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Background. Antigen-specific lymphocyte proliferation of synovial fluid mononuclear cells (SF MNC) has been reported repeatedly in reactive arthritis and Lyme arthritis; however, less information is available on serial investigations of SF MNC in the same patients. [ABSTRACT FROM PUBLISHER]

The cellular immune response seems to be important for the pathogenesis of reactive arthritis (ReA) and a bacteria-specific lymphocyte proliferation (LP) is often found in synovial fluid (SF) of ReA patients. However, the role of the bacteria-specific LP in peripheral blood (PB) is less well defined. In this study, we investigated 215 paired samples of SE and PR from patients with ReA (n=65), undifferentiated oligoarthritis (n=133) and undifferentiated spondylarthropathy (n=17) to analyse the LP in PB and SF in relation to time. In 24 out of 87 patients (27.6%) with a bacteria-specific LP in synovial fluid, a positive LP to the same bacterium was also found in PB. While a positive LP in SF was found most frequently in the first week of the arthritis, a positive LP in PB was detected in 45% of patients when investigated between weeks 2 and 4 after the onset of arthritis, but was rarely found very early and late in the course of the arthritis. The time point seems to be crucial for the investigation of an LP in PB in patients with ReA. [ABSTRACT FROM PUBLISHER]

Objective: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis., Methods: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter., Results: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size., Conclusion: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Involvement of the sacroiliac joints is a hallmark of the spondyloarthropathies, especially in ankylosing spondylitis. The conventional diagnostic imaging of sacroiliitis in early stages might cause problems, because sensitivity of conventional radiographic methods is known to be too low in early stages of the disease. Magnetic resonance imaging of the sacroiliac joints certainly enables one to detect acute as well as chronic inflammatory changes in all stages of the disease. The potential disadvantages of this method are the dependency on the examiner, the lack of standardization, and the relatively high costs. Therefore, the "Workgroup of Diagnostic Imaging in Rheumatology of the Regional Center of Rheumatology of Berlin" including experienced rheumatologists, skeletal radiologists, and orthopedists acquired an imaging graduation for detection of sacroiliitis in consideration of the clinical background, the technical details of the methods, questions of ionizing radiation exposure, and cost effectiveness.

Background: Antigen-specific lymphocyte proliferation of synovial fluid mononuclear cells (SF MNC) has been reported repeatedly in reactive arthritis and Lyme arthritis; however, less information is available on serial investigations of SF MNC in the same patients., Methods: In this study, the synovial lymphocyte proliferation to Yersinia, Chlamydia, Shigella and Borrelia burgdorferi was investigated sequentially at different time points in 28 patients with reactive arthritis, undifferentiated oligoarthritis or Lyme arthritis responding to one of these bacteria., Results: The same bacterium was always recognized in arthritis triggered by Chlamydia, Shigella or Borrelia, with much variation in the proliferative response. Only the Yersinia-specific responses changed specificity, suggesting that the proliferative response to Yersinia is non-specific in some patients., Conclusions: Our data support the concept of a local antigen-specific T-cell response in reactive arthritis or Lyme arthritis but not the concept suggested by others that a switch to an autoimmune response takes place in long-standing disease.

Objective: To determine the prevalence of sicca symptoms and Sjögren's syndrome (SS) in spondyloarthropathy (SpA) patients with ankylosing spondylitis (AS) and undifferentiated SpA (uSpA)., Methods: Patients with SpA with inflammatory back pain and/or peripheral arthritis presenting to the university outpatient clinic were diagnosed as AS (n = 40) and uSpA (n = 65) according to established criteria. Patients with SpA with sicca symptoms and/or positive antinuclear antibody (ANA) were investigated for SS by minor salivary gland biopsy and/or sialography. To assess sicca symptoms in this cohort systematically we mailed a validated questionnaire with 6 questions on dryness of eyes and mouth to all 105 SpA patients and 150 healthy controls, a positive answer to > or = 3 questions was taken as suggestive of SS. There was no significant difference in baseline characteristics between patients and controls., Results: In 8/105 SpA patients (5 uSpA, 3 AS; 6 female, 2 male) SS diagnosis by the European criteria indicated a frequency of 7.6%. Of 105 SpA patients, 12 were ANA+ (11.4%), of whom 7 had SS; thus, ANA were detected in 7/8 SpA patients with SS (88%). Of the 84 SpA patients responding to the questionnaire (80%), 10 gave a positive answer to > or = 3 questions (11.9%) compared to 2 of 131 (1.5%) controls (87.3%) (odds ratio = 8.7, 95% CI 2.3-32.5, p < 0.01)., Conclusion: The data suggest increased prevalence of sicca symptoms and SS in SpA patients with AS and uSpA. The occurrence of a secondary SS in a variety of inflammatory diseases suggests that salivary gland involvement in these conditions results from as yet unidentified shared pathogenic mechanisms resulting in nonspecific inflammation in this location.

Objective: To determine the overall prevalence of spondylarthropathy (SpA) among whites., Methods: To screen for SpA symptoms, such as inflammatory back pain (IBP), joint swelling, psoriasis, and uveitis, or a specific family history, questionnaires were mailed to 348 blood donors (174 HLA-B27 positive and 174 HLA-B27 negative). From the responding 273 persons (78%; 140 B27 positive, 133 B27 negative), 126 were selected for further evaluation based on the symptoms reported. Of this group, 90 persons agreed to undergo physical examination (71.4%; 46 B27 positive, 44 B27 negative). There was no difference between the B27-positive and -negative groups in terms of age (mean +/- SD 38.4 +/- 10 versus 39.5 +/- 11 years) and sex ratio (67% versus 68% were men). In addition, 58 donors (32 B27 positive, 26 B27 negative) agreed to undergo magnetic resonance imaging (MRI) of the sacroiliac joints. A diagnosis of SpA and ankylosing spondylitis (AS) was made according to the European Spondylarthropathy Study Group criteria and the New York criteria., Results: SpA was diagnosed in 20 persons: 19 of 140 B27-positive (13.6%) and 1 of 133 B27-negative (0.7%) subjects (15 male and 5 female). AS was diagnosed in 9 persons (7 male and 2 female; 45%), undifferentiated SpA (USpA) in 7 (5 male and 2 female; 35%), psoriatic arthritis (PsA) in 3 (2 male and 1 female; 15%), and chronic reactive arthritis (ReA; Reiter's syndrome) in 1 (male; 5%). On the basis of a B27 frequency of 9.3% among the population of Berlin (3.47 million persons), the estimated prevalence of SpA was 1.9%, AS was 0.86%, USpA was 0.67%, and PsA was 0.29%. The relative risk of developing SpA in B27-positive subjects was calculated as 20.7 (95% confidence interval 4.6-94.2; P = 0.001). Of 58 persons with IBP, sacroiliitis was detected by MRI in 15 of 32 B27-positive (46.9%) and 1 of 26 B27-negative (3.9%) subjects (P = 0.002). Four of these 16 donors did not fulfill diagnostic criteria for SpA., Conclusion: With a calculated prevalence of 1.9%, spondylarthropathies are among the most frequent rheumatic diseases in the white population. HLA-B27 positive persons carry a 20-fold increased risk of developing SpA. AS and USpA are the most frequent SpA subtypes. Persons with IBP who are B27 positive have a 50% likelihood of having sacroiliitis.

Objective: To estimate the frequency of and to identify possible risk factors involved with terminating an initial disease modifying antirheumatic drug (DMARD) therapy. We hypothesized that treatment termination depends not only on side effects and inefficacy but also on the therapeutic setting and the health beliefs of the patient., Methods: We observed an inception cohort of 302 patients with early rheumatoid arthritis (< 2 years) and first prescription of DMARD for 3 years. Survival analysis was used to estimate treatment continuation under rheumatological care. The study group comprised 4 rheumatological outpatient clinics and 7 private practices in Berlin., Results: Of the initial cohort 80% continued the same drug or were in remission after one year, 70% after 2 years. Within the first 2 years, methotrexate therapy was terminated in 15% of the cases and sulfasalazine therapy in 40%, respectively. In both forms of therapy, the discontinuation rate was dependent on initial disease activity. However, the influence of the patient's psychological status at baseline was equally strong. DMARD treatment was terminated earlier and more frequently in patients with poor psychological well being. These findings hold true after controlling for disease activity or severity., Conclusion: Patient psychological well being and disease activity at start of initial DMARD therapy are important predictors of early drug discontinuation. By influencing psychological well being (e.g., by patient education programs), continuation of DMARD therapy might be further improved.

Objective: To investigate whether a predominant type 1 T helper (Th1) or Th2 cytokine pattern is present in the joints of patients with reactive arthritis (ReA), and whether the cytokine pattern can be modulated by cytokines or anticytokines., Methods: Eleven patients with ReA following infection with either Chlamydia trachomatis, Yersinia enterocolitica, or Salmonella enteritidis were investigated for the presence of Th1/Th2 cytokines in the joints. Release of the bacteria-specific cytokines interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-10 (IL-10), and IL-4 was measured in synovial fluid mononuclear cells (SFMC) using enzyme-linked immunosorbent assay and polymerase chain reaction. In the synovial membrane, secretion of IFN gamma and IL-4 was determined by immunohistologic analysis. Cytokine regulation was studied by adding cytokines and anticytokines to the cultures., Results: Upon stimulation with specific bacteria, SFMC secreted low amounts of IFN gamma and TNF alpha, but high amounts of IL-10. IL-10 was responsible for the suppression of IFN gamma and TNF alpha, as judged by the effect of adding either anti-IL-10 antibodies or exogenous IL-10 to these cultures. The addition of neutralizing anti-IL-12 to the cultures completely abolished the effects of anti-IL-10, suggesting that inhibition of the Th1-like cytokines by IL-10 is mediated through suppression of IL-12 synthesis. Exogenous IL-12 clearly enhanced IFN gamma and TNF alpha secretion. In the synovial membrane, a higher number of cells were positive for the Th2 cytokine IL-4, compared with the amount of IFN gamma-secreting cells., Conclusion: These data indicate that a Th2 cytokine pattern predominates in the joints of patients with ReA. Since Th1 cytokines are necessary for the elimination of ReA-associated bacteria, Th2 cytokines might contribute to bacterial persistence in the joint. Therefore, the IL-10/IL-12 balance appears to be crucial for regulation of the cytokine pattern in the joints of patients with ReA.

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.

Objective: Bacteria play a crucial pathogenetic role in reactive arthritis (ReA) and other forms of spondyloarthropathy (SpA) and in Lyme arthritis. Although there is evidence of local persistence of bacterial antigens no definitive method revealing microbes in peripheral joints has been established. We detected DNA of individual bacteria in synovial material by PCR. Applying molecular technology we screened simultaneously for 8 bacterial genomes in arthritis and sacroiliitis., Methods: Sacroiliac (SI) biopsy specimens taken from the SI joint of 8 patients with ankylosing spondylitis (AS, n = 5) and undifferentiated SpA (uSpA, n = 3) by computed tomography guided biopsy were investigated for presence of bacterial DNA. Similarly, synovial membrane samples obtained by office arthroscopy from 15 patients with ReA (n = 5), uSpA (n = 3), undifferentiated oligoarthritis (uOligo, n = 3), and rheumatoid arthritis (RA, n = 4) were screened. Nested PCR was performed for DNA of the following bacteria: Chlamydia trachomatis, C. pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi., Results: No bacterial DNA was found in the SI biopsies of patients with uSpA and AS. DNA of B. burgdorferi (n = 2) and C. trachomatis (n = 1) was detected in 3 patients with uOligo, but not in patients with ReA or RA. DNA of other microbes including K. pneumoniae was not found. Patients' mean disease duration was 5.3 years (2 mo-8.4 yrs)., Conclusion: We found bacterial DNA in peripheral joints of patients with uOligo, while in patients with ReA, AS, and uSpA no bacterial DNA was detected in peripheral or SI joints. The failure to detect bacterial DNA in patients with SpA suggests autoimmune mechanisms operate in later stages of disease.

Objective: To investigate whether type 1 helper (Th1) or Th2 cytokines are found in the joints of patients with Lyme arthritis, and whether the cytokine pattern can be modulated by cytokines or anticytokines., Methods: The cytokine pattern in the joints of 10 patients with Lyme arthritis was investigated. Expression of interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and IL-10 was measured by enzyme-linked immunosorbent assay (ELISA), after stimulation of synovial fluid mononuclear cells (SFMC) with Borrelia burgdorferi (Bb) in the supernatant. Expression of cytokine messenger RNA and protein in synovial membrane (SM) and nonstimulated SFMC was studied using semiquantitative reverse transcriptase-polymerase chain reaction and immunohistologic techniques. The effects of recombinant cytokines or neutralizing anticytokine antibodies on cytokine production in Bb-stimulated SFMC were investigated by ELISA., Results: SFMC produced high amounts of IFN gamma and TNF alpha, but little or no IL-4, upon stimulation with Bb antigen, indicating a Th1-type cytokine pattern. In SM, IFN gamma was detectable in all patients, while the other cytokines were less frequently found. Serial sections of SM revealed that all cytokines were located in the same area. The Th1 response, especially the production of TNF alpha, could be down-regulated in vitro by both endogenous and exogenous IL-10, but not by IL-4 or anti-IL-12., Conclusion: A Th1-type cytokine pattern was found in the joints of patients with Lyme arthritis. This Th1 response could be down-regulated by IL-10, suggesting insufficient IL-10 production in vivo.

Objective: To evaluate computed tomography (CT) guided corticosteroid injections of inflamed sacroiliac (SI) joints in patients with spondyloarthropathies (SpA), and to evaluate dynamic magnetic resonance imaging (DMRI) of the SI joints in serial examinations of these patients, who had different degrees of inflammatory back pain., Methods: We examined and treated 30 patients with ankylosing spondylitis (n = 9) or undifferentiated SpA (n = 11) (14 women and 16 men, mean age 36.5 +/- 13.4 years, mean disease duration 5.4 +/- 4.0 years) who had severe inflammatory back pain for more than 3 months. All patients had DMRI of the SI joints before and 4-6 months after a CT guided injection of 40 mg triamcinolone acetonide into SI joints (n = 54; 24 patients received injections in both joints). Enhancement of the contrast agent gadolinium-DTPA was quantified by calculating the enhancement of the contrast agent gadolinium-DTPA was quantified by calculating the enhancement gradient Fenh. A subjective index with a visual analog scale (0 = no pain, 10 = very severe pain) was used for assessment of back pain. Followup visits were done every 3 months for a maximum of 18 months., Results: There was significant improvement of inflammatory back pain and sacroiliitis at 5.2 +/- 1.3 months after therapy in 25/30 patients (83.3%). The differences between the Fenh values before (98.2 +/ 56.1) and after (44.3 +/- 31.2) therapy and of the subjective pain index (8.5 +/- 1.5 and 3.0 +/- 2.3, respectively) were statistically significant. Subjective improvement lasted a mean of 8.9 +/- 5.3 months., Conclusion: CT guided corticosteroid injection of inflamed SI joints is a useful option in therapy for sacroiliitis in patients with SpA. Different degrees of inflammation in the SI joints can be quantitatively assessed by DMRI.

Objective: To investigate the efficacy of oral type II collagen in the treatment of early rheumatoid arthritis (RA)., Methods: Ninety patients with RA (disease duration < or = 3 years) were treated for 12 weeks with oral bovine type II collagen at 1 mg/day (n = 30) or 10 mg/day (n = 30) or with placebo (n = 30), in a double-blind randomized study., Results: There were no significant difference between the 3 groups in terms of response to treatment. However, we observed a higher prevalence of responders in the type II collagen-treated groups: 7 responders in the 10-mg type II collagen group and 6 in the 1-mg group, versus 4 in the placebo group. Furthermore, 3 patients in the 10-mg type II collagen group and 1 patient in the 1-mg type II group, but no patients in the placebo group, had very good response. A total of 14 patients had to be withdrawn from the study: 2 because of side effects (nausea) and 12 because of lack of efficacy., Conclusion: Only a minority of patients responded to treatment with oral type II collagen. These results justify further efforts to identify which patients will have good response to such therapy.

Objective: To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS)., Patients and Methods: Computed tomography-assisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization., Results: Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique., Conclusion: The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI joints of 5 patients with active AS. The finding of abundant TNF alpha message in these joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.

Objective: To evaluate the new magnetic resonance imaging (MRI) method of dynamic MRI with fast imaging in the diagnosis of sacroiliitis among patients with spondylarthropathy., Methods: Fifteen patients with a history of inflammatory back pain without radiographic evidence of grade II or greater sacroiliitis (group 1), 25 patients with definite ankylosing spondylitis (group 2), and 12 patients with noninflammatory spinal pain (controls) (group 3) were examined. Dynamic MRI with fast imaging was performed after intravenous bolus injection of the contrast agent gadolinium-diethylenetriamine pentaacetic acid. The degree of enhancement was graded as representing acute sacroiliitis, latent sacroiliitis, or no sacroiliitis., Results: Acute sacroiliitis was detected in 22 of 30 sacroiliac (SI) joints in group 1 patients and in 27 of 50 SI joints in group 2 patients; latent sacroiliitis was seen in 25 of 80 SI joints in patients from groups 1 and 2. No group 3 patient was found to have sacroiliitis., Conclusion: Early sacroiliitis can be demonstrated by dynamic MRI in spondylarthropathy patients in whom abnormalities are not revealed by conventional radiography.

The diagnosis of reactive arthritis relies mainly on the presence of clinical symptoms caused by the initiating infection in the urogenital or enteral tract. An oligoarthritis mainly of the lower limbs occurs 1-6 weeks later. Chlamydia trachomatis and Yersinia enterocolitica are the most frequent triggers of reactive arthritis. Since the infections caused by these microbes are clinically often asymptomatic diagnostic evaluation can be difficult; serology is often nonspecific and cultures are mostly negative. The microscopic detection of bacterial antigens in the joint and the determination of a bacteria specific lymphocyte proliferation in the synovial fluid have changed the pathogenetic concept of reactive arthritis. However, these methods are technically difficult and not suitable for daily routine. There is no indication for short-term antibiotic treatment, as is often prescribed, except in the case of Chlamydia-induced urethritis, which should be treated in any case to prevent the onset or a relapse of reactive arthritis; the sexual partner must also be treated. Long-term therapy with various antibiotic regimens is now being tested in clinical trials. The symptomatic therapy of arthritis comprises physical methods and the use of nonsteroidal anti-inflammatory drugs; intra-articular administration of corticosteroids is of benefit in some cases. If the arthritis takes a chronic course disease modifying drugs such as sulfasalazine are partly successful; in refractory cases arthroscopic synovectomy may become necessary.

Juvenile chronic arthritis is a heterogenous disease with an ill-defined pathogenesis. In our study, synovial fluid (SF) and peripheral blood (PB) of 70 children with oligoarthritis were investigated; bacteria-specific lymphocyte proliferation and antibodies to arthritogenic bacteria were determined. Specific cellular immune responses in SF but not in PB were found in 4/7 patients with either Lyme- or reactive arthritis (60%). In comparison, in subgroup JCA II (n = 45) encompassing mainly elder HLA B27 positive boys, a specific response in SF but again not in PB was detected in 10 children to Yersinia enterocolitica (YE), in four children either to Borrelia burgdorferi (BB) and Chlamydia trachomatis (CT), and in one child to Campylobacter jejuni (CJ). In contrast, in subgroup JCA I (n = 17) encompassing mainly young ANA-positive girls with chronic iridocyclitis, no specific response was found. The correlation of the synovial cellular and the humoral immune responses was 100% in the case of BB and 50% for YE; no antibodies against CT or CJ were detectable. Neither specific cellular nor humoral immune responses were detected against Salmonella or Shigella. We conclude that, in the pathogenesis of some patients with JCA, bacterial microbes have a triggering role. Mainly YE, but also BB and CT are responsible for cases of JCA in which no symptomatic infection preceded.

Normal human adrenocortical cells (from multi-organ donors) were incubated with corticotropin (tetracosactide), highly purified human beta-lipotropin, synthetic human beta-lipotropin, gamma 2-melanocyte stimulating hormone and beta-endorphin. Corticotropin stimulated cortisol, aldosterone and 18-hydroxycorticosterone production starting at 10(-12)-10(-11) mol/l in normal adrenocortical cells. Purified human beta-lipotropin also stimulated steroidogenesis but 100-1000-fold higher concentrations of the peptide were needed. In contrast, synthetic human beta-lipotropin was without any effect on steroid production up to concentrations of 10(-7) mol/l. Synthetic beta-lipotropin (5 x 10(-10) mol/l) did not significantly change the dose-response curve for corticotropin (10(-13) mol/l-10(-9) mol/l) versus the three steroids measured. gamma 2-Melanotropin and beta-endorphin (10(-6) mol/l) stimulated the secretion of cortisol, but not of aldosterone. Since synthetic human beta-lipotropin has no effect on human adrenocortical cells, the purified beta-lipotropin must be contaminated with traces of corticotropin. Since pathologically elevated levels of proopiomelanocortin-derived peptides will rarely exceed plasma concentrations of 10(-10) mol/l, our findings in vitro do not support a physiological or pathophysiological role of the peptides examined in the regulation of adrenal steroid secretion.

An adrenal tumour was incidentally discovered with no clinical signs of Cushing's syndrome. The endocrine evaluation revealed the unique hormonal constellation of an increased urinary cortisol excretion rate, unequivocal suppressibility of plasma and urinary cortisol by dexamethasone, but only to a residual level in the low normal range which probably reflected ACTH-independent 'autonomous' cortisol secretion. After removal of the adrenal mass, urinary cortisol secretion and dexamethasone suppressibility were normalized. In vitro, the tumour cells were as sensitive towards ACTH as 'normal' human adrenal cells, but showed a reduced cortisol production rate per cell. We suppose that the adrenal mass participated in the diurnal rhythm of ACTH-mediated cortisol secretion in vivo, which resulted in an increased cortisol secretion. During the night, when ACTH levels were low, the cortisol production decreased and the hormone levels were probably too low to suppress ACTH. We regard the hormonal findings in our patients as 'Pre-Cushing's syndrome', although the absence of clinical features of Cushing's syndrome remains unclear. We suggest that every patient with an incidentally discovered adrenal mass should have an endocrinological evaluation because the results may help to decide whether or not the adrenal tumour should be removed.