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Biomedical subjects

I Sipilä

Publications and source records attributed to I Sipilä.

At least 19 recordsLinked to original sources
PubMed2004

Use of percutaneous estrogen gel for induction of puberty in girls with Turner syndrome.

The aim of pubertal induction by estrogen in hypogonadic girls is to achieve physical and psychological development similar to that in natural puberty. We investigated the use of percutaneous estradiol gel for induction of puberty in girls with Turner syndrome (TS).Twenty-three girls with TS and hypogonadism were included in the study. The initial percutaneous dose of 0.1 mg ended as 1.5 mg in the fifth year. The efficacy of the treatment was monitored by measuring height, weight, skeletal age, pubertal status, and serum hormone levels and gynecological ultrasonographic examinations throughout the study. Mean serum estradiol concentrations increased from 22.2 pmol/liter at baseline to 162.2 pmol/liter, and mean FSH levels decreased from 77.4 IU/liter at baseline to 19.2 IU/liter after 5 yr. There were no significant differences between GH users and nonusers with regard to height sd score, weight sd score, bone age acceleration, or adult height. The development of secondary sexual characteristics and uterine growth progressed gradually during the study. All girls reached at least stage B4P4. With percutaneous estradiol gel, the development of secondary sexual characteristics and uterine growth proceeded gradually, mimicking natural puberty. Estradiol gel was safe, easy to use, and well accepted by the subjects and provides an excellent way to individualize pubertal induction.

Administration, Cutaneous↗
PubMed2003

HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families.

The diabetes predisposing effect of HLA genes is defined by a complex interaction of various haplotypes. We analyzed the disease association of HLA DRB1-DQA1-DQB1 genotypes in a large nuclear family cohort (n = 622) collected in Finland. Using the affected family based artificial control approach we aimed at characterizing all detectable disease-specific HLA haplotype and genotype effects. The DRB1*0401-DQB1*0302 haplotype was the most prevalent disease susceptibility haplotype in the Finnish population followed by (DR3)-DQA1*05-DQB1*02 and DRB1*0404-DQB1*0302. DRB1*0405-DQB1*0302 conferred the highest disease risk, although this haplotype was very rare. The DRB1*04-DQB1*0304 was also associated with increased disease risk, an effect detected for the first time in the Finnish population. The following haplotypes showed significant protection from the disease and are listed in decreasing order of the strength of their effect: (DR7)-DQA1*0201-DQB1*0303, (DR14)-DQB1*0503, (DR15)-DQB1*0602, DRB1*0403-DQB1*0302, (DR13)-DQB1*0603, (DR11/12/13)-DQA1*05-DQB1*0301, (DR1)-DQB1*0501. In addition to the DRB1*0401/0404-DQB1*0302/(DR3)-DQA1*05-DQB1*02 genotype and DRB1*04-DQB1*0302 homozygous genotypes, heterozygous combinations DRB1*0401-DQB1*0302/(DR13)-DQB1*0604, approximately /(DR8)-DQB1*04, approximately /(DR9)-DQA1*03-DQB1*0303, approximately /(DR1)-DQB1*0501 and approximately /(DR7)-DQA1*0201-DQB1*02 were also disease-associated. As a new finding in this population, the (DR3)-DQA1*05-DQB1*02 homozygous and (DR3)-DQA1*05-DQB1*02/(DR9)-DQA1*03-DQB1*0303 heterozygous genotypes conferred disease susceptibility. Similarly, the DRB1*0401-DQB1*0302/(DR13)-DQB1*0603 genotype was disease predisposing, implying that DQB*0603-mediated protection from diabetes is not always dominant. Comparison of our findings with published data from other populations indicates a significant disease-specific heterogeneity of the (DR8)-DQB1*04, (DR7)-DQA1*0201-DQB1*02 and (DR3)-DQA1*05-DQB1*02 haplotypes.

Adult↗
PubMed2001

A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomised controlled trial.

BACKGROUND: The role of oestrogens in the closure of growth plates in both sexes is unequivocal. We postulated that inhibition of oestrogen synthesis in boys with delayed puberty would delay maturation of the growth plates and ultimately result in increased adult height. METHODS: We did a randomised, double-blind, placebo-controlled study in which we treated boys with constitutional delay of puberty with testosterone and placebo, or testosterone and letrozole. Boys who decided to wait for the spontaneous progression of puberty without medical intervention composed the untreated group. FINDINGS: Letrozole effectively inhibited oestrogen synthesis and delayed bone maturation. Progression of bone maturation was slower in the letrozole group than in the placebo group. In 18 months, bone age had advanced 1.1 (SD 0.8) years in the untreated group and 1.7 (0.9) years in the group treated with testosterone and placebo, but only 0.9 (0.6) years in the letrozole group (p=0.03 between the treatment groups). Predicted adult height did not change significantly in the untreated group and in the placebo group, whereas in the group treated with letrozole the increase was 5.1 (3.7) cm (p=0.004). INTERPRETATIONS: Our findings suggest that if oestrogen action is inhibited in growing adolescents, adult height will increase. This finding provides a rationale for studies that aim to delay bone maturation in several growth disorders.

Adolescent↗
PubMed2001

Post-prandial insulin lispro vs. human regular insulin in prepubertal children with Type 1 diabetes mellitus.

AIMS: To study whether post-prandial insulin lispro (PL) could be used as a part of insulin therapy instead of premeal human regular insulin (HR) in prepubertal children with Type 1 diabetes mellitus (Type 1 DM). PATIENTS AND METHODS: In this open, randomized cross-over study patients used either PL or HR at breakfast and at dinner. After a 1-month screening period, patients were randomized to treatment with PL or HR for 3 months and then they crossed over to the other insulin for an additional 3 months. The patients were 24 prepubertal children with Type 1 DM (median age 6.2 years, duration of diabetes 37 months). Home monitoring of 1-day glucose profiles at meals (premeal, 1 h and 2 h after breakfast and after dinner) and HbA1c were measured before randomization, before cross-over, and at the last visit. Data on hypoglycaemic episodes were collected at each of the seven visits. The variables were compared between the two treatments. RESULTS: Of the patients 22/24 completed the study. There were no major differences in the glucose excursions between PL and HR after breakfast (mean +/- SD: 1-h PL 3.7 +/- 4.7 vs. HR 2.9 +/- 3.9 mmol/l, P = 0.3; 2-h -0.9 +/- 5.4 vs. 0.3 +/- 4.5 mmol/l, P = 0.2, respectively) or after dinner (1-h PL -2.5 +/- 4.8 vs. HR -0.4 +/- 3.7 mmol/l, P = 0.07, 2-h -4.1 +/- 5.2 vs. -0.7 +/- 5.0 mmol/l, P = 0.05, respectively). Mean change of HbA1c was similar in both treatment groups (PL 0.2 +/- 0.8% vs. HR -0.4 +/- 0.7%, P = 0.1). The frequency of hypoglycaemic episodes was 4.9 per patient per month during treatment with PL, and 4.4 during HR (P = 0.3). CONCLUSION: Treatment with post-prandial lispro as a meal insulin is as effective and safe as traditional treatment with regular insulin in young children.

Child↗
PubMed2001

Exercise induced hypoglycaemic hyperinsulinism.

BACKGROUND: Hyperinsulinism in childhood is often caused by genetic defects involving the regulation of insulin secretion leading to recurrent episodes of hypoglycaemia. We report two patients with exercise induced hypoglycaemia. METHODS: Standardised short exercise tests with frequent blood glucose and plasma insulin measurements were performed in the patients and young healthy controls. RESULTS: Short term exercise resulted in insulin induced hypoglycaemia 15 to 50 minutes after the end of exercise. A massive burst of insulin secretion was observed within a few minutes of the start of exercise in both patients. By contrast glucose and insulin concentrations remained unchanged in healthy controls. CONCLUSIONS: Hyperinsulinaemic hypoglycaemia after moderate physical exercise represents a rarely described phenotype of hyperinsulinism with an as yet unknown defect in the regulation of insulin secretion. It should be suspected in individuals with recurrent exercise related syncope or disturbance of consciousness.

Adolescent↗
PubMed1999

Reduced brain creatine in gyrate atrophy of the choroid and retina with hyperornithinemia.

OBJECTIVE: To analyze in vivo brain creatine (Cr) content in gyrate atrophy of the choroid and retina with hyperornithinemia (GA). BACKGROUND: GA is caused by inherited deficiency of ornithine-delta-aminotransferase activity. Patients lose their vision by middle age and develop selective atrophy of type II skeletal muscle fibers. As demonstrated by MRS, the patients' skeletal muscles have diminished stores of high-energy Cr phosphate. Minor structural and electrophysiologic abnormalities in the brain of these patients also imply that the CNS may be affected. METHODS: The authors acquired proton MR spectra of the basal ganglia of 22 healthy control subjects and 20 GA patients. Nine patients received supplementary Cr or its precursors, and one child was on an arginine-restricted diet to normalize plasma ornithine concentration. The ratios of N-acetylaspartate (NAA) to Cr, NAA to choline (Cho), and Cho to Cr, and the ratios of NAA, Cho, and Cr to tissue water were calculated. RESULTS: NAA/Cr (Cho/Cr) in the untreated and treated patients and control subjects were (mean +/- SD) 3.3+/-0.4, 2.0+/-0.4, and 1.5+/-0.7 (1.9+/-0.3, 1.3+/-0.4, and 0.9+/-0.2), indicating that Cr content in untreated GA patients was proportionally and markedly diminished, and partially corrected by therapy (p < 0.0001). NAA/Cho was similar in all three groups. Cr/water in the untreated patients was only 46%, and increased to 75% of the control ratios in the treated patients (p < 0.0001). CONCLUSIONS: Hyperornithinemia-associated Cr deficiency in GA also affects the CNS, further supporting the possibility that Cr deficiency also has a pathogenetic role in the retina. The deficiency was partially corrected by Cr supplementation and an arginine-restricted diet.

Adolescent↗
PubMed1999

Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia.

BACKGROUND: Eye fundus destruction and type II muscle fiber atrophy in gyrate atrophy of the choroid and retina with hyperornithinaemia (GA) may be mediated by elevated ornithine concentrations which strongly inhibit creatine biosynthesis. This results in deficiency of creatine phosphate (PCr), a key intracellular energy source, as we have demonstrated in skeletal muscle of the patients by 31P magnetic resonance spectroscopy (31P MRS). MATERIALS AND METHODS: Possible correction of the relative PCr deficiency by long-term daily exogenous supplementation of creatine or its precursors was investigated in four GA patients receiving creatine and in five patients treated with guanidinoacetic acid-methionine combination. The relative PCr concentration, expressed as PCr/Pi (Pi; inorganic phosphate) or as PCr/ATP ratios, was compared with the values of untreated GA patients, and matched healthy volunteers. RESULTS: Muscle PCr/Pi ratios (mean +/- SD) of the untreated and creatine supplemented GA patients and controls were 4.9 +/- 1.4, 7.9 +/- 0.4 and 8.4 +/- 1.3. Guanidinoacetate-methionine combination was similarly effective (respective PCr/Pi ratios: 4.9 +/- 0.7, 6.3 +/- 1.1 and 10.7 +/- 2.8). CONCLUSION: Supplementation with creatine or creatine precursors almost normalised low muscle PCr/Pi ratios of patients with GA.

Adolescent↗
PubMed1998

Growth hormone treatment of short children born small-for-gestational-age: the Nordic Multicentre Trial.

The aims of this study were to evaluate the efficacy and safety of different doses of growth hormone (GH) treatment in prepubertal short children born small-for-gestational-age (SGA). Forty-eight children born SGA from Sweden, Finland, Denmark and Norway were randomly allocated to three groups: a control group of 12 children received no treatment for 2 y, one group was treated with GH at 0.1 IU/kg/d (n=16), and one group was treated with GH at 0.2 IU/kg/d (n=20). In total 42 children completed 2 y of follow-up, and 24 children from the treated groups completed 3 y of treatment. Their mean (SD) age at the start of the study was 4.69 (1.61) y and their mean (SD) height was -3.16 (0.70) standard deviation scores (SDS). The children remained prepubertal during the course of the study. No catch-up growth was observed in the untreated group, but a clear dose-dependent growth response was found in the treated children. After the third year of treatment, the group receiving the higher dose of GH, achieved their target height. The major determinants of the growth response were the dose of GH used, the age at the start of treatment (the younger the child, the better the growth response) and the family-corrected individual height deficit (the higher the deficit, the better the growth response). Concentration of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 increased during treatment. An increase in insulin levels was found without negative effects on fasting glucose levels or glycosylated haemoglobin levels. GH treatment was well tolerated. In conclusion, short prepubertal children born SGA show a dose-dependent growth response to GH therapy, and their target height SDS can be achieved within 3 y of treatment given GH at 0.2 IU/kg/d. However, the long-term benefit of different regimens of GH treatment in children born SGA remains to be established.

Body Height↗
PubMed1998

Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients.

Aspartyglucosaminuria (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases. An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation. These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine. Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation. Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermates. However, in the Morris water maze test, a slow worsening of performance could be seen with age. The phenotype mimics well AGU in humans, the patients characteristically showing only slowly progressive mental retardation and relatively mild skeletal abnormalities.

Acetylglucosamine↗
PubMed1997

Growth impairment and growth hormone therapy in children treated for malignant brain tumours.

UNLABELLED: Eighty-two children with malignant brain tumours were treated according to the "8 in 1" chemotherapy protocol in Finland during 1986 to 1993. Thirty-seven with brain tumours not involving the hypothalamic-pituitary region are still alive and tumour-free. The growth and response to growth hormone (GH) therapy in these children was analysed. Children who received craniospinal irradiation had the most severe loss of height SDS, being -1.07 within 3 years of the diagnosis. Even children with no irradiation to the hypothalamic-pituitary axis had a mean change in height SDS of -0.5 after 3 years. Fifteen of 23 children who received craniospinal irradiation and two out of eight children who received cranial irradiation have received GH therapy. A catch-up growth response to the daily GH therapy with the mean dose of 0.7 IU/kg per week was complete in 3 years (+1.87 SDS), irrespective of craniospinal irradiation, in children who were treated at prepubertal age but was seen in none of the children who had reached pubertal age. CONCLUSION: Growth impairment and GH deficiency are common in children treated for malignant brain tumours. The response to GH therapy is good in prepubertal children in terms of increased growth velocity, although the final height is not yet known.

Adolescent↗
PubMed1996

Recombinant human growth hormone improves growth in children receiving glucocorticoid treatment after liver transplantation.

Linear growth is often impaired after successful liver transplantation. The cause is multifactorial; poor graft function and long term glucocorticoid treatment are the main factors responsible. The efficacy and safety of recombinant human GH (rhGH) treatment were assessed in eight growth-retarded children (five boys and three girls) with liver transplants. Immunosuppression comprised azathioprine, cyclosporin, and methylprednisolone. rhGH was administered in a dose of 1 IU/kg x week, given by daily sc injections. The median age at the start of treatment was 9.7 yr (range, 5.9-14.9 yr). All but one of the patients remained prepubertal during treatment. The median growth rate increased from 3.2 to 7.l cm/yr (P = 0.025) and height SD score increased from -3.9 to -3.1 (P = 0.036) during the first year of rhGH treatment. Serum insulin-like growth factor I and insulin-like growth factor-binding protein-3 levels increased significantly during treatment. Graft function was normal in all except one patient, and no rejections or other serious side-effects were documented. In conclusion, rhGH treatment is effective in short, non-GH-deficient, liver-transplanted children receiving long term glucocorticoid treatment. Due to potential risk of allograft rejection, close monitoring of liver function and immunosuppression is required.

Azathioprine↗
PubMed1995

Craniofacial and dental characteristics of Silver-Russell syndrome.

We found significant differences in a craniometric, cephalometric, and dental study of 19 Silver-Russell syndrome patients (13 without growth hormone treatment) with appropriate controls. Although head circumference was normal for age, head length was increased, while cranial and facial widths and facial heights were reduced. Posterior facial height, posterior cranial base length, cranial base height, and mandibular body size were significantly smaller than in healthy children of the same height. Articulatory speech disorders were common. Enamel defects pointed to an early prenatal insult. Delayed dental age and small mandibular and cranial base dimensions support the possibility of physiological growth hormone deficiency in many Silver-Russell syndrome children; however, facial soft tissue structures were strikingly different from those observed in classical growth hormone deficiency.

Abnormalities, Multiple↗
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↗