Methotrexate therapy in rheumatoid arthritis. A two year prospective follow-up.

One hundred and thirty seven rheumatoid arthritis (RA) patients refractory to D-penicillamine and some of them (15%) refractory to other slow active drugs were treated with oral methotrexate (MTX) (10-15 mg weekly). After 12-24 months of treatment, 94 and 74 patients respectively showed a significant improvement as judged by duration of morning stiffness (p less than 0.0001), grip strength (p less than 0.0001), degree of joint swelling (p less than 0.01) and tenderness (p less than 0.0001) compared to pre-treatment values. This clinical improvement was also associated with a decrease of erythrocyte sedimentation rate (p less than 0.001), decrease of C-reactive protein (p less than 0.0001) and with improvement of anaemia (p less than 0.05). No changes were seen in rheumatoid factor titres. Seventy-four of the patients were followed for up to 24 months. Thirty-one of them (23%) had complete remission and 43 (31%) had an excellent response. Adverse drug reaction during MTX therapy included: elevated liver enzymes in 34 patients, mucosal ulcers in 21, nausea and vomiting in 8, diarrhoea in 4, leukopenia in 2, interstitial pneumonitis in one, intestinal bleeding in one and finally septic arthritis in another patient. The majority of these side effects were resolved without sequelae. However, 15 patients (11%) with adverse drug reactions had to discontinue the treatment. Forty-one of our patients who received a cumulative mean dose of MTX of 1550.5 +/- 235.5 mg underwent a percutaneous liver biopsy. Ten patients had normal tissue, 12 had minimal changes, 13 nonspecific changes and 6 patients had mild fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

CT demonstration of normal gastric wall thickness: the value of administering gas-producing and paralytic agents.

The authors analysed the CT-findings in 100 normal subjects who underwent a modified double-contrast technique (D.C.). The mean gastric wall thickness in four areas was measured and the contribution of the D.C. technique is discussed.

Gastroscopic removal of a phytobezoar formed in a patient with mixed connective tissue disease.

An unusual case of a phytobezoar encountered in a patient with mixed connective tissue disease, is presented. Removal was accomplished in three days by liquid diet, gastric lavage and disruption of the bezoar with gastroscopic suction.

Epithelial HLA-DR expression and lymphocyte subsets in gastric mucosa in type B chronic gastritis.

Lymphocyte subpopulations (B, T4, T8), monocytes/macrophages (LeuM5, KiM5) and HLA-DR antigen expression were studied immunohistochemically in frozen sections from 32 antral and 37 fundal biopsies of type-B chronic gastritis. Aberrant HLA-DR antigen expression in epithelial cells of gastric mucosa was found in all cases closely related to mononuclear infiltrates. Epithelial HLA-DR expression and mononuclear infiltrates were practically absent in foci of intestinal metaplasia. These findings suggest that an immunopathologic mechanism probably plays a role in initiation or perpetuation of type-B chronic gastritis.

[The natural course of primary Sjögren's syndrome (a clinical study)]. / Estestvennoe techenie pervichnogo sindroma Shegrena (klinicheskoe issledovanie).

In this work the authors analyzed the clinical course and diagnostic procedures of 104 patients with primary Sjogren's syndrome (pSS): 57 patients diagnosed and followed-up at Ioannina University and 47 similar patients treated at the National Institute of Health (USA). Both studies have shown that pSS is predominantly a female disease with a latent period of 6-8 yrs from the time of the first symptom to the time of final diagnosis. Although the syndrome begins almost exclusively with glandular manifestations (xerostomia, xerophthalmia or parotid gland enlargement), in a respectable percentage of patients it eventually progresses to extraglandular involvement. pSS can be potentially complicated by benign (pseudolymphoma) or malignant (lymphoma) lymphoproliferative disorders.

Esophageal manometric findings in autoimmune rheumatic diseases: is scleroderma esophagus a specific entity?

In order to assess whether distal esophageal hypomotility in scleroderma is unique to this disease or not, we studied 25 normal volunteers and 109 patients with autoimmune rheumatic diseases (27 with primary Sjögren's syndrome, 25 with idiopathic Raynaud's phenomenon, 25 with rheumatoid arthritis, 19 with scleroderma, 5 with undifferentiated connective tissue disease, 3 with systemic lupus erythematosus, 2 with mixed connective tissue disease, 2 with sclerodermatomyositis, and one with morphea). Esophageal dysfunction typical of scleroderma was present in 17 patients (15.6%), of whom 13 had scleroderma (68%) and one each primary Sjögren's syndrome, rheumatoid arthritis, undifferentiated connective tissue disease, and mixed connective tissue disease. Twenty-two percent of all patients had nonspecific esophageal motility changes, clustered among primary Sjögren's syndrome, idiopathic Raynaud's phenomenon, and rheumatoid arthritis. We conclude that lower esophageal hypomotility, although most frequent in scleroderma, is not unique to this disease and can be encountered in several other auto-immune rheumatic diseases.

Serum isoamylases in liver diseases.

Total serum amylase and its pancreatic and salivary isoamylase activities were studied in serum from 30 normal volunteers and 30 patients with liver disease. Isoenzyme analysis was performed by inhibitor assay and electrophoretic techniques. Six out of 30 patients had total serum amylase activities which exceeded the mean +/- 2 SD value for normal volunteers. The prominent type of isoenzyme was the pancreatic, except for patients with alcoholic cirrhosis. There was no evidence of any other type of isoenzyme by the electrophoretic method, nor was there an age-dependent isoamylase distribution.

The gastrointestinal involvement in primary Sjögren's syndrome.

Gastrointestinal manifestations in patients with primary Sjögren's syndrome (SS), which is an autoimmune exocrinopathy, include dysphagia, nausea, epigastric pain, dyspepsia and nutritional deficiencies. In this report, we are presenting the nature and incidence of esophageal, pancreatic and liver involvement in our primary SS patients. Esophageal motility was studied in 27 patients with primary SS and 25 normal age and sex matched volunteers. Esophageal dysfunction was detected in 11 of the 27 patients (40.71%). Individual analysis of the esophageal motility studies showed different patterns of esophageal dysfunction. These esophageal abnormalities did not correlate with the parotid flow rate, the degree of inflammatory infiltrate of the minor salivary glands, the extraglandular manifestations or the presence of autoantibodies. Sera from 25 patients with primary SS were studied for the total serum alpha-amylase activity and isoamylases. Sera from 81 normal age and sex matched volunteers were used as controls. None of these patients had abdominal pain or gastrointestinal symptoms at the time of blood collection. The presence of hyperamylasemia of P-type and S-type in 6/25 patients (24%) probably reflects a slow, subclinical, inflammatory process of the exocrine glands. Clinical and biochemical evaluation of the liver function was studied in 22 primary SS patients. One of them had abnormal liver function tests and another hepatomegaly and splenomegaly. Percutaneous liver biopsies in both revealed chronic active hepatitis.

Oesophageal dysfunction in patients with primary Sjögren's syndrome.

Oesophageal motility was studied in 22 patients with primary Sjögren's syndrome and 20 normal volunteers. Oesophageal dysfunction was detected in eight of the 22 patients (36.4%) with primary Sjögren's syndrome. No abnormalities were detected in the normal subjects. Individual analysis of the oesophageal motility studies showed different patterns of oesophageal dysfunction; aperistalsis (three patients), triphasic tertiary contractions (two patients), frequent non-peristaltic contractions (two patients), and low contractions (one patient). These oesophageal abnormalities did not correlate with the parotid flow rate, the degree of inflammatory infiltrate of the minor salivary glands, the extraglandular manifestations, or the presence of autoantibodies.

Subclinical manifestations of autoimmune rheumatic diseases in primary Raynaud's phenomenon.

Twenty-nine patients with primary Raynaud's phenomenon underwent functional (pulmonary functional studies and oesophageal manometry), histologic (minor salivary gland biopsy) and serologic (autoantibodies) evaluation for subclinical manifestations of autoimmune rheumatic disease (ARD). Seven (24%) has strong evidence and eight (27%) possible evidence of ARD. All patients with strong evidence of ARD had Raynaud's phenomenon with a duration of less than five years. This study suggests that such manifestations are frequent in patients wih primary Raynaud's phenomenon and can be detected with non-aggressive methods which should be used early in the course of their disease.

Sialochemistry of patients with autoimmune rheumatic disease with and without histological manifestations of Sjögren's syndrome.

Fifty-one patients with autoimmune rheumatic diseases underwent biopsy of the labial minor salivary glands. These patients were divided according to histopathology of lip biopsies into three groups (negative lip biopsy, 1+ and 2+). From all the patients stimulated parotid salivary flow was measured. In the saliva sodium, potassium, magnesium, alpha-amylase, and immunoglobulin levels (IgA, IgG, IgM) were measured. It is shown that patients with advanced chronic inflammatory disease of the minor salivary glands have decreased stimulated salivary flow. However, no statistically significant differences were observed in the biochemical markers tested between the histopathological groups examined.

Serum isoamylases in patients with autoimmune rheumatic diseases.

We studied sera of 107 patients with autoimmune rheumatic diseases (46 with classical rheumatoid arthritis (RA), 36 with systemic lupus erythematosus (SLE) and 25 with primary Sjögren's syndrome (SS). None of these patients had abdominal pain or gastrointestinal symptoms at the time of blood collection. We used as controls 81 normal age and sex matched volunteers. The presence of hyperamylasemia i) of P-type in 6 of 46 patients (13%) with RA and ii) of P-type and S-type in 11 of 36 patients (30.5%) with SLE and 6 of the 25 patients (24%) with primary SS suggests that asymptomatic pancreatic damage in autoimmune rheumatic diseases may occur frequently especially in patients with SLE. We conclude that the hyperamylasemia in these patients probably reflects a slow, subclinical, inflammatory process of the exocrine glands.

Ethnic 'hyperamylasaemia': clarification by isoamylase analysis.

Total serum amylase and its pancreatic (P-type) and salivary (S-type) isoamylase activities were measured in 92 individuals without pancreatic or salivary disease. They were divided into three ethnic sub-groups resident in the UK, namely native Britons, Asians and West Indians. The mean total amylase activity was highest in West Indians (383 U/l), intermediate in Asians (317 U/l) and lowest in Britons (179 U/l). Nine of the 28 Asians and 8 of the 16 West Indians had total amylase activities above the upper end of the reference range for Britons. Such a finding, if accompanied by abdominal symptoms, could lead to exhaustive pancreatic investigation in these ethnic groups unless the appropriate reference range is used. Isoenzyme analysis by inhibitor and electrophoretic techniques indicated that the increase in total amylase was due to increase in S-type isoamylase, P-type isoamylase or both. There was a good correlation between results by the two methods. These differences in serum amylase seem to be genetically determined.

Soluble fibrin complexes and fibrinogen heterogeneity in diabetes mellitus.

The presence of soluble fibrin complexes (SFC) measured by gel filtration of plasma on 4% agarose columns, fibrinogen heterogeneity on 3.5% SDS-polyacrylamide gels and the concentrations of several plasma proteins were evaluated in 39 patients with diabetes mellitus (DM) and 19 matched control subjects. A small but significant increase of SFC was found in DM (p less than 0.01). On individual basis 51.2% of the patients had increased SFC (greater than M + 2 SD of the controls). Polyacrylamide gel electrophoresis of the SFC showed no evidence of cross-linking or proteolysis. Plasma clots formed in the presence of EDTA and trasylol were analysed in SDS-polyacrylamide gels in a normal and two lower molecular weight fibrin bands (band I, II, III). The percentage of band I fibrinogen was in diabetics (65.3 +/- 4.7%) lower than that of the controls (71.8 +/- 4.5%) (p less than 0.01). Fibrinogen levels, antithrombin III, alpha 1-antitrypsin, alpha 2-macroglobulin and plasminogen were significantly increased in DM. We suggest that in DM there is an enhancement of intravascular fibrin formation and accelerated fibrinogen degradation to lower molecular weight forms.