The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis

OBJECTIVE: To describe cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) expression in muscle tissue in patients with idiopathic inflammatory myopathies (IIM) - dermatomyositis (DM) and polymyositis (PM) and to find out if any differences between affected and non-affected muscles detected by MRI exist. METHODS: Samples of muscle tissue from 7 patients with dermatomyositis (DM) and from 4 with polymyositis (PM) were obtained by needle biopsy from affected and non-affected sites distinguished by magnetic resonance imaging. In situ hybridization with antisense mRNA probes was employed to detect COX-1, COX-2 and 5-LOX mRNA. RESULTS: Expression of COX-1, COX-2, and 5-LOX mRNA was found in all samples - in the muscle cells, inflammatory cells and in vessels. COX-1 mRNA expression predominated in the inflammatory cells and vessels and was higher in affected than in non-affected sites detected by MRI (mean intensity 3.22+/-0.67 vs. 2.0+/-0.87; p = 0.0006). The expression of COX-2 mRNA was high mainly in inflammatory cells and/or vessels and was increased in MRI-detected affected tissues (3.5+/-0.88; 1.9+/-1.1; p = 0.003), as was the expression of COX-2 mRNA in muscle cells (2.1+/-1.0 vs. 1.3+/-1.0; p = 0.021). 5-LOX mRNA was largely expressed in muscle cells from MRI-detected affected sites and the signal intensity was higher in comparison with samples taken from non-affected tissues detected by MRI (3.22+/-0.7 vs. 1.67+/-0.7; p = 0.0007). CONCLUSION: Expression of COX-1, COX-2 and 5-LOX mRNA was observed for the first time in muscle tissues from IIM patients. This expression was increased in affected tissues detected by MRI, which may suggest a role of COX-1, COX-2, and 5-LOX in the pathogenesis of IIM.     

Effects of colchicine on the intestinal transport of endogenous lipid. Ultrastructural, biochemical, and radiochemical studies in fasting rats

The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, we have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of [14C]linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that (a) colchicine causes significant changes in enterocyte ultrastructure and (b) colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte.     

Serum calprotectin may reflect inflammatory activity in patients with active rheumatoid arthritis despite normal to low C-reactive protein

Approximately half of patients with rheumatoid arthritis (RA) have normal C-reactive protein (CRP) levels. Calprotectin is a promising and likely more specific biomarker of disease activity than conventionally used acute phase reactants. We aimed to analyse the levels of serum calprotectin in RA patients with clinically active disease and with normal/low CRP. A total of 160 RA patients underwent clinical examination (DAS28-ESR and CDAI). The levels of calprotectin were analysed in patients with moderate to high disease activity with normal/low CRP levels and in 32 healthy subjects. The discriminatory capacity of calprotectin to identify clinically active patients in spite of normal/low CRP was assessed using ROC curves. Out of all RA patients, 74/160 (46.3%) were in remission or had low disease activity according to DAS28 and had normal/low CRP levels. However, 51/160 (32%) had normal/low CRP levels despite having moderate to high disease activity. In these patients, calprotectin levels were significantly higher than those in patients who had normal/low CRP and were in remission or showed low disease activity (2.7?±?1.5 vs. 2.1?±?1.2 μg/mL, p?=?0.043), which differed from those in healthy subjects (2.7?±?1.5 vs. 1.9?±?1.2 μg/mL, p?=?0.011). The discriminatory capacity for calprotectin to distinguish clinically active vs. inactive disease despite normal/low CRP using AUC of the DAS28 was 0.607 (95% CI 0.503 to 0.711, p?=?0.043). The present study demonstrates that calprotectin may reflect inflammatory activity in RA patients where CRP fails to do so.     

Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein

BACKGROUND: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders-for example, rheumatoid arthritis. OBJECTIVE: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)-a marker of articular cartilage destruction. METHODS: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA. RESULTS: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease. CONCLUSION: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker.     

Prognostic implications of cytogenetic studies in an intensively treated group of children with acute lymphoblastic leukemia

We assessed the prognostic significance of leukemia cell cytogenetics by analyzing bone marrow aspirates obtained at time of diagnosis in 165 children on a single protocol for acute lymphoblastic leukemia (ALL). These children were assigned to six mutually exclusive cytogenetic categories as follows: (1) hyperdiploid, with 50 or more chromosomes (n = 35); (2) hyperdiploid, with 47 to 49 chromosomes (n = 11); (3) diploid (n = 42); (4) pseudodiploid (n = 34); (5) hypodiploid (n = 9); and (6) insufficient data (n = 34). At a median follow-up of 5 years, there were no statistically significant differences between any of these cytogenetic categories in either event-free or overall survival. Those children with chromosomal translocations (n = 26) appeared to fare the same as those lacking translocations (n = 105). The absence of karyotypic prognostic significance was observed not only within the overall group, but also when the results were stratified by standard- risk and high-risk status. Of the specific structural chromosome changes that we studied, only the Philadelphia chromosome (Ph) appeared to confer a poor prognosis, although there were too few such cases to achieve statistical significance. Although we did not detect the event- free survival differences that have been described previously in hyperdiploid, hypodiploid, and pseudodiploid childhood ALL, our findings must be viewed as preliminary given the small number of children in some of the cytogenetic categories. We think that the prognostic implications of these cytogenetic features might have been nullified by improvements in therapy.     

Macro- and microcirculatory assessment of cold sensitivity after traumatic finger amputation and microsurgical replantation

INTRODUCTION: Finger replantations after traumatic amputation are associated with good prognosis and acceptable functional results. However, cold sensitivity is a common and sometimes disabling sequelae after digital replantation. The exact causes of cold intolerance are still unclear; neural as well as vascular mechanisms have been discussed. We examined the macro- and microvascular performance of replanted fingers using high-resolution color-coded sonography for the assessment of skin vessel density of the fingertips as well as nailfold capillary microscopy and laser Doppler anemometry. Subsequently, we correlated these findings with the presence of cold sensitivity of the replanted digits. PATIENTS AND METHODS: Thirty-seven patients (mean age 45 years; range 19-72) with 40 traumatic finger amputations and microsurgical replantations were studied. The mean time interval between amputation and examination was 57.7 months (range 13-95). Macro- and microvascular examination consisted of electronic oscillograms of both arms, photoplethysmograms of all fingers before and after cold test, duplex ultrasound of the finger arteries, high-resolution color-coded sonography of the fingertips and nailfold capillary microscopy with laser Doppler anemometry. RESULTS: Cold sensitivity was present in 33 (83%) of the 40 replanted fingers. Peripheral arterial disease of the upper extremity could be excluded as all oscillograms showed normal findings. A vasospastic reaction after cold test was documented in 74% (30 of 38) of the replanted fingers, compared to 24% (9 of 38) of the contralateral uninjured fingers. Raynaud's phenomenon was restricted to replanted fingers and occurred in 10 of 40 patients (25%). Compared with the contralateral fingertips, reduced skin vessel density was found in 27 of 36 (75%) replants. Nailfold capillary microscopy revealed uncharacteristic morphologic patterns. The capillary flow velocity was 0.28 +/- 0.12 mm/s in the replanted fingers and 0.48 +/- 0.23 mm/s in their unaffected counterparts (P < 0.001). Correlating these findings with the presence of cold intolerance, reduced skin vessel density in the fingertips was significantly different between cold-sensitive replants and those without cold sensitivity (P = 0.05). Reduced skin vessel density was not related to the extent of reconstruction of nerves (P = n.s.), arteries (P = n.s.) and veins (P = n.s.). CONCLUSIONS: Our results do not confirm hypotheses that cold sensitivity after finger replantations is caused by macrovascular problems nor do they support assumptions of a primary capillary microcirculatory failure. Our findings of reduced vessel density point towards diminished thermoregulatory capacities in the fingertips of cold-sensitive replanted digits.     

Erhöhte Tagesschläfrigkeit in Österreich

Background

The prevalence of excessive daytime sleepiness has been studied in many countries. Results differ remarkably depending on the definition and methods used. The objective of the present study was to evaluate the prevalence of excessive daytime sleepiness in the Austrian population and to study the association with different sleep- and health-related variables.

Methods

The data were derived from a survey conducted by the Austrian Sleep Research Association (ASRA). The sample included 1000 people from all Austrian provinces and was representative for the Austrian population.

Results

Of the persons interviewed, 20.2% reported frequently having difficulties in staying awake in monotonous situations during the day. 11.5% reported falling asleep involuntarily during the day. Risk factors for excessive daytime sleepiness were short sleep duration, snoring, use of hypnotics, and high blood pressure.

Conclusion

In the Austrian population, one out of five persons frequently has difficulties staying awake in monotonous situations during the day, and one out of ten persons falls asleep involuntarily during the day. While the association between excessive daytime sleepiness and sleep-related breathing disorders is well known, insufficient sleep syndrome and use of hypnotics might still be underestimated risk factors for excessive daytime sleepiness. Considering the high prevalence and the associated risks, excessive daytime sleepiness represents a relevant health problem in the Austrian population.     

Four patients with myelodysplastic syndrome with translocation (1;7)(p11;p11) including one patient with independent clones del(7)q22) [corrected] and t(1;7)(q21;q11)

A translocation involving the short arm of chromosome #1 and the short arm of chromosome #7, [t(1;7)(p11;p11)] was present in four patients with myelodysplastic syndrome (MDS). Two of these patients had prior lymphoproliferative disorders and developed MDS following prolonged therapy with alkylating agents. One of the patients with prior therapy history has two additional independent abnormal clones: one with a partial deletion of the long arm of #7 and the other with t(1;7)(q21;q11). A third patient had a family history of leukemia in both the father and a brother, both of whom developed acute nonlymphocytic leukemia following an MDS phase. The last patient was an elderly woman with no predisposing features.