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Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality.

OBJECTIVE: Pneumonia due to Pneumocystis carinii has been increasingly reported in patients with connective tissue diseases, but the frequency of this complication is not known. We sought to determine the frequency of P carinii pneumonia (PCP) in patients with connective tissue diseases, and to determine the role that a hospital's acquired immunodeficiency syndrome (AIDS)-related experience may have in the diagnosis of PCP in these patients. METHODS: We used a state hospitalization registry to identify all patients with PCP and either rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, polymyositis, dermatomyositis, polyarteritis nodosa, or scleroderma who had an emergent or urgent hospitalization in California from 1983 to 1994. We compared patient and hospital characteristics between these patients and patients with connective tissue diseases hospitalized with other types of pneumonia. RESULTS: Two hundred twenty-three patients with connective tissue diseases were diagnosed with PCP in the 12-year study period. The frequency of PCP ranged from 89 cases/10,000 hospitalizations/year in patients with Wegener's granulomatosis to 2 cases/10,000 hospitalizations/year in patients with rheumatoid arthritis. Compared with 5,457 patients with connective tissue diseases and pneumonia due to other organisms, patients with PCP were more likely to be younger, to be male, to have private medical insurance, and to have systemic lupus erythematosus, Wegener's granulomatosis, inflammatory myopathy, or polyarteritis nodosa rather than rheumatoid arthritis, and were less likely to be African American. Hospital size, teaching status, urban/rural location, proportion of admissions due to AIDS or PCP, and proportion of patients with pneumonia undergoing bronchoscopy were each associated with the likelihood of diagnosis of PCP in univariate analyses, but only the number of patients with PCP being treated at a hospital (odds ratio [OR] 1.03 for each additional 10 cases/year, 95% confidence interval [95% CI] 1.01-1.05) was associated with the likelihood of diagnosis of PCP in multivariate analyses. Patients were also somewhat more likely to be diagnosed with PCP if there had previously been a case of PCP in a patient with a connective tissue disease at the same hospital (OR 135, 95% CI 0.98-1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics. CONCLUSION: PCP is an uncommon, but often fatal, occurrence in patients with connective tissue disease. A hospital's prior experience with patients with PCP is associated with the likelihood that this condition is diagnosed in patients with connective tissue diseases who present with pneumonia, suggesting that diagnostic suspicion is an important factor in the correct identification of affected patients.

Adult↗

AAEM minimonograph #38: neuropathies in connective tissue disease.

Neuropathies are common in patients with known or suspected connective tissue disease. A vasculitic mononeuropathy multiplex is often seen in patients initially presenting with polyarteritis nodosa or developing arteritis as a complication of rheumatoid arthritis. However, vasculitic neuropathy may become confluent and present as as distal symmetrical polyneuropathy or occur without systemic necrotizing vasculitis. Distal symmetrical polyneuropathies without associated vasculitis are also common in many connective tissue diseases. Compression neuropathies, especially carpal tunnel syndrome, occur with increased frequency in rheumatoid arthritis. Finally, certain neuropathies may be the major presenting feature of particular connective tissue diseases. For example, trigeminal neuropathy often heralds the onset of systemic sclerosis or mixed connective tissue disease, and sensory neuronopathy may be the initial presenting feature of Sjögren's syndrome.

Connective Tissue Diseases↗

[Cells of hematopoietic origin in the connective tissue of various organs in xenogeneic murine radiation chimeras].

The distribution of donor cells in the connective tissue of different organs of xenogeneic (rat in mouse) radiation chimaeras was studied under the normal conditions and upon its de novo formation. The donor cells were identified by means of indirect immunofluorescent method with the use of specific antiserum against surface antigens of the rat bone marrow cells. It was shown that macrophages of subcutaneous connective tissue, lung alveolar macrophages, Kuppfer's cells, macrophages of intestinal mucosa in the long living radiochimaeras were represented by the donor cells. The fibroblast-like cells of donor origin were found in the subcutaneous loose connective tissue, among the connective tissue elements of cross striated muscles, in the cardiac muscle, in the intestinal mucosa. The repopulation of Peyer's patches of the radiochimaeras by the donor cells was demonstrated. The macrophages of hemopoietic origin (donor origin) were found in the inflammatory granuloma in the brain cortex. The donor cells were found in the connective tissue of mammary glands following the hormonal stimulation. Differences were found with respect to binding of the antiserum used to cells of the capsule around the foreign body in different organs of xenogeneic chimaeras.

Animals↗

Tenascin in connective tissue development and pathogenesis.

The extracellular matrix glycoprotein, tenascin (tenascin-C) is selectively expressed at sites of tissue remodeling in developing and pathological connective tissues, including cartilage, bone, and dermis. Functional studies suggest that tenascin is important for chondrocyte differentiation and feather bud elongation. Tenascin is able to stimulate cell migration and proliferation in some cell types and its tissue distribution is often correlated with these processes. Tenascin is a poor adhesive substratum for cells, and its effects on cell behavior may be mediated by effects on cell shape. In normal adult connective tissues, tenascin is strongly expressed at sites of contact between elements of the musculoskeletal system, suggesting an additional role for tenascin in matrix organization.

Animals↗

Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria.

The connective tissue diseases include a heterogeneous group of conditions characterized by a wide variety of signs and symptoms. There also exists, however, a group of systemic autoimmune disorders with signs and symptoms not sufficiently evolved to fulfill any of the accepted classification criteria for the defined connective tissue diseases. These conditions have been defined as undifferentiated connective tissue syndromes, latent lupus, incomplete lupus, and undifferentiated connective tissue diseases. After an analysis of the existing literature, we discuss the possible significance of the undifferentiated diseases among the already defined connective tissue diseases and make a proposal for preliminary classification criteria for these conditions.

Connective Tissue Diseases↗

Structural changes in the intramuscular connective tissue during development of bovine semitendinosus muscle.

Structural changes in the intramuscular connective tissue during development of bovine semitendinosus muscle were investigated using the cell-maceration method for scanning electron microscopy, by which cellular elements were eliminated and collagen fibrils and fibres were exposed. The endomysium was discontinuous and showed various shapes and sizes in the muscle of 7-month fetuses. The perimysium consisted of collagen fibres in loose contact with each other. In the muscle of neonatal calves, the endomysium consisted of cylindrical sheaths and displayed a honeycomb structure, and the perimysium was composed of several layers of collagen fibres. Collagen fibrils in the endomysium bound ever more closely with each other, and collagen fibres in the perimysium increased in thickness, and the wavy pattern of collagen fibres became more regular with growth of cattle. We have examined the mechanical strength of the intramuscular connective tissue by our new method, 'intramuscular connective tissue (IMCT) model'. The IMCT model is composed of collagen fibrils and fibres which maintains the organization in the endomysium and perimysium in situ. The shear-force value of the model increased rapidly from the 7th fetal month to the neonatal stage, and increased linearly with postnatal ageing thereafter. Changes in the arrangement of collagen fibrils and fibres seem to closely related to an increase in the mechanical strength of the intramuscular connective tissue during development of bovine skeletal muscle.

Animals↗

The relationship between connective tissue and its microvasculature in the healthy dog gingiva.

The morphological consistency of subepithelial connective tissue and its vascular architecture was studied in the healthy gingiva of adult mongrel dogs. Corrosion-cast specimens of the vasculature and specimens of well-separated connective tissue from the lamina propria were observed by SEM. Specimens injected with india ink also were examined employing light microscopy. Summarizing the results: 1) Beneath the buccal gingival epithelium, short conical papillae were seen in the subepithelial connective tissue. The capillary structure throughout this region was basically of the loop type, the overall appearance of which replicated the papillae. The papilla disappeared at the muco-gingival junction, so that after the transition to the alveolar mucosa, no papillary formation was observed. The vasculature had transformed from loop to network structure. 2) Beneath the sulcular gingival epithelium, the subepithelial connective tissue displayed a smooth concavity with no papillae. In this region, the capillaries formed a flat, dense network in accordance with the morphology of the connective tissue. The capillary network suddenly disappeared at the terminal edge of the inner epithelium. The vessels of the lamina propria located immediately beneath the network reduced their lumina at the margin and formed the plexus of the periodontium, displaying a rather open network.

Acrylic Resins↗

Human histologic evaluation of root coverage obtained with a connective tissue with partial thickness double pedicle graft. A case report.

The use of a connective tissue graft combined with a pedicle graft has been proven an effective method to achieve root coverage. However, little is known about the histologic results in humans. A connective tissue with partial thickness double pedicle graft was performed on 2 teeth scheduled for extraction for prosthetic reasons. The procedures were clinically successful (100% and 83.3% root coverage). At 6 months postoperative, the teeth were extracted with conservative block sections and analyzed histologically. Two different healing patterns were seen. The first was characterized by a long junctional epithelial attachment that extended well beyond the original gingival margin and occasionally almost to the original bone level with minimal connective tissue adjacent to the tooth. The other pattern was a short junctional epithelium that stopped at the previously exposed root surface. In this pattern, there was predominately connective tissue adjacent to the tooth with some isolated areas of epithelium. No new bone or cementum was seen in any section. The use of a technique that combines a connective tissue graft with a pedicle graft can produce root coverage and a successful clinical result. However, the histological evaluation of this case report revealed that true regeneration was not seen in this study, only repair.

Alveolar Process↗

Toxemia of pregnancy. Part II. Immunofluorescent studies with placental connective tissue antisera: the possibility of characteristic lesions.

Seventeen placentas from term gestation complicated by toxemia of pregnancy and 17 normal controls were tested by the fluorescent antibody technic. Antisera to normal placental connective tissue and toxemic placental connective tissue were used. The antisera were obtained by the injection into rabbits of placental extracts rich in connective tissue elements from normal and toxemic placentas. The antitoxemic antisera, after absorption with soluble sonic fraction of normal placentas, stained the following elements exclusively in 14 of the 17 placentas: part of the syncytial knots, fibrillar elements in the adventitia of blood vessels, and amorphous deposition of connective tissue. In each of the remaining three placentas at least two of the lesions were observed. The observation of bright fluorescence in part of the syncytiotrophoblasts and the syncytial knots in toxemic placentas led to the suggestion that they arise late in pregnancy during the disease. The thin fibrillar elements and the amorphous deposition of connective tissue were documented in the various developmental stages in toxemic and normal placentas as well. These findings established possible characteristic lesions in the placenta of pregnancies complicated by toxemia.

Adolescent↗

Identification of human connective tissue in transplant of human oral mucosa in nude mice.

The present study describes a method for identification of connective tissue of human oral mucosal transplants in nude mice. The method was based on the development of a murine antiserum to human fibroblasts. After absorption with murine fibroblasts the antiserum in an immunofluorescence method appeared to react specifically with human connective tissue of frozen sections, whereas the antiserum did not react with murine connective tissue. The antiserum, applied to frozen sections of human oral mucosal transplants in nude mice, could distinguish between human and murine connective tissue in the sections. The ability to distinguish between the two types of tissue was utilized to elucidate a possible relation between epithelial morphology and underlying type of connective tissue. It was found that the formation of rete ridges of transplanted human oral epithelium was dependent on the presence of subepithelial human connective tissue. The method described may be useful for the recognition of human tissue in experimental studies of human transplants to other species.

Adolescent↗

Mitral valve prolapse and joint hypermobility: evidence for a systemic connective tissue abnormality?

Clinical evidence for an abnormally of extracardiac connective tissue was sought in 21 patients with idiopathic mitral valve prolapse and was compared to that in 21 matched controls. The incidence of rheumatic and orthopaedic complaints and the prevalence of hypermobile joints, Marfanoid habitus, and skeletal deformity were compared in the 2 groups. Skin thickness and elasticity were measured, and the mean values in the 2 groups were compared. hypermobile joints were significantly commoner in patients with mitral valve prolapse. Easy bruising was reported significantly more commonly by patients with mitral prolapse; the incidence of other rheumatic complaints was similar in the 2 groups. There was no significant difference in skin thickness, skin elasticity, and the prevalence of either skeletal deformity or Marfanoid habitus between patients with mitral valve prolapse and controls. The results support previous evidence of an association between mitral valve prolapse and benign hypermobility of the joints, but emphasise that many patients with mitral valve prolapse have no clinically apparent connective tissue abnormality outside the heart. It remains uncertain whether the valve lesion in these patients represents a tissue-specific abnormality of mitral valve collagen or the only clinical expression of a minor systemic connective tissue abnormality.

Adult↗

[Pulmonary artery hypertension associated with connective tissue diseases].

MOST IMPORTANT: Pulmonary hypertension (PH) is a severe, potentially life-threatening complication of connective tissue diseases, among which scleroderma is first line. The aim of this paper was to review the literature and report our experience with this particular complication of connective tissue diseases. In our centre of pulmonary vascular diseases, connective tissue diseases represent the third cause of PH. RESULTS: Scleroderma and particularly its limited cutaneous variant, the CREST syndrome, is the most common connective tissue disease affected by pulmonary hypertension. It can be related to a specific lung parenchymal involvement (hypoxic PH), to an isolated pulmonary vascular involvement or to a cardiac dysfunction secondary to specific myocardial lesions. DIAGNOSIS: Echocardiography is an excellent examination to detect pulmonary hypertension. However, right heart catheterisation is necessary to confirm the diagnosis of pulmonary hypertension and to test vasoreactivity with a potent vasodilator such as nitric oxide (NO). REGARDING TREATMENTS: Oral calcium channel blockers are indicated in patients who are responders to acute NO tests. Treatment with continuous intravenous prostacylin is obviously an improvement, at least functionally, although it appears less effective than in primary PH. With the new subcutaneous, oral and inhaled vasodilatators (prostaglandin and endothelin receptor antagonists), a few cases of improvement of PH with intensive immunosuppressive therapy were observed, essentially during systemic lupus erythematosus and Sharp syndrome. IN PRACTICE: PH is a severe complication of connective tissue diseases. Early detection of this complication should allow an earlier and more aggressive therapeutic approach in these patients, before irreversible vascular lesions occur.

Adult↗

Differential response to transforming growth factors-beta(1) and beta(2): connective tissue deposition in animal models.

The ability of transforming growth factor (TGF)-beta(1) and TGF-beta(2) to promote connective tissue deposition were compared in different animal models. A single subcutaneous injection of TGF-beta(2) in collagen/heparin gel carrier promoted markedly more extensive development of connective tissue than TGF-beta(1) at the site of injection in both neonatal and adult mice. Both TGF-beta(1) and TGF-beta(2) promoted deposition of dense and well-vascularized connective tissue matrix infiltrated with macrophages and fibroblasts. However, the results of immunohistochemical analyses suggested that TGF-beta(2) promoted an accumulation of more macrophages in the connective tissue than TGF-beta(1). Similar differences in the extent of connective tissue development were observed in neonatal mice when these factors were administered as a solution, without the collagen/heparin gel carrier. TGF-beta(2) was also more potent than TGF-beta(1) in domestic pigs. However, in guinea pigs, TGF-beta(1) promoted more extensive connective tissue development than TGF-beta(2). These results suggest that the differential connective tissue response to TGF-beta(1) and TGF-beta(2) is species dependent. However, the differences in the physical and chemical properties of these factors may account in part for the differential response as well.

Journal Article↗

Role of the extracellular matrix in the degradation of connective tissue.

Cell-matrix interactions have an important impact on regulating connective tissue degradation during physiological and pathological processes, e.g., development, wound healing and tissue remodeling and tumor invasion and metastasis. Connective tissue breakdown is initiated by a specific class of enzymes, the matrix metalloproteinases, which include the type I collagenases, the type IV collagenases/gelatinases and the stromelysins and which vary with respect to their substrate specificities. The activity of the metalloproteinases is regulated by de novo synthesis of the proenzymes, the activation of the zymogens and by the presence of the inhibitors, TIMPs. This tight control is required in order to guarantee normal functioning of connective tissue.

Animals↗

Subperiosteal connective tissue grafts for pocket reduction and preservation of gingival esthetics: a case report.

BACKGROUND: Clinical studies and recent histological evidence following mucogingival surgery for the treatment of gingival recession have documented that when closely adapted to a previously exposed root surface, connective tissue is capable of forming a new attachment. Despite these findings, no clinical tests have been conducted to examine the ability of connective tissue to reduce probing depth (PD) and increase clinical attachment levels (CAL) when it is implanted into periodontal osseous defects. The purpose of this paper is to report the clinical results on a patient following 2 subperiosteal connective tissue grafts. METHODS: Subperiosteal connective tissue grafts were placed in 2 sites of periodontal bone loss and deep pocketing in one patient. Following flap reflection and root preparation, a connective tissue graft 1.5 to 2.0 mm in thickness was draped and sutured over each osseous defect and then completely covered by the external flap. RESULTS: Ten months following subperiosteal connective tissue grafting, tooth #7 had 4 mm of CAL gain. Tooth #10 had 3 mm of CAL gain 8 months postoperatively. Both teeth had 1 mm gain in gingival recession. Both teeth probed 3 mm postoperatively. CONCLUSIONS: When connective tissue was grafted into 2 periodontal osseous defects, there were significant reductions in probing depth and gains in CAL. There was minimal postoperative gingival recession. The new clinical attachment gain remained stable for 8 to 10 months following subperiosteal connective tissue grafting.

Alveolar Bone Loss↗

Turnover in periodontal connective tissues: dynamic homeostasis of cells, collagen and ground substances.

The connective tissues of the periodontium are composed of two soft tissues and two hard tissues--each of which has unique features. This review considers the constituents of normal, healthy periodontal connective tissues together with an appraisal of the changes in the connective tissue matrices of the periodontium which occur during the development of periodontitis. Recent developments in this field have paved the way for new and exciting vistas in periodontal diagnosis and regeneration which, ultimately, are two important goals in periodontal therapy.

Collagen↗

Connective tissue changes in immobilised muscle.

The reduction in fibre length of muscles immobilised in a shortened position is accompanied by reduced compliance of the muscle. Since the intramuscular connective tissue framework distributes the forces passively imposed on a muscle by stretching, it was decided to investigate the amount and distribution of connective tissue in immobilised muscles. Biochemical analysis of the hydroxyproline content of muscles immobilised in the shortened position for different periods of time showed an increase in the ratio of collagen to muscle fibre tissue. This occurred during the first few days of immobilisation, before there was any significant loss of sarcomeres. Thus the increase in connective tissue appeared to result directly from immobilisation rather than from redistribution of connective tissue, following shortening of the fibres. A detailed histological analysis of muscle sections stained for connective tissue with Sirius Red showed that the early increase in connective tissue in immobilised muscles occurred in the perimysium rather than the endomysium, although after a longer period of immobilisation there was also a thickening of the endomysium. Ultrastructural analysis of the perimysium in normal muscle showed that the angle the collagen fibres made with the muscle fibres changed with the state of stretch of the muscle; when the muscle was shortened, the angle was larger than when the muscle was lengthened. In immobilised muscle, collagen fibres were found to be arranged at a more acute angle to the axis of the muscle fibres than was found in normal muscle; this would be expected to affect the compliance of the muscle. The experiments described indicate that the increased stiffness of immobilised muscles could result from both quantitative and qualitative changes in the connective tissue.

Animals↗

[Histochemical aspects of the aging of connective tissue].

The senile involution of the peri-vascular connective tissue is followed by structural and functional modifications of the small vessels, especially pre-capillary arterioles and venules of the efferent system. Each modification, including the physico-chemical modification of the basal membrane of the connective tissue ("peri-microvascular sheath of proteoglycans" according to Merlen) causes a reaction response of the capillary endothelium with thickening of the basal membrane, as seen in skin biopsies of the leg after elastic bandage contention of long duration. The smallest arteries, the "padded" arterioli and the microvenules of the valves, the arteriovenous anastomoses, the smallest veins and the interstitial lymphatic channels form with the basal substance of the connective tissue to which they are incorporated, a true "functional" unit (Curri and Tischendorf, 1954).

Aging↗