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Biomedical subjects

T Heikkinen

Publications and source records attributed to T Heikkinen.

At least 19 recordsLinked to original sources

The effects of long-term treatment with metrifonate, a cholinesterase inhibitor, on cholinergic activity, amyloid pathology, and cognitive function in APP and PS1 doubly transgenic mice.

Recent studies in cell cultures have shown that modulating the cholinergic activity can influence the processing and metabolism of amyloid precursor protein (APP). To investigate whether acetylcholinesterase inhibitors (ChEIs) could decrease production of amyloid beta-peptide (A(beta)) and slow down the accumulation of A(beta) also in vivo, we chronically administered metrifonate (100 mg/kg, po), a second-generation ChEI, to 7-month-old doubly transgenic APP+PS1 mice and their nontransgenic littermate controls for 7 months. Behavioral studies, including open field test, T maze, and water maze, were conducted after 6 months treatment with metrifonate, and the mice were sacrificed at the age of 14 months for biochemical and histological analyses. The long-term treatment with metrifonate failed to inhibit the marked overproduction and deposition of A(beta) in the APP+PS1 mice; in contrast, it increased both A(beta)40 and A(beta)42 levels in the hippocampus. However, the A(beta)42 to 40 ratio was significantly reduced by the treatment. In addition, the number of amyloid plaques in the hippocampus did not differ between the treatment and the control groups. Tolerance to cholinesterase inhibition might be induced in the mouse brain because the inhibition rate of AChE was attenuated from about 80 to 50% during the experiment in both APP+PS1 and nontransgenic mice. The metrifonate treatment did not affect cognitive testing parameters but reduced swimming speed and locomotor activity in both genotypes. Our results do not support the idea that ChEIs would slow down the progression of amyloid pathology in Alzheimer's disease.

Alzheimer Disease↗

Deciduous tooth crown size and asymmetry in strabismic children.

OBJECTIVES: To explore deciduous tooth crown dimensions in strabismic children and the relationship between the type of strabismus and tooth crown mesio-distal (M-D) and labio-lingual (L-L) size asymmetries. MATERIAL: Dental casts at mixed dentition of 2159 Collaborative Perinatal Study black and white children were measured, 123 of them strabismic at 1 year of age, age ranging from 6 to 12 years. METHODS: Directional and fluctuating asymmetries in antimeric teeth were explored in various types of strabismus having unilateral, bilateral or alternating expression. ANOVA and T-square test were used for size comparisons and calculated asymmetries were explored by comparing the variances and Pearson correlations. RESULTS: Strabismus was associated with significant M-D size increase of deciduous maxillary canines in black boys and white girls, black girls had size reduction in their mandibular canine, but white boys were unaffected. Right side size dominance was found in the strabismic children in the lower second deciduous molar M-D dimensions and in the children with alternating strabismus in their upper deciduous canine M-D dimensions. Children with unilateral strabismus had random fluctuating dental asymmetry in their upper deciduous second molar L-L dimensions when compared with healthy normals. Higher left-right correlations were found in lower second deciduous molar dimensions in strabismic girls when compared with that in controls and in strabismic boys, suggesting better developmental canalization in female. CONCLUSIONS: Asymmetries in the head area, such as promoted here in strabismic children, may have associations with asymmetries in the dentition, focusing the embryonal origins and timing of developmental processes.

Analysis of Variance↗

Does training in a virtual reality simulator improve surgical performance?

BACKGROUND: The development of computerized surgical simulators in a virtual reality environment demands models for proper validation. Recent investigations have shown that a virtual reality simulator (MIST-VR) is a reliable tool for the assessment of laparoscopic psychomotor skills and that it improves the automation of the so-called fulcrum effect. Therefore, we set out to determine whether training with the MIST-VR would improve the surgical performance of surgically inexperienced medical students and to see if results obtained in the simulator would correlate with surgical performance. METHODS: A total of 29 medical students were randomized into two groups. One group received preoperative MIST-VR training. Both groups then performed a simulated laparoscopic appendectomy in a pig. The operations were videotaped and examined by three independent observers. RESULTS: There was no significant difference in performance between the two groups. The performance with the MIST-VR correlated with the results in surgery. CONCLUSION: A method that can measure surgical skill, based on the scoring of independent observers who view videotaped performances, seems to be reliable. MIST-VR did not improve the surgical skills of the subjects, but the results with MIST-VR did predict surgical outcome.

Clinical Competence↗

Is a dissection balloon beneficial in totally extraperitoneal endoscopic hernioplasty (TEP)? A randomized prospective multicenter study.

BACKGROUND: Laparoscopic hernioplasty has been criticized because of its technical complexity and increased costs. Disposable dissection balloons can be used to facilitate the creation of the initial working space in totally extraperitoneal endoscopic hernioplasty (TEP), but their use adds to the cost of the operation. METHODS: A total of 322 men with unilateral, primary, or recurrent inguinal hernias were randomized to undergo TEP with or without a dissection balloon. RESULTS: In the group with the balloon, three of 161 patients (2.5%) required conversion to transabdominal preperitoneal hernioplasty (TAPP), or open herniorraphy, whereas 17 of 161 patients (10.6%) were converted to TAPP or open herniorraphy in the group without the balloon (p = 0.002). The mean operation time was 55 min in the group with the balloon and 63 min in the group without the balloon (p = 0.004). There was no difference between them in postoperative morbidity, and there were no major complications in either group. The recurrence rate was 3.1% in the group with the balloon and 3.7 % in the group without the balloon (p = 0.8). CONCLUSION: The use of a dissection balloon in TEP reduces the conversion rate and may be especially beneficial early in the learning curve.

Adult↗

Transplacental transfer of amitriptyline and nortriptyline in isolated perfused human placenta.

RATIONALE: Although tricyclic antidepressants (TCAs) have gained wide acceptance for use in the treatment of depression in pregnant women, their pharmacokinetics during pregnancy have been poorly characterized. The aim of the present study was to investigate the transplacental transfer of amitriptyline (AMI) and its main active metabolite nortriptyline (NOR) in isolated perfused human placenta. METHODS: Nine term human placentae were obtained immediately after delivery with maternal consent and a 2-h non-recirculating perfusion of a single placental cotyledon was performed. AMI (200 ng/ml) and NOR (150 ng/ml), with antipyrine as a reference compound, were added to the maternal reservoir and their appearance to the fetal circulation was followed for 2 h. AMI and NOR concentrations were measured by high performance liquid chromatography (HPLC) and antipyrine concentrations spectrophotometrically. RESULTS: The mean (SD) transplacental transfers (TPT(SS)%) for AMI and NOR were 8.2 (2.3)% and 6.5 (1.8)%, respectively, calculated as the ratio between the steady-state concentrations in fetal venous and maternal arterial sides. The TPTs of AMI and NOR were 81% and 62% of the freely diffusable antipyrine. The absolute fraction of the dose that crossed the placenta (TPT(A)) was moderately, but significantly higher for AMI (7.7%) than for NOR (5.7%) (P=0.037). In all perfusions, steady state at the fetal side was reached by 30 min for AMI and by 50 min for NOR in the fetal side. The viability of the placentae was retained during the 2-h perfusion, as evidenced by unchanged pH of the perfusate and by stable perfusion pressures in fetal artery and stable antipyrine transfer. CONCLUSIONS: Both AMI and NOR cross the human placenta. However, the fetal exposure with NOR may be somewhat smaller compared with AMI, probably due to the higher lipophilicity of AMI.

Adult↗

Hip fractures in Finland and Great Britain--a comparison of patient characteristics and outcomes.

All hip fracture patients (age <50 years, pathological and subtrochanteric fractures excluded) were registered at admission to hospital and at 4 months (mortality up to 1 year) between 1989 and 1997 in Peterborough District Hospital (2083 patients) and Oulu University Hospital (1702 patients). The mean age at fracture was 80.3 years in Peterborough and 78.3 years in Oulu. Respectively, 69% and 62% of the patients had been living in their own homes, 50% and 54% had been able to walk alone unassisted. In Oulu, the patients were discharged after a mean stay of 7.1 days, most of them to health care centre hospitals (71%) and only 21% to their original place of residence. In Peterborough 81% were discharged to their original place of residence after a mean stay of 15.6 days. At 4 months, 54% were living at their own homes in Peterborough and 44% in Oulu. The overall mortality at 1 year was 27.1% in Peterborough and 24.9% in Oulu.

Aged↗

Tooth eruption symmetry in functional lateralities.

Dental casts and oral photographs from a cross-sectional sample of 2092 young North Americans with detailed information on functional lateralities (eyedness, handedness and footedness) were examined to compare the proportions of symmetrical and asymmetrical eruption of the antimeric (left-right, contralateral pair) permanent teeth using a four-grade eruption scale. The proportion of symmetrically erupting antimeric teeth was higher for some teeth in those with non-right-sidedness of the feet and eyes, but not significantly so in the case of handedness. Left-footedness was significantly (95% confidence interval) associated with an increased proportion of symmetrical pairs of the maxillary first molar and mandibular lateral incisor, and non-right-eyedness with an increased proportion of symmetrical eruption and left/right non-balanced proportions of asymmetrical eruption in maxillary central incisors. True right-sidedness (hand, foot and eye) was significantly (P< or =0.05) associated with advanced eruption of the left mandibular first molar. It is suggested that while the timing of antimeric tooth emergence and clinical eruption is primarily programmed before crown mineralization, starting approximately at the 30th gestational week in the case of first permanent molars, symmetrical/asymmetrical tooth emergence and eruption may provide information a posteriori on prenatal and early postnatal growth and development.

Body Patterning↗

Effect of chemical pollution on forms of 137Cs, 90Sr and 239,240Pu in arctic soil studied by sequential extraction.

The aim of the present study was to determine the forms of 137Cs, 90Sr and 239,240Pu occurring in different soil horizons using sequential extraction of samples taken from four sites located along a pollution gradient from the copper-nickel smelter at Monchegorsk in the Kola Peninsula, Russia, and from a reference site in Finnish Lapland in 1997. A selective sequential-leaching procedure was employed using a modification of the method of Tessier, Cambell and Bisson ((1979). Analytical Chemistry, 51, 844-851). For 137Cs the organic (O) and uppermost mineral (E1) layer were studied, for 90Sr and 239,240Pu only the uppermost organic layer (Of). The fraction of 137Cs occurring in readily exchangeable form in the organic layer was about 50% at the reference site and decreased as a function of pollution, being 15% at the most polluted site in the Kola Peninsula. There was a clear positive correlation in the O layer between the distance from the smelter and the percentage of 137Cs extracted in the readily exchangeable fraction (Spearman correlation rsp = 0.7805, p = 0.0001), whereas in the E1 layer no correlation was evident. The distribution of 90Sr in the Of layer was similar at all sites, with the highest amounts occurring in exchangeable form and bound to organic matter, whereas stable Sr showed a somewhat different distribution with the highest amount in the oxide fraction. Most of the 239,240Pu was bound to organic matter. Chemical pollution affected the exchangeable fraction of 239,240Pu, which was about 1% at the most polluted site and 4-6% at the other sites.

Arctic Regions↗

Spatial working memory improvement by an alpha2-adrenoceptor agonist dexmedetomidine is not mediated through alpha2C-adrenoceptor.

1. Aged alpha2C-adrenoceptor knockout and wild type mice were used to investigate whether alpha2C-adrenoceptors are involved in mediating the beneficial effects of alpha2-adrenoceptor agonist, dexmedetomidine, on spatial working memory. 2. A win-stay task in the radial arm maze was used to dissociate the effects of dexmedetomidine on working vs. reference memory. In addition, the animals were tested in simple response habit learning in the T-maze. 3. Knockout mice made more working memory errors after the change of the baited arm in radial arm maze, but after training reached again as accurate level of performance as wild type controls. Dexmedetomidine 5 and 10 microg/kg alleviated the increase in spatial working memory errors after the change of the baited arm in knockout mice. Knockout and wild type mice performed equally well in T-maze, and dexmedetomidine had no effect on this simple response learning. 4. The present results indicate that alpha2-adrenoceptor agonists have a selective effect on spatial working memory not only in monkeys but also in mice. Further, this study confirms our earlier finding that the presence of alpha2C-adrenoceptors is not necessary for the spatial working memory enhancing effect of alpha2-adrenoceptor agonists.

Adrenergic alpha-Agonists↗

Permanent tooth crown dimensions in prematurely born children.

AIM: The aim was to examine the effect of preterm birth on permanent tooth crown dimensions. MATERIALS AND METHODS: The data consisted of 328 prematurely born white and black children and 1804 control children who participated in the cross-sectional study of the Collaborative Perinatal Project (USA) in the early 1960s and 1970s. The dental examinations were carried out in a standardized fashion at ages varying from 6 to 12 years in 95% of cases. Tooth crown size measurements were performed on the dental casts with an electronic measuring device and readout by two experienced observers according to precise definitions generally quoted in the anthropological and genetic literature. The preterm and control groups were divided by sex and race. RESULTS: The results show both increased and decreased tooth crown dimensions in the prematurely born children. Significantly increased dimensions were found in the means of the intercuspal distances of the first permanent molars in the white boys and in the mesiodistal dimensions (MD) of the lower lateral incisors and the upper left first molar in the black girls. By contrast, there were decreased intercuspal distances, MD and labiolingual (LL) tooth crown dimensions in the white girls and black boys. The statistical method used was the Mann-Whitney's U-test (Willcoxon Rank-Sums test). CONCLUSIONS: The findings partly support previous reports of decreased tooth crown dimensions in preterm infants, but the increased dimensions found in the preterm white boys and black girls differ from earlier reports. Our results indicate the importance of environmental factors including neonatal factors in determining permanent tooth crown dimensions. Growth patterns, the buffering capacity and the timing of sensitive moments in tooth crown volume gain may vary between the sexes and ethnic groups and the possible effect of the accelerated growth period in preterm infants (catch-up growth) may influence the determination of permanent tooth crown dimensions.

Adolescent↗

Outpatient laparoscopic cholecystectomy. A prospective study with 100 consecutive patients.

One hundred patients with cholelithiasis were included in a prospective consecutive follow-up study to evaluate laparoscopic cholecystectomy in a day surgical setting. The median operating time was 70 min. In 96% of the patients, it was possible to perform peroperative cholangiography. The median time off work was 7 days and the median time to full recovery was 14 days. Five patients were admitted due to weakness/nausea. Six patients were admitted due to conversion to open surgery or choledocholithiasis. Eighty-nine patients were treated in ambulatory surgery. We conclude that laparoscopic outpatient cholecystectomy can be performed safely with a low unplanned admission rate.

Journal Article↗

The role of respiratory viruses in otitis media.

Evidence derived from numerous studies ranging from animal experiments to extensive clinical trials supports a crucial role for respiratory viruses in acute otitis media. Viral infection of the upper respiratory tract initiates the whole cascade of events that ultimately leads to development of acute otitis media, and viruses contribute to the pathogenesis of this disease by several mechanisms. Recent data indicate that at least some types of viruses actively invade the middle ear and may also interfere with the outcome of otitis media. The availability of effective vaccines against the principal viruses predisposing to acute otitis media could be expected to result in a substantial reduction in the incidence of this disease.

Adenoviridae Infections↗

Validity of ultrasonography in diagnosis of acute maxillary sinusitis.

BACKGROUND: Accurate diagnosis of maxillary sinusitis is difficult on the basis of clinical examination only because the signs and symptoms of sinusitis are nonspecific. A simple, rapid, and readily available method for diagnosing maxillary sinusitis in primary care would increase the accuracy of the diagnoses and thus reduce unnecessary antibiotic treatment. OBJECTIVE: To investigate the validity of ultrasonography compared with radiography and magnetic resonance imaging (MRI) in detection of maxillary sinusitis. DESIGN: Ultrasonography and plain-film radiography of the paranasal sinuses were performed on all patients and MRI was performed on 40 randomly selected patients on day 7 of the study. SETTING: Study office at the Department of Pediatrics of Turku University Hospital, Turku, Finland. PATIENTS: One hundred ninety-seven young adults who contacted the study office within 48 hours of the onset of symptoms of the common cold. MAIN OUTCOME MEASURES: Detection rates of maxillary sinusitis by ultrasonography, radiography, and MRI. RESULTS: Acute maxillary sinusitis was diagnosed in 24% of the sinuses by radiography and in 28% by MRI. Compared with MRI findings, the sensitivity of ultrasonography for detection of maxillary sinusitis was 64% (specificity, 95%). Using a 2-step diagnostic approach in which radiological findings were additionally considered in cases of negative ultrasound findings, a sensitivity of 86% (specificity, 95%) was observed. CONCLUSIONS: The high specificity of ultrasonography indicates that a positive ultrasound finding can be regarded as evidence of maxillary sinusitis. The addition of plain-film radiography in cases of negative ultrasound findings increases the diagnostic sensitivity to clinically acceptable levels without loss in specificity. Active use of ultrasonography would substantially decrease the need for radiological imaging of the sinuses and also help reduce unnecessary antibiotic treatment in primary care. Arch Otolaryngol Head Neck Surg. 2000;126:1482-1486

Acute Disease↗

Viral-Bacterial Synergy in Otitis Media: Implications for Management.

Despite the extensive use of broad-spectrum antibiotics, poor clinical response to the treatment of acute otitis media is common. Evidence derived from numerous studies during the past two decades supports a crucial role for respiratory viruses in the etiology and pathogenesis of acute otitis media, and recent studies indicate that viruses may also have a profound adverse effect on the resolution of this disease. Viruses seem to interact with bacteria and enhance the local inflammatory process in the middle ear. Effective adjuvant therapies are needed to improve outcome in children with otitis media. Increasing knowledge of the role of viruses, viral-bacterial interaction, and host inflammatory mechanisms in otitis media may lead to major improvements in the management of this disease.

Journal Article↗

Intranasal fluticasone propionate does not prevent acute otitis media during viral upper respiratory infection in children.

BACKGROUND: Acute otitis media (AOM) is the most common complication of a viral upper respiratory infection (URI) in children. The virus-induced host inflammatory response in the nasopharynx plays a key role in the pathogenesis of AOM. Suppression of this inflammatory process might prevent the development of AOM as a complication. OBJECTIVE: We sought to assess the effect of intranasally administered fluticasone propionate on prevention of AOM during a viral respiratory infection. METHODS: A total of 210 children (mean age, 2.1 years; range, 0.7-3.9 years) with normal middle ear status and URI of 48 hours' duration or less were randomly allocated to receive either fluticasone (100 microg twice daily) or placebo for 7 days. The specific viral cause of the infection was determined from nasopharyngeal aspirates obtained at the first visit. The children were re-examined at the end of the 7-day medication period. RESULTS: In the fluticasone group AOM developed in 40 (38.1%) of 105 children compared with 29 (28.2%) of 103 children receiving placebo (P =.13). The viral cause of the respiratory infection was determined in 167 (86.1%) of 194 children from whom a nasopharyngeal aspirate was obtained. In children with rhinovirus infection, AOM developed significantly more often in the fluticasone group (45.7%) than in the placebo group (14.7%, P =.005). CONCLUSION: Intranasally administered fluticasone does not prevent the development of AOM during URI but may increase the incidence of AOM during rhinovirus infection.

Acute Disease↗

A single intramuscular dose of ceftriaxone changes nasopharyngeal bacterial flora in children with acute otitis media.

The increasing prevalence of drug-resistant bacteria is attributed to the extensive use of antibiotics, which causes selective pressure on the nasopharyngeal bacterial flora. Shortened courses of antibiotics have been proposed to decrease the development of resistant strains. We determined the effect of a single intramuscular dose of ceftriaxone (50 mg/kg) on the nasopharyngeal bacterial flora in 167 children (median age 13 mo) with acute otitis media. Nasopharyngeal samples for bacterial culture were obtained before and 5 d after treatment with ceftriaxone. Before treatment, Moraxella catarrhalis was isolated in 99 (59%) children, Streptococcus pneumoniae in 87 (52%), and Haemophilus influenzae in 53 (32%). After treatment, M. catarrhalis was found in 62 (37%) children, which constitutes a 37% decrease in the colonization rate by this pathogen (p < 0.001). S. pneumoniae was isolated in 50 (30%; 43% decrease) and H. influenzae in 17 (10%; 68% decrease) children after treatment (p < 0.001 for both). Before treatment, 60% of pneumococcal isolates were sensitive to penicillin, 26% were of intermediate susceptibility, and 14% were penicillin-resistant. Eradication of S. pneumoniae occurred mainly in children with penicillin-sensitive isolates. As a consequence, only 24% of pneumococcal isolates that remained after treatment were sensitive to penicillin, 59% were penicillin-intermediate, and 16% were penicillin-resistant. A single dose of ceftriaxone resulted in significant changes in the nasopharyngeal bacterial flora, increasing the relative prevalence of pneumococcal strains with decreased susceptibility to penicillin.

Acute Disease↗