Richard J. Lemen

Assessment of lactose absorption by measurement of urinary galactose

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.

Variability of Pulmonary Responsiveness to Aerosolized Histamine in Normal Rabbits

Considerable between-subject variability in pulmonary responsiveness to histamine has been reported in normal human subjects, dogs, guinea pigs, and rhesus monkeys, but rabbits have not been studied. We determined the between- and within-rabbit variability of pulmonary histamine responsiveness in 34 anesthetized and mechanically ventilated New Zealand White rabbits. In 30 rabbits, 5 breaths of aerosolized histamine were delivered in 9 increasing concentrations ranging from 0.01 to 100 mg/ml. Eleven of 30 rabbits were rechallenged with histamine on 1-4 additional occasions over a 3-week period. In the remaining 4 rabbits, 9 doses of distilled H2O were aerosolized to determine the degree of spontaneous variability in measurements of lung resistance (RL) and dynamic lung compliance (Cdyn). We defined an increase in RL of greater than 50% of baseline (TD50RL) and a decrease in Cdyn of greater than 25% of baseline (TD25Cdyn) as being significant based on observations in these 4 rabbits. These limits exceeded the 99.9 percentile of spontaneous variability in RL and Cdyn. Pulmonary responsiveness to histamine varied widely, with a greater than 10,000-fold range in TD50RL and a 1,000-fold range in TD25Cdyn between the most and least sensitive rabbits. The variability of this responsiveness was log-normally distributed. It was not correlated with age, sex, or baseline RL and Cdyn. In contrast, within-rabbit responses to histamine challenge were quite reproducible. Five of 30 rabbits were killed at the conclusion of their histamine challenges for pathologic examination of their lungs. No evidence of airway inflammation was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of acute hypoxia to alter pulmonary prostaglandin metabolism in dogs

We studied the effects of acute hypoxia (Fi02 = 0.09-0.11, 20 min.) on transpulmonary plasma prostaglandin (PG) concentrations in ten anesthetized, paralyzed, artificially ventilated dogs. Concentrations of 6-keto-PGF1 alpha, TxB2, PGE2, PGF2 alpha, and 13,14-dihydro-15-keto-PGF2 alpha were measured from the pulmonary artery and abdominal aorta using radioimmunoassay. In an additional six dogs, the effects of arachidonic acid (AA) infusions (100 mcg/kg/min) during normoxia and acute hypoxia were determined. Compared to normoxic conditions, acute hypoxia increased pulmonary artery pressure (p less than 0.05), decreased both the arterial oxygen tension (PaO2) and the alveolar-to-arterial oxygen tension gradient (A-aDO2) (p less than 0.05), but did not affect transpulmonary plasma PG concentrations. AA infusions significantly (p less than 0.05) increased 6-keto-PGF1 alpha independent of FiO2. Acute hypoxia failed to elicit a pulmonary pressor response in the AA-treated animals although PaO2 and A-aDO2 decreased (p less than 0.05). These data in healthy dogs suggest that (1) acute hypoxia does not alter net pulmonary PG metabolism, (2) prostacyclin synthesis is stimulated by increased plasma AA concentrations and (3) this effect may block normal pressor responses to hypoxic stimuli.

Canine parainfluenza type 2 and Bordetella bronchiseptica infection produces increased bronchoalveolar lavage thromboxane concentrations in beagle puppies

Acute infections in beagle puppies with canine parainfluenza virus type 2 (CP12), and CP12 in combination with Bordetella bronchiseptica (Bb) produce bronchiolitis and increased airways responsiveness to aerosolized histamine during the acute infection. In order to determine whether these observations were associated with increased levels of eicosanoids, the stable metabolites of thromboxane A2 and prostacylin, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha) respectively, and leukotriene B4 were measured in the bronchoalveolar lavage (BAL) fluid of 25 beagle puppies (age = 76 +/- 1 days, mean +/- SEM) 3-4 days after no infection (control, n = 6), inoculation with both CP12 and Bb (CP12-Bb, n = 11), inoculation with CP12 alone (CP12, n = 4), and inoculation with Bb alone (Bb, n = 4). In addition, plasma levels of TXB2 and 6-keto-PGF1 alpha were measured before and after infection in the CP12-Bb and control groups. The BAL concentration of thromboxane B2 was increased in the CP12-Bb group (520 +/- 120 pg/ml), but not in the CP12 (88 +/- 40 pg/ml), Bb (235 +/- 100 pg/ml), or control groups (120 +/- 60 pg/ml, p less than 0.01). There also was a borderline increase in BAL concentration of LTB4 in the CP12-Bb group. No differences were observed in the BAL concentration of 6-keto PGF1 alpha. Furthermore, neither TXB2 nor PGF1 alpha was elevated in the plasma of control or CP12-Bb puppies. These data suggest that increased thromboxane concentrations in BAL fluid are associated with histamine hyperresponsiveness during acute infection in the CP12-Bb group.

Nedocromil Sodium Inhibits Canine Adenovirus Bronchiolitis in Beagle Puppies

Nedocromil sodium is a nonsteroidal anti-inflammatory drug used to control asthmatic attacks. Our hypothesis is that nedocromil sodium inhibits virus-induced airway inflammation, a common trigger of asthma. We nebulized nedocromil sodium into beagle dogs (n = 10, mean ± SEM ages: 149 ± 13 days) before and after inoculation with canine adenovirus type 2 (CAV2). Control dogs (n = 10) received saline aerosols and were either infected with CAV2 (Sa1/CAV2, n = 7, mean ± SEM ages: 140 ± 11 days) or were not infected (Sal/Sal, n = 3, ages: 143 ± 0 days). All dogs were anesthetized with choralose (80 mg/kg IV), intubated, and mechanically ventilated. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed using standard techniques. Pulmonary function tests revealed no significant change between the nedocromil sodium and non-nedocromil-treated groups. The percentage of infected bronchioles was quantitated as the number of inflamed airways of 40 bronchioles examined times 100 for each dog. Nedocromil-treated dogs had significantly (p < 0.05) less mucosal inflammation (mean ± SEM, 39% ± 5%), epithelial denudation (36% ± 5%), and BAL neutrophilia (11 ± 3) than did Sal/CAV2 dogs (51% ± 6%, 57% ± 4%, and 33% ± 8%, respectively). We concluded that pretreatment with nedocromil sodium aerosols attenuated CAV2-induced airway inflammation in these beagle puppies.