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OBJECTIVE: Measure the fraction of inspired oxygen (F(IO(2))) in infants receiving supplemental oxygen via nasal cannula and identify clinical variables that affect F(IO(2)). METHODS: Hypopharyngeal gas samples were obtained from 20 infants receiving oxygen via nasal cannula at flows between 0 and 4 L/min. F(IO(2)) was calculated using the alveolar gas equation and measurements of partial pressure of oxygen in the samples and the barometric pressure. RESULTS: F(IO(2)) increased as oxygen flow was increased. F(IO(2)) exceeded safe levels (> 60%) in two thirds of samples when the oxygen flow was 2 L/min or higher. Tachypnea (respiratory rate > 40 breaths/min) was associated with lower F(IO(2)). CONCLUSION: Infants receiving oxygen via nasal cannula at > or = 2 L/min may be at risk for hyperoxic lung injury. Therefore, we recommend using the lowest possible oxygen flow needed to maintain normoxia in infants requiring prolonged oxygen therapy via nasal cannula.
Assuntos
Oxigenoterapia , Oxigênio/administração & dosagem , Humanos , Lactente , Pressão Parcial , RespiraçãoRESUMO
OBJECTIVE: To test the hypothesis that cerebral and other regional organ blood flow would be maintained during partial liquid ventilation (PLV) in an animal model of acute lung injury during different ventilation strategies. DESIGN: A prospective, randomized study. SETTING: Animal research facility. SUBJECTS: Sixteen piglets, 2 to 4 wks of age. INTERVENTIONS: Severe lung injury was induced in infant piglets by repeated saline lavage and high tidal volume ventilation. Animals were then randomized to either conventional volume-controlled ventilation or PLV. MEASUREMENTS AND MAIN RESULTS: Organ blood flow was determined in both groups using radiolabeled microspheres under four conditions: high mean airway pressure, Paw; high Paco(2), high Paw; normal Paco(2); low Paw, high Paco(2); low Paw, normal Paco(2). There were no differences in cerebral blood flow during conventional ventilation and PLV, regardless of ventilation strategy. CONCLUSIONS: These results suggest in an acute lung injury model, PLV does not affect cerebral blood flow or other regional organ blood flow over a range of airway pressures.
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Aminofilina/uso terapêutico , Diurese/efeitos dos fármacos , Diuréticos/uso terapêutico , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Tacrolimo/efeitos adversos , Imunologia de Transplantes , Criança , Pré-Escolar , Humanos , Lactente , Rim/fisiopatologia , Estudos Retrospectivos , Tacrolimo/farmacocinéticaRESUMO
OBJECTIVE: The most severe form of generalized junctional epidermolysis bullosa, the Herlitz variant, is associated with a number of extracutaneous manifestations. We report on a 45-day-old infant with laryngotracheobronchial mucosa involvement who underwent successful tracheal extubation after 10 days of orotracheal intubation and mechanical ventilatory support. Issues regarding airway management and mechanical ventilatory support in the pediatric intensive care unit are discussed.
RESUMO
OBJECTIVE: To investigate the usefulness of hydroxychloroquine (HCQ) dose-loading to increase the percentage of responders or rate of response in treating rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with early RA (mean duration 1.5 years) were enrolled in a 24-week trial. Patients were stabilized with 1,000 mg naproxen/day and then began a 6-week, double-blind trial comparing treatment with HCQ at 400 mg/day (n = 71), 800 mg/day (n = 71), and 1,200 mg/day (n = 66), followed by 18 weeks of open-label HCQ treatment at 400 mg/day. RESULTS: All patients had mild, active disease at the time of initiation of HCQ treatment (31-43% rheumatoid factor positive; no previous disease-modifying antirheumatic drugs; mean swollen joint count 8.6-10.4). Based on the Paulus criteria, response during the 6-week double-blind portion of the study was 47.97%, 57.7%, and 63.6% in the 400 mg/day, 800 mg/day, and 1,200 mg/day groups, respectively (P = 0.052). Discontinuations for adverse events were dose related (3 in the 400 mg/day group, 5 in the 800 mg/day group, 6 in the 1,200 mg/day group). Most involved the gastrointestinal (GI) system, with the background naproxen treatment possibly contributing. Ocular abnormalities occurred in 17 of 212 patients (8%) but were not dose related. CONCLUSION: Dose-loading with HCQ increased the degree of response at 6 weeks in this group of patients with early, predominantly seronegative RA. Adverse GI events were dose related, while adverse ocular events were not.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Oftalmopatias/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Naproxeno/uso terapêutico , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
cAMP activated insertion of the cystic fibrosis transmembrane conductance regulator (CFTR) channels from endosomes to the apical plasma membrane has been hypothesized to regulate surface expression and CFTR function although the physiologic relevance of this remains unclear. We previously identified a subpopulation of small intestinal villus epithelial cells or CFTR high expressor (CHE) cells possessing very high levels of apical membrane CFTR in association with a prominent subapical vesicular pool of CFTR. We have examined the subcellular redistribution of CFTR in duodenal CHE cells in vivo in response to the cAMP activated secretagogue vasoactive intestinal peptide (VIP). Using anti-CFTR antibodies against the C terminus of rodent CFTR and indirect immunofluorescence, we show by quantitative confocal microscopy that CFTR rapidly redistributes from the cytoplasm to the apical surface upon cAMP stimulation by VIP and returns to the cytoplasm upon removal of VIP stimulation of intracellular cAMP levels. Using ultrastructural and confocal immunofluorescence examination in the presence or absence of cycloheximide, we also show that redistribution was not dependent on new protein synthesis, changes in endocytosis, or rearrangement of the apical cytoskeleton. These observations suggest that physiologic cAMP activated apical membrane insertion and recycling of CFTR channels in normal CFTR expressing epithelia contributes to the in vivo regulation of CFTR mediated anion transport.
Assuntos
Membrana Celular/fisiologia , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Mucosa Intestinal/fisiologia , Mucosa Intestinal/ultraestrutura , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Membrana Celular/ultraestrutura , AMP Cíclico/metabolismo , Cicloeximida/farmacologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Citoplasma/fisiologia , Duodeno , Endocitose/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Masculino , Microscopia Imunoeletrônica , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: To determine whether pretreatment with a 21-aminosteroid, U-74389G, can prevent subsequent DNA injury in bleomycin-exposed lungs. SUBJECTS: Thirty-six adult male Sprague-Dawley rats. DESIGN: Controlled animal laboratory investigation of DNA injury in vivo. INTERVENTIONS: Animals were treated with 21-aminosteroid (10 mg/kg) or vehicle and subsequently received intratracheal instillation of bleomycin (1.75 U) or normal saline. MEASUREMENTS AND MAIN RESULTS: Twenty-four hours after bleomycin exposure, the 21-aminosteroid-treated animals had decreased evidence of DNA injury, expressed as percentage of DNA fragmentation normalized to the control group (113.5 +/- 6 [SEM] vs. 132 +/- 3.9%, p < or = .05), and activity of the DNA repair enzyme poly ADP-ribose synthetase (3.4 +/- 0.2 vs. 5.6 +/- 0.9 pmol nicotinamide adenine dinucleotide/min/mg protein, p < or = .05). Only bleomycin-exposed (+ vehicle) animals demonstrated significant evidence of increased DNA injury vs. the intratracheal saline-exposed control groups. CONCLUSIONS: The 21-aminosteroid pretreatment decreases subsequent pulmonary DNA injury induced by bleomycin exposure. This finding is likely due to the 21-aminosteroid's iron-chelating and cell-permeating abilities, and suggests that these agents may be effective in other diseases where iron-dependent free radical reactions occur.
Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Antioxidantes/uso terapêutico , Bleomicina/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pregnatrienos/uso terapêutico , Pré-Medicação , Animais , Antibióticos Antineoplásicos/metabolismo , Antioxidantes/metabolismo , Bleomicina/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Quelantes de Ferro/metabolismo , Ligases/análise , Pulmão/metabolismo , Masculino , Poli Adenosina Difosfato Ribose/metabolismo , Pregnatrienos/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
High-frequency ventilation is indicated when acute hypoxemic respiratory failure is associated with an ongoing air leak. This report describes the successful use of high-frequency oscillatory ventilation in a child with pulmonary contusions and traumatic pulmonary pseudocysts who experienced severe air leak syndrome on conventional mechanical ventilation.
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Cistos/terapia , Ventilação de Alta Frequência , Lesão Pulmonar , Acidentes de Trânsito , Pré-Escolar , Contusões/complicações , Contusões/terapia , Cistos/complicações , Cistos/etiologia , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Pneumopatias/terapia , Masculino , Traumatismo MúltiploRESUMO
The medical records of patients with acquired immunodeficiency syndrome were reviewed to evaluate the effect of our adoption to the pediatric population of the National Institutes of Health recommendation for adjunctive corticosteroid therapy in adults with Pneumocystis carinii pneumonia. In 21 episodes of P. carinii-related respiratory failure, only adjunctive corticosteroids were associated with a significant improvement in survival to successful removal of the tracheal tube, from a historical rate of 11% to 91%.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/terapia , Síndrome da Imunodeficiência Adquirida/complicações , Corticosteroides/uso terapêutico , Pneumonia por Pneumocystis/terapia , Insuficiência Respiratória/terapia , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Doença Aguda , Adolescente , Adulto , Anti-Infecciosos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Humanos , Lactente , Intubação Intratraqueal , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/mortalidade , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To determine if a new class of agents, the 21-aminosteroids, which are reportedly potent inhibitors of iron-dependent lipid peroxidation, could protect rats from bleomycin-induced pulmonary fibrosis. SUBJECTS: Fifty-five adult male Sprague-Dawley rats. DESIGN: Prospective, randomized, blinded, controlled trial. INTERVENTIONS: The rats were subjected to intratracheal bleomycin (or saline vehicle), and were then treated with the 21-aminosteroid, U74389F (20 mg/kg/day), or vehicle, for the next 7 days. MEASUREMENTS AND MAIN RESULTS: At 21 days after bleomycin administration, pulmonary fibrosis was assessed histologically as percent of lung fields with evidence of fibrosis. Pulmonary fibrosis was assessed biochemically by measuring pulmonary elastin and hydroxyproline content. To determine if a protective effect of U74389F was linked to the 21-aminosteroid's ability to suppress lipid peroxidation, two products of lipid peroxidation were assayed in the lungs at 7 and 14 days after bleomycin exposure. By histologic assessment, the 21-aminosteroid-treated, bleomycin-exposed animals were found to have significantly decreased the extent of pulmonary fibrosis when compared with the bleomycin control group (mean 48.6 +/- 20.0 [SD] % [n = 9] vs. 68.4 +/- 19.6% [n = 11]; p < .05). In addition, lung elastin was decreased by approximately 75% (p < .05) and hydroxyproline was decreased by approximately 50% (NS) in the 21-aminosteroid-treated group when compared with the bleomycin control group. At 7 and 14 days after bleomycin exposure, all bleomycin-exposed animals had evidence of increased lipid peroxidation (conjugated dienes and thiobarbituric acid-reactive substances), but the 21-aminosteroid-treated, bleomycin-exposed animals had significantly decreased evidence of lipid peroxidation when compared with bleomycin controls. CONCLUSIONS: The 21-aminosteroid can substantially protect animals from bleomycin-induced pulmonary fibrosis and may prove useful in other lung diseases where iron-dependent, free-radical reactions and/or lipid peroxidation are presumed mechanisms of toxicity.
Assuntos
Pregnatrienos/farmacologia , Fibrose Pulmonar/patologia , Animais , Antioxidantes/farmacologia , Bleomicina , Elastina/metabolismo , Hidroxiprolina/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Estudos Prospectivos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
Normal lung development involves septation of the large air saccules present at birth to form smaller diameter alveoli with a much increased surface area for respiratory exchange. This process in the newborn animal is markedly inhibited by hyperoxia, and the altered lung morphology that results may be permanent. We tested whether treatment of neonatal rats with the new 21-aminosteroid (21-AS) drug, U-74389F (15 mg/kg/d), could protect against O2-induced inhibition of normal lung development. By morphometric analysis after 10 d in > 95% O2, the lungs of the animals treated with this potent iron chelator and inhibitor of lipid peroxidation showed a substantial protective effect--with reduced mean air space diameter and significantly increased internal surface area compared with O2 control pups. [Air control mean air space diameter = 47.4 microns, internal surface area = 1014 cm2; O2 controls = 61.0 microns (increases 29%), 769 cm2 (decreases 24%); O2 21-AS = 53.4 microns (increases 13%), 919 cm2 (decreases 9%); p < 0.05 between O2 groups.] Similarly, inhibition of lung elastin deposition (involved in septation process) during hyperoxia was significantly ameliorated by 21-AS treatment. In addition, follow-up studies of young adult rats demonstrated permanently enlarged lung alveoli and reduced surface area after neonatal high O2 exposure. These chronic morphologic effects were also significantly reduced by neonatal 21-AS treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Antioxidantes/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/crescimento & desenvolvimento , Oxigênio/toxicidade , Pregnatrienos/farmacologia , Animais , Animais Recém-Nascidos , Elastina/metabolismo , Feminino , Radicais Livres , Peroxidação de Lipídeos/efeitos dos fármacos , Lesão Pulmonar , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Most previous studies in isolated perfused lungs have utilized measurements of solute flow from alveolar to vascular space to characterize the barrier and transport properties of the alveolar epithelium. In this study, we measured flux of a series of nonionic hydrophilic solutes and sodium across the alveolar epithelium of the isolated rat lung from perfusate to airspace (P-->A), as well as from airspace to perfusate (A-->P). Apparent permeability-surface area products (PS) were calculated from the rates of isotope appearance downstream in either the airspace or the perfusate. Equivalent pore analysis of data for P-->A solute flow demonstrated a small pore population with radius 0.6 nm occupying 85% of the total pore area and a large pore population with radius 3.8 nm occupying 15% of the total area. Similar analysis of A-->P solute flux demonstrated a small pore population of 0.6 nm occupying 86% of the total pore area and a large pore population with radius 2.9 nm occupying 14% of total pore area. The ratio (R) of PSP-->A divided by PSA-->P was 0.8 for the nonionic hydrophilic solutes, while R for sodium was 0.5. In the presence of amiloride and ouabain, R for sucrose was unchanged while R for sodium increased to 0.8 due to a fall in PSA-->P. The difference between R for sodium and R for the passively transported solutes, and the reduction in this difference in the presence of sodium transport inhibitors, are consistent with active sodium reabsorption by the intact alveolar epithelium. Differences in measured unidirectional passive solute fluxes probably result from unequal effective surface areas for diffusion from vascular space to airspace and vice versa in the anatomically complex mammalian lung.
Assuntos
Pulmão/metabolismo , Amilorida/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Técnicas In Vitro , Transporte de Íons/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Ouabaína/farmacologia , Perfusão , Permeabilidade , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismo , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo , Sacarose/metabolismoRESUMO
Oral ketoprofen (200-300 mg/day) and indomethacin (100-150 mg/day) were compared in a 12-week double blind study involving 140 patients with rheumatoid arthritis. The treatments were generally equally effective in most assessments, producing highly significant (p less than 0.01) improvements from baseline values within one week. Only isolated statistically significant differences (p less than 0.05) were detected between the 2 treatments: ketoprofen had a more pronounced effect than indomethacin in functional class (Weeks 1 and 12), swollen joint score (Week 1), and patients' global assessments (Week 12); indomethacin was significantly superior in improving grip strength at Week 4. The clinical significance of these statistically established differences may be questioned. The incidence of side effects, primarily gastrointestinal and neurologic, was also comparable in the 2 treatments.
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Artrite Reumatoide/tratamento farmacológico , Indometacina/uso terapêutico , Cetoprofeno/uso terapêutico , Fenilpropionatos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Indometacina/efeitos adversos , Cetoprofeno/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Medição da Dor , Distribuição AleatóriaRESUMO
In a multicenter, randomized, double-blind, parallel trial, the efficacy and tolerability of two regimens of naproxen sodium were compared in a two-day treatment of moderate to severe pain following open surgery of the hip, shoulder, knee, and ankle joints. Of 147 patients enrolled, the data of 99 were valid for efficacy analysis, 45 in the low-dose regimen (day 1, 1,100 mg; day 2, 825 mg) and 54 in the high-dose regimen (1,650 mg/day). At 12 interviews each day, patients evaluated intensity of pain using numerical scales and recorded complaints. At the end of the study, overall efficacy was evaluated. Although there were no statistically significant differences between the two regimens for efficacy or tolerability, the high-dose regimen achieved greater pain relief in patients who had hip or shoulder surgery, suggesting that this regimen had greater cumulative efficacy for these patients.