ABSTRACT
Recently discovered 42 AChE inhibitors binding at the catalytic and peripheral anionic site were identified on the basis of molecular docking approach, and its comparative quantitative structure-activity relationship (QSAR) models were developed. These structurally diverse inhibitors were obtained by our previously reported high-throughput in vitro screening technique using 384-well plate's assay based on colorimetric method of Ellman. QSAR models were developed using (i) genetic function algorithm, (ii) genetic partial least squares, (iii) support vector machine and (iv) artificial neural network techniques. The QSAR model robustness and significance was critically assessed using different cross-validation techniques on test data set. The generated QSAR models using thermodynamic, electrotopological and electronic descriptors showed that nonlinear methods are more robust than linear methods, and provide insight into the structural features of compounds that are important for AChE inhibition.
ABSTRACT
The atom-centered partial charges-approximation is commonly used in current molecular modeling tools as a computationally inexpensive alternative to quantum mechanics for modeling electrostatics. Even today, the use of partial charges remains useful despite significant advances in improving the efficiency of ab initio methods. Here, we report on new parameters for the EEM and SFKEEM electronegativity equalization-based methods for rapidly determining partial charges that will accurately model the electrostatic potential of flexible molecules. The developed parameters cover most pharmaceutically relevant chemistries, and charges obtained using these parameters reproduce the B3LYP/cc-pVTZ reference electrostatic potential of a set of FDA-approved drug molecules at best to an average accuracy of 13 +/- 4 kJ mol(-1); thus, equipped with these parameters electronegativity equalization-based methods rival the current best non-quantum mechanical methods, such as AM1-BCC, in accuracy, yet incur a lower computational cost. Software implementations of EEM and SFKEEM, including the developed parameters, are included in the conformer-generation tool BALLOON, available free of charge at http://web.abo.fi/fak/mnf/bkf/research/johnson/software.php.
Subject(s)
Drug Discovery , Pharmaceutical Preparations/chemistry , Calibration , Computer Simulation , High-Throughput Screening Assays , Models, Molecular , Molecular Conformation , Reproducibility of Results , Software , Static ElectricityABSTRACT
Conformational activation increases the affinity of integrins to their ligands. On ligand binding, further changes in integrin conformation elicit cellular signalling. Unlike any of the natural ligands of alpha2beta1 integrin, human echovirus 1 (EV1) seemed to bind more avidly a 'closed' than an activated 'open' form of the alpha2I domain. Furthermore, a mutation E336A in the alpha2 subunit, which inactivated alpha2beta1 as a collagen receptor, enhanced alpha2beta1 binding to EV1. Thus, EV1 seems to recognize an inactive integrin, and not even the virus binding could trigger the conformational activation of alpha2beta1. This was supported by the fact that the integrin clustering by EV1 did not activate the p38 MAP kinase pathway, a signalling pathway that was shown to be dependent on E336-related conformational changes in alpha2beta1. Furthermore, the mutation E336A did neither prevent EV1 induced and alpha2beta1 mediated protein kinase C activation nor EV1 internalization. Thus, in its entry strategy EV1 seems to rely on the activation of signalling pathways that are dependent on alpha2beta1 clustering, but do not require the conformational regulation of the receptor.
Subject(s)
Enterovirus B, Human/physiology , Enterovirus B, Human/pathogenicity , Integrin alpha2beta1/metabolism , Amino Acid Substitution , Animals , Binding Sites , CHO Cells , Cell Line , Chlorocebus aethiops , Cricetinae , Cricetulus , Humans , In Vitro Techniques , Integrin alpha2beta1/chemistry , Integrin alpha2beta1/genetics , Models, Molecular , Mutagenesis, Site-Directed , Protein Conformation , Protein Structure, Tertiary , Receptors, Virus/chemistry , Receptors, Virus/genetics , Receptors, Virus/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Signal Transduction , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
ShaEP is a tool for rigid-body superimposition and similarity evaluation of ligand-sized molecules. Molecular overlay methods traditionally work on either substructures, molecular surfaces or interaction fields, or atom-centered Gaussian functions representing the molecular volume. While substructure searches are unlikely to reveal hits that are chemically different from the template structure, the other methods are capable of "scaffold hopping". Methods that match characteristic points in interaction fields can find alignments in situations where only some portions of the structures match but potentially miss good alignments if the used point sets are not detailed enough, which in turn increases the runtime of the used graph algorithms beyond practical limits. The faster, polynomially scaling volumetric methods consider the whole space to be equally important, which works well for molecules of equal size but partial matches might go undetected. ShaEP aims to capture the strengths of both field-based and volumetric approaches. It generates initial superimpositions using a matching algorithm on graphs that coarsely represent the electrostatic potential and local shape at points close to the molecular surfaces. The initial alignments are then optimized by maximization of the volume overlap of the molecules, computed using Gaussian functions. ShaEP overlays drug-sized molecules on a subsecond timescale, allowing for the screening of large virtual libraries. The program is available free of charge from www.abo.fi/fak/mnf/bkf/research/johnson/software.php.
Subject(s)
Static Electricity , Cluster Analysis , Molecular Structure , X-RaysABSTRACT
Collagen receptor integrins alpha 1 beta 1 and alpha 2 beta 1 can selectively recognize different collagen subtypes. Here we show that their alpha I domains can discriminate between laminin isoforms as well: alpha 1I and alpha 2I recognized laminin-111, -211 and -511, whereas their binding to laminin-411 was negligible. Residue Arg-218 in alpha1 was found to be instrumental in high-avidity binding. The gain-of-function mutation E318W makes the alpha 2I domain to adopt the "open" high-affinity conformation, while the wild-type alpha 2I domain favors the "closed" low-affinity conformation. The E318W mutation markedly increased alpha 2I domain binding to the laminins (-111, -211 and -511), leading us to propose that the activation state of the alpha 2 beta 1 integrin defines its role as a laminin receptor. However, neither wild-type nor alpha 2IE318W domain could bind to laminin-411. alpha 2IE318W also bound tighter to all collagens than alpha 2I wild-type, but it showed reduced ability to discriminate between collagens I, IV and IX. The corresponding mutation, E317A, in the alpha 1I domain transformed the domain into a high-avidity binder of collagens I and IV. Thus, our results indicate that conformational activation of integrin alpha 1I and alpha 2I domains leads to high-avidity binding to otherwise disfavored collagen subtypes.
Subject(s)
Collagen/metabolism , Integrin alpha1/chemistry , Integrin alpha2/chemistry , Laminin/metabolism , Arginine/chemistry , Collagen/classification , Humans , Integrin alpha1/genetics , Integrin alpha1/metabolism , Integrin alpha2/genetics , Integrin alpha2/metabolism , Models, Molecular , Mutation , Protein Binding , Protein Isoforms/metabolism , Protein Structure, TertiaryABSTRACT
Activation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate (TPA) induces ligand-independent aggregation of a cell surface collagen receptor, alpha2beta1 integrin. Concomitantly, TPA increases the avidity of alpha2beta1 for collagen and the number of conformationally activated alpha2beta1 integrins. The structural change was shown using a monoclonal antibody 12F1 that recognizes the "open" (active) conformation of the inserted domain in the alpha2 subunit (alpha2I). Amino acid residue Glu-336 in alpha2 subunit is proposed to mediate the interaction between alpha2I domain and beta1 subunit. Glu-336 seems to regulate a switch between open and "closed" conformations, since the mutation alpha2E336A inhibited the TPA-related increase in the number of 12F1 positive integrins. E336A also reduced cell adhesion to collagen. However, E336A did not prevent the TPA-related increase in adhesion to collagen or alpha2beta1 aggregation. Thus, alpha2beta1 integrin avidity is regulated by two synergistic mechanisms, first an alpha2E336-dependent switch to the open alpha2I conformation, and second an alpha2E336-independent mechanism temporally associated with receptor aggregation.
Subject(s)
Collagen Type I/metabolism , Extracellular Matrix/metabolism , Integrin alpha2beta1/metabolism , Protein Conformation/drug effects , Animals , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , CHO Cells/drug effects , CHO Cells/metabolism , Carcinogens/pharmacology , Cell Adhesion , Cricetinae , Cricetulus , Humans , Integrin alpha2beta1/genetics , Ligands , Mutation/genetics , Osteosarcoma/metabolism , Osteosarcoma/pathology , Protein Binding , Protein Kinase C/metabolism , Receptors, Collagen/metabolism , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
Infantile neuronal ceroid-lipofuscinosis (infantile CLN1) is a progressive and uniformly fatal lysosomal storage disease of the nervous system. The purpose of this study was to compare the findings of various radiological examinations of the brain in the course of infantile CLN1 in order to evaluate the relative usefulness of the methods and their potential for monitoring therapeutic interventions. We examined eight infantile CLN1 patients, 51 studies, in various stages of the disease--preclinical to late stage--with proton magnetic resonance spectroscopy (1H-MRS), MRI, and perfusion SPECT, and in addition three benzodiazepine (BZ) receptor ligand SPECT studies. Both 1H-MRS and MRI showed abnormal findings before clinical manifestations of the disease. Cortical hypoperfusion and loss of cortical BZ receptors revealed by SPECT appeared simultaneously with clinical signs. After the age of 4 years MRI and SPECT alterations progressed minimally, whereas 1H-MRS showed progressive deterioration of neurometabolism. Of the four methods used in this study, MRI proved to be the most practicable for diagnosing infantile CLN1; the final diagnosis of infantile CLN1 is confirmed by the characteristic clinical picture and DNA or PPT enzyme analysis. The combination of 1H- MRS and MRI could be most useful for monitoring therapeutic interventions.
Subject(s)
Aspartic Acid/analogs & derivatives , Magnetic Resonance Imaging , Neuronal Ceroid-Lipofuscinoses/metabolism , Neuronal Ceroid-Lipofuscinoses/pathology , Tomography, Emission-Computed, Single-Photon , Aspartic Acid/metabolism , Brain/blood supply , Brain/metabolism , Brain/pathology , Child , Child, Preschool , Choline/metabolism , Creatinine/metabolism , Humans , Infant , Infant, Newborn , Magnetic Resonance Spectroscopy , Oximes , RadiopharmaceuticalsABSTRACT
Integrin alpha(1)beta(1) is one of four collagen-binding integrins in humans. Collagens bind to the alphaI domain and in the case of alpha(2)I collagen binding is competitively inhibited by peptides containing the RKKH sequence and derived from the metalloproteinase jararhagin of snake venom from Bothrops jararaca. In alpha(2)I, these peptides bind near the metal ion-dependent adhesion site (MIDAS), where a collagen (I)-like peptide is known to bind; magnesium is required for binding. Published structures of the ligand-bound "open" conformation of alpha(2)I differs significantly from the "closed" conformation seen in the structure of apo-alpha(2)I near MIDAS. Here we show that two peptides, CTRKKHDC and CARKKHDC, derived from jararhagin also bind to alpha(1)I and competitively inhibit collagen I binding. Furthermore, calorimetric and fluorimetric measurements show that the structure of the complex of alpha(1)I with Mg(2+) and CTRKKHDC differs from structure in the absence of peptide. A comparison of the x-ray structure of apo-alpha(1)I ("closed" conformation) and a model structure of the alpha(1)I ("open" conformation) based on the closely related structure of alpha(2)I reveals that the binding site is partially blocked to ligands by Glu(255) and Tyr(285) in the "closed" structure, whereas in the "open" structure helix C is unwound and these residues are shifted, and the "RKKH" peptides fit well when docked. The "open" conformation of alpha(2)I resulting from binding a collagen (I)-like peptide leads to exposure of hydrophobic surface, also seen in the model of alpha(1)I and shown experimentally for alpha(1)I using a fluorescent hydrophobic probe.
Subject(s)
Crotalid Venoms/pharmacology , Integrin alpha1beta1/chemistry , Metalloendopeptidases/pharmacology , Peptide Fragments/pharmacology , Amino Acid Sequence , Binding Sites , Binding, Competitive , Calorimetry, Differential Scanning , Collagen Type I/metabolism , Crotalid Venoms/chemistry , Crystallization , Crystallography, X-Ray , Fluorescent Dyes , Humans , Integrin alpha1beta1/antagonists & inhibitors , Integrin alpha1beta1/metabolism , Magnesium/metabolism , Metalloendopeptidases/chemistry , Models, Molecular , Molecular Structure , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Protein Conformation , Protein Structure, Secondary , Recombinant Proteins , Spectrometry, Fluorescence , Bothrops jararaca VenomABSTRACT
The integrins alpha(1)beta(1), alpha(2)beta(1), alpha(10)beta(1), and alpha(11)beta(1) are referred to as a collagen receptor subgroup of the integrin family. Recently, both alpha(1)beta(1) and alpha(2)beta(1) integrins have been shown to recognize triple-helical GFOGER (where single letter amino acid nomenclature is used, O = hydroxyproline) or GFOGER-like motifs found in collagens, despite their distinct binding specificity for various collagen subtypes. In the present study we have investigated the mechanism whereby the latest member in the integrin family, alpha(11)beta(1), recognizes collagens using C2C12 cells transfected with alpha(11) cDNA and the bacterially expressed recombinant alpha(11) I domain. The ligand binding properties of alpha(11)beta(1) were compared with those of alpha(2)beta(1). Mg(2+)-dependent alpha(11)beta(1) binding to type I collagen required micromolar Ca(2+) but was inhibited by 1 mm Ca(2+), whereas alpha(2)beta(1)-mediated binding was refractory to millimolar concentrations of Ca(2+). The bacterially expressed recombinant alpha(11) I domain preference for fibrillar collagens over collagens IV and VI was the same as the alpha(2) I domain. Despite the difference in Ca(2+) sensitivity, alpha(11)beta(1)-expressing cells and the alpha(11) I domain bound to helical GFOGER sequences in a manner similar to alpha(2)beta(1)-expressing cells and the alpha(2) I domain. Modeling of the alpha I domain-collagen peptide complexes could partially explain the observed preference of different I domains for certain GFOGER sequence variations. In summary, our data indicate that the GFOGER sequence in fibrillar collagens is a common recognition motif used by alpha(1)beta(1), alpha(2)beta(1), and also alpha(11)beta(1) integrins. Although alpha(10) and alpha(11) chains show the highest sequence identity, alpha(2) and alpha(11) are more similar with regard to collagen specificity. Future studies will reveal whether alpha(2)beta(1) and alpha(11)beta(1) integrins also show overlapping biological functions.
Subject(s)
Collagen/chemistry , Collagen/metabolism , Integrins/chemistry , Integrins/metabolism , Receptors, Collagen/chemistry , Receptors, Collagen/metabolism , Amino Acid Motifs , Animals , Calcium/metabolism , Cell Adhesion , Cells, Cultured , DNA, Complementary/metabolism , Dose-Response Relationship, Drug , Humans , Kinetics , Magnesium/metabolism , Mice , Models, Molecular , Peptides/chemistry , Phenylalanine/chemistry , Precipitin Tests , Protein Binding , Protein Structure, Tertiary , Recombinant Proteins/metabolismABSTRACT
We present a case report of acute bilateral excercise-induced compartment syndrome in the adductor longus muscles, which was treated with bilateral medial fasciotomies. Postoperatively, the healing process of the adductor muscles was followed up by repeated MR imagings over six months. Myonecrosis was found in peroperative muscle biopsies. Pain and muscle swelling subsided soon after the fasciotomy, correlating with the early postoperative MR findings. Four months postoperatively, the signal intensity of the adductor muscles was normal in T1- and T2-weighted images, but the normal fibre structure of the adductor muscles could only be seen 6 months postoperatively. At six month's control checkup there was no subjective weakness of the adductors, and hyperesthesia had disappeared and the patient was capable of normal activities.
Subject(s)
Athletic Injuries/diagnosis , Compartment Syndromes/diagnosis , Magnetic Resonance Imaging/methods , Thigh/injuries , Adult , Athletic Injuries/surgery , Compartment Syndromes/etiology , Compartment Syndromes/surgery , Follow-Up Studies , Humans , Male , Muscle, Skeletal/injuries , Treatment OutcomeABSTRACT
A 30-year-old father and his 2 sons with slight hyperkinesia and mildly dysmorphic features and their close relatives were examined clinically and with computed tomography (CT) and magnetic resonance imaging (MRI). Neurophysiological and biochemical examinations were normal; however, brain MRI of the father and sons revealed extensive cerebral white matter changes. No radiological progression could be detected at a 13-year follow-up examination of the father, and proton magnetic resonance spectroscopy (MRS) of the father at the age of 30 years was normal. MRI findings in the relatives were normal, suggesting an autosomal dominant syndrome due to a new mutation in the father.
Subject(s)
Brain Diseases/genetics , Cerebral Cortex/abnormalities , Adult , Cerebral Cortex/pathology , Child , Chromosomes, Human, Pair 18/genetics , Humans , Magnetic Resonance Imaging , Male , PedigreeABSTRACT
OBJECTIVE: To correlate the phenotypes with the genotypes of 10 Finnish juvenile neuronal ceroid lipofuscinosis (JNCL; late-onset Batten disease) patients who all are compound heterozygotes for the major 1.02-kb deletion in the CLN3 gene. METHODS: The mutations on the non-1.02-kb deletion chromosomes were screened in 6 patients; in the other 4 patients the mutations were known (one affecting a splice site, two missense mutations, and one deletion of exons 10 through 13). Clinical features were examined, and MRI, MRS, somatosensory evoked magnetic field (SEF), and overnight polysomnography (PSG) studies were performed. RESULTS: A novel deletion of exons 10 through 13 was found in 6 patients belonging to three families. In the patients carrying the deletions of exons 10 through 13 the clinical course of the disease was fairly similar. Variation was greatest in the time course to blindness. In these patients the mental and motor decline was slower than in classic JNCL, but more severe than in the two patients with missense mutations in exons 11 and 13. MRI showed brain atrophy in 4 patients. One patient had hyperintense periventricular white matter, otherwise brain signal intensities were normal. SEFs were enhanced in patients older than 14 years, whereas in PSG all but the youngest 6-year-old patient showed epileptiform activity in slow-wave sleep. CONCLUSIONS: JNCL can manifest as at least three different phenotypes: classic, delayed classic, and protracted JNCL with predominantly ocular symptoms. Finnish compound heterozygotes have the delayed classic or the protracted form of JNCL.
Subject(s)
Heterozygote , Neuronal Ceroid-Lipofuscinoses/genetics , Adolescent , Adult , Age of Onset , Case-Control Studies , Child , Chromosome Deletion , Evoked Potentials, Somatosensory/physiology , Exons , Female , Genotype , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Magnetoencephalography , Male , Mutation, Missense , Phenotype , PolysomnographyABSTRACT
We performed a subgroup analysis of the first European Stroke Prevention Study including 1,306 patients recruited in a single center, Kuopio, Finland, to investigate whether or not antiplatelet therapy is effective in the secondary prevention of stroke in hypertensive patients with transient ischemic attack (TIA) or stroke. The patients were treated with aspirin, 990 mg/day, plus dipyridamole, 225 mg/day, or placebo for 2 years. The patients with high systolic blood pressure (> or = 140 mm Hg; n = 1.105) or high diastolic blood pressure (> or = 85 mm Hg; n = 1,120) at entry, were classified into subgroups by blood pressure level. The effect of treatment was statistically significant in all subgroups with high systolic (end-point reduction, 55.2-68.2%) and diastolic blood pressure (end-point reduction, 47.3-82.1%). Risk reduction was, however, greatest in patients with the highest diastolic blood pressure. One possible explanation is that platelets are more activated in these patients, and this can be effectively prevented by antiplatelet therapy. Further studies are needed to confirm this hypothesis.
Subject(s)
Aspirin/therapeutic use , Cerebrovascular Disorders/prevention & control , Dipyridamole/therapeutic use , Hypertension/complications , Ischemic Attack, Transient/complications , Platelet Aggregation Inhibitors/therapeutic use , Blood Pressure/drug effects , Cerebrovascular Disorders/complications , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Hypertension/drug therapy , Ischemic Attack, Transient/drug therapy , Male , Middle AgedABSTRACT
A new clinical scoring system, including subjective assessment of symptoms and evaluation of ankle range of motion and isokinetic measurement of ankle plantar flexion and dorsiflexion strengths, is presented in 101 patients (86 men, 15 women) who had repair of a closed Achilles tendon rupture. Twenty-one patients were competitive athletes and 70 were recreational athletes. Eighty-one percent of the ruptures were related to sports, and 32% occurred while playing volleyball. Twenty-six patients had previous Achilles tendon symptoms. At followup, an average of 3.1 years after repair, the overall result scores were excellent in 34 cases, good in 46, fair in 17, and poor in four. Only age was a predictor of overall results. The isokinetic strength scores were excellent or good in 72 cases, fair in 18, and poor in 11. Presence of systemic diseases, activity level, previous Achilles tendon symptoms, and later return to physical exercise were predictors of strength results. Gender, body weight, height, period between rupture and operation, surgeon, rupture site, operative method, complications, and thickness, width, and area of the Achilles tendon at followup were not related significantly to the outcome.
Subject(s)
Achilles Tendon/injuries , Achilles Tendon/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Prognosis , Rupture , Treatment OutcomeABSTRACT
Antiplatelet treatment is well established in the secondary prevention of ischemic cerebrovascular events. The reasons for the occurrence of stroke, even though the patient receives drug treatment, have remained unclear. We performed a subgroup analysis of the European Stroke Prevention Study (ESPS 1) to investigate the efficacy of treatment in patients with different cardiovascular risk factors. The ESPS 1 recruited 1306 patients with TIA, RIND or stroke in one single center of Kuopio in Finland. The patients were treated with aspirin 990 mg/day+dipyridamole 225 mg/day or placebo for 2 years or until an endpoint. The endpoints were stroke or death from any cause. The risk factors for endpoints were analyzed by Cox univariate regression analyses. The effect of a single risk factor on the efficacy of antiplatelet therapy was analyzed by Cox proportional hazards model in subgroups according to the significant risk factors found in the univariate analysis. The efficacy of treatment was statistically significant in all subgroups except diabetics and current smokers for the stroke endpoint. When the combined endpoint of stroke or death was used, the treatment failed also to show statistical significance in patients with coronary heart disease. This lack of efficacy might be due to the small sample size. The efficacy of treatment was significantly better in TIA patients than in stroke patients when analyzed with stroke as an end point. This study provides strong evidence that the effectiveness of antiplatelet treatment in ischemic stroke and TIA patients is independent of most cardiovascular risk factors. Furthermore, all patients with TIA and ischemic stroke should receive secondary prevention regardless of whether or not there are risk factors.
Subject(s)
Cerebrovascular Disorders/drug therapy , Ischemic Attack, Transient/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Aspirin/therapeutic use , Cerebrovascular Disorders/prevention & control , Dipyridamole/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Europe , Female , Finland , Humans , Logistic Models , Male , Middle Aged , Proportional Hazards Models , Regression Analysis , Risk FactorsABSTRACT
We determined the incidence of a total Achilles tendon rupture in the city of Oulu and changes over the 16-year period 1979-1994. During this time, 110 ruptures occurred. The incidence increased from 2 ruptures/10(5) inhabitants in 1979-1986 to 12 in 1987-1994, with a mean of 7. The peak annual incidence, 18, was recorded in 1994. The incidence was highest in the age group 30-39 years. Male dominance was 5.5:1, and 81% of the ruptures were related to sports, with 88% occurring in ball games. The mean age was significantly lower for the sports injuries.
Subject(s)
Achilles Tendon/injuries , Adult , Aged , Athletic Injuries/epidemiology , Female , Finland/epidemiology , Humans , Incidence , Male , Middle Aged , Rupture/epidemiologyABSTRACT
The association between ABO blood groups and Achilles tendon (AT) ruptures was studied in 215 consecutive AT rupture patients treated at Oulu University Hospital during the 16-year period from 1979 to 1994 as compared with control material consisting of earlier blood group determinations performed on an unselected sample of 5,536 young Finnish male adults. There was no blood group O dominance or other statistical differences in ABO blood groups between the patients with AT rupture and the control population (chi 2 3.79, P = 0.28), the A/O ratio being 1.82 in the rupture group and 1.42 in the controls. We found no blood group O dominance in competitive athletes, recreational athletes or non-athletes, in patients with sports-related AT ruptures or non-sports-related ruptures and in younger (< 45 years) or older (> or = 45--years) patients. In conclusion, our results do not confirm early findings of blood group O dominance in patients with AT rupture.
Subject(s)
ABO Blood-Group System/blood , Achilles Tendon/injuries , Athletic Injuries/blood , Adult , Age Distribution , Athletic Injuries/epidemiology , Female , Finland , Humans , Male , Middle Aged , Retrospective Studies , Rupture/blood , Rupture/epidemiology , Sex DistributionABSTRACT
Liberation of the carboxy-terminal propeptide of type I procollagen (PICP) and the amino-terminal propeptide of type III procollagen (PIIINP) into body fluids reflects synthesis of the respective collagen types. Here, we followed PICP and PIIINP in serum with specific radioimmunoassays after hip surgery. Preoperative median of S-PICP was 112 micrograms/liter (range 87 to 154, n = 9), the 1-day median being 58 micrograms/liter (33 to 79). The corresponding medians for S-PIIINP were 4.4 micrograms/liter (3.5 to 7.0) and 3.3 micrograms/liter (2.0 to 3.5). The medians reached their maximums 14 days after surgery, 172 micrograms/liter (122 to 440) for S-PICP and 12.4 micrograms/liter (8.0 to 15.4) for S-PIIINP, after which the preoperative values were slowly approached over several months. Comparable results were found in a greater sample (n = 50). Our results indicate that the synthesis of structural collagen is inhibited immediately after surgery, but the inhibition is soon overcome by active collagen synthesis at the site of trauma. Collagen metabolism remains activated for several months after surgery.
Subject(s)
Collagen/biosynthesis , Hip Joint/surgery , Hip Prosthesis , Humans , Peptide Fragments/metabolism , Postoperative Period , Procollagen/metabolism , Reoperation , Surgical Wound Infection/metabolismABSTRACT
We carried out 102 hip revision arthroplasties using an uncemented isoelastic femoral stem on 92 patients between 1985 and 1989. The proximal femoral bone stock had deteriorated in 45%. Eleven patients died during the mean follow up of 5.7 years. The femoral component has been revised again for loosening in 13, for infection in 5 and for dislocation in 3. Radiographs of 70 hips showed incipient migration at 3 months in 20, and at the time of review 27 hips had migrated 5 mm or more. Nine stems had migrated more than 8 mm and were judged to be loose. There were 11 fractures before operation and 15 during operation; they all healed. Slight cortical hypertrophy of not more than 2 mm was present in most cases. Three patients (4 hips) were excluded because of severe systemic illness. Of the remaining 66 hips, the clinical outcome was excellent in 18%, good in 50%, fair in 26% and poor in 6%. The isoelastic stem is associated with poor primary fixation which is indicated by early subsidence. The results, with a total failure rate of 33%, are unsatisfactory and the isoelastic femoral stem used in this series cannot be recommended for revision operations.
Subject(s)
Hip Prosthesis/instrumentation , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Bone Cements , Bone Remodeling , Female , Follow-Up Studies , Hip Prosthesis/methods , Humans , Male , Middle Aged , Prosthesis Design , Prosthesis Failure , Reoperation , Treatment FailureABSTRACT
From 1983 to 1985 we performed 114 primary hip replacements in 108 consecutive osteoarthritic patients using a non-cemented RM isoelastic femoral stem. After a mean follow-up of 8.2 years, ten patients had died, 11 hips had been revised, six patients had been lost to follow-up and two had been excluded due to severe general illnesses. Of 85 arthroplasties (in 79 patients) 14 could not be assessed because of other illness or disability. The 71 remaining were reviewed by questionnaire and radiography; an excellent or good overall functional result was found in 31, 16 were fair and 24 were poor. Radiographically, 21 of 71 stems were judged to be loose and ten showed osteolytic foci, six of these without obvious loosening. We conclude that the isoelastic RM stem shows a high rate of loosening, but that this is not always associated with a poor subjective result. Regular radiographic review is necessary. The results are worse than those reported for other uncemented stems and for cemented stems.