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Biomedical subjects

O Simell

Publications and source records attributed to O Simell.

At least 199 records · Page 11Linked to original sources
PubMed1985

Gyrate atrophy of the choroid and retina. A five-year follow-up of creatine supplementation.

Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration with a 10-20-fold elevation of plasma ornithine due to deficient activity of ornithine aminotransferase. Type II fibres of the skeletal muscle are atrophic and contain tubular aggregates in electron microscopy. Deficient creatine and creatine phosphate formation have been postulated to be involved in the pathogenesis of GA. The five-year follow-up results of oral creatine supplementation in 13 patients are presented. Visual function tests and fundus photographs showed progression of GA during the treatment. The velocity of the progression varied considerably between individuals. Generally, the progression was rapid in the young patients and slow in the more advanced stages. Abnormalities in the skeletal muscle decreased or disappeared rapidly. They reappeared in the few patients who discontinued the medication. The difference in the therapeutic effect on the skeletal muscle and eye is discussed.

Adolescent↗
PubMed1985

Chronic non-specific diarrhoea.

Recurrent, unexplained diarrhoea is the most common intestinal complaint in children aged 6 months to 3 years. We studied 27 consecutive children with this complaint and followed them up until the age of 5 years. Diarrhoea began at the mean age of 9 months (range 4 to 16 months) and resolved in 21 children by 3 years of age. Twelve children had had infantile colic earlier. In six patients diarrhoea was caused by food allergy (cows' milk allergy and allergy to fresh vegetables). Episodes of diarrhoea persisted in four of these six. Twenty one children had unexplained diarrhoea: this resolved in 19. Nutritional deficiencies were rare; only one child had iron deficiency. Relative weights of the children were significantly lower at 2 years than at 1 year of age. At 5 years of age six of the children continued to have episodes of diarrhoea, and abdominal pains, headaches, and atopy occurred more commonly than in the general population. We suggest that there are two major subgroups among children with recurrent diarrhoea--children with food allergy and those who react to environmental stresses with a variety of somatic symptoms.

Chronic Disease↗
PubMed1985

Ornithine loading did not prevent induced hyperammonemia in a patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

Impairment of urea cycle function in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is presumably caused, in some patients, by deficient transport of ornithine from cytoplasm into mitochondria. We studied the effect of L-ornithine on L-alanine-induced hyperammonemia in a French-Canadian proband with the syndrome by giving: a 90-min intravenous alanine load (6.6 mmol/kg) together with ornithine (1.1 mmol/kg); an intravenous ornithine bolus (0.3 mmol/kg) followed by ornithine infusion (1.1 mmol/kg) 90 min prior to loading with alanine and ornithine; ornithine supplementation per os (1 g, four times daily X 2 wk) prior to loading with alanine and ornithine. Blood ammonia increased from high normal values to 975, 990, and 750 mumol/liter (normal less than 70) and urinary orotic acid from trace to 539, 494, and 1296 mumol/mmol creatinine (normal 5-11) after the respective loads. Plasma alanine peaked at 1.56-4.24 mmol/liter and ornithine at 1.29-1.95 mmol/liter, but other amino acids were stable. Therefore, ornithine loading did not protect this hyperornithinemia-hyperammonemia-homocitrullinuria patient from hyperammonemia induced by amino-nitrogen loading. Renal fraction excretion of citrulline, lysine, ornithine, glycine, alanine, and tyrosine increased more than 3-fold during ornithine priming, whereas all amino acids were excreted in excess after alanine + ornithine loads; homocitrulline excretion remained unchanged; some urine collections indicated "negative reabsorption" (i.e. apparent secretion) of lysine, histidine, and citrulline. Dietary supplementation with ornithine could deplete lysine pools by impairing lysine reabsorption.

Alanine↗
PubMed1985

Methionine in paracetamol tablets, a tool to reduce paracetamol toxicity.

The analgesic effect, toxicity and kinetics of oral paracetamol were compared with those of paracetamol + l-methionine (5:1). The analgesic effect of paracetamol, studied in the Randall-Selitto test in rats, was not changed by methionine: ED50 was 94.6 mg/kg without methionine and 94.1 mg/kg with it. However, methionine reduced the acute toxicity (LD50) of paracetamol by 50% (p less than 0.05) in non-fasted, fasted and phenobarbital-pretreated mice. In a randomized cross-over study in 10 human volunteers the pharmacokinetics of paracetamol (1,500 mg) was not affected by methionine (300 mg). The absorption of methionine from the combination tablets was rapid, peak concentrations occurred in plasma at 30 min and were 3-4 times higher than after paracetamol tablets not containing methionine. Methionine in products containing paracetamol should increase their safety and be the simplest way to reduce the high mortality in paracetamol overdosage.

Acetaminophen↗
PubMed1984

Serum and hair zinc as predictors of clinical symptoms in acrodermatitis enteropathica.

Hair- and serum-zinc concentrations were measured in six patients with acrodermatitis enteropathica before and sequentially after cessation of zinc supplementation; supplementation was restarted when symptoms appeared. Serum zinc correlated accurately with zinc dosage and was lowest when symptoms of deficiency appeared. Hair zinc was initially age- and body size-related and was minimally influenced by the supplementation break. Adult patients had continuously normal concentrations. In paediatric patients hair zinc was low. Their serum concentrations should probably be maintained slightly above or at the upper limit of reference values for prolonged periods for normalization of hair and perhaps tissue zinc contents.

Acrodermatitis↗
PubMed1984

Human milk protein and medium-chain triglyceride oil supplementation of human milk: plasma amino acids in very low-birth-weight infants.

Fifty-one very low-birth-weight infants (birth weight less than 1,520 g) randomly fed either human milk or human milk supplemented with human milk protein and/or with medium-chain triglyceride (MCT) oil were observed. Plasma amino acids from these infants were studied at 2, 8, and 10 weeks. Medium-chain triglyceride oil supplementation had minimal or no influence on plasma amino acids. Human milk protein supplementation resulted in increased concentrations of all amino acids at all ages studied. The concentrations were 1.5- to threefold as compared with values in infants not given protein supplements. However, the concentrations of methionine, tyrosine, phenylalanine, and lysine remained far below values considered harmful. The age at which maximal plasma amino acid concentrations in infants given human milk protein supplementation occur coincides with the age of the lowest serum albumin concentrations in infants fed only human milk. This suggests that high plasma amino acid concentrations may hasten albumin synthesis in very low-birth-weight infants.

Amino Acids↗
PubMed1983

Oral administration of urea cycle intermediates in lysinuric protein intolerance: effect on plasma and urinary arginine and ornithine.

In lysinuric protein intolerance, an autosomal recessive disorder of amino acid transport, oral citrulline increases the plasma concentration of urea cycle intermediates more than does oral arginine or ornithine. The clinical improvement suggests that citrulline affords the best means of correcting the ornithinopenic malfunction of the urea cycle.

Administration, Oral↗
PubMed1983

Nitrogen utilization during postoperative, low nitrogen, high caloric parenteral nutrition.

Twenty elderly patients having undergone colonic resection were randomized into two regimens of postoperative parenteral nutrition. Fructoglucose satisfied the basal caloric needs of the patients. Amino acids were given as a mixture that provided 0.11 (0.09-0.14; mean and range) g/kg/day of nitrogen only. In half of the patients the energy intake was doubled with fat emulsion. The mean nitrogen-energy ratios in grams of nitrogen/kcal/day were 1:201 and 1:336 in the two groups, respectively. Both regimens were given for three days, starting from the first postoperative day. On the first day, the mean nitrogen balance was negative in both groups. On the third day, the mean balance was slightly positive in the amino acid, fructoglucose plus fat emulsion group, but negative in amino acid plus fructoglucose group. Amino acid concentrations in plasma and urine were markedly elevated in both groups, but relative concentrations in plasma remained rather normal. Apparently, a positive postoperative nitrogen balance can be obtained with restricted amino acid supply, if energy is provided in abundance.

Journal Article↗
PubMed1983

Oral administration of epsilon N-acetyllysine and homocitrulline in lysinuric protein intolerance.

The defect of epithelial diamino acid transport in lysinuric protein intolerance (LPI) results from an abnormality of the basolateral cell membranes. Therefore the lysine deficiency, which is one of the consequences of this defect, cannot be corrected by oral administration of lysine, either in free or peptide form. In search of useful lysine derivatives, we studied in patients with LPI the absorption after oral administration of homocitrulline and epsilon N-acetyllysine. Acetyllysine, but not homocitrulline, normalized the subnormal plasma lysine concentrations.

Administration, Oral↗
PubMed1983

"Basolateral" and mitochondrial membrane transport defect in the hepatocytes in lysinuric protein intolerance.

In lysinuric protein intolerance, diamino acid transport is defective at the basolateral membrane of the jejunal and renotubular epithelia. The plasma has depressed concentrations of ornithine and arginine but, in contrast, supranormal levels of another urea cycle intermediate, citrulline. The patients have "ornithinopenic" postprandial hyperammonemia. The concentrations of the diamino acids and citrulline in the patients' liver were normal or elevated rather than depressed. Their extrarenal plasma clearance of citrulline and its conversion to arginine and ornithine were retarded. A hypothesis reconciles these apparently conflicting findings: in the hepatocytes the transport defect is located in the "basolateral" cell membrane and in the mitochondrial membranes. The diamino acids accumulate in the cytoplasm, because exit from the cells and transport into the mitochondria are impaired, but these acids are depleted in the mitochondria, where ornithine is needed in the urea cycle. As a result, the urea cycle is reversed at this point, producing citrulline.

Adolescent↗
PubMed1983

Plasma amino acids after a feed of human milk or formula at three months of age.

Prefeeding plasma amino acid concentrations were higher and glycine-to-valine ratios lower in formula-fed infants as compared to breast-fed infants at 3 months of age. After a human milk meal (true protein, 0.8 g/100 ml) or formula meal (1.5 g/100 ml), all essential and several nonessential amino acids peaked at 30-60 min. The postprandial increments were greater and lasted longer after formula, reflecting the amounts of individual amino acids in the feeds. The changes resembled those seen in adults, and were smaller than those observed in these infants at 1 week of age. These data indicate that gastrointestinal, hepatic, and endocrine responses to a meal are immature at the age of 3 months.

Amino Acids↗
PubMed1982

Plasma amino acids in preterm infants after a feed of human milk or formula.

Prefeeding and sequential postprandial plasma amino acid concentrations were measured in 31 healthy preterm infants with gestational ages between 33 and 37 weeks at the ages of 4 to 12 days, to characterize changes after quantitatively and qualitatively different protein loads. All infants had previously been fed with human milk. The infants received a normal feed of pooled human milk (true protein 0.8 gm/dl) or of adapted or nonadapted milk formula (protein 1.5 gm/dl) from a bottle. The concentrations of all essential and several nonessential amino acids, including arginine and ornithine, rose sharply in plasma. Glycine decreased, and alanine increased slowly. Postprandial alterations in plasma total amino acids seemed to reflect the protein content of the different milks. In preterm infants, fed at three- to four-hour intervals, plasma amino acid concentrations fluctuate continuously. Thus in long-term studies and in screening, samples should be taken immediately before feeds. Postprandial plasma amino acid measurements may prove to be a useful means for testing the infant's ability to handle the protein or individual amino acid loads in various feeds.

Amino Acids↗
PubMed1982

Plasma amino acids in term neonates after a feed of human milk or formula. II. Characteristic changes in individual amino acids.

Postprandial changes in plasma amino acids were studied in 23 term neonates who had previously been breast-fed ad libitum. As a test meal the infants received from a bottle a weight-based amount of banked human milk (true protein 0.8 g/100 ml) or formula with either 1.5 or 3.0 g of protein (adapted or non-adapted) per 100 ml. As regards the essential amino acids, all rose markedly in the plasma after the feed. The postprandial increments were relatively highest for the branched-chain amino acids, which rose 50-300% above the prefeeding concentrations. Peak values were found after human milk at 30 min but after formulas at 60 min. In extent and duration the rises were directly proportional to the amino acid loads given. This was also true for most semi- and non-essential amino acids, but plasma glycine, in contrast, regularly decreased, and plasma alanine continued to rise until 120 min after the beginning of the feed; neither change correlated with intake. After the milk feeds commonly given to neonates, postprandial alterations in plasma amino acids seem to be highly predictable.

Amino Acids↗
PubMed1981

Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina is a disease characterized by progressive constriction of visual fields, a 10-fold to 20-fold elevation in plasma ornithine, and depressed activity of L-ornithine:2 oxoacid aminotransferase. Morphologically conspicuous but clinically unimportant atrophy of Type II muscle fibers progresses concomitantly with the eye disease. A pathogenic component of the disease may be deficient formation of creatine, caused by hyperornithinemia, which leads to a shortage of cellular phosphocreatine energy stores. To test the therapeutic value of replenishing the postulated deficiency of creatine, we supplemented the diet of seven patients with 1.5 g of creatine daily. During one year of this treatment the diameters of Type II muscle fibers increased from 34.1 +/- 7.1 to 49.9 +/- 7.0 micron (mean +/- S.D.) (P less than 0.001). There was no significant increase in the diameters of Type I fibers. The visual-field tests showed no further constriction during the therapy. Fundus photography revealed slow impairment at an age otherwise associated with rapid progression of the disease. These promising preliminary results need further evaluation with long-term follow-up studies.

Administration, Oral↗
PubMed1981

Plasma conjugated cholic acid in premature and term newborns and young infants.

Bile acid handling by neonates, both premature (Group I, mean gestational age 34.3 weeks; Group II, 36.6 weeks) and full-term (Group III, 40.2 weeks) and by 3-month-old infants (Group IV) was assessed by measuring plasma concentrations of conjugated cholic acid (CCA) before and at successive intervals after feeds. The prefeeding CCA concentrations were highest in Group I (log mean 8.2; range 1.8--28.6 mumol/l) and lower in Groups II (7.5; 2.6--22.4 mumol/l), III (5.1; 2.1--11.1 mumol/L), and IV (2.2; 0.5--6.1 mumol/l). The mean postprandial increments correlated with maturity: the rises for Groups I--IV were 3.7, 4.3, 1.0 and 0.7 mumol/l, respectively. Peak values were consistently reached at 30 min after the start of the feed, i.e. strikingly earlier than in older children and adults. After the peaks the return to prefeeding levels occurred rapidly in Groups II--Iv but more slowly in the most premature infants (Group I). The rapid postprandial rise may be due to many factors, e.g., passive jejunal absorption, immature hepatic clearing mechanisms, or rapid transit of bile acids to the ileum. Hence, measurements of postprandial plasma bile acids would appear ill-suited for detection of disturbed ileal function in young infants. The high concentrations in healthy newborns suggest that caution is necessary in interpreting plasma bile acid concentrations during the first few weeks of life, especially in premature infants.

Cholic Acids↗