Fredric Daum

Intestinal osmolality and carbohydrate absorption in rats treated with polymerized glucose

The effect of passive antibody (p.a.) on the antibody response to ingested Bovine Seriun Albumin (USA) was compared to intravenous (i.v.) and subcutaneous (s.c.) immunization. Antibody to BSA was measured by the Farr-technique and quantitatively expressed as μg BSA-N binding capacity/ml of serum (ABC 33). 18 rabbits, passively imunized to BSA fron a pool of high titered antiserum had a mean ABC 33 of 17.2. Four of these animals received no antigen (group I), 5 were fed 0.156 BSA in witer (gr. II), and 3 received 5 rag BSA s.c. (gr. III); 50 mg BSA was given i.v. to 3 aniraala (gr. IV) and 20 ag BSA i.v. to another 3 (gr. V). Control animals for groups II - V were actively immunized in the same way without prior administration of p.a. Catabolism of p.a. was similar in groups I and II (mean ABC 33 on day 25: gr: I 1.4 ± 0.5, gr. II 0.9 ± 0.5). Subsequently, serum anti-BSA in gr. II increased to 6,6 ± 5.7 on day 63 (control 3.6 ± 2.2, p> 0.05). In gr. III, mean ABC 33 was lowest on day 14 (2.2 ± 1.4) and increased to 51.7 ± 21.7 (control 9.4 ± 8.4, p<0.02). In gr. IV mean ABC 33 increased from day 7 (0.4 ± 0.7) to 3.1 ± 2.8 (control 0.3 ± C.5, P<0.05). No active immunity developed in gr. V (control 0.17 ± 0.21). Confirming previous data, p.a. enhanced or suppressed parenteral immunization depending on routes of immunization and antigen/antibody ratios. In contrast, p.a. did not influence oral immunization and its catabolism was not affected by the ingested antigen.Summary: The intestinal osmolal physiology and absorption of comparable preparations of polymerized glucose and glucose were evaluated in isolated segments of rat duodenum. The acute rise in the osmolality of the succus entericus after 5% polymer injections (298 mOsm/kg at 3 min, 311 mOsm/kg at 30 min) was significantly less than that noted after 5% glucose (387 mOsm/kg at 3 min, 351 mOsm/kg at 30 min). At 60 min a steady state had been established and no significant difference was found. Ten percent polymer was superior to 10% glucose as it also produced a lower luminal osmolality (351 mOsm/kg versus 427 mOsm/kg at 30 min). Luminal polyethylene glycol concentrations revealed comparable increases in intraluminal water content after 10% polymer and 5% glucose (22% versus 25% at 30 min). After polymer injections, 4 times as much glucose was present in the mucosa as in the succus, whereas, after 5% glucose injections, a high concentration of glucose remained in the succus.These results indicate that polymer solutions produce lower luminal osmolality than glucose solutions of similar weight. Additionally, enhanced glucose absorption by the mucosal cell is suggested in animals injected with polymer. Polymerized glucose should, therefore, provide twice the calories of glucose without a disparate increase in the intestinal osmolality and intraluminal diffusion of extracellular water.Speculation: A polymerized glucose preparation, when administered orally, produces a lower immediate intraluminal solute content and osmolality than a glucose solution of the same concentration by weight when each has comparable electrolytes. Hydrolysis of the polymer within the intestinal lumen and on contact with the brush border of the intestine provides nutrient without increase in water movement into the proximal small bowel. Because of these properties, such a polymer may be useful in the oral nutritional rehabilitation of neonates and infants with diarrhea. It remains to be seen whether the pathogenesis of the diarrheal state may also prove to be of significance in determining the beneficial effect of this therapy.

EFFECTS OF PHOTOTHERAPY ON INTESTINAL DISACCHARIDASE ACTIVITY IN THE RAT

Diarrhea occurs in some newborns undergoing phototherapy for hyperbilirubinemia presumably due to decreased intestinal lactase activity. Such an effect may result directly from photo-energy or photo-oxidative products on the enzyme. To study the mechanism of this diarrheal state, a congenitally jaundiced homozygote Gunn rat (jj) and a non-icteric heterozygote litter mate (Jj) were used. Both jj and Jj adult rats were shaved of hair, treated with phototherapy for 48 hours, sacrificed, and the activity of lactase and sucrase determined in intestinal mucosal scrappings. In 5 therapy treated jj rats, lactase and sucrase activities were 2.1 and 14.1 umol/g/min respectively, compared to 4.7 and 24.0 in 5 untreated jj controls (p < .05 lactase, and p < .001 sucrase). There were no significant changes in disaccharidase activities in a group of 13 similarly treated Jj rats. A stable mucosal peptidase, GGTP, was unaffected in jj and Jj phototherapy treated rats. Bile collected from a treated jj rat had no effect on disaccharidase activities when incubated with mucosa in vitro. Incubation of mucosa with serum from a treated jj rat similarly had no effect on disaccharidase activities. The in vivo decrease in disaccharidase activities in phototherapy treated jaundiced rats (jj) but not in their anicteric litter mates (Jj) suggests that the photo-oxidative products and not direct light-energy alters disaccharidase activities. The mechanism for inhibition remains unknown.

The effect of phototherapy on intestinal mucosal enzyme activity in the Gunn rat.

Infants undergoing phototherapy may develop loose stools. Acquired lactase deficiency secondary to this treatment modality was suggested as a cause for the diarrhea. The effects of light energy directly on intestinal enzymes and indirectly through bilirubin photooxidation products were studied. Adult homozygote and heterozygote Gunn rats were treated with light for varying periods while littermate controls were kept in the dark. Intestinal lactase, sucrase and GGTP activities and serum bilirubin concentrations were determined. Jaundiced and non-jaundiced 1-week-old suckling Gunn rats were treated with light for 96 h, and intestinal lactase activity determined. No decreases in lactase, sucrase or GGTP activities were observed suggesting the reported diarrheal states following phototherapy are not related to light energy or photooxidation products.

FAILURE AND HAZARDS OF SUPERIOR MESENTERIC ARTERIAL INFUSION OF VASOPRESSIN FOR CONTROL OF BLEEDING VARICES IN CHILDREN

In adults with cirrhosis and hemorrhage from esophageal varices, infusion of vasopressin into the superior mesenteric artery (SMA) has resulted in the rapid control of bleeding, often within minutes. Three children with chronic liver disease, cirrhosis, and bleeding varices documented by fiberoptic endoscopy, received vasopressin by continuous SMA infusion. The dose of vasopressin used was 0.1 to 0.4u/min for a period of 50 to 145 hours. Despite receiving the maximal dose of vasopressin recommended for adults over a prolonged period of time, the three patients continued to have intermittent but significant bleeding requiring further blood transfusion. Transient side effects of vasopressin included mild to severe water intoxication and significant bradycardia with loss of all palpable pulses without other signs of vascular instability. Early and late complications of the transfemoral arterial catheterization in one child included paresthesias in the ipsilateral extremity within 24 hours of catheterization and severe ischemic changes 10 days later requiring three thrombectomies. The failure of continuous prolonged intraarterial vasopressin infusion to adequately control bleeding and the complications associated with this procedure suggest that the use of this therapy may not be appropriate for children with cirrhosis and varices.

GASTROINTESTINAL ENDOSCOPY IN CHILDREN AND ADOLESCENTS

Flexible fiberoptic endoscopy has proven useful in studying adults with gastrointestinal complaints, but its usefulness in children and adolescents has not been demonstrated. During a two year period, 61 upper gastrointestinal endoscopic procedures and 67 colonoscopies were safely performed under sedation in patients ages 10 weeks to 19 years. A diagnosis was established in 11 of 26 gastroscopies for recurrent pain or vomiting. These diagnoses included webs, esophageal disorders, and ulcers. Radiology had previously failed to clearly establish these diagnoses. Gastrosocopy was performed in 24 patients for evaluation of an acute bleeding episode and in 4 with suspected non-bleeding varices. The bleeding site was visualized in 6 of 8 children, but in only 1 of 16 adolescents. Removal of foreign bodies and follow-up studies accounted for 7 additional gastroscopies. 49 colonoscopies were performed in patients with inflammatory bowel disease and 16 studies provided information not available on barium enema examination. Colonoscopy was more sensitive in determining the activity of disease in ulcerative colitis and the extent of disease in granulomatous colitis. Colonoscopy was also performed in 18 patients because of bleeding. Polyps were removed in 7 patients and a colonic ulcer noted in 1 child. In the remaining 10, the source of bleeding was not determined despite intensive diagnostic investigation. These data demonstrate a safe and important adjunctive role for fiberoptic endoscopy in children and adolescents.

ASYMPTOMATIC TRANSIENT UVEITIS IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE

Acute symptomatic anterior uveitis has been seen in patients with inflammatory bowel disease (IBD). In the absence of ocular symptoms, anterior uveitis has not been appreciated in children with IBD. Tb determine if children with IBD might have ophthalmologic signs of uveitis without visual complaints, eye examinations were performed in 19 children with granulomatous bowel disease (GBD) and 7 with ulcerative colitis (UC). In those with GBD, 6 had uveitis by slit lamp examination while no abnormalities were noted in those with UC. The abnormalities consisted of cells and flare in the anterior chamber. Despite a predominance of girls (11) and whites (16) among the 19 children with GBD, all were male and 3 black in the group with asymptomatic uveitis. All 6 with uveitis demonstrated colonic involvement. There were no positive correlations between the presence of uveltis and bowel symptoms, duration of illness, extra-intestinal manifestations, or specific treatment regimens. Contrary to observations in adults with acute anterior uveitis, none of the 6 children had radiographic evidence of spondylitis and 5 were HLA-B27 negative. Repeat eye examinations 6 to 8 months later, revealed no evidence of uveitis in 4 of 5 children. These data suggest that asymptomatic, transient uveitis is common in children with GBD and that males, blacks, and those children who have colonic involvement may be at greater risk.