Variations in glycerol kinetics in Reye's syndrome.

Glycerol kinetics and adverse affects were studied in nine patients with Reye's syndrome. Glycerol was given by continuous infusion over 2 hr, half over the first 0.5 hr and the remainder over the next 1.5 hr. The dose was adjusted to keep intracranial pressure less than or equal to 15 mmHg. At steady state, serial blood samples were collected during glycerol infusion and analyzed by an enzymatic assay specific for glycerol. At 0.75 to 1.75 gm/kg/2 hr glycerol doses, the serum levels ranged from 1.48 to 5.83 mg/ml. Total body clearance ranged from 1.99 to 5.1 ml/kg/min. Glycerol clearance was not related to serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), or serum ammonia levels. Glycerol provided effective control of intracranial pressure in all patients. Temporary elevation of serum creatinine and blood urea nitrogen (BUN) and presence of hemolysis in two patients, appeared to be related to glycerol.

Catecholamine and octopamine concentrations in brains of patients with Reye syndrome.

Dopamine, norepinephrine, and octopamine levels were estimated in regions of brains obtained postmortem from children who died with Reye syndrome and from age-matched controls. Hypothalamic norepinephrine levels were greatly decreased (to 30 percent of control, p less than 0.02) and octopamine levels were increased (to 700 percent of control, p less than 0.01). Levodopa had little effect on the physiologic condition of the patients. However, CNS dopamine and homovanillic concentrations were not elevated by levodopa, indicating that in the present cases levodopa was not metabolized to its catecholamine products. The findings indicate that the encephalopathy of Reye syndrome (as in other types of hepatic coma) may be linked to the presence of false transmitters in the brain and that levodopa is a rational therapy if administered before irreversible CNS changes occur.

Constipation and dietary fiber intake in children.

OBJECTIVE: Severe constipation in children is associated with rectal overdistension and insensitivity. Treatment typically involves three phases: disimpaction (days to weeks), laxative use (months), and a high-fiber diet (lifelong). The purpose of this survey is a discussion of therapies that recognize the unique problems that children with severe constipation have. METHODS: Four-day diet logs were obtained from children who had no history of chronic bowel disease. Their intake of dietary fiber was determined from the logs and was compared with the dietary fiber ingested by children who had chronic constipation. These data sets were compared in light of our current understanding of the need for dietary fiber. RESULTS: Approximately half of the children from families who were health conscious enough to request dietary evaluation still fell below the age + 5 guidelines for grams of dietary fiber intake per day. The children referred to use with chronic constipation had all been instructed "to eat a high-fiber diet." Those constipated patients were consuming less than one fourth of the recommended fiber intake. CONCLUSIONS: This survey underscored the difficulties in beginning and in maintaining high-fiber diets in children. When families receive advice to administer a high-fiber diet, they are unable to accomplish this unless they receive intensive and ongoing dietary counseling. Even among health-conscious families, only half of the children received the recommended amounts of dietary fiber. Further public education in this regard is warranted.

Chronic nonspecific diarrhea: the value of a preliminary observation period to assess diet therapy.

Eighteen children with chronic, nonspecific diarrhea were evaluated prospectively to determine "basal" fat consumption and the response of their diarrhea to diets containing either 25% or 50% of total calories as fat. In the observation period, prior to initiating any alteration in dietary fat content, diarrhea subsided. Only five of the 18 patients had a low fat intake (less than 27% of total calories) at the outset of the study, and spontaneous resolution of the diarrhea precluded an assessment of the effect of altering fat intake on stool frequency. We are, therefore, impressed that a preliminary observation period, in which details of the diarrhea are documented, is essential to evaluate any treatment modality for this poorly defined condition.

Is combination therapy for encopresis nutritionally safe?

Chronic constipation accounts for 3% to 5% of pediatric primary care outpatient visits. The most severely affected of this group develop a flaccid colon insensitive to distention, and encopresis. Laxatives and lubricants have been the standard therapeutic agents during the bowel decompression phase of encopretic therapy. Fiber has been the cornerstone of maintenance programs. Each of these agents is accompanied by considerable anxiety in the lay literature. This study evaluates the safety of combined high-fiber, laxative, and lubricant therapy on bowel movement frequency, fecal soiling, and nutritional status over a 6-month period. Blood chemistry values, dietary fiber intake, defecation pattern, and psychological profile were evaluated before and after the 6-month study. Biochemical and anthropometric indicators of nutritional status were not adversely affected by the therapy. Seventy-five percent of the children were able to remain free of soiling and the remaining 4 of 16 had soiling episodes reduced to a frequency of less than once a week. This study confirms that children with encopresis can respond to a combined program of increased fiber intake, laxatives, and mineral oil following a complete bowel cleanout, without experiencing deleterious effects.

Differentiating cyclic from chronic vomiting patterns in children: quantitative criteria and diagnostic implications.

OBJECTIVE: To establish criteria to differentiate two patterns of vomiting and to identify the predominant diagnoses for each group. METHODS: All children 2 to 18 years of age referred to a pediatric gastroenterology service who presented with recurrent vomiting (three episodes of vomiting within a 3-month period) as a primary complaint from 1985 to 1991 were retrospectively reviewed (n = 106). The vomiting pattern (emeses per hour and episodes per month), diagnostic studies, and therapeutic responses were compared by Mann-Whitney U and chi-squared tests. RESULTS: Based on the criteria of peak intensity (four or more emeses per hour) and frequency (nine or fewer episodes per month), two subgroups were differentiated: chilcren with a cyclic pattern (n = 34), who vomited at a higher peak intensity (12.6 +/- 1.6 vs 1.5 +/- 0.1 emeses per hour) but at a lower frequency (1.9 +/- 4.8 vs 36.6 +/-0.3 episodes per month) than those with a chronic pattern (n = 72). Among children with a cyclic patern, nongastrointestinal (65%) causes, especially peptic and infectiouus disorders, predominated over nongastrointestinal ones (10%). CONCLUSIONS: On the basis of quantitative historical criteria, children with recurrent vomiting can be classified into two subgroups that seem to be clinically and etiologically distinct. Abdominal migraine was the dominant diagnosis in those with cyclic vomiting, whereas peptic and infectious gastrointestinal disorders predominated in those with chronic vomiting. This differentiation between cyclic and chronic patterns of vomiting may be a useful diagnostic clue to the clinician.

A new micromethod for the quantification of low molecular weight oligomers of polyethylene glycol.

We describe a gas-liquid chromatographic technique for quantifying the low molecular weight (Mr 106-634) oligomers of polyethylene glycol (PEG) in clinical specimens. The deionized sample, containing tetra-ethylene glycol as an internal standard, is applied on column. This technique readily quantifies as little as 2.5 micrograms of an individual oligomer; with such a quantity, the coefficient of variation is +/- 2.5 percent (N = 25 analyses). Small volumes (250 microliter) of urine are conveniently analyzed, and a single column can be utilized for the analysis of approximately three hundred specimens. We have analyzed timed urine specimens from humans who received 0.15 g of PEG 400 per kilogram. Individuals varied markedly with regard to the total amount of PEG excreted into the urine; each subject, however, consistently excretes a uniform percentage of the ingested dose. The urinary oligomeric profile of PEG does not vary from subject to subject nor from hour to hour, during the first six hours following oral administration, so that a random urine obtained during this period provides a reliable clinical specimen. This technique should facilitate clinical studies that utilize polyethylene glycol 400 as an index of passive intestinal transport.

Thin-layer and gel permeation chromatographic separation of low molecular weight polyethylene glycol oligomers.

We describe a gel permeation and a thin-layer chromatographic technique for the complete resolution of oligomers of ethylene glycol up to a chain length of fourteen ethylene oxide [OCH2CH2] units. We employed columns of Bio-Gel P-2 with 0.02 mol/l ammonium acetate as the eluant to prepare milligram quantities of each of the individual oligomers. Thin-layer chromatography on silica gel G plates with an ethyl acetate/methanol/water solvent provides a sensitive and simple method for monitoring multiple specimens. We determined the flame ionization detector response of purified individual ethylene glycol oligomers relative to tetraethylene glycol. These data permit the accurate quantification of the oligomeric profile of commercially available mixtures of low molecular weight polyethylene glycols (PEG). When PEG 400 is administered orally to normal subjects, aged three months through adulthood, they excrete in their urine a mixture of unmetabolized oligomers with a mean molecular weight of 360 +/- 14 daltons. The ability to measure absolute, rather than relative, amounts of ethylene glycol oligomers will permit more accurate studies of passive intestinal permeability in human subjects.

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.

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.

Intestinal metaplasia is age related in Barrett's esophagus.

The correlation among cellular characteristics of Barrett's esophagus, patient age, and malignant neoplasm is not well documented. This study, which describes a population of 66 patients with Barrett's esophagus spanning 1 to 80 years of age, analyzes the cellular constituents of their lesional tissues by endoscopic biopsy and histochemical and morphometric studies. Goblet cell metaplasia, identified in 50% (n = 14) of pediatric patients, increased significantly to involve 84% (n = 32) of biopsy specimens from adult patients with Barrett's esophagus. This increase was exponential by linear regression analysis (R2 = .64) between the ages of 5 and 29 years. Pediatric patients usually had 25 or less goblet cells per square millimeter of Barrett mucosa with no identifiable epithelial dysplasia or cancer; Nissen fundoplication lessened esophageal inflammation, but the Barrett mucosa persisted. Goblet cell metaplasia maintained a plateau (mean of 57 cells per square millimeter of Barrett mucosa) between the ages of 41 and 80 years. Dysplasia, in situ carcinoma, or invasive carcinoma was found in patients with Barrett's esophagus who were aged 41 years or older. This study demonstrates persistence of Barrett mucosa, increased incidence of goblet cell metaplasia, and predictable changes in goblet cell number with advancing patient age. The relationship between Barrett mucosa and malignant neoplasm remains uncertain, but the goblet cell may serve as a marker of disease chronicity in which setting neoplasia evolves.

Acetylthiocholinesterase staining activity of rectal mucosa. Its use in the diagnosis of Hirschsprung's disease.

Increased acetylthiocholinesterase (AchE) reactivity in the rectal lamina propria and lamina muscularis mucosae was used to diagnose Hirschsprung's disease. We processed 131 specimens with the AchE reaction; 43 were suction biopsy specimens and the rest were full-thickness specimens. Of the 68 specimens in which neurocytes were present, none demonstrated a diffuse increase in the number of nerve fibers. However, 15 showed focal increases in the numbers of fibers that were not large enough to be regarded as indicative of Hirschsprung's disease. All patients with a diffuse increase in nerve fibers, regardless of the type of biopsy, were shown to have Hirschsprung's disease. The AchE staining reaction did, however, produce a 29% rate of false-negative reactions (16 of 56 specimens) in patients with Hirschsprung's disease. These data demonstrate that an abnormal pattern of AchE reaction is diagnostic of aganglionic megacolon, whereas a normal pattern does not exclude the disease.

The Internet as a source for current patient information.

OBJECTIVE: The purpose of this study was to assess the quality of information a lay person could obtain from Internet (Net) sources regarding the treatment of childhood diarrhea. It also afforded an opportunity to evaluate the awareness and compliance of the general medical community with the American Academy of Pediatrics (AAP) guidelines on the management of acute diarrhea. METHODS: This was a prospective, open, observational, literature review performed with a computer workstation and medical library. The AAP practice parameter on the management of acute gastroenteritis in young children was selected as the current standard by which to judge all other documents. The Net was searched, and all documents retrievable from the first 300 references were evaluated for compliance with current recommendations on the management of diarrhea in children. RESULTS: Of 60 articles published by traditional medical sources, only 12 (20%) conformed to current AAP recommendations for treatment of children. The source of the information, even if from a major academic medical center, did not improve the likelihood of compliance. CONCLUSIONS: As demonstrated by information supplied on World Wide Web sites by traditional medical sources, recommendations for the treatment of acute diarrhea show a low percentage of concurrence with the AAP guidelines. Major medical institutions, schools, and hospitals need to devise ways to carefully monitor and establish quality control of what is being distributed from their home pages. Patients must be warned about the voluminous misinformation available on medical subjects on the Net.

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.

Increased tissue conductance and ion transport in guinea pig ileum after exposure to Staphylococcus aureus delta-toxin in vitro.

Prior studies had shown that Staphylococcus aureus delta-toxin was able to inhibit water absorption in guinea pig ileum and to elevate the cyclic AMP content of this tissue, but was unable to elicit certain cyclic AMP-mediated changes in Y-1 adrenal or Chinese hamster ovary cells. Because water movement passively follows the net movement of electrolytes in the gut, this study investigated the effect of delta-toxin on ion transport in guinea pig ileum maintained in vitro. The transmural potential difference (PD) of guinea pig ileum was measured and nullified with an automatic voltage clamp. The short circuit flowing under these conditions (I(sc)) was measured, and the conductance was calculated (I(sc)/PD). Unidirectional (22)Na(+) and (36)Cl(-) fluxes were measured. In a glucose-free Ringer solution, delta-toxin caused an immediate spike in PD and I(sc), and the extent and duration of the spike generally increased with increasing toxin concentration. The conductance of ileum was increased by delta-toxin, and this effect on conductance could be blocked by lecithin, a known inhibitor of delta-toxin. Tissue in the presence of glucose did not exhibit a spike in PD or I(sc) when exposed to delta-toxin. In a glucose-free medium, delta-toxin caused a 1.5- to 2.5-fold increase in both the unidirectional absorption and secretion of Na(+) and Cl(-), whereas the net secretion of Na(+) increased above basal levels. The observation that delta-toxin causes a prompt increase in intestinal ion flux lends credence to the concept that the elevation in cellular cyclic AMP, which occurs later, is a secondary response to the toxin. The rapid increase in ion flux may reflect the ability of delta-toxin to augment intercellular movement of ions across the mucosa rather than the stimulation of transcellular processes.

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.

Efficient storage system for breath hydrogen.

Recommended materials for breath hydrogen collection (plastic syringes with twist lock closure) are only adequate for relatively brief periods because of gradual hydrogen loss and considerable variability between duplicate samples. To document the most favorable storage conditions for breath hydrogen, we compared hydrogen retention in plastic syringes using a conventional twist-in-lock closure versus a simple, inexpensive syringe closure, a Critocap. Hydrogen retention was studied at 25, 5, and -20 degrees C in two different syringe brands over 72 h of storage. An analysis of variance confirms the superiority of Critocaps over twist-in-lock closures (p less than 0.001). Reliability was maximal when samples were placed in environments less than 5 degrees C. When storage time was extended to 7 days, mean hydrogen retention was 86 +/- 6% (means +/- SD).

The jejunal absorption of glucose oligomers in the absence of pancreatic enzymes.

We compared the absorption of carbohydrate from solutions of glucose oligomers and glucose in jejunal Thiry-Vella fistulae, a preparation deprived of pancreatic secretions. The studies were performed with two concentrations (90 and 360 mg/dl) of both glucose and the glucose oligomers. Carbohydrate absorption from glucose solutions (33.1 +/- 2.8, 115.9 +/- 8.9 micrograms/cm/min) was significantly greater (P less than 0.025; P less than 0.005) than that from oligomer solutions (26.6 +/- 2.1 and 92.4 +/- 9.0 micrograms/cm/min). Thin-layer analyses of the perfusates demonstrate digestion of oligomers with a chain length up to eleven and suggest digestion of oligomers of even greater chain length. Atrophy of the jejunal mucosa occurred over the course of the study as evidenced by a decrease in the ratio of villous height to crypt depth from 3.8 to 0.3, and by a 80% decrease in the activity of maltase, sucrase, and lactase. Atrophy was accompanied by a significant decline in the absorption of both glucose oligomers (P less than 0.005) and glucose (P less than 0.01) from the more concentrated solutions but the decrement in absorption of both carbohydrates was similar: glucose oligomers, 79.3 +/- 19.4 micrograms/cm/min; and glucose, 69.8 +/- 14 micrograms/cm/min (P greater than 0.20). Water absorption was enhanced by both carbohydrates, but there was no demonstrable difference between solutions of glucose and glucose oligomers. The osmolality of the solutions clearly influenced water absorption (P less than 0.025) but failed to effect the absorption of carbohydrates.