Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast.

The effect of selenium supplementation on plasma selenium concentrations and lymphocyte-proliferation responses to mitogens was investigated in 22 elderly institutionalized subjects. Subjects were assigned to a 6-mo trial with either 100 micrograms Se/d (as selenium-enriched yeast) or a placebo. Plasma selenium concentrations of the selenium-supplemented group increased from 0.84 +/- 0.26 to 1.55 +/- 0.33 mumol/L (mean +/- SD) after 2 mo and the values plateaued thereafter. The mean response of lymphocytes to mitogens in elderly subjects tended to be lower than responses in healthy adults, although responses remained within the 5-95% confidence-interval limit for healthy adults. During selenium supplementation the proliferative response to pokeweed mitogen increased significantly (+79% of baseline concentrations after 4 mo, P less than 0.01) and reached the upper limit of the usual range for adults after 6 mo (+138%, P less than 0.001). In accordance with previous studies in animals and in vitro, this investigation demonstrates for the first time immunostimulatory properties of selenium-enriched yeast in elderly humans.

The effects of non-steroidal anti-inflammatory drugs on cholinergic and histamine-induced contractions of guinea-pig isolated ileum.

1 Eleven non-steroidal anti-inflammatory drugs (NSAID) reversibly inhibited contractions of the longitudinal muscle of the guinea pig isolated ileum induced by acetylcholine, histamine, electrical transmural stimulation and nicotine in this order of increasing potency. 2. After the addition of prostaglandins E1, E2 or F2alpha, with partially effective concentrations of NSAID (but not with higher concentrations which almost totally prevented the responses) the inhibitory effects of NSAID were reversibly lost, except for electrically induced contractions and prostaglandin F2alpha. 3 The effects of NSAID may be due to actions on biological membranes or on distribution of ions in addition to their inhibitory effect on prostaglandin synthesis. Prostaglandins may reverse the inhibition by non-selective sensitization of smooth muscle to various agonists.

Lymphatic disorders in rheumatoid arthritis.

Lymphedema is a rare complication of rheumatoid arthritis (RA). Diagnosis is clinical: long-standing, painful swelling of a whole limb in association with RA. Cases described in the literature are predominantly of the upper limbs, sometimes bilateral. Diagnosis can be confirmed by biopsy of lymph nodes, lymphography, or preferably lymphoscintigraphy. The etiology of the edema is unknown. Mechanical obstruction and lymphangitis have been suggested. Pharmacological and surgical treatment of the edema have been disappointing, and treatment of the underlying RA does not improve the lymphedema. Physical treatment of the affected limb, such as massage, manual drainage techniques, light compression bandaging, and exercise, has been moderately effective.

Selenium in rheumatic diseases.

Selenium is involved in several important biochemical pathways relevant to rheumatic diseases. Experimental and clinical studies suggest that selenium modulates the inflammatory and immune responses. Patients suffering from inflammatory rheumatic diseases often have low selenium levels, but this finding does not correlate with disease severity. Selenium supplementation needs stricter selection criteria and better ascertainment of dose to obtain a stimulatory or inhibitory effect relevant to the disease state. Prevention of marginal selenium deficiency by moderate supplementation might enhance host defense mechanisms.

A double-blind, parallel trial of oxaprozin versus naproxen in the treatment of osteoarthritis.

A double-blind trial was carried out in 24 patients with osteoarthritis of the knee or hip to compare the efficacy and tolerance of oxaprozin with that of naproxen. Patients were assigned at random to receive fixed doses of either 1200 mg oxaprozin once daily or 250 mg naproxen 3-times daily over a period of 8 weeks. Assessments made on entry and after 4 and 8 weeks of treatment showed that in the oxaprozin group there were significant mean decreases, indicating improvement in patient's condition, with respect to observer's opinion, patient's opinion, pain intensity and activity impairment at both on-therapy visits. In the naproxen group, there were significant mean decreases with respect to observer's opinion, patient's opinion, pain intensity and time to walk 15 metres. None of the mean differences between the groups was statistically significant. Adverse effects were reported for 3 of the 12 oxaprozin patients and 6 of the 12 naproxen patients. The specific adverse effects noted for more than 1 patient were diarrhoea for oxaprozin and dyspepsia for naproxen. No difference between the groups was statistically significant from this point of view. Laboratory determinations showed no toxicity in either group. It is concluded that once-daily oxaprozin is an effective and well-tolerated form of treatment for osteoarthritis, equivalent to naproxen given 3-times daily.

A double-blind comparison of slow-release and standard tablet formulations of fentiazac in the treatment of patients with tendinitis and bursitis.

Two double-blind studies were carried out to compare the effectiveness and tolerance of a slow-release tablet formulation of 300 mg fentiazac, given once daily, with the standard tablet formulations of 100 mg, given 4-times daily, or 200 mg, given twice daily. A total of 60 patients suffering from acute bicipital tendinitis and/or subdeltoid bursitis was studied, 15 patients on the slow-release and 15 on one of the two standard tablets in each of the two trials. Patients were assessed on entry and at Days 7 and 14 of treatment. The results in both studies showed that there was significant improvement in tenderness, pain on movement, overall pain and in the range of movement after treatment, there being no significant difference between those receiving the slow-release form or the standard tablets. Tolerance was good in all groups and only a few minor or moderate side-effects, mainly of a gastro-intestinal type, were reported.

Fentiazac in the treatment of osteoarthritis and tendinitis.

In a double-blind trial in 20 patients with osteoarthritis, treatment was given at random with either 200 mg fentiazac or 50 mg indomethacin twice daily for 6 weeks. Both treatments produced marked improvement in pain and the other variables studied but, apart from blood pressure which was raised in the indomethacin group, no significant differences between treatments were observed. In a second double-blind trial involving 24 patients with acute non-articular rheumatism, mainly tendinitis, 200 mg fentiazac twice daily was compared with 200 mg phenylbutazone twice daily over a period of 2 weeks. No significant difference in improvement was found between treatments in any of the clinical variables studied, although there was a trend in favour of fentiazac, particularly in the relief of tenderness. No difference was noted in the incidence or nature of side-effects, which were mainly gastro-intestinal in origin, reported by patients in the treatment groups in either study.

Tiapride versus glafenine: a double-blind comparative study in the management of acute rheumatic pain.

A double-blind study was carried out in 42 patients suffering from acute rheumatic pain to compare the analgesic effectiveness and tolerance of tiapride with that of glafenine, a widely used analgesic in Europe. Patients were allocated at random to receive either 100 mg tiapride or 200 mg glafenine 3-times daily over a period of 14 days. Pain intensity was rated daily by the patients using a visual analogue scale and an overall assessment of response to treatment was made by both patients and physician at the end of the study. The results showed that, whilst both treatments resulted in a marked reduction in mean pain scores, pain disappeared completely in 16 (76%) of the 21 patients treated with tiapride compared with 9 (43%) of the 21 receiving glafenine. There was also a significant difference in favour of tiapride in the physician's overall assessment of response which was considered as excellent in 71% of the patients on tiapride compared with 31% receiving glafenine. Both treatments were well tolerated and few side-effects were reported. Drowsiness occurred in 6 patients on tiapride but this was only mild in 5 and moderate in the other patient.

A study of the effects of amodiaquine on the guinea-pig isolated ileum.

Amodiaquine (3.5 . 10(-7) mol/l), a 4-amino-quinoline antimalarial, increases the responses of the guinea-pig isolated ileum to direct (acetylcholine, histamine, barium, chloride), partially (5-hydroxytryptamine, PGE1 and F2 alpha) and totally (electrical stimulations, nicotine) indirect agonists. Moreover it reverses inhibitions of the electrical induced contractions by acetylcholine antagonists (atropine), acetylcholine release blocking agents (morphine, tetrodotoxin, procaine, noradrenaline) and prostaglandin synthesis inhibitors (indomethacin, ibuprofen, flufenamine acid, hydrocortisone). From 2.7 . 10(-6) mol/l, it induces dose-related tonic contractions which are totally and reversibly abolished by indomethacin as well as by the prostaglandin antagonist, polyphloretin phosphate, but not by atropine, morphine and tetrodotoxin. This indicates that amodiaquine exerts both a direct muscular non selective ileal sensitization to various agonists and, but at higher concentrations, a contractile effect apparently dependent on prostaglandin synthesis and release. At even higher concentrations (5.4 . 10(-6) mol/l) an effect of amodiaquine on acetylcholine release was demonstrated by the observation of phasic contractions inhibited by atropine, morphine and tetrodotoxin. These effects are different from those found by us with several other antimalarial compounds in the same preparation.

Sensitization by caerulein of guinea-pig ileum to contractions by acetylcholine, histamine, 5-hydroxytryptamine and nicotine.

Low concentrations (0.63 and 1.25 ng/ml) of caerulein increase the submaximal contractions of the guinea-pig isolated ileum induced by several agonists and electrical stimulation. These effects of the polypeptide are due partly to neuronal pathways (i.e., a ganglionic stimulation) and partly to a non specific muscular sensitization. At higher concentrations of caerulein the effects of all the agonists were decreased. This seems related to the contractile effect of the peptide itself on the longitudinal muscle which interfers non specifically with the development of contractions induced by any other agonist.

The effects of antiinflammatory steroids on the response of the guinea-pig isolated ileum to acetylcholine, histamine, nicotine, 5-hydroxytryptamine and electrical stimulation.

High concentrations of antiinflammatory steroids (2.5-40 microgram/ml) reversibly inhibited the electrically induced contractions of the guinea-pig isolated ileum. At 40 microgram/ml they also reversibly inhibited contractions elicited by acetylcholine, histamine nicotine and 5-hydroxytryptamine. PGE1 (2.5 ng/ml), PGE2 (2.5 ng/ml) and PGF 2 alpha (25 ng/ml) antagonized these effects. The inhibition of contractions elicited by direct agonists were less pronounced than those elicited by indirect or partly indirect agonists. The inhibitory effect of steroids may be related to non-specific actions on biological membranes. An overall sensitization of the smooth muscle by PG's may explain their antagonism to inhibition by steroids.

Interest of zinc determination in leucocyte fractions for the assessment of marginal zinc status.

In order to test the sensitivity of leucocyte zinc determination in the assessment of zinc status, an isolation procedure of mononuclear (MNC) and polymorphonuclear (PMNC) cell fractions was developed. Zinc concentrations in cells from healthy subjects were (mean +/- SD, in mumol/10(10) cells): 0.81 +/- 0.24 in MNC and 0.55 +/- 0.06 in PMNC. In patients suffering from several diseases known to be associated with a marginal impairment in zinc status (cirrhosis, cancer, obesity, endocrine and rheumatic diseases), these concentrations did not differ from those in controls except in rheumatic patients in whom MNC zinc was increased (1.05 +/- 0.42 mumol/10(10) cells) and correlated with erythrocyte sedimentation rate (r = 0.41, P less than 0.01). This relation was also significant in the whole study population (r = 0.39, P less than 0.01). Leucocyte zinc therefore appears to have a limited value in the assessment of marginally impaired zinc status, except in inflammatory states.

Colchicine in therapy. State of the art and new perspectives for an old drug.

Colchicine is the most specific treatment in acute gouty attacks. In several European countries, oral colchicine is still used for routine treatment of acute gout. Its selectivity is used as a diagnostic tool. It is also active in the treatment of acute crises of chondrocalcinosis and more occasionally of other arthritic crises (e.g. sarcoidosis). Colchicine appears to be the necessary adjuvant prophylactic drug when starting a hypouricemic treatment with uricosuric or uricolytic drugs for avoiding acute gouty crisis due to sudden mobilisation of the uric acid pool. Besides gout, colchicine is the drug of choice for treating familial mediterranean fever. It appears to be helpful in the treatment of Behçet's disease. It seems also useful for treating fibrosing conditions such as liver cirrhosis and scleroderma. As an adjuvant therapy, it helps treating dermatological disorders which are associated with leucocyte migration as an essential pathogenic factor (e.g. psoriasis, dermatitis herpetiformis, necrotising vasculitis ...). It has been advocated as an adjuvant therapy in malignant diseases as a support in radiotherapy and as an useful drug in various other diseases where it has been tried occasionally (e.g. Paget's disease of the bone, idiopathic thrombocytopenic purpura, disc syndrome). This very old drug remains a modern therapeutic agent.

Effects of nimesulide and sodium diclofenac on interleukin-6, interleukin-8, proteoglycans and prostaglandin E2 production by human articular chondrocytes in vitro.

OBJECTIVES: The aim of this study was to investigate the effects of two nonsteroidal anti-inflammatory drugs (NSAIDs), nimesulide and sodium diclofenac, on the production of proteoglycans (PG), prostaglandin E2 (PGE2) and cytokines (IL-6 and IL-8) by human articular chondrocytes in vitro. METHODS: Enzymatically isolated chondrocytes were cultured under constant agitation in a well defined culture medium. Specific radioimmunoassays were used to quantify PG and PGE2 production. Cytokine production (IL-6 and IL-8) was assayed by enzyme amplified sensitivity immunoassays (EASIAs). RESULTS: At a concentration of 3 micrograms/ml, nimesulide did not affect the PG production by chondrocytes. This concentration was superior to the highest level of nimesulide found in the synovial fluid of patients with rheumatoid arthritis 3 hours after the last oral administration of nimesulide (100 mg twice daily for 7 days). At 6 micrograms/ml a significant reduction in the PG content was obtained in the cellular phase in 5 out of the 8 cultures investigated. No similar effect was observed in the culture supernatants. Above this concentration nimesulide inhibited PG production in a dose-dependent manner. At concentrations ranging from 0.005 to 1 microgram/ml diclofenac did not significantly alter PG production. At therapeutic concentrations PGE2 production was totally inhibited by nimesulide, thus suggesting that PG inhibition is not linked to PGE2 production. Nimesulide inhibited PGE2 production by unstimulated (IC50 = 6 ng/ml) and IL-1 beta-stimulated (IC50 = 6.9 ng/ml) chondrocytes. At these concentrations, PGE2 production was fully inhibited by diclofenac. Furthermore, both nimesulide and diclofenac at therapeutic concentrations significantly decreased spontaneous and IL-1 beta-stimulated IL-6 production by human chondrocytes, but did not modify IL-8 production. CONCLUSION: From the results of this study we conclude that nimesulide and diclofenac at therapeutic concentrations are potent inhibitors of PGE2 and IL-6 production while they do not modify proteoglycan or IL-8 production.

Effects of selenium supplementation on immune parameters in gut failure patients on home parenteral nutrition.

The relationships between some parameters of the immune response and selenium were investigated in five patients receiving home parenteral nutrition for short-bowel syndrome. They were first submitted to a relative depletion by providing 20 micrograms selenium/day as L-selenomethionine for 1 mo. Then, daily selenium intake was raised to 200 micrograms for 2-4 mo. On entering the study, the patients presented a relatively good health status, and immunological parameters were at the lowest limit of the normal range. Four patients rapidly responded to the 200-micrograms supplementation by a continuous increase in their plasma selenium levels, whereas the fifth patient showed a moderate and late increase. At the end of the trial, there was an improvement in the lymphocyte response to pokeweed and phytohemagglutinin mitogens in four patients and to CD3 in three patients. The response to two of three antigens (Candidin, Varidase) tested was also enhanced in the same patients, but the response to the third antigen (tetanus toxoid) was uniformly low in all patients. The only patient showing essentially no immune improvement after selenium supplementation was the one with a low and delayed increase in plasma selenium. This study supports a role for selenium in the maintenance of an optimal immune response in humans.

Oesophageal involvement in rheumatoid arthritis patients: a study with oesophageal radionuclide transit using 81Krm.

Rheumatoid arthritis (RA) is an inflammatory disease affecting mainly the joints. In addition, signs of systemic disease are likely to be present although they are not always clinically evident. Oesophageal motility dysfunction, present in 75% of progressive systemic sclerosis patients, was also reported in various other connective tissue diseases. The present study involved 32 rheumatic patients devoid of any gastrointestinal complaints or diseases: 16 RA, nine Raynaud's syndrome and seven mild osteoarthritis as controls. Oesophageal transit was assessed by using 81Krm radionuclide scan, a sensitive and non-invasive technique. Diffusing lung capacity for carbon monoxide (DLCO) was performed as evidence of subclinical systemic involvement. Abnormal oesophageal transit was observed in 5/16 RA (31%). Two of them were subsequently discarded due to the presence of asymptomatic goiter and asymptomatic gastrointestinal reflux leaving 3/14 RA for analysis. They all had extra-articular features (EAF) (pericarditis, nodules) and two of them had diminished DLCO. Two with Raynaud's syndrome had abnormal oesophageal transit but none of the controls had abnormal oesophageal transit. Upper gastrointestinal dysfunction after exclusion of symptomatic patients appears thus to be not very frequent in RA, even when a sensitive technique is used. Radionuclide transit scanning of the oesophagus is not a more useful method than others in detecting early EAF in RA.

Potentiation by sulphydryl agents of the responses of guinea-pig isolated ileum to various agonists.

Sulphydryl agents (dithiothreitol, mercaptoethanol, monothioglycerol, cysteine, glutathione) increase non-specifically the potency of various agonists (acetylcholine, 5-hydroxytryptamine, nicotine, bradykinin, prostaglandin E2) on the guinea-pig ileum. These effects are of non-cholinergic origin and are not related to prostaglandin synthesis. Sulphydryl agents act directly on the smooth muscle cells of the guinea-pig ileum most probably by reducing disulphide bonds located on the membrane surface and by this mechanism modulate the muscular contractile activity.

Correlation plasma levels, NSAID and therapeutic response.

A regular control of nonsteroidal anti-inflammatory drug (NSAID) plasma levels may be useful to avoid undesirable side-effects to monitor therapeutic progress to see if patients are complying with their prescription. Trying to establish a relationship between the plasma concentration of a drug and its clinical effects requires a few prerequisites which may or may not be fulfilled according to the NSAID (e.g. a drug acting by itself, a reversible action, no tolerance to the drug, a highly specific and sensitive enough analytical method of the drug, similar free drug concentrations in the plasma and at the receptor sites,...), the most important of them-which is also probably the most difficult to fulfil in the case of rheumatic diseases-being that the clinical effect of the drug must be easily measured. In fact, the evidence for a good correlation between clinical effects and drug plasma levels are very scarce in the field of NSAID. The best correlation was obtained with salicylates for which ranges of plasma concentrations needed for observing therapeutic effects in rheumatoid arthritis as well as in juvenile rheumatoid arthritis have been established. Similar correlations have been made for side effects such as tinnitus or headaches as well as for toxic manifestations of salicylism. However, many individual variations have been described and there is considerable overlap between therapeutic and toxic concentrations. According to different authors there are or there are no correlations between phenylbutazone plasma levels and either is therapeutic or its side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

About five cases of acute rheumatic fever in the adult.

We describe five cases of acute rheumatic fever in adults (applying Jones's criteria and exclusion of other common causes of acute polyarthritis in adults). The polyarthritis was migratory in three patients and additive in two. Severe tenosynovitis was present in three patients. Only one patient had carditis and received corticoids. The others improved with aspirin. The disease subsided after a time period varying from one week to two months and did not relapse.

Ochronosis: a case report with severe ochronotic arthropathy.

Alkaptonuria is a rare inborn metabolic disorder in which ochronotic pigment is deposited in connective tissue and cartilage. Ochronotic arthropathy is the consequence of longstanding alkaptonuria and leads to progressive joint disability. We report a case of a 67-year old man with severe ochronotic arthropathy involving the spine, the knees, the shoulders and the hips.