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ID PMID Title PublicationDate abstract
9467349 Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjögr 1997 Jun Pilocarpine HCl has been shown to stimulate parotid and submandibular gland salivary flow. The purpose of this study was to determine whether this cholinergic-muscarinic drug also stimulates labial (minor) salivary gland (LSG) flow and to relate that with whole unstimulated salivary (WUS) flow rates. Subjects diagnosed with primary Sjögren's syndrome (SS-1; n = 9) or secondary Sjögren's syndrome (SS-2; n = 9) were enrolled in this study after meeting stringent enrollment criteria. An age-gender matched control group was also enrolled. The labial saliva was collected in a standardized manner on Periopaper for 5 min and the volume was analysed by the Periotron. Whole unstimulated salivary samples were collected for 5 min by the method of Mandel and Wotman (1976). Each subject was dosed with pilocarpine HCl (5 mg; tablets; p.o.). After 60 min the LSG flow as well as the WUS flow was determined again as previously. The results indicated a significant (> 180%) increase in both labial salivary gland flow as well as whole salivary flow in the SS-1 and SS-2 subjects (mean +/- s.e.m.): [SS-1: WUS = 0.1080 +/- 0.03 vs 0.2242 +/- 0.03 ml per 5 min; LSG = 93.1 +/- 22.2 vs 167.8 +/- 15.9 microliters/5 min; P < 0.001; SS-2: WUS = 0.1384 +/- 0.02 vs 0.2775 +/- 0.09 ml per 5 min; LSG = 97.7 +/- 20.2 vs 182.8 +/- 17.9 microliters per 5 min; P < 0.001]. These results indicate a significant increase in labial salivary gland flow as well as whole salivary flow as stimulated by pilocarpine HCl in Sjögren's syndrome patients.
9237100 Phage-displayed La/SS-B antigen as a diagnostic reagent. 1997 Jun BACKGROUND: The detection of antibodies to La/SS-B, a nuclear RNA-binding protein in mammalian cells, aids in the diagnosis of Sjogren's syndrome and systemic lupus erythematosus (SLE). This is performed conventionally by immunoprecipitation using a crude splenic extract and more recently, by the more sensitive and rapid enzyme-linked immunosorbent assay (ELISA) which uses a purified La/SS-B antigen. The latter antigen is obtained from cellular extracts of the antigen or from bacterial cell lysates containing the recombinant antigen usually by affinity chromatographic method. OBJECTIVE: To produce a La/SS-B antigen for use in ELISA that can be obtained easily and inexpensively without the need for extensive purification (including affinity chromatography). STUDY DESIGN: The antigen was produced as a fusion protein of the minor coat protein of M13 bacteriophage and used in this phage-associated form in an ELISA. La/SS-B cDNA derived from Hep-2 cells was cloned into the phagemid, pCANTAB-5E, and transfected to Escherichia coli. Phage clones selected for the presence of insert both by gene and antigenic analyses were used in the ELISA to detect anti-La/SS-B antibodies from patients with Sjogren's syndrome and SLE. RESULTS: A phage clone was obtained which contained a La/SS-B cDNA fragment truncated at the C-terminal end (after base-pair 631). The phage-displayed antigen derived from this clone was obtained by precipitation of the phage particles from the bacterial culture supernatant with polyethylene glycol. Used in the ELISA, this antigen detected 27 of 28 precipitin-positive sera and was negative for 50 control sera. The soluble (phage-free) form of the antigen was obtained from a nonsuppressor host as a cell lysate which could not be used in this form in an ELISA for antibody detection. It was useable, however, in Western blot analysis which confirmed the reactivity of the recombinant antigen. CONCLUSION: Phage-displayed antigens may be used in place of soluble forms of these antigens in detection assays which have the advantage that they are easy and inexpensive to produce.
9125110 Molecular cloning of anti-SS-A/Ro 60-kDa peptide Fab fragments from infiltrating salivary 1997 Mar 6 Anti-SS-A/Ro antibodies are commonly found in systemic autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus, and some of these antibodies appear to be responsible for certain pathological lesions including congenital heart block in neonatal lupus. In this study, we generated three human antibody Fab fragments that specifically bind to SS-A/Ro 60-kd peptide from salivary gland lymphocytes of a patient with Sjögren's syndrome by using a phage-display technique. Sequence analysis demonstrated that two of the three Fab clones (E-42 and E-60) used homologous heavy chains derived from the germline VH gene DP73 in combination with different light chains which were derived from germline V kappa gene L6 and V lambda gene DPL23. The third Fab clone (E-56) used another heavy chain derived from the germline VH gene DP31 in combination with the identical light chain as that of E-42. All three Fab clones revealed a high number of somatic mutations that likely occurred in the context of antigen selection. These findings suggest the restricted usage of VH and VL genes of anti-SS-A/Ro antibodies in salivary gland lymphocytes of the patient.
9168649 [Interstitial pneumonia with Sjögren's syndrome: successful treatment with steroids and a 1997 Mar A 44-year-old woman was admitted to our hospital complaining of dyspnea. A chest X-ray film obtained on admission showed bilaterally shrunken lungs, and peripheral bundle-like and linear shadows. A chest CT scan revealed marked thickening of bronchovascular bundles and low lung volumes. Mild dryness of the mouth, and the results of a Rose-Bengal test, Schirmer test, and sialography led to the diagnosis of primary Sjögren's syndrome. Corticosteroid pulse therapy was followed by slight improvement. To determine the pathological diagnosis and to plan further therapy, video-assisted thoracoscopic lung biopsy was done. Examination of the biopsy specimen revealed alveolitis and infiltration of lymphocytes, which suggested active interstitial pneumonia. Therapy with corticosteroids and the immunosuppressant azathioprine was followed by marked improvement.
9175026 Immunologically restricted and inhibitory anti-Ro/SSA in monozygotic twins. 1997 A pair of monozygotic twins with Sjögren's syndrome are described who both have large amounts of anti-Ro/SSA in their sera by ELISA, but no precipitin in double immunodiffusion. Unique among previously encountered specimens, sera from the twins inhibit the formation of Ro/SSA-precipitins in double immunodiffusion by known anti-Ro/SSA positive SLE patients. The twins have near identical, clonally restricted anti-Ro/SSA autoantibodies as evaluated by isoelectric focusing and bind the same 60 kD Ro/SSA peptides. Thus, this pair of monozygotic twins has an identical fine specificity in their immune response to 60 kD Ro/SSA, despite potential differences in their immune response generated by random processes in the formation of immunoglobulin molecules and T cell receptors. These data imply that the anti-Ro/SSA found in these sera binds less than three epitopes such that soluble antigen/antibody complexes are formed instead of an insoluble complex that precipitates.
9008604 Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren's s 1997 Jan OBJECTIVE: To assess the role of Fas-mediated apoptosis in the salivary glands of patients with primary Sjögren's syndrome (SS). METHODS: Expression of Fas, Fas ligand (FasL), and bcl-2 in salivary gland biopsy material was detected in situ by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. DNA fragmentation in apoptotic cells was assessed by the enzymatic incorporation of labeled nucleotides (digoxigenin-dUTP). RESULTS: The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis. The majority of infiltrating lymphocytes in SS were Fas+ and bcl-2+, while few lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell death of lymphocytes, particularly in dense periductal foci. Lymphocytic cell death was significantly lower (P < 0.0001) in these foci compared with that in the interstitium. CONCLUSION: Infiltrating lymphocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though they may express Fas. The presence of bcl-2 in these cells may explain their inability to undergo apoptosis. The acinar epithelial cells, in contrast, may undergo Fas-mediated apoptosis. These results suggest that the Fas death pathway may be an important mechanism leading to the glandular destruction found in SS.
11151264 [Nonpreserved topical steroids and lacrimal punctal occlusion for severe keratoconjunctivi 2000 Nov PURPOSE: To analyze the efficacy of topical nonpreserved steroids before punctal occlusion in the treatment of severe keratoconjunctivitis sicca associated with Sjögren's syndrome. METHODS: We performed a prospective study including 15 patients, 30 eyes, (group 1) treated with topical nonpreserved steroids for 2 weeks and then punctal occlusion, and 15 patients, 30 eyes, (group 2) treated directly with punctal occlusion. Symptom severity (0-3+) and corneal fluorescein staining (0-9+) were evaluated after a week and after two months, and results were statistically compared between both groups with the t Student test. RESULTS: Symptom severity was negative in 67% of patients of group 1 and in 27% of patients of group 2 (p=0.0001 ) after a week, and in 80% of patients in group 1 and in 33% of patients of group 2 (p=0.0003) after 2 months. Corneal fluorescein staining was negative in 67% (OD) and 73% (OI) of patients of group 1 and in 33% (AO) of patients of group 2 (p=0.0001, AO) after a week, and in 80% (AO) of patients of group 1 and in 60% of patients of group 2 (AO) (p=0.0001, AO) after 2 months. There were no patients with side effects or complications. CONCLUSIONS: Topical nonpreserved steroid therapy for two weeks before punctal occlusion is effective in controlling symptoms and corneal fluorescein staining in patients with severe keratoconjunctivitis sicca associated with Sjögren's syndrome.
10805264 Lower urinary tract symptoms in patients with Sjögren's syndrome and systemic lupus eryth 2000 Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are autoimmune diseases which have many similarities with interstitial cystitis (IC), a urinary bladder disease with unknown etiology. This survey on the occurrence, severity and nature of lower urinary tract symptoms among patients suffering from SS or SLE showed that these patients have significantly more urinary complaints, especially irritative bladder symptoms, than age- and sex-matched controls. We studied 36 patients with SS, 85 patients with SLE and 121 controls. In these groups, 25%, 29% and 66%, respectively, were free of urinary symptoms. The prevalences of mild symptoms were 61%, 62% and 27%, and severe symptoms 14%, 9% and 7% in the respective groups. SS and SLE patients with urinary complaints reported mostly urinary frequency (27% and 62%) and suprapubic pain (36% and 34%). The most common symptom in the control group was stress urinary incontinence. The frequency of lower urinary tract problems in patients with SS and SLE supports the concept that autoimmune disorders also have bladder affections.
9664105 Clinical expression of autoimmune diseases in older adults. 1998 Aug Aging modifies the clinical presentation and course of autoimmune disorders. In the older person who carries a complement of predisposing genes, environmental factors may alter a senescent immune system and trigger the onset of autoimmunity. In this article about autoimmune diseases of the older adult, the authors discuss the epidemiology, clinical presentations, laboratory and radiographic findings, and management of systemic lupus erythematosus, primary Sjogren's syndrome, and idiopathic inflammatory myopathies.
9649652 Schnitzler's syndrome versus adult onset Still's disease. 1998 Mar We report the case of a 50-year-old man with a 4-year history of high spiking fever accompanied by a widespread, urticarial, non-pruritic or only sometimes mildly pruritic eruption and arthralgia. He also had generalized lymphadenopathy, hepatosplenomegaly, and hyperosteoses of the lower lumbar spine. Laboratory examination revealed an elevated erythrocyte sedimentation rate, elevated white blood cell and platelet counts, hypoalbuminemia, and elevated serum IgM with IgM kappa monoclonal immunoglobulin. We diagnosed his condition as Schnitzler's syndrome, in contrast to the diagnosis of adult onset Still's disease, for which he had been initially followed up by his internist. We compare clinical and histopathological findings for both diseases and, as this patient meets two of the six existing diagnostic criteria for adult onset Still's disease, we propose that Schnitzler's syndrome is an important entity to be added to the list of differential diagnoses for adult onset Still's disease.
9310103 Disturbances of autonomic nervous function in primary Sjögren's syndrome. 1997 Autonomic nervous function was evaluated by deep breathing [expiration/inspiration (E/I) ratio] and tilt table tests [acceleration (AI) and brake indices (BI)] in 19 patients with primary Sjögren's syndrome (pSS) and in 56 age matched controls. The E/I-ratio and systolic blood pressure (at rest, 1, and 8 min after tilt) were found to be significantly reduced (p < 0.001, p < 0.05, p < 0.01, p < 0.01 respectively) in patients with pSS whereas neither AI, BI nor diastolic blood pressure did differ significantly between patients and controls (NS). The van Bijsterveld's score correlated negatively with the AI (r = -0.77, p < 0.001) as well as the BI (r = -0.60, p < 0.01). No correlations were found between the 3 autonomic nerve function parameters (E/I-ratio, AI, BI) and unstimulated whole sialometry or salivary gland scintigraphy. We conclude that autonomic disturbances, mainly affecting the parasympathetic nerves are associated with pSS.
11604590 Role of viruses in systemic lupus erythematosus and Sjögren syndrome. 2001 Sep Systemic lupus erythematosus and Sjögren syndrome remain elusive in the description of their underlying etiologic causes and pathogenic mechanisms. Although underlying genetic predisposition appears to contribute to both diseases based on twin and other genetic studies, additional factors must play a role. Over the decades additional factors, such as hormonal influence, UV light, environmental exposures (e.g., silica, solvents), and infectious agents have been postulated to play a role. Over the past few years additional information has been published concerning roles of various infectious agents in both lupus and Sjögren syndrome. Although the understanding of this field is still incomplete, significant advances are being made.
9669460 The effect of acupuncture in the treatment of patients with primary Sjögren's syndrome. A 1998 Apr Twenty-one patients, 20 women and 1 man, participated in a controlled study. All patients were diagnosed with primary Sjögren's syndrome (primary SS) according to the Copenhagen and San Diego criteria. The patients were randomly assigned to either a group receiving acupuncture treatment or a control group with no active treatment. The patients in the control group received acupuncture after 10 weeks when the acupuncture treatment was completed in the first group. A majority of the patients subjectively reported some improvement after treatment, and a significant increase in paraffin-stimulated saliva secretion was found after treatment. No statistically significant differences between the acupuncture group and the control group were seen in unstimulated salivary secretion or most of the subjective variables. The study showed that acupuncture is of limited value for patients with primary SS.
9147852 [Cell-mediated immunity in patients with Sjogren's syndrome]. 1997 Jan 22 BACKGROUND: Sjögren's syndrome (SS) is considered an autoimmune immunopathological disease, which is characterized by disorders of humoral and cell-mediated immunity. The objective of the work was to assess the ratio of T and B lymphocytes, subpopulations of T lymphocytes and NK cells in the peripheral blood of patients suffering from SS. METHODS AND RESULTS: The investigated group was formed by 22 patients with the diagnosis of primary SS (mean age 55.7 years, range 39-83 years), 17 patients with the diagnosis of secondary SS (mean age 60.5 years, range 45-79 years). The ration of CD3-, CD4-, CD8-, CD19-, CD5-, CD25- HLA DR- cells in full blood was assessed by the monoclonal antibody technique of direct immunofluorescence, using evaluation by means of a flow cytometer. The results were compared by statistical methods with a control group of blood donors using Student's t-test, A relative increase of the ratio of CD3- T lymphocytes was revealed in patients with primary SS (75.3 +/- 17.9 %, p = 0.380) and secondary SS (73.7 +/- 11.8, p = 0.326), as compared with controls (65.3 +/- 10.3%). The absolute number of the subpopulation of suppressor helper inducer CD4+ T lymphocytes was markedly lower in patients with primary SS (0.056 +/- 0.27 - 10(9)/l, p = 0.0154), as compared with controls (0.81 +/- 0.27, 10(9)/l. The relative number of suppressor cytotoxic CD8- T lymphocytes was significantly higher in patients with primary SS (33.7 +/- 15.0%, p = 0.0001 and secondary SS (30.5 +/- 11.0%, p = 0.0002), as compared with controls (17.2 +/- 6.0%). The absolute number of inhibitory cytotoxic T lymphocytes was significantly higher in patients with primary SS (0.47 +/- 0.3. 10(9)/1, p = 0.0084) and patients with secondary SS (0.48 +/- 0.3, 10(9)/l, p = 0.0072). The relative number of CD57+ NK cells was significantly higher in patients with primary SS (21.1 +/- 11.0%, p = 0.0001) and secondary SS (19.3 +/- 11.7%, p = 0.0023). The absolute number of NK cells was significantly higher in patients with primary SS (0.28 +/- 0.20, 10(9)/l, p = 0.0025 and in patients with secondary SS (0.31 +/- 0.23, 10(9)/l, p = 0.01). CONCLUSIONS: The revealed statistically significant increases in the number of T lymphocytes in patients with Sjögren's syndrome is probably caused by a significant increase of the subpopulation of CD8+ suppressor cytotoxic T lymphocytes. The latter probably overlap with the population of NK cells. These immunological abnormalities are even more marked in patients with primary Sjögren's syndrome due to the decrease of the absolute number of CD4+ helper inducer T lymphocytes.
11315932 Expression of host defense scavenger receptors in spondylarthropathy. 2001 Apr OBJECTIVE: Reactive arthritis (ReA) is postulated to be caused by a defective host defense against gram-negative bacteria. HLA-B27 could play a role in this process, but does not account for the many HLA-B27 negative patients. The objective of this study was to test the expression of 3 macrophage scavenger receptors (SRs) that are responsible for innate immunity against gram-negative bacteria: SR class A type I (SR-AI), SR-AII, and the macrophage receptor with collagenous structure (MARCO). We postulate that defects in such receptors might also contribute to the host risk factors that increase the predisposition to ReA and perhaps other subtypes of spondylarthropathy (SpA). METHODS: Peripheral blood, synovial fluid, and synovial tissue samples were obtained from patients with recent Salmonella infection, ReA, other SpA, and rheumatoid arthritis (RA). The expression of SRs receptors was assessed by semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: Evaluation of the peripheral blood mononuclear cells (PBMC) from 4 patients who were recently infected with Salmonella, showed that PBMC from 2 patients who developed ReA expressed positive levels of MARCO, while PBMC from 2 patients who recovered from infection without sequelae did not. The synovial fluid mononuclear cells (SFMC) from some ReA patients expressed MARCO, but the levels were only moderate. The level of MARCO in the SFMC from the SpA patient group was low. In marked contrast, MARCO expression was high in almost all samples of RA SFMC. These findings also extended to synovial tissues. CONCLUSION: Expression of the host defense gene MARCO was susceptible to modulation, not only during infections, but also in the inflammatory arthritis conditions RA and SpA. MARCO is a variable to be considered as a candidate factor that might contribute to ReA.
9195515 Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multip 1997 Jun OBJECTIVE: Bacteria play a crucial pathogenetic role in Lyme arthritis (LA), reactive arthritis (ReA), other forms of spondyloarthropathy (SpA), and possibly in undifferentiated oligoarthritis (uOligo). Polymerase chain reaction (PCR) technology has been applied to detect bacterial DNA of individual microbes in synovial fluid (SF) of patients with arthritides. We screened for DNA sequences of 8 bacterial species simultaneously in SF of patients with inflammatory joint disease. METHODS: We examined 104 SF samples of 96 patients with ReA (n = 13), undifferentiated SpA (uSpA, n = 10), uOligo (n = 50), juvenile chronic arthritis (JCA, n = 13), and rheumatoid arthritis (RA, n = 10). A nested PCR approach was developed to detect DNA sequences of 8 bacteria: Chlamydia trachomatis, C. pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi. The detection limit was determined at 10 bacterial/sample. Serology and lymphocyte proliferation assay were done in parallel in most patients. RESULTS: In 12 cases bacterial DNA of B. burgdorferi (n = 7), C. trachomatis (n = 2), C. jejuni (n = 2), and C. pneumoniae (n = 1) was detected in patients with uOligo (n = 9) and JCA (n = 3), while no evidence of bacterial DNA was found in patients with ReA, uSpA, and RA. Shigella flexneri DNA was detected in 4 cases, but the significance of this finding remains uncertain due to the high sequence homology of this species with Escherichia coli. DNA of Y. enterocolitica, S. enteritidis, or K. pneumoniae was not found. A positive serologic response was found in 7/9 PCR positive patients. In 11/96 cases antibodies to 2 or more bacteria were found in parallel (11.5%). Antigen specific lymphocyte proliferation was observed in 5/9 PCR positive patients. CONCLUSION: Bacterial DNA was detected in peripheral joint of patients with uOligo and JCA, but not in ReA, uSpA, or RA in this study. The detection of bacterial DNA in synovial material by PCR technology gives useful diagnostic information, especially when antibodies against several microbes are present or antibodies are not detectable. Failure to detect bacterial DNA in patients with ReA and uSpA with longstanding disease suggests that in later stages autoimmune mechanisms may operate.
9640134 Multiple extra-articular synovial cyst formation: case report and review of the literature 1998 Mar OBJECTIVE: To investigate the clinical manifestations and the treatment strategy of a very rare entity of disease manifesting as multiple extra-articular cystic synovitis with recurrent polyarthralgia. METHODS: A 47 year old male patient with multiple extra-articular synovial cysts was followed up prospectively for 13 years. The clinical manifestations and response to various treatments were recorded. Comparisons are made among the five reported cases (including the present case). RESULTS: Multiple synovial cysts over the tendon sheath and bursae appeared successively with and without antecedent growth of nodules during 13 years of follow up. Although polyarthralgia and high titred rheumatoid factor persisted throughout the course, there were no roentgenographical changes of joints specific to rheumatoid arthritis (RA). The synovial cysts and arthralgia failed to respond to any of the disease modifying anti-rheumatic drugs (DMARDs) prescribed. Systemic involvements such as pulmonary interstitial fibrosis and skin ulcers were also noted, but they were not progressive. CONCLUSIONS: Multiple extra-articular cystic synovitis is an uncommon disease entity closely related to RA. It has been reported exclusively in Japanese subjects and therefore some cultural factors, either genetic or environmental, may contribute to its development.
9251892 The mechanisms of action of disease-modifying antirheumatic drugs: a review with emphasis 1997 Aug 1. Rheumatoid arthritis (RA) is probably the most common source of treatable disability. A major problem in modern rheumatology is that the mechanism(s) of action of the currently used disease-modifying antirheumatic drugs (DMARDs) remain unclear. Many of these drugs entered rheumatology mainly through clinical intuition and have been used for decades. 2. The former T-cell-centered paradigm of rheumatoid inflammation has given way to a model of inflammation highlighting the macrophage and its proinflammatory cytokines. In particular, tumor necrosis factor alpha (TNF-alpha) has gained prominence as a central proinflammatory mediator in RA, and antibodies against TNF-alpha have been successfully used in patients with RA. 3. This review will summarize the recent advances in determining the mechanisms of action of the currently used DMARDs, with particular emphasis on their effects on the induction of TNF-alpha and interleukin 1 (IL-1) in mononuclear phagocytes. Although some DMARDs, such as auranofin, antimalarials and tenidap, act as inhibitors of the induction of these cytokines in monocytes or macrophages or both, other drugs, such as methotrexate, D-penicillamine and aurothiomalate, do not seem to affect either TNF-alpha or IL-1. 4. The drugs' effects on proinflammatory cytokine induction are correlated to those on other macrophage responses.
10987869 Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid. 2000 Sep BACKGROUND: Immunosuppressive medications typically used to treat the immunobullous disorders pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid can have serious adverse effects. The tetracycline family of antibiotic drugs has been shown to be effective in the treatment of these conditions with a more favorable side effect profile. Minocycline hydrochloride use has been associated with various forms of hyperpigmentation, and its incidence is well reported in acne vulgaris and rheumatoid arthritis. We examined a series of 9 patients treated with minocycline for pemphigus or pemphigoid, most of whom have developed cutaneous hyperpigmentation. OBSERVATIONS: Seven of 9 patients treated with minocycline, 50 mg daily (1 patient) or 100 mg twice daily (8 patients), for pemphigus vulgaris, pemphigus foliaceous, or bullous pemphigoid developed hyperpigmentation, which necessitated discontinuing therapy. Five of these patients had experienced notable clinical improvement of their immunobullous disease with minocycline therapy. The average duration of treatment was 8.2 months (range, 1-25 months). The second most common adverse effect in our group was oral candidiasis, which occurred in 2 patients. CONCLUSIONS: We found a favorable response to minocycline therapy in 5 of 9 patients. However, 7 patients developed localized hyperpigmentation as early as 1 month after starting medication use. This incidence of minocycline-induced hyperpigmentation is significantly higher in immunobullous disease than in acne vulgaris or rheumatoid arthritis. This increased incidence may be related to an increase in pigment deposition complexed with collagen during the remodeling process, subclinical inflammation, or glucocorticosteroid-induced skin fragility. The hyperpigmentation process was reversible, as most of our patients had fading of their pigmentation after minocycline cessation.
9025950 Domain-directed polymerase chain reaction capable of distinguishing bacterial from host DN 1997 Jan 15 The use of a broad-range PCR to target conserved sequences in the bacterial ribosome has long been recognized as an approach to investigating idiopathic human diseases for the presence of bacteria. An important example is rheumatoid arthritis where the hypothesis of a bacterial etiology remains viable despite failure of previous methods to identify a causative organism. Practical implementation of this strategy, however, was impeded by requirements unique to the study of these diseases. Hence, an adequately characterized method for achieving this has not appeared. We now describe such a method based on the use of a broadly reactive pair of deoxyinosine-containing primers. Detailed characterization addressing these requirements provided evidence that DNA from at least 96% of potential prokaryotic pathogens would be detected. The sensitivity was shown to approximate that of a single organism per reaction. Importantly, this sensitivity was shown to be maintained among multiple targets and to be unimpaired by a large excess of human DNA. Similar results were obtained with extracts of inflamed human synovial fluid to which as little as 0.01 pg of bacterial DNA or, alternately, a single organism per reaction was added. This method was also shown correctly to detect the causative bacteria in clinically infected synovial fluids, further documenting its applicability to such specimens. Finally, it was converted to an in situ method by which bacterial sequences were histochemically localized to Michaelis-Guttman bodies in tissue sections from a patient with malakoplakia, a poorly understood infectious disease. The broad reactivity and high sensitivity achieved by this approach translate into a high likelihood of detecting an unknown bacterium if present in a clinical specimen. Conversely, if properly controlled, the failure of this method to detect such organisms can provide evidence supporting rejection of the bacterial etiology hypothesis, an important aspect unique to this approach. For those bacterial sequences that are detected, the ability to localize them in situ would help define their histologic context and hence facilitate their pathogenetic interpretation. The present method should therefore be appropriate for use in systematically studying rheumatoid arthritis as well as a number of other important idiopathic disorders where a bacterial etiology is suspect.