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Biomedical subjects

M K Salo

Publications and source records attributed to M K Salo.

At least 19 recordsLinked to original sources
PubMed2003

Investigation of the mechanisms of therapy-related hypoglycaemia in children with acute lymphoblastic leukaemia.

AIM: To determine the mechanisms of fasting hypoglycaemia occurring during maintenance therapy (MT) for childhood acute lymphoblastic leukaemia (ALL). METHODS: Thirty-five children and adolescents with ALL, aged 2.4-17.4 y, were fasted for up to 16 h during MT. Nineteen of the children developed hypoglycaemia after 11 to 16 h of fasting. Blood samples for determination of metabolic changes were taken on completion of fasting. Nineteen patients underwent a glucagon stimulation test after 4 to 16 h of fasting during MT. Erythrocyte concentrations of the metabolites of methotrexate (E-MTX) and 6-mercaptopurine (E-TGN) were measured at the time of fasting. Fifteen out of 19 patients who became hypoglycaemic were re-studied 3 to 4 mo after cessation of therapy. RESULTS: In the hypoglycaemia group, plasma levels of gluconeogenic amino acids alanine and glutamine were lower (medians 117 vs 190 micromol L(-1), p = 0.009, and medians 396 vs 448 micromol L(-1), p = 0.031, respectively) than in the normoglycaemia group. Serum levels of free carnitine were lower (medians 20.3 vs 29.8 micromol L(-1), p = 0.027), free fatty acids higher (medians 3.09 vs 1.23 mmol L(-1), p < 0.001) and marked dicarboxylic aciduria was more common in the patients with hypoglycaemia (in 14/16 vs in 2/14, p < 0.001). Impaired responses to glucagon stimulation occurred in 36% (4/11) in the hypoglycaemia group and in 12.5% (1/8) in the normoglycaemia group (p = 0.243). No significant differences were detected in E-MTX and E-TGN between the groups. Most of the metabolic abnormalities returned to normal after cessation of chemotherapy. CONCLUSIONS: Low levels of gluconeogenic amino acids, especially of alanine, are associated with hypoglycaemia. Reduced hepatic glycogen stores may also be involved in the aetiology.

Adolescent↗
PubMed2001

Fasting hypoglycemia is common during maintenance therapy for childhood acute lymphoblastic leukemia.

Nineteen of 35 children (54%) with acute lymphoblastic leukemia receiving maintenance therapy consisting of daily oral 6-mercaptopurine and weekly oral methotrexate developed hypoglycemia (blood glucose level <2.7 mmol/L [50 mg/dL] or <2.9 mmol/L [54 mg/dL] with symptoms) during 16 hours of overnight fasting. In 15 of 15 re-studied children, fasting tolerance had improved, and in 67% (10/15), it had become normal a few months after cessation of therapy.

Adolescent↗
PubMed2000

Under recognition of late onset ornithine transcarbamylase deficiency.

Late onset ornithine transcarbamylase deficiency (McKusick 311250) is reported in four Finnish patients, two boys and two heterozygous girls. The subtle onset and course of ornithine transcarbamylase deficiency emphasises the need for plasma ammonia and amino acid measurements in clinical situations suggesting a disorder of this nature.

Age of Onset↗
PubMed2000

Hereditary tyrosinaemia type I: from basics to progress in treatment.

Hereditary tyrosinaemia type I is the most common of the diseases caused by defects in tyrosine metabolism. The underlying genetic defect is a mutation in the gene for fumarylacetate hydrolase (FAH), and more than 30 different mutations in this gene have been identified. The main clinical consequences of this defect include hepatic involvement, with a high risk for liver cancer, and renal tubular dysfunction. Restriction of phenylalanine and tyrosine from the diet along with supportive measures can ameliorate the symptoms, but cure has so far been possible only with liver transplantation. Recent discovery of a pharmacological treatment with a peroral inhibitor of tyrosine catabolic pathway, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), offers a new promising tool for the treatment of patients with hereditary tyrosinaemia type I. Mouse models of FAH deficiency have been successfully used in experimental gene therapy, and these studies indicate that future management of tyrosinaemia with a gene therapeutic approach may become feasible.

Animals↗
PubMed1999

Fatty acids in substitute formulas for cow's milk allergy.

BACKGROUND: The role of dietary fats in food-related allergic symptoms is increasingly being investigated, since the pivotal role of fat-derived inflammatory substances, e.g., leukotrienes, has been realized. The objective of this study was to describe the fatty acid composition of several commercially available infant formulas that are used as substitutes for adapted cow's milk formulas. METHODS: Samples of nine formulas (two soy, two extensively hydrolyzed casein, three extensively hydrolyzed whey, and two amino-acid-based formulas) and human milk as control were analyzed by gas chromatography. RESULTS: The quantity of fatty acids in the formulas was within the breast-milk range. The percentage of energy derived from fat was below the European Society for Pediatric Gastroenterology and Nutrition recommendations in two cases, but, in the others, it roughly met the recommendations. The percentage of energy derived from linoleic acid was as recommended in all but two cases, where it was higher than recommended. As indicated by a quality indicator, the linoleic to alpha-linolenic acid ratio, altogether four formulas were within either the recommendations or the analyzed breast-milk range. In three cases, it was 1.5-2.5 and in two cases 4-5 times higher than recommended. CONCLUSIONS: There are recommendations for infant formulas to meet nutritional requirements of fat intake, and the analyzed formulas are in most cases within the suggested ranges. However, little is known of requirements in allergic or inflammatory conditions, and whether these described fatty acid compositions are pro- or anti-inflammatory.

Dietary Fats, Unsaturated↗
PubMed1999

Plasma chain-breaking antioxidants in preterm infants with good and poor short-term outcome.

Many complications of prematurity have been suggested to result from free radical generation and an inadequacy of antioxidative capacity. We measured the plasma total peroxyl radical-trapping capability (TRAP) and concentrations of the main chain-breaking antioxidants contributing to it, i.e. uric acid, ascorbic acid, alpha-tocopherol, protein sulfhydryl groups and bilirubin, in 21 preterm infants with a mean birth weight of 1440 g and gestational age of 30 wk. The infants were divided into two groups according to their short-term outcome; the good outcome group (GOG) (N = 11) with no signs of morbidity and the poor outcome group (POG) (N = 10) with intraventricular haemorrhage and/or bronchopulmonary dysplasia and/or retinopathy. Arterial blood samples were obtained 3 and 10 days postpartum. TRAP was measured with a chemiluminescent method. As a comparison, venous blood samples from 13 adults (aged from 18 to 34) were used. At day 3 the poor outcome group had significantly higher TRAP than the good outcome or control group, mainly because of elevated uric acid concentration. Also the concentration of unidentified antioxidants was significantly lower in GOG. By day 10 the TRAP decreased substantially in both groups. However, from the components of TRAP, both ascorbate and the unidentified fraction decreased more in POG (p = 0.017 and 0.021, respectively). Furthermore in POG on day 10 urate concentration did not significantly differ from day 3 values. In conclusion, in preterm infants high TRAP was associated with high plasma uric acid concentration and a poor short-term prognosis.

Adolescent↗
PubMed1999

Serum type III procollagen in children with type I hereditary tyrosinemia.

BACKGROUND: Type I hereditary tyrosinemia leads to hepatic dysfunction and fibrosis and is associated with a high risk of hepatic malignancy. Serum N-terminal propeptide of type III procollagen is a sensitive marker of organ fibrosis of diverse origins. The current study was conducted to determine whether analysis of serum levels of type III procollagen in hereditary tyrosinemia would be useful in the follow-up of the progressive liver disease and eventually in detecting hepatic malignancy. METHODS: Serum N-terminal propeptide of type III procollagen was sequentially studied in 10 children with type I hereditary tyrosinemia. RESULTS: At diagnosis of type I hereditary tyrosinemia, serum N-terminal propeptide of type III procollagen ranged from 0.6 to 2.9 multiples of age-related median. During follow-up, serum N-terminal propeptide of type III procollagen decreased, yet remained elevated 0.2 to 2.6 years after diagnosis. Children with the acute type of the disease tended to have higher serum N-terminal propeptide of type III procollagen than did those with the chronic type. Porphyria crises were associated with elevated serum type III procollagen. The one patient receiving 2-(2-nitro-4-trifluoromethyl-benzoyl)-1,3-cyclohexanedione (NTBC) did not differ from the other ones in serum type III procollagen levels. Serum N-terminal propeptide of type III procollagen did not increase with developing hepatocellular carcinoma. CONCLUSIONS: Serum N-terminal propeptide of type III procollagen may be useful in monitoring the hepatopathy in type I hereditary tyrosinemia but is not useful in detecting malignant transformation in the liver.

Adolescent↗
PubMed1998

Elimination diet in cow's milk allergy: risk for impaired growth in young children.

OBJECTIVE: The objective of this study was to evaluate the nutritional impact of therapeutic elimination diets and to identify risk factors predisposing infants with food allergy to poor growth. STUDY DESIGN: We studied 100 children (mean age 7 months) with atopic dermatitis and challenge-proven cow's milk allergy and evaluated their growth during the symptomatic period before diagnosis and during the therapeutic elimination diet. RESULTS: Clinical control of symptoms was achieved in all patients. The mean length SD score and weight-for-length index of patients decreased compared with those in healthy age-matched children, p < 0.0001 and p = 0.03, respectively. Low serum albumin was present in 6% of the patients, 24% had an abnormal urea concentration, and 8% had a low serum phospholipid docosahexaenoic acid. The delay in growth was more pronounced in a subgroup of patients with early onset than in those with later of symptoms (F = 6.665, p < 0.0001). The duration of breast-feeding correlated positively with the sum of n-3 polyunsaturated fatty acids (r = 0.39, p = 0.001) and with the relative amount of docosahexaenoic acid (r = 0.36, p = 0.002). CONCLUSION: A delicate balance exists between the benefits and the risks of elimination diets.

Case-Control Studies↗
PubMed1997

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency with the G1528C mutation: clinical presentation of thirteen patients.

Long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase is one of three enzyme activities of the mitochondrial trifunctional protein. We report the clinical findings of 13 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. At presentation the patients had had hypoglycemia, cardiomyopathy, muscle hypotonia, and hepatomegaly during the first 2 years of life. Seven patients had recurrent metabolic crises, and six patients had a steadily progressive course. Two patients had cholestatic liver disease, which is uncommon in beta-oxidation defects. One patient had peripheral neuropathy, and six patients had retinopathy with focal pigmentary aggregations or retinal hypopigmentation. All patients were homozygous for the common mutation G1528C. However, the enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activities of the mitochondrial trifunctional protein were variably decreased in skin fibroblasts. Dicarboxylic aciduria was detected in 9 of 10 patients, and most patients had lactic acidosis, increased serum creatine kinase activities, and low serum carnitine concentration. Neuroradiologically there was bilateral periventricular or focal cortical lesions in three patients, and brain atrophy in one. Only one patient, who has had dietary treatment for 9 years, is alive at the age of 14 years; all others died before they were 2 years of age. Recognition of the clinical features of long-chain 3-hydroxyacyl-CoA deficiency is important for the early institution of dietary management, which may alter the otherwise invariably poor prognosis.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

Mutation analysis for prenatal diagnosis of hereditary tyrosinaemia type 1.

Hereditary tyrosinaemia type 1 is a rare but serious metabolic disorder with an autosomal recessive mode of inheritance. We describe the prenatal diagnosis of an affected fetus performed by DNA-mutation analysis and a subsequent pregnancy with a healthy child in the same family.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Impact of solid food on plasma arachidonic and docosahexaenoic acid status of term infants at 8 months of age.

We studied healthy term infants at 6 and 8 months of age to assess the effect of fat-containing solid foods (mashed veal, chicken, and pork provided in ready-to-feed cans) on plasma long-chain polyunsaturated fatty acid (LCP) status. Twenty-one infants were breast-fed and 49 were formula-fed. The fat of the formula contained 16.2% linoleic acid and 2.3% alpha-linolenic acid but no LCPs. The solid-food intake was assessed with a 7-day dietary record. Blood samples were obtained at 6 and 8 months of age, and the fatty acid composition of plasma cholesteryl esters (CE) and phospholipids (PL) were analyzed with capillary gas liquid chromatography. The solid food-derived fat intake was higher in the formula-fed than in the breast-fed group at 6 months, and it increased significantly in both groups (from 0.15 to 0.39 g/kg/day and from 0.24 to 0.43 g/kg/day in breast-fed and formula-fed groups, respectively). The relative plasma concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) were significantly lower in the formula-fed than in the breast-fed group at both 6 and 8 months. In the formula-fed group at 8 months, the proportion of solid food-derived fat correlated positively with plasma 20:4n-6, and the mean percentage of PL-20:4n-6 were 8.0% (95% confidence interval, 7.4-8.5) and 9.0% (8.3-9.7) in its lowest and highest quartiles, respectively. In the breast-fed group, solid food-derived fat intake had no effect on plasma 20:4n-6. The two groups were similar in that solid-food fat had no effect on plasma PL- or CE-22:6n-3. In conclusion, the introduction of meat containing solid foods to formula-fed infants increases their plasma 20:4n-6, but not to levels found in breast-fed infants. Further studies are needed to establish an optimal fatty acid composition of solid foods during weaning.

Arachidonic Acid↗
PubMed1995

The fatty acid composition of banked human milk and infant formulas: the choices of milk for feeding preterm infants.

The fatty acid composition of 48 samples of banked human milk for preterm infants and four standard infants formulas available in Finland were analysed by capillary gas liquid chromatography. The banked milk was collected from mothers who had given birth 0-8 weeks previously. Saturated fatty acids accounted for approximately 50% of the fatty acids in both human milk and the formulas, while the relative content of monoenoic fatty acids tended to be higher in human milk than in the formulas. The relative content of 18:2n-6 was higher in the formulas (range 14.7%-23.2%) than in human milk (median 9.1%, range 6.3%-13.4%). Fat of banked human milk contained 0.9% and 0.7% polyunsaturated fatty acids with 20 and 22 carbon atoms (LCP), respectively, which is comparable to that of fresh mature human milk. In contrast, LCP could not be detected in any of the formulas. Conclusion. Banked human milk is a good source of LCP and offers a good alternative to LCP containing formulas.

Arachidonic Acid↗
PubMed1995

Fatty acid composition of plasma and red blood cell phospholipids in preterm infants from 2 weeks to 6 months postpartum.

The purpose of this study was to follow the long-chain polyunsaturated fatty acid (LCP) status in initially human milk-fed preterm infants from 2 weeks to 6 months postpartum. Twenty-two infants aged 27-33 weeks of gestation at birth who had a birthweight of 710-2525 g were fed human milk for > or = 4 weeks. After discharge from the hospital, they were either human milk-fed or formula-fed according to their mothers' decision: 10 were fully breast-fed for 6 months and 12 were formula-fed after discharge at 1-2 months. The formula fat contained 20% 18:2n-6 and 3% 18:3n-3 but was devoid of long-chain polyunsaturated fatty acids (LCP). Blood samples were taken at 2 weeks, 3 months, and 6 months postpartum. Percentage fatty acid compositions in red blood cell (RBC) and plasma total phospholipids were analyzed by capillary gas liquid chromatography. In formula-fed infants, the change from human milk to formula resulted in a significant rise in plasma and RBC 18:2n-6 and 18:3n-3 and a decrease in plasma 20:4n-6. Interestingly, RBC 20:4n-6 remained constant in both groups, even after 4-5 months of formula feeding. In the formula-fed group, RBC 22:5n-6 showed an increasing trend. The largest changes were seen in 22:6n-3; in the formula-fed group, it decreased in both plasma and RBC, whereas in the human milk-fed group, it showed an increasing trend.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The nephropathy of type I tyrosinemia after liver transplantation.

Type I tyrosinemia (HTI) is an autosomally recessively inherited disease caused by deficiency of fumarylacetoacetate hydrolase. The disease manifests with liver failure, renal tubular defects, and neurologic crises. Currently orthotopic liver transplantation (OLT) enables patients to survive. However, renal fumarylacetoacetate hydrolase deficiency is not corrected by OLT, and the long-term prognosis of the nephropathy is not known. We investigated tyrosine metabolism, GFR, renal tubular function, and histopathology before and 18-36 mo after OLT in eight patients with HTI. Progressive renal dysfunction was not documented despite continuing, although diminished, urinary succinylacetone excretion in all patients. The mean GFR was 82 mL/min/1.73 m2 before and 102 mL at 18 mo and 93 mL at 36 mo after OLT. All patients showed tubular dysfunction before OLT. At 18 mo, glucosuria occurred in one, amino aciduria and phosphaturia in three, and hypercalciuria in six patients. Only hypercalciuria was seen at 36 mo. Renal biopsies showed mild nonspecific changes caused either by minimal progression of the renal disease or by mild cyclosporine nephrotoxicity. In conclusion, patients with HTI had normal GFR, but showed signs of tubular dysfunction 18-36 mo after OLT. Renal function and histopathology should be monitored after OLT for HTI.

Amino Acid Metabolism, Inborn Errors↗