Corneal crystals, myopathy and nephropathy: a new syndrome?

A case with ocular (corneal crystals and retinal pigment epithelial mottling), muscle (oropharyngeal and hand weakness and atrophy), and renal (proteinuria and hypertension) abnormalities is described. We believe that this represents a previously unrecognized syndrome.     

Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Detection of the Arg702Trp, Gly908Arg and Leu1007fsinsC polymorphisms of the NOD2/CARD15 gene by real-time PCR with melting curve analysis.

Crohn's disease is a complex disorder, with multiple genetic traits. A frameshift mutation (Leu1007fsinsC) and two missense mutations (Gly908Arg and Arg702Trp) in the NOD2/CARD15 gene are strongly associated with susceptibility to Crohn's disease. The presence of one of these risk alleles confers a 2- to 4-fold increase in the risk of developing Crohn's disease, and the presence of two mutant alleles increases the risk over 20-fold. To facilitate the analysis of these polymorphisms, we developed three LightCycler assays to detect the missense mutations Arg702Trp and Gly908Arg and the frameshift mutation Leu100fsinsC in the NOD2/ CARD15 gene. All three assays can be run simultaneously on one LightCycler using identical cycling parameters. Analysis of 53 DNAs from Crohn's patients helped to identify carriers at allele frequencies similar to other Caucasian populations. The sequencing of such DNAs confirmed the accuracy of the assays. In conclusion, we present three rapid and robust assays to detect the Arg702Trp, the Gly908Arg and the Leu1007fsinsC ins mutations in the NOD2/CARD15 gene [corrected]     

Latency variability and temporal interrelationships of the auditory event-related potentials (N1, P2, N2, and P3) in normal subjects

Peak latency variation and the temporal interrelationships of the auditory event-related potential were investigated in 12 normal adults (ages 28-42). Measures of variation were based on both conventional averages and single trials. Estimates of N1, P2, N2 and P3 latencies were made on a trial-by-trial basis to target stimuli recorded from Fz, Cz and Pz scalp locations. Results showed that single-trial latency variability of the auditory ERP differed both among the various components and between subjects. Larger standard deviations were measured for the later N2 and P3 components than the earlier N1 and P2 components. Regression analyses between various component latencies indicated a strong covarying relationship between N2 and P3, with N2 accounting for up to 61% of the variance of P3 latency at Pz. Earlier N1 and P2 components added little to the overall prediction of either P3 or N2. For the other components, P2 accounted for 9-16% of the variance of N2, while N1 accounted for approximately 1% of the variance of N2; N1 accounted for 8-10% of the latency variation of P2. The correlations between single-trial peak latencies and RTs were positive but of low magnitude. The highest correlations between peak latency and RT were found for N2 (r = 0.33) and P3 (r = 0.24). The low correlations between the single-trial latencies of N1 and P3 suggest that the processes reflected by these components are independent and support a distinction between the earlier and the later components of the ERP. The close temporal coupling between N2 and P3 suggests that N2 may reflect cognitive properties in common to P3 in stimulus evaluation processes.