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1.
Ophthalmic Genet ; 41(3): 223-234, 2020 06.
Article in English | MEDLINE | ID: mdl-32316871

ABSTRACT

BACKGROUND: Stickler syndrome is a collagenopathy caused by mutations in the genes COL2A1 (STL1) or COL11A1 (STL2). Affected patients manifest ocular, auditory, articular, and craniofacial manifestations in varying degrees. Ocular symptoms include myopia, retinal detachment, cataract, and glaucoma. The aim of this systematic review was to evaluate the prevalence of ocular manifestations and the outcome of prophylactic treatment on reducing the risk of retinal detachment. METHOD: A systematic literature search was performed in the PubMed database. Information on the cross-study prevalence of myopia, retinal detachment, cataract, glaucoma, visual impairment, severity and age of onset of myopia and retinal detachments. Studies that reported on the outcome of prophylactic treatment against a control group were explored. RESULTS: 37 articles with 2324 individual patients were included. Myopia was found in 83% of patients, mostly of a moderate to severe degree. Retinal detachments occurred in 45% of patients. Generally, the first detachment occurred in the second decade of life in STL1 patients and later in STL2. Cataracts were more common in STL2 patients, 59% versus 36% in STL1. Glaucoma (10%) and visual impairment (blind: 6%; vision loss in one eye: 10%) were rare. Three studies reported on the effect of prophylactic treatment being protective. CONCLUSION: Ocular manifestations are common in Stickler patients, but the comparison between studies was difficult because of inconsistencies in diagnostic and inclusion criteria by different studies. Sight-threatening complications such as retinal detachments are common but although prophylactic therapy is reported to be effective in retrospective studies, evidence from randomized trials is missing.


Subject(s)
Arthritis/prevention & control , Collagen Type II/genetics , Collagen Type XI/deficiency , Connective Tissue Diseases/prevention & control , Hearing Loss, Sensorineural/prevention & control , Mutation , Retinal Detachment/prevention & control , Vitreous Detachment/prevention & control , Arthritis/genetics , Arthritis/pathology , Collagen Type XI/genetics , Connective Tissue Diseases/genetics , Connective Tissue Diseases/pathology , Cryotherapy , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/pathology , Humans , Laser Therapy , Retinal Detachment/genetics , Retinal Detachment/pathology , Vitreous Detachment/genetics , Vitreous Detachment/pathology
2.
Georgian Med News ; (270): 130-135, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28972498

ABSTRACT

Research objective - to study the state of health of staff of service of fire extinguishing and accident rescue services department for definition of the priority directions of rendering the treatment-and-prophylactic help and rehabilitation of employees. By means of an information and analytical method the retrospective analysis of reports about the registered diseases, their result and the reasons of temporary disability of staff of service of fire extinguishing and accident rescue services department of Department on emergency situations of Almaty in 2011-2016 has been carried out. Statistical processing of the received results of research is carried out by means of Student's t-criterion. The conducted research showed that the high level of primary incidence is characteristic of the staff of service of fire extinguishing and accident rescue services department, at the same time the most significant are diseases of respiratory organs, traumas, poisoning and some other consequences of influence of the external reasons, diseases of bone and muscular system and connecting tissue, blood circulatory system illness. Studying of the state of health of staff of service of fire extinguishing and rescue services allowed to establish the priority directions of rendering the treatment-and-prophylactic help and rehabilitation. Their contents are defined by need of concentration of efforts on prevention, treatment and rehabilitation of the most widespread diseases causing the maximum damage to health.


Subject(s)
Firefighters , Health Status , Cardiovascular Diseases/prevention & control , Connective Tissue Diseases/prevention & control , Connective Tissue Diseases/rehabilitation , Digestive System Diseases/prevention & control , Digestive System Diseases/rehabilitation , Humans , Musculoskeletal Diseases/prevention & control , Musculoskeletal Diseases/rehabilitation , Primary Prevention , Respiratory Tract Diseases/prevention & control , Respiratory Tract Diseases/rehabilitation , Wounds and Injuries/prevention & control , Wounds and Injuries/rehabilitation
3.
Pathol Int ; 67(5): 235-246, 2017 May.
Article in English | MEDLINE | ID: mdl-28393435

ABSTRACT

Platelet-derived growth factor (PDGF) is one of the major mitogens and chemoattractants for mesenchymal and glial cells. Nowadays, the expression of PDGFs are recognized widely in our body, and emerging data indicate the relevance of PDGFs in the homeostatic control of systemic connective tissue as well as parenchymal cells such as neurons. Aberrant PDGF signal is primarily tumorigenic, and also regulates tumor microenvironments. The roles of the PDGF signal in tumorigenesis are diverse depending on the type of cancer, and anti-PDGF therapy needs to be carefully designed based on the information of each tumor cell type and the surrounding microenvironment. PDGFs and receptors (PDGFRs) are abundant in neurons and glial cells, and are neuroprotective through the regulation of neurovascular unit. PDGF signal is functionally correlated with neurotransmission, and can be pathogenetically correlated with psychosomatic neurological diseases. Growing genetic information has been unraveling novel connective tissue diseases and vascular abnormalities in which aberrant PDGF signaling is etiologically correlated. Novel therapeutic approaches targeting PDGF signal are beginning to emerge in various diseases.


Subject(s)
Neoplasms/pathology , Nervous System Diseases/pathology , Platelet-Derived Growth Factor/metabolism , Receptors, Platelet-Derived Growth Factor/metabolism , Signal Transduction , Vascular Diseases/pathology , Carcinogenesis , Connective Tissue Diseases/pathology , Connective Tissue Diseases/prevention & control , Fibrosis/pathology , Fibrosis/prevention & control , Humans , Neoplasms/prevention & control , Nervous System Diseases/prevention & control , Neurons/pathology , Vascular Diseases/prevention & control , Vascular Remodeling
4.
G Ital Med Lav Ergon ; 36(4): 372-5, 2014.
Article in Spanish | MEDLINE | ID: mdl-25558738

ABSTRACT

This paper describes the project "Information Flows", its contents of INAIL data about accidents and occupational diseases reported and recognized and its usefulness for programs of preventive initiatives undertaken by INAIL and by the responsible structures in the single italian regions. We propose some processings of data and suggest how their collection, according to criteria based on occupational medicine, industrial hygiene and epidemiology and a careful analysis and processing of data from more sources could lead to an extension of the workers protection, relatively to "unrecognized" occupational diseases, diseases caused by the "old" risks and the identification of occupational diseases caused by "new" risks.


Subject(s)
Government Agencies/organization & administration , Information Systems/organization & administration , Occupational Diseases/prevention & control , Preventive Medicine/organization & administration , Workers' Compensation/organization & administration , Accidents, Occupational/prevention & control , Accidents, Occupational/statistics & numerical data , Connective Tissue Diseases/epidemiology , Connective Tissue Diseases/etiology , Connective Tissue Diseases/prevention & control , Humans , Insurance Claim Reporting , International Classification of Diseases , Italy/epidemiology , Musculoskeletal Diseases/epidemiology , Musculoskeletal Diseases/etiology , Musculoskeletal Diseases/prevention & control , National Health Programs/organization & administration , National Health Programs/statistics & numerical data , Neoplasms/epidemiology , Neoplasms/etiology , Neoplasms/prevention & control , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Risk Factors
6.
Kardiologiia ; 48(10): 57-64, 2008.
Article in Russian | MEDLINE | ID: mdl-18991837

ABSTRACT

Undifferentiated connective tissue dysplasia (UCTD) is one of most common diseases of the connective tissue. High frequency of UCTD in population along with the fact that it can provoke a number of other diseases make UCTD an important object of the modern biomedical research in the areas of cardiology, neurology, rheumatology and pulmonology. Modern diagnostics and determination of the predisposition to UCTD allow elaboration of personalized therapy. In particular, Mg-containing supplements and medications can be effectively used in the therapy of UCTD. In one of our previous works we have analyzed possible molecular mechanisms of UCTD etiology as well as therapeutic action of magnesium. The use of data on nucleotide polymorphisms as complementation of standard medical diagnostics is one of perspective trends of the post-genomic medical research. The present work suggest a number of nucleotide polymorphisms that can be used in genetic association analyses of the UCTD as of well as therapeutic efficiency of magnesium treatment. Selection and analysis of the polymorphisms was done on the base of molecular mechanisms we had proposed earlier, comprehensive analysis of published data and also with the use of an integral approach to analysis of the functional effects of the nucleotide polymorphisms and corresponding amino acid substitutions.


Subject(s)
Connective Tissue Diseases/genetics , Connective Tissue Diseases/pathology , Gene Expression/genetics , Polymorphism, Single Nucleotide/genetics , Alleles , Connective Tissue Diseases/prevention & control , Genome , HLA-B Antigens/genetics , Humans , Magnesium Oxide/therapeutic use , Matrix Metalloproteinase 2/genetics , Phenotype , Receptors, Calcium-Sensing/genetics , TRPM Cation Channels/genetics
7.
J Am Acad Orthop Surg ; 14(7): 387-96, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16822886

ABSTRACT

The goals of flexor tendon repair are to promote intrinsic tendon healing and minimize extrinsic scarring in order to optimize tendon gliding and range of motion. Despite advances in the materials and methods used in surgical repair and postoperative rehabilitation, complications following flexor tendon injuries continue to occur, even in patients treated by experienced surgeons and therapists. The most common complication is adhesion formation, which limits active range of motion. Other complications include joint contracture, tendon rupture, triggering, and pulley failure with tendon bowstringing. Less common problems include quadriga, swan-neck deformity, and lumbrical plus deformity. Meticulous surgical technique and early postoperative tendon mobilization in a well-supervised therapy program can minimize the frequency and severity of these complications. Prompt recognition of problems and treatment with hand therapy, splinting, and/or surgery may help minimize recovery time and improve function. In the future, the use of novel biologic modulators of healing may nearly eliminate complications associated with flexor tendon injuries.


Subject(s)
Connective Tissue Diseases/etiology , Connective Tissue Diseases/prevention & control , Joint Diseases/etiology , Joint Diseases/prevention & control , Plastic Surgery Procedures/adverse effects , Tendon Injuries/complications , Tendon Injuries/surgery , Humans
8.
Ann Acad Med Stetin ; 52 Suppl 2: 11-6, 2006.
Article in Polish | MEDLINE | ID: mdl-17471833

ABSTRACT

The majority of connective tissue diseases, with the exception of scleroderma which is usually diagnosed past the age of 40 years, may affect women of reproductive age. Questions concerning the impact of the connective tissue disease upon pregnancy, interactions of pregnancy with the disease, and influence of the disease on fetal development are not easily answered. However, our knowledge on the pathogenesis of connective tissue diseases and the mechanisms of action of various antibodies is increasing, enabling improved disease control and reduction of adverse pregnancy outcomes. Multicenter, prospective clinical studies verified some unproven opinions about the adverse influence of pregnancy on scleroderma or systemic lupus erythematosus, as well as about their unavoidably fatal interactions with pregnancy. Careful pregnancy planning and cooperation of the rheumatologist, obstetrician and neonatologist helps avoid disease exacerbation and fetal misdevelopment. Acetylsalicylic acid and heparin reduce the adverse effect of antiphospholipid antibodies. Still, miscarriage, intrauterine fetal death, intrauterine growth retardation, and prematurity are more often encountered in women with systemic lupus erythematosus. However, the risk of adverse pregnancy outcome in these patients is gradually falling. Active lupus nephritis, hypertension, presence of antiphospholipid antibodies, and history of miscarriage are important risk factors. Pregnancy in women with diffuse type of scleroderma is of worse prognosis, often resulting in prematurity and low birthweight. Establishing the risk of immunosupressive and anti-inflammatory therapies enables better treatment of connective tissue diseases in pregnancy. Currently there is no doubt that pregnancy is contraindicated only in a small group of high-risk patients with connective tissue disease.


Subject(s)
Abortion, Spontaneous/epidemiology , Connective Tissue Diseases/epidemiology , Fetal Diseases/epidemiology , Pregnancy Complications/epidemiology , Pregnancy, High-Risk , Antiphospholipid Syndrome/epidemiology , Causality , Comorbidity , Connective Tissue Diseases/prevention & control , Female , Humans , Infant, Newborn , Lupus Erythematosus, Systemic/epidemiology , Lupus Nephritis/epidemiology , Preconception Care , Pregnancy , Pregnancy Complications/prevention & control , Pregnancy Outcome , Prenatal Care , Scleroderma, Systemic/epidemiology
9.
Ann Med ; 37(1): 2-12, 2005.
Article in English | MEDLINE | ID: mdl-15902842

ABSTRACT

Recent data demonstrate the fundamental role of endothelin in the pathogenesis of fibrosis, and the anti-fibrotic potential of dual endothelin receptor antagonists such as bosentan. Although transforming growth factor-beta, aldosterone and connective tissue growth factor, have already been established as contributors to the process of fibrosis, endothelin now emerges as a key player, which may have a role both in the initiation and in maintenance of fibrosis, and may mediate the pro-fibrotic effects of the other agents. Bosentan is an orally active, dual endothelin receptor antagonist, which competitively antagonizes the binding of endothelin to both endothelin receptors ETA and ETB. Bosentan prevents endothelin-induced fibroblast proliferation and extracellular matrix deposition and contraction, and reduces cardiac, hepatic, pulmonary and renal fibrosis in different disease models characterized by the activation of the endothelin system. Bosentan even reverses existing fibrosis, possibly by its effect of stimulating matrix metalloproteinase type 1 (collagenase) expression. The anti-fibrotic effects of bosentan extend to fibrosis induced by mediators other than endothelin such as transforming growth factor-beta, angiotensin II and aldosterone, indicating a central role of endothelin and endothelin receptors in fibrotic processes.


Subject(s)
Connective Tissue Diseases/prevention & control , Endothelin Receptor Antagonists , Endothelins/physiology , Sulfonamides/therapeutic use , Administration, Oral , Animals , Bosentan , Cell Division/drug effects , Connective Tissue Diseases/metabolism , Fibroblasts/drug effects , Fibroblasts/pathology , Fibrosis/drug therapy , Fibrosis/metabolism , Humans , Sulfonamides/administration & dosage
10.
Strabismus ; 12(3): 141-8, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15370521

ABSTRACT

PURPOSE: To investigate the influence of 5-fluorouracil (5-FU) and mitomycin C (MMC) on the postoperative adhesions following strabismus surgery in rabbits. METHODS: Twenty-one New Zealand white rabbits were used in this prospective, masked, controlled trial. Both eyes of 20 animals underwent 3-mm recession of the superior rectus muscle (SRM). In group I (io animals), one eye of each animal received topical application of MMC (0.2 mg/ml) for 5 minutes and the other eye (control eye) was treated with balanced salt solution (BSS) using an intraoperative sponge. In group II (10 animals), a randomly chosen eye of each animal was treated with 5-FU soaked sponges (50 mg/ml) for 5 minutes and the fellow eye (control eye) with BSS. Two eyes of a rabbit were included as unoperated controls. Four weeks after the surgery, conjunctival vascularity and postoperative adhesions between the SRM Tenon's capsule (TC) and SRM sclera (scl) were assessed. Additionally, eyes were enucleated and evaluated histopathologically for evidence of scarring, granuloma formation, and muscle tissue changes under a light microscope. RESULTS: MMC-treated eyes had a higher rate of avascular conjunctiva compared to both controls and 5-FU-treated eyes. Mean adhesion scores, particularly between the SRM-scl, were lower in eyes treated with antiproliferative agents compared to controls. The difference was statistically significant in MMC-treated eyes for the adhesions between SRM-scl (p = 0.03). Histopathological examination revealed less scarring and granuloma formation in MMC- and 5-FU-treated eyes compared to their control eyes. CONCLUSIONS: MMC, and to a lesser extent 5-FU, are shown to be effective in reducing postoperative scarring following strabismus surgery in rabbits. It seems reasonable to suggest that antimetabolites should be used for cases having an increased risk of postoperative adhesions.


Subject(s)
Connective Tissue Diseases/prevention & control , Fluorouracil/administration & dosage , Mitomycin/administration & dosage , Postoperative Complications/prevention & control , Scleral Diseases/prevention & control , Strabismus/surgery , Animals , Cicatrix/prevention & control , Intraoperative Care , Oculomotor Muscles/drug effects , Oculomotor Muscles/surgery , Rabbits , Surgical Sponges , Tissue Adhesions
11.
J Surg Res ; 120(2): 225-9, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15234217

ABSTRACT

BACKGROUND: Tendon repair and subsequent immobilization is frequently complicated by postoperative stiffness secondary to inflammation and peritendinous adhesions. Thermal preconditioning is known to reduce inflammation by inducing formation of cytoprotective heat shock proteins. This study evaluates the role of thermal preconditioning following complete division and repair of the Achilles tendon, with subsequent immobilization, mimicking the typical clinical scenario. MATERIALS AND METHODS: Twenty-four New Zealand White rabbits were used in the study. The treatment group underwent thermal preconditioning, by elevating their core temperature to 41.5 degrees C for 20 minutes. The Achilles tendon of the hindlimb was divided and repaired 18 hours following thermal preconditioning. The animals were sacrificed following 3 weeks of immobilization. Range of movement of the ankle, tendon gliding, quantity of adhesions, and weight of repaired tendons were assessed. RESULTS: Loss of range of movement at the ankle was significantly less in the treatment group versus controls (P = 0.02). The quantity of adhesions and weight of the repaired tendons were significantly reduced in the treatment group (P = <0.001 and P = 0.005, respectively). Tendon gliding relative to the surrounding soft tissue was also significantly improved in the treatment group (P = 0.002). CONCLUSION: Preconditioned animals demonstrated a significantly better range of ankle movement, decreases in adhesion formation and in the gliding, and dimensions of tendons. Thermal preconditioning therefore has the potential to improve clinical results in tendon surgery following repair and immobilization.


Subject(s)
Achilles Tendon/physiopathology , Achilles Tendon/surgery , Connective Tissue Diseases/prevention & control , Heat-Shock Proteins/metabolism , Orthopedic Procedures/adverse effects , Achilles Tendon/pathology , Animals , Ankle/physiopathology , Conditioning, Psychological , Connective Tissue Diseases/etiology , Connective Tissue Diseases/pathology , Elasticity , Hot Temperature , Immobilization , Inflammation/etiology , Organ Size , Postoperative Period , Rabbits , Range of Motion, Articular , Tissue Adhesions/etiology , Tissue Adhesions/pathology , Tissue Adhesions/prevention & control
12.
Rev. argent. reumatol ; 15(1): 10-10, 2004. ilus
Article in Spanish | BINACIS | ID: bin-1772

ABSTRACT

Introduccion: la necesidad de un abordaje integral bio-psico-social de los pacientes con enfermedad cronica, presenta la dificultad de evaluar adecuadamente las intervenciones psicosociales que se deben realizar, como p. ej: la educacion del paciente basada en principios psiconeuroendocrinoinmunologicos, aplicados en reuniones grupales, llamadas de Calidad de Vida (CV), destinadas a crear y/o mejorar las estrategias de afrontamiento de los pacientes para el manejo de su enfermedad. Objetivos: 1) Evaluar a traves de tests psicometricos la influencia de un tratamiento medico-psicologico integrado 2) Ofrecer en un espacio transicional una instancia de psicoaprendizaje y de manejo del estres cronico. 3) Observar si esto influye en la evolucion de la enfermedad de base, su actividad y requerimientos. Material y metodos: se estudiaron 12 pacientes, de sexo femenino, con edad mediana de 36.8 años. Todas las pacientes habian estado internadas con diagnostico de: 1 paciente artitris reumatoidea (AR), 8 pacientes lupus eritematoso sistemico (LES), 2 pacientes esclerodermia (ESP), 1 paciente fibromialgia (FM). El estado de actividad de la enfermedad fue registrado con los respectivos metodos: AR con el core set del American College of Rheumatology (ACR), LES con SLEDAI, ESP con compromiso de organo, y FM con FIQ. Se evaluo impacto de la enfermedad en la CV de las pacientes con SF36, depresion con Beck Depresion Inventory (BDI), estres con Escala de Holmes modificada. Se registro ademas concurrencia al grupo, cumplimiento del tratamiento internaciones, desarrollo social y actividades fuera del hogar. Resultados: De 12 pacientes 3 (25 por ciento) realizaron el programa en sesiones individuales y 9 (75 por ciento) completaron las sesiones programadas; cinco (41.6 por ciento) pacientes retomaron su actividad laboral. En las 12 pacientes se ha registrado menor numero de reactivacion anual de la enfermedad y cumplen adecuadamente con el tratamiento. Cuatro de ellas han sobrellevado eventos traumaticos sin reactivar la enfermedad. El numero de hospitalizaciones de 12/12 en 1998 fue de 4/12 en los 4 años subsiguientes. La media estadistica del BDI antes del tratamiento fue de 28.92 (DS 3.75) y despues del tratamiento 20.83 (DS 3.66) p<0.005 (AU)


Subject(s)
Quality of Life/psychology , Patient Education as Topic , Psychometrics , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/psychology , Connective Tissue Diseases/prevention & control
13.
Arch Phys Med Rehabil ; 84(5): 770-7, 2003 May.
Article in English | MEDLINE | ID: mdl-12736896

ABSTRACT

OBJECTIVE: To assess the contribution of magnetic resonance imaging (MRI) in the diagnosis of tibial stump bursitis, in the establishment of differential diagnosis, and in the therapeutic management prosthetic-stump interface, mainly by adaptation of the prosthetic device. DESIGN: Two-year, prospective, consecutive series. SETTING: University-affiliated prosthetic and rehabilitation center and university department of radiology. PARTICIPANTS: A group of 17 persons with stump problems identified from a total of 139 consecutive below-knee amputees with prosthesis problems. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical symptoms and MRI. RESULTS: Clinical symptoms (variable stump volume, fluctuating mass at palpation with or without mechanical pain) were suggestive of bursitis in 10 patients. MRI confirmed bursitis in 9 and identified 1 in whom clinical signs suggested neuroma, giving an incidence of 10 of 139 amputees (7.2%). MRI identified 13 sites of bursitis (adventitious bursa, 11; synovial bursitis, 2) and 5 localized areas of soft tissue inflammation. MRI showed diffuse muscular edema at 1 site of clinically suspected bursitis, and bursitis at another site of suspected neuroma. Calcified bursitis was observed in 1 case. Bone abnormalities associated with bursitis (n=7) included osteophytes or fracture (n=4) or bone marrow edema (n=3). Two asymptomatic neuromas were also identified. MRI-guided modifications of the prosthetic interface led to favorable outcome in all cases. CONCLUSION: Bursitis, adventitious bursae, and areas of localized soft-tissue inflammation are different aspects of the same disorder resulting from a mechanical conflict between the stump and the prosthesis socket. Besides contributing to diagnosis, MRI provides a precise assessment necessary for correcting the prosthesis-stump interface in a way that reduces mechanical stress and subsequently cures bursitis.


Subject(s)
Amputation Stumps , Artificial Limbs/adverse effects , Bursitis/diagnosis , Bursitis/etiology , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/etiology , Magnetic Resonance Imaging/methods , Tibia , Adolescent , Adult , Aged , Bursitis/prevention & control , Connective Tissue Diseases/prevention & control , Diagnosis, Differential , Female , Humans , Inflammation , Male , Middle Aged , Prospective Studies , Prosthesis Fitting/methods , Risk Factors , Stress, Mechanical
14.
Am J Pathol ; 159(6): 1981-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11733347

ABSTRACT

Calcification of elastin occurs in many pathological cardiovascular diseases including atherosclerosis. We have previously shown that purified elastin when subdermally implanted in rats undergoes severe calcification and aluminum chloride (AlCl(3)) pretreatment of elastin inhibits calcification. In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl(3) pretreatment. Subdermal implantation of AlCl(3)-pretreated elastin showed significantly lower MMP-9 and MMP-2 activity surrounding the implant as compared to the control implants. AlCl(3) pretreatment also significantly inhibited elastin implant calcification at the seven-day implant period (AlCl(3)-pretreated 4.07 +/- 1.27, control 23.82 +/- 2.24 microg/mg; p<0.0001). Moreover, elastin gel zymography studies showed that gel pretreatment with AlCl(3) inhibited elastolysis by MMP-9. We also demonstrate significant suppression of MMP-2 activity in aortic wall segments of AlCl(3)-pretreated porcine bioprosthetic heart valve implants as compared to control valve implants in sheep mitral valve replacement studies. AlCl(3) pretreatment also significantly inhibited calcification of elastin in this model. Thus, we conclude that aluminum ion binding to elastin prevents MMP-mediated elastolysis and thus prevents elastin calcification.


Subject(s)
Aluminum Compounds/pharmacology , Calcinosis/prevention & control , Chlorides/pharmacology , Connective Tissue Diseases/prevention & control , Elastin/drug effects , Matrix Metalloproteinases/metabolism , Aluminum Chloride , Animals , Aorta/drug effects , Aorta/enzymology , Calcinosis/metabolism , Connective Tissue Diseases/metabolism , Elastic Tissue/drug effects , Elastic Tissue/metabolism , Elastic Tissue/pathology , Elastin/metabolism , Heart Valve Prosthesis , Immunohistochemistry , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase Inhibitors , Mitral Valve/surgery , Rats , Rats, Sprague-Dawley , Sheep , Swine
15.
Clin Nephrol ; 51(1): 54-8, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9988148

ABSTRACT

Three patients with extensive, symptomatic tumoral calcinosis (TC) were studied after renal transplantation. Changes in TC-related symptoms, radiological appearances, calcium, phosphate and intact parathyroid hormone concentrations were recorded. All patients noted an immediate reduction in pain and in 2 patients the TC rapidly resolved. Their TC was not palpable by 6 months and radiographs showed near complete resolution at 12 months. Both developed hypercalcemia and in one patient this was associated with polyuria and renal impairment. Bisphosphonates reduced the hypercalcemia but increasing the corticosteroids had no effect. The third patient remained dialysis dependent due to technical problems and rejection but continued on immunosuppression to preserve residual graft function. His TC improved symptomatically but grew radiologically. These cases demonstrate that rapid resolution of TC may occur after successful renal transplantation and that bisphosphonates can ameliorate the associated hypercalcemia. Early symptomatic benefit may occur without graft function and is probably due to the anti-inflammatory action of corticosteroids.


Subject(s)
Calcinosis/diagnostic imaging , Connective Tissue Diseases/diagnostic imaging , Kidney Transplantation , Adult , Calcinosis/prevention & control , Connective Tissue Diseases/prevention & control , Female , Humans , Hypercalcemia/etiology , Immunosuppression Therapy , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Male , Middle Aged , Radiography , Time Factors
16.
J Dent Res ; 76(9): 1529-37, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9294486

ABSTRACT

The exact molecular mechanisms of the loosening of a dental implant are not well-known. The characteristics of implant sulci are similar to those of periodontal sulci regarding gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF). Proteolytic enzymes, matrix metalloproteinases (MMPs), participate in peri-implant tissue remodeling. Clodronate is a well-tolerated bisphosphonate-group drug currently used in bone-resorption-related diseases in humans. The mechanisms of bisphosphonate action are not clarified. Collagenase activity in diseased PISF was significantly higher than in the clinically healthy group. Immunoblotting disclosed that diseased PISF contained increased immunoreactives MMP-8 compared with the healthy PISF. The residual latent collagenase activity in the diseased PISF was activated by gold thioglucose and inhibited completely by 100 microM of doxycycline closely resembling pure neutrophil collagenase (MMP-8). The presence of MMP-8 in diseased but not in clinically healthy PISF may prove to be a useful biochemical indicator to monitor peri-implant health and disease. Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC50] was achieved by 150 microM of clodronate), an osteoactive, antiresorptive bisphosphonate. Furthermore, the new finding suggests an extended and hitherto-undescribed potential for clodronate in preventing the loosening of both implants and teeth, based on a dual beneficial effect: prevention of both bone resorption/osteolysis and of soft tissue/dental ligament destruction. Potential new therapeutic indications based on the collagenase-inhibiting effect of clodronate provide potential new therapeutic indications for a variety of diseased involving connective tissue breakdown, such as periodontal disease, arthritides, and tumor invasion.


Subject(s)
Calcium/metabolism , Clodronic Acid/pharmacology , Collagenases/analysis , Enzyme Inhibitors/pharmacology , Gingival Crevicular Fluid/enzymology , Adult , Anti-Bacterial Agents/pharmacology , Arthritis/prevention & control , Aurothioglucose/pharmacology , Biomarkers/analysis , Bone Remodeling/drug effects , Bone Resorption/drug therapy , Bone Resorption/prevention & control , Clodronic Acid/administration & dosage , Connective Tissue Diseases/prevention & control , Dental Implants , Dental Restoration Failure , Dose-Response Relationship, Drug , Doxycycline/pharmacology , Enzyme Activation , Enzyme Inhibitors/administration & dosage , Humans , Immunoblotting , Matrix Metalloproteinase 8 , Matrix Metalloproteinase Inhibitors , Middle Aged , Osteolysis/prevention & control , Periodontal Diseases/prevention & control , Periodontal Ligament/drug effects , Periodontitis/enzymology , Tooth Mobility/prevention & control
17.
J Biomed Mater Res ; 38(1): 25-33, 1997.
Article in English | MEDLINE | ID: mdl-9086414

ABSTRACT

Tendon adhesion is acknowledged to be a function of both an overwhelming inflammatory response at the surgical site and the loss of physical separation that is normally present between the tendons and the synovial sheath. Adhesions bind the flexor tendons to each other and to surrounding structures, interfering with their normal gliding function. The clinical result of adhesion formation following flexor tendon surgery is poor digital function. This study investigated the effect of intraoperative treatments of high viscosity absorbable gels made of various combinations of hyaluronic acid and nonsteroidal anti-inflammatory drugs, on adhesion formation in a leghorn chicken flexor tendon model. Forty-eight mature, white leghorn chickens were used to verify the surgical model and to test five different gel treatments. The gels were formed from: 2% sodium hyaluronate in phosphate buffered saline alone or combined with 1 mg/mL tolmetin sodium; 1 mg/mL naproxen sodium; 0.216 g/mL calcium acetate; or 0.216 g/mL calcium acetate plus 1 mg/mL naproxen sodium. The gels were applied by injecting 0.2 mL of the specified composition into the intrasheath space near the conclusion of the surgical procedure. Gross and histological evaluations were conducted to analyze the efficacy. All of the treatments significant reduced the extent and severity of postsurgical tendon adhesion in this animal model as compared with the control (no gel treatment) (p < 0.05). The combination of naproxen sodium and calcium acetate in a high viscosity sodium hyaluronate carrier was the most effective composition. The combination of a high viscosity gel and nonsteroidal anti-inflammatory drugs appears to maintain the natural separation between the tendons and their sheaths and decrease the tissue inflammatory response through mediating two of the major stimuli in adhesion formation.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Connective Tissue Diseases/prevention & control , Hyaluronic Acid/therapeutic use , Tissue Adhesions/prevention & control , Animals , Chickens , Connective Tissue Diseases/complications , Connective Tissue Diseases/pathology , Disease Models, Animal , Gels , Postoperative Complications , Tissue Adhesions/complications , Tissue Adhesions/pathology
18.
Genet Test ; 1(4): 237-42, 1997.
Article in English | MEDLINE | ID: mdl-10464652

ABSTRACT

Marfan syndrome (MFS), a common connective tissue disorder, is caused by fibrillin-1 (FBN1) mutations that are scattered throughout the gene and are largely unique to individual families. Mutation detection in this large gene of 65 exons is a considerable technical challenge. To develop an efficient method capable of identifying all possible mutations in this gene, we have explored the use of a novel denaturing high-performance liquid chromatography (DHPLC) system. This technique compares two or more chromosomes as a mixture of denatured and reannealed PCR amplicons. Under partially denaturing conditions, heteroduplexes can be separated from homoduplexes. A panel of 94 DNA samples from individuals with MFS or related connective tissue disorders was screened exon-by-exon by this method. A total of 66 unique heteroduplex profiles was identified. Sequencing of the amplicons detected 37 novel and two previously reported mutations, as well as 15 novel and 10 known polymorphisms or unique sequence variants that are probably of no clinical significance. Of the 34 mutations found in definitive MFS cases, 16 were identified in the 21 samples that had not been screened before (76% detection rate) and 17/40 (43%) were in samples previously screened by other mutation detection methods. In 32 individuals with MFS-related phenotypes, five FBN1 mutations were identified (16%). Our results demonstrate the power of the DHPLC method to detect FBN1 mutations. It should be applicable for mutation screening in any gene in a large population.


Subject(s)
Chromatography, High Pressure Liquid , Connective Tissue Diseases/genetics , DNA Mutational Analysis/methods , Genetic Testing/methods , Heteroduplex Analysis , Marfan Syndrome/genetics , Microfilament Proteins/genetics , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/prevention & control , Evaluation Studies as Topic , Exons/genetics , Fibrillin-1 , Fibrillins , Frameshift Mutation , Genetic Carrier Screening , Humans , Introns/genetics , Marfan Syndrome/diagnosis , Marfan Syndrome/prevention & control , Mutation , Nucleic Acid Hybridization , Point Mutation , Polymorphism, Genetic
19.
J Orthop Res ; 13(2): 296-304, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7722767

ABSTRACT

To clarify the proteolytic cascade in the loosening of total hip prostheses, the presence, tissue localization, and content of the serine proteinase, elastase, and its endogenous inhibitor, alpha 1-antitrypsin, were studied in periprosthetic tissues around 12 loose hip prostheses by immunohistochemistry, spectrophotometric enzyme assay, and immunoblot analysis, and the results were compared with those in control synovial tissue samples from eight knees. Increased numbers of elastase-immunoreactive cells and elevated elastase activity, inhibited by the addition of native alpha 1-antitrypsin, were observed both in the interface tissues between the bone and implants and in the pseudocapsular tissues from around loose hip prostheses. Elevated elastase activity, uninhibited by alpha 1-antitrypsin in situ and inhibited by the addition of native inhibitor, suggests a proteinase-inhibitor imbalance that contributes to the weakening of periprosthetic tissues and thus causes the loosening of hip prostheses.


Subject(s)
Connective Tissue Diseases/prevention & control , Hip Prosthesis , Knee Joint/enzymology , Pancreatic Elastase/metabolism , Synovial Membrane/enzymology , alpha 1-Antitrypsin/metabolism , Adult , Aged , Aged, 80 and over , Connective Tissue Diseases/enzymology , Connective Tissue Diseases/pathology , Electrophoresis, Polyacrylamide Gel , Female , Humans , Immunoblotting , Immunoenzyme Techniques , Immunohistochemistry , Knee Joint/drug effects , Knee Joint/pathology , Male , Middle Aged , Pancreatic Elastase/antagonists & inhibitors , Prosthesis Failure , Spectrophotometry , Synovial Membrane/drug effects , Synovial Membrane/pathology , alpha 1-Antitrypsin/physiology
20.
Ann R Coll Surg Engl ; 75(2): 119-22, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8386491

ABSTRACT

In varicose vein surgery, significant postoperative morbidity results from subcutaneous haematoma formation and limb swelling after saphenous vein stripping. We investigated the effectiveness of a high-compression short-stretch adhesive bandage compared with non-adhesive crêpe in reducing haemorrhage after stripping of varicose veins. Using 99mTc-labelled red blood cells, the degree of postoperative bleeding was assessed in 10 patients with bilateral varicose veins allocated for stripping and ligation. High-compression adhesive bandaging was applied to the experimental limb and a non-adhesive bandage to the contralateral control limb. Results show that adequate compression bandaging can decrease subcutaneous haematoma formation after stripping of varicose veins.


Subject(s)
Bandages , Connective Tissue Diseases/prevention & control , Hemorrhage/prevention & control , Postoperative Complications/prevention & control , Varicose Veins/surgery , Adult , Female , Humans , Male , Middle Aged , Postoperative Care/methods , Pressure , Sodium Pertechnetate Tc 99m
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