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Biomedical subjects

A A Colin

Publications and source records attributed to A A Colin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cystic fibrosis: predictors of accelerated decline and distribution of disease in 230 patients.

OBJECTIVE: The purpose of this study was to determine predictors of accelerated deterioration in radiographic manifestations of cystic fibrosis. The incidence and distribution of focally accentuated disease were also studied. MATERIALS AND METHODS: From 230 patients, 3038 chest radiographs were scored using the Brasfield system. Scores were plotted against age, and a single age-based severity curve was created. Specific observations (at least one episode in the first 5 years of life of air trapping, linear markings, nodular cystic lesions, or large lesions) were assessed to determine predictors of accelerated decline in scores compared with the aggregate scores plotted in the age-based severity curve. Specific observations were noted as present or absent and graded as to severity. A specific observation was counted as present if seen on at least one occasion. (The number of occasions on which the observation was made did not affect statistical analysis.) We also evaluated the distribution of lung disease by assessing the severity and nature of disease through specific lobar distribution. RESULTS: Males showed a slightly greater rate of radiologic decline. Early development of air trapping or bronchiectasis was associated with an accelerated rate of decline over time. Lobe-dominant disease occurred in one third of all images and in two thirds of the patients. It varied with age in its incidence, location, and etiology. CONCLUSION: Hyperinflation or bronchiectasis that occurs before age 5 is associated with accelerated radiographic deterioration. The incidence and location of lobe-dominant disease varied with age in these patients.

Adolescent↗
PubMed1996

Vitamin A status in acute exacerbations of cystic fibrosis.

Vitamin A is an essential nutrient for epithelial cell maintenance and repair, and it is known that infectious stresses may depress plasma vitamin A concentrations. Patients with cystic fibrosis are at risk for vitamin A deficiency because of fat malabsorption as well as for the inflammatory stresses of pulmonary exacerbations of their underlying disease. We therefore hypothesized that acute pulmonary exacerbations of CF would depress plasma retinol concentrations, and that these concentrations would return to baseline values when clinical symptoms improved. We prospectively studied 35 CF patients (mean age: 24.2 y) consecutively admitted with pulmonary exacerbations. Plasma retinol, vitamin E, retinol binding protein (RBP), and C-reactive protein (CRP) concentrations were measured on hospital admission and discharge. Dietary intake was measured by using a semiquantitative food-frequency questionnaire. Regression analysis was used to identify significant clinical and laboratory correlates of retinol concentrations. On admission, mean (+/- SD) concentrations of plasma retinol were 1.14 +/- 0.5 mumol/L compared with 1.70 +/- 0.6 mumol/L on discharge (P = 0.0001). Of 35 subjects, 8 (22.9%) had plasma retinol concentrations considered to be in the deficient range (< 0.70 mumol/L). Concurrently, mean concentrations of plasma RBP increased during hospital admission (from 1.46 to 2.24 mumol/L, P = 0.003), and the mean CRP concentration declined (from 25.7 to 9.8 mg/L, P = 0.002). Significant positive correlations were found between plasma retinol concentrations at admission and age, weight, body mass index, triceps-skinfold-thickness percentile, midupper arm circumference percentile, plasma vitamin E, and RBP concentration, thus suggesting that better-nourished patients had more optimal vitamin A status. At admission, plasma retinol concentrations were negatively correlated with maximum body temperature and CRP concentrations, which indicated that the body's acute-phase response was associated with the depression in retinol concentrations. We conclude that plasma retinol concentrations are depressed in acute pulmonary exacerbations of cystic fibrosis, and that concentrations considered to be in the deficient range are common. Vitamin A metabolism during acute inflammatory stress deserves further study.

Acute Disease↗
PubMed1996

Aerosolized recombinant human DNase in hospitalized cystic fibrosis patients with acute pulmonary exacerbations.

The goal of this study was to evaluate the safety and efficacy of recombinant human DNase (rhDNase) in hospitalized patients with cystic fibrosis (CF) experiencing acute pulmonary exacerbations. Eighty patients with documented CF were enrolled at 11 CF centers when admitted for antibiotic therapy. Patients were at least 5 yr old with a forced vital capacity (FVC) > or = 35% of predicted and an oxygen saturation > or = 90% on a fraction of inspired oxygen (FIO2) < 0.5. Patients were randomized to receive rhDNase 2.5 mg in 2.5 ml excipient twice a day (n = 43) or 2.5 ml excipient alone twice daily (n = 37) along with conventional treatment for exacerbations. Administration of rhDNase was not associated with acute adverse events or deaths, and no patients experienced allergic or anaphylactic reactions. Although forced expiratory volume in one second (FEV1) and FVC improved in both treatment groups during the double-blind period, there were no statistically significant differences in the mean change from baseline in FEV1 or FVC between the two groups. rhDNase therapy is safe and well tolerated in CF patients with acute exacerbations requiring hospitalization, but the study did not demonstrate a statistically significant therapeutic effect of rhDNase when added to a regimen of antibiotics and chest physical therapy.

Acute Disease↗
PubMed1996

Pulmonary function and clinical observations in men with congenital bilateral absence of the vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) was once thought to be a distinct clinical entity, but genetic similarities in men with cystic fibrosis (CF) and CBAVD are described increasingly. We evaluated the clinical status, growth and nutritional state, and respiratory function of 18 men with CBAVD to determine whether these men with different CF transmembrane regulator (CFTR) genotypes may have clinical evidence of mild CF. Following a thorough history and examination, pulmonary function tests, sweat test, and renal ultrasound were performed. Genetic evaluation for 50 known CF mutations, screening for private mutations (single-strand conformational polymorphism and direct sequencing), and assay of the length of the polypyrimidine tract in the splice site acceptor of intron 8 was performed. A history of pulmonary disease was present in three, and an additional man had some features suggestive of malabsorption. Results of general physical examination and anthropomorphic measurements were unremarkable in all patients, with a mean (SD) body mass index of 26 (3). Pulmonary function tests of large and small airway function as well as lung volumes were normal in all except one whose results were consistent with moderate asthma. Five men were compound heterozygotes for CFTR mutations, four of whom had positive sweat tests (sweat chloride > 60 mEq/L). Twelve men were heterozygotes for CFTR mutations while no mutations were identified in one man. Although putative etiologic factors may suggest that men with CBAVD and CFTR mutations could be considered within the spectrum of clinical CF, the authors suggest that in men with CBAVD without any other clinical features of CF, the diagnosis of CF may not be made.

Adult↗
PubMed1996

Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

Adolescent↗
PubMed1995

Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: a short-term, double-blind study followed by six months open-label treatment.

Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to dramatically reduce the viscoelasticity of the sputum from CF patients. Phase II and III clinical trials have shown the drug to be safe, and that patients with a forced vital capacity (FVC) of > 40% predicted show an improvement in pulmonary function when receiving rhDNase. The current study evaluates the safety and efficacy of rhDNase in the most severly ill CF patients (FVC < 40% predicted). A double-blind, randomized, placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for a period of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy patients were recruited for the double-blind study, and 64 entered the OEP of whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice daily. In both the double-blind period and the OEP the drug appeared to be safe. During the double-blind study, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference between the groups. In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18%, respectively, for all patients participating. In conclusion, DNase is safe when administered in conjunction with a rigorous regimen of chest physiotherapy to severely ill patients (FVC < 40% predicted) with CF. The double-blind, 14 day study showed no significant improvement in pulmonary function but some patients may have improved after longer administration of rhDNase.

Administration, Inhalation↗
PubMed1994

Cystic fibrosis.

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Anti-Bacterial Agents↗
PubMed1993

Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF. The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes. Recombinant human DNase I (rhDNase) reduces the viscosity of CF sputum in vitro. To test the hypothesis that rhDNase would improve pulmonary function in children and adults with CF, we compared the efficacy and safety of 10-day administration of three doses of aerosolized rhDNase (0.6, 2.5, or 10.0 mg twice daily) in 181 outpatients using a randomized, placebo-controlled parallel design. Forced vital capacity (FVC) improved 10 to 12% (p < 0.05 to 0.001), and forced expiratory volume in one second (FEV1) improved 10 to 15% (p < 0.001) across all doses of rhDNase compared with placebo. The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 (p < 0.001). rhDNase was associated with a decreased perception of dyspnea and an improved perception of well-being. No patients developed detectable anti-rhDNase antibodies or bronchial reactivity to rhDNase. Some patients experienced mild upper airway irritation, but no major adverse events were reported. Administration for 10 days of aerosolized rhDNase to pediatric and adult outpatients with CF improves lung function and is well tolerated. Although all three doses were efficacious, the greatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups.

Adolescent↗
PubMed1990

Comparison of unbound and total serum theophylline concentrations with those of stimulated and unstimulated saliva in asthmatic children.

Unstimulated saliva, citric acid stimulated saliva, and serum were collected from 31 asthmatic children taking theophylline. Salivary theophylline concentrations, and total and unbound serum theophylline concentrations were measured. The correlation coefficients between both types of saliva, and total and unbound serum theophylline were all statistically significant (p less than 0.001). The highest correlation coefficients were obtained with stimulated saliva and total serum concentrations (r = 0.98), and stimulated saliva and unbound serum (r = 0.96). The coefficients when unstimulated saliva was compared to either total or unbound serum concentrations were 0.90 and 0.89, respectively. Serum binding of theophylline averaged 58.1%. Unstimulated saliva had a higher mean theophylline concentration than stimulated saliva. The results suggest that salivary monitoring using stimulated saliva may be used to predict serum concentrations with a high degree of confidence when the saliva levels are substantially lower than, higher than, or in the middle of the therapeutic range, but there is a considerable degree of uncertainty when the salivary values are near the lower or upper end of the therapeutic range.

Adolescent↗
PubMed1990

Changes in the contribution of the rib cage to tidal breathing during infancy.

As the shape, compliance, and deformability of the rib cage (RC) change during infancy, RC participation in quiet breathing may increase. We used respiratory inductive plethysmography (RIP) to determine the relative contributions of the RC and abdomen (AB) to tidal volume (VT) in 20 studies in 14 healthy infants 1 to 26 months of age during quiet natural sleep. RIP was calibrated with simultaneous flow measurements (anesthesia mask and pneumotachograph) by the least squares method of statistical analysis. We analyzed segments of breathing with and without flow measurement for RIP-derived VT, change in RC volume (Vrc) and AB volume (Vab) with each breath and the RC contribution to tidal breathing (%RC = Vrc/Vrc + Vab). The %RC increased with age: %RC = 1.4 age (months) + 33 (r = 0.69, p less than 0.01). After 9 months of age, %RC resembled that found in quietly sleeping adolescents. Mask placement increased VT in all but one subject (mean increase, 29 +/- 23% of baseline +/- SD; p less than 0.001, paired t test). In infants younger than 10 months of age, mask placement also increased %RC (without mask, 40 +/- 9%; with mask, 46 +/- 10% p less than 0.02). We conclude that by 1 yr of age, the RC contribution to tidal breathing during quiet sleep is similar to that of the adolescent, suggesting that major developmental changes in RC shape, compliance, and deformability take place during infancy.

Abdominal Muscles↗
PubMed1990

Water, electrolyte, and endocrine homeostasis in infants with bronchiolitis.

Twenty-two of 23 consecutive infants with bronchiolitis, 5.5 +/- 3.5 mo of age, showed a 1.9 +/- 1.4% increase in body weight, increased urinary osmolality of 737 +/- 193 mmol/L with low plasma osmolality of 275 +/- 4 mmol/L, and markedly elevated plasma antidiuretic hormone (ADH) levels of 114 +/- 225 pg/mL. Increased ADH, which usually suppresses plasma renin activity, was associated with increased plasma renin activity of 11-55 ng angiotensin 1/mL/h (normal for age less than 10 ng angiotensin 1/mL/h). Hyperaldosteronism was evident from the low fractional excretion of sodium of 0.27 +/- 0.2% and high fractional excretion of potassium of 21 +/- 15%. Serum sodium concentrations were normal. All of the pathologic findings returned to normal when the bronchiolitis subsided. A control group of 10 infants with nonrespiratory febrile illness did not show any of the above abnormalities. Thus, bronchiolitis of infancy is characterized by both increased ADH secretion and hyperreninemia with secondary hyperaldosteronism, which induce water retention but counterbalance each other with respect to serum sodium. Increased ADH secretion as well as increased plasma renin activity are not "inappropriate," but rather suggest a response to the perception of hypovolemia by intrathoracic receptors. We therefore conclude that the clinical management of bronchiolitis requires close monitoring of body wt and plasma osmolality-urinary osmolality relationship; serum sodium levels may be misleading.

Blood Volume↗
PubMed1990

Practical approach to the diagnosis and treatment of apnea of infancy.

Twenty-three infants aged 6 days to 9 months, sequentially referred for apnea or apparent life-threatening events (ALTE), were studied. A selective approach consisting of hospitalization, prolonged cardiorespiratory monitoring, and a graduated investigative protocol yielded positive findings in 75% of the subjects. Polysomnographic study and continuous esophageal pH monitoring were found to be the most informative. In addition to other appropriate therapeutic interventions, cardiorespiratory home monitoring was prescribed for four patients. In three nonmonitored subjects apnea recurred. Two infants died, one with homocystinuria complicated by brain hemorrhage and another with a fulminant viral infection. These investigative results and their outcome indicate that in cases of apnea or ALTE in apparently healthy infants, in-patient monitoring and evaluation is of much value. Home monitors should only be recommended in a selected group of patients, and an adequate follow-up and support system is essential.

Female↗
PubMed1989

The ameliorating effect of lumbar puncture in viral meningitis.

To test the hypothesis that lumbar puncture in viral meningitis results in symptomatic improvement, a group of 48 children was studied. Twenty-six patients had proved aseptic meningitis, and 22 had infections outside the central nervous system. Before and after lumbar puncture each subject was repeatedly scored for symptoms independently by the attending pediatrician and a parent. Marked symptomatic improvement in children with meningitis was demonstrated following lumbar puncture, while no significant change was demonstrated in the control group. The mechanism underlying this improvement is not clear; however, we consider a number of possible explanations.

Age Factors↗
PubMed1989

Transition from dynamically maintained to relaxed end-expiratory volume in human infants.

Newborn infants, in contrast to adults, dynamically maintain end-expiratory lung volume (EEV) above relaxation volume. The purpose of this study was to determine at what age children develop a breathing strategy that is relaxed, i.e., determined by the mechanical characteristics of the lung and chest wall. Forty studies were performed in 27 healthy infants and children aged 1 mo to 8 yr during natural sleep. Volume changes were recorded with the use of respiratory inductance plethysmography (RIP). The volume signal was differentiated to yield flow. Flow-volume representations were generated for a random sample of the recorded breaths to determine the predominant breathing strategy utilized, i.e., relaxed, interrupted, or indeterminate. The respiratory pattern was predominantly interrupted below 6 mo of age and predominantly relaxed over 1 yr of age. Mixed patterns were observed in children 6-12 mo of age. The number of breaths that could not be classified (indeterminate) decreased with age. Respiratory frequency measured from the sample of breaths decreased with age and was accompanied by an increase in expiratory time. We conclude that a relaxed EEV develops at the end of the first year of life and may be related to changes in the mechanical properties of the chest wall associated with growth as well as changes in respiratory timing.

Analog-Digital Conversion↗
PubMed1989

Changes of time constants during infancy and early childhood.

We used respiratory inductance plethysmography to record tidal respiration in 27 healthy unsedated infants and children 1 mo to 8 yr of age during sleep. Rib cage and abdominal outputs were present at approximately equal gains and summed to obtain an estimate of volume. Flow-volume curves were generated from the uncalibrated volume signal and its flow derivative. Expiratory time constants (tau) were obtained by visually drawing a line through the linear portion of the expiratory flow-volume relationship. tau increased significantly during the first 10 mo of life. After 10 mo, the estimated rate of increase of tau for older children was less than 5% of the estimated initial rate and not significantly different from zero. Prolongation of tau was paralleled by an increase in expiratory time (Te), and no changes in Te/tau were observed in the first 2 yr of life. These changes in tau likely reflect the increase in lung compliance induced by rapid alveolar growth during infancy. After the first year, expiratory time constants appear to remain relatively constant and may be consistent with balanced changes in compliance and resistance beyond infancy.

Aging↗
PubMed1988

Environmental overheating as a cause of transient respiratory chemoreceptor dysfunction in an infant.

A central hypoventilatory state developed in a 6-month-old boy with environmentally induced hyperthermia. The condition subsided within 24 hours of mechanical ventilation. Hypoxic and hypercapneic challenges performed 2 weeks later showed complete resolution of the respiratory chemoreceptor dysfunction. The damage to the CNS caused by accidental hyperthermia in general, and more specifically to the respiratory center, and its possible etiologic role in the pathophysiology of sudden infant death syndrome are discussed.

Chemoreceptor Cells↗