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Silicon analysis of breast and capsular tissue from patients with saline or silicone gel breast implants: II. Correlation with connective-tissue disease.

The silicone breast implant controversy rages on. Recent work has demonstrated that normal or baseline breast tissue silicon levels in women who had had no prior exposure to any type of breast implant may be as high as 446 microg/gm of tissue. These data ranged from 4 to 446 microg/gm of tissue, with a median of 27.0 microg/gm of tissue. In addition, numerous other epidemiologic and rheumatologic studies have demonstrated no association between silicone breast implants and any connective-tissue diseases. Despite these reports, the use of silicone implants remains restricted. The present study measured breast and capsular tissue silicon levels from 23 breasts in 14 patients with saline implants, and from 42 breasts in 29 patients with silicone implants. No patient in the saline implant group presented with signs or symptoms of connective-tissue disease. Patients with silicone implants, however, were divided into three groups based on the presence or absence of signs or symptoms of connective-tissue disease: group I, no symptoms or signs; group II, + symptoms, no signs; and group III, + symptoms, + signs. Six patients in group III were diagnosed with a specific connective-tissue disease, including systemic lupus erythematosus, rheumatoid arthritis, or scleroderma. The most common indications for implant removal or exchange were capsular contracture and implant rupture, although 41 percent of patients with silicone implants expressed media-related concern over the implant issue. The most common symptoms described by patients in groups II and III were joint pain and stiffness, arm pain and numbness, and fatigue. In all groups, capsular tissue silicon levels were significantly greater than breast tissue levels. This finding may indicate that the capsule serves as a barrier to the distribution of silicone from the implant into adjacent breast tissue. Although breast tissue silicon levels in patients with silicone implants were not significantly greater than those in patients with saline implants (p = 0.48), capsular tissue levels in patients with silicone implants were, indeed, significantly greater than those in patients with saline implants (p < 0.001). However, no statistically significant differences in tissue silicon levels were observed with relation to the presence or absence of connective-tissue disease signs or symptoms in patients with silicone implants (groups I to III). Therefore, these data strengthen the conclusion that there is no association between tissue silicon levels and connective-tissue disease.

Breast↗

Configuration of the connective tissue in the posterior atlanto-occipital interspace: a sheet plastination and confocal microscopy study.

STUDY DESIGN: The connective tissue structures in the posterior atlanto-occipital region were investigated using E12 sheet plastinations and confocal microscopy. OBJECTIVES: To define the relationship between rectus capitis posterior minor (RCPm), posterior atlanto-occipital (PAO) membrane, nuchal ligament, and the spinal dura in the PAO interspace. SUMMARY OF BACKGROUND DATA: It has been speculated that connections between the dura and muscles and/or ligaments in the PAO interspace may transmit forces from the cervical spine joint complexes to the pain-sensitive dura, generating cervicogenic headaches. Anatomic structures involved in these connections include the RCPm, PAO membrane, and nuchal ligament. However, there is little information about the nature of these connections and the relationships between these anatomic structures. METHODS: The study used a combined approach, consisting of the gross anatomic dissection of nine cadavers and the E12 sheet plastination method for thirteen adult human cadavers, five of which were further examined using confocal microscopy. RESULTS: The study demonstrates that (1) the tendinous fibers from the medial and deep part of the RCPm muscle are continuous antero-inferiorly with the spinal dura; (2) the PAO membrane is part of the RCPm fascia and tendon and the perivascular sheathes; (3) antero-inferiorly the PAO membrane fuses with the spinal dura rather than the atlas; and (4) the nuchal ligament does not exist in the PAO interspace. CONCLUSIONS: The connective tissue structures that connect the spinal dura to the RCPm muscle in the PAO interspace are the RCPm fascia and tendinous fibers and perivascular sheathes.

Aged↗

Propagation in cardiac tissue adjacent to connective tissue: two-dimensional modeling studies.

The conditions for activation transmission across a region of extracellular space was demonstrated in two-dimensional preparations with results consistent with those previously seen in the one-dimensional fiber studies. In addition, one sees changes in action potential morphology which occur in the tissue nearest the connective-tissue border as well as changes in conduction velocity along the border. These results hinge on an adequate representation of the connective-tissue region achieved by careful implementation of the boundary conditions in the intracellular and interstitial spaces and the expansion of the connective-tissue discretization to a "double-tier network" description. Through a series of simulations, a clear dependence on fiber orientation is illustrated in the efficacy to transmit activation. The collision of a front with an embedded connective-tissue region was also examined. The results revealed that fibers aligned normal to a planar stimulus would more greatly disrupt the advancement of a planar front. Such pronounced disruptions have been shown to be proarrhythmic in the literature. The increasing evidence of the ability of connective tissue to transmit activation has implications in understanding spread of activation through infarcted tissues and through the healthy ventricular wall in the presence of connective-tissue sheets.

Action Potentials↗

Spinal cord transection: a quantitative analysis of elements of the connective tissue matrix formed within the site of lesion following administration of piromen, cytoxan or trypsin.

Long-Evans hooded rats were cordotomized at the T-5 level and given either (1) cyclophosphamide (cytoxan), an immunosuppressive, (2) piromen, a bacterial polysaccharide-nucleic acid complex, (3) topical and systemic trypsin, or (4) no further specific treatment. Because of past and present controversy surrounding the proposed ability of these agents to promote spinal cord regeneration, a systematic study, employing light and electron microscopy, and quantitative methods in a single animal model, was done in order to re-evaluate the effects of each treatment upon the connective tissue matrix which forms in the defect left by transection. After an initial inflammatory reaction during the first week after surgery, the lesion zone is characterized either by areas of dense collagenous connective tissue with occasional fibroblasts and macrophages, or a loose areolar tissue with numerous sheets and cords of mesodermal cellular elements but minimal collagen. By 45 days postoperatively (dpo), axons supported by Schwann cells invade and become entangled in the loose connective tissue matrix. With longer postoperative survival, cysts appear craniad and caudad to the lesion and erode much of the scar together with viable neural tissue. Giving cytoxan or piromen did not result in any qualitative alteration of the scar matrix as evidenced by electron microscopy. Quantitative analysis revealed a slight reduction in the fibrous connective tissue component of the scar at 45--90 dpo, but this was transient when longer postoperative periods were studied. Trypsin caused a significant reduction in the amount of fibrous connective tissue with a concomitant increase in loose connective tissue and the appearance of a few distinctive, compact bundles of unmyelinated axons lacking Schwann cells. Consistent behavioral changes were not observed in any group which could distinguish them from the controls. Our results appear to contradict the findings of Matinian and Andreasian (1976) who reported return of normal sensori-motor function in 80% of their animals treated with topical and systemic trypsin. It is concluded that a major impediment to whatever longterm regenerative potential exists within the spinal cord is the lack of axonal guiding elements within the scar, but more importantly, the severe erosion of the remaining spinal cord due to cyst enlargement.

Animals↗

Healing following implantation of periodontitis-affected roots into gingival connective tissue.

The aim of the present investigation was to examine if a new connective tissue attachment can be established on a previously periodontitis involved root surface, located in contract with gingival connective tissue during healing. A total of 28 teeth in one dog (beagle) and two monkeys (Macaca cynomolgus) were subjected to experimental periodontal tissue breakdown by placing cotton floss ligatures or orthodontic elastics around the teeth. The ligatures were left in situ until about 50% of the supporting tissues had been lost. Following resection of the crowns, the teeth were root filled and the exposed parts of the roots thoroughly scaled and planed. Each root was extracted and implanted into grooves prepared in edentulous areas of the jaws in such a way that the root was embedded to half its circumference in bone, leaving the remaining part to be covered by the gingival connective tissue of the repositioned flap of the recipient site. Root implantation and sacrifice of the animals were scheduled to allow for observation periods of 2 and 3 months of healing. An analysis of histologic specimens, obtained from biopsies of the recipient site tissues, disclosed that a new fibrous attachment failed to form on a previously "exposed" root surface located in contact with gingival connective tissue. In areas of the roots where the periodontal ligament tissue was preserved prior to transplantation, a fibrous reattachment occurred between the root and the adjacent gingival tissue. The results indicate that gingival connective tissue does not possess the ability to establish conditions which enable the formation of a new connective tissue attachment.

Alveolar Process↗

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↗

Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden.

OBJECTIVE: To examine the relation between connective tissue disease and related conditions and breast implants. DESIGN: Retrospective cohort study of all women in the Swedish national inpatient registry who underwent breast augmentation surgery with artificial implants during 1964-93, compared with women who underwent breast reduction surgery during the same period. SETTING: Sweden. SUBJECTS: 7442 women with implants for cosmetic reasons or for reconstruction after breast cancer surgery and 3353 women with breast reduction surgery. MAIN OUTCOME MEASURES: Subsequent hospitalisation for definite connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and Sjögren's syndrome) or related disorders. RESULTS: 29 women with implants were hospitalised for definite connective tissue disease compared with 25.5 expected based on general population rates (standardised hospitalisation ratio 1.1 (95% confidence interval 0.8 to 1.6)). There were no diagnoses of systemic sclerosis, and no significant excess in risk for polymyalgia rheumatica, fibromyalgia, and several related disorders. Among women who underwent breast reduction surgery, 14 were hospitalised for definite connective tissue disease compared with 10.5 expected (standardised hospitalisation ratio 1.3 (0.7 to 2.2)). Compared with the breast reduction group, women with breast implants showed a slight reduction for all definite connective tissue disease (relative risk 0.8 (95% confidence interval 0.5 to 1.4)). CONCLUSIONS: This large nationwide cohort study shows no evidence of association between breast implants and connective tissue disease.

Adult↗

[Associations between chronic irritation of tonsils, indurations of connective tissue areas and brachialgia paresthetica nocturna].

UNLABELLED: Projective and reflex zones of inner organs to the body's surface are well described but there are only few clinical studies about abnormal zones. OBJECTIVE: The aim of our study was to investigate associations between chronic irritation of tonsils, abnormalities of the connective tissue areas over the musculus trapezius and the severity of brachialgia paresthetica nocturna. METHODS: Cross sectional study in 100 adult pain patients from an outpatient pain department. Patients with tonsillectomy were excluded. Examinations of tonsils and the connective tissue area were done separately by two mutually blinded physicians. Both were also blinded to the patients' evaluation of his/her brachialgia. RESULTS: Regardless of the lateralization, the severity of the tonsil irritations was correlated with the abnormalities of the connective tissue areas (Spearman's rho = 0.82; 95% confidence interval (CI): 0.74-0.87; p < 0.001) and the severity of the brachialgia (rho = 0.64, CI: 0.50-0.74; p < 0.001), furthermore indurations of connective tissue areas correlated with the severity of brachialgia homolaterally (rho = 0.57; CI: 0.42-0.69; p < 0.001). These correlations are considerably higher than those of other connective tissue areas. CONCLUSIONS: The results support the existence of easy to diagnose reflex zones, at least in a highly selected population of pain patients. They can give plausible hints for naturopathic treatments of brachialgia paresthetica nocturna, i.e. treatment of the relevant connective tissue zone above the M. trapezius.

Adolescent↗

Elevated plasma hydroxyproline. A possible risk factor associated with connective tissue injuries during overuse.

Basal plasma hydroxyproline was measured in 104 male Navy Seal candidates 1 week into their intense physical training program, which lasted 7 weeks, and correlated to the incidence of connective tissue injuries incurred later in the training program. Eleven subjects (10.6%) were diagnosed as having connective tissue injuries. Those subjects with connective tissue injuries had a significantly higher (P less than 0.05) mean plasma hydroxyproline value (4.02 micrograms/ml) than subjects without injury (3.10 micrograms/ml). The majority of graduates (75%) had plasma hydroxyproline values less than 3.3 micrograms/ml. These graduates represented the strongest and most enduring injury-free subjects. Of the subject pool who incurred connective tissue injuries, only 27% had plasma hydroxyproline values less than 3.3 micrograms/ml. The majority of the injured subjects (73%) had plasma hydroxyproline values greater than or equal to 3.3 micrograms/ml. In conclusion, there is a relationship between initial training basal plasma hydroxyproline levels and connective tissue injuries later incurred in an intense physical training program. These data suggest that elevated plasma hydroxyproline levels may represent a risk factor associated with connective tissue injuries.

Adolescent↗

Electrical impedance along connective tissue planes associated with acupuncture meridians.

BACKGROUND: Acupuncture points and meridians are commonly believed to possess unique electrical properties. The experimental support for this claim is limited given the technical and methodological shortcomings of prior studies. Recent studies indicate a correspondence between acupuncture meridians and connective tissue planes. We hypothesized that segments of acupuncture meridians that are associated with loose connective tissue planes (between muscles or between muscle and bone) visible by ultrasound have greater electrical conductance (less electrical impedance) than non-meridian, parallel control segments. METHODS: We used a four-electrode method to measure the electrical impedance along segments of the Pericardium and Spleen meridians and corresponding parallel control segments in 23 human subjects. Meridian segments were determined by palpation and proportional measurements. Connective tissue planes underlying those segments were imaged with an ultrasound scanner. Along each meridian segment, four gold-plated needles were inserted along a straight line and used as electrodes. A parallel series of four control needles were placed 0.8 cm medial to the meridian needles. For each set of four needles, a 3.3 kHz alternating (AC) constant amplitude current was introduced at three different amplitudes (20, 40, and 80 microAmps) to the outer two needles, while the voltage was measured between the inner two needles. Tissue impedance between the two inner needles was calculated based on Ohm's law (ratio of voltage to current intensity). RESULTS: At the Pericardium location, mean tissue impedance was significantly lower at meridian segments (70.4 +/- 5.7 Omega) compared with control segments (75.0 +/- 5.9 Omega) (p = 0.0003). At the Spleen location, mean impedance for meridian (67.8 +/- 6.8 Omega) and control segments (68.5 +/- 7.5 Omega) were not significantly different (p = 0.70). CONCLUSION: Tissue impedance was on average lower along the Pericardium meridian, but not along the Spleen meridian, compared with their respective controls. Ultrasound imaging of meridian and control segments suggested that contact of the needle with connective tissue may explain the decrease in electrical impedance noted at the Pericardium meridian. Further studies are needed to determine whether tissue impedance is lower in (1) connective tissue in general compared with muscle and (2) meridian-associated vs. non meridian-associated connective tissue.

Adult↗

Connective tissue analysis of the canine circle of Willis in hypertension.

The collagen and elastin contents of the major arterial components of the canine circle of Willis (basilar artery, posterior cerebral artery, internal carotid artery, middle cerebral artery, and anterior cerebral artery) were determined as measures of the passive mechanical properties of these vessels. Studies were carried out in seven normotensive dogs and seven dogs in which experimental renal hypertension of 3 months duration had been induced. In the normotensive animals, the collagen content of the middle cerebral artery exceeded that of the other vessels considered. The elastin content and the total connective tissue were not significantly affected by arterial site. The middle cerebral artery collagen to elastin ratio was greater than corresponding values for the basilar, posterior cerebral, and internal carotid arteries. Connective tissue differences were less pronounced in the hypertensive animals. No component of the canine circle of Willis in the hypertensive dogs showed a significantly different collagen content, elastin content, total connective tissue content, or collagen to elastin ratio. In comparing cerebral vessels from normotensive and hypertensive dogs, total connective tissue values were greater in hypertension for all arterial sites considered. These acute physiological changes in connective tissue content over small distances in intracranial blood vessels from normotensive animals, together with unique connective tissue responses of these vessels to short term hypertension, may suggest additional possible factors important in the natural history of cerebrovascular pathological conditions.

Animals↗

Effects of periodontal cell grafts and enamel matrix proteins on the implant-connective tissue interface: a pilot study in the minipig.

We have developed an experimental model to help identify and characterize factors necessary for periodontal connective tissue attachment formation on dental implants. In this pilot study, we report the effect of autogenous periodontal cell grafts, with and without the a pplication of enamel matrix derivative (EMD), on the implant-connective tissue interface. Periodontal ligament (PDL) and gingival connective tissue (GCT) cultures were established from an adult minipig. Implants were placed in osteotomies prepared with exaggerated countersinks that served as recipient sites for autogenous cell grafts in bilateral edentulated posterior mandibular sextants. In addition, 1 side received an application of EMD before placement of the autogenous cell grafts. A bioabsorbable membrane covering the coronal portion of the implants was placed before closure. After 8 weeks, quantitative histomorphometric and qualitative light microscopic analyses revealed that the implants that received gelatin vehicle alone were surrounded by bone, whereas the implants that received GCT cell grafts were mostly surrounded by fibrous connective tissue. In contrast, implants that received PDL cells without the application of EMD demonstrated good bone contact, but strands of epithelium were observed in the implant-connective tissue interface. Implants that received PDL cells and EMD also had good bone contact but without evidence of epithelium. A cementum-like interface was not observed in any of the groups. Results of this pilot study suggest that EMD and the type of cell populations present in the implant wound-healing environment may alter the implant-connective tissue interface.

Animals↗

[Proposal of a questionnaire for the characterization of the prevalence of digestive symptoms in connective tissue diseases].

BACKGROUND: Connective tissue diseases may damage multiple organic systems, including digestive system. In this one, the degree of injury vary according to the associated disease. Despite the significant frequency of gastrointestinal involvement, there are few studies characterizing the prevalence of digestive symptoms in connective tissue diseases. Furthermore, most of the studies available are less detailed and based in personal experiences or reviews of records. AIM: To establish a reliable list of gastrointestinal symptoms found in the progressive systemic sclerosis, rheumatoid arthritis, polymyositis/dermatomyositis, mixed connective tissue disease and systemic lupus erythematosus, through a medical interview and a predefined questionnaire of symptoms. PATIENTS AND METHODS: There were studied 99 patients, 90% females, mean age 45 years. The whole group were composed of 35 rheumatoid arthritis, 26 progressive systemic sclerosis, 21 systemic lupus erythematosus, 12 polymyositis/dermatomyositis and 5 mixed connective tissue disease. Each patient was submitted to an interview with a well trained doctor and answered a structured questionnaire, containing 17 questions. RESULTS: It was found a high prevalence of digestive symptoms in all five connective tissue diseases searched. Many of them were present in more than 50% of the patients. Called special attention the detection of some manifestations neglected by the literature like, for example, fecal incontinence. Also, disagreeing with other authors, was the finding of multiple gastrointestinal manifestations associated with rheumatoid arthritis. It was particularly surprising the occurrence of dysphagia in one third of the rheumatoid arthritis group. CONCLUSIONS: The connective tissue diseases are usual causes of many gastrointestinal complaints. The use of an interview plus predefined questionnaire seems a very effective way to identify and characterize symptoms and is even sometimes able to uncover features unknown before. Finally, the lack of studies, specially updated studies, did not allow more comprehensive comparisons.

Adult↗

Integrated connective tissue in bioabsorbable barrier material and periodontal regeneration.

The objective of this study was to evaluate the relationship between integrated connective tissue (ICT), that is, the presence of connective tissue into the membrane structure, and the clinical outcome of membrane-supported periodontal surgery. Twenty-six systemically healthy subjects affected by chronic adult periodontitis were enrolled in the study. One tooth site per patient, associated with an angular bony defect and an attachment loss of > 7 mm, was selected to be treated by means of a guided tissue regeneration procedure using a bioabsorbable membrane. Barrier material was surgically removed after 4 weeks for SEM analysis. For each treated site, the difference in clinical attachment loss, probing depth, and gingival recession between the baseline examination and follow-up 6 months after the second surgery was calculated. Gain of attachment was statistically (P < 0.001) greater in sites with no membrane exposure when compared to sites with exposed barrier material (5.5 +/- 1.0 vs. 4.0 +/- 0.6), while further gingival recession was greater (3.0 +/- 0.9 vs. 2.1 +/- 0.5) in sites with clinically exposed membranes. The results of SEM analysis revealed that when connective tissue structures were observed on membrane surfaces, no bacteria could be detected; conversely, areas heavily colonized by bacteria did not show the presence of connective tissue. Regression analysis indicated that integrated connective tissue on the external layer of the barrier material was positively correlated with the amount of attachment gain and negatively with the amount of gingival recession. Bacterial colonization of the membrane was negatively correlated with attachment gain and positively with gingival recession. It was concluded that connective tissue integration is an important biological phenomenon in preventing membrane exposure and bacterial plaque colonization and thus in enhancing the clinical outcome following guided tissue regeneration surgery.

Absorption↗

Evaluation of human recession defects treated with coronally advanced flaps and either enamel matrix derivative or connective tissue. Part 2: Histological evaluation.

BACKGROUND: A number of surgical procedures are effective in covering denuded root surfaces. The first paper in this series evaluated the subepithelial connective tissue graft and the coronally advanced flap with enamel matrix derivative (EMD). That paper revealed no significant difference in the percent of root coverage between the two treatments (P = 0.82). There is limited human histological evidence of the type of attachment achieved with these types of procedures. This paper presents a human case report detailing the histological nature of the attachment of these two treatments to the root surfaces previously exposed by recession. METHODS: One patient presented with two hopeless teeth that were randomized to receive either a subepithelial connective tissue graft or a coronally advanced flap plus EMD. The surgery was accomplished in accordance to the protocol previously described. The teeth and a small collar of tissue were removed at 6 months and underwent histological analysis. RESULTS: Histological evaluation of the subepithelial connective tissue graft revealed a connective tissue attachment between the tooth and graft, and no histological evidence of cementum, bone, or periodontal ligament (PDL) and, therefore, regeneration. In addition, there appeared to be some resorption of the dentin adjacent to the graft. Histological evaluation of the coronally advanced flap with EMD revealed new cementum, organizing PDL fibers and islands of condensing bone at a constant distance from the root surface. CONCLUSIONS: The subepithelial connective tissue graft in this study was found to have adhered to the root surface primarily by a connective tissue attachment with some evidence of root resorption. The coronally advanced flap with EMD was found histologically to have all the tissues necessary for regeneration: new cementum, organizing PDL fibers, and islands of condensing bone. These histologic sections strongly suggest that enamel matrix derivative works in a biomimetic fashion by mimicking the natural process of tooth development.

Adult↗

[Newer approach of screening test for antinuclear antibodies: an enzyme-linked immunosorbent assay detecting antinuclear antibodies characteristic of connective tissue diseases].

An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of antinuclear antibodies (ANAs) previously established as diagnostic and/or prognostic marker ANAs for various connective tissue diseases. The antigen used in ELISA is a mixture of purified recombinant or natural antigens including single-and double-stranded DNA, RNP, Sm, SS-A/Ro, SS-B/La, centromere, topoisomerase I and Jo-1 antigens. Thirty hundred and fifty nine patients sera from a variety of connective tissue diseases and 113 normal human sera (NHS) were examined. ELISA ANAs were positive in 3.5% of NHS and 80.2% of patients sera at cut off index 11.5, whereas indirect immunofluorescent antinuclear antibodies (FANAs) using HEp-2 cells were positive in 9.7% of NHS and 92.5% of patients sera at 1:160 serum dilution. More than 80% of sera from systemic lupus erythematosus, mixed connective tissue disease and primary Sjögrens disease were ELISA ANAs positive. Mean value of ELISA ANAs was highest in sera of patients with MCTD. ELISA ANAs were positive in 92.5% of sera with marker ANAs for connective tissue diseases. Mean value of ELISA ANAs was higher in sera with more than two marker ANAs than in sera with a single ANA or in sera without marker ANAs. In contrast incidence and mean value of ELISA ANAs were low in sera positive for anti topoisomerase I antibody or anti Jo-1 antibody. Sensitivity, specificity and agreement (accuracy) for connective tissue diseases with marker ANAs were as follows: ELISA ANAs (at index 11.5): 92.5%, 88.3% and 90.9%: FANAs (at 1:160 serum dilution): 99.0%, 70.4% and 88.1%, respectively. ELISA ANAs, thus, are specific for connective tissue diseases when compared to FANAs and previous ELISA for the detection of total ANAs. Moreover, ELISA ANAs are able to measure precise ANAs titers and are much less labor intensive when screening a large number of clinical specimens.

Adult↗

Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort of patients with connective tissue disease.

BACKGROUND: Two types of antineutrophil cytoplasmic antibodies (ANCA), antiproteinase 3 antibodies (anti-PR3) and antimyeloperoxidase antibodies (anti-MPO), are useful in the diagnosis of such types of vasculitis as Wegener granulomatosis and microscopic polyangiitis. Connective tissue diseases frequently appear in the differential diagnosis of this spectrum of vasculitis. OBJECTIVE: To determine the prevalence of ANCA in patients with connective tissue disease. DESIGN: Blinded, controlled study of a 5-year inception cohort. SETTING: Tertiary-care university teaching hospitals. PATIENTS: 70 patients with rheumatoid arthritis, 70 patients with systemic lupus erythematosus, 45 patients with scleroderma, 36 patients with inflammatory myositis, 44 patients with the sjögren syndrome, 33 patients with the antiphospholipid syndrome, and 165 patients with early undifferentiated connective tissue disease (EUCTD). Serum was taken from 200 blood donors and 52 patients who had known vasculitis and positive results on tests for anti-PR3 or anti-MPO; these patients served as controls. MEASUREMENTS: The presence of anti-PR3 and anti-MPO was determined by combining the results of indirect immunofluorescence tests for cytoplasmic (C-ANCA) and perinuclear (P-ANCA) patterns with the results of enzymelinked immunosorbent assays (ELISAs) directed to measure antigen. RESULTS: Cytoplasmic ANCA was not detected in any study or control patient. Perinuclear ANCA was commonly detected among patients with lupus (31%) but was uncommon among patients in other groups (0% to 5%). In all cases, P-ANCA was associated with the presence of antinuclear antibodies. Atypical ANCA immunofluorescence patterns were fairly common in all groups (11% to 39%). Antiproteinase 3 was detected by ELISA in study patients (1 patient with rheumatoid arthritis, 1 with lupus, 1 with polymyositis, and 6 with EUCTD). Antimyeloperoxidase was detected by ELISA in 2 study patients (1 with rheumatoid arthritis and 1 with lupus). None of the patients with positive ELISA results had evidence of renal vasculitis during follow-up. When an ANCA scoring system that combines immunofluorescence and ELISA was used, the test specificity for vasculitis was 99.5% among patients with connective tissue disease. CONCLUSIONS: Patients with connective tissue disease are known to develop multiple autoantibodies; positivity for anti-PR3 and anti-MPO ANCA in such patients is highly specific for anti-PR3. However, P-ANCA immunofluorescence, which may have positive results because of the presence of antinuclear antibodies, is not a specific marker of anti-MPO. A rigorous ANCA testing system that combines the results of immunofluorescence with those of ELISA is highly specific for Wegener granulomatosis and related vasculitides even in patients with connective tissue disease.

Antibodies, Antineutrophil Cytoplasmic↗

[Undifferentiated connective tissue disease: clinical and serological profile of 578 patients followed for five years: disease course, prognosis and therapy].

INTRODUCTION: Evolution of immunopathological diseases is usually slow and progressive. The term the undifferentiated connective tissue disease (UCTD) is used to describe the phase preceding a defined connective tissue diseases (CTD). AIMS: The objective of this work was evaluate the clinical and serological profile of patients with UCTD, who had been followed between 1994-1999. They have investigated the frequency and the type the developed autoimmune diseases from UCTD. PATIENTS: A total of 578 UCTD patients were evaluated. RESULTS: In 143/578 patients (24.7%) with the UCTD differentiated to systemic connective tissue diseases (28 systemic lupus erythematosus, 26 mixed connective tissue disease, 19 progressive systemic sclerosis, 3 polymyositis/dermatomyositis, 45 Sjögren syndrome, and 22 systemic vasculitis). 86.7 percent (124/143) of the systemic connective disease developed in first two years of UCTD. The condition of 435/578 (75.2%) remained UCTD after 5 years, among them in 82 patients with UCTD was regression of the symptoms. The presence of the fever and anti-DNS antibodies correlated with SLE (P = 0.0104, Fisher exact test), arthritis/arthralgia and anti-RNP antibodies with MCTD (P = 0.0302), Raynaud phenomenon and ANA positivity with PSS (P = 0.0144), xerostomia/xerophtalmia and anti-SSA/SSB antibodies with Sjögren syndromes (P = 0.0144). CONCLUSIONS: The UCTD in our patients seem to represents an dynamic phase, one part of the patients show progression to definite connective tissue diseases, one part show regression, and on part of the patients stay in UCTD phase.

Adult↗