Effect of Vigabatrin on the Electroencephalogram in Rats

Vigabatrin (gamma-vinyl GABA; GVG) is a new antiepileptic drug (AED) that increases the level of the inhibitory transmitter, gamma-aminobutyric acid (GABA) in the brain. We evaluated the effect of GVG on the EEG of normal rats. GVG was administered intraperitoneally (i.p.) at a dose of 100 mg/kg once a day for 12 days. EEG was recorded at baseline, on the fourth day, at the end of the 12-day GVG period and 10 days after discontinuation of GVG. GVG increased the amplitude of delta (1-4 Hz) and theta (4-8 Hz) frequency bands and resulted in slowing of the peak frequency (Fp) and mean frequency (Fm) in both the frontal and occipital cortex, especially during waking-immobility. EEG changes normalized within 10 days after the last GVG injections. The results suggest that a relationship may exist between the EEG changes and increase in GABA levels with GVG.     

Healing the vasculature: angioprotective therapy moves from the bench to the clinic

Advances in immunosuppression have extended the lifetime of most types of organ grafts, leading to improved long-term outcomes after transplantation. The fact that death of the transplant patient with a functioning graft currently represents the leading cause of late graft loss is sometimes viewed as testament to this success. However, this interpretation is misleading because patient death often results from the systemic effects of immunosuppressive treatment. Prominent among the latter are atherosclerosis, infection, and malignancy. Vascular disease, manifesting as transplant arteriopathy, also contributes to chronic allograft failure, another major cause of late graft loss. Overall, arteriosclerosis (systemic and graft specific) accounts for about 50% of late graft loss, making it a compelling therapeutic priority that has yet to be effectively tackled in the clinic. The advent of novel immunosuppressive compounds with angioprotective properties and a tighter control of metabolic risk factors for vascular disease have the potential to overcome this obstacle and further improve transplant outcomes. Targeted modulation of growth factor and hormone receptor activity by nonimmunosuppressive, low-molecular-weight compounds represents a complementary approach to this problem. Here we trace the development and assess the potential of the most promising angioprotective therapies currently in, or approaching, the clinic and outline a structured rationale for their efficient evaluation.     

Vortex Shaped Current Sources in a Physical Torso Phantom

Recent studies reported differential information in human magnetocardiogram and in electrocardiogram. Vortex currents have been discussed as a possible source of this divergence. With the help of physical phantom experiments, we quantified the influence of active vortex currents on the strength of electric and magnetic signals, and we tested the ability of standard source localization algorithms to reconstruct vortex currents. The active vortex currents were modeled by a set of twelve single current dipoles arranged in a circle and mounted inside a phantom that resembles a human torso. Magnetic and electric data were recorded simultaneously while the dipoles were switched on stepwise one after the other. The magnetic signal strength increased continuously for an increasing number of dipoles switched on. The electric signal strength increased up to a semicircle and decreased thereafter. Source reconstruction with unconstrained focal source models performed well for a single dipole only (less than 3-mm localization error). Minimum norm source reconstruction yielded reasonable results only for a few of the dipole configurations. In conclusion active vortex currents might explain, at least in part, the difference between magnetically and electrically acquired data, but improved source models are required for their reconstruction.     

Expression kinetics and subcellular localization of HIV-1 regulatory proteins Nef,Tat and Rev in acutely and chronically infected lymphoid cell lines

Summary Information concerning the expression kinetics and subcellular localization of HIV regulatory proteins is of importance in understanding the viral pathogenesis and may be relevant for drug and vaccine development, as well. We have used combined immunocytochemistry and in situ hybridization to study firstly, the order of expression of regulatory HIV-1 proteins Nef, Rev and Tat in relation to non-spliced and spliced mRNA expression and secondly, the subcellular localization of these proteins in acutely and chronically infected human T-cell lines. We used monoclonal antibodies against HIV-1 Nef, Tat, Rev and gp160, and RNA probes reacting either with all mRNAs (nef) or only with the full-length mRNA (gag-pol). In acutely infected MT-4 and H9 cells, four distinct phases of infection could be defined. In the first phase lasting from 0 to 6 h post-infection, only incoming virus could be demonstrated by gp160 immunocytochemistry. During the second, regulatory phase (6–9 h), abundant cytoplasmic expression of Nef, Rev and Tat proteins and a positive in situ RNA hybridization with the nef probe was seen, while the in situ hybridization with full-length mRNA probe and immunohistochemistry for gp160 were still negative. The productive phase (12–48 h) was characterized by abundant expression of full-length mRNA and gp160, and by the nuclear localization of Nef and Tat proteins. In contrast, an antibody that recognized the RRE binding region of the Rev protein localized Rev in the cytoplasm both during the regulatory and productive phase. During the fourth, cytopathic phase, the expression of mRNA or viral proteins decreased and the regulatory proteins studied were again mainly localized in the cytoplasm. Based on the results, we speculate that HIV Nef may function as a nuclear factor, and that Tat is possibly bound by cellular proteins before its transport to the nucleus.     

Personal Values that Support and Counteract Utilization of a Screening Test for Prostate Cancer

The main aim of the current research was to discover the personal values that may support men's prostate cancer screening decisions in the future. We asked for participants’ past behavior and future behavioral intentions, and also considered their real-life behavior. The sample consisted of 371 men, of which 93 were first-time patients at the Andrology Unit. The results show that Security value was related to past participation, while Achievement, Stimulation, and Traditions counteracted this. Present prostate-testing behavior was related only to higher Security values. Predictors of future behavioral intentions were Security, Self-direction, and Benevolence, which described 21% of the total variability. Considering informed decision-making processes, our results suggest that men who hold Security, Self-direction, and Benevolence values are more likely to participate in office-based initial screening. The study indicates the need to offer office-based initial screening to those age-eligible men whose values do not support participation.     

Self-reported health-related quality of life of children and adolescent survivors of extracranial childhood malignancies: a Finnish nationwide survey

Purpose  

The purpose of this Finnish total cohort survey was to assess and compare the self-reported health-related quality of life (HRQL) in childhood cancer survivors to that of matched controls, to analyse demographic and disease-related factors explaining survivors’ HRQL, and to compare the results of two different HRQL instruments, 16D/17D and PedsQL™.     

Late QRS Activity in Signal‐Averaged Magnetocardiography,Body Surface Potential Mapping,and Orthogonal ECG in Postinfarction Ventricular Tachycardia Patients

Background: Delayed electrical activity necessary for re‐entrant ventricular tachycardia (VT) is detectable noninvasively with high resolution techniques. We compared high resolution signalaveraged analysis of magnetocardiography (MCG), body surface potential mapping (BSPM), and orthogonal three‐lead ECG (SA‐ECG) in the identification of patients prone to VT after myocardial infarction (Ml). Methods: Patients with remote myocardial infarction and cardiac dysfunction were studied, 22 with (VT group) and 22 without VT (control group). MCG with seven channels and BSPM with 63 and SA‐ECG with three orthogonal leads were registered. After signal‐averaging and highpass filtering, three time domain analysis (TDA) parameters describing late electrical activity were computed: QRS duration (QRSd), root mean square amplitude (RMS) of the last 40 ms of QRS, and the duration of the low‐amplitude QRS end (LAS). Results: All parameters by each method were significantly different between the patients’groups. For example, LAS parameter in MCG was 59 (SD 22) ms in the VT group vs. 37 (SD 13) ms in controls (P < 0.001), 77 (SD 22) ms vs. 56 (SD 19) ms in BSPM (P = 0.002), and 60 (SD 24) ms vs. 39 (SD 22) ms in SA‐ECG (P = 0.005). The combination of LAS parameter in MCG and SA‐ECG resulted in improved performance in comparison to any single parameter with 95% sensitivity and 68% specificity. Conclusions: All three high resolution methods identified VT propensity among post‐Mi patients with cardiac dysfunction and between‐method differences were small. Information in MCG and SA‐ECG may be complementary and their combination could be of value in postinfarction arrhythmia risk assessment. A.N.E. 2002;7(4):389–398     

Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer.METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as “front-positive” and in 41% as “front-negative”. The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the “front-positive” tumors.CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.