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ID PMID Title PublicationDate abstract
11490515 Antibodies to Ro and La. 1998 Feb Precipitating antibodies to Ro and La occur in a subset of patients with systemic lupus erythematosus (SLE) constituting just under 50 and 20% respectively of the total spectrum. These precipitating autoantibodies are even more prevalent in primary Sjögren's syndrome (SS) occurring in 60-80% (anti-Ro) and 40-60% (anti-La) of that disease. Patients with an overlap of SLE and SS virtually all possess both anti-Ro and anti-La. These autoantibodies appear years before the appearance of clinical disease as evidenced by the behavior of women who possess them and herald this presence by having children born with the manifestations of neonatal lupus, principally a characteristic lupus dermatitis or complete congenital heart block. The close association of several clinical manifestations involving the skin, lung, and blood elements suggests a pathogenic role for these autoantibodies in disease expression. The elucidation of these relationships should greatly improve our understanding of the etiopathogenesis of both SLE and SS.
11490513 The role of apoptosis in Sjögren's syndrome. 1998 Feb It has been suggested that defects in the modulation of programmed cell death/apoptosis might lead to autoimmune disease, such as Sjögren's syndrome (SS) and systemic lupus erythematosus. In this review some basic information on apoptosis is introduced together with three aspects on apoptosis in relation to SS: i) defective apoptosis could lead to lymphoid cell accumulation and chronic inflammation in exocrine glands; ii) increased apoptosis of epithelial cells might explain the loss of secreting epithelium; and iii) orderly destruction of cellular components might induce autoantibody production. Altogether, the idea that defects in the apoptotic process could be of importance for explaining autoimmune diseases, makes research on the different factors in this pathway valuable for achieving a better understanding of the etiopathogenesis of SS.
11371117 Non-Hodgkin's lymphoma & primary biliary cirrhosis with Sjögren's syndrome. 2001 Apr Sjögren's syndrome (SS) is an autoimmune disease characterized by a lymphocytic infiltration of the salivary and lacrimal glands leading to a progressive destruction of these glands due to the production of autoantibodies. This disorder is either isolated (primary SS) or associated with other systemic diseases (secondary SS). The occurrence of B-cell non-Hodgkin's lymphoma (NHL) represents the major complication in the evolution of SS patients. The risk of developing NHL, which is equivalent for both primary and secondary SS, was estimated to be 44 times greater than that observed in a comparable normal population. NHLs in SS patients occur preferentially in the salivary glands and in other mucosa-associated lymphoid tissues (MALT). However, it can also occur in the lymph nodes or bone marrow. We documented a case of low-grade B-cell lymphoma of MALT in the right eyelid and primary biliary cirrhosis (PBC) of a patient with SS. To the best of our knowledge, this is the first case reported in Korea.
10403275 Lymphoma development in Sjögren's syndrome: novel p53 mutations. 1999 Jul OBJECTIVE: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrations of the exocrine glands. Disease progression may lead to uncontrolled clonal proliferation of B lymphocytes and development of lymphoma. This study was undertaken to examine the possible involvement of the cell cycle checkpoint genes p53 and p21 in the pathophysiology of the syndrome. METHODS: Protein expression of p53 and p21 was studied, by immunohistochemistry and Western blot analysis, in minor salivary gland (MSG) biopsy specimens from 7 patients with SS and 5 control subjects. In addition, sequence analysis of the p53 gene was performed on DNA samples obtained from MSG biopsy samples of the same 7 patients with SS and from 4 patients with SS and in situ non-Hodgkin's lymphoma (NHL). RESULTS: The study revealed increased protein expression of p53 and p21 in MSG biopsy specimens from patients as compared with controls, while sequence analysis showed that the p53 gene was of the wild type. Furthermore, sequence analysis of the p53 gene from patients with SS and in situ NHL revealed 2 novel mutations in exon 5 of the p53 gene. These mutations are single-base substitutions and appear to be functional since exon 5 is included in the coding region of the p53 gene. CONCLUSION: This is the first report on wild-type p53 gene activation in SS. Our findings indicate a probable role for the DNA damage response genes in the pathogenesis of this syndrome. The novel mutations of the p53 gene implicate dysregulation of this tumor suppressor gene as a possible mechanism for lymphoma development in SS.
9649694 Analysis of T cell receptor Vbeta repertoires of annular erythema associated with Sjögren 1998 Jun Sjögren's syndrome (SjS) is an autoimmune disorder characterized by lymphocytic infiltration into the lacrimal and salivary glands. Annular erythema has recently been reported to be a specific, cutaneous manifestation associated with SjS. In this study, the T cell receptor (TCR) Vbeta gene usage and expansion was examined in annular erythema associated with SjS (AESjS) in 7 patients with primary SjS (5 definite and 2 probable), using reverse transcriptase polymerase chain reaction (RT-PCR) amplification of 22 Vbeta gene families. For 4 out of the 7 patients, the TCR V repertoire in lesional skin of AESjS was compared with paired peripheral blood mononuclear cells (PBL). In one case, two lesional tissue specimens biopsied from different sites of AESjS (face and trunk) were examined. As a control, the TCR Vbeta repertoire was examined from the lesional skin of butterfly rash biopsied from 3 cases of systemic lupus erythematosus (SLE). Results showed that TCR Vbeta 2 was detected in 6 out of the 7 cases of AESjS, although diverse usage was observed. TCR Vbeta 2 and 17 (but particularly Vbeta 2) were predominantly expressed in AESjS in comparison with paired PBL. In the case which presented AESjS at two separate sites, Vbeta 2, 6, 18 and 19 were preferentially expressed in both skin sites as compared with PBL. On the other hand, TCR Vbeta 6, 13-2 and 14 were commonly demonstrated in the cutaneous lesions of SLE. These results suggest that (1) the TCR Vbeta usage by infiltrating T cells in AESjS is not strictly limited, however, Vbeta 2 may play an important role in the induction of AESjS, and that (2) different subsets of TCR Vbeta genes are used in the lesional skin of SjS and SLE, which might account for the clinical and histological differences seen in the erythema found in these two autoimmune disorders.
9505077 [A patient with mixed collagen disease, antiphospholipid syndrome and Sjögren syndrome]. 1998 Jan 15 A 32-year-old female patient is described who suffered from common symptoms such as Raynaud's phenomenon and swollen fingers, high titers of antibodies to U1RNP, SLE-like findings, scleroderma-like findings and polymyositis-like findings. A diagnosis of mixed connective tissue disease (Sharp-syndrome) was established. In addition, the patient had antibodies against cardiolipin, thrombocytopenia, recurrent fetal loss and a history of deep venous thrombosis of her left leg which is typical for an antiphospholipid syndrome. The symptoms dry eyes and dry mouth pointed at secondary Sjögren's syndrome. The diagnosis of these disease entities and the therapeutic regimens are described and discussed.
9267756 Severe, chronic anorexia and extensive leg ulcerations as presenting signs of primary Sjö 1997 We report the case of a 75-year-old woman with a 15-year history of inappetance resulting in weight loss of approximately 40 kg. On physical examination, the skin of the lower extremities was markedly hyperpigmented with a brown-greyish hue. In addition, the skin of the legs was infiltrated, erythematous, riddled with erosions and necrotic ulcers. Clinical and laboratory evaluation revealed sicca syndrome, a pronounced polyclonal hypergammaglobulinemia (60 g/l), high levels of antinuclear, anti-SSA and anti-SSB antibodies. Histological examination of involved skin demonstrated a leukocytoclastic vasculitis.
11461185 Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune 2001 Aug Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases.
9512498 Cloning of the gene for interstitial collagenase-3 (matrix metalloproteinase-13) from rabb 1998 Apr 1 Cartilage, bone and the interstitial stroma, composed largely of the interstitial collagens, types I, II and III, are remodelled by three members of the metalloproteinase (MMP) family, collagenase-1 (MMP-1), collagenase-2 (MMP-8) and collagenase-3 (MMP-13). MMP-1 and MMP-13 may contribute directly to disease progression, since they are induced in patients with rheumatoid arthritis and osteoarthritis. The study of MMP-1 and MMP-13 gene regulation in models of arthritic disease has been problematic because mice and rats, which are typically used, only possess a homologue of MMP-13. Here we show that in contrast with mice and rats, rabbits possess distinct genes homologous to human MMP-1 and MMP-13. Furthermore, rabbit MMP-13 is expressed simultaneously with MMP-1 in chondrocytes and synovial fibroblasts in response to the cytokines interleukin-1 and tumour necrosis factor-alpha, or the phorbol ester PMA. The time course of MMP-13 induction is more rapid and transient than that of MMP-1, suggesting that distinct mechanisms regulate the expression of these two collagenases. We have cloned the rabbit MMP-13 gene from synovial fibroblasts and demonstrated that the rabbit gene shares greater homology with human MMP-13 than does the mouse interstitial collagenase. Together with the fact that mice and rats do not possess a homologue to human MMP-1, our data suggest that the rabbit provides an appropriate model for studying the roles of interstitial collagenases in connective-tissue diseases, such as rheumatoid arthritis and osteoarthritis.
10540197 Thalidomide analogue CC1069 inhibits development of rat adjuvant arthritis. 1999 Nov The cytokine tumour necrosis factor-alpha (TNF-alpha) has been implicated in the aetiology of rheumatoid arthritis in humans as well as of experimental arthritis in rodents. Thalidomide, and to a greater extent the new thalidomide analogue CC1069, inhibit monocyte TNF-alpha production both in vitro and in vivo. The aim of the present study is to establish whether these drugs block production of TNF-alpha as well as IL-2 by rat leucocytes and whether this inhibition affects the development of rat adjuvant arthritis (AA). Cultured splenocytes were stimulated with either lipopolysaccharide (LPS) or concanavalin A (Con A) in the presence of thalidomide, CC1069, or solvent, and the production of TNF-alpha and IL-2 were compared. Next, adjuvant was injected into the base of the tail of rats without or with daily intraperitoneal injections with 100-200 mg/kg per day thalidomide or 50-200 mg/kg per day CC1069. Disease activity, including ankle swelling, hind limb radiographic and histological changes, weight gain, and ankle joint cytokine mRNA levels, were monitored. CC1069, but not the parent drug thalidomide, inhibited in vitro production of TNF-alpha and IL-2 by stimulated splenocytes in a dose-dependent manner. In vivo, a dose-dependent suppression of AA disease activity occurred in the CC1069-treated animals. In contrast, thalidomide-treated rats experienced comparable arthritis severity to placebo-treated animals. There was also a reduction in TNF-alpha and IL-2 mRNA levels in the ankle joints of CC1069-treated rats compared with thalidomide- and placebo-treated arthritic rats. Early initiation of CC1069 treatment suppressed AA inflammation more efficiently than delayed treatment. We conclude that thalidomide, which did not suppress TNF-alpha or IL-2 production in vitro by Lewis rat cells, did not suppress development of rat AA. However, the development of rat AA can be blocked by the thalidomide analogue CC1069, which is an efficient inhibitor of TNF-alpha production and IL-2 in vitro.
9589803 Development of an HPLC assay to study the effect of endogenous and exogenous substances on 1998 Mar The mechanism of action of non-steroidal anti-inflammatory drugs which are used in high doses in chronic inflammatory conditions is not clearly understood. Their known protein-stabilizing properties could play a significant role. The inhibition of cyclooxygenase may not be essential for their anti-rheumatic activity, since compounds with strong anti-denaturant properties and devoid of anti-inflammatory activity were shown to be effective in an experimental model of rheumatoid arthritis. Hence, to develop new anti-rheumatic drugs it is essential that a simple in vitro method to evaluate the anti-denaturant activity of endogenous and exogenous compounds is available. We developed a new assay, using gel permeation high performance liquid chromatography, to study the effect of endogenous and exogenous compounds on heat-induced aggregation of human serum albumin in conditions in which protein precipitation does not occur. Non-steroidal anti-inflammatory drugs like diclofenac, ibuprofen and naproxen inhibited the aggregation of albumin at low concentrations (EC50 10(-4)-10(-5) mol/l) comparable to those active in a classical turbidimetric method, whereas the effect of weak stabilizers, like sodium cloride and formic, fumaric, maleic, malonic, and succinic acid (EC50 10(-1)-10(-2) mol/l in the Mizushima test) was not detectable. Furthermore, the HPLC assay allowed the examination of a number of coloured substances, including bilirubin, which appeared to be a strong stabilizer of its physiological carrier, albumin. These data could be clinically relevant, since the drugs examined are used at very high doses in rheumatoid arthritis and related conditions, with plasma levels that could cause significant stabilization of serum albumin and perhaps other proteins.
9279889 Effect of vehicles and penetration enhancers on the in vitro and in vivo percutaneous abso 1997 Aug PURPOSE: Low-dose methotrexate (MTX) is approved for the treatment of recalcitrant rheumatoid arthritis (RA). The objective of this study was to determine the effect of vehicles and penetration enhancers on the percutaneous absorption of MTX and its analog edatrexate (EDAM), and develop transdermal (TD) delivery systems of the drugs for the treatment of RA. METHODS: From previously published pharmacokinetic parameters with low-dose MTX therapy, and considering a 50 cm2 diffusional area, the target steady state in vitro TD flux for MTX was calculated to be 35 micrograms/cm2/hr. Modified Franz diffusion chambers and hairless mouse skin were used for in vitro skin permeation studies. Hairless mice were used for in vivo studies. Delivered amounts of MTX and EDAM were determined by assaying the receiver phase fluid (or blood) with validated reversed phase HPLC methods. RESULTS: Intrinsic partition coefficient of MTX was low (log P = -1.2). Target MTX fluxes of > or = 35 micrograms/cm2/hr were achievable only with 1-15% (v/v) Azone in propylene glycol (PG). Flux of EDAM (85 micrograms/cm2/hr) was higher than MTX from an isopropyl alcohol (IPA)-5% (v/v) Azone system. Clinically significant steady state in vivo blood concentration of MTX and EDAM was achieved using delivery systems containing > or = 2.5% Azone in PG. Area under the drug concentration-time curves (AUC0-24 hr) for MTX were 2379 and 3534 ng*hr/ml from PG-2.5% Azone and PG-7.5% Azone systems respectively. AUC0-24 hr of EDAM was 6893 ng*hr/ml using a PG-2.5% Azone system. CONCLUSIONS: Results of this study show the feasibility of using a transdermal delivery system of MTX and EDAM for the treatment of rheumatoid arthritis.
11729665 [A case of primary Sjögren syndrome with repeated purpura]. 2001 Oct In Sjögren syndrome, purpura is one of its various well known eruptions. Although this disease state is assumed to be based on hypergammaglobulinemia, the details of its mechanism are unknown. We experienced a case involving a female patient with primary Sjögren syndrome showing repeated purpura on the legs, and examined her blood viscosity and histopathology. This girl developed Sjögren syndrome and was admitted to our hospital at 12-years-old. She underwent steroid treatment because of aggravation of the xerosis state and prominent purpura on the legs. Hypergammaglobulinemia was improved during the course; however, purpura appeared repeatedly. Although her blood viscosity was slightly higher than normal, this had no relation to purpura and serum gamma globulin values. Skin biopsy revealed necrotizing angiitis. These results suggest that the purpura of this case was caused not only by hyperviscosity from the hypergammaglobulinemia but also involvement of vasculitis by the primary disease.
11093440 No signs of autonomic nervous system dysfunction in primary Sjörgen's syndrome evaluated 2000 Nov OBJECTIVE: Autonomic neuropathy is associated with increased mortality. In patients with primary Sjögren's syndrome (SS), disturbances in the autonomic nervous system have been described using conventional cardiovascular reflex tests. Heart rate variability (HRV) measured from Holter recording has proved to be a reliable and sensitive method in assessing autonomic function and prognosis. We evaluated cardiovascular autonomic function based on HRV in patients with primary SS compared to the general population. METHODS: We analyzed HRV from 24 h electrocardiography recordings in 28 patients with primary SS and 28 healthy age and sex-matched population-based controls. RESULTS: There were no significant differences in time or frequency domains or nonlinear measures of HRV between the groups. CONCLUSION: The prevalence of autonomic disturbances is not increased in patients with primary SS compared to the general population.
10396249 Hypokalaemic paralysis revealing Sjögren syndrome in an elderly man. 1999 Feb A 73 year old white man presented with life threatening hypokalaemic paralysis requiring admission to an intensive care unit. Biochemical investigations showed severe hypokalaemia with hyperchloraemic metabolic acidosis, a spot urine pH of 6.5, and a positive urinary anion gap, establishing the diagnosis of distal renal tubular acidosis. Autoimmune tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Full recovery followed potassium and alkali replacement. This dramatic presentation of Sjögren syndrome has not previously been reported in an elderly man.
9844061 Modes of epithelial cell death and repair in Sjögren's syndrome (SS). 1998 Dec We evaluated possible modes of epithelial cell destruction and restoration in minor salivary gland biopsies from patients with SS. Minor salivary gland biopsies from 10 primary Sjögren's syndrome (pSS) patients and eight control individuals were evaluated by immunohistochemical staining for the expression of apoptosis-related molecules, substances released by activated cytotoxic T cells, as well as proteins involved in epithelial cell repair. The results were analysed by computer screen analysis and they were expressed as average percentages. Apoptosis-promoting molecules, Fas antigen and Fas ligand were observed in ductal and acinar epithelial cells as well as in infiltrating mononuclear cells of minor salivary glands from SS patients in comparison with control biopsies. Bax protein, which acts as a death-promoter message, was expressed in the ductal and acinar epithelial cells and in mononuclear infiltrating cells of SS patients compared with control individuals, while Bcl-2, an inhibitor of apoptosis, was primarily found in the lymphocytic infiltrates. In situ DNA fragmentation assay (TUNEL) revealed that epithelial cells were apoptotic in patients with SS compared with control subjects. Immunohistochemical staining for perforin and granzyme B, released from granules of activated cytotoxic lymphocytes, revealed their presence in lymphocytic infiltrates of patients with SS compared with control biopsies. pS2, a member of the trefoil protein family which functions as promoter of epithelial cell repair and cell proliferation, was expressed in epithelial cells in biopsies from SS patients. These studies suggest that the functional epithelium of minor salivary glands in patients with SS appears to be influenced by both intrinsic and extrinsic mechanisms of destruction, while a defensive mechanism of epithelial restoration seems to be active.
9780554 [Primary Sjögren syndrome. Study of a population of patients at the Hospital Universitari 1998 Sep Sjögren's syndrome is an autoimmune exocrinopathy of unknown etiology. It is characterized by a chronic inflammatory process that leads to functional impairment and destruction of lachrymal and salivary glands. There is a primary and a secondary form of the disease; the latter accompanies a well defined connective tissue disease. As far as we know, there are no previous reports of primary Sjögren's syndrome in Venezuela. The main purpose of this study was to present the clinical findings and outcome of a population of patients diagnosed and followed in our hospital. A population of fifty-four patients predominantly females (96%) with a mean age of 42 (range 24 to 84) was studied. The presence of articular symptoms was the most common extraglandular manifestation (87%), followed by enlargement of parotideal glands (52%). Parotid enlargement and renal disease were observed with a higher frequency than previously reported in the literature. Recurrent enlargement of parotideal glands has been related to lymphoid malignant transformation in these patients. Our findings seem to suggest that the pattern of clinical expression of primary Sjögren's syndrome may be influenced by the genetic make-up of the population under study, and possibly by local environmental influences. Two of our cases developed pseudolymphoma, a transitional stage between the benign lymphoproliferation of primary Sjögren's syndrome and lymphoma. Furthermore, in this relatively small sample six patients have died during a short follow-up period, suggesting a potentially more aggressive course of the disease in our patients.
11407090 Infliximab in the treatment of adult Still's disease refractory to conventional therapy. 2001 May In this study we evaluated the efficacy of Infliximab in the treatment of adult Still's disease (ASD) refractory to conventional therapy. Three patients with chronic and active ASD unresponsive to corticosteroids and methotrexate were given intravenous Infliximab infusions at a dosage of 3 mg/kg at weeks 0, 2, 6 and then once every 8 weeks. Methotrexate was maintained in all cases at a dosage of 15 mg/week, whereas the prednisone dose was modified according to disease activity. The follow-up lasted 50 weeks and disease activity improved in all cases during Infliximab therapy. Two patients presented arthralgias and sore throat at 20 and 28 weeks, that was rapidly controlled by Infliximab reinfusion every 4 weeks. One patient relapsed at 18 weeks and dropped out at 22 weeks due to an urticarioid rash after the beginning of the fifth infusion. Infliximab may be effective in the treatment of relapse of ASD refractory to conventional therapy and requiring continuous high dose corticosteroid medication. Further studies are needed to evaluate the long-term safety, efficacy and the optimal schedule of infusion.
11002406 Sjögren's syndrome: a possible pathogenetic mechanism involving somatostatin. 2000 Sep Sjögren's syndrome is a chronic systemic disease that primarily affects the salivary and lacrimal glands. The pathogenesis of Sjögren's syndrome is unknown. We hypothesize that reduced somatostatin activity is an important factor in promoting immune dysregulation in patients affected by Sjögren's syndrome. Somatostatin is a multifunctional peptide with potent immunomodulatory properties. Its effects include reduced lymphocytic activity, reduced gastric and intestinal secretions, activation of the hypothalamic-pituitary axis, and anti-inflammatory action, all opposite to the general presentation in Sjögren's syndrome. We suggest that the activity of somatostatin is low in patients affected by this disease, and this contributes significantly to the pathology observed.
9927101 Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with S 1999 Jan 25 BACKGROUND: Patients with Sjögren syndrome (SS) experience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to diminished secretions, with resultant symptoms of xerostomia and xerophthalmia. Although pilocarpine hydrochloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. OBJECTIVE: To assess the safety and efficacy of pilocarpine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, doubleblind, placebo-controlled trial. METHODS: After providing written informed consent, 373 patients with primary or secondary SS and clinically significant dry mouth and dry eyes were randomized to receive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were assessed by questionnaires with visual analog scales or categorical checkboxes. Whole-mouth salivary flow rates were measured. RESULTS: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement compared with the placebo group (P< or =.01) in global assessments of dry mouth, dry eyes, and other symptoms of dryness (P< or =.05). Salivary flow was significantly increased 2- to 3-fold (P<.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were reported. CONCLUSION: Administration of 5-mg pilocarpine tablets 4 times daily (20 mg/d) was well tolerated and produced significant improvement in symptoms of dry mouth and dry eyes and other xeroses in patients with SS.