Differential involvement of the human temporal lobe structures in short- and long-term memory processes assessed by intracranial ERPs

Intracranial event-related potentials (ERPs) elicited during a recognition memory task were recorded in 25 epileptic patients by using depth electrodes sampling four different regions within the temporal lobe (amygdala, hippocampus, anterior and posterior temporal cortices). The task was a continuous recognition memory task in which repeated items were presented after 6 or 19 intervening items following their first presentation. This study was performed to investigate the respective role of the different temporal lobe structures in short-term memory (STM) and long-term memory (LTM) processing. Subregions of the temporal lobe were differently involved in these two memory systems. The posterior temporal cortex is specifically involved in STM processing, whereas the amygdala, hippocampus, and anterior temporal cortex contribute to both STM and LTM. Moreover, it appeared that the latter structures play their own role in LTM. The anterior temporal cortex and amygdala may contribute to recency discrimination, and the hippocampus seems rather to be involved in maintaining memory traces. These findings suggest that the temporal lobe structures may function in a complementary way by subserving different aspects of information processing.     

Synthesis,biological activity and conformational analysis of cyclic GRF analogs

A novel cyclic GRF analog, cyclo(Asp⁸-Lys¹²)-[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂, i.e. cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂, was synthesized by the solid phase procedure and found to retain significant biological activity. Solid phase cyclization of Asp⁸ to Lys¹² proceeded rapidly (～2h) using the BOP reagent. Substitution of Ala¹² with d -Ala² and/or NH₂-terminal replacement (desNH₂-Tyr¹ or N-MeTyr¹) in the cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ system resulted in highly potent analogs that were also active in vivo. Conformational analysis (circular dichroism and molecular dynamics calculations based on NOE-derived distance constraints) demonstrated that cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ contains a long α-helical segment even in aqueous solution. A series of cyclo^8.12 stereoisomers containing d -Asp⁸ and/or d -Lys¹² were prepared and also found to be highly potent and to retain significant α-helical conformation. The high biological activity of cyclo^8.12[N-MeTyr¹,d -Ala²,Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ may be explained on the basis of retention of a preferred bioactive conformation.     

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in athletes. Blood sampling and doping control

1 The pharmacokinetics of recombinant human erythropoietin (rHuEpo) were initially determined in two healthy volunteers after a single subcutaneous dose (50  u  kg⁻¹). Twenty subjects then received repeated subcutaneous administrations of high dose (200  u  kg⁻¹) rHuEpo and 10 subjects received placebo. An immunoradiometric assay was used to measure the concentrations of erythropoietin (Epo) in serum and urine.
2 Serum Epo concentration-time profiles were best described by a one-compartment open model with zero-order input. The mean elimination half-life (±s.d.) was 42.0±34.2  h. Clearance, uncorrected for bioavailability, was 0.05±0.01  l  h⁻¹  kg^{& minus;1}. Erythropoietin concentrations returned to normal values in serum and urine, 7 and 4 days after the last administration, respectively.
3 The recombinant hormone was well tolerated. Significant changes in reticulocytes and red blood cells, haemoglobin concentrations and haematocrit were observed after administration of rHuEpo. In the control group, these parameters remained unchanged.
4 The change in reticulocytes was used as an index of the therapeutic effect of rHuEpo. The concentration-effect relationship was best described by an exponential model.
5 These data show the limitations of the measurement of Epo concentrations in blood and urine samples, collected in athletes during competition, for antidoping control. Epo doping can be detected only during or within 4 to 7 days of ending, a course of rHuEpo.     

CD44 IS AN INDEPENDENT PROGNOSTIC FACTOR IN CONVENTIONAL RENAL CELL CARCINOMAS

PURPOSE: CD44 is a transmembrane glycoprotein involved in cell-cell and cell-matrix interactions. De novo expression of CD44 and its variant isoforms has been associated with aggressive behavior in various tumors. Since few data are available concerning the role of CD44 in the biological behavior of locally confined renal tumors, we analyzed the expression of CD44 in a large set of conventional renal cell carcinomas to determine its prognostic value in association with other clinicopathologic variables. MATERIALS AND METHODS: Ninety-one patients with locally confined conventional renal cell carcinomas were studied. CD44 standard form (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin-embedded tumor tissue by immunohistochemistry. The prognostic value of the usual clinicopathological variables and CD44 expression was tested using Kaplan-Meier plots by the log rank test and Cox multiple hazard regression analysis. RESULTS: No immunostaining was observed in normal renal tissue. Thirty-two of the 66 conventional renal cell carcinomas (48%) showed CD44H membranous staining of the tumor cells. Only 2 cancers displayed CD44v6 immunostaining. Among the different clinicopathological variables analyzed, tumor stage (p = 0.001), nuclear grade (p = 0.01), size (p = 0.02), vascular (p = 0.05) and perirenal adipose tissue invasion (p = 0.005), and CD44H expression (p = 0.01) were found to be significant prognostic parameters for survival using univariate analysis. Moreover, multivariate analysis indicated stage, nuclear grade and CD44 expression as independent prognostic factors both for overall and disease-free survival. CONCLUSION: CD44 can be considered as a useful prognostic parameter in conventional renal cell carcinoma and may be used in evaluation of the outcome of these tumors.     

Entrainment of Typical AV Nodal Reentrant Tachycardia Using Para-Hisian Pacing:

INTRODUCTION: Despite the ability to cure atrioventricular nodal reentrant tachycardia (AVNRT) by radiofrequency catheter ablation with a high success rate, the exact localization of the tachycardia circuit is still not well established. The presence of AV nodal tissue between the typical AVNRT circuit and the His bundle, constituting a lower common pathway (LCP), remains controversial. METHODS AND RESULTS: Entrainment of AVNRT during para-Hisian stimulation allows accurate measurement of the His- to- atrial (HA) interval which is part of the same circuit as that of the tachycardia. With an LCP, during tachycardia, there is simultaneous conduction from the low turnaround of the circuit to the atrium (via the fast pathway) and to the His bundle (via the LCP). However, during entrainment by para-Hisian pacing, the impulse has to retrogradely depolarize sequentially the LCP and the fast pathway. Therefore, in the presence of an LCP, the HA interval duration during tachycardia (HAt) should be shorter than that of during entrainment by para-Hisian stimulation (HAe). We considered an LCP present when Hae - HAt was > or = 10 msec. Entrainment of typical AVNRT with para-Hisian stimulation was performed in 23 consecutive patients (21 females) with a mean age of 45+/-17 years. LCP was considered to be present in 18 of 23 patients (78%). In addition, transient His-bundle dissociation from the ongoing tachycardia occurred in seven patients (30%). CONCLUSION: These results support the presence of a LCP during typical AVNRT.     

Update on Interventions in Renal Artery Stenosis

Noninvasive techniques such as ultrasound and renal scanning have improved the frequency of detection of renal artery stenosis in patients with arterial hypertension, renal insufficiency, or multivascular disease. The results of conventional balloon angioplasty on nonostial renal artery stenoses caused by fibromuscular dysplasia or atherosclerosis showed a high recurrence rate and a moderate impact on the management of hypertension. In patients with ostial lesions, the results of angioplasty were disappointing with low initial success rates and a high rate of restenosis. Other limitations of balloon angioplasty include initial failure or suboptimal result, occluding dissection, and short- or mid-term restenosis. The immediate procedural results of renal artery stenting are excellent, with a low complication rate and satisfactory restenosis rate. Long-term effects on renal function and blood pressure seem to be good. Systematic stent placement is indicated for ostial stenosis. For nonostial lesions, the indication for stent placement may be reserved for residual stenosis or dissection. The indication for a stent would probably be more liberal in cases of bilateral lesions or lesions in a solitary kidney. Multicenter studies probably will be needed to assess the indications and benefits obtained in different clinical and anatomical situations.     

Update on Percutaneous Mechanical Mitral Commissurotomy

A reusable metallic valvotomy device has been developed with the goals of improving the results of percutaneous mitral valvotomy and increasing the cost-effectiveness of the procedure. The device consists of a detachable and reusable metallic dilator with two articulated bars screwed at the distal end of a catheter. Using transseptal catheterization, the device is placed across the valve over a traction guidewire and then opened gradually by means of pliers up to a maximum of 40 mm. To date, the device was used in 168 patients with a broad spectrum of mitral valve disease. The procedure was successful in 95% of cases and resulted in an increase in mitral valve area from 1.01 ± 0.8 to 2.20 ± 0.7 cm². No increase in mitral regurgitation was noted in 87% of cases. Bilateral splitting of the commissures was observed in 89%. Complications included the following: 2 severe mitral regurgitations (one requiring surgery), 1 pericardial tamponade, 1 transient cerebrovascular embolic event. The maximum number of consecutive patients treated with the same device was 35. The results obtained are at least comparable to those of current balloon techniques and confirm the possibility of safe multiple reuses of the device after sterilization.     

Underdetection of Ventricular Tachycardia Using a 40 ms Stability Criterion: Effect of Antiarrhythmic Therapy

Inappropriate shocks can complicate cardioverter defibrillator therapy. Among solutions proposed to avoid oversensing are algorithms to reduce inappropriate detection of atrial fibrillation (AF) or sinus tachycardia. In patients not on antiarrythmic drugs, an interval stability criterion of 40 ms has been validated with the Medtronic PCD to discriminate ventricular tachycardia (VT) from AF. With this algorithm, VT is considered stable if no interval varies from one of the three preceding in tervals by more than 40 ms. If an interval does not fulfill this criterion, the VT event counter is reset to zero. The aim of this study was to investigate the incidence of underdetection when this criterion is ap plied in patients treated with antiarrhythmic drugs. We studied 132 sustained monomorphic VTs induced in 42 patients during 101 electrophysiological studies (EPS). EPS were performed without treatment (group I. 24 patients, 44 VTs); on Class Ia drug (group II, 17 patients, 24 VTs); Class Ic drug (group III, 22 patients, 39 VTs); or sotalol (group IV, 17 patients, 25 VTs). The endocardial electrogram of all VT episodes was digitized and the stability algorithm was applied. The reset arrhythmias were distributed among no delay, small, moderate (<10 s) and important (>15 s) delay in VT detection. The relation be tween drug use and reset was analyzed. Beset was found in 86 (65%) of induced VTs. No difference in heart rate or induction mode was shown between reset and nonreset VTs. There was a significative asso ciation between drag use and reset probability (Chi² significantly different, P < 0.05). In patients treated with Class Ic drugs, the probability of finding an important delay in VT detection was 12.5% versus 0% in nontreated patients or in patients treated with sotalol. We conclude that a stability criterion of 40 ms is probably safe in nontreated patients but should be used with caution in patients treated with antiarrhythmics, especially in the presence of Class Ic drags.     

Percutaneous Implantation of Aortic Valve Prosthesis in Patients with Calcific Aortic Stenosis: Technical Advances, Clinical Results and Future Strategies

To date, one third of patients with symptomatic aortic stenosis are not operated on because of advanced age, depressed left ventricular function, or comorbidities. Whereas balloon aortic valvuloplasty can be used as a palliative treatment in this population, the hemodynamic and clinical benefits of the procedure are only temporary. With the goal of offering to this subset of patients a nonsurgical therapeutic option with improved results and longer term positive outcomes, we developed a percutaneous implantable bioprosthetic heart valve able to be inserted within the native diseased aortic valve using cardiac catheterization techniques. The first human implant was performed by our group in April 2002 using the antegrade transeptal approach. Since then, we have implanted the valve on compassionate basis in a series of nonsurgical elderly patients with end-stage aortic stenosis and multiple comorbidities, all declined by cardiac surgeons for valve replacement. This article describes the technical improvements of the device and implantation protocols, provides clinical results of the first series of patients, and outlines strategies for future development of the percutaneous heart valve.