Biomedical subjects

S Ikonen

Publications and source records attributed to S Ikonen.

33 records · Page 2Linked to original sources

PubMed1999

Short versus prolonged indomethacin therapy for patent ductus arteriosus in preterm infants.

OBJECTIVE: To evaluate whether a prolonged low-dose course of indomethacin would produce an improved closure rate and have fewer side effects compared with a short standard dosage schedule in the management of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN: Sixty-one infants of gestational ages 24 to 32 weeks with a PDA confirmed with echocardiography were randomized to receive 0.2 to 0.1 to 0.1 mg/kg indomethacin in 24 hours (short course, n = 31) or 0.1 mg/kg every 24 hours 7 times (long course, n = 30). Echocardiography was done 3, 9, and 14 days after the treatment was started, and side effects were monitored. RESULTS: Primary PDA closure occurred more often in the short course group (94% vs 67%, P =.011), but the sustained closure rates were not different (74% vs 60%). Surgical PDA ligations were less frequent in the short course group than in the long course group. The short course group had a shorter duration of oxygen supplementation, less frequent symptoms of necrotizing enterocolitis, and a lower rate of urea retention. Mortality and other neonatal morbidity rates were similar. CONCLUSION: A prolonged low-dosage indomethacin regimen offers no advantage compared with a standard-dosage short course in the management of a hemodynamically significant PDA in preterm infants.

Cyclooxygenase Inhibitors↗

PubMed1999

Frequency and risk factors in bronchopulmonary dysplasia in a cohort of very low birth weight infants.

Frequency and perinatal risk factors in bronchopulmonary dysplasia (BPD) were retrospectively evaluated in a cohort of 242 infants with birth weights less than 1501 g born in one hospital in 1990-1994. At 28 days' postnatal age, 30.7% (59/192) of the infants alive received oxygen supplementation and showed typical radiological changes in chest X-rays. At 36 weeks' corrected gestation, 13.0% (24/184) of the survivors fulfilled these criteria. In multivariate analysis, low birth weight and gestational age, male sex, packed red cell infusions and long duration of ventilator therapy were correlated with an increased risk of BPD at 28 days' postnatal age. Only 49% of the infants with BPD had had respiratory distress syndrome, and 49% of them recovered from BPD by 36 weeks' corrected gestational age. Preeclampsia, low birth weight, rapid birth weight recovery, packed red cell infusions, long duration of ventilator therapy, patent ductus arteriosus and hyperoxia were associated with BPD beyond 36 weeks' corrected gestation. No infant born small for gestational age recovered from BPD before 36 weeks' corrected gestation. The frequency of BPD at 28 days' postnatal age seems to be increasing, but half of the patients recover before term. Factors other than respiratory distress syndrome, especially small birth weight, early weight gain and possibly intrauterine growth retardation are becoming more important risk factors of BPD beyond 36 weeks' corrected gestation.

Birth Weight↗

PubMed1999

Cord blood concentrations of vitamin A in preterm infants.

Plasma vitamin A concentrations were measured in cord blood samples from 56 infants of gestational ages < 33 weeks. Outcome was followed prospectively. Mothers' dietary habits and use of multivitamins during pregnancy were evaluated by means of a questionnaire. Vitamin A concentrations less than 1.05 micromol/l (low) were measured in 22, but levels below 0.7 micromol/l (deficient) only in two cases. The concentrations were not correlated with the infants' gestational ages. Infants with low concentrations were significantly more often multiplets compared to those with normal levels and the vitamin A concentrations of the multiplets were significantly lower than those of the singletons. The outcome measures used and the mothers' dietary habits and multivitamin use were similar in cases with low and normal vitamin A concentrations. Multiple gestation seems to be correlated with low plasma vitamin A concentrations in preterm infants at birth, and a complete assessment of vitamin A status to detect possible deficiency might be indicated in these cases.

Adult↗

PubMed1999

Very low birthweight, bronchopulmonary dysplasia and health in early childhood.

The impact of very low birthweight (<1500g) and bronchopulmonary dysplasia (BPD) on respiratory morbidity, on need of medical resources and rehabilitation at 2-8 y of age, and on the everyday life of the child's family was evaluated by means of a questionnaire addressed to parents of 143 very low birthweight children, 36 of whom had had BPD at 28 d postnatal age, and 131 term controls. In the preceding year, respiratory symptoms provoked by exercise, use of inhaled medications, regular follow-up visits and hospitalizations, need for physiotherapy, occupational therapy, technical aids and financial support from society had been more common in the very low birthweight groups compared to children born at term. Children with BPD suffered respiratory infections and needed antibiotic courses more frequently than term controls. Repeated antibiotic courses, physiotherapy and occupational therapy were more common among very low birthweight children with BPD than among those without. Concern for the child and the impact of the child's health on his or her everyday life and the parents' work and education were more often reported in target families than in term controls. Compared to term families, more parents in the BPD group felt that the child's health affected the pasttimes of other family members. To the families concerned, very low birthweight and BPD constitute a significant burden far beyond the neonatal period. Validated scales for the assessment of their quality of life are needed to develop supportive measures and to evaluate the effects of such interventions.

Adult↗

PubMed1998

D-cycloserine, a partial NMDA receptor-associated glycine-B site agonist, enhances reversal learning, but a cholinesterase inhibitor and nicotine has no effect.

The present study examined the efficacy of single and combined treatments with an anticholinesterase, tetrahydroaminoacridine, nicotine and a glycine-B site partial agonist, D-cycloserine, in alleviating the water maze reversal learning defect induced by a medial septal lesion. D-cycloserine (3 and 10 mg/kg) improved reversal learning. Tetrahydroaminoacridine (1 and 3 mg/kg) and nicotine (0.1 and 0.3 mg/kg) had no effect on reversal learning. A combination of tetrahydroaminoacridine 3 mg/kg or nicotine 0.3 mg/kg and D-cycloserine 10 mg/kg was not more effective than D-cycloserine 10 mg/kg alone in improving reversal learning. This suggests that stimulation of NMDA mechanisms may more effectively improve in medial septal-lesioned rats reversal learning processes than stimulation of cholinergic activity.

Alzheimer Disease↗

PubMed1998

Tetrahydroaminoacridine, a cholinesterase inhibitor, and D-cycloserine, a partial NMDA receptor-associated glycine site agonist, enhances acquisition of spatial navigation.

The present study examines the efficacy of single and combined treatments with an antiocholinesterase, tetrahydroaminoacridine (THA, i.p.), and a glycine-B site partial agonist, D-cycloserine (DCS, i.p.) to alleviate water maze (WM) spatial navigation defect induced by medial septal (MS) lesion. THA 3 and DCS at 3 or 10 mg/kg improved acquisition of the WM test, but only DCS improved spatial bias. These drugs had no effect on consolidation. A combination of THA 3 and DCS 10 mg/kg enhanced WM acquisition more effectively than either of the treatments on their own. This suggests that combined modulation of acetylcholine and NMDA mechanisms may have greater therapeutic effect to stimulate cognitive dysfunctions.

Animals↗

PubMed1998

Apamin improves spatial navigation in medial septal-lesioned mice.

We investigated the effects of acute i.p. injections of the Ca2+-dependent K+ channel blocker, apamin, on water maze spatial navigation, Y-maze and passive avoidance behavior in intact and medial septal-lesioned mice. Apamin 0.02, 0.06 or 0.2 mg/kg (i.p.) administered 30 min before or immediately after the training did not affect the performance of intact mice. Apamin 0.02 or 0.06 mg/kg (i.p.) administered immediately after the daily training did not affect the performance of medial septal-lesioned mice. Apamin 0.02 and 0.06 mg/kg (i.p.) administered 30 min before daily training reversed the navigation failure present in medial septal-lesioned mice during the initial and reversal learning stages of the water maze task. Apamin had no effect on the cognitive performance in Y-maze or passive avoidance tests. The results indicate that blockade of Ca2+-dependent K+ channels may facilitate acquisition of spatial navigation performance, but has no effect on consolidation, inhibitory avoidance and spontaneous alternation behavior in mice.

Animals↗

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↗

PubMed1998

Monitoring the CNS pathology in aspartylglucosaminuria mice.

Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.

Animals↗

PubMed1998

Magnetic resonance imaging of clinically localized prostatic cancer.

PURPOSE: We assess the accuracy of endorectal coil magnetic resonance imaging (MRI) for detecting tumor localization, capsular penetration and seminal vesicle invasion in clinically organ confined prostate cancer. We also evaluate intra-observer and interobserver agreement in interpreting MRI studies. MATERIALS AND METHODS: MRI studies of 51 consecutive patients a mean of 61 years old with biopsy proved prostate cancer were retrospectively read twice by 2 radiologists in random order. Both radiologists marked tumor localization, capsular penetration and seminal vesicle invasion on standard tumor maps. These findings were compared with the histopathological results of radical prostatectomy specimens. RESULTS: The overall accuracy of detecting cancer localization was 61%. The detection rate for cancer foci less than 5 mm. was only 5% but for lesions greater than 10 mm. it was 89%. There was 91 and 80% accuracy for detecting capsular penetration and seminal vesicle invasion, respectively. Sensitivity and specificity were 60 and 63, 13 and 97, and 59 and 84% for localization, capsular penetration and seminal vesicle invasion, respectively. Intra-observer and interobserver agreement ranged from fair to good (kappa coefficient 0.240 to 0.647). CONCLUSIONS: Endorectal MRI seems to be better than previously reported for detecting seminal vesicle invasion and tumor foci in the anterior half of the prostate. Sensitivity in detecting minor capsular penetration of the tumor was low, which can probably be improved by methodological development. MRI may be useful for locating cancer foci in patients with high prostate specific antigen values but repeatedly negative biopsy findings.

Aged↗

PubMed1979

Placenta as an indicator of fetal postnatal prognosis.

468 placentas were studied microscopically and by gross examination. Velamentous insertion of the umbilical cord, placenta circumvallate, retroplacental hematoma in connection with ablation of the placenta, and cord prolapse were found to be causative factors in asphyxia of the newborn. The increased placental weight was characteristic in maternal diabetes, hepatosis and, sometimes, in cases of infant malformations and specific inflammations. So-called embryonal persistence was often found histologically in these changes. Small fibrous placentas and those with ramification defects were commonly encountered among cases of toxemia and prolonged gestation. Microscopical placental maturation defects were not indicative of the fetal condition. Thus, only the changes found at gross examination appeared to be a significant indicator of the fetal prognosis.

Apgar Score↗

PubMed1978

Results of hearing testing at 7-year follow-up of kanamycin-treated newborn infants.

A follow-up study 7--8 years after kanamycin treatment of 83 newborn infants in the Tampere University Central Hospital is described. The Apgar scores ranged from 1 to 10, about half of the patients being premature. Only in 1 case (1.2%) a slight bilateral high-tone loss was found. This patient's birth had been complicated by ablation of the placenta with subsequent cesarean section and he had neonatal sepsis as well. The cause of this hearing defect is thus not necessarily the use of kanamycin. Because of the extended use of reserve antibiotics, microorganisms resistant to modern antibiotics may necessitate in some vital cases the use of kanamycin. Our results indicate that, if serum concentrations are monitored adequately, the use of kanamycin does not necessarily result in a hearing defect.

Audiometry↗

PubMed1975

Nephrotoxicity of Cortinarius speciosissimus: a histological and enzyme histochemical study.

The nephrotoxicity of the mushroom species Cortinarius speciosissimus was studied in the rat. Dried, homogenized mushroom was given orally via gastric tubing. The development of the kidney damage was followed by both histological and enzyme histochemical methods. The first signs of kidney damage were interstitial infiltrates occurring mainly in the outer medullary zone, observed two days after the administration of the mushroom. Focuses of inflammation, which gradually scarred, appeared after four days. Chiefly necrotic changes occurred in the tubuli of the cortical zone. Valine residue cleaving aminopeptidase disappeared from the necrotic tubuli at a noticeably greater rate than arginine residue cleaving aminopeptidase. A high activity of arginine residue cleaving aminopeptidase was observed in the inflammatory focuses located in the outer medullary zone, showing the important role of this enzyme in kidney inflammation.

Aminopeptidases↗

PubMedDate not supplied

Effects of metrifonate on the hippocampal theta rhythm of freely moving intact and MS-lesioned mice.

Changes in hippocampal electroencephalogram (EEG) have been suggested to be closely associated with spatial learning ability. Spatial learning can be improved in medial septal (MS)-lesioned mice by metrifonate, a cholinesterase inhibitor. We designed this study to investigate the effects of metrifonate on the hippocampal theta oscillation of intact and MS-lesioned mice. Intact and MS-lesioned C57BL mice were treated with acute injections of metrifonate (doses: 15, 50 and 100 mg/kg ip). These included a dose that considerably improved spatial memory of MS-lesioned mice in our earlier study. In addition, subtype selective muscarinic agents, BIBN-99, AF267B and AF150(S) were used. Recordings of hippocampal theta during movement and awake immobility revealed a dramatic reduction of theta in the lesioned animals. Metrifonate induced prominent changes in the EEG of intact mice, but not of MS-lesioned mice. The effect of metrifonate was not mimicked by two selective M(1)-agonists and was augmented by a combined injection of a selective M(2)-antagonist. These data suggest that improved spatial learning by the cholinesterase inhibitor metrifonate is unrelated to its effects on the hippocampal EEG. These two effects may be mediated through different muscarinic receptor subtypes.

Animals↗

PubMedDate not supplied

Place cell rigidity correlates with impaired spatial learning in aged rats.

In humans and in animals, some aged individuals are severely impaired in learning and memory capacity whereas others perform as well as young adults. In the present study, the spatial memory capacity of young and aged rats was characterized by the Morris water maze task, and then firing patterns of hippocampal "place cells" were assessed as the animals explored a familiar environment and a geometrically-altered version of the environment. Spatial representations of hippocampal cells in young and memory-intact aged rats changed upon exposure to the altered environment. In contrast, spatial representations of many cells in aged, memory-impaired rats were unaffected by the environmental alteration. Furthermore, combining all groups, the extent to which spatial representations distinguished the familiar and altered environments predicted learning capacity in the water maze. These findings suggest that a major component of memory impairment in aging may be the failure of the hippocampus to encode subtle differences in contextual information that differ across multiple experiences, such as the sequence of training trials in the water maze.

Aging↗