Prevalence and clinical manifestations of ankylosing spondylitis in young Greek males.

Increased awareness and sensitivity of general physicians have increased the early diagnoses of seronegative arthritis in young patients, while new agents such as anti-TNF blockers have significantly changed the treatment of the disease. To investigate the prevalence, the clinical manifestations, and the ability for military service of young Greek males (18-30 years old) with ankylosing spondylitis (AS) in the pre-anti-TNF era. We retrospectively studied the AS cases recorded from 1989 to 1995 of the rheumatology department of the largest General Military Hospital in Greece; the diagnosis was based on the modified New York criteria for AS. A total of 285 AS cases were diagnosed among 357,184 young men. The overall prevalence of AS on December 1995 was estimated at 8.2 cases per 10,000 young men (95 % C.I. 7.2-9.2). All the patients had chronic back pain. Two hundred forty (84 %, 95 % C.I. 79-88 %) patients presented sacroiliitis of whom 163 (68 %, 95 % C.I. 62-73 %) were bilateral. Two hundred five patients (72 %, 95 % C.I. 66-77 %) had peripheral joint involvement. Thirty-one patients presented with anterior uveitis (11 %, 95 % C.I. 8-15 %). One patient had IgA nephropathy. None had gut involvement. HLA-B27 antigen was found in 257 patients (90 %, 95 % C.I. 86-93 %). Ninety-one patients (32 %, 95 % C.I. 27-38 %) had permanent discharge from the military service, while 128 (45 %, 95 % C.I. 39-51 %) were able for auxiliaries attendances. The prevalence of AS for the age group 18-30 years old in this young Greek men cohort was significantly lower than in other Caucasian European populations, and the clinical manifestations were considered as mild.

Mediterranean diet intervention for patients with hyperuricemia: a pilot study.

Dietary interventions have been suggested to be a safe cost-efficient way to control hyperuricemia. The aim of the study is to assess the potential of mediterranean diet as intervention to control the level of urate in patients with hyperuricemia in a small sample of patients. Patients with asymptomatic hyperuricemia were recruited from outpatient clinics and were enrolled into personal Mediterranean diet-based programs. Body mass index (BMI), serum urate, lipid profile and indirect calorimetry were measured at the beginning and then monthly for the first 3 months and then at the sixth month. At the same time, patients' compliance with the Mediterranean diet was assessed by a formal interview and standard questionnaire. Only six out of twelve patients managed to complete the diet (dropout rate 50 %). Their BMI remained constant during the trial period in the level of 1st degree obesity (BMI = 31.46). The mean value of serum urate at the beginning of the study was 9.12 mg/dl. After the first month, there was a reduction in urate by 20 % with mean urate at 6.92 mg/dl. The second, third and sixth month mean urate levels were 6.32, 6.1 and 6.4 mg/dl, respectively. The effect of the mediterranean diet was rapid at the first month and remained constant throughout the dietary intervention, suggesting that it might have a clinically significant effect on urate level thus providing a cost-efficient and safe alternative to pharmaceutical intervention as first-line treatment of hyperuricemia.

The engineered human anti-tumor necrosis factor-alpha antibody CDP571 inhibits inflammatory pathways but not T cell activation in patients with rheumatoid arthritis.

OBJECTIVE: We investigated the effect of an engineered human anti-tumor necrosis factor-alpha antibody, CDP571, on immune functions as well as bone and cartilage turnover in patients with rheumatoid arthritis (RA) in a placebo controlled trial. We also assessed the effects of repeated treatment with CDP571 in an open label continuation study. METHOD: Thirty-six patients were treated with either placebo or 0.1, 1, or 10 mg/kg of CDP571 given as an intravenous infusion. The followup period was 8 weeks. Lymphocyte phenotype, soluble CD4 (sCD4), soluble interleukin 2 receptor (sIL-2R), IL-6, and stromelysin levels in the blood were measured before and after treatment; bone and cartilage markers (pyridinoline, deoxypyridinoline, N-terminal telopeptide) were similarly assessed in the urine. Patients who completed a placebo controlled trial of CDP571 were offered further treatment with CDP571. They received a maximum of 2 further doses of 1 mg/kg (7 patients) or 10 mg/kg (9 patients) in an open study. RESULTS: Plasma IL-6 level was statistically significantly reduced in the 1 and 10 mg/kg groups. In the 10 mg/kg group, there were also reductions in plasma stromelysin and urine bone markers, although there was no change in sCD4 and sIL-2R levels. Repeat doses of CDP571 were well tolerated and continued to suppress the acute phase response and disease activity. CONCLUSION: Treatment with 10 mg/kg of CDP571 reduced IL-6 and surrogate markers of bone turnover in RA, suggesting that CDP571 might prevent joint damage in RA. Since there was no effect on lymphocyte markers despite the marked reduction in inflammation, CDP571 appears to have no effect on ongoing CD4 T cell activation.

Chronic sialadenitis in patients with nodal osteoarthritis.

Amongst the patients attending our combined oral medicine/rheumatology clinic, we have identified a subset presenting with xerostomia due to non-specific sialadenitis, who also suffer from generalized nodal osteoarthritis (NOA). We have called this combination SOX syndrome: sialadenitis, osteoarthritis and xerostomia. In this study, we have examined the characteristics of these patients clinically and histologically, and then determined the prevalence of SOX syndrome in patients with NOA compared to healthy age-matched controls. Patients were obtained from rheumatology clinics and a local old people's home. The series consisted of 35 patients with NOA and 18 age- and sex-matched controls without evidence of NOA or inflammatory rheumatic disease. There was no significant difference in age and sex between the two groups. None were on drugs known to induce xerostomia. The subjects were assessed for whole salivary, parotid saliva and lacrimal flow, autoantibodies, rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). The whole saliva flow (mean +/- 95% CI) was 0.32 +/- 0.07 ml/min for the NOA group and 0.54 +/- 0.17 ml/min for the control group. The difference is statistically significant (P < 0.05, two-tailed Student's t-test). No statistically significant difference was found in the parotid and lacrimal flow rates of NOA and controls. Nine of the 35 NOA patients had reduced whole salivary flow (normal range > 0.02 ml/min) compared with only one out of 18 in the control group (P > 0.05, chi 2 test). All NOA patients with xerostomia and reduced whole salivary flow were RF, anti-Ro and anti-La negative, and had a normal ESR. Thus, 25% of subjects with NOA had clinical and laboratory features of SOX syndrome, suggesting that this is a defined disease entity.

Endogenous opioid tone in patients with rheumatoid arthritis.

We have previously shown that there is deficient hypothalamic-pituitary-adrenal (HPA) responsiveness in rheumatoid arthritis (RA) patients. The basis for this deficient response is not known. The purpose of the project was to investigate whether the defective HPA response in RA patients is the result of increased endogenous opioid tone secondary to chronic pain which can suppress corticotrophin-releasing hormone (CRH) production. We conducted a double-blind placebo-controlled cross-over trial to study the effect of the opiate antagonist, naloxone, on psychometric function together with plasma adrenocorticotrophic hormone (ACTH), cortisol and prolactin. Seven RA patients with active and established disease and eight healthy controls were studied. Each received either a bolus i.v. infusion of 20 mg naloxone or normal saline. After at least 72 h, they received naloxone if they had previously received normal saline or vice versa. The pain score was statistically significantly higher at baseline in the RA group compared with controls (5.7 +/- 3.25 vs 0.35 +/- 0.21, P < 0.001). No difference was found in the other psychometric assessments throughout the study. Patients receiving normal saline did not show any significant change in cortisol or ACTH. Cortisol and ACTH showed a sharp and significant rise after naloxone treatment in both RA and normal subjects (P < 0.001 and P < 0.01), but no difference was observed between the two groups. The mean prolactin level showed no significant change in both groups after any treatment. We conclude that endogenous opioid tone does not appear to be a major contributor to the HPA defect in RA. However, the number of patients studied was small and this result will require confirmation from larger trials.

Cytidine deaminase may be a useful marker in differentiating elderly onset rheumatoid arthritis from polymyalgia rheumatica/giant cell arteritis.

OBJECTIVE: PMR/GCA is a relatively common inflammatory disease in the elderly population. Clinical differentiation from a polymyalgic onset of RA in the elderly can be difficult. We have examined in a preliminary study the hypothesis that serum cytidine deaminase (CD) may be valuable in the differential diagnosis of these disorders. METHODS: CD was assayed by a spectrophotometric method in 20 patients with active PMR/GCA, both before and after treatment with prednisolone, and was compared with serum CD levels in 20 patients with active RA. RESULTS: CD levels were within the normal range (< 10 units/ml) in 36 of the 40 samples from patients with PMR/GCA: The mean CD in pre-treatment samples was 8.64 units/ml (SD 7.09), and after treatment 7.20 units/ml (SD 3.53). The mean serum CD in the RA patients was 21.33 units/ml (SD 8.94), significantly higher than in PMR/GCA (p < 0.0001). CONCLUSION: Serum CD levels were significantly different when proven PMR was compared with established, long-standing RA. Therefore, serum CD could be a useful diagnostic marker for differentiating PMR/GCA from active RA in older patients.

Benign osteopetrosis, in a patient with sickle-cell beta+ (beta+) thalassaemia.

We describe a case of a patient suffering from benign osteopetrosis and sickle-cell beta+ thalassaemia. This case allows us to study the combined action of various pathogenetic mechanism involved in both diseases. The coexistence of osteopetrosis with sickle-cell beta+ thalassaemia seems to intensify the anaemia and sickling, but does not appear to modify the course of the osteopetrosis.

Diltiazem induces remission of calcinosis in scleroderma.

There is no widely accepted treatment for the calcinosis which occurs in scleroderma and dermatomyositis. We report a case of a 62-yr-old woman with active scleroderma complicated by tuberose calcinosis. The calcinosis, which had previously been unchanged for several years, regressed over a 2-yr period during which diltiazem was used to treat hypertension. This effect could not be explained by altered disease activity or renal function but, we suggest, may be due to inhibition of calcium influx into cells. This treatment merits further evaluation.

The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis.

Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF alpha) have been implicated in the pathogenesis of rheumatoid arthritis (RA), and have therefore become therapeutic targets. An engineered human antibody, CDP571, that neutralizes human TNF alpha was administered intravenously in single doses of 0.1, 1.0 or 10 mg/kg to patients with active RA (n = 24). The effects of the antibody were compared in a double-blind fashion with those of placebo (n = 12). In an open continuation phase patients were given either 1.0 or 10 mg/kg. We found that CDP571 was well tolerated and caused reductions in markers of disease activity such as erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP): this was confirmed by a reduction in the disease activity score (DAS). There was a reduction in the number of tender joints, maximal in degree and duration after 10 mg/kg. Patients also documented a reduction of pain and relief of arthritis symptoms. The effects of 10 mg/kg CDP571 on ESR, CRP, tender joints, pain and symptom relief compared to placebo were statistically significant at weeks 1 or 2. The continuation phase, although open, confirmed both the safety and the beneficial effects of CDP571 in active RA. In conclusion CDP571, an engineered human anti-TNF alpha antibody, is well tolerated and, after a single dose of 10 mg/kg, provides improvements in symptoms, signs and serological markers of disease activity in patients with active RA.

Trends and geographical distribution of childhood leukemia in Greece in relation to the Chernobyl accident.

Parts of Greece have been exposed to fallout radiation from the Chernobyl accident as much as any of the countries boardering with the former Soviet Union, because of the direction of the prevailing winds after the accident. Although fallout radiation did not reach levels expected to be associated with measurable effects, there is widespread concern in Greece that the incidence of childhood leukemia may be rising in the more heavily affected parts of Greece. Patient discharge data from all Greek hospitals treating childhood leukemia were used to calculate the annual incidence of the disease from January 1980 to June 1986 (preaccident period), from July 1986 to June 1988 (immediate postaccident period) and from July 1988 to June 1991 ("relevant" post-accident period, that accommodates the presumed latent period of the disease). Fallout radiation measurements (in Bq/kg Cs-137) were used to create 17 regions of similar (within regions) but highly variable (between regions) levels of fallout deposition. Background radiation (in Bq/kg Ra-226) and annual incidence of childhood leukemia by region were also estimated. There was no evidence of increased incidence of childhood leukemia during the immediate or the "relevant" post-Chernobyl period in any part of the country. Furthermore, regression analyses did not show any significant or suggestive association of childhood leukemia by region with either background or fallout radiation. These results indicate that the Chernobyl accident did not affect noticeably the incidence of childhood leukemia in Greece during the five-year post accident period.

Age of exposure to infections and risk of childhood leukaemia.

PIP: Between January and August 1992 in Greece, researchers conducted telephone interviews with parents of children with leukemia (136 cases, most in Attica [Athens and its environs] and the others on the island of Crete) and with parents of children not afflicted with leukemia (187 controls) to determine whether childhood leukemia may be a result of a subclinical infection at an earlier age. They controlled for place of residence when they conducted the multiple logistic regression analyses. They used attendance at a day care facility as a proxy for earlier infection because children come in close contact with each other at day cares, thereby exposing them to many infectious agents. Children who attended a day care had a lower relative risk of developing leukemia than those who did not attend day care (.67), but attendance did not have a significant protective effect. It did appear to have a significant protective effect for children who attended day care during infancy (for at least 3 months during the first 2 years of life), however, (relative risk = .28; p = .03). Significance remained even when the researchers considered different operational definitions of early attendance. Exposure to magnetic fields appeared to have a protective effect also against the development of childhood leukemia, but this effect did not reach significance (p = .07). The relative risk for 100 m from an electricity substation was 0.35. There was a slight, but insignificant increase in the relative risk for children living close to power lines, however (1.19 for 5 m; p = .63). Significant risk factors included young age at diagnosis and mothers with less than high school education.^ieng