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Biomedical subjects

O Simell

Publications and source records attributed to O Simell.

At least 235 records · Page 13Linked to original sources
PubMed1975

Diamino acid transport into granulocytes and liver slices of patients with lysinuric protein intolerance.

Uptake of diamino acids by isolated granulocytes and by liver slices was studied in patients with LPI and in control subjects. 14-C-Labeled lysine, arginine, and ornithine were used in the granulocyte assay and a nonmetabolizable diamino acid analog, l-homoarginine, in the liver assay. Kinetic studies on diamino acid uptake by the granulocytes were consistent with the existence of one transport system common to the three diamino acids. The maximal velocity of uptake was approximately equal for the three amino acids and similar in patients and control subjects. In the liver slices, at least two transport systems became apparent as substrate concentration was varied from 4.0-0.025 mM. A low concentration system with high affinity and very small capacity for transport was similar in patients and control subjects. A high concentration system was also present in both groups, but in the patients had only 1/7 of the maximal capacity observed in the control subjects. This defect grossly incapacitated the diamino acid uptake of the liver. In LPI, the observed defect, in conjunction with the deficient absorption in the kidneys and intestine, explains the lack of ornithine at the site of urea synthesis, which is evident from the impaired and ornithine-correctable urea production.

Adolescent↗
PubMed1974

Renal handling of diamino acids in lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare recessively inherited disease in which one of the fundamental physiological defects is in the mechanism by which diamino acids are transported by the kidney. The purpose of the present studies was to examine that mechanism in four controls and seven patients with LPI. Two types of studies were conducted. In the first set, the renal handling of l-arginine and l-ornithine was evaluated by gradually increasing the plasma concentration of each of these amino acids by constant infusion techniques. In the second set of studies, the possible existence of competitive inhibition between l-arginine, l-ornithine, and l-lysine was examined. In the control subjects, there was almost complete reabsorption of arginine and ornithine, with increases in their filtered loads to 50-100 times normal. With further increases in the filtered loads of these amino acids, there was a gradual decrease in their fractional reabsorption. Mutual competitive inhibition was suggested by the observation that an increase in the filtered load of one diamino acid was associated with a decrease in the reabsorption of the other two. In LPI, the fasting plasma diamino acid concentrations were significantly lower than in the controls. With low filtered loads, the fractional reabsorption of the diamino acids was clearly below normal. This defect diminished with higher loads. A stepwise increase in the plasma concentration of one diamino acid resulted in a biphasic response. Initially, net tubular secretion of the other diamino acids was noted, but later was followed by return to net absorption. When two diamino acids were infused simultaneously, net absorption of both took place, though less efficiently than in the controls. We conclude that the renal reabsorption mechanism is defective in patients with LPI. With low normal filtered loads, there is increased fractional excretion of all three diamino acids resulting in low serum concentrations of these compounds. However, at higher artificially elevated concentrations of diamino acids, the capacity of the renal transport system in these patients appears normal.

Adolescent↗
PubMed1974

Lysinuric protein intolerance.

Lysinuric protein intolerance is an autosomal recessive disorder which first appears as failure to thrive, vomiting and diarrhea in the infant after weaning from mother's milk. Later it manifests as failure to grow, muscular weakness and osteopenia associated with aversion to animal protein. Some patients become mentally retarded and have periods of stupor. The disease is characterized by marked lysinuria, and hyperammonemia after protein intake. According to accumulating evidence, the basic defect is deficient transport of diamino acids in the intestine, liver and kidney tubuli. Effective treatment is provided by supplementing protein food with extra arginine.

Adult↗
PubMed1972

Saccharopinuria.

Explore the source record for details and available documents.

Adipates↗
PubMedDate not supplied

Neurological development of 5-year-old children receiving a low-saturated fat, low-cholesterol diet since infancy: A randomized controlled trial.

CONTEXT: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention is compatible with normal growth, but its effect on neurological development is unknown. OBJECTIVE: To analyze how parental counseling aimed at keeping children's diets low in saturated fat and cholesterol influences neurodevelopment during the first 5 years of life. DESIGN: Randomized controlled trial conducted between February 1990 and November 1996. SETTING: Outpatient clinic of a university department in Turku, Finland. PARTICIPANTS: A total of 1062 seven-month-old infants and their parents, recruited at well-baby clinics between 1990 and 1992. At age 5 years, 496 children still living in the city of Turku were available to participate in neurodevelopmental testing. INTERVENTION: Participants were randomly assigned to receive individualized counseling aimed at limiting the child's fat intake to 30% to 35% of daily energy, with a saturated:monounsaturated:polyunsaturated fatty acid ratio of 1:1:1 and a cholesterol intake of less than 200 mg/d (n = 540) or usual health education (control group, n = 522). MAIN OUTCOME MEASURES: Nutrient intake, serum lipid concentrations, and neurological development at 5 years, among children in the intervention vs control groups. RESULTS: Absolute and relative intakes of fat, saturated fatty acids, and cholesterol among children in the intervention group were markedly less than the respective values of control children. Mean (SD) percentages of daily energy at age 5 years for the intervention vs control groups were as follows: for total fat, 30.6% (4.5%) vs 33.4% (4.4%) (P<. 001); and for saturated fat, 11.7% (2.3%) vs 14.5% (2.4%) (P<.001). Mean intakes of cholesterol were 164.2 mg (60.1 mg) and 192.5 mg (71. 9 mg) (P<.001) for the intervention and control groups, respectively. Serum cholesterol concentrations were continuously 3% to 5% lower in children in the intervention group than in children in the control group. At age 5 years, mean (SD) serum cholesterol concentration of the intervention group was 4.27 (0.63) mmol/L (165 [24] mg/dL) and of the control group, 4.41 (0.74) mmol/L (170 [29] mg/dL) (P =.04). Neurological development of children in the intervention group was at least as good as that of children in the control group. Relative risks for children in the intervention group to fail tests of speech and language skills, gross motor functioning plus perception, and visual motor skills were 0.95 (90% confidence interval [CI], 0.60-1.49), 0.95 (90% CI, 0.58-1.55), and 0.65 (90% CI, 0.39-1.08), respectively (P =.85,.86, and.16, respectively, vs control children). CONCLUSION: Our data indicate that repeated child-targeted dietary counseling of parents during the first 5 years of a child's life lessens age-associated increases in children's serum cholesterol and is compatible with normal neurological development. JAMA. 2000;284:993-1000

Child Development↗
PubMedDate not supplied

Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults.

BACKGROUND: Intranasally applied insulin is one of the antigen-specific therapies currently tested in clinical type 1 diabetes prevention trials, for example, in the Type 1 Diabetes Prediction and Prevention Study (DIPP). The possibility that the therapy may cause hypoglycaemia or local irritation and the poorly known immunological safety of mucosal application of the antigen in healthy subjects prompted this study. METHODS: We used a randomised, placebo-controlled, double-blinded crossover study design with 3-week treatment periods to study the effects of once-daily intranasal application of human short-acting insulin without absorption-enhancing adjuvants in 20 non-diabetic adults. The selected 60 IU dose of insulin was equivalent to the weight-based dose used for the DIPP children. We investigated self-monitored blood glucose concentrations, nasal insulin effects and induction of diabetes-associated autoantibodies. RESULTS: The two treatment periods showed no differences in blood glucose concentrations or in the frequency of blood glucose values higher than 3.0 mmol/L. Of the eight measured hypoglycaemic values, only one, which occurred during placebo therapy, was associated with symptoms. Rhinoscopy revealed no nasal irritation, and mucociliary clearance, nasal airway patency and nasal airflow resistance were not affected by the insulin therapy. Eleven subjects complained of transient nasal stinging or unpleasant odour and one subject reduced the dose because of nasal irritation. The treatment did not induce production of any of the four diabetes-associated autoantibodies. CONCLUSIONS: Short-term use of intranasal insulin without absorption enhancers was predominantly well tolerated, the risk of hypoglycaemia was minimal and no objective nasal adverse effects were detected.

Administration, Intranasal↗
PubMedDate not supplied

Genetic screening for individuals at high risk for type 1 diabetes in the general population using HLA Class II alleles as disease markers. A comparison between three European populations with variable rates of disease incidence.

BACKGROUND: To develop screening strategies for identification of individuals at increased genetic risk for type 1 diabetes in three populations with variable disease incidence rates and distinct ethnic origin. METHODS: A stepwise HLA DQB1-DQA1-DRB1-based screening approach was evaluated. Patients with childhood-onset type 1 diabetes were recruited from Finland (n = 1739), Hungary (n = 149), and Greece (n = 119). Consecutive newborns (2568 from Finland and 1047 from Greece) or healthy schoolchildren (n = 177 from Hungary) served as controls. RESULTS: The DQB1*02/0302 genotype conferred the highest disease risk in all populations. The DQB1*02/y (y not equal DQB1*0301,*0302,*0602,*0603, *0604) genotypes were more common and conferred a higher disease risk in the Greek population (OR 4.9) compared to the Finns (OR 1.2). DQB1*0302/x (x not equal DQB1*02, *0301, *0602, *0603, *0604) genotypes were, in contrast, more prevalent among Finnish cases (32.7%) as compared to Hungarians (18.1%) or Greeks (13.5%). The protective DQB1*0602 or *0603 positive genotypes were most common in the Finns, while DQB1*0301 was more common in Hungarians and Greeks. In all groups, DQA1 and DRB1*04 typing considerably increased the sensitivity of the DQB1-based screening. The different high-risk genotype combinations present in about 10% of the background population had a diagnostic sensitivity of 60% in Finland and 80% in Hungary and Greece. CONCLUSIONS: HLA DR-DQ-based screening is a feasible tool for the identification of individuals at increased genetic risk for type 1 diabetes in populations with diverse genetic background. The risk markers should, however, be individually selected for the target population since the screening efficiency of various markers is highly dependent on the ethnic group studied.

Biomarkers↗
PubMedDate not supplied

West syndrome: individualized ACTH therapy.

Individualized ACTH treatment of the West syndrome (WS) was assessed in a prospective multicenter study, in which each patient's dosage was increased stepwise according to response. Our series included six patients with cryptogenic and 24 with symptomatic infantile spasms. During the treatment period the total ACTH dose ranged from 58 to 373 i.u./kg. In the cryptogenic group one patient responded to pre-ACTH pyridoxine and four to the lowest dosage of ACTH (3 i.u./kg daily) with cessation of spasms and good outcome; one patient needed the highest dosage (12 i.u./kg daily) for cessation of seizures and became developmentally retarded. In the symptomatic group, 21 of the 24 patients needed 6-12 i.u./kg daily; 12 became seizure-free or having infrequent non-IS fits. Complications such as arterial hypertension, cerebral ventricle dilatation, cardiac hypertrophy, and prolonged adrenocortical hyporesponsiveness were related to the dose. The individualization provides all the benefits of ACTH treatment with minimal side effects and cost.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Genetic homogeneity of lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder in which transport of the cationic amino acids lysine, arginine and ornithine is defective at the basolateral membrane of the epithelial cells in the intestine and renal tubules. LPI is unusually common in Finland, but patients have been described on all continents. Linkage analysis in Finnish LPI families recently assigned the LPI gene locus to a 10 cM interval between markers D14S72 and MYH7 on the long arm of chromosome 14. In the present study linkage analysis of LPI families from six different non-Finnish populations strongly suggests genetic homogeneity in LPI. Peak lod scores were obtained at the chromosomal area between D14S72 and MYH7 with the same markers as in the Finnish families. The non-Finnish families showed no linkage disequilibrium except in an Italian family cluster, whereas strong allelic association in the Finnish families implies that LPI in Finland is caused by a founder mutation.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Sucrose intake since infancy and dental health in 10-year-old children.

The dental health of children in western countries has improved without a concomitant decrease in the mean sucrose consumption. Our aim was to analyse the association of long-term sucrose consumption with dental health in children representing the highest (n = 33, 18 boys) and the lowest 5 percentiles (n = 33, 21 boys) of sucrose intake, in a study where food consumption was prospectively recorded from infancy to 10 years of age. The sum of decayed, missing and filled teeth in the primary (dmft) and permanent (DMFT) teeth was assessed. Children's sucrose intake in the high intake group was constantly higher than in their counterparts (p < 0.001), and already exceeded 10% of energy intake (E %) at 2 years of age. The mean +/- SD of the dmft + DMFT scores was higher in the high than in the low sucrose intake group (3.9 +/- 3.9 and 1.9 +/- 2.5, respectively; p = 0.032). We conclude that a persistently high sucrose intake increases the risk of dental caries in children.

Analysis of Variance↗