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Papers by Daniel Caplan

Research paper thumbnail of Evidence for Hypertyraminemia in Reye's Syndrome

Pediatrics, Jul 1, 1979

Utilizing a specific and sensitive radioimmunoassay, palsma and urine tyramine were measured in 1... more Utilizing a specific and sensitive radioimmunoassay, palsma and urine tyramine were measured in 14 consecutive patients with liver biopsy-proven Reye's syndrome. Plasma tyrosine was measured in 11 of these patients. The results revealed significant (P less than .003) elevation in plasma (3.4 +/- .52 ng/ml) (mean +/- SEM) and urine (1.00 +/- .26 mg/24 hr) tyramine as well as plasma tyrosine (204 +/- 52.5 mumole/liter) at the onset of the disease when compared to the levels of tyramine and tyrosine in a group of hospitalized patients without hepatic disorders. Furthermore, there was a positive correlation between plasma tyramine and days in coma (r = .86; P less than .001), and between plasma tyramine and tyrosine (r = 0.80; P less than .001). These data suggest that there is s substantial disturbance of tyrosine metabolism in Reye's syndrome and that the accumulation of this amino acid and its metabolite, tyramine, may contribute to the encephalopathy of this disease.

Research paper thumbnail of Hypercatecholaminemia in Reye's Syndrome

Pediatrics, Apr 1, 1984

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radio... more To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's syndrome as compared with concentrations in a control population. Hypercatecholaminemia may contribute to the encephalopathy of Reye's syndrome.

Research paper thumbnail of Hypercatecholaminemia in Reye's syndrome

Pediatrics, 1984

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzy... more To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's sy...

Research paper thumbnail of Abnormal regulation of pyridoxal 5'-phosphate in Reye's syndrome

Clinical chemistry, 1983

Seeking to determine the effect of liver disease associated with Reye's syndrome on the regul... more Seeking to determine the effect of liver disease associated with Reye's syndrome on the regulation of plasma pyridoxal 5'-phosphate, we measured this compound in plasma from 11 patients with biopsy-proven Reye's syndrome. Its concentrations in plasma are significantly higher [37.5 (SD 6.13) micrograms/L] at the onset of the disease than after treatment [8.50 (SD 2.9) micrograms/L] or in a group of hospitalized patients with no evidence of liver disease [8.4 (SD 1.5) micrograms/L]. The concentration of pyridoxal 5'-phosphate in plasma at the time the patients entered the hospital correlated significantly with their activities of serum alanine aminotransferase.

Research paper thumbnail of Low levels of pyridoxal 5'-phosphate in patients with cystic fibrosis

Pediatrics, 1986

To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate... more To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, we measured this compound in plasma from 56 patients with cystic fibrosis. The concentration of PLP in plasma was assayed by a radioenzymatic technique. The results of this study showed that PLP concentration was decreased significantly (6.44 +/- 5.20 ng/mL, mean +/- SD; median 4.45 ng/mL) in patients with cystic fibrosis as compared with a group of hospitalized children with neither cystic fibrosis nor hepatic disease serving as a control group (13.2 +/- 5.04 ng/mL, mean +/- SD; median 12.5 ng/mL). Additionally, 25% of the population with cystic fibrosis exhibited exceedingly low plasma PLP level (less than 2.75 ng/mL). In patients with cystic fibrosis, significant inverse linear associations were found between plasma PLP and serum levels of SGOT and SGPT (PLP v SGOT: r = -.60, P less than .03; PLP v SGPT: r = -.50, P less than .03). T...

Research paper thumbnail of Biliary Atresia: An Evolving Perspective

Southern Medical Journal, 1986

From 1967 to 1984, 50 of our patients with extrahepatic biliary atresia had surgical exploration.... more From 1967 to 1984, 50 of our patients with extrahepatic biliary atresia had surgical exploration. Of 40 biliary drainage procedures, bile drained in 21 (52%). Thirty-four patients had portoenterostomy, three had portocholecystostomy, and the most recent six patients had a valved hepatoduodenal conduit. Successful biliary drainage was related to the presence of microscopic ducts at the porta hepatis in 20 of 21 infants. Twenty patients are alive, 12 from two to six years postoperatively (one with a liver transplant). Seven have normal serum bilirubin values. Height and weight exceed the 50th percentile in 5/15 patients studied. Multiple episodes of cholangitis have occurred in 11 patients with portoenterostomy and two with hepatoduodenal conduits. In 12 patients, hemorrhage from the stoma necessitated closure of the stoma before 1 year of age. Five of the six patients with hepatoduodenal conduit are alive two years postoperatively.

Research paper thumbnail of 1240 Platelet Monoamine Oxidase (Mao) Activity in Reye's Syndrome (RS)

Research paper thumbnail of 1596 HYPERTYRAMENEMIA AND HYPERPODIACTINEMIA IN REYE'S SYN-DROME: CORROBORaTION OF THE FALSE NEUROTRANSMITTER HYPOTHESIS

Research paper thumbnail of Reye's Syndrome: Success of Supportive Care

New England Journal of Medicine, 1978

Research paper thumbnail of Metabolic Risk Factors for Stone Formation in Patients with Cystic Fibrosis

The Journal of Urology, 2002

Purpose: Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic a... more Purpose: Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis.

Research paper thumbnail of Salicylate and mitochondrial monoamine oxidase function in Reye's syndrome

Journal of Pharmaceutical Sciences, 1987

The main objective of this investigation was to study the effect of salicylate on platelet mitoch... more The main objective of this investigation was to study the effect of salicylate on platelet mitochondrial monoamine oxidase (MAO) activity isolated from blood of two patients with Reye's syndrome. Comparative studies were made with hospitalized children without Reye's syndrome (n = 27) and healthy children (n = 19) serving as controls. Platelet MAO was measured by a radioenzymatic technique with [14C]tyramine as a substrate. The results of this study showed that salicylate (1.0 mM) caused an appreciable inhibition of the platelet MAO activity of patients with Reye's syndrome at the onset of the illness. This was demonstrated by a greater than 50% reduction in enzyme maximum velocity (Vmax) value. The salicylate MAO-inhibitory effect was maintained throughout the duration of the illness. Salicylate had only a minimal MAO-inhibitory effect on platelets isolated from blood of recovered Reye's syndrome patients, healthy controls, and non-Reye's hospitalized children, and no apparent effect on enzyme Vmax values. These preliminary findings suggest that salicylate-induced mitochondrial injury may affect MAO function in children with Reye's syndrome.

Research paper thumbnail of Knowledge of Physician Prescriptions and Adherence to Treatment Among Children with Cystic Fibrosis and Their Mothers

Journal of Developmental & Behavioral Pediatrics, 1999

This investigation examined factors related to adherence to treatment regimens for children with ... more This investigation examined factors related to adherence to treatment regimens for children with cystic fibrosis (CF) and their mothers. Subjects were 45 children with CF who ranged in age from 6 to 10 years and their mothers. Findings revealed that children's and parents' reports of level of adherence were related to their knowledge of the specific details associated with medically prescribed treatments. In this sample, 12% to 32% of mothers did not have an accurate understanding of physician recommendations for their children's treatments. When controlling for individual differences in the prescribed treatment regimens, parents' and children's knowledge of what had been prescribed accounted for a significant portion of the variance in the children's reported treatment-related behaviors. Results are discussed in terms of implications for future intervention research aimed at enhancing adherence to treatment as well as for future directions for clinical efforts in this area.

Research paper thumbnail of Quantitative changes of serum lipoprotein-X after cholestyramine administration in infants with cholestatic biliary tract and liver disease

European Journal of Clinical Investigation, 1978

Lipoprotein-X (LP-X) was determined before and after the administration of cholestyramine in fift... more Lipoprotein-X (LP-X) was determined before and after the administration of cholestyramine in fiftyfive infants with persistent cholestatic jaundice to differentiate between intra-and extrahepatic disease.

Research paper thumbnail of Treatment of Lower Respiratory Tract Infections Due to Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Clinical Infectious Diseases, 1984

Research paper thumbnail of Simultaneous Occurrence of Extrahepatic Biliary Atresia and Fetal Alcohol Syndrome

Archives of Pediatrics & Adolescent Medicine, 1979

Page 1. Simultaneous Occurrence of Extrahepatic Biliary Atresia and Fetal Alcohol Syndrome Since ... more Page 1. Simultaneous Occurrence of Extrahepatic Biliary Atresia and Fetal Alcohol Syndrome Since the 1973 report by Jones and Smith1 of eight infants born to moth-ers who had heavy ethanol intake throughout pregnancy ...

Research paper thumbnail of Composition of Parotid Saliva on Different Days in Patients With Cystic Fibrosis

Archives of Pediatrics & Adolescent Medicine, 1972

... In earlier studies the authors4·5 have claimed a deficiency in ductal reabsorption of sodium ... more ... In earlier studies the authors4·5 have claimed a deficiency in ductal reabsorption of sodium in parotid sa¬ liva. ... Other than sodium and chloride concentrations in nonstimulated sa¬ livas, the remainder of the data col¬ lected from eleven pairs during both periods of ...

Research paper thumbnail of Bolus Inhalation of rhDNase with the AERx System in Subjects with Cystic Fibrosis

Journal of Aerosol Medicine, 2003

Inhaled recombinant human deoxyribonuclease (rhDNase) delivered by nebulizer improves pulmonary f... more Inhaled recombinant human deoxyribonuclease (rhDNase) delivered by nebulizer improves pulmonary function and reduces the rate of pulmonary exacerbations in cystic fibrosis subjects. Standard jet nebulizers are relatively inefficient and require a delivery time of 10-20 min. We conducted an open-label, proof-of-concept study to evaluate whether bolus inhalation of rhDNase with a more efficient delivery system was safe and effective in cystic fibrosis subjects. The AERx system used for this study aerosolized 1.35 mg of rhDNase in three inhalations at a single sitting. The predicted AERx lung dose was approximately 0.68 mg, a dose consistent with lung doses of rhDNase given by jet nebulizer. In our 16 subjects with cystic fibrosis, a mean relative increase in FEV(1) of 7.8% (p < or = 0.001) was observed after 15 days of bolus delivery of rhDNase with the AERx system. The safety profile of rhDNase given as a bolus was similar to that observed with traditional nebulizer delivery. This study demonstrated that bolus inhalation of rhDNase was feasible, reasonably well-tolerated, and associated with improvement in pulmonary function in this small group of cystic fibrosis subjects.

Research paper thumbnail of Evidence for Hypertyraminemia in Reye's Syndrome

Pediatrics, Jul 1, 1979

Utilizing a specific and sensitive radioimmunoassay, palsma and urine tyramine were measured in 1... more Utilizing a specific and sensitive radioimmunoassay, palsma and urine tyramine were measured in 14 consecutive patients with liver biopsy-proven Reye's syndrome. Plasma tyrosine was measured in 11 of these patients. The results revealed significant (P less than .003) elevation in plasma (3.4 +/- .52 ng/ml) (mean +/- SEM) and urine (1.00 +/- .26 mg/24 hr) tyramine as well as plasma tyrosine (204 +/- 52.5 mumole/liter) at the onset of the disease when compared to the levels of tyramine and tyrosine in a group of hospitalized patients without hepatic disorders. Furthermore, there was a positive correlation between plasma tyramine and days in coma (r = .86; P less than .001), and between plasma tyramine and tyrosine (r = 0.80; P less than .001). These data suggest that there is s substantial disturbance of tyrosine metabolism in Reye's syndrome and that the accumulation of this amino acid and its metabolite, tyramine, may contribute to the encephalopathy of this disease.

Research paper thumbnail of Hypercatecholaminemia in Reye's Syndrome

Pediatrics, Apr 1, 1984

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radio... more To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's syndrome as compared with concentrations in a control population. Hypercatecholaminemia may contribute to the encephalopathy of Reye's syndrome.

Research paper thumbnail of Hypercatecholaminemia in Reye's syndrome

Pediatrics, 1984

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzy... more To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's sy...

Research paper thumbnail of Abnormal regulation of pyridoxal 5'-phosphate in Reye's syndrome

Clinical chemistry, 1983

Seeking to determine the effect of liver disease associated with Reye's syndrome on the regul... more Seeking to determine the effect of liver disease associated with Reye's syndrome on the regulation of plasma pyridoxal 5'-phosphate, we measured this compound in plasma from 11 patients with biopsy-proven Reye's syndrome. Its concentrations in plasma are significantly higher [37.5 (SD 6.13) micrograms/L] at the onset of the disease than after treatment [8.50 (SD 2.9) micrograms/L] or in a group of hospitalized patients with no evidence of liver disease [8.4 (SD 1.5) micrograms/L]. The concentration of pyridoxal 5'-phosphate in plasma at the time the patients entered the hospital correlated significantly with their activities of serum alanine aminotransferase.

Research paper thumbnail of Low levels of pyridoxal 5'-phosphate in patients with cystic fibrosis

Pediatrics, 1986

To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate... more To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, we measured this compound in plasma from 56 patients with cystic fibrosis. The concentration of PLP in plasma was assayed by a radioenzymatic technique. The results of this study showed that PLP concentration was decreased significantly (6.44 +/- 5.20 ng/mL, mean +/- SD; median 4.45 ng/mL) in patients with cystic fibrosis as compared with a group of hospitalized children with neither cystic fibrosis nor hepatic disease serving as a control group (13.2 +/- 5.04 ng/mL, mean +/- SD; median 12.5 ng/mL). Additionally, 25% of the population with cystic fibrosis exhibited exceedingly low plasma PLP level (less than 2.75 ng/mL). In patients with cystic fibrosis, significant inverse linear associations were found between plasma PLP and serum levels of SGOT and SGPT (PLP v SGOT: r = -.60, P less than .03; PLP v SGPT: r = -.50, P less than .03). T...

Research paper thumbnail of Biliary Atresia: An Evolving Perspective

Southern Medical Journal, 1986

From 1967 to 1984, 50 of our patients with extrahepatic biliary atresia had surgical exploration.... more From 1967 to 1984, 50 of our patients with extrahepatic biliary atresia had surgical exploration. Of 40 biliary drainage procedures, bile drained in 21 (52%). Thirty-four patients had portoenterostomy, three had portocholecystostomy, and the most recent six patients had a valved hepatoduodenal conduit. Successful biliary drainage was related to the presence of microscopic ducts at the porta hepatis in 20 of 21 infants. Twenty patients are alive, 12 from two to six years postoperatively (one with a liver transplant). Seven have normal serum bilirubin values. Height and weight exceed the 50th percentile in 5/15 patients studied. Multiple episodes of cholangitis have occurred in 11 patients with portoenterostomy and two with hepatoduodenal conduits. In 12 patients, hemorrhage from the stoma necessitated closure of the stoma before 1 year of age. Five of the six patients with hepatoduodenal conduit are alive two years postoperatively.

Research paper thumbnail of 1240 Platelet Monoamine Oxidase (Mao) Activity in Reye's Syndrome (RS)

Research paper thumbnail of 1596 HYPERTYRAMENEMIA AND HYPERPODIACTINEMIA IN REYE'S SYN-DROME: CORROBORaTION OF THE FALSE NEUROTRANSMITTER HYPOTHESIS

Research paper thumbnail of Reye's Syndrome: Success of Supportive Care

New England Journal of Medicine, 1978

Research paper thumbnail of Metabolic Risk Factors for Stone Formation in Patients with Cystic Fibrosis

The Journal of Urology, 2002

Purpose: Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic a... more Purpose: Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis.

Research paper thumbnail of Salicylate and mitochondrial monoamine oxidase function in Reye's syndrome

Journal of Pharmaceutical Sciences, 1987

The main objective of this investigation was to study the effect of salicylate on platelet mitoch... more The main objective of this investigation was to study the effect of salicylate on platelet mitochondrial monoamine oxidase (MAO) activity isolated from blood of two patients with Reye's syndrome. Comparative studies were made with hospitalized children without Reye's syndrome (n = 27) and healthy children (n = 19) serving as controls. Platelet MAO was measured by a radioenzymatic technique with [14C]tyramine as a substrate. The results of this study showed that salicylate (1.0 mM) caused an appreciable inhibition of the platelet MAO activity of patients with Reye's syndrome at the onset of the illness. This was demonstrated by a greater than 50% reduction in enzyme maximum velocity (Vmax) value. The salicylate MAO-inhibitory effect was maintained throughout the duration of the illness. Salicylate had only a minimal MAO-inhibitory effect on platelets isolated from blood of recovered Reye's syndrome patients, healthy controls, and non-Reye's hospitalized children, and no apparent effect on enzyme Vmax values. These preliminary findings suggest that salicylate-induced mitochondrial injury may affect MAO function in children with Reye's syndrome.

Research paper thumbnail of Knowledge of Physician Prescriptions and Adherence to Treatment Among Children with Cystic Fibrosis and Their Mothers

Journal of Developmental & Behavioral Pediatrics, 1999

This investigation examined factors related to adherence to treatment regimens for children with ... more This investigation examined factors related to adherence to treatment regimens for children with cystic fibrosis (CF) and their mothers. Subjects were 45 children with CF who ranged in age from 6 to 10 years and their mothers. Findings revealed that children's and parents' reports of level of adherence were related to their knowledge of the specific details associated with medically prescribed treatments. In this sample, 12% to 32% of mothers did not have an accurate understanding of physician recommendations for their children's treatments. When controlling for individual differences in the prescribed treatment regimens, parents' and children's knowledge of what had been prescribed accounted for a significant portion of the variance in the children's reported treatment-related behaviors. Results are discussed in terms of implications for future intervention research aimed at enhancing adherence to treatment as well as for future directions for clinical efforts in this area.

Research paper thumbnail of Quantitative changes of serum lipoprotein-X after cholestyramine administration in infants with cholestatic biliary tract and liver disease

European Journal of Clinical Investigation, 1978

Lipoprotein-X (LP-X) was determined before and after the administration of cholestyramine in fift... more Lipoprotein-X (LP-X) was determined before and after the administration of cholestyramine in fiftyfive infants with persistent cholestatic jaundice to differentiate between intra-and extrahepatic disease.

Research paper thumbnail of Treatment of Lower Respiratory Tract Infections Due to Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Clinical Infectious Diseases, 1984

Research paper thumbnail of Simultaneous Occurrence of Extrahepatic Biliary Atresia and Fetal Alcohol Syndrome

Archives of Pediatrics & Adolescent Medicine, 1979

Page 1. Simultaneous Occurrence of Extrahepatic Biliary Atresia and Fetal Alcohol Syndrome Since ... more Page 1. Simultaneous Occurrence of Extrahepatic Biliary Atresia and Fetal Alcohol Syndrome Since the 1973 report by Jones and Smith1 of eight infants born to moth-ers who had heavy ethanol intake throughout pregnancy ...

Research paper thumbnail of Composition of Parotid Saliva on Different Days in Patients With Cystic Fibrosis

Archives of Pediatrics & Adolescent Medicine, 1972

... In earlier studies the authors4·5 have claimed a deficiency in ductal reabsorption of sodium ... more ... In earlier studies the authors4·5 have claimed a deficiency in ductal reabsorption of sodium in parotid sa¬ liva. ... Other than sodium and chloride concentrations in nonstimulated sa¬ livas, the remainder of the data col¬ lected from eleven pairs during both periods of ...

Research paper thumbnail of Bolus Inhalation of rhDNase with the AERx System in Subjects with Cystic Fibrosis

Journal of Aerosol Medicine, 2003

Inhaled recombinant human deoxyribonuclease (rhDNase) delivered by nebulizer improves pulmonary f... more Inhaled recombinant human deoxyribonuclease (rhDNase) delivered by nebulizer improves pulmonary function and reduces the rate of pulmonary exacerbations in cystic fibrosis subjects. Standard jet nebulizers are relatively inefficient and require a delivery time of 10-20 min. We conducted an open-label, proof-of-concept study to evaluate whether bolus inhalation of rhDNase with a more efficient delivery system was safe and effective in cystic fibrosis subjects. The AERx system used for this study aerosolized 1.35 mg of rhDNase in three inhalations at a single sitting. The predicted AERx lung dose was approximately 0.68 mg, a dose consistent with lung doses of rhDNase given by jet nebulizer. In our 16 subjects with cystic fibrosis, a mean relative increase in FEV(1) of 7.8% (p < or = 0.001) was observed after 15 days of bolus delivery of rhDNase with the AERx system. The safety profile of rhDNase given as a bolus was similar to that observed with traditional nebulizer delivery. This study demonstrated that bolus inhalation of rhDNase was feasible, reasonably well-tolerated, and associated with improvement in pulmonary function in this small group of cystic fibrosis subjects.