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Demonstration of thyrotropin binding sites in orbital connective tissue: possible role in the pathogenesis of thyroid-associated ophthalmopathy.

The thyrotropin (TSH) receptor is implicated in the pathogenesis of thyroid-associated ophthalmopathy, but its presence has not been demonstrated in orbital tissues. Binding of 125I-TSH to porcine orbital connective tissue and thyroid membranes was studied. At pH 7.4 125I-TSH bound to thyroid membranes with high affinity, but not to orbital connective tissue membranes. At pH 5.2, binding of 125I-TSH was evident on thyroid and orbital connective tissue membranes, although of low affinity. Low affinity binding at pH 5.2, could also be demonstrated on orbital fibroblasts; binding to membranes prepared from extraocular muscle, or from abdominal adipose tissue was not detected. Immunoglobulin G from healthy subjects (n = 17) and patients with ophthalmopathy (n = 19) were tested for inhibition of 125I-TSH binding to membranes. As anticipated patients' IgG exhibited greater inhibition than normal controls with thyroid membranes at pH 7.4 (p < 0.001). Similar results were obtained with thyroid membranes (p < 0.05), and orbital connective tissue membranes at pH 5.2 (p < 0.001). Significant correlations were found when percentage inhibition by IgG was compared between: thyroid membranes at pH 7.4 and thyroid membranes at pH 5.2, orbital connective tissue membranes at pH 5.2 and thyroid membranes at pH 7.4, and orbital connective tissue membranes at pH 5.2 and thyroid membranes at pH 5.2. A low affinity TSH-binding site is present in orbital connective tissue, and is recognized by IgG's from patients with ophthalmopathy which suggests that TSH receptor antibodies may target the orbit.

Adolescent↗

Connective tissue and bacterial deposits on rubber dam sheet and ePTFE barrier membranes in guided periodontal tissue regeneration.

The aim of this study was to compare the connective tissue and bacterial deposits on rubber dam sheets and expanded polytetrafluoroethylene membranes used as barrier membranes in guided tissue regeneration for periodontal treatment. Twenty patients having intrabony defects and/or furcation defects were surgically treated by guided tissue regeneration employing either rubber dam sheets (10 patients) or expanded polytetrafluoroethylene membranes (10 patients) as barrier membranes. Four to six weeks after the first operation, membranes were retrieved from the lesion sites and processed for scanning electron microscopy. The lesion-facing surfaces of membranes were examined for the presence of connective tissue and bacterial deposits. The differences between the numbers of fields and the distributions of connective tissue and bacteria on both types of membranes were analysed by the Chi-square test at the level of 0.05 significance. The results showed a lot of fibroblasts with their secreted extracellular matrices, known as components of the connective tissue on rubber dam sheets and expanded polytetrafluoroethylene membranes. There was no significant difference in the total number of connective tissue on both types of membranes (P = 0.456). Many bacterial forms including cocci, bacilli, filaments and spirochetes with the interbacterial matrices were identified. The total number of bacteria on rubber dam sheets was statistically less than that on expanded polytetrafluoroethylene membranes (P < 0.001). The comparable number of connective tissue on both types of membranes suggests that the healing process under both types of membranes was also comparable. Therefore, the rubber dam sheet might be used as a barrier membrane in guided tissue regeneration.

Alveolar Bone Loss↗

The respiratory system in connective tissue diseases.

Adolescents with connective tissue diseases (CTDs) are at risk for community-acquired and opportunistic respiratory tract infections; it is mandatory to consider an infectious etiology in the differential diagnosis. The authors highlight the respiratory manifestations of the more common CTDs seen in adolescence, and also discuss useful diagnostic tests and drug regimens.

Adolescent↗

Covering denuded maxillary root surfaces with the subepithelial connective tissue graft.

The subepithelial connective tissue graft is an esthetic gingival grafting procedure used to cover denuded single and multiple surfaces primarily of maxillary anterior and bicuspid teeth. A clinical study of 10 private practice periodontal patients is presented with results of 97.04% root coverage achieved on average in 21 sites treated, which had an average recession of 3.86 mm. The technique and the rationale for its use are presented with documented case report results.

Adult↗

When to suspect connective tissue disease.

When a connective tissue disease is suspected, physical and historical data should be collected to build a case for a clinical syndrome. Negative serologic results may be helpful; positive ones must be used with awareness of their limitations. If a diagnosis is not clinically evident or serologically confirmed, observation may be preferable to overdiagnosis and unnecessary treatment. If the syndrome is atypical, physicians should look for evidence of clinical overlap and reevaluate regularly with an open mind.

Connective Tissue Diseases↗

Inhibition of connective tissue formation in dermal wounds covered with synthetic, moisture vapor-permeable dressings and its reversal by transforming growth factor-beta.

An investigation of synthetic, adherent, moisture vapor-permeable dressings (SAM) on dermal wounds healing by secondary intent has yielded the novel observation that SAM dressings severely inhibited the deposition of granulation tissue and subsequent collagenous tissue when compared with air-exposed wounds in mouse and guinea pig systems. Repair tissue was quantitated histomorphometrically in full-thickness wounds covered with SAM or left air-exposed for periods up to 3 weeks. Early in healing, mouse wounds left open to the atmosphere formed a scab which overlay a large volume of granulation tissue derived from two sources, one lateral, and the other deep and centrally located. In contrast, SAM-covered wounds contained only a small amount of granulation tissue which was derived solely from lateral sources. Granulation tissue was replaced by fibrous connective tissue over time, and this was always less in SAM-covered wounds. Deposition of large amounts of connective tissue in air-exposed wounds was associated with significant polymorphonuclear and mononuclear cell infiltrates, while the lack of granulation tissue formation in SAM-covered sites was associated with reduced inflammation. Dressing-induced inhibition of connective tissue could be partially reversed by treatment with transforming growth factor-beta form 1 or 2. Deposition of granulation tissue in large lenticular wounds in guinea pig skin, but not in 6-mm punch wounds, was also inhibited when the wounds were covered with SAM, and the morphology of air-exposed and SAM-covered wounds was similar to that in mice. SAM-covered wounds in mice and guinea pigs may be useful as models of chronic non-healing wounds.

Animals↗

[Mortality and risk of cancer in systemic connective tissue diseases].

The systemic connective tissue diseases represent a broad spectrum of multiorgan disorders. This report reviews our current knowledge of mortality and the risk of cancer in these diseases. The relationship between clinical manifestations and reduced survival in systemic sclerosis, systemic lupus erythematosus and polyarteritis nodosa is addressed in detail. Moreover, we outline the increased risks of cancer in dermatomyositis and lymphoma in primary Sjögren's syndrome, as well as cancer of the bladder in patients with Wegener's granulomatosis who have been treated with cyclophosphamide. Finally, the conflicting results regarding mortality in temporal arteritis are discussed.

Connective Tissue Diseases↗

The association between connective tissue laxity and the risk of an abdominal aortic aneurysm.

AIMS: to investigate whether connective tissue laxity is associated with abdominal aortic aneurysms (AAA). METHODS: a nested case control study in a population-based screening programme. The presence of pes planus, scoliosis, pectus deformities, flexible auricular cartilages and Gorling's sign were combined with the Beighton joint mobility score to form a connective tissue laxity score. The association between connective tissue laxity and the risk of AAA was investigated through a logistic regression model. Type III collagen turnover was assessed using a serum radio-immunoassay for type III procollagen (PIIINP). RESULTS: data from 231 controls (aortic diameter <2.5 cm) and 190 cases (AAA >2.9 cm) were analysed. Odds ratios (OR), adjusted for known confounders were 3.1 (95% CI: 1. 1-8.6) for the highest group of connective tissue scores and 2.4 (95% CI: 1.0-5.4) for the middle group, compared with those with no signs of abnormal connective tissue function. There was no difference in mean collagen turnover between cases and controls, nor between those with a stable AAA >4 cm and those with an expanding AAA. CONCLUSION: connective tissue laxity is associated with a higher risk of having an AAA. The collagen turnover is similar in subjects with an AAA and controls. Aneurysms may be associated with abnormal connective tissue rather than an increased breakdown of normal collagen.

Aortic Aneurysm, Abdominal↗

[Clinical presentation of connective tissue dysplasia in adults].

Connective tissue dysplasia (CTD) markers (anthropometric parameters, joint hypermobility, state of the skin, osteomuscular system, etc.) as well as external respiration function, echocardiography, occlusive plethysmography data were assessed in 402 healthy subjects (142 males and 260 females, mean age 28.4 +/- 0.5 years). Four basic CTD symptom complexes were identified: ligamentous-articular, cutaneous, osteomuscular and cardial. Control group consisted of subjects free of CTD markers (n = 61). Combination of the above four symptom complexes occurred in 8.5% examinees. These show psychoemotional disorders, impaired function of external respiration, decreased size of the heart, low arterial pressure, affection of capillary and venous circulation.

Adult↗

Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils.

Fibrillin, a connective tissue macromolecule (Mr = 350,000) which is normally insoluble in its tissue form, has been purified from the medium of human skin fibroblast and ligament cells in culture. Analysis of the amino acid composition indicates that fibrillin contains approximately 14% cysteine, of which one-third appears to be in the free reactive sulfhydryl form. Electron microscopic images of fibrillin reveal an extended, flexible molecule approximately 148 nm long and 2.2 nm wide. These length measurements are consistent with shape calculations based upon velocity sedimentation data. It is likely that the material we have purified from cell culture medium represents monomeric fibrillin consisting of a single polypeptide chain. Additional ultrastructural immunohistochemical data presented here suggest a model for the parallel, head-to-tail alignment of fibrillin molecules in microfibrils.

Amino Acids↗

Bilateral exudative pleuritis, an unusual pulmonary onset of mixed connective tissue disease.

In mixed connective tissue disease (MCTD) pulmonary involvement has been reported. In most patients diffuse interstitial pulmonary abnormalities are present. We describe an unusual pulmonary onset of MCTD in an 18-year-old woman. She presented with a bilateral pleural exudate containing many granulocytes (95%) and only a few monocytes (5%). High titers of antinuclear antibodies were found. One week after hospitalization, an erythema on both hands and forearms developed. Skin biopsy demonstrated discrete IgM-C3 depositions along the basal membrane of the epidermis, antinuclear antibodies in the nuclei of the keratocytes in the dermis and granular depositions of IgM in the blood vessel walls of the upper dermis. Lung function tests improved without corticosteroid treatment and diffusing capacity remained normal.

Adolescent↗

Pathogenesis of cervical artery dissections: association with connective tissue abnormalities.

BACKGROUND: The etiology of spontaneous cervical artery dissection (CAD) is largely unknown. An underlying connective tissue disorder has often been postulated. OBJECTIVE: To further assess the association of CAD with ultrastructural abnormalities of the dermal connective tissue. METHODS: In a multicenter study, skin biopsies of 65 patients with proven nontraumatic CAD and 10 control subjects were evaluated. The ultrastructural morphology of the dermal connective tissue components was assessed by transmission electron microscopy. RESULTS: Only three patients (5%) had clinical manifestations of skin, joint, or skeletal abnormalities. Ultrastructural aberrations were seen in 36 of 65 patients (55%), consisting of the regular occurrence of composite fibrils within collagen bundles that in some cases resembled the aberrations found in Ehlers-Danlos syndrome type II or III and elastic fiber abnormalities with minicalcifications and fragmentation. A grading scale according to the severity of the findings is introduced. Intraindividual variability over time was excluded by a second biopsy of the skin in eight patients with pronounced aberrations. Recurrent CAD correlated with connective tissue aberrations. In addition, similar connective tissue abnormalities were detected in four first-degree relatives with familial CAD. CONCLUSION: CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

Adult↗

Cryoglobulinemias and connective tissue diseases.

Cryoglobulinemias in connective tissue diseases (CTD) represent, according to various authors, 12-30% of all cryoglobulinemia cases. Among CTD, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome are the diseases most frequently involved in the presence of cryoglobulins (8-48%). The cryoglobulinemias are mostly of the third type and sometimes of the second type. When clinical symptoms are present, usually they are represented by Raynaud's phenomenon, arthralgias, urticaria, purpura and liver involvement. However, the presence of cryoglobulins in a patient with CTD often does not correlate with clinical picture and other laboratory findings. Eight of our 28 cases (15 SLE and 13 RA) showed third type cryoglobulinemias (7 IgM-IgG and one IgM-IgG-Clq) with a remarkable decrease of serum C4 levels.

Adult↗

Connective tissue diseases and pregnancy.

Connective tissue diseases (CTD) such as systemic lupus erythematosus diffuse or limited systemic sclerosis and numerous others affect women frequently during the childbearing period. Every pregnancy in a patient with CTD should be regarded as high-risk pregnancy, and requires intensive monitoring and immediate treatment of clinical problems. For these reasons, for women suffering from CTD, who are pregnant or who intend to become pregnant, an interdisciplinary setting addressing all aspects of rheumatology, ob-gyn and neonatalogy needs to be provided. This setting includes particular diagnostic tools and laboratory parameters prior to and during pregnancy as well as in the post-partal period. Aside overt organ dysfunction, key problems in pregnant CTD patients consist mainly of haemostaseological problems such as antiphospholipid antibodies, neonatal lupus erythematosus, congenital heart block and drug therapy of the underlying disease, which will be outlined in this review.

Connective Tissue Diseases↗

[New viewpoints on the development, maturation, and aging of cataneous connective tissue].

The clinical theoretical findings on skin connective tissue during the three periods of life result in new aspects of reaction possibilities of the skin under physiological and pathological conditions. The level of replication and production metabolism of skin connective tissue is high during development, maturation and ageing. Proteoglycans or glycosaminoglycans and collagen of skin connective tissue show remarkable turnover rates, during the three life periods, aging included. The interactions between these structure macromolecules and their microheterogeneity are regarded, beside elastin and denaturated collagen and their relationships. Finally the synthesis of proteoglycans and glycosaminoglycans and of collagen as well as the several influences on the several synthesis steps are shown. Therewith we receive new aspects for the therapy of skin diseases.

Aging↗

Glomerulonephritis in children with mixed connective tissue disease.

AIMS: Mixed connective tissue disease (MCTD) has overlapping clinical features with systemic lupus erythematosus (SLE). Renal biopsy is necessary for all children with SLE to evaluate the prognosis, because they are at a quite high risk of developing renal complications. Furthermore, lupus nephritis and hypocomplementemia usually precede the appearance of clinical manifestations. Immune complex-mediated nephritis is one of the major complications of MCTD. Juvenile MCTD is known to be associated with a higher risk of nephritis than adult MCTD. However, it is uncertain whether all children with MCTD should be subjected to a renal biopsy, and whether most of those with hypocomplementemia present nephropathy, as in patients with SLE. We examined the histopathological characteristics of juvenile MCTD nephritis, the importance of renal biopsy and the implications of hypocomplementemia in our patients and reported cases of MCTD. MATERIAL AND METHODS: We performed renal biopsy in 11 children with MCTD and found 6 patients with glomerulonephritis. In addition, we studied the frequency and the characteristics of glomerulonephritis in 71 cases of juvenile MCTD (our 11 patients and 60 reported cases). We also analyzed the relationship between hypocomplementemia and pathological features in 41 cases of MCTD nephritis (23 adults, 18 children). RESULTS: 6 of our 11 patients had glomerulonephritis, but of them four had no abnormality in urinalysis at the time of biopsy. In 5 patients renal biopsy showed normal findings. Review of 71 cases of juvenile MCTD showed that of them 28% presented latent asymptomatic nephritis at the time of biopsy. Membranous nephropathy (MN) and mesangial proliferative glomerulonephritis (MPG) were common in MCTD. Interestingly, hypocomplementemia was more frequently observed in patients with MN or mixed form of MN and MPG (MPG/MN) than simple MPG based on our review of 41 cases (p < 0.01). CONCLUSION: A more aggressive indication of renal biopsy should be considered in children with MCTD because of the high incidence of non-clinical nephritis. The hypocomplementemia observed in patients with MCTD suggests the high frequency of glomerulonephritis, including membranous lesions.

Adolescent↗

[Interstitial lung disease in patients with connective tissue diseases].

Interstitial lung disease is a significant prognostic factor in connective tissue diseases. To further clarify clinical and immunological features of interstitial lung disease, we studied 894 consecutive patients with connective tissue diseases first evaluated between 1970 and 1993. Interstitial lung disease was found in 101 of 181 (56%) patients with systemic sclerosis, 92 of 183 (50%) with overlap syndrome, 35 of 76 (46%) with polymyositis/dermatomyositis, and 13 of 444 (3%) with systemic lupus erythematosus (p < 0.05, systemic lupus erythematosus vs. other connective tissue diseases). The presence of interstitial lung disease correlated with decreased survival in systemic sclerosis and in polymyositis/dermatomyositis, but not in overlap syndrome or in systemic lupus erythematosus. Interstitial lung disease in patients with connective tissue diseases was classified into two types: acute (n = 8) and chronic (n = 233). Among the 8 patients with acute disease, 4 (all with dermatomyositis) died of respiratory failure and 3 (all with systemic lupus erythematosus) responded to corticosteroids. Among the 233 patients with chronic interstitial lung disease, 20 had polymyositis/dermatomyositis with anti-aminoacyl tRNA synthetase antibodies and 40 had overlap syndrome with anti-U1 RNP antibodies. Respiratory failure in these patients was not frequent and occurred late in the course of the disease. As a cause of death, respiratory failure was associated with autoantibodies to topoisomerase I and aminoacyl tRNA synthetase but not anti-U1 RNP. Autoantibodies to aminoacyl tRNA synthetases were detected before the development of interstitial lung disease in 9 patients with polymyositis/dermatomyositis. We conclude that the clinical features of interstitial lung disease associated with connective tissue diseases vary with the type of connective tissue disease, and that analysis of autoantibodies can be useful in establishing a diagnosis and in forecasting the course and outcome.

Adult↗

Connective tissue metabolism in diabetic peripheral nerves.

Diabetes mellitus is associated with multiple connective tissue changes, such as generalized thickening of basement membranes. These alterations are suspected of contributing to the development of diabetic long-term complications encountered in many organs, including kidney, eye and peripheral nerves. The latter tissue, however, has gained relatively little attention with respect to connective tissue changes associated with diabetes. The morphological alterations of connective tissue in the diabetic peripheral nerve include thickening of basement membranes, increased diameter of endoneurial collagen fibrils, and accumulation of microfibrillar material. Recent studies have further elucidated the changes in the extracellular matrix of diabetic nerves and the molecular mechanisms underlying these alterations. For instance, elevated glucose concentrations modulate the expression of several proteins of the extracellular matrix in cultured nerve-derived connective tissue cells. In this article, we review the recent progress in the field of connective tissue alterations in diabetes and particularly in the diabetic peripheral nerve.

Connective Tissue↗