RESUMO
Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood. Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation. While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation. With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation. Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients. These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function. This effect may have application for the treatment of diseases characterized by endothelial dysfunction.
Assuntos
Mercaptoetanol , Óxido Nítrico/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , S-Nitrosotióis , Administração por Inalação , Adulto , Transporte Biológico , Endotélio Vascular/metabolismo , Feminino , Antebraço , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Químicos , Óxido Nítrico/administração & dosagem , Óxido Nítrico/sangue , Nitritos/sangue , Compostos Nitrosos/sangueRESUMO
Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of beta-chain cysteine 93, raise the possibility of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P(50), did not respond to inhaled NO, either in controls or in individuals with sickle cell disease. At baseline, the arterial and venous levels of nitrosylated hemoglobin were not significantly different, but NO inhalation led to a dose-dependent increase in mean nitrosylated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are too low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion.
Assuntos
Anemia Falciforme/sangue , Eritrócitos/metabolismo , Hemoglobina A/metabolismo , Hemoglobina Falciforme/metabolismo , Óxido Nítrico/sangue , Óxido Nítrico/farmacologia , Oxigênio/sangue , Oxiemoglobinas/metabolismo , Administração por Inalação , Adulto , População Negra , Feminino , Humanos , Cinética , Masculino , Óxido Nítrico/administração & dosagem , Pressão Parcial , Valores de Referência , Estados Unidos , População BrancaRESUMO
BACKGROUND: Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number of solid tumors, including ovarian cancer and breast cancer. PURPOSE: Our purpose was to conduct a phase II clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF). METHODS: A prospective phase II clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/m2 paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 micrograms/kg per day was given to ameliorate myelo-suppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 micrograms/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy. RESULTS: Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients; 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy. CONCLUSIONS: We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower dose in similar cohorts of patients treated without G-CSF. Comparison of phase II studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer.
Assuntos
Doenças da Medula Óssea/prevenção & controle , Carcinoma/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Doenças da Medula Óssea/induzido quimicamente , Esquema de Medicação , Resistência a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Compostos de Platina/uso terapêutico , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To increase the taxol dose beyond the current standard dose intensity of 175 mg/m2 per 21 days in patients with refractory ovarian cancer. PATIENTS AND METHODS: Fifteen patients who had platinum-refractory or recurrent advanced-stage ovarian cancer were treated with taxol in a phase I trial and were given granulocyte-colony stimulating factor (G-CSF). Taxol was administered at doses of 170, 200, 250, and 300 mg/m2 every 3 weeks. G-CSF was given as a daily subcutaneous injection that started 24 hours after the completion of the taxol infusion. RESULTS: Four patients required either taxol dose reduction or delay. The dose-limiting toxicity (DLT) was peripheral neuropathy, and it occurred at 300 mg/m2. This toxicity was manifested clinically as a stocking-and-glove sensory disturbance that primarily affected proprioception, and was associated with objective changes on nerve conduction studies in affected individuals. Mucositis was rarely observed. Substantial myelosuppression was observed, but was not dose-limiting. Five of 14 assessable patients experienced an objective response to therapy, with another five individuals who experienced a 30% to 45% reduction in tumor mass. CONCLUSION: Taxol can be safely administered in doses up to 250 mg/m2 with G-CSF support, which may make it possible to study taxol dose intensification.
Assuntos
Alcaloides/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Doenças da Medula Óssea/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Alcaloides/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Carcinoma/tratamento farmacológico , Avaliação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel , Resultado do TratamentoRESUMO
PURPOSE: To study the effect of the multidrug-resistance reversal agent R-verapamil on the pharmacokinetic behavior of paclitaxel. METHODS: Six women with breast cancer who received paclitaxel as a 3-hour infusion with and without R-verapamil were monitored with frequent plasma sampling up to 24 hours postinfusion. Paclitaxel concentrations were measured using a reverse-phase high-pressure liquid chromatography assay. RESULTS: Concomitant administration of R-verapamil resulted in a decrease in mean (+/- SD) paclitaxel clearance from 179 +/- 67 mL/min/m2 to 90 +/- 34 mL/min/m2 (P < .03) and in a twofold increase in paclitaxel exposure (area under the curve [AUC]). The mean end-infusion paclitaxel concentration was also twofold higher: 5.1 +/- 1.8 mumol/L versus 11.3 +/- 4.1 mumol/L (P < .03). CONCLUSION: The alteration in paclitaxel pharmacokinetics when paclitaxel and R-verapamil are coadministered complicates the interpretation of response and toxicity data from clinical trials of this drug combination.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Paclitaxel/farmacocinética , Verapamil/uso terapêutico , Neoplasias da Mama/sangue , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Quimioterapia Combinada , Feminino , Humanos , Taxa de Depuração Metabólica/efeitos dos fármacos , Paclitaxel/uso terapêuticoRESUMO
The administration of interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells can mediate the regression of cancer. Treatment with IL-2 is associated with significant cardiorespiratory effects, as well as a leaky capillary syndrome requiring careful fluid management. A mild reversible depression of cardiac function is also associated with IL-2 treatment. All patients treated with recombinant IL-2 alone, with transfer of LAK cells, or with cyclophosphamide between December 1984 and September 1987 (total of 423 treatment courses in 317 total patients) were evaluated as to the development of significant cardiorespiratory toxicity. Of the 423 treatment courses, only 1.8% were associated with severe peripheral edema and only 2.8% and 3.1% respectively, were associated with significant ascites or pleural effusions. Thirty-nine of 423 patients (9.2%) had severe respiratory distress and 27 patients required intubation (6.4%). Cardiovascular effects included tachycardia and hypotension requiring vasopressor administration in 65% and intravenous (IV) fluid administration. Weight gain greater than or equal to 10% of body weight was noted in 32% of the 423 patients. Arrhythmias were primarily supraventricular (9.7%) and responded well to conventional medical treatments. Angina or ischemic changes were noted in 2.6% of patients and myocardial infarction in 1.2%. IL-2 caused peripheral vasodilation, with a significant decrease in peripheral vascular resistance (2,254 +/- 398 v 1,303 +/- 351 dyne.s.cm-5, P less than .0001), and an increase in heart rate (66.2 +/- 10 v 104.3 +/- 9.6 beats/min, P less than .0001). There was also evidence of mild cardiac dysfunction, with a significant decrease in the left ventricular stroke work (LVSW) index (P less than .0001) and ejection fraction (LVEF) (from 58% +/- 10% to 52% +/- 9%, P less than .03). A repeat LVEF performed after 1 to 3 months, had returned to baseline values (60% +/- 10%). A mean 64% increase in the rate of disappearance of radioactive iodine (125I) albumin (P less than .05) consistent with the development of a leaky capillary syndrome was noted. Patients with underlying cardiorespiratory diseases may be at greater risk during IL-2 administration and should not be selected to undergo this treatment.
Assuntos
Doenças Cardiovasculares/etiologia , Hemodinâmica , Interleucina-2/efeitos adversos , Pneumopatias/etiologia , Neoplasias/terapia , Adulto , Feminino , Humanos , Interleucina-2/uso terapêutico , Ativação Linfocitária , Linfocinas/administração & dosagem , Linfocinas/isolamento & purificação , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS: We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS: The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION: Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/farmacocinética , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Coração/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Trombocitopenia/induzido quimicamenteRESUMO
The objective of this phase I trial was to determine the maximal tolerated dose (MTD) of Taxol and doxorubicin administered as a simultaneous intravenous infusion over 72 hours every 21 days. Granulocyte-colony stimulating factor (G-CSF) 10 micrograms/kg, was administered on days 4-18 of each cycle. The treated population consisted of metastatic breast cancer patients previously untreated with chemotherapy for metastatic disease, who had not received doxorubicin in the adjuvant setting and who had bidimensionally measurable disease. The MTD was determined to be 75 mg/m2 of doxorubicin and 160 mg/m2 of Taxol. The dose-limiting toxicity of the combination was clinical typhlitis in three of three patients. Other significant toxicities included grade 3 diarrhea at the higher dose levels and grade 4 neutropenia in all patients. Eighteen patients were treated on this initial phase I study. The overall response rate was 62%, with 6% complete responses and 56% partial responses. The combination of doxorubicin and Taxol by 72-hour continuous infusion with G-CSF is an active regimen in patients with metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Paclitaxel/administração & dosagem , Feminino , Coração/efeitos dos fármacos , Humanos , Metástase Neoplásica , Paclitaxel/efeitos adversosRESUMO
Erysipelothrix rhusiopathiae rarely causes bacteremia, and it has never been reported to cause septic shock. A 58-year-old man with fulminant hyperdynamic shock associated with E. rhusiopathiae bacteremia is described. Erysipelothrix must be considered when a patient with an appropriate history presents with septic shock.
Assuntos
Infecções por Erysipelothrix/diagnóstico , Sepse/diagnóstico , Choque Séptico/diagnóstico , Animais , Braquiúros , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Profissionais/etiologiaRESUMO
The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Pulmão/patologia , Pneumonia por Pneumocystis/complicações , Adolescente , Adulto , Biópsia , Vasos Sanguíneos/patologia , Criança , Pré-Escolar , Cistos/patologia , Exsudatos e Transudatos/metabolismo , Feminino , Granuloma/complicações , Granuloma/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Pneumonia por Pneumocystis/metabolismo , Pneumonia por Pneumocystis/patologia , Alvéolos Pulmonares/metabolismo , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologia , Vasculite/complicações , Vasculite/patologiaRESUMO
Lymphocytic interstitial pneumonitis (LIP) and nonspecific interstitial pneumonitis (NIP) are pulmonary complications of human immunodeficiency virus (HIV) infection that occur in the absence of a detectable opportunistic infection or neoplasm. We reviewed lung biopsy specimens from 50 adult HIV-infected patients, of whom four had LIP and 46 had NIP. The majority (47 of 50) of specimens from patients with NIP showed mild chronic interstitial pneumonitis (CIP/NIP), with three showing features of diffuse alveolar damage, organizing phase. In contrast to CIP/NIP, the five specimens from four patients with LIP demonstrated more extensive lymphocytic interstitial infiltrates that extended into the alveolar septal interstitium. The majority of the interstitial lymphocytes in both NIP and LIP were of T-cell origin and stained for UCHL-1. The etiologies of NIP and LIP remain unknown. Since the common opportunistic infections were excluded by routine methods, we sought, with special techniques, to investigate whether HIV, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) could be identified in lung biopsy specimens from these patients. By in situ hybridization, we found one LIP specimen with expression of large amounts of HIV RNA primarily within macrophages in germinal centers; in the remaining specimens, occasional cells expressing HIV RNA were found (two LIP and four NIP). Neither CMV nor EBV was found by in situ hybridization in seven specimens; in these same specimens EBV was detected using the polymerase chain reaction in only one case of NIP, similar to results in control specimens. These results, together with the knowledge that lymphocytic pulmonary lesions may be caused by lentiviruses in humans and animals, suggest that HIV plays a significant role in the pathogenesis of both NIP and LIP in adult HIV-infected patients; in contrast, our data do not demonstrate a direct role for either EBV or CMV.
Assuntos
Infecções por HIV/complicações , Fibrose Pulmonar/microbiologia , Adulto , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/complicações , Feminino , HIV/isolamento & purificação , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , Sistema Linfático/patologia , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologiaRESUMO
STUDY OBJECTIVE: To assess the risk for complications with the use of sedation and analgesia techniques in pediatric fiberoptic bronchoscopy. DESIGN: A retrospective case series. SETTING: The ICU of a 325-bed tertiary care research hospital. PATIENTS: Patients from 1 to 18 years of age who underwent fiberoptic bronchoscopy with BAL or transbronchial biopsy between June 1991 and December 1995 and received IV sedation and analgesia. INTERVENTIONS: None. METHODS: A retrospective chart review was performed. Extracted data included anesthetics and sedatives used and their per kilogram dosages, procedure durations, and complications including oxygen desaturations < 90%, vital sign alterations that required intervention, and emergence reactions to ketamine. RESULTS: A total of 103 bronchoscopies were performed on 64 patients. Ketamine was used as the primary anesthetic in 60 procedures (58%). A combination of fentanyl and midazolam was used in 38 of the 43 remaining procedures. A variety of combinations were used in the five remaining procedures. Complications occurred in 13 procedures and included oxygen desaturations, stridor, cough, apnea, and nasal bleeding. Twelve of the 13 complications occurred in patients with a diagnosis of HIV infection. Eight of the13 complications involved children < or = 3 years of age. CONCLUSIONS: Pediatric bronchoscopy is a safe and valuable procedure. However, in this study, anesthetic selection was shown to adversely affect the complication rate in the subsets of children < or = 3 years of age and with an underlying diagnosis of HIV infection.
Assuntos
Analgésicos , Anestésicos Dissociativos , Broncoscopia , Fentanila , Hipnóticos e Sedativos , Ketamina , Midazolam , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Estudos RetrospectivosRESUMO
Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was a strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock.
Assuntos
Hidratação , Coração/fisiopatologia , Hemodinâmica , Infecções/terapia , Choque Séptico/terapia , Cuidados Críticos , Eritrócitos , Coração/diagnóstico por imagem , Humanos , Infecções/fisiopatologia , Contração Miocárdica , Cintilografia , Choque Séptico/fisiopatologia , Cloreto de Sódio/uso terapêutico , Volume Sistólico , TecnécioRESUMO
Septic shock in humans is usually characterized by a high cardiac output, a low systemic vascular resistance, reversible depression of left ventricular ejection fraction, and transient left ventricular dilatation. The relationship of left ventricular to right ventricular function in septic shock is poorly understood. To evaluate right ventricular vs left ventricular performance and to evaluate the relation of biventricular performance to survival, we performed serial hemodynamic and radionuclide angiographic studies in 39 patients with septic shock. Right ventricular ejection fraction was calculated using the two regions of interest method. There were 22 survivors and 17 nonsurvivors. Comparing initial with final (after recovery for survivors; within 24 hours of death for nonsurvivors) studies, each survivor's cardiovascular performance returned toward normal, with significant increases in mean arterial pressure, left and right ventricular ejection fraction, and right ventricular stroke work index. Their profiles also demonstrated significant decreases in central venous pressure, pulmonary artery wedge pressure, pulmonary artery mean pressure, and left and right ventricular end-diastolic volume indices. From initial to final study in the nonsurvivors, there was a statistically significant increase in heart rate but no change in any other cardiovascular parameter, indicating a persistence of the initial cardiovascular dysfunction until death. Comparing serial studies, the pattern of change in right vs left ventricular function was very similar (same direction in 82 percent of patients). Thus, myocardial depression in human septic shock affects both ventricles simultaneously with a similar pattern of dysfunction.
Assuntos
Coração/fisiopatologia , Choque Séptico/fisiopatologia , Adolescente , Adulto , Idoso , Pressão Sanguínea , Volume Cardíaco , Criança , Diástole , Feminino , Coração/diagnóstico por imagem , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Ventriculografia com Radionuclídeos , Choque Séptico/diagnóstico por imagem , Volume Sistólico , Resistência VascularRESUMO
Interleukin-2, a lymphocyte product, has well demonstrated antitumor activity in humans. Early clinical studies showed hemodynamic alterations in patients receiving the drug as antitumor immunotherapy. We serially assessed interleukin-2-associated hemodynamic parameters and left ventricular ejection fractions in five patients with neoplastic diseases unresponsive to conventional therapies. By day 4 of therapy, compared with baseline (preinterleukin-2), all patients developed tachycardia (p less than 0.01), decreased mean arterial blood pressure (p less than 0.05), increased cardiac index (p less than 0.05), and decreased systemic vascular resistance (p less than 0.01). In addition, left ventricular ejection fraction fell from 58.0 +/- 4.7 to 36.4 +/- 4.0 percent (0.05 less than p less than 0.10), which was associated with a trend toward left ventricular dilatation manifested by an increase in left ventricular end-diastolic volume index. Transient renal dysfunction was noted in all five patients, and one developed transient respiratory failure; both types of organ dysfunction recovered to baseline values after cessation of immunotherapy. Thus, interleukin-2 induces multiple reversible cardiovascular abnormalities that are similar to the hemodynamic manifestations of human septic shock.
Assuntos
Coração/fisiopatologia , Hemodinâmica , Interleucina-2/efeitos adversos , Adulto , Pressão Sanguínea , Débito Cardíaco , Volume Cardíaco , Feminino , Frequência Cardíaca , Humanos , Interleucina-2/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Choque Séptico/fisiopatologia , Volume Sistólico , Resistência VascularRESUMO
We assessed qualitative and quantitative differences in surfactant lipid composition of bronchoalveolar lavage (BAL) fluid in patients with acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii (PC) pneumonia. Five normal volunteers and 27 patients with human immunodeficiency virus (HIV) infection underwent BAL for evaluation of possible pulmonary infection. Bronchoalveolar lavage studies in eight patients were negative for PC organisms, and 19 were positive. Pneumocystis carinii pneumonia was graded (mild vs moderate to severe) by initial alveolar-arterial oxygen gradient. Bronchoalveolar lavage fluid was centrifuged, the lipids were extracted from the supernatant, and total lipid profiles of dephosphorylated glycerolipids were analyzed as trimethylsilylether derivatives by high temperature gas-liquid chromatography. Phospholipase A2 levels were determined using a radiolabeled E coli membrane method. Compared to the normal volunteers (109 +/- 13 micrograms/5 ml) and the PC negative group (107 +/- 13 micrograms/5 ml), total BAL lipid was reduced for both the mild PC pneumonia group (73 +/- 10 micrograms/5 ml) and the moderate to severe PC pneumonia group (46 +/- 4 micrograms/5 ml). There was a parallel reduction of diacylglycerol lipids: normal volunteers, 52 +/- 7 micrograms/5 ml; PC negative, 52 +/- 9 micrograms/5 ml; mild PC pneumonia, 35 +/- 7 micrograms/5 ml; and moderate to severe PC pneumonia, 15 +/- 2 micrograms/5 ml. Phospholipase A2 activity in moderate to severe PC pneumonia was twice that of the PC negative patients, and 30 times that for normals. The data demonstrate a marked diminution in surfactant glycerophospholipid in patients with AIDS and PC pneumonia and suggest a potential role for surfactant abnormality in the pathophysiology of this disease.
Assuntos
Infecções por HIV/metabolismo , Lipídeos/análise , Fosfolipases A/análise , Pneumonia por Pneumocystis/metabolismo , Surfactantes Pulmonares/química , Adulto , Líquido da Lavagem Broncoalveolar/química , Broncoscopia , Diglicerídeos/análise , Ácidos Graxos não Esterificados/análise , Glicerídeos/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/análise , Fosfolipases A2 , Fosfolipídeos/análiseRESUMO
STUDY OBJECTIVE: To investigate the pathogenesis of lung injury in Pneumocystic carinii pneumonia and nonspecific interstitial pneumonitis (NIP), common pulmonary complications of human immunodeficiency virus (HIV) infection. The efficacy of corticosteroid therapy in P carinii pneumonia and the observation that bronchoalveolar lavage (BAL) neutrophilia predicts a poor prognosis support the premise that the lung injury of P carinii pneumonia is due to the host's inflammatory response to the infection. DESIGN: In vitro measurements on previously collected BAL fluid samples. SETTING: The Clinical Center of the National Institutes of Health, a research hospital and tertiary care referral center. PATIENTS: Five normal volunteers, 5 asymptomatic HIV-positive patients, 10 HIV-positive patients with NIP (5 asymptomatic and 5 with respiratory symptoms), and 19 HIV-positive patients with P carinii pneumonia. MEASUREMENTS AND RESULTS: BAL leukotriene B4 (LTB4), interleukin 8 (IL-8), and phospholipase A2 (PLA2) were measured. IL-8 and PLA2 were elevated in patients with P carinii pneumonia, and IL-8 correlated with BAL fluid absolute neutrophil count. LTB4, IL-8, and PLA2 levels were elevated in patients with NIP; LTB4 and PLA2 levels correlated with absolute neutrophil count, and IL-8 correlated with alveolar-arterial oxygen pressure difference. IL-8 was elevated in the asymptomatic HIV-positive patients, and there was a trend toward elevation of PLA2 in this group. CONCLUSION: IL-8 appears to play a role in the pathogenesis of lung injury in P carinii pneumonia and may be the principal neutrophil chemotaxin in this disease; PLA2 may also be involved in the pathogenesis of P carinii pneumonia. Both LTB4 and IL-8 may be involved in the recruitment of neutrophils and subsequent lung injury of NIP. These data suggest that there are varying mechanisms by which inflammatory cells are recruited to the lung in different HIV-related lung diseases.
Assuntos
Infecções por HIV/complicações , Interleucina-8/análise , Leucotrieno B4/análise , Pneumopatias/metabolismo , Infecções Oportunistas Relacionadas com a AIDS/metabolismo , Adulto , Líquido da Lavagem Broncoalveolar/química , Cromatografia Líquida de Alta Pressão , Feminino , Soropositividade para HIV/metabolismo , Humanos , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Fosfolipases A/análise , Fosfolipases A2 , Pneumonia por Pneumocystis/metabolismo , Fibrose Pulmonar/complicações , Fibrose Pulmonar/metabolismoRESUMO
Aerosolized pentamidine has been recommended as an alternative mode of antipneumocystis prophylaxis in human immunodeficiency virus-infected children with trimethoprim-sulfamethoxazole intolerance. However, there have been no definitive data concerning the most appropriate dose and the tolerance of aerosolized pentamidine in children. In the present study, we assessed the tolerance of aerosolized pentamidine in older children using a regimen similar to the one recommended in adults. A 300-mg dose of pentamidine was administered to our human immunodeficiency virus-infected patients monthly using the Respirgard II nebulizer. Patients were assessed for their heart rate, respiratory rate, breath sounds and oxygen saturations during and after pentamidine aerosolization. During a 21-month period (August, 1989, to May, 1991), 22 patients (mean age, 9.8 +/- 0.6 years; range, 3 to 15 years) received a total of 185 treatments. Patients complained of either a bitter taste (16 of 22) or developed short periods of coughing (15 of 22) during the aerosol. Five patients developed reversible bronchospasm requiring bronchodilators; no patients developed oxygen desaturation. None of the patients developed Pneumocystis carinii pneumonia during the limited protocol follow-up (mean, 9.8 months). Thus aerosolized pentamidine for antipneumocystis prophylaxis is well-tolerated in older children. However, more comprehensive investigations of efficacy are indicated.
Assuntos
Infecções por HIV/complicações , Infecções Oportunistas/prevenção & controle , Pentamidina/administração & dosagem , Pneumonia por Pneumocystis/prevenção & controle , Administração por Inalação , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Infecções Oportunistas/complicações , Pentamidina/uso terapêutico , Pneumonia por Pneumocystis/complicaçõesRESUMO
The potential complications of percutaneous venous catheterizations are many and include pneumothorax, subclavian and carotid artery puncture, hematoma, air embolism, catheter malposition, catheter fragment embolization, venous thrombosis and infection. This case report describes a patient who developed angiographically documented pulmonary emboli associated with the changing of a central venous catheter over a guidewire using Seldinger technique. This episode adds the possibility of acute pulmonary emboli to the list of potential complications from central venous catheterizations.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Embolia Pulmonar/etiologia , Doença Aguda , Adulto , Cateterismo Venoso Central/instrumentação , Cateterismo Venoso Central/métodos , Humanos , MasculinoRESUMO
Pulmonary infiltrates in the patient with acquired immunodeficiency syndrome (AIDS) may be associated with a spectrum of unusual neoplastic and infectious process. Transbronchial biopsy frequently reveals the cause of these infiltrates; however, when transbronchial biopsy is nondiagnostic or contraindicated, or if the patient fails to improve after a diagnostic transbronchial biopsy, further investigation is warranted to direct appropriate therapy. Efficacy of 23 open-lung biopsies in 19 AIDS patients with pulmonary infiltrates was evaluated to define the indications for and the diagnostic yield of open-lung biopsy. Pulmonary infiltrates were recognized for a mean duration (+/- standard error) of 16 +/- 2 days before open-lung biopsy and were associated with fever and cough. These patients did not have prior transbronchial biopsy, and open-lung biopsy was diagnostic in all of these. Prior transbronchial biopsy performed in the remaining 16 patients was nondiagnostic in 10. Open-lung biopsy was diagnostic in 70% of these patients (Pneumocystis carinii pneumonia, 2 patients; Kaposi's sarcoma, 3 patients; Kaposi's sarcoma and Legionella pneumophila, 1 patient; cytomegalovirus, 1 patient). The other 6 patients having a previous diagnostic transbronchial biopsy failed to improve with therapy, and open-lung biopsy resulted in a therapeutic change in 67% of these patients. Two deaths were attributable to open-lung biopsy in patients with postoperative thrombocytopenic hemorrhage. Open-lung biopsy should be performed in AIDS patients when transbronchial biopsy is nondiagnostic or contraindicated, or in patients who fail to improve with appropriate therapy after diagnostic transbronchial biopsy, especially in patients with Kaposi's sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS)