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Biomedical subjects

O Simell

Publications and source records attributed to O Simell.

At least 19 recordsLinked to original sources
PubMed1995

Prospective randomised trial in 1062 infants of diet low in saturated fat and cholesterol.

Interventions to avoid atherosclerosis might be more successful if launched early in life when eating and life-style patterns are formed, but dietary interventions have been limited by fears of diet-induced growth failure. We investigated the effects of a diet low in saturated fat and cholesterol on serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a randomised study. Every 1-3 months, families in the intervention group received dietary advice aimed at adequate energy supply, with low fat intake (30-35% energy, polyunsaturated/monounsaturated/saturated fatty acid ratio 1/1/1, and cholesterol intake < 200 mg daily). Infants in control families consumed an unrestricted diet. 3-day food records were collected at ages 8 and 13 months. Growth was carefully monitored. Between 7 and 13 months serum cholesterol and non-high-density-lipoprotein cholesterol concentrations did not change significantly in the intervention group (mean change -0.03 [SD 0.72] mmol/L and 0.01 [0.67] mmol/L) but increased substantially in the control group (0.24 [0.64] mmol/L and 0.23 [0.60] mmol/L; p for difference in mean changes between groups < 0.001). Daily intakes of energy and saturated fat were lower in the intervention than in the control group at 13 months (4065 [796] vs 4370 [748] kJ, p = 0.033, and 9.3 [3.5] vs 14.5 [4.8] g, p < 0.001, respectively), and intake of polyunsaturated fat was higher (5.8 [2.2] vs 4.4 [1.4] g, p < 0.001). Growth did not differ between the groups and was as expected for children at this age. Serum cholesterol concentrations fell significantly in parents of intervention-group infants. The increases in serum cholesterol and non-high-density-lipoprotein cholesterol concentration that occur in infants between the ages of 7 and 13 months can be avoided by individualised diets, with no effect on the children's growth.

Cholesterol↗
PubMed1995

Serum insulin profiles in consecutive children 2 years after the diagnosis of IDDM.

We studied associations of 24-h serum insulin profiles with insulin dose, age, gender, haemoglobin A1c (HbA1c) and C-peptide values, as well as blood glucose profiles in 77 consecutive children-nine aged 2-4, 14 aged 5-8, 26 aged 9-12, and 28 aged 13-17 years--2 years after the onset of insulin-dependent diabetes mellitus (IDDM). Mean weight-based insulin doses in the four age groups were similar (0.7 +/- 0.2 U.kg-1.day-1 in all); body surface-area-based doses differed. Insulin doses correlated significantly with the 24-h mean and area-under-the-curve (AUC) values, and with mean values at 03.00 hours of serum insulin in the children aged 5-8 and 13-17 years. The mean insulin concentrations of the age groups (95% confidence intervals) increased with age [6.1 (3.8, 9.7), 7.6 (5.9, 9.8), 10.4 (8.6, 12.4), and 14.0 (11.6, 16.8) mU/l; p < 0.0002]. The 24-h mean of serum insulin together with HbA1c concentration predicted 32% of the variation of mean blood glucose concentrations. Of children aged less than 9 years, 50% had insulin values less than 5 mU/l (healthy subjects' lower reference limit), and 14% were of less than 2 mU/l (detection limit of the assay) at 03.00 hours. At 07.00 hours, 82% had insulin values of less than 5 mU/l, and 36% were of less than 2 mU/l, respectively. Some young children had night-time hypoglycaemia with simultaneous hypoinsulinaemia. Insulin profiles correlated poorly with the HbA1c and peak C-peptide values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Effect of alloxan on the endocrine function of human fetal islet-like cell clusters--an in vitro study.

We studied the effects of alloxan on insulin and glucagon secretion, islet insulin content, and morphology of human fetal islet-like cell clusters (ICCs). ICCs were derived after collagenase digestion and culture of pancreata from two fetuses. Culture medium (RPMI 1640) containing either 2.0 (low) or 11.1 (high) mM glucose was used during the alloxan exposure. Alloxan exposure lasted for 5 min at room temperature, with final concentrations of 0.3, 1, 3, 10, 30 and 100 mM. Medium samples were collected for hormone assays on days 0, 1, 2, 3, 6, and 10 and islet insulin contents were measured on day 10 after alloxan treatment. Electron microscopy of ICCs was done 24 h after the drug exposure. Control ICCs steadily increased their insulin secretion during the whole study period. Alloxan concentrations above 0.3 mM significantly (p < 0.01) decreased insulin secretion at the low glucose concentration. High glucose protected beta cells from alloxan toxicity. There was no difference in islet insulin contents between alloxan-treated and control cultures. Glucagon secretion by glucose media was not affected by alloxan exposure. All islet cells including beta cells remained intact in electron microscopy. The results suggest a block in insulin secretion by alloxan, but beta cells appear to recover at least partly in their insulin-secreting capacity.

Alloxan↗
PubMed1995

Short-term and long-term initial stay in hospital of children with insulin-dependent diabetes: adjustment of families after two years.

A randomized prospective trial on the effect of the length of initial hospital stay (23 +/- 4 days and 9 +/- 3 days) in 61 consecutive children with newly diagnosed diabetes was carried out. Since the metabolic outcome was similar in the treatment groups for the first two years, we analyzed the adjustment and subjective well-being of families to the diabetes after a two-year follow-up period. A semi-structured interview by a psychologist who was blinded to the initial treatment length and medical history of the child showed that 74% of the families in the short-term and 58% in the long-term treatment groups had good overall psychosocial ability to function (ns); there were no unusual fears in 37% and 15% of the families (ns), respectively. After short-term treatment, families needed slightly but not significantly less time to be confident about the management of diabetes in the family. These findings show that the short-term initial hospital stay does not unfavorably affect the adjustment of the family to diabetes and should probably be preferred over the long-term initial hospital stay.

Adolescent↗
PubMed1994

Individualized dietary counselling of families: serum cholesterol concentration and growth of children aged 7-13 months.

We studied the effect of a change in dietary fat composition on serum total and high-density lipoprotein cholesterol and growth in healthy infants between 7 and 13 months of age. The intervention families (n = 22) received individualized dietary counselling when the infant was 7, 8 and 10 months of age. The intervention diet was designed to have a fat content of 35-45 E% of total energy intake in infants aged 7-12 months and 30-35 E% after 12 months of age. The ratio of saturated to monounsaturated to polyunsaturated fatty acids was designed to be 1:1:1. The children in the control group (n = 23) were given no specific advice on the fat composition of the diet. Intake of polyunsaturated fatty acids was significantly higher in the intervention group than in the controls (5.9 E% versus 3.6 E%, p < 0.05). Serum total cholesterol concentration decreased significantly in the intervention group during the study from 4.16 +/- 0.41 mmol/l to 3.86 +/- 0.48 mmol/l (p < 0.05). The infants of both groups grew like average Finnish children. Modification of dietary fat composition, as widely recommended for adults and older children to prevent coronary heart disease, decreases cholesterol values in infants without affecting their normal growth.

Cholesterol↗
PubMed1994

Sonography in the detection of achilles tendon xanthomata in children with familial hypercholesterolaemia.

Patients with heterozygous familial hypercholesterolaemia (FH) are at high risk for the development of coronary artery disease. Achilles tendon xanthomata are often the first clinical manifestation of FH, but are seldom palpable earlier than during the third decade. Twenty-one FH children aged 3-18 years underwent high-frequency ultrasound examination of the achilles tendon. Hypoechoic infiltration of the normal tendon structure was demonstrated in 8 of 21 (38%) of the FH children. The findings were similar in boys and girls. Control subjects (n = 68) aged 1-25 years had no sonographically detectable tendon abnormalities. The thickness of the achilles tendon of the FH children was (mean +/- SD) 7.1 +/- 1.5 mm (range 5-10 mm). The respective values for the controls were 5.8 +/- 1.0 mm (3-7 mm. We conclude that ultrasound examination sensitively detects cholesterol accumulation in the achilles tendon of FH children before tendon xanthomata are clinically evident.

Achilles Tendon↗
PubMed1994

Flow rate and composition of whole saliva in rural and urban Tanzania with special reference to diet, age, and gender.

The association of flow rate and biochemical and microbiological characteristics of saliva with diet was studied in 83 12-year-old children and in 127 adults (84 in the age group 35-44 years, 43 in the age group 65-74 years) living in rural and urban communities in Tanzania. No significant differences were observed between the salivary flow rates of the rural and urban subjects. The mean salivary flow rates were slightly lower in women than in men and significantly lower in the 12-year-old children than in the two older age groups (p < 0.05). The buffer effect was higher in the rural than the urban population. Further, it was lower in women than in men (p < 0.001). Salivary protein, IgG, and sialic acid concentrations were significantly higher in the rural than in the urban population, whereas amylase activity and IgA concentrations were lower. Microbiological studies showed mutans streptococci in 97% of the rural and in 91% of the urban subjects (n.s.). Lactobacilli grew significantly less often in the rural than urban samples (p < 0.01). Analyses of 24-hour dietary recalls showed that the rural and urban diets differed. The proteins in the rural diet were largely of plant origin, while in the urban diet animal proteins dominated. The rural diet contained also less sucrose but more fibre (mainly from grain) than the urban diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Serum levels of oncofetal markers CA 125, CA 19-9, and alpha-fetoprotein in children with hereditary tyrosinemia type I.

Hereditary tyrosinemia type I (HTT-I) is an inherited metabolic disorder with severe liver disease and a high risk for hepatic malignancy. Patients with HTT-I are monitored with repeated analyses of serum amino acids, urine succinylacetone, and serum alpha-fetoprotein (AFP). Oncofetal markers CA 125 and CA 19-9 are elevated in serum of patients with various gastrointestinal diseases and malignancy. To study the biology of oncofetal antigens in tyrosinemia and to assess the possible usefulness of these markers in HTT-I, we studied serum concentrations of CA 125 (n = 160) and CA 19-9 (n = 188), together with AFP (n = 337), in serial samples from 10 patients. At early stages of the disease, most children with an acute type of disease had a remarkably elevated serum CA 125 concentration (153-1560 IU/L) that normalized gradually after the institution of therapy. Serum CA 125 levels may thus reflect acute metabolic imbalance in fulminant HTT-I. The patients with a chronic type of disease showed CA 125 levels within the normal range at diagnosis that slowly increased as the liver condition worsened. These concentrations, however, never reached values seen in acute HTT-I. Serum concentration CA 19-9 in HTT-I was mostly normal. Serum AFP levels fluctuated in all patients and positively correlated with tests for metabolic state and biliary function. A distinct increase in the serum AFP level was recorded in association with the detection of massive hepatocellular carcinoma and also preceded metabolic imbalance leading to porphyria crises.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Vascular addressins are induced on islet vessels during insulitis in nonobese diabetic mice and are involved in lymphoid cell binding to islet endothelium.

In the nonobese diabetic (NOD) mouse, lymphocytic and monocytic infiltration of the pancreatic islets leads to beta cell destruction. To investigate the mechanisms by which lymphocytes enter the NOD pancreas, pancreata were immunostained using monoclonal antibodies to a variety of adhesion molecules known to be involved in lymphocyte binding to vascular endothelium, an initial step in the migration of lymphocytes from blood into organized lymphoid and inflamed tissues. These adhesion molecules include: lymphocyte homing receptors involved in tissue-selective binding of lymphocytes to peripheral lymph node (L-selectin) or mucosal lymphoid tissue (LPAM-1, alpha 4 beta 7-integrin) high-endothelial venules (HEV); and HEV ligands peripheral vascular addressin (PNAd) and mucosal vascular addressin (MAdCAM-1). In NOD pancreata, alpha 4 beta 7 is expressed on most infiltrating cells at all stages of insulitis, whereas L-selectin expression is more pronounced on cells in the islets at later stages. During the development of insulitis, MAdCAM-1 and to a lesser extent PNAd became detectable on vascular endothelium adjacent to and within the inflamed islets. The Stamper-Woodruff in vitro assay was used to examine lymphoid cell binding to such vessels. These functional assays show that both the mucosal (MAdCAM-1/alpha 4 beta 7) and the peripheral (PNAd/L-selectin) recognition systems are involved in this binding. Our findings demonstrate that expression of peripheral and mucosal vascular addressins is induced on endothelium in inflamed islets in NOD pancreas, and that these addressins participate in binding lymphoid cells via their homing receptors. This suggests that these adhesion molecules play a role in the pathogenesis of diabetes in these mice by being involved in the migration of lymphocytes from blood into the inflamed pancreas.

Animals↗
PubMed1992

Mumps and Coxsackie B3 virus infection of human fetal pancreatic islet-like cell clusters.

Islet-like cell clusters (ICCs) prepared from human fetal pancreases were infected with mumps or coxsackie B3 virus. Double-labeled antibody technique showed that the viruses infected both insulin-secreting and other pancreatic cells and that secretion of immunoreactive insulin into the culture medium of the mumps virus-infected cells had already ceased on day 7. The mumps virus-infected ICC clusters produced virus for 14 days, and the mumps virus antigen was detected in the ICCs through the whole 22-day observation period. The coxsackie B3 virus-infected ICCs contained cells highly positive for viral antigen during the first 2 days after infection, and the infectious virus was detected in the culture medium for 22 days. This in vitro model indicates that mumps and coxsackie B3 viruses infect human fetal pancreatic endocrine cells and are able to alter beta-cell function. Coxsackie B3 virus infection in ICCs is lytical and seems to lead to rapid cell destruction, but long-lasting, restricted mumps virus infection in human fetal pancreatic ICCs offers an interesting model to study the effects of viral infection in the endocrine pancreas and beta cell.

Cells, Cultured↗
PubMed1992

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.

Antigens, CD↗
PubMed1991

Randomised prospective study of short-term and long-term initial stay in hospital by children with diabetes mellitus.

To assess how an isolated change in the pattern of care influences outcome of care and hospital use, a randomised prospective 2-year study was done in which 31 of 61 consecutive children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) were admitted to hospital at disease onset for about a week and compared with the other 30 children who were admitted for about 4 weeks. Insulin treatment and education about diabetes were similar in the two groups. Duration of initial stay in hospital had no effect on metabolic control during the 2 years but time since diagnosis was significant with respect to effect on haemoglobin A1 (p = 0.001), haemoglobin A1c (p = 0.004), and insulin dose (p less than 0.001). At 2 years, 45% of the children in the short-term group and 29% in the long-term group were C-peptide positive (p = NS); C-peptide positivity correlated with age. A change in the pattern of care of children with IDDM, led to a pronounced decrease in hospital use by this patient group. Irrespective of the length of initial stay in hospital, equally good metabolic control was obtained in both groups for 2 years.

Adolescent↗
PubMed1991

Lack of glucose-induced functional maturation during long-term culture of human fetal islet cells.

To investigate the long-term effects of glucose on the function of human fetal islets we cultured islet-like cell clusters (ICC) obtained from 12 human fetuses with a mean age of 16.1 weeks in media containing 2.8, 11.1 or 16.7 mM glucose. On the 8th day of culture, the ICC that had been maintained in 16.7 mM glucose contained 60% less insulin than the ICC cultured in 2.8 mM glucose. However, insulin release was similar in both groups, and was not affected by a 24-h incubation in high vs. low glucose. Also (pro) insulin biosynthesis was not significantly affected. During a 24-day culture period, the total release of insulin and glucagon was similar in all glucose concentrations. The ICC released about 75% of their insulin content but only 15% of their glucagon content during the last 48 h of the 24-day culture period, again regardless of glucose concentration in media. Insulin release was insensitive to acute glucose and leucine challenges in perifusion experiments after culture for 1, 5, 8 or 16 days in 11.1 mM glucose, whereas glucagon was always a potent stimulus. In conclusion, the function of cultured young human fetal islet cells is remarkably independent of glucose, even during prolonged exposure. Moreover, the primary role of glucagon in fetal life may be that of a paracrine stimulator of beta-cell function.

Arginine↗
PubMed1991

Children in sauna: hormonal adjustments to intensive short thermal stress.

Hormonal response to Finnish sauna bath was investigated in 20 prepubertal children (age 5-10 years). Blood leukocyte count, plasma potassium, serum aldosterone, growth hormone and prolactin concentrations increased; plasma volume, plasma sodium, catecholamines, serum antidiuretic hormone, atrial natriuretic peptide (ANP), cortisol, and thyrotropin concentrations remained unchanged during sauna bath. One hour after sauna, serum thyrotropin, atrial natriuretic peptide and blood glucose concentrations decreased, whereas the rest of the hormones remained unchanged. Our results implicate that maintenance of homeothermia resulted in moderate hormonal changes in children during Finnish sauna bath which indicate similar adequate hormonal thermoregulatory adjustment as previously documented in adults.

Catecholamines↗
PubMed1990

Tuberous sclerosis and infantile spasms.

The short- and long-term outcome and special problems of 24 children with infantile spasms and tuberous sclerosis (TS) was studied. The diagnosis of TS is frequently missed: white spots on the skin have to be carefully looked for. In the present study, these spots were always found, and calcifications or hypodense areas of the brain were revealed by CT scans before one year of age. In addition to epilepsy, manifestations of TS included: giant cell astrocytoma, iridic heterotopia, cardiac rhabdomyoma, brain cysts, polycystic kidneys with severe arterial hypertension, retinal phakomas, angiofibroma and white spots on the skin. Long-term outcome was poor. None of the children had normal intelligence and all but one had epilepsy, which was often intractable. Behavioural problems were common. The prognosis, in terms of later intelligence, epilepsy and behavioural problems, was worse than in those with 'idiopathic' infantile spasms or in those with simultaneous neurological disorders. An early diagnosis of TS in patients with infantile spasms clarifies the prognosis and avoids some of the hazards of ACTH therapy. TS children have a high relapse rate after ACTH therapy, so prolonged courses may be indicated.

Adolescent↗