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Ultrastructural changes in the intestinal connective tissue of Xenopus laevis during metamorphosis.

Ultrastructural changes in the intestinal connective tissue of Xenopus laevis during metamorphosis have been studied. Throughout the larval period to stage 60, the connective tissue consists of a few immature fibroblasts surrounded by a sparse extracellular matrix: few collagen fibrils are visible except close to the thin basal lamina. At the beginning of the transition from larval to adult epithelial form around stage 60, extensive changes are observed in connective tissue. The cells become more numerous and different types appear as the collagen fibrils increase in number and density. Through gaps in the thickened and extensively folded basal lamina, frequent contacts between epithelial and connective tissue cells are established. Thereafter, with the progression of fold formation, the connective tissue cells become oriented according to their position relative to the fold structure. The basal lamina beneath the adult epithelium becomes thin after stage 62, while that beneath the larval epithelium remains thick. Upon the completion of metamorphosis, the connective tissue consists mainly of typical fibroblasts with definite orientation and numerous collagen fibrils. These observations indicate that developmental changes in the connective tissue, especially in the region close to the epithelium, are closely related spatiotemporarily to the transition from the larval to the adult epithelial form. This suggests that tissue interactions between the connective tissue and the epithelium play important roles in controlling the epithelial degeneration, proliferation, and differentiation during metamorphic climax.

Animals↗

Early events associated with periodontal connective tissue attachment formation on titanium and hydroxyapatite surfaces.

Endosseous dental implants can support at least three types of biomaterial/connective tissue interfaces: osseointegration, fibro-osseous integration, and periodontal connective tissue attachment. Although a periodontal connective tissue attachment offers distinct advantages, only osseointegration and fibro-osseous integration are at present clinically achievable. Recent studies indicate a periodontal regeneration-competent cell population and an appropriate biomaterial substrate both are required for periodontal connective attachment formation on biomaterial surfaces. We therefore have developed an in vitro model to characterize the effects of various biomaterial substrates on the early events of periodontal connective tissue attachment formation. Primary cultures of periodontal ligament and gingival connective tissue cells were cultured on uncoated (control) and coated (titanium- and hydroxyapatite-coated) tissue culture plastic, and the level of cell proliferation, collagen, and noncollagen protein synthesis, alkaline phosphatase activity, and expression of a 42 kD cementum extracellular matrix protein were measured over 5, 7, and 9 days in culture. While all three substrates supported cell attachment, proliferation, and protein synthesis, only uncoated and titanium-coated tissue culture plastic supported expression of the cementum extracellular matrix protein after 9 days of culture. In addition, the levels of cell proliferation and collagen and noncollagen protein synthesis for cells grown on hydroxyapatite-coated surfaces lagged behind cells cultured on the control or titanium-coated surfaces at each of the three time points. These data suggest that biomaterial substrates markedly can influence the temporal sequence of extracellular matrix proteins associated with periodontal connective tissue attachment formation. In addition to surface composition (titanium versus hydroxyapatite), surface properties (e.g., topography) also may have an effect on periodontal connective tissue attachment formation. This model may be of use in designing biomaterials to support the formation of periodontal connective tissue attachment in vivo.

Animals↗

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↗

Immunopathology of skeletal muscle. The value of direct immunofluorescence in the diagnosis of connective tissue disease.

Whitaker and Engel in 1972 first described immunoglobulin deposition in muscle biopsy specimens in connective tissue disorders. In order to confirm and extend their observations and in the hope of identifying features that may differentiate skeletal muscle involvement in connective tissue diseases from other neuromuscular diseases, a series of 80 muscle biopsy specimens were examined using direct immunofluorescence. Three distinctive direct immunofluorescence patterns consisting of vascular, sarcolemma-basement membrane, and fiber staining were identified in skeletal muscle biopsy specimens from 35 patients, 31 of whom had a connective tissue disease. A vascular staining pattern showing a granular deposition of immunoglobulin or complement was seen in 15 patients, all of whom had a connective tissue disease. Routine stains generally did not reveal vessel abnormalities. A sarcolemma-basement membrane staining pattern was demonstrated around the sarcoplasmic membrane in 29 cases. Twenty-six of these patients had a connective tissue disease. There was no correlation with inflammation, fiber necrosis, or degree of connective tissue replacement. Fibers staining for immunoglobulin or complement, seen in 14 cases, generally occurred in morphologically normal fibers. Thirteen of these patients had a connective tissue disease. Since the pathologic change in muscle in the collagen vascular diseases often consists of the nonspecific findings of focal fiber necrosis frequently without inflammatory infiltrates, direct immunofluorescence may be useful in the diagnosis and classification of muscle diseases in the collagen vascular disorders. Furthermore, the findings of immunoglobulin deposition either within vessels or within individual muscle fibers suggest that immunological mechanisms may be responsible for muscular abnormalities in the connective tissue diseases.

Basement Membrane↗

Development and organization of the pelvic connective tissue in the human fetus.

The developmental changes in the pelvic connective tissue were studied in 200-600 microns sections through the pelves of human fetuses and newborn children, plastinated with an epoxy resin. Three periods are important for the differentiation of the pelvic connective tissue in fetuses. During a first or mesenchymal period (9-12-week-old fetuses), all pelvic regions identical with the so-called pelvic spaces in the adult are filled with loose undifferentiated mesenchyme. Some pelvic organs are covered by a layer of condensed mesenchyme which later constitutes the connective tissue sheath of these organs. During a second or fibrous period (13-20-week-old fetuses), dense connective tissue predominates. It is arranged in circular and semicircular systems covering the rectum, the bladder and the urethra as well as the peritoneal pouches. The arrangement of dense connective tissue is the same in the male and in the female fetus. No ligaments were found within the pelvic cavity apart from the pubovesical and the puboprostatic ligaments. The connective tissue sheaths of the pelvic organs differ from one another. At the level of the pelvic floor only some of them are directly connected with the parietal pelvic fascia. The pelvic spaces are filled by loose connective tissue. During a third or adipose period (21-38-week-old fetuses) adipose tissue develops within the different compartments of the pelvic cavity so that the clear organization found during the second period is abolished.

Abortion, Induced↗

Meta-analyses of the relation between silicone breast implants and the risk of connective-tissue diseases.

BACKGROUND: The postulated relation between silicone breast implants and the risk of connective-tissue and autoimmune diseases has generated intense medical and legal interest during the past decade. The salience of the issue persists, despite the fact that a great deal of research has been conducted on this subject. To provide a stronger quantitative basis for addressing the postulated relation, we applied several techniques of meta-analysis that combine, compare, and summarize the results of existing relevant studies. METHODS: We searched data bases and reviewed citations in relevant articles to identify studies that met prestated inclusion criteria. Nine cohort studies, nine case-control studies, and two cross-sectional studies were included in our meta-analyses. We conducted meta-analyses of the results of these studies, both with and without adjustment for confounding factors, and a separate analysis restricted to studies of silicone-gel-filled breast implants. Finally, we estimated the annual number of new cases of connective-tissue disease that could be attributed to breast implants. RESULTS: There was no evidence that breast implants were associated with a significant increase in the summary adjusted relative risk of individual connective-tissue diseases (rheumatoid arthritis, 1.04 [95 percent confidence interval, 0.72 to 1.51]; systemic lupus erythematosus, 0.65 [95 percent confidence interval, 0.35 to 1.23]; scleroderma or systemic sclerosis, 1.01 [95 percent confidence interval, 0.59 to 1.73]; and Sjögren's syndrome, 1.42 [95 percent confidence interval, 0.65 to 3.11]); all definite connective-tissue diseases combined (0.80; 95 percent confidence interval, 0.62 to 1.04); or other autoimmune or rheumatic conditions (0.96; 95 percent confidence interval, 0.74 to 1.25). Nor was there evidence of significantly increased risk in the unadjusted analyses or in the analysis restricted to silicone-gel-filled implants. CONCLUSIONS: On the basis of our meta-analyses, there was no evidence of an association between breast implants in general, or silicone-gel-filled breast implants specifically, and any of the individual connective-tissue diseases, all definite connective-tissue diseases combined, or other autoimmune or rheumatic conditions. From a public health perspective, breast implants appear to have a minimal effect on the number of women in whom connective-tissue diseases develop, and the elimination of implants would not be likely to reduce the incidence of connective-tissue diseases.

Autoimmune Diseases↗

EDTA separation and recombination of epithelium and connective tissue of human oral mucosa. Studies of tissue transplants in nude mice.

A possible epithelial-mesenchymal interaction in determining epithelial histologic features of human oral mucosa was examined. The study comprised 74 biopsies of normal buccal mucosa and 54 biopsies of normal palatal mucosa. Epithelium was separated from connective tissue by the use of 1 mM ethylenediamine tetraacetate dihydrate. Self-recombined and cross-recombined epithelial and connective tissues and connective tissue sheets alone were transplanted to subcutaneous sites of nude mice. Histologic examination of cross-recombined palatal epithelium/buccal connective tissue transplants showed a change in keratinization pattern but no major change in number of epithelial cell layers as the result of connective tissue influence. Transplanted sheets of connective tissue after growth for 14 days showed that complete separation of biopsies from buccal mucosa had been obtained. However, palatal mucosa had been incompletely separated as evidenced by re-epithelialization of most of the connective tissue transplants. The consequences of the incomplete palatal epithelium-connective tissue separation are discussed.

Adolescent↗

Experimental diabetes and the lung. II. In vivo connective tissue metabolism.

In vivo lung connective tissue and DNA synthesis, following intraperitoneal injection of [14C]proline and [3H]thymidine, were studied in streptozotocin-induced diabetic rats fed ad libitum. Insulin-treated diabetic and normal rats similarly fed, and undernourished rats weight-matched to the untreated diabetics, served as comparison groups. The ratio of unbound [14C]hydroxyproline to total [14C]hydroxyproline in the lung was used to assess connective tissue degradation. Compared to the normal group, the untreated diabetic animals showed similar synthesis of collagen and elastin, reduced synthesis of total protein and DNA, and decreased degradation of connective tissue. When compared with the normal group, the undernourished animals showed diminished synthesis of total protein, collagen, elastin, and DNA, and increased degradation of connective tissue. In comparison to the undernourished group, the untreated diabetic animals indicated increased synthesis of collagen and elastin, and diminished degradation of connective tissue; total protein and DNA syntheses were similar. The insulin-treated diabetic animals showed increased collagen and DNA synthesis. We conclude that experimental diabetes has a profound effect on lung connective tissue metabolism, supporting previous observations of connective tissue abnormalities and morphometric changes. The increase in lung collagen and elastin in diabetes is in part due to reduced breakdown of the connective tissue proteins.

Animals↗

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↗

Relationships between epithelium and connective tissue in inflamed gingiva.

Since chronic inflammation has been associated with degenerative and proliferative responses in connective tissue and epithelium, it was decided to investigate quantitatively the proportions of epithelium and connective tissue in inflamed gingiva. Forty-five midfacial gingival sites were assessed prior to biopsy for the presence or absence of bleeding after probing using a controlled insertion force fo 25 g. In order to delineate the corresponding area for histologic analysis, a reference incision was made on the facial surface of the gingiva which demarcated the depth and mesio-distal extent of the area probed. Step-serial bucco-lingual sections were morphometrically analyzed to determine the percentages of epithelium, inflamed, and noninflamed connective tissues coronal to the reference incision. The data was compared with respect to the presence or absence of bleeding after probing. Specimens which bled after probing had significantly less epithelium and more connective tissue. The increase in overall connective tissue was due to a significant increase in the inflamed component, and it appeared that the decrease in epithelium corresponded to the increase in inflamed connective tissue. The findings of diminished epithelium overlying inflamed connective tissue reinforces the concept that connective tissue status is important for determining structure and function of epithelium.

Adult↗

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↗

Prognostic factors for the development of rheumatoid arthritis and other connective tissue diseases in patients with palindromic rheumatism.

OBJECTIVE: Palindromic rheumatism is characterized by attacks of acute arthritis of short duration. In the long term, a substantial proportion of patients will develop rheumatoid arthritis (RA) or other connective tissue diseases, but the determinants of subsequent chronic disease have not been adequately established. We identify clinical prognostic factors for the development of RA and other connective tissue diseases in patients with palindromic rheumatism in a retrospective cohort study. METHODS: The medical records of 4900 patients with arthritis referred from 1986 to 1996 to 3 rheumatologists at an academic center were reviewed. One hundred sixty patients were diagnosed as having palindromic rheumatism. After review, 127 complied with diagnostic criteria for palindromic rheumatism. Disease duration was estimated as time of first attack until the last consultation, or the development of RA or other connective tissue disease. Survival analysis including Cox regression was used to identify clinical variables associated with the risk of developing RA or other connective tissue disease, adjusting for varying disease duration. RESULTS: Sixty-five percent of the patients were female. Age at onset was 40+/-12 years. Mean disease duration was 6+/-6 years, and mean followup by the rheumatologists was 40+/-45 months. Joints more frequently affected were wrist, knee, and metacarpophalangeal. Forty-three patients (34%) subsequently developed a connective tissue disease including 36 (28%) RA, 3 (2%) systemic lupus erythematosus, and 4 (3%) other connective tissue diseases. In the final Cox regression model the hazard ratio for development of a connective tissue disease in the presence of a positive rheumatoid factor (RF) was 2.9 (p = 0.002), for proximal interphalangeal (PIP) joint involvement 2.4 (p = 0.02), for wrist involvement 2.5 (p = 0.05), for female sex 2.2 (p = 0.05), and for age at onset 1.03 (per year) (p = 0.001). Female patients with positive RF and involvement of the hands had an 8-fold risk of developing disease, compared with patients with one or fewer of these features. CONCLUSION: Positive RF and early involvement of the wrist and PIP joints predict the subsequent development of RA or other connective tissue disease in patients with palindromic rheumatism, and identify a group of patients at increased risk.

Adult↗

Comparative connective tissue structure-function relationships in biologic pumps.

A complex connective tissue framework exists in mammalian hearts that surrounds and interconnects individual myocytes and fascicles of cells. Recent evidence suggests that this connective tissue plays a role in maintaining shape, modulating contractile forces, and mediating elastic recoil during cavity filling and contraction. In order to analyze the involvement of connective tissue in pump contraction and recoil, we examined silver impregnated connective tissue in rat hearts which spontaneously jet through fluid ex vivo by contracting their cavities forcefully and then sucking fluid for the next cycle, and compared them to frog hearts which beat actively under the same conditions, but do not demonstrate jet propulsion. A further analysis was carried out in unrelated but analogous models: the squid and octopus. The former jets rapidly through the ocean, while the latter moves sinuously along the seabed. We observed highly interconnected myocytes in the rat heart, whereas frog myocytes are individually wrapped by connective tissue but are not interconnected. The squid mantle muscle is surrounded by a complex connective tissue grid that is tethered to each muscle cell, whereas the octopus mantle muscle cells are surrounded by connective tissue but are not tethered. These observations suggest that myocyte connective tissue tethering may be necessary for muscle cavities to generate forceful and coordinated contractions sufficient for rapid ejection and suction of fluid.

Animals↗

[Stereo architecture of the connective tissue papillae of lips and gingiva in newborn dogs].

The surface structure of the connective tissue papillae of lips and gingiva of newborn dogs 1 and 4 weeks after birth were observed by scanning electron microscopy. 1. Long term HCl treatment successfully removed the epithelial cell layer from the connective tissue over a large area of fixed material. 2. Connective tissue papillae of labial skin, labial mucosa and alveolar and gingival mucosa were exposed and it became clear that connective tissue papillae were highly developed at the labial margin and just beneath the gingival margin. 3. In the hair growing area of the labial skin, connective tissue papillae became smaller, and some ridge-like structures were found running vertically. 4. On the lining mucosa such as the labial and alveolar mucosa, the surface of the connective tissue papillae showed only ridge-like structures running vertically. 5. From the results of both light and electron microscopy, we concluded that there was a tendency for the area to have a thick epithelial cell layer which contained highly developed connective tissue papillae. This suggested that the blood vessels in the connective tissue papillae can carry nutrients closer to more epithelial cells penetrating deeply into the epithelium thickness.

Animals↗

Relationships between the arteries and veins and the connective tissue system in the human orbit.

The arteries and veins in the apical region of the orbit occupy different areas. Furthermore, there is a difference in their relationships to the connective tissue system. In this part of the orbit, where only a few connective tissue septa are present, the arteries are mainly concentrated in the inner-space. The veins, on the other hand, are predominantly found peripherally, outside the muscle cone. The arteries are surrounded by adipose tissue. They are only in contact with connective tissue fibres when perforating the septa on their way to the outer regions of the inner-space. A small number of vessels, the posterior ciliary arteries and the central artery of the retina, keep their central position, grouped around the optic nerve. The conduct of this group of arteries in respect to the connective tissue is somewhat different than that of the other arteries. The ciliary arteries and the central retinal artery have varying contacts with the optic sheath. In contrast to the arteries, which in general lack firm connections with fibrous connective tissue, the major veins are encased in the tight connective tissue of the orbital fissures, or enveloped in connective tissue septa. For the smaller veins, these fibrous relationships are usually less intimate and occasionally disrupted. More extensive discussion and conclusions will be given in the following article. This will deal with the rest of the retrobulbar part of the orbit.

Adult↗

Some histological aspects of the structure of the connective tissue system and its relationships with the blood vessels in the human orbit.

The connective tissue septa in the human orbit are organized in a constant and characteristic fashion. In the collagen fibre meshwork of the septa, anteroposteriorly directed collagen fibre bundles are relatively rare. The number of smooth muscle cells present in a septum depends on the orbital level explored. In the apical region only few of these cells are found, at eye-ball level they are more numerous. No further regularity in distribution of smooth muscle cells in the septa is present. All connective tissue septa contain elastic fibres. Blood vessels and connective tissue form an integrated system. The venous walls merge with the fibrous structure of the septa; the arteries only make contact with the septa when they perforate them. In doing so, the arteries mainly run between the septal fibre bundles, only loosely connected to some of them. The microvascular system is predominantly confined to the adipose tissue compartments. The interrelationships of the vascular system and the connective tissue system are likely to be important factors in controlling and regulating orbital blood-flow. In addition, the well-defined morphological organization of the connective tissue in its interrelationships with the vascular system might serve a mechanical regulating function by both allowing and restricting certain eye-ball movements. For these functions, the physico-chemical properties of the connective tissue system and the microstructure of the vascular system are probably of considerable interest. Thus, the highly organized architecture of the connective tissue system in the human orbit together with its intricate interrelationships with the vascular system, might prove to be important for mechanical as well as metabolic purposes and so have consequences for interventions, diagnostic or surgical, in the orbit.

Blood Vessels↗

The connective tissue of the adult female pelvic region. A musculo-fibrous apparatus.

From histologically stained transparent 0.7-0.8 cm thick serial sections of adult female pelves transparent glass-plate reconstructions of the connective tissue septa system were prepared. The analysis of these reconstructions revealed a bilateral symmetry and an interindividual uniformity of the connective tissue system and the adipose tissue components lying in between. The connective tissue system separating different functional compartments in the retroperitoneal space in order to envelop the muscles, the bones, the vessels and the viscera, forms a substaining system interwoven with the connective tissue elements of the musculus levator ani and perforating the muscle, and continues into the connective tissue system in the fossa ischiorectalis upto the fascia perinei superficialis is reached. The fasciae of the pelvic muscles, the sacro-tuberal and sacro-spinal ligaments and the ligaments of the uterus appear to be completely involved in this system of connective tissue septa. The connective tissue system links the pelvic viscera up to the muscular and bony parts of the locomotive systems of the trunk and the legs, giving a rise to a functional entity. The formulation of the hypothesis of this entity raised new questions about the structure of the different connective tissue septa in the female pelvic region.

Connective Tissue↗

Self-reported breast implants and connective-tissue diseases in female health professionals. A retrospective cohort study.

OBJECTIVE: To evaluate the association of breast implants with connective-tissue diseases. DESIGN AND PARTICIPANTS: Retrospective cohort study of 395,543 female health professionals who completed mailed questionnaires for potential participation in the Women's Health Study. A total of 10,830 women reported breast implants and 11,805 reported connective-tissue diseases between 1962 and 1991. Cox proportional hazards regression models were used in analyses. MAIN OUTCOME MEASURE: Self-reported connective-tissue diseases. RESULTS: Compared with women who did not report breast implants, the relative risk (RR) of the combined end point of any connective-tissue disease among those who reported breast implants was 1.24 (95% confidence interval, 1.08 to 1.41, P = .0015). With respect to the individual diseases, the finding for other connective-tissue diseases (including mixed) was statistically significant (P = .017), the findings for rheumatoid arthritis, Sjogren's syndrome, dermatomyositis or polymyositis, or scleroderma were of borderline statistical significance (.05 < P < .10), and the finding for systemic lupus erythematosus was not statistically significant (P = .44). There were no clear trends in RR with increasing duration of breast implants. CONCLUSION: These self-reported data from female health professionals are compatible with prior reports from other cohort studies that exclude a large hazard, but do suggest small increased risks of connective-tissue diseases among women with breast implants. The very large sample size makes chance an unlikely explanation for the results, but bias due to differential overreporting of connective-tissue diseases or selective participation by affected women with breast implants remains a plausible alternative explanation. The major contribution of this and other observational analytic studies has been to exclude large risks of connective-tissue diseases following breast implants.

Adult↗