Vascular endothelial growth factor in patients with psoriatic arthritis.

OBJECTIVE: To determine the levels of vascular endothelial growth factor (VEGF) in patients with active psoriatic arthritis, patients with inactive psoriatic arthritis, and healthy controls. Serum VEGF levels were correlated with clinical and laboratory features in patients with active psoriasis arthritis. METHODS: Serum samples from 14 patients with active psoriatic arthritis, 14 patients with inactive psoriatic arthritis, and 9 healthy controls were investigated. VEGF levels in the serum were measured using a sensitive sandwich ELISA. RESULTS: The mean serum VEGF concentration in patients with active PA was 394.4 pg/ml (394 +/- 171.8), in patients with inactive PA 200.4 pg/ml (200.4 +/- 115.7), and in healthy subjects 214.3 pg/ml (214.3 +/- 162.1). Patients with active psoriasis arthritis had significantly higher levels of VEGF compared to patients with inactive psoriasis arthritis and healthy individuals (p > 0.001). In contrast, VEGF levels were comparable in patients with inactive psoriatic arthritis and controls (p =0.659). Furthermore, in patients with psoriatic arthritis, VEGF levels were positively correlated with ESR, HAQ, PASI and VAS. CONCLUSION: VEGF levels may be regarded as a good indicator of active psoriasis arthritis.

Short-term infliximab therapy improves symptoms of psoriatic arthritis and decreases concentrations of cartilage oligomeric matrix protein.

OBJECTIVE: The aim of the current study was to evaluate the short-term effects of anti-tumour necrosis factor alpha (infliximab) therapy on serum cartilage oligomeric matrix protein (COMP) levels, a possible biomarker of cartilage destruction. METHODS: Nine consecutive patients with active psoriatic arthritis (PsA) were treated with infliximab for 6 weeks. Serum COMP levels were measured and correlated to pre-established disease activity outcome variables: pain as assessed by the patient, using the 100 mm visual analogue scale (VAS), duration of morning stiffness (MGST), swollen joint count (SJC), tender joint count (TJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: Significant improvements in MGST, VAS, SJC and TJC values were observed after 6 weeks of therapy. Similar significant improvements were demonstrated in the ACR response rate and in eight (89%) patients the ACR20 was achieved. ESR and CRP decreased significantly over 6 weeks. Serum COMP levels also decreased significantly after 6 weeks of treatment (12.99 +/- 1.71 baseline, 10.22 +/- 1.1 after 6 weeks, P < 0.008). CONCLUSION: The results of our study suggest that short-term therapy with infliximab leads to decreased COMP levels in patients with PsA. COMP seems to be a good candidate for a biomarker reflecting cartilage response to this treatment in PsA patients.

Strength and endurance training lead to different post exercise glucose profiles in diabetic participants using a continuous subcutaneous glucose monitoring system.

BACKGROUND: Although both strength training (ST) and endurance training (ET) seem to be beneficial in type 2 diabetes mellitus (T2D), little is known about post-exercise glucose profiles. The objective of the study was to report changes in blood glucose (BG) values after a 4-month ET and ST programme now that a device for continuous glucose monitoring has become available. MATERIALS AND METHODS: Fifteen participants, comprising four men age 56.5 +/- 0.9 years and 11 women age 57.4 +/- 0.9 years with T2D, were monitored with the MiniMed (Northridge, CA, USA) continuous glucose monitoring system (CGMS) for 48 h before and after 4 months of ET or ST. The ST consisted of three sets at the beginning, increasing to six sets per week at the end of the training period, including all major muscle groups and ET performed with an intensity of maximal oxygen uptake of 60% and a volume beginning at 15 min and advancing to a maximum of 30 min three times a week. RESULTS: A total of 17,549 single BG measurements pretraining (619.7 +/- 39.8) and post-training (550.3 +/- 30.1) were recorded, correlating to an average of 585 +/- 25.3 potential measurements per participant at the beginning and at the end of the study. The change in BG-value between the beginning (132 mg dL(-1)) and the end (118 mg dL(-1)) for all participants was significant (P = 0.028). The improvement in BG-value for the ST programme was significant (P = 0.02) but for the ET no significant change was measured (P = 0.48). Glycaemic control improved in the ST group and the mean BG was reduced by 15.6% (Cl 3-25%). CONCLUSION: In conclusion, the CGMS may be a useful tool in monitoring improvements in glycaemic control after different exercise programmes. Additionally, the CGMS may help to identify asymptomatic hypoglycaemia or hyperglycaemia after training programmes.

Continuous glucose monitoring in diabetic long distance runners.

Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the "Fernwärme run" (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwärme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo- and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

HFE genotyping demonstrates a significant incidence of hemochromatosis in undifferentiated arthritis.

OBJECTIVE: Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Among Northern Europeans the carrier frequency is estimated to be 1 in 10, while up to 1 in 200 is affected by the disease. Arthropathy is one early clinical manifestation of this disease, but the articular features are often misdiagnosed. In this study the two frequent mutations of the HLA-linked hemochromatosis gene (HFE) were investigated in a rheumatology clinic population. METHODS: Two hundred and six consecutive patients (mean age 57.7 years; 38 male/168 female) attending a rheumatology clinic over a period of 14 months were screened for HFE mutations (C282Y and H63D). All standard diagnostic procedures were used to identify the aetiology of the arthropathy. Mutations were evaluated by separation on PAGE of digested PCR amplificates of DNA (by SnapI and Bcl-I, for C282Y and H63D, respectively) obtained from PBMCs. RESULTS: The C282Y and H63D allele frequencies were 4.5 and 12.8 in patients with rheumatic diseases. Five patients were homozygote for H63D (2.4%), and one for C282Y (0.5%). Five patients were compound heterozygous (2.4%). The observed C282Y allele frequency in rheumatic patients with undifferentiated arthritis was 12.9 and exceeded that of healthy subjects (p = 0.01). CONCLUSIONS: Determination of the HFE genotype is clinically useful in patients with arthritis of unknown origin, to allow early diagnosis of hemochromatosis.

Pamidronate increases bone mineral density in women with postmenopausal or steroid-induced osteoporosis.

INTRODUCTION: We aimed to determine the efficacy and safety of a cyclic intravenous therapy with pamidronate in patients with postmenopausal or glucocorticoid-induced osteoporosis. METHODS: We enrolled 86 Austrian female patients with postmenopausal (n = 69, mean age 68.13 +/- 1.14) or glucocorticoid-induced (n = 17, mean age 66.89 +/- 2.03) osteoporosis defined as a T-score of < -2.5 for bone mineral density (BMD) of the lumbar spine L1-L4. Patients received a single intravenous dose of 30 mg pamidronate at 3 months intervals. The per cent change in BMD was primary, whereas the safety and the biological response were secondary endpoints. RESULTS: Seventy-six female patients (88%) completed study. Sixty patients received pamidronate therapy for the treatment of late postmenopausal osteoporosis and 16 patients received the same treatment for glucocorticoid-induced osteoporosis. At the end of the trial, lumbar spine (L1-L4) BMD increased significantly in patients with postmenopausal osteoporosis (P = 0.000067), whereas in patients with glucocorticoid-induced osteoporosis no significant change was observed (P = 0.724). The increase in the Ward's triangle BMD did not reach significance level in postmenopausal women receiving pamidronate (P = 0.0740). However, pamidronate treatment for glucocorticoid-induced osteoporosis resulted in a significant increase in Ward's triangle BMD (P = 0.0029). The efficacy of pamidronate treatment for postmenopausal osteoporosis was also reflected in a decrease in circulating biochemical markers for bone formation, including alkaline phosphatase and osteocalcin. In addition, pamidronate was well tolerated with no incidence of severe gastrointestinal events. CONCLUSION: Cyclic intravenous administration of pamidronate is well-tolerated therapy in postmenopausal osteoporosis, and increases spinal BMD. Randomized controlled studies with adequate number of patients are needed to test the efficacy of the compound in the treatment of glucocorticoid-induced osteoporosis.

Acute-phase response and immunological markers in morbid obese patients and patients following adjustable gastric banding.

OBJECTIVE: We measured markers of acute-phase response and immunological markers in morbid obese patients and in formerly morbid obese patients after a massive weight loss following adjustable gastric banding (GB). SUBJECTS: A total of 49 morbid obese female patients with a body mass index (BMI) above 40 kg/m(2) were investigated during a study period of 6 months. Of these, 24 patients received a gastric banding (GB) and lost a minimum of 20 kg in 1 y (GB group) and 25 patients maintained their weight (obese group). In sum, 13 normal weight subjects (BMI<24 kg/m(2)) were taken for controls. METHOD: Plasma concentration of the acute-phase proteins, C-reactive protein (CRP), orosomucoid, complement factors C3 and C4 and white blood cell count, lymphocyte subsets and serum immunoglobulins were analyzed. RESULTS: Acute-phase proteins were significantly lower in GB compared to morbid obese patients and remained significantly elevated in GB compared to controls. In addition, leukocytes, polymorphonuclear leukocytes and lymphocytes were significantly lower after GB and reached levels comparable to controls (except PMN). No difference in CD3 counts was observed in the three groups. CD4 increased and CD8 decreased in obese and GB patients when compared to controls whereas no statistical difference was found between obese and GB patients. CONCLUSION: Our results confirm the positive effect of GB followed by a massive weight loss without apparent malnutrition. Subclinical chronical inflammation in morbid obese patients leads to irregularities in leukocyte and lymphocyte subsets. These alterations can be positively influenced by GB.

Distribution of patients with Wilson disease carrying the H1069Q mutation in Austria.

BACKGROUND/AIMS: More than 100 different mutations of the Wilson disease (WD) gene have been reported so far, but only the H1069Q mutation is frequently found in patients of North and East European origin. We wanted to know if there is a connection between the migration pattern in Central Europe and the geographical distribution of this mutation in Austria. METHODS: One hundred and nine patients (91 index patients and 18 asymptomatic siblings) with WD diagnosed in Austria were included in this study. Eighty-one of the 91 index patients were born in Austria. Evaluation criteria included the place of birth of each member of the study group, as well as of his parents and grandparents. RESULTS: Out of the 81 index patients born in Austria, 72 were tested for the H1069Q mutation. Twelve (16.7%) were homozygous carriers of the H1069Q mutation, 29 (40.3%) were compound heterozygous and 31 (43.0%) had an unknown mutation on both chromosomes. Eight of the twelve H1069Q homozygotes were born close to the northeastern border of Austria (neighboring the Czech Republic, Slovakia and Hungary). Compound heterozygous patients showed a more variable geographical distribution with respect to their birthplace. The patients with unknown mutation were scattered all over Austria. CONCLUSION: These data provide further evidence that the H1069Q mutation originates from Eastern Europe. In patients from these countries the PCR-based testing for this mutation may be useful for differential diagnosis and family studies.

Screening for Wilson's disease in patients with liver diseases by serum ceruloplasmin.

BACKGROUND/AIMS: A low serum ceruloplasmin level is considered a diagnostic test for Wilson's disease. To examine whether it is useful to detect presymptomatic patients with Wilson's disease, serum ceruloplasmin was determined by radial immunodiffusion (normal: 20-60 mg/dl) in all patients (n = 2867) admitted for evaluation of a liver disease in 1993 and 1994. METHODS: Patients with levels lower than 20 mg/dl were further evaluated by determination of serum copper concentration, urine copper excretion and ophthalmological examination. If possible, a liver biopsy was performed and the hepatic copper content was determined by flame atomic absorption spectroscopy. RESULTS: Seventeen patients had serum ceruloplasmin levels < 20 mg/dl. One had asymptomatic Wilson's disease (no Kayser-Fleischer rings or neurological symptoms). In the other 16 patients Wilson's disease was excluded. Based on elevated hepatic copper concentration, there were considered as heterozygous carriers of the WD gene. The remaining patients had various liver diseases (acute viral hepatitis in three, chronic hepatitis in two, drug-induced liver disease in three, alcoholic induced liver disease in two) or malabsorption (n = 3). CONCLUSIONS: The positive predictive value of low serum ceruloplasmin was only 5.9%. Although helpful for identifying presymptomatic Wilson's disease, screening by determination of serum ceruloplasmin in unselected patients with clinical or laboratory evidence of liver disease is neither feasible nor cost effective.