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Biomedical subjects

J Heikkilä

Publications and source records attributed to J Heikkilä.

At least 19 recordsLinked to original sources
PubMed2006

Surgical treatment of partial tears of the proximal origin of the hamstring muscles.

BACKGROUND: Hamstring injuries are common especially in athletes. Partial and complete tears of the proximal origin may cause pain and functional loss. OBJECTIVE: To evaluate the results of surgical treatment for partial proximal hamstring tears. METHODS: Between 1994 and 2005, 47 athletes (48 cases, 1 bilateral) with partial proximal hamstring tears were operated on. The cases were retrospectively analysed. Before surgery, 42 of the patients had undergone conservative treatment with unsatisfactory results, whereas in five patients the operation was performed within four weeks of the injury. RESULTS: The mean length of the follow up was 36 months (range 6-72). The result of the operation was rated excellent in 33 cases, good in nine, fair in four, and poor in two. Forty one patients were able to return to their former level of sport after an average of five months (range 1-12). CONCLUSION: In most cases, excellent or good results can be expected after surgical repair of partial proximal hamstring tears even after conservative treatment has failed.

Adolescent↗
PubMed2005

Cooperative activation of transcription by autoimmune regulator AIRE and CBP.

Autoimmune regulator (AIRE) is a transcriptional regulator that is believed to control the expression of tissue-specific genes in the thymus. Mutated AIRE is responsible for onset of the hereditary autoimmune disease APECED. AIRE is able to form nuclear bodies (NBs) and interacts with the ubiquitous transcriptional coactivator CBP. In this paper, we show that CBP and AIRE synergistically activate transcription on different promoter reporters whereas AIRE gene mutation R257X, found in APECED patients, interferes with this coactivation effect. Furthermore, the overexpression of AIRE and CBP collaboratively enhance endogenous IFNbeta mRNA expression. The immunohistochemical studies suggest that CBP, depending on the balance of nuclear proteins, is a component of AIRE NBs. We also show that AIRE NBs are devoid of active chromatin and, therefore, not sites of transcription. In addition, we demonstrate by 3D analyses that AIRE and CBP, when colocalizing, are located spatially differently within AIRE NBs. In conclusion, our data suggest that AIRE activates transcription of the target genes, i.e., autoantigens in collaboration with CBP and that this activation occurs outside of AIRE NBs.

Animals↗
PubMed2004

Treatment of experimental autoimmune encephalomyelitis with a neurotropic alphavirus vector expressing tissue inhibitor of metalloproteinase-2.

Prompted by our recent observations of increased MMP-8 and MMP-9 with simultaneous downregulation of tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-3 mRNA levels in the central nervous system (CNS) of mice with severe experimental autoimmune encephalomyelitis (EAE), we used Semliki Forest virus (SFV) to transfer and express recombinant murine TIMP-1-3 genes in the CNS. TIMP-1, TIMP-2 and TIMP-3 expression was confirmed in cultured cells and in the CNS of infected mice. Following intraperitoneal infection with 10(6) plaque-forming units (PFU) of SFV-TIMP, focal TIMP protein expression was achieved throughout the brain. Although already treatment with empty vector inhibited development of EAE to some extent, the expression of TIMP-2 by the virus significantly enhanced the inhibition. TIMP-3-administered mice also had lower disease grade, but the inhibition was not statistically significant. In contrast, SFV-TIMP-1 had no effect, similar to co-infection with TIMP-2 and TIMP-3. We found TIMP-2 expression also by non-infected CNS-resident cells surrounding the virus-positive areas, suggesting a bystander TIMP-2 induction. These data strengthen the view that matrix metalloproteinases are involved in the pathogenesis of EAE and provide clear evidence that virus-mediated delivery of their protein inhibitors can be effective in preventing the clinical disease. TIMPs might be candidates for novel treatment regimens in CNS autoimmune disorders, such as multiple sclerosis.

Animals↗
PubMed2004

Psychodynamic personality profile in first-episode severe mental disorders.

OBJECTIVE: The aim of this study was to relate measures of psychoanalytically derived personality traits to descriptive diagnosis and psychopathology in severe mental disorders. METHOD: Sixty-one consecutive first-episode patients with schizophrenia, bipolar disorder and severe major depression were interviewed. Personality traits were assessed with the Karolinska Psychodynamic Profile (KAPP) and compared with the DSM-IV diagnosis and symptom clusters derived from the BPRS. RESULTS: There were no marked differences in personality traits between the three diagnostic groups, between schizophrenia and affective disorders or between psychotic and non-psychotic illness. However, personality traits had significant associations with symptoms, especially with the emotional retardation cluster. CONCLUSION: Our findings do not support the hypothesis that severe mental disorders would differ from each other in terms of long-standing psychodynamic personality profiles. Certain dysfunctional personality traits may predict especially negative emotional symptoms and possibly also predispose a person to them.

Adult↗
PubMed2003

Intraoperative imaging in a comprehensive neuronavigation environment for minimally invasive brain tumour surgery.

BACKGROUND: Development of an image-guided operation theatre offering multimodal information for mini-invasive neurosurgical brain tumour operations. METHODS: A multi-purpose resistive low-field MR scanner with on-off capability, was installed in a radio frequency-shielded operating room with in-room control panel and display. Intraoperative ultrasound imaging with Doppler mode as needed is used to provide check-up image data between intraoperative MR-imaging sessions. Cortical stimulation and registration are performed during awake craniotomies. The neuronavigation systems are customised arm-based and passive optical. The navigation systems show the positions of the ultrasound probe, cortical stimulation electrode, biopsy needles, endoscope and other instruments on the intraoperative MR-images. FINDINGS: Since 1999, 70 patients (mean age 47, range 3-88 years) have been operated with intraoperative MR-guidance (including 10 tumour biopsies, 56 resections). Twenty-one patients (mean age 46, range 16-67 years) underwent awake craniotomy and tumour resection secured with cortical stimulation and usually preoperative fMR-imaging. The present operating environment offered useful multimodal information for surgery of brain tumours in critical locations. Surgical mortality was 0%, morbidity included 3 (4.3%) infections and 2 (2.9%) permanent hemiparesis. Further removal of tumour was continued in 17 cases (57%) out of the 30 cases where intraoperative MR imaging was used for controlling completeness of the resection.

Adolescent↗
PubMed2003

Acute traumatic extension deficit of the knee.

The purpose of this study was to evaluate the events leading to acute traumatic extension deficit of the knee and the arthroscopic findings in these patients. A total of 78 consecutive patients treated in the Turku university hospital during the years 1994-1996 were included. The mean annual incidence of acute traumatic extension deficits of the knee in our study was 1.1 per 10 000 inhabitants. The single most common (33%) event causing the extension deficit was non-sports related twisting of the knee. Various sports related activities accounted for 42% of the extension deficits, and soccer was the most common sport in this group. In conclusion, acute traumatic extension deficit of the knee is usually a sign of serious intra-articular damage, and the most likely finding (in 82% of the patients in our study) is either a meniscal rupture, an anterior cruciate ligament (ACL) rupture, a patellar dislocation, or a combination of these. The lesions in these knees require prompt evaluation by an orthopaedic surgeon mainly because of the high number of bucket-handle and menisco-capsular insertion ruptures of the menisci, which are possibly suitable for repair.

Acute Disease↗
PubMed2002

Acute traumatic hemarthrosis of the knee. Is routine arthroscopic examination necessary? A study of 320 consecutive patients.

BACKGROUND AND AIMS: Distortions and contusions of the knee are common. Fairly often they will result in hemarthrosis. The purpose of this study was to evaluate the findings in patients with acute traumatic hemarthrosis of the knee and based on these findings estimate the necessity of acute arthroscopic examination. MATERIAL AND METHODS: A total of 320 patients were examined arthroscopically between the years 1994 to 96 in the Turku University Hospital. Patients with other than chondral or osteochondral fractures were excluded. RESULTS: The most common arthroscopic findings were rupture of the ACL (45%), dislocation of the patella (23%) and meniscal tear (21%). In only 113 (35%) cases an immediate therapeutic procedure was performed in addition to the arthroscopic examination. CONCLUSIONS: Based on our findings we believe that routine arthroscopic examination is not necessary in patients with acute traumatic hemarthrosis of the knee. In our opinion the patient should be examined and followed by an orthopedic surgeon and if a lesion requiring operative treatment is diagnosed or suspected, an arthroscopic examination should be scheduled. The timing of the procedure should be such that all possible lesions encountered can be treated in the same operation.

Acute Disease↗
PubMed2001

Magnesium potentiation of the function of native and recombinant GABA(A) receptors.

Mg2+ decreased basal and GABA-inhibited t-butylbicyclophosphoro[35S]thionate binding to GABAA receptor ion channels in rat brain sections up to 1 mM, but increased the binding at 10 mM. The Mg2+-effect was detectable in the presence of a specific GABA site competitive antagonist. Two-electrode voltage clamp recordings of recombinant alpha1beta2gamma2S, alpha1beta2, alpha2beta2gamma2S and alpha2beta2 GABAA receptors revealed a potentiation by 0.1-1 mM Mg2+ of EC20 GABA-evoked ion currents. At 10 mM, Mg2+ decreased the currents. In the absence of GABA, Mg2+ did not evoke any currents. The results show that physiologically relevant Mg2+ concentrations affect the GABA responses on GABAA receptors in native and the main recombinant receptor subtypes, suggesting putative Mg2+ binding sites on the receptor complex.

Action Potentials↗
PubMed2001

Predictors of social relations in persons with schizophrenia living in the community: a Nordic multicentre study.

BACKGROUND: Deinstitutionalisation has led to persons with serious mental illness spending most of their time outside psychiatric institutions. Not much is known about their social life. The paper presents the results of structured interviews with non-institutionalised persons with schizophrenia about treatment, care and social network. The network data are analysed from three perspectives: finding predictors of the number and of the quality of social contacts, and establishing the respective variables that characterise persons with high, and those with low, scores on both the quantity and quality dimensions of social integration. METHODS: Random samples of persons with schizophrenia receiving outpatient services in ten psychiatric centres in the four Nordic countries were interviewed. The following instruments were used: Interview Schedule for Social Interaction (ISSI), Camberwell Assessment of Needs, Lancashire Quality of Life Profile, General Assessment of Functioning (GAF) and Brief Psychiatric Rating Scale (BPRS), in addition to a checklist covering the utilisation of different services. The ISSI provided the main data for this paper. A restricted number of possible predictors were used in General Linear Model (GLM) factorial analysis and discriminant analysis. RESULTS: A total of 418 persons took part in the study. The overall participation rate was 55%. Social integration in terms of number of contacts was related to a high GAF score, few BPRS negative and hostility symptoms, having contact with user organisations and living in urban (in contrast to rural) areas. Availability of emotional relations was predicted by female sex, low scores on the BPRS hostility dimension, high GAF score, having contact with one's family more than once a month, and living in urban areas. Work, adequate leisure activities and GAF score discriminated between the best and worst integrated groups. CONCLUSIONS: Living in urban areas, being female, having a high GAF score and low scores on hostility predicted better integration in terms of number of contacts and emotional relations.

Adult↗
PubMed2001

The relationship of handedness to asymmetry in the occlusal morphology of first permanent molars.

Handedness has been shown to be related to a number of systematic asymmetries in body dimensions, dermatoglyphic patterns and cerebral morphology. The aim here was to compare linear and angular tooth crown asymmetries of the permanent molars in healthy right-handed and left-handed subjects. The material comprised 27 children with recorded concordant left-side dominance of hand, eye and foot. The controls were an age- and sex-matched group with right side dominance. The material is based on the Collaborative Perinatal Project where detailed medical records and the dentitions, including accurate dental impressions, of over two thousand American children were examined in the USA in the sixties. Machine vision technique was used to obtain accurate three-dimensional information from the occlusal surfaces of the first permanent upper and lower molars. The directional asymmetry values of angular measurements of mandibular first molars showed evidence of asymmetry of opposite direction between the two examined groups. The results indicate that occlusal morphology of first permanent molars may be affected by handedness, and this tendency is most evident in the angular measurements of the mandibular molars. Fluctuating asymmetry did not differ significantly between the examined groups.

Child↗
PubMed2000

Stereospecific modulation of GABA(A) receptor function by urocanic acid isomers.

A deamination product of histidine, urocanic acid, accumulates in the skin of mammals as trans-urocanic acid. Ultraviolet (UV) irradition converts it to the cis-isomer that is an important mediator in UV-induced immunosuppression. We have recently shown that urocanic acid interferes with the agonist binding to GABA(A) receptors. We now report that the effects of urocanic acid on binding of a convulsant ligand (t-butylbicyclo[35S]phosphorothionate) to GABA(A) receptors in brain membrane homogenates are dependent on pH of the incubation medium, the agonistic actions being enhanced at the normal pH of the skin (5.5). Using Xenopus laevis oocytes expressing recombinant rat alpha1beta1gamma2S GABA(A) receptors, the low pH potentiated the direct agonistic action of trans-urocanic acid under two-electrode voltage-clamp, whereas cis-urocanic acid retained its low efficacy both at pH 5.5 and 7.4. The results thus indicate clear differences between urocanic acid isomers in functional activity at one putative receptor site of immunosuppression, the GABA(A) receptor, the presence of which in the skin remains to be demonstrated.

Animals↗
PubMed2000

Effect of aging time of sol on structure and in vitro calcium phosphate formation of sol-gel-derived titania films.

Titanium and its alloys have been used successfully in the manufacture of orthopedic and dental implants to replace damaged bone tissue. In this study, different sol-gel-derived TiO(2) coatings were produced on titanium substrates using different aging times (5, 10, 24, or 48 h) of the sol before dipping the coatings and varying numbers (one, three, or five) of coating layers. The influence of the aging time of the sol on the structure of the titania coatings with respect to in vitro bioactivity was investigated. The in vitro bioactivity tests were done in a simulated body fluid (SBF). The sol properties were monitored using a capillary viscometer and dynamic light scattering to determine the viscosity and particle size, respectively. The topography of the films was characterized using atomic force microscopy. The various sol aging times and numbers of layers produced differences in the topography of the titania films. For the coatings with one and three layers, the aging of the sols had an influence on the height of the peaks (lower with longer aging times) although the peak distance was about the same. The number of coating layers had a stronger influence. The distribution of the peak distances became narrower with an increasing number of coating layers. The coating with three layers (top coating prepared after 24 h of sol aging) and the coatings with five layers had a similar distribution of peak distances (15-50 nm), which was favorable for calcium phosphate formation. On these substrates, calcium phosphate formation started within 3-6 days of immersion in SBF. The aging time of the titania sol and the number of coating layers were found to have a strong influence on the surface topography in the nanometer scale of the titania films. The results indicate that the topography of the outermost surface is of importance for in vitro bioactivity.

Alloys↗
PubMed2000

Long-range interactions in neuronal gene expression: evidence from gene targeting in the GABA(A) receptor beta2-alpha6-alpha1-gamma2 subunit gene cluster.

Clustering of GABA(A) receptor alpha1, alpha6, beta2, and gamma2 subunit genes on mouse chromosome 11/human chromosome 5 may have functional significance for coordinating expression patterns, but until now there has been no evidence for cross-talk between the genes. However, altering the structure of the alpha6 gene, specifically expressed in the cerebellum, with neomycin gene insertions in two different experiments unexpectedly reduced the expression of the widespread alpha1 and beta2 genes in the forebrain. There were corresponding reductions in the levels of alpha1 and beta2 subunit proteins and in autoradiographic ligand binding densities to GABA(A) receptors in the forebrain of alpha6-/- mice. The gamma2 mRNA level was not changed, nor were beta3 and delta mRNAs. The data suggest that elements in the neo gene may have an influence over long distances in the GABA(A) subunit gene complex on as yet undefined structures coordinating the expression of the alpha1 and beta2 genes.

Animals↗
PubMed2000

Enhanced locomotor stimulation by NMDA receptor antagonists in alcohol-sensitive ANT rats.

The ability of the antagonists for the N-methyl-D-aspartate (NMDA) type of glutamate receptor to modulate locomotor activity were compared in alcohol-sensitive (or alcohol-nontolerant, ANT) and alcohol-insensitive (or alcohol-tolerant, AT) rat lines. Both rat lines showed altered locomotor activity after acute injections of a competitive antagonist (LY235959), a glycine-site antagonist (L-701,324), or noncompetitive antagonists [MK-801, phencyclidine (PCP), and ketamine] of the NMDA receptor. MK-801 at 0.5 mg/kg caused a strong increase in horizontal activity in both rat lines, the effect being significantly greater in the ANT rats. There was a subpopulation among AT rats that was almost completely unresponsive to MK-801. This insensitivity to MK-801 correlated with the lack of c-fos induction in the retrosplenial and cingulate cortices. Fos immunoreactive cells in these brain regions after MK-801 treatment were more numerous in ANT than AT rats, although c-fos induction in the inferior olivary nucleus was similar in all animals after MK-801. The ANT rats showed greater locomotor stimulation also after ketamine and LY235959, while stimulation induced by PCP and depression induced by L-701,324 did not differ between the rat lines. The data suggest that altered NMDA receptor-mediated processes may correlate with differences in innate alcohol sensitivity in the ANT/AT rat model.

Alcohol Drinking↗
PubMed2000

Elevated hypothalamic/midbrain serotonin (monoamine) transporter availability in depressive drug-naive children and adolescents.

Cumulative data suggest depression in adulthood being connected to reduced availability of brain serotonin while the role of dopamine remains less specific. Prospective studies have shown a continuity of depressive episodes from childhood to adulthood, combined with poor social function and excess mortality. The object of this study was to examine whether alterations in brain serotonin and/or dopamine transporter levels are already present in depressive children and adolescents. We examined 41 drug-naive patients (aged 7-17) by single photon emission tomography (SPET) using iodine-123-labelled 23-carbomethoxy-3P3(iodophenyl) tropane [123I]beta-CIT as a tracer for monoamine transporters. In addition to the ordinary clinical examination, the patients were given a structured interview and information was gathered from teachers and parents with questionnaires. The diagnoses were established by consensus evaluation between three child psychiatrists. To test the serotonin hypothesis and the dopamine hypothesis regarding depression in children and adolescents, the series was divided into groups with depression present (31) and no depression present (10). In this study, the depressive child and adolescent patients had significantly higher serotonin transporter availability (P < 0.02) in the hypothalamic/midbrain area. Age did not correlate to the hypothalamic/midbrain serotonin transporter binding ratio. No significant difference in dopamine transporter availability in striatum was found between the depressive and the nondepressive children and adolescents.

Adolescent↗
PubMed1999

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. METHODS: In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

Aged↗