Biomedical subjects

A Hiltunen

Publications and source records attributed to A Hiltunen.

13 recordsLinked to original sources

PubMed2002

The reliability of diagnosis of infection during revision arthroplasties.

BACKGROUND: Follow up studies have shown that 0.5 to 4% of the total joint arthroplasties will be complicated by infection. Distinction between aseptic loosening and infection is important for prediction of the final outcome after revision arhtroplasty but also for the choice of operative treatment. However, diagnosis of low grade chronic infection is extremely demanding. MATERIALS AND METHODS: 68 hip and knee revision arthroplasties were reviewed retrospectively in order to evaluate the reliability of pre- and perioperative analysis of infection during total joint revision arthroplasties. The sensitivity and specificity for clinical signs, blood white-cell count, C-reactive protein level, radiographic analysis, bone and leukocyte scans, joint aspirations, and gram staining were determined. Tissue sample were harvested and cultured in all cases. Positive cultures were regarded as a true infection. RESULTS: We were not able to characterize the infection by clinical signs. Also no single test was able to show the presence of infection in all cases. The best results were obtained from pre- and perioperative joint aspirations. Joint aspiration showed 1.0 specificity and 0.75 sensitivity. CONCLUSION: It is clear from this study that no single test is able to show the presence of infection in every case. Classical clinical signs, laboratory tests, special imaging studies and joint aspirations have all yielded a notable rate of false negative results. Therefore, we recommend that, if arthroplasty patients have pain in prosthetic joint without clear radiological evidence of loosening, bone scans and preoperative joint aspirations should be undertaken. Also, if radiological evidence of loosening is accompanied with one or more of following criteria; C-reactive protein level elevated, radiologic evidence of infection, loosening within the first five years after implantation. In case of infection a delayed two-stage reconstruction should be managed.

Aged↗

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

Induction of periosteal callus formation by bone morphogenetic protein-2 employing adenovirus-mediated gene delivery.

Although the chondrogenic response of periosteum is well established in healing fractures, the mechanisms mediating the proliferation and differentiation of periosteal chondroprogenitor cells are poorly understood. In the present study we demonstrate that bone morphogenetic protein-2 (BMP-2), introduced by adenovirus-mediated gene transfer, alone is capable of inducing callus formation at the site of periosteal injection. Both immunohistochemistry and Northern analysis demonstrated activation of type II collagen production between days 4 and 7 after the injection, followed by activation of type X collagen expression. The activation of chondrogenesis was associated with increased expression of L-Sox5 and Sox9, suggesting that the BMP-2 effect is mediated via Sox proteins. This capacity of adenovirus-mediated overproduction of BMP-2 to induce chondrogenesis (and subsequent endochondral ossification) should be useful for tissue engineering of cartilage and bone.

Adenoviruses, Human↗

PubMed2001

Accelerated up-regulation of L-Sox5, Sox6, and Sox9 by BMP-2 gene transfer during murine fracture healing.

Fracture repair is the best-characterized situation in which activation of chondrogenesis takes place in an adult organism. To better understand the mechanisms that regulate chondrogenic differentiation of mesenchymal progenitor cells during fracture repair, we have investigated the participation of transcription factors L-Sox5, Sox6, and Sox9 in this process. Marked up-regulation of L-Sox5 and Sox9 messenger RNA (mRNA) and smaller changes in Sox6 mRNA levels were observed in RNAse protection assays during early stages of callus formation, followed by up-regulation of type II collagen production. During cartilage expansion, the colocalization of L-Sox5, Sox6, and Sox9 by immunohistochemistry and type II collagen transcripts by in situ hybridization confirmed a close relationship of these transcription factors with the chondrocyte phenotype and cartilage production. On chondrocyte hypertrophy, production of L-Sox5, Sox9 and type II collagen were down-regulated markedly and that of type X collagen was up-regulated. Finally, using adenovirus mediated bone morphogenetic protein 2 (BMP-2) gene transfer into fracture site we showed accelerated up-regulation of the genes for all three Sox proteins and type II collagen in fractures treated with BMP-2 when compared with control fractures. These data suggest that L-Sox5, Sox6, and Sox9 are involved in the activation and maintenance of chondrogenesis during fracture healing and that enhancement of chondrogenesis by BMP-2 is mediated via an L-Sox5/Sox6/Sox9-dependent pathway.

Animals↗

PubMed2001

Association between pleural plaques and coronary heart disease.

OBJECTIVE: The aim of this study was to verify a clinical impression that patients with coronary heart disease disproportionately frequently have calcified pleural plaques. METHODS: Chest X-rays were collected from 148 patients referred consecutively to the Helsinki University Central Hospital for coronary angiography and from 100 consecutive lung cancer patients seen at the same hospital. The radiographs were analyzed for the presence of calcified pleural plaques according to the classification the International Labour Office. A generalized linear model with binomial distribution and log link was used to estimate the relative risks and their 95% confidence intervals (95% CI). RESULTS: The prevalence of calcified pleural plaques was 35% for the coronary patients and 19% for the lung cancer patients. Calcified pleural plaques were more common among the men than the women, and the risk increased with age. The relative risk of calcified pleural plaques, adjusted for age and gender, was 2.19 (95% CI 1.44-3.32) for the coronary patients as compared with the lung cancer patients. CONCLUSIONS: Further studies with better information on past exposure to asbestos and other potential risk factors are warranted to confirm the observations and to examine whether the association between coronary heart disease and calcified pleural plaques is related to an etiologic or an individual susceptibility factor common to both of these conditions.

Adult↗

PubMed2000

Expression of cathepsins B, H, K, L, and S and matrix metalloproteinases 9 and 13 during chondrocyte hypertrophy and endochondral ossification in mouse fracture callus.

Fracture repair provides an interesting model for chondrogenesis and osteogenesis as it recapitulates in an adult organism the same steps encountered during embryonic skeletal development and growth. The fracture callus is not only a site of rapid production of cartilage and bone, but also a site of extensive degradation of their extracellular matrices. The present study was initiated to increase our understanding of the roles of different proteolytic enzymes, cysteine cathepsins B, H, K, L, and S, and matrix metalloproteinases (MMPs) 9 and 13, during fracture repair, as this aspect of bone repair has previously received little attention. Northern analysis revealed marked upregulation of cathepsin K, MMP-9, and MMP-13 mRNAs during the first and second weeks of healing. The expression profiles of these mRNAs were similar with that of osteoclastic marker enzyme tartrate-resistant alkaline phosphatate (TRAP). The changes in the mRNA levels of cathepsins B, H, L, and S were smaller when compared with those of the other enzymes studied. Immunohistochemistry and in situ hybridization confirmed the predominant localization of cathepsin K and MMP-9 and their mRNA in osteoclasts and chondroclasts at the osteochondral junction. MMP-13 was present in osteoblasts and individual hypertrophic chondrocytes near the cartilage-bone interphase. In cartilaginous callus, the expression of cathepsins B, H, L, and S was mainly related to chondrocyte hypertrophy. During bone remodeling both osteoblasts and osteoclasts contained these cathepsins. The present data demonstrate that degradation and remodeling of extracellular matrices during fracture healing involves activation of MMP-13 production in hypertrophic chondrocytes and osteoblasts, and cathepsin K and MMP-9 production in osteoclasts and chondroclasts.

Animals↗

PubMed1999

Comparison of urinary 5-hydroxytryptophol, breath ethanol, and self-report for detection of recent alcohol use during outpatient treatment: a study on methadone patients.

This study compared urinary 5-hydroxytryptophol (5HTOL) with breath-ethanol testing as objective ways to disclose recent drinking by outpatients attending a methadone maintenance treatment clinic. Information about quantity and frequency of alcohol use was obtained by confidential self-reports. Random screening was performed on Mondays-Fridays in connection with routine clinic visits for methadone dosing. An observed urine sample for monitoring of illicit drug use and determination of 5HTOL, expressed as a ratio to 5-hydroxyindole-3-acetic acid (5HIAA), was obtained from 202 patients (59 women and 143 men), 16 of whom refused to complete the self-report and/or do a breath-ethanol test. Patients taking disulfiram or calcium carbimide for alcohol detoxification were excluded. Among the 177 subjects remaining, 47 (26.6%) reported intake of any alcohol on the previous day (range, 10-230 g ethanol; median, 40). Only four of those could be identified by a positive breath-test, while 17 showed a urinary 5HTOL/5HIAA ratio above the cutoff limit. Their alcohol consumption (median, 60 g) was significantly higher compared with those showing ratios within the reference interval (median, 35 g). The sensitivity of 5HTOL/5HIAA testing for detecting self-reported drinking in excess of 50 g ethanol was 77%. An additional nine patients who claimed abstinence still showed abnormal 5HTOL/5HIAA ratios, and so did three of the patients who refused to do a breath-ethanol test and/or complete the self-report. Altogether, 59 of 190 methadone-maintained patients (31.1%) had been drinking any alcohol on the previous day (i.e. Sunday-Thursday) according to self-report and/or urinalysis data, 29 (49.2%) of whom were identified by the urinary 5HTOL/5HIAA ratio and only four (6.8%) by utilizing breathalyzer.

Alcohol Drinking↗

PubMed1995

Expression of type VI, IX and XI collagen genes and alternative splicing of type II collagen transcripts in fracture callus tissue in mice.

The levels of six mRNAs coding for constituent alpha-chains of three minor collagens of cartilage were analyzed in an experimental fracture model in normal and transgenic Del1 mice harboring a deletion mutation of exon 7 in the type II collagen gene. Reduced and retarded chondrogenesis in Del1 mice was evident in callus samples as reduced mRNA levels for the cartilage specific type IX and XI collagens at days 7 and 9 of fracture healing. Analysis of the calluses for alternative splicing of pro alpha 1(II) collagen mRNA also suggested retarded chondrogenesis in Del1 calluses. Another developmentally regulated step in limb development, a switch between alternative promoters of the alpha 1(IX) collagen gene, was also seen during fracture healing but was less obvious in Del1 calluses. Finally, the current data suggest that the abnormality in bone remodelling in Del1 mice involves activation of the genes coding for alpha 1(XI) and alpha 2(VI) collagens.

Alternative Splicing↗

PubMed1994

Retarded chondrogenesis in transgenic mice with a type II collagen defect results in fracture healing abnormalities.

We have examined the biological and biomechanical consequences of defective type II collagen production for fracture repair employing a genetically engineered mouse line Del1 which was generated by microinjection of a 39-kb mouse pro alpha 1(II) collagen gene construct containing a deletion of exon 7 and intron 7 (Metsäranta et al. [1992] J. Cell Biol. 118:203-212). Standardized tibial fractures were produced in transgenic Del1 mice and their nontransgenic littermates were used as controls. The fracture callus tissues were analyzed at days 7, 9, 14, 28, and 42 using radiography, histomorphometry, biomechanical testing, and Northern analysis of mRNAs for several tissue-specific matrix components. Deficient production of cartilage in Del1 mice resulted in reduced radiographic callus size, smaller cross-sectional area, and impaired biomechanical properties when compared with fractures of nontransgenic control mice. The differences were most evident in 14-day fracture calluses. Consequently mRNAs for cartilage-specific type IX and X collagens and aggrecan were also reduced in Del1 calluses. Levels of type II collagen mRNAs were unaffected since the mutated transgene produced additional type II collagen mRNA molecules. Further abnormalities in the fracture repair process of Del1 mice were observed in callus remodeling. In the control animals a typical feature of external callus remodeling was reduction of callus size during endochondral ossification between days 14 and 28. Such reduction was not observed in the transgenic mice. Histological examination of fracture calluses suggested also a reduction in trabecular surface area, which was found to be even more pronounced in metaphyseal bone of Del1 mice. Despite these differences the biomechanical properties of the calluses in the two groups became similar by day 28 of fracture healing. The results thus suggest that reduced chondrogenesis due to the presence of mutated transgenes in Del1 mice not only causes a temporary impairment in biomechanical properties of healing fractures but also affects later stages of callus remodeling.

Animals↗

PubMed1994

Detoxification from methadone maintenance treatment in Sweden: long-term outcome and effects on quality of life and life situation.

Of 59 subjects who have undergone voluntary and serious attempts to terminate methadone maintenance treatment (MMT) within the framework of the Swedish methadone program, 50 could be reached for an interview. Of these, 25 were classified--with some reservations--as successful (Group 1), i.e., they lived opiate-free and to all appearances well-ordered lives. The other 25 had failed in their attempts (Group 2) and were all in methadone treatment, most functioning well. A comparison was made between the two groups with regard to change in perceived quality of life and actual life situation from the time before the detoxification attempts were begun (Period 1) until the time preceding the interview (Period 2). The results indicate that Group 1 has achieved a higher quality of life and a more stable actual life situation compared with Group 2.

Adaptation, Psychological↗

PubMed1993

A standardized experimental fracture in the mouse tibia.

The increased use of transgenic mice as experimental animals provides new opportunities to study the biology of fracture repair. We have developed a technique for the production of a standard closed experimental fracture in the mouse tibia. A 0.2 mm stainless-steel rod was introduced into the medullary cavity and the pre-nailed tibial shaft was fractured by an impact device, which resulted in a reproducible transverse or slightly oblique fracture pattern. The intramedullary rod maintained axial alignment, and the fractures united without displacement. On the basis of measurements of callus geometry, four-point bending tests, biochemical analyses, and quantitative histology, the progress of callus formation and remodeling occurred in a predictable sequence of healing phases. The ultimate bending loads of the fractures increased with time, reaching 74% of the strength of intact control tibias in 4 weeks. The stiffness values of the fractures returned to normal levels and, as determined radiographically, the fractures united by external callus in 4 weeks. Radiographically, callus size, cross-sectional callus area, and callus mass peaked at 2 weeks and decreased thereafter, indicating the start of external remodeling. Histologically, the amount of mesenchymal tissue was maximal at days 5 and 7. The callus cartilage area peaked at day 9; at its maximum, it accounted for 46% of the total callus area. Early periosteal formation of membranous new bone, followed by endochondral ossification, resulted in a linear increase of callus bone during the healing process. The healing sequence of the mouse tibial fracture was similar to that seen in the rat tibia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Regulation of extracellular matrix genes during fracture healing in mice.

The expression of several collagens, cartilage proteoglycan core protein (aggrecan), and osteonectin was investigated during healing of standardized fractures of the mouse tibia. Total RNA was extracted from fracture calluses and normal bone, and analyzed by Northern hybridization using specific cDNA probes. Based on the predominant fibrillar collagen type expressed, three phases of fracture healing were observed. Type III collagen expression characteristic for the inflammatory stage increased first, followed by Type II collagen expression indicative of the cartilaginous reparative phase, and by Type I collagen production, characteristic for the ossification and remodelling stages. Type IX collagen and aggrecan expression coincided with Type II collagen expression during the chondrogenesis. The mRNA for Type X collagen, a marker for hypertrophic chondrocytes during endochondral ossification, occurred somewhat later than that of other cartilage-specific genes. Osteonectin mRNA was present throughout the healing process and peaked during rapid new bone growth. This study confirms that the pattern of gene expression in the murine system is similar to, but somewhat faster than, other species analyzed (rat, rabbit, human).

Aggrecans↗

PubMed1980

The metabolism of arachidonic acid in isolated hamster, rat and guinea pig lungs.

The perfusion effluent from isolated rat lungs caused relaxations of superfused strips of bovine (BBBCA) and pig (PCA) coronary arteries. The effluent from hamster lungs had similar effect on BCA. Bolus injections of arachidonate (AA, 10-20 microgram) into rat lungs caused further relaxations of superfused BCA and contractions of rat stomach strip (RSS). AA injections into guinea pig lungs resulted in dose dependent contractions of BCA and PCA. Similar dose dependent contractions of PCA and RSS were seen in hamster experiments, however the responses of BCA varied with the AA dose. Infusion of AA (5-25 microgram/min) into guinea pig lungs resulted in dose dependent contractions of superfused PCA and BCA. In hamster experiments AA infusion (5 microgram/min) caused a small relaxation of BCA, but had no effect on PCA. When 14C-AA was injected into the pulmonary circulation, the amounts of metabolites were greater in the perfusion effluent from hamster than from rat lungs. In rat lungs 6-oxo-PGF1 alpha was one of the main metabolites. In contrast, in hamster lungs this metabolite represented only a small part of the total metabolite formation. Thromboxane B2 was one of the main metabolites formed in hamster lungs and its rate of formation increased greatly with increasing AA doses. The results indicate that the metabolite pattern of arachidonate in isolated rat lungs is different from that in hamster and guinea pig lungs. The total rate of AA metabolism in rat lungs is smaller than in hamster lungs.

Animals↗