Critical peripheral ischemia precipitated by severe episode of Raynaud's phenomenon in a patient with aPL-positive systemic lupus erythematosus, upon high titer anti-RNP seroconversion.

A 35-year-old female with long standing aPL-positive lupus without history of thromboembolic events, who has developed critical peripheral ischemia (CPI) is described. An episode of severe Raynaud's phenomenon rapidly progressed to an extensive digit-threatening ischemia, involving bilateral hands and feet. She was successfully treated with corticosteroids, anticoagulation, iloprost, sildenafil, and nifedipine. Her serological studies were remarkable for the emergence of high titer anti-RNP seroconversion and an increase in aPL titer, suggesting that these autoantibodies played a role in the pathogenesis of CPI. It is important to note that such observation should herald this potentially devastating complication of systemic lupus erythematosus.

Anti-heat-shock protein antibodies in rheumatic and autoimmune diseases.

The heat-shock proteins (hsp) are a family of molecules that have different molecular weights and are thought to operate as scavengers that trap abnormal proteins and protect the stressed cells. These molecules, which have been conserved during evolution, have highly identical stretches of their amino acid sequence in bacteria as well as in humans. Experiments show that arthritis patients manifest T-cell responses to the hsp-65-kD molecule, as do rats with adjuvant arthritis. The B cell response to hsp has not been extensively studied. Autoantibodies against hsp 65, 70, and 90 have been detected in various rheumatic and autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, and inflammatory bowel diseases. The frequency of these antibodies varies among studies and is mainly dependent on the methods of detection. Studies on sensitivity and specificity of these antibodies do not exist; therefore, their significance should be interpreted cautiously.

Saliva: an additional diagnostic tool in Sjögren's syndrome.

OBJECTIVE: To assess the available data and the place of salivary analysis in the diagnosis of Sjögren's syndrome (SS). METHODS: A Medline search of English language articles published between 1985 and 1996 and a manual search of the reference lists of relevant articles formed the data sources. These were combined with our clinical and experimental experience in this field. Each method of salivary analysis was assessed according to study design, type of saliva used for the study, sensitivity/ specificity for the diagnosis of SS, and correlation to the histopathological findings. RESULTS: Increased levels of salivary Na+, immunoglobulins (particularly IgA), anti-Ro and La antibodies, lactoferrin, lysozyme, beta 2 microglobulin, prostaglandin E2, thromboxane B2, interleukin-6, and hyaluronic acid have been detected in various studies. Results varied according to the different methods used for saliva collection. CONCLUSION: Although many changes have been detected in various constituents of saliva in SS patients, no test has proved sensitive or specific enough for diagnosing SS.

The absorption of low-dose methotrexate in patients with inflammatory bowel disease.

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.

Agaridoxin: a fungal catecholamine which acts as an alpha 1 agonist of mammalian hypothalamic adenylate cyclase.

Agaridoxin, a catecholamine isolated from mushrooms, and 4 synthetic analogues cause activation of adenylate cyclase in the presence of guanylyl imidodiphosphate (Gpp(NH)p) in membrane particles prepared from rat hypothalamus. These compounds also activate adenylate cyclase preparations from rat kidney, liver and cerebral cortex. In the presence of tyrosinase, these compounds are readily oxidized to quinones which lack agonist activity. Studies with selective adrenergic blockers suggest that agaridoxin acts at an alpha 1-type receptor. Agaridoxin-mediated adenylate cyclase stimulation is most effectively antagonized by WB-4101 and phenoxybenzamine, while propranolol and yohimbine are without inhibitory effect. Agaridoxin and the alpha 1 agonist methoxamine inhibited the binding of [3H]WB-4101 in rat hypothalamic and cerebral cortical membranes. The values of Ki for both compounds are lower than that of norepinephrine. The agaridoxin analogue, 4-aminocatechol hydrochloride, is a more effective and potent adenylate cyclase activator than agaridoxin or methoxamine.

Jaccoud's arthropathy and psoriatic arthritis.

A patient with long-standing psoriatic arthritis developed an arthropathy of the hands characterized by subluxations of the metacarpophalangeal joints without erosive changes. This is to the best of our knowledge the first reported case describing Jaccoud's arthropathy associated with psoriatic arthritis.

Abdominal fat tissue aspirate in amyloidosis of familial Mediterranean fever.

Abdominal fat tissue aspirates from 20 patients with biopsy-proved amyloidosis were investigated by polarized microscopy after staining with Congo-red. Positive results were obtained in 4 of 5 patients with primary amyloidosis (AL) and in none of 15 with amyloidosis (AA) of Familial Mediterranean Fever (FMF). We suggest that although this technique is simple, safe and effective in other forms of amyloidosis, it cannot be used as a diagnostic tool in FMF patients suffering from amyloidosis.

Sleep disturbances, fibromyalgia and primary Sjögren's syndrome.

OBJECTIVE: To investigate the association and prevalence of sleep disturbances and fibromyalgia (FM) in a group of patients with primary Sjögren's syndrome (pSS). METHODS: Sixty-five patients with pSS were investigated. A 10-point Mini Sleep Questionnaire (MSQ) was completed focusing on sleep complaints. The same questionnaire was also used in three control groups: Group A-67 patients with rheumatoid arthritis. Group B-53 patients with rheumatoid arthritis (RA) and sicca symptoms; Group C-31 patients with osteoarthritis. All patients with pSS were also studied fro the presence of FM. RESULTS: Moderate or severe sleep disturbances were reported by 49 out of 65 pSS patients (75%). This frequency was significantly higher than that reported by patients in the three control groups (p < 0.001). FM was present in 36 out of 65 pSS patients (55%) and was associated with sleep disturbances. FM or sleep disturbances were not associated with any clinical or laboratory parameters. CONCLUSION: Our results suggest that sleep abnormalities and FM in pSS patients are frequent and their etiology might involve other mechanisms besides joint pain or sicca symptomatology.

Primary Sjögren's syndrome and primary biliary cirrhosis: differences and similarities in the autoantibody profile.

Sera from 61 patients with primary biliary cirrhosis (PBC) and 23 patients with primary Sjögren's syndrome (pSS) were tested for the presence of autoantibodies to 15 different antigens (PDH, RNP, SS-A, SS-B, Sm, Scl-70, H2AH2B, Jo-1, collagen-type I, GBM, GM <--> 1, Sulf, GD1b, MPO, PR3). Patients with pSS had significantly (p < 0.01) higher frequencies of antibodies to SS-A, SS-B and RNP (78%, 52%, 22% vs 29%, 20%, 5%, respectively) when compared to patients with PBC. On the other hand, patients with PBC had significantly (p < 0.01) higher frequencies of antibodies to PDH, Sm, Jo-1, collagen and MPO (80%, 34%, 26%, 52%, 67% vs 13%, 9%, 13%, 13%, 9%, respectively) as compared with patients with pSS. For all the other autoantibodies, no significant differences were found between PBS and pSS patients. These data on the similarities in autoimmunity between two diseases with different clinical presentations shed more light on the mosaic of autoimmunity.

Salivary and serum soluble interleukin-2 receptor in primary Sjögren's syndrome.

Salivary and serum concentrations of soluble interleukin-2 receptor (sIL-2R) were studied in a group of patients with Sjögren's syndrome and a group suffering from dry mouth. Salivary sIL-2R levels was significantly higher (57.9+/-15.1 vs 16.7+/-4.7 pg/ml) (p < 0.05) in the group of 26 patients with Sjögren's syndrome than in the dry-mouth group. Both the salivary and the serum sIL-2R of normal controls were below the level of detection. No significantly statistical differences were noted between the concentrations of serum sIL-2R in either abnormal groups. No correlations were found between salivary or serum sIL-2R and the erythrocyte sedimentation rate, C-reactive protein, the presence of various autoantibodies or the focus score from lip biopsies in the group of patients with Sjögren's syndrome. The results show that, although the salivary sIL-2R does not actually reflect the extent of inflammation, it might have an important role in the diagnosis of Sjögren's syndrome.

Identification of mycolutein and pulvomycin as aureothin and labilomycin respectively.

Two antibiotics isolated from a culture MA-2465 were identified as aureothin and labilomycin, the chemical structures of which had been reported previously. It was also concluded that mycolutein and pulvomycin isolated as antibiotics in 1955 and 1957 respectively are also identical with aureothin and labilomycin. A cursory study of MA-2465 indicates that it is distinctly different from the culture which was first observed to produce labilomycin and is probably different from the organism first noted to produce aureothin.

C-reactive protein levels in patients with rheumatoid arthritis: the impact of therapy.

C-reactive protein levels were measured in sera of 111 patients with rheumatoid arthritis and were compared with erythrocyte sedimentation rate. The patients were divided into six groups according to drug therapy. Comparison between the groups suggests that CRP correlates best with ESR in patients treated with penicillamine and in patients in clinical remission. Patients treated with gold, NSAID or methotrexate have a weaker correlation between the two parameters, while steroid therapy yields the poorest correlation which is not statistically significant. Our data suggest that although CRP is a sensitive index of disease activity, the specific drug taken by the patient must be considered before interpreting the results.

Systemic lupus erythematosus presenting as catatonic schizophrenia.

A patient fulfilling the diagnostic criteria for systemic lupus erythematosus and presenting with catatonic schizophrenia is described. Psychiatric features of the disease and their management are discussed.

Skin ulcer as the presenting symptom of primary antiphospholipid syndrome--resolution with anticoagulant therapy.

A 51-year-old woman with unilateral foot ulcers as the presenting symptom of primary antiphospholipid syndrome is described. Therapy with anticoagulants resulted in complete disappearance of the ulcers.

Effect of spa therapy in Tiberias on patients with ankylosing spondylitis.

Fourteen patients with ankylosing spondylitis (AS) were treated in a pilot study for two weeks at a Tiberias spa with a combination of hot mineral water baths and mud packs. A significant improvement was noticed in morning stiffness, finger to floor distance and the overall well-being assessment both by the patient and the physician. A significant reduction in the use of analgesics and NSAIDs was also noted in most of the patients. Improvement in all parameters began after one week of treatment and was still present at three months.

Sjogren's syndrome in Israel: primary versus secondary disease.

Sixty Israeli patients, 30 with primary Sjögren's syndrome (SS) and 30 with rheumatoid arthritis (RA) and secondary SS, were evaluated. The Schirmer-1 test and a positive labial salivary gland biopsy were found to be the most helpful tools in assessing the diagnosis of SS. Extraglandular features such as Raynaud's phenomenon, lymphadenopathy and CNS involvement as well as parotid gland enlargement (p < 0.05) were more common in primary SS. Antinuclear antibodies, especially anti-Ro (SSA) and anti-La (SSB) were also more common in primary SS (p < 0.05). Our results are in accord with those of many European centers, despite the different genetic background.