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Biomedical subjects

G B Odell

Publications and source records attributed to G B Odell.

At least 37 records · Page 2Linked to original sources

The in vitro and in vivo photoreactivity of bilirubin: I. Laser-defined wavelength dependence.

Monochromatic light was provided by a continuous wave Argon ion laser. We chose to study the in vitro effects of light at 457.9, 465.8, 476.5, 488.0, 501.7, and 514.5 nm as representative of a reasonably evenly spaced sampling across the blue-green spectrum. The in vivo experiments were conducted at 457.9, 476.5, 488.0, and 514.5 nm. In vitro light at 488.0 nm appeared to be more effective than the others studied. After 24 h of irradiance, the in vivo decline in serum bilirubin concentration produced by light at 488.0 nm was one-and-one-half, two, and four times as effective as light at 457.9, 476.5 and 514.5 nm, respectively. By 48 h of exposure, the declines produced by light at 457.9 nm and 488.0 nm are significantly superior to that at 476.5 nm and 514.5 nm, but they do not differ from one another.

Animals↗

Enteral administration of agar as an effective adjunct to phototherapy of neonatal hyperbilirubinemia.

Phototherapy increases the biliary excretion of unconjugated bilirubin. In this form, bilirubin would be subject to enterohepatic circulation, and the true efficacy of phototherapy would be blunted. We tested the hypothesis that sequestration of lumenal unconjugated bilirubin by enteral agar administration would enhance the efficacy of phototherapy in jaundiced infants. Fifty-two infants were studied, 21 control and 31 agar-supplemented. The birth weights, sex distribution, and postnatal age at onset of phototherapy did not differ between the two groups of infants; pre- and post-phototherapy bilirubin concentrations also did not differ between the groups. The bile acid concentrations and bilirubin saturation indices were also similar. The rate of declination of the plasma bilirubin concentrations after 24 h of phototherapy was greater and significantly more uniform in the agar-supplemented infants (-1.59 +/- 2.3 versus -2.51 +/- 1.44). Stool frequencies were greater in control infants (5.5 versus 4.3 per 24 h) whereas fecal bilirubin excretions were greater in agar-supplemented infants during the second day of phototherapy (1.32 versus 3.29 mg . kg-1 . 24 h-1). Agar supplementation reduced the duration of phototherapy by 23% (37.6 +/- 3.2 versus 48.1 +/- 5.0 h).

Agar↗

Comparison of effectiveness of pancreatic enzyme preparations in cystic fibrosis.

To evaluate claims that enteric-coated pancreatic enzyme preparations are more effective than conventional digestants in managing malabsorption in cystic fibrosis (CF), we conducted a trial comparing the efficacy of pancrealipase (enzyme supplement containing lipase, amylase, and protease) in the form of pH-sensitive microspheres (Pancrease) with that in the form of encapsulated enzyme powder (Cotazym). Ten boys with CF received equivalent dosages in a controlled, double-blind fashion using a random sequence of capsule administration with crossover and "washout" periods. Patients experienced significantly enhanced nitrogen and fat absorption while receiving either enzyme when compared with placebo. The enteric-coated product promoted significantly improved fat absorption as compared with the conventional enzyme capsule. Both enzyme preparations caused significantly improved protein absorption as compared with placebo, but there as no significant difference between the two products in the degree of effect on azotorrhea.

Adolescent↗

Essential fatty acid deficiency after hepatic portoenterostomy for biliary atresia.

Gas chromatography was used to determine the fatty acid composition of total lipids extracted from plasma and erythrocytes of five patients who had received an hepatic portoenterostomy for treatment of extrahepatic biliary atresia. Three patients, including one with successful surgery, demonstrated evidence of essential fatty acid deficiency, including decreased levels of linoleic and arachidonic acids with concomitant increases in palmitoleic and oleic acids. In two of these patients, the ratio of 5,8 11-eicosatrienoic acid to arachidonic acid ("triene/tetraene") exceeded 0.3, diagnostic of essential fatty acid deficiency. Even patients with successful hepatic portoenterostomy are at risk to develop essential fatty acid deficiency.

Bile Ducts↗

The effect of bilirubin on the function of hamster small intestine.

Jaundice phototherapy is associated with a significant incidence of watery diarrhea. We have postulated that acute intestinal secretion, rather than malabsorption of dietary carbohydrate, is an effect of a photoproduct of bilirubin upon the intestinal mucosa. Because of major effect of phototherapy is the hepatic excretion of nonconjugated bilirubin, we investigated the effect of bilirubin on small intestinal function in the hamster in vivo. The entire small intestine was luminally perfused in vivo with solutions containing bilirubin (0.125 to 0.75 mmole/liter) and net water and sodium fluxes were measured. Control animals absorbed both water (J H2O(net) = 58.9 microliter/min/g) and sodium (J Na(net) = 4.55 microEq/min/g), but animals perfused with bilirubin (greater than or equal to 0.25 mmole/liter) exhibited secretion of water (J H2O(net) = -39.0--85.9) and sodium (J Na(net)=-9.91--18.24). The rate of water secretion was positively related to the concentration of bilirubin in the infusate (r=0.749; p less than 0.001). The concentration of bilirubin in ultrafiltrates of perfusate was likewise positively related to its concentration in the infusate (r = 0.844; p less than 0.001), indicating the potential importance of soluble forms of bilirubin in inducing secretion. Possible epithelial injury was studied by measuring the concentration of DNA in the perfusate and the activity of disaccharidases in postperfusion mucosa, and the possible role of cyclic adenosine monophosphate as a mediator of the secretory process was investigated by determining its concentration in postperfusion mucosa. Perfusion with 0.5 mM bilirubin, which produced significant secretion, did not cause loss of DNA (0.284 versus 0.244 mg/liter) or mucosal lactase activity (56 versus 53 units/g) or enhancement of cyclic adenosine monophosphate concentration (14.9 versus 14.12 pmoles/mg protein).

Animals↗

Bilirubin, UDP-glucuronyl transferase of liver in postmature rats. A functional and morphologic comparison.

Postmaturity was induced in dated pregnancies in Wistar rats by daily injection of 25 units of chorionic gonadotrophin, beginning on day 18 of gestational life. Animals were either delivered operatively on day 23 of postconceptual age or allowed to deliver spontaneously on day 24 by stopping the gonadotrophin. The hepatic bilirubin UDP-glucuronyl transferase activity (E.C.2.4.1.17) was quantitated in these animals and compared with that of control animals of normal gestations operatively and spontaneously delivered of similar postconceptual age. Normal animals at birth have very little hepatic bilirubin UDP-glucuronyl transferase activity, but it rapidly achieves adult activities in the first 4 days of neonatal life. In contrast, the postmature animals of 23 and 24 days of postconceptual age exhibited marked suppression of the hepatic bilirubin UDP-glucuronyl transferase activity, but they exhibited rapid neonatal maturation after delivery. The ultrastructure of the hepatocytes from the postmature rats of 24 days postconceptual age exhibited the same paucity of smooth endoplasmic reticulum of 21-day rats, which is in striking contrast to of postnatal life. The findings are interpreted to suggest that the intrauterine milieu actually suppresses fetal maturation of liver function.

Animals↗

Acute cholestasis in patients with toxic- shock syndrome.

Serum liver function tests were performed in 22 females fulfilling the criteria for toxic-shock syndrome. All patients showed evidence of hepatic dysfunction during their hospital course. These findings included hyperbilirubinemia in the absence of laboratory evidence for significant hemolysis, mold elevation of the transaminases, threefold increase in their serum bile salt concentration, and hypoalbuminemia. These findings are best explained by hypoperfusion of the liver and a canalicular injury secondary to staphylococcal exotoxin. Cholestasis appears to be a universal finding in toxic-shock syndrome.

Alanine Transaminase↗

Increased osmotic fragility of erythrocytes in chronically jaundiced rats after phototherapy.

Littermate homozygous (jj) and heterozygous (Jj) Gunn rats, were irradiated with blue fluorescent light for 18 hours continuously. The incident irradiance was 1.5 mWatts/cm2 in the 420--480 nm band pass. The influence of the irradiance on circulating erthrocytes was studied by testing their osmotic fragility before and after the irradiance. The non-jaundiced, Jj, animals did not exhibit any increase in the osmotic fragility of their erythrocytes. The osmotic fragility of the erythrocytes from jaundiced, jj, animals was the same as the Jj animals prior irradiance. However, the fragility of the erythrocytes from the jj animals was significantly increased after the 18 hours of irradiance. The results indicated that the photodynamic action of bilirubin may be present in vivo.

Animals↗

Hepatic bilirubin UDP-glucuronyltransferase in patients with sickle cell anemia.

In sickle cell anemia the shortened survival of red blood cells presents the liver with an augmented load of bilirubin for hepatic clearance. To determine the effects of this excessive bilirubin load on the microsomal conjugating enzyme, hepatic bilirubin UDP-glucuronyltransferase, levels of this enzyme were measured in liver biopsies from patients with sickle cell anemia and several comparison groups. UDP-glucuronyltransferase activity in 14 patients with sickle cell anemia was 2-fold greater (P less than 0.005) than in 14 nonjaundiced comparison patients without liver disease. The elevated UDP-glucuronyltransferase activity in sickle cell anemia was similar to that found in 10 patients who chronically ingested drugs (barbiturates or estrogens) known to increase UDP-glucuronyltransferase activity. These observations suggest enhanced conjugation of bilirubin in patients with sickle cell anemia may result from substrate (bilirubin) induction of UDP-glycuronyltransferase.

Adolescent↗

The influence of fatty acids on the binding of bilirubin to albumin.

The influence of free fatty acids (FFA's) on the albumin binding of bilirubin was studied in vitro in the plasma of infants with neonatal hyperbilirubineamia and in solutions employing crystalline albumin to which bilirubin and FFA (oleic acid) were added. The bilirubin saturation index (SI) was utilized to distinguish between that fraction of bilirubin bound at the primary (high-affinity) site of albumin and bilirubin bound at secondary sites from which it is easily dissociated by salicylate. The relative saturation of albumin with bilirubin was also measured by addition of salicylate to whole blood samples where bilirubin was also measured by addition of salicylate to whole blood samples where bilirubin dissociated from the albumin could be sequestered by the red cells. The present studies indicate that FFA's influence the binding of bilirubin in two ways. At molar ratios of FFA to albumin (2:1 to 4:1), the FFA's compete with bilirubin for binding at the high-affinity site so that a significant portion of the bilirubin is transported at secondary sites, making it susceptible to displacement by water-soluble organic anions. At high molar ratios (greater than 5:1) FFA's compete with bilirubin for albumin binding at the secondary sites as well. In contrast to crystalline albumin where the first two molar equivalents of FFA do not influence the binding of bilirubin to albumin, all FFA concentrations in hyperbilirubinemic plasma reduce the affinity of albumin for bilirubin at its high-affinity site even though there is a molar excess of albumin over bilirubin.

Bilirubin↗