H. Juhling McClung

Acute liver disease and encephalopathy mimicking Reye syndrome. A report of three cases.

Three patients are described whose clinical presentation suggested Reye syndrome, and in whom the initial laboratory investigations supported the diagnosis. The subsequent clinical and biochemical evolution of the illness differed from that of Reye syndrome. The liver biopsy of each patient revealed changes in centrilobular hepatocytes rather than the diffuse small droplet fatty change characteristic of Reye syndrome. In each of them normal liver functions were regained. The findings in these patients suggest that a firm diagnosis of Reye syndrome cannot be made without histologic examination of the liver.

Early Changes in the Permeability of the Blood-Brain Barrier Produced by Toxins Associated with Liver Failure

ABSTRACT: Our study was designed to determine whether substances that appear in the serum during the course of liver failure have a detrimental effect on the passive permeability of the blood-brain [blood-cerebrospinal fluid (CSF)] barrier. Lactic acid, octanoic acid, and ammonia were infused into rabbits for 4 h. The permeability changes of the blood-brain barrier were quantified by infusing polyethylene glycol 400 (PEG 400) and measuring the quantity and average mol wt of the PEG 400 that entered the CSF. The lipid solubility and effective diffusional radius of the PEG molecules were also quantified to provide greater precision for measurements using this probe. None of the animals receiving toxic infusions became seriously ill during the infusions. Low dose infusions of lactic acid, octanoic acid, and ammonia increased the effective pore diameter of the blood-brain barrier from 7.3 A to an average of 8.5 Å. The amount of PEG entering the CSF increased from 1.7 to 4.0 (p < 0.025), 4.7 (p < 0.025), and 6.7 (p < 0.001) mmol/L, respectively. Rabbits with galactosamine-induced liver failure had 10.1 mmol/L PEG 400 in the CSF (p > 0.001) before any evidence of cerebral edema. These changes occur soon after these toxins accumulate in the plasma and may alone or together with other toxins account for the permeability changes that allow seurotoxic substances to enter the brain during hepatic disease and encephalopathies such as Reyes syndrome.

The contribution of salivary amylase to glucose polymer hydrolysis in premature infants.

ABSTRACT. To determine whether salivary amylase of premature infants can function as a surrogate for pancreatic amylase, we evaluated its production in the infant, acid resistance, and hydrolytic potency in a simulated oropharyngeal, gastric, and intestinal environment. The activity of salivary amylase in 11 prematures varied between 1 and 33 U/ml; the isozymic profile and acid resistance of the premature salivary amylase were identical to those of the enzyme of adults. A “modular” formula containing 7 g/dl of a 14C labeled long chain glucose polymer with degrees of polymerization ranging between 18 and 29 glucose units was prepared. Salivary amylase, 1.1 U/ml, was added to this formula. The progressive breakdown of the 14C polymers as the milk was subjected to oropharyngeal, gastric, and intestinal phase environments was evaluated by quantifying the liberation of short-chain oligomers from the 14C labeled substrates. The gastric pH was varied between 2 and 5 and the gastric incubation time was either 5 or 180 min. Substantial gastric phase breakdown only occurred after 3 h of exposure at the higher pHs of 4 (12%) and 5 (32%). During the intestinal phase, salivary amylase activity resumed. Prior gastric phase pH affected ultimate intestinal phase breakdown, p<0.001; after 5-min gastric phases at pHs ranging from 2 to 5, the intestinal phase breakdown ranged from 17 to 55%. We conclude that the limited salivary amylase in the saliva of premature infants can produce significant glucose polymer digestion in both the stomach and small intestine but the digestion falls substantially short of that accomplished by usual concentrations of pancreatic amylase.

Monitoring of intestinal transplant rejection

Our results show that maltase, sucrase, and lactase activity are present at a normal level in nonrejecting small bowel transplants after an initial postoperative decline. This confirms that the disaccharide absorbing capacity of these grafts is intact. In allogeneic bowel, however, the levels of maltase and sucrase decline as histologic rejection occurs. These results suggest that serial maltase, sucrase, and possibly lactase levels in allogeneic intestinal transplants may serve as a useful adjunct in the monitoring of small bowel transplant rejection.

Enterohepatic Distribution of Carnitine in Developing Piglets: Relation to Glucagon and Insulin

ABSTRACT: L-Carnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, and in vitro jejunal carnitine transport in piglets aged 1–36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age (p = 0.035 and 0.026, respectively). Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon (p = 0.0006), insulin (p = 0.0001), and glucagon:insulin ratio (p = 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal glucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R = 0.802, p = 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns.

Rectal Myopathy in Chronically Constipated Children

We examined full-thickness rectal biopsies from 30 children who had chronic constipation, including 5 children with constipation associated with clinical symptoms of intestinal pseudo-obstruction. Biopsies from 9 patients who required colonic interposition and from 7 with Hirschsprungs disease were used as controls. Tissues were evaluated for muscularis mucosae thickness (in mm), for absolute circular and longitudinal muscle layer thicknesses and their ratio, and for the intensity of neural vasoactive intestinal peptide (VIP) immunohistochemical staining. Atrophy of the rectal musculature with focal muscle fiber vacuolation or muscle fiber disappearance was found in all children with chronic constipation. Muscularis mucosae thickness was increased (P < .01) and the circular-to-longitudinal muscle ratio was decreased in the constipation group, with the greatest degree of atrophy being demonstrated in the circular layer. Two of the patients had additional biopsies up to 9 years after the first that illustrate progressive myopathic changes over time. This study demonstrates muscular atrophy in the rectum of children with chronic constipation. Besides primary idiopathic disease, potential etiologies include chronic distention, denervation, functional obstruction from obstipation, alteration in gut hormones, and toxic, ischemic, or neural injury.

Recurrent pancreatitis in three patients with chronic idiopathic intestinal pseudo-obstruction.

Chronic idiopathic intestinal pseudo-obstruction is a syndrome with substantial morbidity and mortality associated both with the syndrome and with its therapy. Standard therapy has included prokinetic agents and intravenous nutritional support when oral feedings are inadequate to maintain nutriture. We report three children with chronic intestinal pseudo-obstruction who experienced one or more attacks of pancreatitis. Two patients developed pseudocysts. One patient died. All three patients underwent cholecystectomy; one had stones, one had acalculous cholecystitis, and one had a normal gallbladder. All patients received prokinetic agents and total parenteral nutrition as therapy for their pseudo-obstruction. Candidate mechanisms to explain the etiology for pancreatitis in chronic intestinal pseudo-obstruction include biliary dysmotility associated with pseudo-obstruction and excessive cholinergic stimulation due to therapy with prokinetic agents.

Galactose-Containing Carbohydrates Are Preferentially Absorbed in the Neonatal Pig Colon

Previous studies on the piglet colon in newborns cleared of bacterial metabolic activity showed a capacity for lactose absorption. Colonic absorption occurred at a flux rate equal to the assimilation of lactose by the small intestine but by a process that did not involve either glucose-galactose sodium cotransport or simple diffusion. Surprisingly, colonic lactose transport did not require either fermentation or cleavage of the disaccharide for uptake. Experiments were designed to test the selectivity of the colonic transport process for a variety of carbohydrates. Colonic tissues from 4-7-d-old piglets were mounted in Ussing chambers and the mucosal-to-serosal flux of radiolabeled carbohydrates was compared with that of lactose. The results showed a 3-4-fold greater flux of galactose-containing sugars as compared with glucose-containing carbohydrates at concentrations up to 40 mM. Even lactulose, a synthetic disaccharide assumed to require bacterial digestion before assimilation, was transported readily.N-Acetylgalactosamine, a component of colonic mucus, inhibited the flux of lactose, whereas N-acetylglucosamine did not. Similarly, lactosylated BSA inhibited lactose flux, whereas nonlactosylated BSA did not. The capacity of the colon of the newborn to differentiate moieties as similar as glucose and galactose suggests an absorptive process for carbohydrates with a high degree of discrimination.

Failure to conserve lactose and glucose polymers during frozen storage of fecal specimens: methods for preservation.

Freezing is often used to retard bacterial enzymatic activity in fecal specimens collected to quantify specific carbohydrates. The effectiveness of freezer storage on preservation of lactose and glucose polymers was assessed. The data showed that more than 50% of lactose that was added to fecal supernatants that were stored without treatment for more than 50 days at -20 degrees C was lost. Adjustment of pH with HCl (pH 4.9), with HgCl2 (pH 6.3 or 5.85), or with NaOH (pH 10) improved carbohydrate preservation (P less than 0.0004). Storage of the supernatants of fecal homogenates lessened the loss of carbohydrate compared with the total homogenates (P less than 0.001). In supernatants, degradation occurred via simple hydrolysis; in homogenates, degradation occurred by hydrolysis and fermentation to a variety of end-products. Unprocessed fecal specimens that were frozen for months, then retrieved and incubated with lactose or glucose polymers showed extensive fermentative capacity. Cumulatively, the data indicate that enzymatic activity in feces is not halted by storage in the freezer, even if bacteria have been filtered from the stool.

THE EFFECT OF THE UNSTIRRED WATER LAYER (UWL) ON GLUCOSE OLIGOMER (GO) ASSIMILATION

GOs must pass through the UWL to be digested by brush border glucoamylase which progressively removes glucose units. In the absence of pancreatic amylase (PA), digestion appears rate-limiting for GO absorption. To assess whether the limited diffusivity of long chain GOs affects their assimilation, we evaluated the impact of thinning the UWL on GO uptake in rabbit jejunum proven free of PA. The tissue was mounted in Dietschy chambers, and the thickness of the UWL was adjusted to 140 or 400 um by varying the stirring rate of the mucosal buffer. The uptake of three 14C GOs [glucose (Degree of Polymerization, DP 1), DP 3-8, and DPAVG23] was assessed at cones of 180, 360, and 720 mg/dl.CONCLUSION: The barrier that the UWL presents to the assimilation of GOs is substantially greater for long chain GOs.