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Biomedical subjects

Carlos E Milla

Publications and source records attributed to Carlos E Milla.

11 recordsLinked to original sources
PubMed2006

Inflammatory cytokines and the development of pulmonary complications after allogeneic hematopoietic cell transplantation in patients with inherited metabolic storage disorders.

Patients with inherited metabolic storage disorders are at a higher risk of developing pulmonary complications after hematopoietic cell transplantation (HCT). This single-center prospective study of 48 consecutive inherited metabolic storage disorder patients was performed to identify risk factors for the development of pulmonary complications after HCT. Before HCT, subjects underwent bronchoalveolar lavage (BAL) for cell count, culture, nitrite levels, and analysis of proinflammatory cytokines and chemokines. The overall incidence of pulmonary complications was 52% (infectious, 23%; noninfectious, 29%) over a period of 4 years. Diffuse alveolar hemorrhage was the most frequent noninfectious complication and occurred in 19% of patients, all of whom had a diagnosis of mucopolysaccharidosis (Hurler and Maroteaux-Lamy syndromes). Levels of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha, macrophage inflammatory protein 1alpha, and granulocyte colony-stimulating factor in BAL fluid samples obtained before HCT were higher in patients with mucopolysaccharidoses than in patients with leukodystrophies. In addition, levels of IL-1beta, IL-6, IL-8, and granulocyte colony-stimulating factor were increased in the BAL fluid of patients who developed noninfectious pulmonary complications compared with those who did not develop pulmonary complications. It is interesting to note that most noninfectious pulmonary complications occurred in patients with mucopolysaccharidoses, especially diffuse alveolar hemorrhage, which occurred exclusively in patients with mucopolysaccharidoses. Higher levels of bronchial proinflammatory cytokines and chemokines may be predictive of the development of subsequent posttransplantation noninfectious complications in patients with mucopolysaccharidoses, especially those with Hurler syndrome. Larger studies will be required to further elucidate etiologic mechanisms and predictive factors.

Adolescent↗
PubMed2005

Natural history of pulmonary complications in children after bone marrow transplantation.

We sought, in children after bone marrow transplantation (BMT), (1) to determine the natural history and incidence of pulmonary complications, (2) to evaluate the diagnostic yield of fiberoptic bronchoscopy and bronchoalveolar lavage (BAL); and (3) to determine the effect of bronchoscopy with lavage on patient outcome. The study design was a retrospective review in a tertiary care university hospital of all children undergoing BMT over a 5-year period. Patients were separated into 2 study groups: children with and without pulmonary complications. Pulmonary complications were defined as new or persistent pulmonary infiltrates on chest radiograph or chest computed tomography scan, respiratory symptoms, hypoxemia, or hemoptysis. Three hundred sixty-three pediatric patients underwent BMT between January 1, 1995, and December 31, 1999. Ninety patients (25%) developed pulmonary complications and were evaluated with bronchoscopy and BAL. Patients with pulmonary complications had a higher mortality (65% versus 44%; P < .01). The median posttransplantation survival for children with pulmonary complications was 258 days, compared with 1572 days in patients without pulmonary complications. The incidence of pulmonary complications was increased in patients with allogeneic BMT (P < .01). The time-dependent onset of severe (grade III to IV) graft-versus-host disease increased the relative risk of pulmonary complications by 2.0 (95% confidence interval, 1.1-3.7; P = .02). Pulmonary complications increased the time-dependent relative risk of mortality by 3.5 (95% confidence interval, 2.5-4.8). The diagnostic yield of bronchoscopy with lavage was 46% in patients undergoing BAL. Diagnostic bronchoscopy did not enhance either 30- or 100-day survival. Pathogen identification did not decrease mortality (P = .45). Pulmonary complications occur in 25% of children undergoing BMT and increase the risk of death in the first year after BMT. Although pathogen identification does not confer a survival advantage, rigorous, prospective screening may allow for earlier identification of pathogens and thereby provide a benefit to this uniquely vulnerable population.

Adolescent↗
PubMed2005

Diabetes is associated with dramatically decreased survival in female but not male subjects with cystic fibrosis.

OBJECTIVE: Survival analysis was performed on a prospectively followed cohort of patients with cystic fibrosis (CF) to determine the impact of the development of diabetes on survival. RESEARCH DESIGN AND METHODS: Clinical data were retrieved for patients diagnosed with CF-related diabetes (CFRD) at the Minnesota CF Center in 1987-2002. Kaplan-Meier survival analysis was performed to estimate median survival. Data were analyzed by Cox regression to evaluate the influence of clinical characteristics at the time of CFRD diagnosis on mortality. RESULTS: Clinical information was reviewed from 1,081 CF patients. A total of 123 patients with CFRD with fasting hyperglycemia were identified (58 males). Median survival was 49.5 years for male subjects without diabetes, 47.4 years for male subjects with diabetes, 47.0 years for female subjects without diabetes, and 30.7 years for female subjects with diabetes. Only female sex and forced expiratory volume in 1 s at the time of CFRD diagnosis were significant predictors of the subsequent risk of death (P < 0.001). This strong association was not confounded by CFTR genotype, BMI, steroid use, respiratory pathogens, HbA1c, or pregnancy. CONCLUSIONS: Female subjects with CFRD have a remarkably poorer prognosis compared with all male subjects with CF and female subjects with CF but without diabetes. The etiology of this sex difference is not clear. We speculate it might involve the interaction of female hormones and diabetes on promotion of a proinflammatory state or that androgens might protect male subjects from the catabolic effects of insulin deficiency. Alternatively, the appearance of frank diabetes in female subjects with CF may simply be a marker for some other biological difference that is not immediately apparent.

Adolescent↗
PubMed2004

Peroxidase activity within circulating neutrophils correlates with pulmonary phenotype in cystic fibrosis.

Excess neutrophils are present in the airways of patients with cystic fibrosis (CF). Myeloperoxidase (MPO) activity of acid extracts of sputum is directly correlated with airflow obstruction in CF patients. We hypothesized that the sputum MPO was derived from the MPO of neutrophils that entered the airways from the circulation. Active MPO without protease activity injures airways. If MPO activity from circulating neutrophils that emigrate into the airways of these patients causes increased airway epithelial permeability and mucus-gland secretion, then (1) those patients with greater MPO activity per circulating neutrophil would be more likely to produce sputum and (2) the MPO activity per circulating neutrophil would positively correlate with airflow obstruction. We determined the MPO activity for both circulating and sputum neutrophils. Spirometry and respiratory cultures were obtained simultaneously with blood and sputum samples. CF patients with more MPO activity within their circulating neutrophils were more likely to produce sputum ( P =.001, chi 2 test), and the MPO activity per circulating neutrophil was positively correlated with airflow obstruction as measured on the basis of the ratio of 1-second forced expiratory volume to forced vital capacity ( P <. 03, Kruskal-Wallace test). These associations were independent of age, sex, the results of respiratory-tract culture, or protease activity in the circulating neutrophils. MPO activity in circulating neutrophils from CF patients homozygotic for the deletion of phenylalanine at position 508 in the CF transmembrane regulator protein is directly related to the severity of these patients' pulmonary disease. Our results are consistent with the hypothesis that circulating neutrophils deliver active MPO to the airway, producing airway injury and airflow obstruction in homozygotic delF508 CF patients.

Adolescent↗
PubMed2004

Association of nutritional status and pulmonary function in children with cystic fibrosis.

PURPOSE OF REVIEW: Multiple studies have shown that nutritional status is a strong predictor of morbidity and mortality in patients with cystic fibrosis (CF). Since CF is characterized by progressive lung disease, it could be argued that the underlying lung disease is what determines the nutritional failure seen in most patients. This review will summarize the data available from studies that have attempted to better define this relation and also present a review of the possible mechanisms involved taken from both observational and interventional studies. RECENT FINDINGS: Longitudinal studies with sufficiently large follow-up times have demonstrated that young underweight patients have worst pulmonary function outcomes. More importantly, these studies concur in that the yearly change in growth parameters has a significant effect on the rate at which pulmonary function develops. Although the mechanisms behind this important association are yet unclear, there is some suggestion from interventional studies that the accrual of lean body mass is the factor that is involved in the preservation of lung function. SUMMARY: Nutritional status strongly influences pulmonary health among CF patients. Therefore, aggressive nutritional support aiming at achieving normal growth patterns should lead to adequate development of lung function and maintenance of pulmonary health. However, more research is required with long-term longitudinal studies to better identify the most critical nutritional characteristics influencing this process as well as the most effective nutritional interventions.

Body Mass Index↗
PubMed2003

Safety of inhaled nitric oxide after lung transplantation.

BACKGROUND: The present study tests the hypothesis that therapy with inhaled nitric oxide (iNO) at the time of lung transplantation in patients undergoing bilateral angle lung transplantation: (i) is safe; and (ii) does not increase either the duration of mechanical ventilation or the incidence of acute graft dysfunction. METHODS: We conducted a prospective, non-randomized trial of iNO at 20 parts per million. The treatment group was comprised of 14 patients (10 females, 4 males) undergoing lung transplantation to address severe end-stage lung disease and pulmonary hypertension (mean pulmonary artery pressure > 30 mmHg). Clinical and histologic parameters were compared with 22 historical control subjects who were matched with the study population for age, diagnosis and disease severity (17 females, 5 males) and had undergone lung transplantation in the preceding 2-year time period. No significant differences were noted between the 2 study groups at baseline. RESULTS: No toxic effect of iNO treatment was evident. Although the incidence of acute graft dysfunction was the same in both groups, the occurrence of acute graft rejection in the initial 4 weeks after transplant was less frequent in the iNO group than in the control group (7% vs 32%, p = 0.05). Fifty percent of the treatment group, as compared with 22% of the control group, were discharged from the hospital within 2 weeks of the procedure (p = 0.05). CONCLUSIONS: Early initiation of iNO in lung transplant patients with pulmonary hypertension is safe and may decrease the incidence of acute graft rejection. We speculate that iNO may exert an immunomodulatory effect.

Administration, Inhalation↗
PubMed2003

Longitudinal changes in growth parameters are correlated with changes in pulmonary function in children with cystic fibrosis.

OBJECTIVE: Nutritional status is associated with pulmonary health and survival in children with cystic fibrosis (CF). This study evaluated the weight gain pattern of children with CF in relation to the longitudinal trends of their pulmonary function. Our hypothesis was that children who experience continuous weight gain at a given rate will have better average forced expiratory volume in 1 second (FEV(1)) and change in FEV(1) than children who have weight gain patterns that deviate from this rate, even when total weight gain seems adequate. METHODS: Prospectively collected data were examined in 319 children, aged 6 to 8, who were routinely followed at the Minnesota Cystic Fibrosis Center. One to 67 measurements of weight (kg), height (cm), and FEV(1) (mL) were taken per child during this 2-year period. The data were analyzed by repeated measure regression analysis and by growth pattern analysis. RESULTS: At baseline, a 1-kg higher initial weight was associated with a 55-mL higher average FEV(1). During the follow-up period, a 1-kg gain in weight was associated with an increase in FEV(1) by 32 mL. Children who had a steady weight gain tended to experience greater increases in FEV(1) than children who experienced periodic losses in weight. CONCLUSIONS: We established that children who weigh more and who gain weight at an appropriate and uninterrupted rate have a better FEV(1) trajectory. Aggressive nutritional support to maintain growth in these children may therefore improve FEV(1), which can be taken as a surrogate for better lung health, and may ultimately lead to better survival.

Body Height↗
PubMed2002

Continuous propofol infusion in 142 critically ill children.

OBJECTIVE: In recent years, continuous intravenous propofol infusion has been widely used in pediatric intensive care units. Several case reports have raised concerns about its safety. The objective of this study was to report our experience with continuous intravenous propofol in consecutive patients during an 18-month period. METHODS: The study design was a retrospective review of a case series. Case was defined as a critically ill child who was treated with continuous intravenous propofol. The attending physician staff agreed to prescribe propofol via continuous intravenous infusion at a dose not to exceed 50 microg/kg/min. The protocol allowed for each patient to receive an additional intravenous bolus of propofol at a dose of 1 mg/kg no more than once per hour. The study entailed data collection from consecutive patients who were prescribed a continuous infusion of propofol in either the pediatric intensive care unit or bone marrow transplant unit. RESULTS: Data from 142 patients were analyzed. Each patient enrolled was adequately sedated. Administration of propofol via continuous intravenous infusion was not associated with metabolic acidosis or hemodynamic compromise. No patient in the study group was inadvertently extubated or had a central venous catheter accidentally discontinued. CONCLUSIONS: Propofol can be safely and effectively used to provide sedation to critically ill infants and children. We speculate that continuous infusion of propofol for extended periods of time should not exceed 67 microg/kg/min.

Acidosis↗
PubMedDate not supplied

High-frequency chest compression: effect of the third generation compression waveform.

High-frequency chest compression (HFCC) therapy has become the prevailing form of airway clearance for patients with cystic fibrosis (CF) in the United States. The original square waveform was replaced in 1995 with a sine waveform without published evidence of an equality of effectiveness. The recent development of a triangle waveform for HFCC provided the opportunity to compare the functional and therapeutic effects of different waveforms. Clinical testing was done in patients at home with therapy times recorded with all sputum collected in preweighed sealable vials. The eight study patients with CF were regular users of a sine waveform device. They produced sputum consistently and were clinically stable. They used their optimum frequencies for therapy for each waveform and, for one week for each waveform, collected all sputum during their twice-daily timed HFCC therapies. After collection, these vials were reweighed, desiccated, and reweighed to calculate wet and dry weights of sputum per minute of therapy time. Frequency associated vest pressures transmitted to the mouth, and induced airflows at the mouth were measured in healthy volunteers. The pressure waveforms produced in the vest were, in shape, faithfully demonstrable at the mouth. In the healthy subject the transmission occurred in 2 ms and was attenuated to about 75% of the vest pressure for the triangle waveform and 60% for the sine waveform. All patients produced more sputum with the triangle waveform than with the sine waveform. The mean increase was 20%+ range of 4% to 41%. P value was <.001. Future studies of HFCC should investigate the other effects of the sine and triangle waveforms, as well as the neglected square waveform, on mucus clearance and determine the best frequencies for each waveform, disease, and patient.

Biomedical Engineering↗
PubMedDate not supplied

Different frequencies should be prescribed for different high frequency chest compression machines.

High frequency chest compression (HFCC) is used for treatment and prevention of the lung diseases characterized by impaired mucus clearance and/or cough, where patients are at risk for acquiring acute bronchitis or pneumonia. The HFCC treatment frequencies may be prescribed according to the manufacturers' generic guidelines or may be determined for each individual patient by a "tuning" method that measures, at the mouth, the air volume displacement and the associated airflows produced at each frequency. Tuning is performed while the patient is breathing normally during the HFCC system operation. After measurements for several breaths at one frequency have been collected, the program randomly selects and measures another frequency until the entire frequency range of the machine being tuned has been sampled. Frequencies range from 6 to 21 Hz for the sine waveform machines and from 6 to 25 Hz for the square waveform machines. Each group of flow signals is digitized and analyzed by the program. For each frequency, the HFCC flow velocities and volumes are computed and averaged. These average flows and volumes are rank ordered; the three frequencies with the highest flows and the three frequencies producing the largest volumes are selected for prescription. If the same frequency is selected as one of the three best frequencies for both flow and volume, the next ranked frequency is selected randomly for flow or volume. Significant differences exist between patients and HFCC machines. In a series of 100 cystic fibrosis (CF) patients with varying degrees of lung disease, we found that the best-ranked frequencies varied from patient to patient and did not correlate with patients' age, gender, height, weight, or spirometry parameters. With the sine waveform, the highest HFCC airflows were between 13 and 20 Hz 82% of the time and the largest HFCC volumes were between 6 and 10 Hz 83% of the time. With the square waveform, both the highest average HFCC flow rates and the largest volume average HFCC displacements were between 6 and 14 Hz. Nevertheless, in this sample of 100 consecutive tunings, every frequency from 6 and 20 Hz was a best frequency for at least one patient. These findings provide the basis for recommending a tuning protocol to be used for prescribing frequencies with the various HFCC machines, because they are different from one another. If a patient's tuning cannot be done, it may be useful to prescribe the best frequencies based on the waveform machine he or she uses.

Adolescent↗