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Biomedical subjects

R J Merritt

Publications and source records attributed to R J Merritt.

At least 19 recordsLinked to original sources

Repeated dose study of sucralose tolerance in human subjects.

Two tolerance studies were conducted in healthy human adult volunteers. The first study was an ascending dose study conducted in eight subjects, in which sucralose was administered at doses of 1, 2. 5, 5 and 10mg/kg at 48-hour intervals and followed by daily dosing at 2mg/kg for 3 days and 5mg/kg for 4 days. In the second study, subjects consumed either sucralose (n=77) or fructose (50g/day) (n=31) twice daily in single blind fashion. Sucralose dosage levels were 125mg/day for weeks 1-3, 250mg/day during weeks 4-7, and 500mg/day during weeks 8-12. No adverse experiences or clinically detectable effects were attributable to sucralose in either study. Similarly, haematology, serum biochemistry, urinalysis and EKG tracings were unaffected by sucralose administration. In the 13-week study, serial slit lamp ophthalmologic examination performed in a random subset of the study groups revealed no changes. Fasting and 2-hour post-dosing blood sucralose concentrations obtained daily during week 12 of the study revealed no rising trend for blood sucralose. Sucralose was well tolerated by human volunteers in single doses up to 10mg/kg/day and repeated doses increasing to 5mg/kg/day for 13 weeks. Based on these studies and the extensive animal safety database, there is no indication that adverse effects on human health would occur from frequent or long-term exposure to sucralose at the maximum anticipated levels of intake.

Administration, Oral↗

Biennial survey of clinical nutrition training programs.

Three posttraining program surveys have been done by The American Society for Clinical Nutrition Committee on Subspecialty Training to evaluate the status of training programs in clinical nutrition. This survey updates demographic data about programs and determines which classes are offered or required as a part of basic nutrition-science requirements for nutrition training programs. In addition, the importance of board certification and accreditation of training programs is examined.

Certification↗

Whey protein hydrolysate formula for infants with gastrointestinal intolerance to cow milk and soy protein in infant formulas.

Twenty-one infants less than 6 months of age with gastrointestinal symptoms of cow milk and/or soy protein-based infant formula intolerance (diarrhea in 14, hematochezia in 16, emesis in 8, failure to thrive in 4, and colic in 10) were treated clinically with a whey protein hydrolysate formula. Six patients improved when placed directly on the formula, and 15 remained asymptomatic or improved when given the whey hydrolysate formula following initial treatment with a casein hydrolysate or elemental formula. Eighteen had supporting evidence of an allergic basis for their symptoms, including a family history of allergies in 6, a clinical challenge with the offending formula in 1, laboratory tests consistent with atopy in 11, and/or rectal biopsy with histologic allergic features in 7. The whey hydrolysate formula may be an acceptable alternative to soy or casein hydrolysate formulas in most infants with gastrointestinal symptoms of cow milk and/or formula intolerance.

Food Hypersensitivity↗

Capillary plasma ammonia concentration in neonates receiving total parenteral nutrition. Comparison with arterial and venous concentrations.

Plasma ammonia concentration in neonates has routinely been determined using arterial or venous blood. Expected plasma ammonia values in capillary blood obtained by heelstick have not been determined. We compared ammonia levels in 20 sets of plasma from simultaneously drawn arterial, venous, and capillary blood in a group of neonates receiving total parenteral nutrition. Mean ammonia concentrations in venous (107 +/- 44) and capillary blood (112 +/- 33) were 45% and 51% higher, respectively, than corresponding arterial (74 +/- 22) values (P less than .001). Ammonia levels in blood obtained by venipuncture (Ven), however, did not correlate consistently with arterial (Art) values (r = .43; Art = 51 + 0.21 Ven; P greater than .05). In contrast, ammonia levels in capillary blood (Cap) correlated well with arterial values (r = .86; Art = 10.3 + 0.6Cap; P less than .001). Ammonia levels in neonates may be reliably interpreted using the latter regression equation when blood for analysis is obtained by a properly performed heelstick, allowing the preservation of arteries and veins, and sparing the infant from repetitive needle punctures. Ammonia levels in blood obtained by venipuncture do not adequately correlate with arterial values and therefore may be therapeutically misleading.

Ammonia↗

A subacute rabbit model for hepatobiliary dysfunction during total parenteral nutrition.

Total parenteral nutrition (TPN) in children is associated with the complicating syndromes of cholestasis and cholelithiasis. The causes of these syndromes are not completely clear. Gastrointestinal hypomotility associated with enteral fasting may be involved in the pathogenesis of both syndromes. We compared weanling rabbits maintained solely on TPN with chow pair-fed and free-fed controls over a 10-day period. Gastrointestinal transit time, assessed with a solid marker technique, was significantly greater in the TPN-treated animals. No difference in intestinal or biliary bacterial flora was demonstrated by aerobic or anaerobic cultures. Gallbladder bile contained a higher percentage of lithocholic acid, unconjugated bilirubin, and total calcium in the TPN-treated animals. Markers of hepatic dysfunction were elevated in the serum of the TPN-treated animals. Mild steatosis and edema were the only histologic differences in the livers of the TPN-treated animals. We conclude that gastrointestinal hypomotility associated with enteral fasting plays a role in the pathophysiologic changes leading to TPN-associated hepatobiliary dysfunction. This dysfunction may be mediated by an increase in the absolute and relative concentrations of lithocholic acid in the bile of TPN-treated animals.

Animals↗

Atropine therapy and paralytic ileus in an infant.

Signs of intestinal obstruction developed in a 2-month-old infant with trisomy 21 during atropine therapy. Radiographic evaluation strongly suggested Hirschsprung's disease, but rectal biopsy yielded normal histologic results. Following cessation of atropine use, the symptoms resolved completely. This case report demonstrates the association between atropine therapy and intestinal ileus. Caution is advised when using topical atropine therapy in children, especially those with Down's syndrome.

Administration, Topical↗

An unusual case presentation: pericardial tamponade complicating central venous catheter.

The use of central venous catheters in very low birthweight infants to provide adequate calories for growth is an integral part of the care of the high-risk neonate. The use of surgically placed Broviac catheters has been associated with infectious and mechanical complications. Recently, there has been increasing use of silastic central venous catheters inserted through a peripheral vein and advanced to the right atrium. These catheters have a reported low rate of complications. However, we report a case of a very low birthweight infant in whom a peripherally inserted silastic catheter perforated the wall of the right atrial appendage and led to fatal pericardial tamponade. This is a very rare but nearly always fatal complication. It is potentially avoidable by careful placement of the tip of the central venous catheter, so that it is not impinging on a wall of the heart. Serial venograms may be useful to reconfirm the position of the catheter.

Cardiac Tamponade↗

Biennial survey of physician clinical nutrition training programs.

This is the third survey of physician clinical nutrition training programs. Current training programs were identified, descriptive information obtained, and training program content was compared with that recommended at the 1984 Conference on Clinical Nutrition Training. In general, goals as to the quantity of research, clinical, and teaching training are being met. Virtually all programs provide training in nutritional support activities. Most training programs are not as broad in scope of exposure to the less clinical aspects of nutrition nor to all the illness and age groups recommended by the 1984 conference. Consideration of broadening the scope of physician training programs or redefinition of training guidelines is warranted. A program-certifying agency may be helpful in identifying programs achieving certain minimal standards.

Curriculum↗

Growth failure in infants with bronchopulmonary dysplasia: nutrition and elevated resting metabolic expenditure.

The mechanisms underlying growth failure in infants with bronchopulmonary dysplasia are poorly understood. Thirteen infants with bronchopulmonary dysplasia at 6 months of corrected age and 12 full-term healthy control infants matched for age or size were studied. Resting oxygen consumption was measured during natural sleep, and an estimation of the resting metabolic expenditure by indirect calorimetry was performed. Growth parameters were measured, and a nutritional profile including dietary intake, stool analysis, and serum albumin, cholesterol, glucose, and prealbumin was obtained. Seven of the 13 infants with bronchopulmonary dysplasia had growth failure (defined as length and weight less than the tenth percentile of the Babson growth curves). These infants had lower birth weight, lower gestational age, and a greater number of days spent in supplemental oxygen or on mechanical ventilation. There was no statistical difference between the bronchopulmonary dysplasia-growth failure and bronchopulmonary dysplasia-normal growth infants for dietary intake or stool or serum analyses. However, serum prealbumin showed a significant linear correlation with body weight in infants with bronchopulmonary dysplasia. Resting metabolic expenditure was elevated in infants with bronchopulmonary dysplasia with growth failure and was inversely correlated with body weight in all infants with bronchopulmonary dysplasia. Thus, infants with bronchopulmonary dysplasia and growth failure have increased metabolic demands and decreased prealbumin values suggesting a relative state of protein-calorie malnutrition.

Bronchopulmonary Dysplasia↗

Observations of vitamin A toxicity in three patients with renal failure receiving parenteral alimentation.

Elevated serum retinol concentrations have been previously reported in patients with renal failure, although overt clinical toxicity has been described only rarely. We present three patients with renal failure receiving total parenteral nutrition (TPN) who developed biochemical and clinical findings of hypervitaminosis A. Improvement followed deletion of vitamin A from the TPN. These cases demonstrate that patients with renal failure may be at risk for symptomatic vitamin A toxicity if given TPN with standard retinol supplementation. Such patients should be carefully observed clinically and biochemically if supplementation is given.

Adolescent↗

Cholestasis associated with total parenteral nutrition.

It appears that neonates, especially those with very low birthweights, may be at especially high risk of developing cholestasis associated with total parenteral nutrition (TPN). Within 2 weeks of starting intravenous alimentation, it would appear highly desirable to be able to start at least small enteral feedings to interrupt the physiology of fasting. Such feedings may not have to be of much nutritional benefit to improve cholestasis. Calorie and amino acid intake should be limited to the requirements of the infant being treated. Whether protection of the TPN infusate from light is of benefit remains to be determined. Drug therapies for TPN-associated cholestasis of infancy have not been proven safe or effective. Additional investigations to further clarify the pathogenesis of this syndrome, and clinical studies of prophylaxis and therapy, are needed to enhance our ability to provide nutritionally effective and metabolically safe parenteral nutrition.

Amino Acids↗

Corticosteroid therapy-induced obesity in children.

The severity and persistence of corticosteroid-induced obesity were evaluated retrospectively in 23 children aged 1-14 yrs requiring more than 60 days of therapy with prednisone for idiopathic nephrotic syndrome. Mean relative weight (after clearing of proteinuria) at initiation of therapy was 107 +/- 10 percent. Peak relative weight on therapy was 119 +/- 15 percent following a mean total of 31 months of cumulative steroid therapy. The most recent available relative weight in remission at least 6 months following cessation of therapy was 107 +/- 18 percent. The number of children whose relative weight exceeded 120 percent at initiation of, during and following therapy was 3, 10, and 4, respectively. In those with normal initial relative weight (less than 110%) there was no persistent obesity. Two of three initially obese patients (relative weight greater than 120%) remained obese. All patients with persistent obesity following therapy had initial relative weight of at least 110 percent and peak relative weight of more than 130 percent. The risk of persistent obesity as a result of chronic corticosteroid therapy in initially normal weight children who do not exceed 130 percent relative weight during therapy appears to be small.

Adolescent↗

Evidence of aluminum loading in infants receiving intravenous therapy.

To investigate the possibility that premature infants may be vulnerable to aluminum toxicity acquired through intravenous feeding, we prospectively studied plasma and urinary aluminum concentrations in 18 premature infants receiving intravenous therapy and in 8 term infants receiving no intravenous therapy. We also measured bone aluminum concentrations in autopsy specimens from 23 infants, including 6 who had received at least three weeks of intravenous therapy. Premature infants who received intravenous therapy had high plasma and urinary aluminum concentrations, as compared with normal controls: plasma aluminum, 36.78 +/- 45.30 vs. 5.17 +/- 3.1 micrograms per liter (mean +/- S.D., P less than 0.0001); urinary aluminum:creatinine ratio, 5.4 +/- 4.6 vs. 0.64 +/- 0.75 (P less than 0.01). The bone aluminum concentration was 10 times higher in infants who had received at least three weeks of intravenous therapy than in those who had received limited intravenous therapy: 20.16 +/- 13.4 vs. 1.98 +/- 1.44 mg per kilogram of dry weight (P less than 0.0001). Creatinine clearances corrected for weight did not reach expected adult values until 34 weeks of gestation. Many commonly used intravenous solutions are found to be highly contaminated with aluminum. We conclude that infants receiving intravenous therapy have aluminum loading, which is reflected in increased urinary excretion and elevated concentrations in plasma and bone. Such infants may be at high risk for aluminum intoxication secondary to increased parenteral exposure and poor renal clearance.

Aluminum↗

Treatment of protracted diarrhea of infancy.

Ten patients with protracted diarrhea of infancy received either 8% or 16% of 130 calories/kg/day as amino acids. Patients were treated initially with total parenteral nutrition (TPN) and subsequently with an elemental diet. Nitrogen balance was better during TPN in those who received the higher amino acid intake. No differences were noted between groups in weight gain or restoration of muscle mass. Higher levels of serum urea nitrogen and alkaline phosphatase were noted in patients with the higher amino acid intake; cholestatic liver injury developed in two of these patients. The patients receiving the higher amount of amino acid demonstrated enhanced calciuria during TPN. Other than better nitrogen balance, no clinical benefits and more undesirable side effects were observed in patients receiving 16% amino acid calories.

Alkaline Phosphatase↗

Cholestatic effect of intraperitoneal administration of tryptophan to suckling rat pups.

The potential cholestatic effect of amino acids and metabolites of tryptophan were evaluated by use of seven daily intraperitoneal injections to suckling and weanling rat pups. Of the amino acids present in parenteral nutrition solutions, only tryptophan (given at a dose of 4 mM/kg) produced a significant (p less than 0.01) elevation of serum cholylglycine (12.8 +/- 1.0 microM/liter) as determined by radioimmunoassay, compared to 4.9 +/- 0.4 microM/liter in saline-treated control animals. Total serum conjugates of cholic acid, as determined by radioimmunoassay, were similarly elevated, as was serum alanine aminotransferase. Tryptophan injection resulted in elevated cholylglycine concentrations only at doses of 3 mM/kg/day or higher. Animals more than 2 weeks old did not demonstrate elevation of serum cholylglycine. Injection of light-exposed tryptophan in suckling animals caused a greater elevation of cholylglycine (39.0 +/- 8.6 microM/liter) than freshly prepared tryptophan solutions (p less than 0.005). Tryptophan and its spontaneous degradation products could contribute to the cholestatic liver changes observed during parenteral nutrition therapy.

Alanine Transaminase↗