Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) may be an important mediator of insulin resistance. Infliximab is a chimeric monoclonal, high affinity antibody against the soluble and transmembrane TNFalpha, which can reduce markedly the biological activity of circulating and tissue TNFalpha and is used to treat various autoimmune disorders. OBJECTIVE: To assess the effects of infliximab infusions on insulin sensitivity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: 45 patients (28 with RA, 17 with AS) aged 19-74 years were studied. All patients were treated with intravenous infliximab. A complete biochemical profile was obtained before and after 6 months' treatment with infliximab. The Homoeostasis Model Assessment (HOMA) Index was used to measure insulin resistance and the Quantitative Insulin Sensitivity Check Index (QUICKI) to measure insulin sensitivity. RESULTS: In the whole study group, no significant changes of the HOMA Index or QUICKI were seen. In the tertile of patients with the highest insulin resistance, a significant decrease of the HOMA Index and increase of the QUICKI was found (p<0.01 for both). CONCLUSIONS: The results suggest that infliximab treatment may have beneficial effects on insulin sensitivity in the most insulin resistant patients with RA and AS.

Effects of intranasal salmon calcitonin in juvenile idiopathic arthritis: an observational study.

The aim of this study was to follow the changes in bone mineral density (BMD) and biochemical markers of bone turnover in 10 children (7.5-17.5 years of age) with severe juvenile idiopathic arthritis (JIA), during a 3-year therapy with salmon calcitonin (100 IU/day 2 months on and 2 off for a year and 200 IU/day for 2 years) and calcium (500 mg/day). All patients were functional classes III and IV and were measured at yearly intervals with a dual photon absorptiometer at the lumbar spine. The changes observed were 7.2-9.5% per year for BMD and 2.0-6.0% for volumetric bone mineral density (BMDvol). The bone resorption markers showed significant decreases after a year's treatment (Pyr/Cr from 175+/-15 to 108+/-15 nm/mm, P < 0.001, Pyr-D/Cr from 24.3+/-3.5 to 13.3+/-1.9 nm/mm, P < 0.05, and OHPr/Cr from 57.4+/-11 to 35.1+/-8.4 microg/mg) and smaller changes thereafter. No significant changes were observed in the bone formation markers of osteocalcin and alkaline phosphatase. Serum iPTH, the vitamin D metabolites, and calcium concentrations fluctuated within normal, while calcium excretion increased from 0.3+/-0.1 to 1.9+/-0.4 mg/kg/24 hours, P < 0.001. In conclusion, the present study, despite its limitations of not being placebo controlled, shows possible beneficial effects of intranasal calcitonin on bone resorption and pain relief in JIA patients.

Typing of Salmonella enterica serotype paratyphi C isolates from various countries by plasmid profiles and pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) of 61 Salmonella enterica serotype Paratyphi C isolates from six countries gave five distinct clusters. Twenty-four isolates from five countries were susceptible to 10 antimicrobials tested and gave similar restriction endonuclease digest patterns of the 38-MDa plasmid. In contrast, plasmid and PFGE profiles of 37 multidrug-resistant isolates from Zaire were different from those from other countries.

Interleukins, TNF-alpha and beta-2M in patients with B cell chronic lymphocytic leukemia.

In order to investigate the possible existence of a prognostic factor for B cell chronic lymphocytic leukemia (B-CLL), we determined the serum levels of TNF-alpha, IL-1a, IL-1b, IL-2, sIL-2R, IL-6, IL-10 and beta-2M in 20 patients. We observed significant changes in sIL-2R and beta-2M levels, whereas in all stages of disease, TNF-alpha and other interleukins exhibited only mild changes. An excellent correlation between sIL-2R and beta-2M levels and disease activity wes reported. Patients with aggressive disease (Rai stages III and IV and Richter's syndrome) had increased levels. Patients who responded to therapy and with improved clinical status had decreased sIL-2R and beta-2M levels. However, patients with progressive disease and no response to therapy were associated with increased levels of sIL-2R and beta-2M. In conclusions, as serum levels of sIL-2R and beta-2M are increased in the aggressive stages of B-CLL, they may be used as reliable markers for monitoring B-CLL activity, showing response to treatment and early relapse and/or disease progression.

Prevalence of non-organ-specific autoantibodies in pregnant and non-pregnant healthy women.

The prevalence of autoantibodies during pregnancy was studied. Sera from 568 women (203 pregnant and 365 non-pregnant) were tested for autoantibodies to double-stranded DNA, cardiolipin and extractable cellular antigens. Nineteen out of 203 pregnant women (9.4%) had at least one autoantibody against double-stranded DNA or cardiolipin, mainly of the IgM class. The non-pregnant control group had significantly higher incidence of autoantibodies (17.8%; chi 2 = 7.39, P < 0.01). Sixty-six out of 568 women had had spontaneous abortions in their past medical history, but there was no correlation between them and the presence of anticardiolipin antibodies. Two of the non-pregnant women had anti-Ro(SSA) antibodies. These findings suggest that (a) the prevalence of autoantibodies decreases during pregnancy; and (b) the presence of anticardiolipin antibodies in healthy pregnant women does not correlate with any pregnancy-related complications. However, our results indicated that autoimmunity is a rather common disorder in healthy women.

Autoantibodies in Greek juvenile chronic arthritis patients.

The aim of this study was to investigate sera of Greek patients with juvenile chronic arthritis (JCA) for the presence of autoantibodies and correlate these antibodies with the clinical picture and disease activity. Sera from 69 JCA patients and sera from 66 healthy children matched for sex and age, were tested for antinuclear antibodies (ANAs), antibodies to extractable cellular antigens (ENAs), rheumatoid factor (RF), immunoglobulins (IgG, IgM), antibodies to double stranded (ds) DNA and anticardiolipin (CL). Our results indicate that: (a) autoantibodies to dsDNA are a not uncommon finding in JCA sera; (b) these autoantibodies have a low affinity for the antigen since they are found in low titers only by ELISA, while the Farr assay and Crithidia lucilliae immunofluorescence assay (IF) are negative; and (c) active JCA patients express many autoantibodies.

Clinical and serological spectrum of systemic lupus erythematosus in Greek children.

In the present study 19 Greek Caucasian children with systemic lupus erythematosus (SLE), onset before the age of 16, were followed up for 1-12 years (mean 5.6 yrs.). Diagnosis was determined early in 14 patients and delayed by 2 to 6 years in 5. The clinical manifestations and laboratory findings did not differ significantly from those reported in adults with lupus. The major organ system involvement at onset and early course were skin and joints (80%) followed by kidneys (42%). During the course of the disease 26% of the children developed central nervous system (CNS) involvement. All the patients were treated with steroids and/or cytotoxic drugs in severe uncontrolled progressive disease. At the mean 5.6 years follow-up most patients were in remission on small doses of steroids; one patient still presents signs of active lupus nephritis and one patient died from sepsis. All the patients with CNS involvement recovered without permanent CNS residue.

Factors related to the presence of autoantibodies in patients with chronic mental disorders.

Serum samples from 307 patients with various chronic mental disorders were examined for the presence of several autoantibodies. Autoantibodies detected included antinuclear antibodies (ANA) in 122/307 (39.7%), rheumatoid factor (RF) in 23/307 (7.5%), anticardiolipin antibodies (anti-CL) in 23/304 (7.6%, IgM in 12 patients, IgG in 13 patients). Isolated cases with IgG anti-dsDNA, anti-Ro(SSA), and anti-Ro(SSA)/anti-La(SSB) were also identified. The analysis of data revealed that the aging process in patients studied contributed significantly to the incidence of ANA (p less than 0.0001) and RF (p less than 0.01). In addition, the chronic administration of chlorpromazine (CPZ) was associated with the presence of ANA (p less than 0.03) as well as with the presence of IgM and/or IgG anti-CL antibodies (p less than 0.003). Finally, the diagnosis of schizophrenia correlated with the presence of ANA (p less than 0.001). This study represents the autoantibody profile of patients with chronic mental disorders and emphasizes the multifactorial origin of autoantibody response in psychiatric patients.

Sialochemistry in juvenile chronic arthritis.

Stimulated parotid gland secretions collected from 16 patients with juvenile chronic arthritis (JCA) were analysed and the results compared with those obtained from 83 healthy sex-, age-, and socioeconomic status-matched children. Parotid salivary flow rate was measured and the saliva samples were assayed for calcium, phosphorus, potassium, chloride, sodium, urea, lysozyme, amylase and immunoglobulin levels (IgA, Ig, IgM). Our results showed that parotid flow rate (PFR) values in JCA patients were not statistically different from those in healthy controls. However, the mean salivary concentrations of calcium, phosphorus, potassium, lysozyme and IgA were significantly lower in the patients. These data could provide an explanation for the increased incidence of caries and gingivitis observed in JCA.

Outcome of pregnancy in patients with autoimmune rheumatic disease before the disease onset.

The outcomes of 419 pregnancies of 154 unselected patients with various auto-immune diseases, including 390 pregnancies before the disease onset, were studied retrospectively. The patients comprised 40 with systemic lupus erythematosus (SLE), 72 with rheumatoid arthritis, 21 with primary Sjögren's syndrome (1 degree SS), 14 with progressive systemic sclerosis (PSS), and seven with mixed connective tissue disease. The histories of 267 pregnancies of 98 healthy, age matched women served as controls. Our data indicate that compared with healthy controls autoimmune patients do not experience a higher incidence of fetal loss. The incidence of fetal loss before disease onset in the various groups of autoimmune patients (as well as after disease onset in patients with SLE and RA) was not significantly different from that of controls. Spontaneous abortions in patients with 1 degree SS and PSS before disease onset occurred significantly more frequently (p less than 0.05) than in controls. Nevertheless, it should be noted that this was not the case when the incidence per woman was considered. On the other hand, patients with SLE, both before and after disease onset, experienced a higher incidence of premature deliveries (p less than 0.05). Finally, the analysis of autoantibody profiles, including antibodies to nuclear antigens, to Ro(SSA) cellular antigen, to double stranded DNA, and to cardiolipin, could not demonstrate any association of autoantibodies with any particular pregnancy outcome.

Free urinary cortisol immunoreactive levels in premature and full term infants.

Urinary free immunoreactive cortisol excretion was measured in 20 full term, 20 premature and 20 premature newborns of mothers who had been treated with 12 mg betamethasone 48 hours before delivery. In 10 full term newborns delivered normally, values were 40 +/- 20 nmol/mmol creatinine on the first, 23 +/- 8 on the second and 21 +/- 6 on the third day of life. In 10 full term newborns with stressful delivery, the corresponding values were 63 +/- 39, 44 +/- 33 and 32 +/- 17 nmol/mmol creatinine in the first three days of life. The levels of urinary free immunoreactive cortisol of 10 premature newborns delivered without stress were 170 +/- 116, 91 +/- 75 and 70 +/- 61 nmol/mmol creatinine respectively, on days one, two and three of life. Ten premature infants with respiratory distress syndrome had values of 471 +/- 187, 526 +/- 465 and 636 +/- 906 nmol/mmol creatinine, respectively. The 10 premature newborns whose mothers had received betamethasone, had urinary free immunoreactive cortisol levels of 109 +/- 120, 55 +/- 42 and 66 +/- 84 nmol/mmol creatinine, lower than the other premature infants. This difference, however, was not statistically significant. We conclude that premature infants regardless of stress or normal labor have high urinary free immunoreactive cortisol excretion, suggesting that prematurity per se is a potent stress.

Kidney involvement in primary Sjögren's syndrome.

Kidney involvement is well recognized extraglandular manifestation of primary Sjögren's syndrome. The most common histopathological lesion is an interstitial lymphocytic infiltrate with tubular atrophy and fibrosis. In addition, immune complex associated glomerulonephritis has been reported in sporadic cases with primary Sjögren's syndrome. Here we present our experience on kidney involvement in 36 Greek patients with primary Sjögren's syndrome. The following routine renal laboratory tests were performed in all patients: serum creatinine, creatinine clearance, 24 hour urine protein excretion, urinalysis and plain film of the abdomen. These tests revealed two cases with nephrolithiasis and two with severe proteinuria (24 hour urine protein greater than 3.5 g). Kidney histology in the patients with proteinuria was compatible with membranous and membranoproliferative glomerulonephritis respectively. In fifteen randomly selected patients urinary acidification was studied before and after acute acid loading test (oral administration of NH4Cl). Renal tubular acidosis was found in five patients (one with complete and four with incomplete type). Seven patients voluntarily accepted renal biopsy; five of those had mild form of interstitial nephritis. Two of these patients had renal tubular acidosis. In conclusion, renal involvement (clinical and subclinical) is commonly found in primary Sjögren's syndrome patients.

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.

Anti-Ro(SSA) positive rheumatoid arthritis (RA): a clinicoserological group of patients with high incidence of D-penicillamine side effects.

The clinical, laboratory, histological, and radiological manifestations of 90 Greek patients with anti-Ro(SSA) negative rheumatoid arthritis (RA) were compared with those of 15 Greek patients with anti-Ro(SSA) positive RA. Anti-Ro(SSA) positive RA patients had the same articular and extra-articular manifestations as anti-Ro(SSA) negative patients. However, they were predominantly females with lower rheumatoid factor titres and a high incidence of positive minor salivary gland biopsy specimens for Sjögren's syndrome. Finally, anti-Ro(SSA) positive RA patients frequently experienced penicillamine side effects.

Demonstration and identification of monoclonal proteins in the urine of patients with Sjögren's syndrome.

Fresh sera and concentrated urine from 17 patients with primary Sjögren's syndrome (SS) were fractionated by high-resolution agarose electrophoresis to investigate the presence of monoclonal immunoglobulins or their components. Homogeneous protein bands were found in the gamma-globulin region in 47% of serum samples and 76% of urine specimens of all patients tested. These monoclonal proteins were detected more often in patients with extraglandular SS (77% in serum, 100% in the urine) than in patients with glandular SS (14% in serum, 43% in the urine). Immunofixation electrophoresis showed that the majority of these monoclonal proteins were free kappa or lambda light chains. Fractionation of unconcentrated parotid salivas from five SS patients failed to reveal the presence of monoclonal light chains or immunoglobulins. The present findings further substantiate our previous observation that a monoclonal process coexists with the polyclonal activation in SS patients.

Lactate levels in Brucella arthritis.

In this study the synovial fluid cell types and the synovial fluid lactate levels of patients with Brucella, septic rheumatoid, gouty and osteoarthritic mono-arthritis are presented. It is shown that lactate levels coupled with the clinical picture and the cell type of the synovial fluid appear to be an early additional diagnostic marker for the differentiation between septic, inflammatory and brucella-induced mono-arthritis.

High C-reactive protein response in lupus polyarthritis.

Five out of 6 patients with systemic lupus erythematosus (SLE) and chronic polyarthritis were found to have significantly raised (greater than 20 mg/l.) C-reactive protein (CRP) levels. In contrast, slight elevations in CRP levels were present in only 5 of 16 SLE patients without chronic polyarthritis. Thus, an elevated CRP level might be a distinctive feature of SLE patients with chronic polyarthritis.

Serum C-reactive protein in primary Sjögren's syndrome.

Only 11 out of 50 patients with primary Sjögren's syndrome were found to have minimal or moderate increases of C-reactive protein (CRP) levels. Patients with elevated CRP levels did not differ clinically from those with normal CRP levels. Thus, primary Sjögren's syndrome is one of the inflammatory disorders characterized by a relatively low CRP response.