes or histologic differences between either of the three treatment groups was found in glycogen deposition, extramedullary hematopoiesis or iron metabolism at GD 16.5 and postnatally. It was concluded antenatal betamethasone can cause a decrease in the liver/body weight ratio in the fetal mouse that recovers eventually without any functional impact as assessed histologically.
Assuntos
Anti-Inflamatórios/farmacologia , Betametasona/farmacologia , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/toxicidade , Betametasona/administração & dosagem , Betametasona/toxicidade , Peso Corporal/efeitos dos fármacos , DNA/efeitos dos fármacos , Feminino , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Fígado/citologia , Fígado/embriologia , Fígado/crescimento & desenvolvimento , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Placebos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Distribuição Aleatória , Cloreto de Sódio/farmacologiaRESUMO
The purpose of the study was to assess the safety of the dobutamine stress echocardiography (DASE) in patients with aortic stenosis (AS). 161 patients (mean age 59 +/- 13 years) with AS were prospectively studied with DASE. There were 58 female and 103 male. Dobutamine was given in stepwise increasing doses from 5 to 40 ug/kg/min. Mean maximal dose achieved was 31.4 ug/kg/min. The test was positive in 40 (24.8%) patients. Significant coronary artery disease was present in 60 (37.3%) patients. DASE resulted in significant increase in transvalvular mean gradient from 29.3 +/- 12.5 mmHg at rest to 46.3 +/- 19.3 mmHg at peak dose. There was no significant increase in valve area. There were no death, myocardial infarction or episodes of sustained ventricular tachycardia as a result of DASE. The test was terminated when following conditions were revealed: target heart rate (39.1%), left ventricular asynergy (25.5%), maximal established dose achieved (8.1%), side effects (27.3%). The most common side effects with the need of test cessation were arrhythmias (9.9%) and hypotension (9.9%). The most side effects were usually well tolerated without need of medical treatment. We conclude that DASE may be safely performed in patients with AS. Side effects are more common than in patients with coronary disease, but are usually well tolerated without need of medical treatment.
Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia sob Estresse/efeitos adversos , Ecocardiografia sob Estresse/métodos , Adulto , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Relação Dose-Resposta a Droga , Teste de Esforço , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The aim of the study was to assess the effect of 1-year captopril therapy initiated 1-4 days (mean: 21-24 h) after beginning of AMI on exercise performance and myocardial ischemia during cycle ergometer test. 93 pts with first documented Q-wave AMI, aged L 70 years were qualified for the study. 50 of the pts were randomly included to the captopril group, 43 to the control group. In both groups pts with inferior AMI (accordingly 66% and 72%) and normal LV function (EF > or = 40% in ECHO) were prevailed in the study. Captopril therapy was initiated with the dose of 3.125 mg, then every 8 hours the dose of 6.25 mg was administered in Ist and IInd day, 12.5 mg--in III day and 25 mg from IV day on. Exercise cycle ergometer tests (ExT) were performed in every pt at 14 day, and 1, 3, 6 and 12 months after AMI. The ExT began at 25 W of power and was increased at 2-minute intervals by 25 W until fatigue or other typical cause of termination of the test. In the captopril group duration of ExT lengthened significantly in comparison with initial test (on 14 day) after 3 (6.4 +/- 1.47 vs 5.3 +/- 1.54 min; p < 0.01), 6 (6.7 +/- 1.59 vs 5.3 +/- 1.54 min; p < 0.001) and 12 months (7.0 +/- 1.22 vs 5.3 +/- 1.54 min; p < 0.001). In the control group exercise time was longer after 6 and 12 months compared to initial examination (accordingly 6.4 +/- 1.43 and 6.5 +/- 1.26 vs 4.8 +/- 1.47 min; p < 0.001). However, the differences regarding this time between the captopril and control group were not significant on consecutive control stages. The final result of the test (positive, negative, doubtful) did not differ significantly in both groups on consecutive examination stages. Captopril administered during 1-year period after AMI slightly improved physical working capacity (accelerated the improvement) and had no effect on ischemia during estimated cycle ergometer test. These results may depend on inclusion to the study predominantly pts with normal LV function and interior MI.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Captopril/administração & dosagem , Tolerância ao Exercício/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Isquemia Miocárdica/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Isquemia Miocárdica/etiologiaRESUMO
The objective of this investigation was to determine, in a placebo-controlled manner, whether antenatal exposure to formulations of fenfluramine and dexfenfluramine impacted cardiac development and long-term growth of exposed mice offspring. One hundred forty-four CD-1 mice were randomized to six treatment groups (n=23 or 25) to obtain, per group, 5 gravids for killing on gestational day (GD) 15 and < or =10 deliveries for assessing growth of the offspring. Either fenfluramine preparation was administered in feed bars in two doses: 1 and 3.2 times the equivalent human daily dosage according to body surface area. The drugs were given from 2 weeks before mating until GD 15. The mice ingested each drug at target values, averaging 10.5+/-0.3 and 31.8+/-1.9 mg/kg/d for fenfluramine and 5.0+/-0.2 and 16.2+/-0.4 mg/kg/d for dexfenfluramine. The drug concentration was about 36% in the fetal brain compared with the adult brain. The maternal and the offspring hearts, including mitral and aortic valves, of fenfluramine-exposed mice were indistinguishable from the placebo-exposed mice. The duration of gestation and the litter size were the same between the treatment groups. The mean body weights, body lengths, and head circumferences and early functional testing did not differ significantly between the fenfluramine or dexfenfluramine-exposed offspring and the placebo-exposed offspring. There were no significant treatment differences in growth measured as body weights to PND 120. Neither fenfluramine formulation, given before conception and during gestation, impacted cardiac development and long-term growth of the mice offspring.
Assuntos
Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Fenfluramina/toxicidade , Coração/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Anormalidades Induzidas por Medicamentos , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Valva Aórtica/anatomia & histologia , Valva Aórtica/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dexfenfluramina/farmacocinética , Dexfenfluramina/toxicidade , Feminino , Fenfluramina/farmacocinética , Fertilidade/efeitos dos fármacos , Coração/embriologia , Coração/crescimento & desenvolvimento , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Valva Mitral/anatomia & histologia , Valva Mitral/efeitos dos fármacos , Gravidez , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Distribuição TecidualRESUMO
OBJECTIVE: To show that meconium causes fetal morbidity and death at earlier gestations than reported previously. METHODS: We searched for specimens from 1997 and 1998 with pathologic diagnosis of meconium-induced umbilical vascular necrosis in placentas of nonmalformed fetuses and newborns. Because intra-amniotic infection is known to activate cytokines, and blood pigment is often microscopically indistinguishable from meconium, we removed those confounding considerations by excluding placentas with chorioamnionitis and signs of intra-amniotic bleeding. Light microscopic identification of vacuolar amniotic epithelial degeneration was used to select specimens with meconium because blood does not cause that histopathologic abnormality. We used histochemical procedures to show absence of hemosiderin and presence of bilirubin, and immunocytochemical labeling with interleukin-1beta to show cytokine. RESULTS: Four cases had meconium-induced umbilical vascular necrosis. The gestational ages were 16, 19, 29, and 38 weeks. Two cases were abortuses, the third was stillborn, and the fourth was a small-for-gestational-age liveborn, delivered by cesarean because of repetitive variable decelerations. Luna-Ishak staining showed bilirubin in macrophages between umbilical vascular myocytes and in the Wharton's jelly. Immunocytochemical methods showed interleukin-1beta in those same macrophages. CONCLUSION: Cytokines and other meconium-associated factors may contribute to the pathogenesis of fetal death. Survivors may suffer intraventricular hemorrhage, periventricular leukomalacia, and other morbidity.
Assuntos
Doenças Fetais/etiologia , Mecônio , Artérias Umbilicais/patologia , Veias Umbilicais/patologia , Adulto , Bilirrubina/análise , Feminino , Humanos , Recém-Nascido , Interleucina-1/análise , Macrófagos/química , Necrose , GravidezRESUMO
Lipid cell tumors are extremely rare tumors of the ovary which are usually malignant when larger than eight centimeters. Fibromas, on the other hand, are the most common type of benign ovarian solid tumors. Neither one of these tumors are known to be accelerated by the pregnant state. We report a case of a healthy 15-year-old female who was found to have an ovarian mass during pregnancy. This fibroma weighed more than 3,800 grams and mimicked a lipid cell tumor. Cesarean section and unilateral oophorectomy resulted in a good outcome for both mother and child.
Assuntos
Adenocarcinoma/diagnóstico , Fibroma/diagnóstico , Neoplasias Ovarianas/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Adenocarcinoma/patologia , Adolescente , Cesárea , Diagnóstico Diferencial , Feminino , Fibroma/cirurgia , Seguimentos , Humanos , Neoplasias Ovarianas/cirurgia , Ovariectomia , Gravidez , Complicações Neoplásicas na Gravidez/cirurgia , Resultado da GravidezAssuntos
Hemangiossarcoma/patologia , Neoplasias Pulmonares/patologia , Adulto , Humanos , MasculinoRESUMO
The purpose of the study was to assess the safety, adverse effects and complications of the dobutamine stress echocardiography (ED). 582 patients without previous infarction were prospectively studied with ED. There were 196 female and 368 male, age varied from 27 to 74 years, mean 52. Dobutamine was given in stepwise increasing doses from 5 to 40 mcg/kg/min. Mean maximal dose achieved was 33 mcg/kg/min. Atropine was added in 253 (43%) cases. Significant coronary artery disease was present in 323 patients (53%). There were no death, no myocardial infarction or episodes of sustained ventricular tachycardia as a result of ED. The test was terminated when following conditions were revealed: target heart rate (28.9%), maximal established dose achieved (25.3%), left ventricular asynergy (19.6%), angina pectoris (10.8%), increase of systolic blood pressure above 220 mm Hg (2.6%), hypotension (7.6%), nonsustained ventricular tachycardia (1.7%). The most common non-cardiac side effects were skin tingling (19.8%), atypical chest pain(16.3%), palpitations (13.9%) and headache (7.9%). The most side effects were usually well tolerated, without the need for test cessation. The ED was terminated only in 4 (0.6%) patients because of non-cardiac side effects including nausea (0.3%) and headache (0.3%). We conclude that ED may be safely performed in routine clinical practice. Side effects were rare and usually minor. Most severe ischemic pain was relieved by test interruption and sublingual nitro-glycerine or short acting beta-blocker administration.
Assuntos
Cardiotônicos/efeitos adversos , Dobutamina/efeitos adversos , Eletrocardiografia/efeitos dos fármacos , Adulto , Idoso , Atropina , Doença das Coronárias/diagnóstico , Teste de Esforço/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parassimpatolíticos , Estudos ProspectivosRESUMO
OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner with a mouse model, whether a multidose of betamethasone is more beneficial than a single dose in accelerating fetal lung maturation. STUDY DESIGN: Ninety gravid CD-1 mice were randomly assigned to 1 of 3 groups (n = 30) to receive either a placebo (0.25 mL subcutaneously) or betamethasone (0.1 mg subcutaneously) as a single dose on gestational day 14 or as a multidose twice daily on gestational day 14 and 15. Ten pregnancies in each group were terminated at gestational day 16.5 to observe the neonatal breathing pattern (scale 0 to 5; 5 is unlabored breathing) and the lung histologic findings (scale 0 to 5; 5 is alveolar budding). The lungs of the offspring belonging to the remaining 20 pregnancies in each group were removed and weighed at postnatal day 1, 3, 5, or 120. RESULTS: Fetuses exposed to a multidose of betamethasone displayed a higher breathing score at gestational day 16.5 than either to a single dose or to the placebo (mean score 4.6 vs 3.8 or 1.3; P <. 001). Alveolar development was greater after exposure to a multidose of betamethasone than after a single dose or after a placebo (mean score 4.4 vs 3.5 or 1.6; P <.001). The lung weights at gestational day 16.5 were less after a multidose of betamethasone than after a single dose of either betamethasone or a placebo (18.3 +/- 1.0 g vs 21.4 +/- 1.3 g or 23.3 +/- 1.3 g; P <.02). The lung/body weight ratio was similarly affected. This reduced weight of the lungs persisted postnatally into adulthood. CONCLUSIONS: With a CD-1 mouse model, a multidose of antenatal betamethasone accelerated fetal lung maturation more than after a single dose but was accompanied with a decrease in lung weight that persisted into adulthood.
Assuntos
Betametasona/administração & dosagem , Maturidade dos Órgãos Fetais/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Pulmão/embriologia , Animais , Animais Recém-Nascidos/anatomia & histologia , Animais Recém-Nascidos/fisiologia , Betametasona/uso terapêutico , Esquema de Medicação , Feminino , Idade Gestacional , Glucocorticoides/uso terapêutico , Pulmão/anatomia & histologia , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Placebos , Respiração/efeitos dos fármacosAssuntos
Anorexia/diagnóstico , Faringite/diagnóstico , Abscesso Retrofaríngeo/diagnóstico , Sepse/diagnóstico , Adulto , Anorexia/complicações , Diagnóstico Diferencial , Evolução Fatal , Seguimentos , Humanos , Masculino , Faringite/complicações , Abscesso Retrofaríngeo/etiologia , Sepse/etiologia , Tomografia Computadorizada por Raios XRESUMO
With marked innovations in endosurgical instrumentation, operative laparoscopy to include lymphadenectomy has become feasible and has a valuable role in the management of gynecologic malignancy. We used laparosonic coagulating shears (LCS) for laparoscopic paraaortic lymphadenectomy in two women with cervical carcinoma. Operating times for the laparoscopic portion were 55 and 65 minutes and blood loss was 20 and 30 ml, respectively. No surgical complications were encountered. Lymphatic tissues were evaluated histologically and no thermal artifacts were identified. The major advantage of the ultrasonically activated scalpel of the LCS is the ability to cut and coagulate tissues simultaneously without electrical current. The LCS may afford the surgeon a greater margin of safety than unipolar electrocoagulation scissors by eliminating potential thermal and electrical injury to vital structures. Ultrasonic-activated technology deserves extended clinical investigation in laparoscopic lymphadenectomy to substantiate our preliminary findings, as well as to explore its potential in gynecologic oncology.
Assuntos
Laparoscópios , Excisão de Linfonodo/métodos , Adulto , Carcinoma de Células Escamosas/cirurgia , Feminino , Hemostasia Cirúrgica/instrumentação , Humanos , Laparoscopia/métodos , Excisão de Linfonodo/instrumentação , Pessoa de Meia-Idade , Instrumentos Cirúrgicos , Fatores de Tempo , Ultrassom , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVE: To compare the effects of betamethasone and dexamethasone used to enhance lung maturity of the fetal mouse. METHODS: Adult CD-1 mice were administered a single dose of either a placebo or different strengths of betamethasone (0.01, 0.025, or 0.10 mg) or dexamethasone (0.025 or 0.10 mg) on day 14.0 (74%) of gestation. The eight gravid mice in each treatment cohort were killed on day 16.5 to assess fetal lung maturity (histologic changes and respiratory patterns) in a blinded manner. Another ten gravid mice in each treatment group were allowed to deliver spontaneously to assess perinatal outcomes. RESULTS: Compared with the effects from placebo exposure, the 0.10-mg doses of both betamethasone and dexamethasone demonstrated enhanced histologic maturational changes and improved neonatal respiratory efforts. Betamethasone was twofold to threefold more potent than dexamethasone. The fetal crown-rump lengths and the fetal body, lung, and heart weights were indistinguishable among the three treatment groups. Compared with the fetal liver weight in the placebo group (55.0 +/- 2.2 mg), the liver was less heavy after exposure to 0.10 mg of betamethasone (45.6 +/- 2.0 mg; P < .005), 0.025 mg of dexamethasone (47.6 +/- 1.7 mg; P < .02), or 0.10 mg of dexamethasone (43.8 +/- 1.5 mg; P < .001). No significant differences were observed between the 0.10-mg treatments of either corticosteroid and placebo for the duration of gestation, litter size, survival rate, birth weights, or weight gains to postnatal day 26. CONCLUSION: A single subcutaneous dose of 0.10 mg of betamethasone was twofold to threefold more potent than dexamethasone in accelerating fetal lung maturity without impairing fetal survival or weight gain. The unexpected finding of a reduced fetal liver weight with either corticosteroid warrants clinical correlation.
Assuntos
Betametasona/uso terapêutico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Pulmão/efeitos dos fármacos , Animais , Método Duplo-Cego , Maturidade dos Órgãos Fetais/efeitos dos fármacos , Pulmão/embriologia , Camundongos , PlacebosRESUMO
Aims of the study were to assess the usefulness of global and segmental myocardial contractility parameters detected during dipyridamole echocardiography test in diagnosis of ischaemic heart disease. Dipyridamole time (the time from the onset of dipyridamole infusion to development of asynergy) was also evaluated. The study included 97 patients with suspected or known ischaemic heart disease (32 patients after acute myocardial infarction), mean age 48.5 years. All patients underwent dipyridamole stress echocardiography and afterwards coronary angiography. Significant stenosis (< or = 70% lumen reduction in at least one major coronary vessel) was present in 52 (54%) patients-group I. Normal coronary arteries or no significant stenosis were found in 45 (46%) patients-group II. Significant increase of wall motion score index was observed in group I. No significant change with two and there vessels disease have shorter dipyridamole time than patients with one vessel disease. Significant decrease in ejection fraction during dipyridamole echocardiography test was found in group I, whereas not significant increase in ejection fraction was observed in group II. Dipyridamole echocardiography test is a sensitive, specific and well tolerated test in the diagnosis of ischaemic heart disease.
Assuntos
Dipiridamol , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/diagnóstico por imagem , Adulto , Angiografia Coronária , Dipiridamol/farmacologia , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Sensibilidade e Especificidade , Volume Sistólico/fisiologiaRESUMO
Previously we have shown that a group of patients treated for iron overdose with prolonged deferoxamine (DFO) infusion died of adult respiratory distress syndrome (ARDS). We now describe a model to investigate the mechanism of this pulmonary toxicity. Mice treated with 1 oral dose of iron (Fe) and then multiple injections of DFO, or with the chelated product ferrioxamine alone, did not develop lung lesions, even at doses which induced mortality. To potentiate any possible free radical reaction, other groups of mice were treated similarly while exposed to 75-80% O2 over a 4-day period. Ten of 12 mice receiving 0.75 mg Fe and then DFO (10 mg, 4 times/day for 4 days) with hyperoxia died suddenly. At autopsy the lungs were dark red and solid; sections showed hyaline membranes and alveolar exudates of edema, fibrin, and PMN. Electron microscopy showed massive destruction of the alveolar epithelium; using cerium chloride, a free radical reaction product was demonstrated at the alveolar surface. Lung lavage fluid contained 10-12 x normal levels of protein when the Fe-DFO-O2 group was compared to air or O2 controls. Mice receiving DFO or Fe, plus O2, showed only slight injury and a small increase in alveolar protein. The results indicate that Fe plus DFO generates free radicals in the lung, a reaction potentiated by hyperoxia to produce an ARDS-like picture. This suggests that the pulmonary toxicity of DFO in iron-poisoned patients is due to its prooxidant activity resulting in free radical destruction of the airblood barrier.
Assuntos
Desferroxamina/toxicidade , Pneumopatias/induzido quimicamente , Pneumopatias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Câmaras de Exposição Atmosférica , Líquido da Lavagem Broncoalveolar/metabolismo , Líquido da Lavagem Broncoalveolar/patologia , Modelos Animais de Doenças , Feminino , Compostos Férricos/toxicidade , Radicais Livres/metabolismo , Humanos , Doença da Membrana Hialina/induzido quimicamente , Doença da Membrana Hialina/metabolismo , Doença da Membrana Hialina/patologia , Recém-Nascido , Ferro/toxicidade , Quelantes de Ferro/toxicidade , Pneumopatias/patologia , Camundongos , Camundongos Endogâmicos , Microscopia Eletrônica , Oxigênio/administração & dosagem , Oxigênio/metabolismoRESUMO
The drug of choice for the treatment of iron poisoning is desferrioxamine, though the best route of administration, dose, and duration of treatment are unclear. We report fatal lung injury in four patients who were treated with continuous intravenous infusions. The patients, aged 19-26 years, had received desferrioxamine infusions of 15 mg/kg per h for 65-92 h. Respiratory distress developed after 32-72 h. The patients met clinical, physiological, and necropsy criteria for the diagnosis of adult respiratory distress syndrome (ARDS); none had any of the known risk factors for the development of this disorder. We reviewed the records of forty-three iron-poisoned patients treated with desferrioxamine infusions. No patient treated for less than 24 h had pulmonary complications; however, of the fourteen treated for longer than 24 h, four were the patients with ARDS and four others had pulmonary oedema of other causes. We suggest that the pulmonary complications are caused by continuous infusion of desferrioxamine and that the ARDS in these patient was a consequence of free-radical generation. We recommend that desferrioxamine infusion should not be administered for longer than 24 h.
Assuntos
Desferroxamina/efeitos adversos , Ferro/intoxicação , Síndrome do Desconforto Respiratório/induzido quimicamente , Doença Aguda , Adulto , Desferroxamina/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Intoxicação/terapia , Síndrome do Desconforto Respiratório/patologiaRESUMO
The effect of repeated intermittent hypoxia upon the basal pulmonary vascular tone in the newborn period is unknown. We therefore studied the central hemodynamic response to seven repeated intermittent hypoxic challenges in acutely prepared piglets under 2 weeks of age. Catheters were placed in the aorta, pulmonary artery, and atria, and an electromagnetic flow probe was positioned around the main pulmonary artery. Each hypoxic challenge (Fio2 = 0.14) lasted 5 min, and was separated by an equal duration of ventilation with air. Nine control animals were ventilated with air for 90 min, a period of time equivalent to the seven challenges in the experimental group, and subjected to one hypoxic challenge at the end. Hypoxia uniformly induced pulmonary vasoconstriction. Repeated intermittent hypoxic challenges produced a progressive increase in pulmonary artery pressure and vascular resistance, both during air ventilation and hypoxia. For each challenge, the vascular resistance value achieved during hypoxia was directly related to the immediately preceding air ventilation one, and the magnitude of hypoxic pulmonary vasoconstriction, defined as the incremental change in resistance from air to hypoxia, was not different from the first to the last challenge in the experimental group. In the control group the pulmonary vascular tone did not change during the 90 min of air ventilation, and the single hypoxic challenge induced an increase in pulmonary vascular pressure and resistance similar in magnitude to the first challenge in the experimental group. Indomethacin administration to five experimental animals, after the last challenge, reversed the increase in air ventilation pulmonary artery pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Animais Recém-Nascidos/fisiologia , Hipóxia/fisiopatologia , Circulação Pulmonar , Vasoconstrição , Animais , Gasometria , Eletromiografia , Hemodinâmica , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Indometacina/farmacologia , Tono Muscular , Prostaglandinas/análise , Prostaglandinas/metabolismo , Suínos , Resistência VascularRESUMO
We investigated the role of prostacyclin (PGI2) and thromboxane A2 (TxA2), as evidenced by changes in their stable metabolites, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2), in the pathophysiology of acute bacteremic gram-negative pneumonia. Three groups of dogs were inoculated endotracheally: Group I (n = 5) with sterile broth, and Groups II (n = 5) and III (n = 10) with Pseudomonas aeruginosa. Gas exchange, hemodynamics, and plasma prostaglandins were measured before inoculation and hourly thereafter for 5 h in Groups I and II but only once in Group III, 5 h after inoculation. All animals were then killed, and the extent of pneumonia was assessed by lung wet weight and measurement of the percentage of cardiac output (CO) perfusing pneumonic lung using radionuclide-labeled microspheres. None of these measurements changed significantly in Group I, but all dogs in Groups II and III developed severe pneumonia. In Group II, mean arterial oxygen tension fell from 575 +/- 17 to 237 +/- 59 mm Hg (FIO2 = 1.0), with an increase in pulmonary shunt from 6 +/- 2% to 24 +/- 6%. Although TxB2 levels did not change, plasma 6-keto-PGF1 alpha rose progressively as pneumonia developed from baseline levels (less than 100 pg/ml) to a peak level of 890 +/- 114 pg/ml 5 h after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Epoprostenol/fisiologia , Pneumonia/fisiopatologia , Infecções por Pseudomonas/fisiopatologia , Circulação Pulmonar , Sepse/fisiopatologia , Tromboxano A2/fisiologia , Doença Aguda , Animais , Cães , Epoprostenol/sangue , Hemodinâmica , Pneumonia/sangue , Infecções por Pseudomonas/sangue , Tromboxano A2/sangueRESUMO
Acute bilateral Pseudomonas aeruginosa pneumonia was induced in 10 anesthetized dogs, after which five dogs received intravenous indomethacin (2 mg/kg) (indomethacin group), whereas five others were infused with saline (2 ml/kg) (control group). Plasma levels of 6-ketoprostaglandin F1 alpha(6-keto-PGF1 alpha) and thromboxane B2 (TxB2), stable metabolites of prostacyclin (PGI2) and thromboxane A2 (TxA2), respectively, were measured by radioimmunoassay. Although TxB2 levels were not different before and after inoculation in either group, 6-keto-PGF1 alpha levels increased from their base-line value in each animal as pneumonia developed (indomethacin group: less than 100 to 330 +/- 90 pg/ml; control group: less than 100 to 630 +/- 300 pg/ml). Both prostaglandins fell to less than 100 pg/ml in each dog after indomethacin infusion, whereas they remained elevated in the control group after infusion of normal saline. Perfusion of consolidated lung regions (Qp/QT), measured with radioactive microspheres and expressed as a percent of total pulmonary blood flow, was dramatically reduced after indomethacin (35 +/- 3 to 16 +/- 1%) with consequent improvement in pulmonary shunt (Qs/QT: 30 +/- 8 to 18 +/- 6%) and arterial O2 tension (PaO2: 123 +/- 25 to 274 +/- 77 Torr). These parameters remained unchanged or deteriorated further in the control group after infusion of saline. Three additional dogs with Pseudomonas pneumonia were studied in which the indomethacin-induced reduction in Qp/QT was substantially but not completely reversed by intravenous infusion of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)