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J L Colombo

Publications and source records attributed to J L Colombo.

At least 19 recordsLinked to original sources

Airway reactivity following repeated milk aspiration in rabbits.

Asthma and gastroesophageal reflux (GER) are commonly associated disorders. Microaspiration is one possible link between these processes. The purpose of this study was to assess methacholine reactivity following repeated small-volume aspiration such as may occur with GER. This was also correlated with airway cytology. Five weekly intratracheal instillations of either milk (N = 8) or saline sham controls (N = 7) in volumes of 0.25 mL/kg were performed in anesthetized rabbits. Transpulmonary pressure, flow, tidal volume, central airways resistance, and dynamic lung compliance were measured in anesthetized and paralyzed animals at baseline, after 2 and 5 weeks of instillation, and 3 weeks after the last instillation. Doubling concentrations of methacholine were given until a 50% or greater increase in resistance occurred (PC50R). Bronchial washings for cytological evaluation were performed after the physiologic measurements and before each instillation. There were no significant differences in airway reactivity between baseline and all subsequent observation points within each of the two groups. However, methacholine responsiveness was significantly higher in the milk group before the final instillation (PC50R = 5.84 vs. 12.97 mg/mL, P = 0.03) and at recovery (PC50R = 6.40 vs. 10.56 mg/mL, P = 0.047) when compared to saline controls. This was associated with a higher neutrophil percentage (P = 0.01) at 5 weeks, and eosinophil percentage (P = 0.05) at recovery in the bronchial wash specimens from the milk group. These results show that repeated small-volume aspiration of milk in rabbits causes persistent inflammation and is associated with greater airway reactivity when compared to sham controls. This inflammation was accompanied by either increased neutrophils or eosinophils in bronchial lavage specimens. These findings lend support to a possible role of microaspiration in association with increased airway reactivity in patients with GER.

Animals↗

Effects of standard and high doses of salmeterol on lung function of hospitalized patients with cystic fibrosis.

In a recent investigation we found that hospitalized patients with cystic fibrosis who received 0.5 cc of 0.5% albuterol nebulizer solution TID significantly increased their pulmonary function across the day, but fell back to baseline overnight. To determine whether this fall could be prevented by the long-acting beta-2 agonist salmeterol at both standard (2 puffs: 42 mcg BID) and high (4 puffs, 84 mcg BID) doses, we evaluated the effects of salmeterol vs. albuterol (2 puffs, 180 mcg QID, and 4 puffs, 360 mcg BID) in a placebo-controlled three-way random crossover, double-blind trial. Eighteen patients in the low-dose group and 10 of the same 18 patients in the high-dose group completed the 3 consecutive days of testing and received either salmeterol, albuterol, or placebo with each of four chest physiotherapy sessions given at 7 AM, 11 AM, 3 PM, and 7 PM. At standard doses (2 puffs), the mean percent changes in FEV1 pre- to post-7 AM therapy for salmeterol (5.5%) and albuterol (9.9%) were significantly greater than with placebo (-1.2%) (P < 0.05 and 0.01, respectively). The mean percent changes in FEV1 from morning baseline with salmeterol were also significantly greater than placebo before 3 PM (12.1% vs. 5.4%, P < 0.01), and neither albuterol nor salmeterol were significantly greater than placebo after 3 PM. At standard doses there was a significant carryover effect with salmeterol to the next morning for the FEV1 (7.3%) when compared to placebo (1.5%) and albuterol (-0.7%) (P < 0.05 and 0.05, respectively). At high doses (4 puffs), the mean percent change in FEV1 with pre- to post-7 AM therapy increased to 22.7% and remained significantly greater than with placebo until pretherapy at 7 PM. The carryover effect the next morning was 14.7%. Salmeterol at 4 puffs compared favorably to albuterol nebulizer therapy given TID in both the incidence of responders for the FEV1 (70% vs. 71%) and the mean changes after therapy at 7 AM (22.7% vs. 14.9%), and provided greater carryover effects to the next morning (14.7% vs. -0.7%), thus preventing the fall in pulmonary function back to baseline overnight. We recommend the use of high-dose salmeterol in hospitalized patients with FVC values of 40% of predicted or greater, starting with 2 and increasing to 4 puffs BID as tolerated.

Administration, Inhalation↗

Pleural effusions.

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Anti-Bacterial Agents↗

Anabolic effect of biosynthetic growth hormone in cystic fibrosis patients.

The purpose of this study was to determine whether GH treatment of cystic fibrosis (CF) patients can result in an anabolic effect, i.e., increased weight gain, improved growth rate, nitrogen retention, and improved pulmonary function. Nine prepubertal endocrinologically normal CF patients (3 girls, 6 boys; chronological age (CA) 5.5-9.8 years, and bone age (BA) 4.5-9.0 years), received recombinant human growth hormone (rhGH) 0.3 mg/kg/week subcutaneously for a period of 12 months (N = 8) or 9 months (N = 1). Normal glucose tolerance was determined before treatment. Pulmonary function studies and anthropometric measurements were done every 3 months. Thyroid status, somatomedin C (SmC), BA, and routine chemistries were evaluated every 6 months. The pretreatment growth velocity averaged 5.7 +/- 0.3 (SE) cm/year and significantly increased to 7.8 +/- 0.4 (SE) cm/year during therapy, (P < 0.01). Standard deviation scores (SDS) for height significantly increased during rhGH therapy as compared with pretreatment, (P < 0.05). Weight of the patients during rhGH therapy did not significantly change during or after rhGH therapy. After therapy, all patients showed a significant increase in arm muscle area (AMA) and a significant decrement in arm fat area (AFA) (P < 0.01). Net nitrogen anabolism was negative in all subjects before therapy but became more positive in five patients during rhGH therapy. Three patients achieved positive nitrogen retention. SmC values significantly increased from a mean value of 0.62 +/- 0.1 (SE) U/ml to 1.6 +/- 0.6 (SE) U/ml after therapy. BA advanced 1.0 +/- 0.1 SE per year after treatment. Of the seven patients able to perform adequate pulmonary function testing, improvement occurred in FVC, FEV1.0, and PEFR in 5, 5, and 4 patients, respectively, but these changes did not reach statistical significance. We conclude that biosynthetic rhGH therapy had a significant anabolic effect in CF patients as shown by increased growth velocity, SmC values, increased protein and decreased fet stores, and a positive or less negative net nitrogen retention in five of the patients.

Body Height↗

The effects of albuterol on the lung function of hospitalized patients with cystic fibrosis.

Twenty-four hospitalized patients with cystic fibrosis were enrolled into a 2-d, double-blind, placebo-controlled, randomized crossover trial comparing albuterol inhalation aerosol with a saline placebo. Aerosols were administered with the first three of four chest physiotherapy sessions given 4 h apart. Spirometry was measured before and 45 min after 7:00 A.M. and 3:00 P.M. therapy and before therapy at 7:00 P.M. and 7:00 A.M. the next morning. The mean percent change in FVC, FEV1, and FEF25-75% at 7:00 A.M. was 10.7, 14.8, and 19.6% with albuterol versus 2.4, 1.0, and -0.8% with placebo (p = 0.0012, < 0.0001, and = 0.003, respectively). A greater than 8% change in FEV1 separated changes with albuterol versus placebo with 96% specificity and occurred in 75% of all patients with albuterol; 71% at 7:00 A.M. versus 24% at 3:00 P.M. The reduction in response at 3:00 P.M. (p < 0.01) was presumably due to prolonged effects of morning therapy ( > 4 h). Individual changes in spirometry were significantly more positive and homogeneous with albuterol versus placebo at both 7:00 A.M. and 3:00 P.M. The mean percent change for the FVC, FEV1, and FEF25-75 across the day (7:00 A.M. pretherapy to 7:00 P.M. pretherapy) was 8.1, 10.1, and 9.7% with albuterol versus 3.9, 3.5 and 2.6% with placebo (p = 0.029, 0.036, and 0.232, respectively). The more positive and homogeneous changes in spirometry with albuterol, along with greater changes in these measures across the day when compared with placebo, suggest that albuterol improves pulmonary function in a majority of hospitalized patients with cystic fibrosis.

Adolescent↗

Clinical denouement and mutation analysis of patients with cystic fibrosis undergoing liver transplantation for biliary cirrhosis.

OBJECTIVE: To describe the clinical characteristics of patients with cystic fibrosis considered for liver transplantation and the clinical outcome after transplantation. METHODS: Patient charts were reviewed. Mutation analysis was performed on blood or liver tissue samples with a panel of 17 mutations. RESULTS: Eight patients (five girls) with cystic fibrosis have undergone orthotopic liver transplantation for biliary cirrhosis. Mean age at transplantation was 12.0 years +/- 7.7 years (range, 9 months to 23 years). Preoperatively, seven patients had mild to moderate pulmonary dysfunction and one moderate to severe pulmonary dysfunction. All patients required pancreatic enzyme replacement, and four patients required insulin for diabetes mellitus. The 1-year survival rate was 75%, with no deaths related to septic events. Mean time of follow-up the six operative survivors was 4.1 years +/- 1.9 years. Pulmonary function testing, in those serially tested, showed that forced expiratory volume in 1 second was maintained or improved and that forced vital capacity improved after transplantation. Mutation analysis showed the following genotypes: four patients, delta F508/delta F508; one patient, delta F508/N1303K; and three patients, delta F508/unknown. CONCLUSIONS: Despite the high risk of transplantation, these encouraging results indicate that liver transplantation should be considered for patients with cystic fibrosis and complications of end-stage liver disease. We could not demonstrate an unusual pattern of CF gene mutations in these patients with severe liver disease. It appeared that immunosuppressive agents did not have a deleterious effect on pulmonary function.

Adolescent↗

Mutation analysis and haplotype correlation for 139 cystic fibrosis patients from the Nebraska Regional Cystic Fibrosis Center.

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations with an approximate frequency of one in 2,500 live births and a carrier frequency of one in 25. We studied 400 individuals seen at The Nebraska Regional Cystic Fibrosis Center that included 139 CF patients, 206 parents, and 55 unaffected siblings to determine the frequency of the delta F508, R117H, G542X, S549R/N, G551D, R553X, R560T, and W1282X mutations. In addition, we determined haplotypes on each of these individual's chromosomes using four markers that included XV-2c, KM-19, pMP6d.9, and G2. Results from this study showed that the delta F508 mutation was present in 70% of CF chromosomes. Of the 139 CF patients 74 (53%) were homozygous for the delta F508 deletion, 47 (34%) were heterozygous for the delta F508 deletion and an unknown mutation, and 18 (13%) carried two unknown mutations. Four additional mutations were also found in our population and included G542X (6%), G551D (5%), R553X (4%), and R560T (1%). One patient was documented to be a compound heterozygote for G542X/G551D. A polymorphism, F508C, that has previously been reported in several families was also present in our study. The most common haplotype associated with the delta F508 deletion in our CF patients was the E haplotype (CF Consortium B) while other mutations were associated with a variety of haplotypes.

Base Sequence↗

Unusual form of endobronchial Aspergillosis in a patient with cystic fibrosis.

The isolation of Aspergillus fumigatus from airway secretions from patients with cystic fibrosis (CF) is common and usually denotes asymptomatic colonization or allergic broncho-pulmonary aspergillosis (ABPA). A 12-year-old boy with CF acutely developed moderately severe symptoms of unremitting cough, fever, dyspnea, weight loss, and cyanosis. Chest radiographs demonstrated widespread unilateral infiltrates and volume loss. By bronchoscopy tenacious mucous plugs were seen occluding the left lower lobe bronchus. Cultures from sputum and sequential bronchoalveolar lavage grew Aspergillus fumigatus, but other significant criteria for diagnosing ABPA were lacking. No improvement was seen with a 3 week course of systemic corticosteroid and antibiotic therapy. Treatment with amphotericin B and short-term mechanical ventilation resulted in rapid resolution of all symptoms. This form of endobronchial aspergillosis has not been described previously.

Amphotericin B↗

Comparison of serum amyloid A and C-reactive protein as indicators of lung inflammation in corticosteroid treated and non-corticosteroid treated cystic fibrosis patients.

Serum amyloid A (SAA) and C-reactive protein (CRP) levels were compared in 830 serum samples from 155 cystic fibrosis (CF) patients. Correlation coefficients were calculated for all samples (r = 0.73), for samples from non-corticosteroid treated (CFNS) patients (n = 698, r = 0.80), and for samples from corticosteroid treated (CFS) patients (n = 132, r = 0.35). SAA was the more sensitive indicator of pulmonary inflammation when SAA and CRP were compared to pulmonary function tests of 49 hospitalized patients at admission and discharge. CRP levels were significantly (p less than .05) lower at admission in CFS patients than in CFNS patients, whereas SAA levels were not significantly different between the two groups. All nine CFS patients hospitalized had elevated SAA levels (average 22 times above normal limits) at admission, while only six had elevated CRP levels (average 3.7 times above normal limits) at admission. In the 40 CFNS patients both SAA and CRP levels were significantly elevated at admission. In each case SAA and CRP levels declined as pulmonary functions improved with effective antimicrobial therapy. In three instances SAA levels increased during hospitalization while CRP levels did not. In each case, rising SAA levels indicated clinical deterioration associated with evolving resistance of P. aeruginosa which required a change in antibiotic therapy.

Adolescent↗

Time course of lipid-laden pulmonary macrophages with acute and recurrent milk aspiration in rabbits.

High levels of lipid-laden macrophages (LLM) in bronchial washings have been associated with food aspiration. We studied the time course of appearance and clearance of LLM in rabbits undergoing either a single milk instillation, five weekly milk instillations or saline (control) instillations into the airways. Cells were obtained by bronchoalveolar lavage of intubated rabbits at uniform time intervals following the single or the last of five milk/saline instillations. LLM semi-quantitative indexes were derived using oil-red-O staining. Significantly elevated indexes were found in both milk groups 6 hr after milk instillation. In the single saline and milk instillation groups the indexes were not different beginning on the 4th day, and indexes from 8 of 9 rabbits had returned to baseline by the 6th day. However, indexes remained significantly elevated up to 17 days in the group receiving weekly milk instillations. Indexes from all rabbits in the repeat milk instillation group remained elevated for 12 days or longer. This group also developed increased numbers of binucleated macrophages. Quantitation of LLM in this model appears to be a sensitive indicator of recurrent lipid aspiration, these cells remaining in the airways for several days after the last aspiration event.

Animals↗

The spectrum of Pneumocystis carinii infection after liver transplantation in children.

We report the experience with Pneumocystis carinii lung infections in the 109 children undergoing liver transplantation at our hospital between August, 1985 and May, 1989. PCP developed in 9 of the 86 patients (10%) surviving > or = 6 weeks after transplantation and not receiving P carinii chemoprophylaxis. Of the 59 patients undergoing BAL 2 or more weeks after transplantation there were 16 specimens from 14 patients (24%) positive for P carinii. These patients had a spectrum of illness ranging from asymptomatic to severe pneumonia requiring mechanical ventilation. The mean interval from first transplantation to bronchoalveolar lavage positive for P carinii was 24.9 weeks and the mean interval to first PCP was 28.0 weeks. The earliest and latest occurrences of PCP were 7 weeks and 73 weeks, respectively, after transplantation. There were no complications attributed to BAL.

Adolescent↗

Treatment of life-threatening primary pulmonary hemosiderosis with cyclophosphamide.

This report describes a five-year-old boy with severe pulmonary hemorrhage caused by primary pulmonary hemosiderosis with cow's milk sensitivity. After failing to respond to corticosteroids and azathioprine, he dramatically improved after being given cyclophosphamide. He worsened after discontinuation of cyclophosphamide on two occasions and improved significantly with its reinstitution. Cyclophosphamide was continued for 14 months without further bleeding or adverse effects. The patient has remained in remission for nearly five years. Cyclophosphamide may be a life-saving alternative therapy for refractory pulmonary hemorrhage with pulmonary hemosiderosis.

Child, Preschool↗

Refractory congestive heart failure after ribavirin in infants with heart disease and respiratory syncytial virus.

Although treatment with ribavirin has been known to be associated with a decreased mortality in infants with congenital heart disease (CHD) who have respiratory syncytial virus (RSV), few data are available regarding morbidity. We reviewed records of 10 consecutively hospitalized infants with CHD during a recent RSV epidemic. Despite the presence of left-to-right shunt in each patient, symptoms of RSV were respiratory at presentation. After ribavirin, decreased respiratory symptoms were found in 8 infants but in 2 assisted ventilation were required 1 and 3 days after admission. Congestive heart failure worsened in 8 patients, 6 of whom had improved respiratory status after ribavirin. Of the 8 patients with worse CHF (pulmonary edema), 3 responded to medical management but 5 were refractory and 4 required surgical repair of CHD. One patient died of pulmonary hemorrhage. Medically refractory CHF may develop in infants with CHD who become infected with RSV and are treated with ribavirin. Further studies are needed to determine whether the pulmonary edema is caused by RSV, ribavirin, or combination of effects on pulmonary capillary function or some other unrecognized mechanism.

Heart Defects, Congenital↗

Chlorine inhalation toxicity from vapors generated by swimming pool chlorinator tablets.

We have presented two cases of serious respiratory injury after brief exposure to vapors from solid chlorine compounds. We could find no previous reports of such accidents and, therefore, have related these cases to alert the medical community. We would recommend that physicians caring for children include warnings about these preparations in their routine counseling of parents.

Child↗

Cystic fibrosis complicated by acute leukemia.

During a 3-month period, two men ages 20 and 25 years, respectively, with cystic fibrosis developed acute lymphocytic and nonlymphocytic leukemias, respectively. These two patients were among 120 patients who attended our cystic fibrosis clinic during the last 3 years. Thirty-five of the 120 patients have survived beyond the second decade. The authors ask whether acute leukemia will be recognized with increasing frequency in cystic fibrosis patients who achieve prolonged survival.

Adult↗

Circulating immune complexes in cystic fibrosis and their correlation to clinical parameters.

Circulating immune complexes (CIC) have been found to be elevated in individuals with cystic fibrosis (CF). Previous investigators, using a variety of assays, have reported high levels of CIC in as many as 86% of these patients. Our study followed the progress of 25 patients with CF over a period of 10 months to determine which, if any, clinical parameters correlated with the occurrence and/or concentration of CIC. Immune complex determinations were performed using a coprecipitation method with equine rheumatoid-complement complex. One hundred percent of the CF patients had CIC elevated above normal levels, however, levels of CIC did not correlate with the severity of an individual's acute exacerbation. Clinical parameters including pulmonary function tests, vital signs, total serum IgG levels, and other laboratory studies, were obtained on each individual and analyzed with respect to their relationship to CIC. Only four of 38 parameters examined had p less than 0.05. Factors that showed significant correlation to elevated CIC's in the highly elevated portion of our CIC population were poor NIH score, increased patient age, low peak expiratory flow rate, and elevated total serum IgG. These clinical values are associated more with the measurement of chronic disease. These data suggest that CICs cannot be used as an indication of short-term prognosis or as a monitor to follow the course of acute severe lung infections in the CF patient. Of interest was the observation that all patients who died during the course of the investigation had CIC levels greater than 80 micrograms/ml.

Adolescent↗