Nailfold videocapillaroscopy: a novel possible surrogate marker for the evaluation of peripheral microangiopathy in pulmonary arterial hypertension.

Nailfold videocapillaroscopy (NVC) changes in systemic sclerosis (SSc) are correlated with vascular complications, such as pulmonary arterial hypertension (PAH), supporting a potential link between peripheral and internal organ vasculopathy. The current stage of knowledge regarding NVC and PAH is discussed, focusing on the assessment of peripheral microangiopathy and a potential relationship with functional, echocardiographic, and haemodynamic markers of cardiac dysfunction. A comprehensive literature search was carried out to identify all studies focusing on NVC findings in patients with PAH, diagnosed with right heart catheterization. The majority of the studies examined NVC findings in patients with SSc-PAH, while three studies reported NVC abnormalities in patients with idiopathic PAH. Besides the pulmonary vasculature, a systemic component of microangiopathy seems to be involved in PAH. Well-designed prospective trials are warranted to validate NVC as a biomarker, with clinical implications in the diagnostic evaluation, risk stratification, and overall management of PAH in the daily clinical setting.

Clinical and financial burden of active lupus in Greece: a nationwide study.

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need.

Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by persistent chronic arthritis. Disease risk is believed to be influenced by both genetic and environmental factors. It is well established that the PTPN22 single nucleotide polymorphism (SNP) rs2476601 is associated with JIA susceptibility. It was recently reported in an Australian study that this association is restricted to females and is not observed in males. A significant source of inconsistency amongst the literature on autoimmune disease susceptibility genes stems from an inability to replicate genetic findings across different racial or ethnic groups. We therefore attempted to generate further evidence of the female-specific association of rs2476601 in a homogeneous Greek population. FINDINGS: We genotyped rs2476601 in 128 Caucasian JIA patients (70.3 % female) and 221 healthy controls (28.1 % female) from Northern Greece. Overall, PTPN22 was associated with increased risk of JIA in this Greek sample (OR = 2.3, 95 % CI 1.1 - 5.1, p = 0.038). Sex-stratified analyses showed that, once again, the risk association was restricted to females (Female: OR = 19.9, 95 % CI 1.2 - 342, p = 0.0016; Male: OR = 1.1, 95 % CI 0.3 - 3.1, p = 0.94) supporting the prior findings. CONCLUSIONS: Our data demonstrates that this sex-specific pattern of association is broadly applicable to different populations, and provides further impetus to undertake mechanistic studies to understand the impact of sex on PTPN22 in JIA.

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.

Clinical expression and course in patients with late onset systemic lupus erythematosus.

BACKGROUND: To analyze the pattern of clinical expression and the 5-year disease course in Caucasian patients with late onset of systemic lupus erythematosus (SLE) and to compare the findings with an early onset SLE group. METHODS: Medical records of 551 patients who presented with SLE at hospitals of the region of Thessaloniki between 1989 and 2007 were studied. Patients who developed SLE at or after the age of 50 years were classified as the late onset group, while younger patients served as the early onset group. Data on clinical manifestations and damage accrual at disease onset and at 5 years was obtained and compared between the two groups. RESULTS: In 121 patients, the disease started after the age of 50 years. Elderly patients showed less pronounced female predominance and less often presented with malar rash, nephropathy, fever and lymphadenopathy, while lung involvement, pericarditis and sicca syndrome were more frequent. Damage accrual was similar in both groups. The main causes of damage at 5 years differed, with the elderly exhibiting more cardiovascular damage. They also had a higher incidence of hypertension and osteoporosis at 5 years. CONCLUSIONS: Caucasian SLE patients with late onset of the disease present with different clinical manifestations, suggesting that age affects the expression of SLE. Damage accrual at 5 years is similar in the elderly and the younger patients. However, the causes of this damage and the occurrence of other comorbidities follow a different pattern, possibly reflecting the disease process and the effects of aging.

Investigation of juvenile idiopathic arthritis susceptibility loci: results from a Greek population.

The strategy of studying the putative role of RA susceptibility genetic factors in the development of juvenile idiopathic arthritis (JIA), an autoimmune disease characterized by persistent chronic arthritis, has been proven highly successful so far. Moreover, accumulated evidence indicates that an ethnic heterogeneity of genetic factors exists for rheumatic disorders. We investigated whether five single nucleotide polymorphisms (SNPs), previously found to be associated with JIA in various populations so far, are also associated with JIA in Greece. The sample set consisted of 128 Caucasian JIA patients and 221 healthy controls from Northern Greece. Five Single Nucleotide Polymorphisms (SNPs) markers, namely TRAF1/C5 rs10818488, PTPN22 rs2476601, STAT4 rs7574865, CD247 rs1773560 and PTPN2 rs7234029 SNPs were genotyped in a case-control study with Restriction Fragment Length Polymorphisms (RFLPs) or Taqman primer-probe sets. This study demonstrated for the first time in a Greek population that the PTPN22, TRAF1/C5 and CD247 polymorphisms examined are associated with an increased susceptibility to JIA, thus suggesting that the respective risk alleles may confer susceptibility to clinically distinct disorders. However, our results did not demonstrate any association of STAT4 and PTPN2 SNPs with the disease in our population, thus highlighting the importance of comparative studies in different ethnic populations.

Clinical expression and morbidity of systemic lupus erythematosus during a post-diagnostic 5-year follow-up: a male:female comparison.

The aim of this study was to analyse the prevalence of the most relevant clinical features of the diagnosis of systemic lupus erythematosus (SLE) in a sample of male patients with lupus as well as the incidence of the main causes of morbidity in a 5-year period after the diagnosis. A further aim of this study was to investigate the impact of gender on expression and morbidity of SLE. Data were collected from the medical records of 59 male and 535 female patients with SLE who were diagnosed at the hospitals in the region of Thessaloniki. Several differences in the expression and morbidity of the disease were found in relation to the gender of the patient. Male patients had a higher prevalence of thromboses, nephropathy, strokes, gastrointestinal tract symptoms and antiphospholipid syndrome when compared with female patients, but tended to present less often with arthralgia, hair loss, Raynaud's phenomenon and photosensitivity as the initial clinical manifestations. During the 5-year follow-up, positive associations have been found between male gender and the incidence of tendonitis, myositis, nephropathy and infections, particularly of the respiratory tract. In conclusion, this study has provided information regarding the features of clinical expression and morbidity in male patients, and has shown that gender is a possible factor that can influence the clinical expression of SLE.

Primary adrenal lymphoma presenting as Addison's disease. Case report and review of the literature.

Primary Adrenal Lymphoma (PAL) is a very rare clinical entity. Adrenal insufficiency is a common complication of this pathology. Most patients present with clinical and laboratory findings of adrenal insufficiency and bilateral enlargement of the adrenal glands. We present a 78-year-old woman admitted to our institution with typical clinical and laboratory findings of adrenal insufficiency. Computerized tomography (CT) of the abdomen revealed bilateral enlargement of the adrenal glands. The patient was eventually diagnosed with a diffuse large B-cell lymphoma after a CT-guided needle adrenal biopsy and treated with combined immuno-chemotherapy (R-LPD-COP). Twenty months after the initial evaluation, she is in good condition, with no signs of adrenal insufficiency.

The relative proportions of secreted interleukin-2 and interleukin-10 determine the magnitude of rheumatoid arthritis T-cell proliferation to the recall antigen tuberculin purified protein derivative.

OBJECTIVE: To investigate the mechanisms of the deficient proliferative responses by rheumatoid arthritis (RA) peripheral blood T cells to the recall antigen tuberculin purified protein derivative (PPD). METHODS: The concomitant production of interleukin (IL)-2, IL-10 and lymphocyte proliferation were studied by enzyme-linked immunosorbent assay and [(3)H]thymidine uptake, respectively, in 12 normal controls and eight RA patients. RESULTS: An inverse correlation was found between IL-10 production and proliferation to PPD. The proliferative response was shown to be critically affected by the IL-2:IL-10 ratio so that absolute levels of secreted IL-2 or IL-10 correlated non-significantly with lymphocyte proliferation. CONCLUSION: The deficient T-cell proliferation in RA peripheral blood mononuclear cells is related to the relative proportions of IL-2:IL-10 rather than the absolute amounts secreted.

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.

Treatment of biliary colic with diclofenac: a randomized, double-blind, placebo-controlled study.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used to relieve biliary colic. Follow-up was limited in previous studies, and the role of NSAIDs in the natural history of biliary colic has not been clarified. The purpose of this study was to evaluate the efficacy of diclofenac, a potent NSAID, in the the immediate symptomatic relief of biliary colic and the prevention of cholelithiasis-related complications. METHODS: Fifty-three patients with cholelithiasis and biliary colic were enrolled in this randomized, double-blind, placebo-controlled study. They received a single 75-mg (3 mL) intramuscular injection of diclofenac (n = 27) or similarly administered 3 mL of saline (n = 26). All patients were followed up for at least 3 days. The effect of either treatment was assessed by changes in the severity of pain and the development of cholelithiasis-related complications. RESULTS: Complete relief of pain was obtained in 21 diclofenac and in 7 placebo patients; progression to acute cholecystitis was observed in 4 and 11 patients, respectively. Fewer overall complications were observed in the diclofenac group. CONCLUSIONS: In patients with cholelithiasis who present with biliary colic, a single 75-mg intramuscular dose of diclofenac can provide satisfactory pain relief and decrease substantially the rate of progression to acute cholecystitis.

Responsiveness to recombinant human erythropoietin (rh-Epo) of marrow erythroid progenitors (CFU-E and BFU-E) from B-chronic lymphocytic leukemia (B-CLL).

The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to various concentrations of recombinant human erythropoietin (rh-Epo) (2,5,20,40,100,200 and 500 U/ml) was investigated in vitro in 18 patients with B-chronic lymphocytic leukemia to assess the clinical usefulness of rh-Epo in this disease. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU-E and BFU-E assays. The B-chronic lymphocytic leukemia patients were divided into two groups according to the percentage of lymphocytes in the bone marrow (under 70% and over 70%). Among the patients with few lymphocytes, more than one third demonstrated some degree of response to rh-Epo. Among the patients with a high percentage of lymphocytes in the bone marrow, some revealed no response to rh-Epo, but there were patients who showed a good response to rh-Epo. Because erythroid progenitors from B-chronic lymphocytic leukemia appeared sensitive to rh-Epo in vitro, we propose that high doses of this drug may be clinically effective in some patients with this disease, regardless of the degree of lymphocytic inflitration of the bone marrow.

Interleukin 2-dependent immunoregulatory function in hemodialysis patients with chronic hepatitis C.

To investigate the state of activation of T lymphocytes in hemodialysis patients with chronic hepatitis C, serum levels of soluble interleukin-2 receptors (sIL-2R), interleukin-2 (IL-2) and expression of interleukin-2 receptors (IL-2R) on peripheral T lymphocytes were measured in 30 hemodialysis patients with chronic hepatitis C, 14 hemodialysis patients without hepatitis, 30 patients with chronic hepatitis C and 41 normal subjects. A significant increase in sIL-2R levels was noted in all patients with chronic hepatitis compared to normal controls. This increase was even more significant in hemodialysis patients, while a less significant increase was also found in hemodialysis patients without hepatitis C viral infection. Expression of IL-2R on T lymphocytes was increased only in hemodialysis patients with chronic hepatitis. All patients had low levels of serum IL-2. These findings show that a T-cell activation involving the IL-2 system is present in chronic hepatitis C and that this activation is more prominent in hemodialysis patients, probably due to additional extrahepatic factors.

Greek version of the General Health Questionnaire: accuracy of translation and validity.

The purpose of this study was to examine the accuracy of translation and to test the validity of the Greek version of the General Health Questionnaire (GHQ). In the translation study, the English and the Greek versions of the GHQ were administered to a sample of 50 bilingual respondents. The internal consistency, item-by-item and the subject-by-subject analysis have shown that the 2 versions are equivalent and therefore the Greek translation is highly accurate. In the validity study, 100 consecutive patients attending an internal medicine outpatient clinic completed the Greek version of the GHQ-60 and were interviewed independently using the Present State Examination (PSE). The validity of the shorter forms of the questionnaire (GHQ-30 and GHQ-28) was tested by disembedding the relevant items from the larger set. The correlations obtained between the scores of the questionnaire and the PSE ratings, as well as all the validity indices (sensitivity, specificity, positive predictive value, negative predictive value and overall misclassification rate) were quite satisfactory for all the GHQ forms, thus confirming the validity of the questionnaire in its Greek version. The best cut-off points as found by receiver-operating characteristics analysis were 11/12 for the GHQ-60, 5/6 for the GHQ-30 and 4/5 for the GHQ-28. The revised (CGHQ) scoring system for the GHQ-30 has not been proved superior to the conventional scoring method. The above results are discussed in relation to the pertinent literature and especially the studies carried out in similar settings and in countries with similar cultural backgrounds.

Tuberculous enteritis. Forgotten but not gone.

A case of a young Greek woman with ileocecal tuberculosis secondary to active pulmonary tuberculosis is presented. Diarrhea of six months duration, abdominal pain and loss of weight were the main symptoms. Incidence, pathogenesis and laboratory findings are shortly discussed. The need for continued awareness of the existence of this disease is also emphasized.

Rhabdomyolysis and acute renal failure associated with pyloric stenosis.

Rhabdomyolysis and acute tubular necrosis (ATN) are described in a patient with pyloric stenosis in whom severe hypokalemia developed due to repetitive vomiting. Furthermore, the importance of hypokalemia in the development of acute renal failure is emphasized.

Evaluation of the renal mechanisms for urate homeostasis in uremic patients by probenecid and pyrazinamide test.

The tubular transport of urate was studied in 47 uremic patients and in 20 normal subjects using probenecid and pyrazinamide tests. There was a marked increase in urate excretion per nephron as the renal function deteriorated. Presecretory reabsorption of urate per nephron, which was almost complete in normal subjects, showed a diminution with increasing severity of chronic renal failure. Until the creatinine clearance had decreased to less than 10 ml/min, the secreted urate per nephron remained almost constant, while in the end stage of renal failure it was markedly decreased. With the progression of renal disease, the postsecretory reabsorption of urate per nephron diminished. In patients with a creatinine clearance less than 10 ml/min, it was 4 times lower than in normal subjects. These findings indicate that urate secretion does not contribute to the increase of urate excretion per nephron at any level of renal failure, whereas the impairment of both reabsorptive components accounts for the augmented urate excretion per nephron in uremic patients.