Neuronal activity-induced regulation of Lingo-1

Axonal regeneration after injury can be limited in the adult CNS by the presence of inhibitory proteins such as Nogo. Nogo binds to a receptor complex that consists of Nogo receptor (NgR), p75NTR, and Lingo-1. Nogo binding activates RhoA, which inhibits axonal outgrowth. Here we assessed Lingo-1 and NgR mRNA levels after delivery of BDNF into the rat hippocampal formation, Lingo-1 mRNA levels in rats subjected to kainic acid (KA) and running in running wheels. Lingo-1 mRNA was not changed by running. However, we found that Lingo-1 mRNA was strongly up-regulated while NgR mRNA was down-regulated in the dentate gyrus in both the BDNF and the KA experiments. Our data demonstrate inverse regulation of NgR and Lingo-1 in these situations, suggesting that Lingo-1 up-regulation is one characteristic of activity-induced neural plasticity responses.     

Vitamin K status in cystic fibrosis

Appearance of PIVKA-II (protein induced by vitamin K absence-II) in serum is a biochemical sign of insufficient vitamin K-dependent carboxylation of prothrombin. Plasma concentrations of PIVKA-II and vitamin K1 were determined in 24 children with cystic fibrosis. Eight were supplemented with vitamin K1. The purpose of the study was to determine the occurrence of vitamin K deficiency in cystic fibrosis and to evaluate the effect of vitamin K supplementation. PIVKA-II was detectable in only one unsupplemented child. In this patient, the concentration of vitamin K1 was below the limit of detection of 60 ng/l. Vitamin K1 levels in the other unsupplemented children were normal (mean 476 ng/l = 1 mmol/l). The supplemented patients showed extremely high levels of vitamin K1 (mean 22445 ng/l = 50 nmol/l). In conclusion, vitamin K deficiency occurs infrequently in cystic fibrosis. Checking the coagulation system is advised, but routine vitamin K supplementation is not recommended. If additional vitamin K is needed, the starting dose should not exceed 1 mg daily.     

Determinants of transstenotic gradients observed during angioplasty: An experimental model

Pressure gradient measurement across a stenosis is used during angiopiasty to aid catheter positioning and estimate dilatation efficacy. The angiopiasty catheter itself, however, further reduces lumen size, and therefore augments the transstenotic gradient. To more precisely define the catheter influence on gradient, we derived a theoretical expression relating the measured gradient with the angiopiasty catheter in situ to the “true” gradient; that is, the gradient in the absence of the angiopiasty catheter. We then tested this theoretical construct in a canine femoral artery angiopiasty model. Fifty-four measurements were performed using 23 separate, 3-mm-long, 40 to 70% stenoses. As predicted by the theoretic model, “true” gradient is compounded by the angiopiasty catheter principally as a function of the angiopiasty catheter diameter (Dc) and the stenosis diameter (Ds). The best-fit curve of data points relating “true” and compounded gradients to various Dc and Ds combinations can be expressed as: Measured GRADIENT = K × true gradient, where K = 0.25 (e)^4.47 (Dc÷Ds and e = 2.718. Thus, the transstenotic gradient measured at angiopiasty overestimates “true” resting gradient in a predictable manner, which is dependent on the ratio of Dc to Ds.     

Follow-up of kidney graft recipients with cyclosporine-associated hemolytic-uremic syndrome and thrombotic microangiopathy

The study was based on 462 patients who underwent kidney transplantation from 1986 through 2004. Cyclosporine (CsA)-related thrombotic microangiopathy (TMA) was observed in 15 (3.3%) patients. The donor ages ranged from 9 to 51 years and cold ischemia times from 12 to 31 hours. Hemolytic-uremic syndrome (HUS) developed 2 weeks after transplantation in 14 patients and later in 1 subject. Histopathologic examination demonstrated glomerular-type TMA in 3 patients, a mixed type (glomerular and vascular) in 11 patients, and a nonspecific mesangial widening with tubulointerstitial lesions in 1 patient. Follow-up biopsies revealed resolution of TMA in 4 patients and chronic vascular TMA in 1 patient. Six patients with mixed-type TMA needed transient hemodialysis. No patient with the glomerular-type TMA needed dialysis (P = .103), and 14 of 15 had good resolution of graft function after CsA dose reduction or temporary discontinuation or continuation of optimal dose. Only 1 graft with mixed-type TMA was lost due to irreversible HUS. The mean glomerular filtration rate (GFR), predicted by the Nankivell equation, was 76 +/- 13 mL/min and 80 +/- 27 mL/min at 1 month after discharge for glomerular- and mixed-type TMA, respectively (P > .05). GFRs 1 year after HUS were 82 +/- 12 and 87 +/- 21 mL/min for the glomerular and the mixed types, respectively (P > .05). We concluded that the mixed-type TMA was associated with a more severe early clinical course than the glomerular-type TMA. The 1-year prognosis was good in the majority of patients, with no significant differences between those with the glomerular- and mixed-type TMA.     

Recurrence of atrial tachyarrhythmias in implantable cardioverter-defibrillator recipients

BACKGROUND: Because the natural history of atrial tachyarrhythmia (AT) is not known in patients with implantable cardioverter-defibrillators (ICDs) but without device-based atrial therapies, we aimed to describe the characteristics and recurrence of AT in such patients. METHODS: In this multicenter trial, 269 patients with standard indications for ICD placement and 2 episodes of AT in the preceding year received a dual-chamber ICD capable of logging AT. Patients were randomly assigned to 3-month periods of atrial therapies "on" or "off." This analysis considered only the 118 patients with atrial therapies programmed off at ICD placement. RESULTS: Fifty-eight patients (49%) had at least 1 AT episode longer than 1 minute, and 21 (18%) had at least 1 prolonged episode (>24 hours). The median episode frequency for each patient (episodes per month) was 1.8 episodes longer than 1 minute, 0.8 longer than 1 hour, and 0 longer than 24 hours. The median AT burden was 12.2 hours per month. CONCLUSIONS: Patients with standard ICD indications and history of AT have infrequent episodes, frequent short episodes, or prolonged episodes of AT-atrial fibrillation. However, the clinical characteristics examined did not distinguish among the groups. Improved diagnostic tools may help identify patients at risk for development of AT, thereby allowing specific therapies to be targeted to each group of patients.     

Shape of the left ventricle and its computer modelling

A simple computer program was made to draw different left ventricle shapes in order to support the theory of elongation and to get a visual presentation of the shape of the left ventricle. Experimental data, obtained from echocardiography and Simpson's rule, were used for this program. The results yielded different shapes under different physiological circumstances, indicating the sensitivity of the method. It was concluded that these figures (shapes) support the use of elongation as a shape index.