The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1-receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 +/- 8), infarct size in candesartan-treated groups was smaller (59 +/- 5, 68 +/- 10, 28 +/- 3, and 15 +/- 3, respectively; P<0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 +/- 0.18, 1.80 +/- 0.13), other treatment regimens resulted in improved neuroscores (1.33 +/- 0.16, 1.11 +/- 0.11, 0.73 +/- 0.15; P<0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 +/- 0.09 mL x g(-1) x min(-1) and 44% +/- 7% of baseline compared with 0.49 +/- 0.06 mL x g(-1) x min(-1) and 37% +/- 6%, microspheres and laser-Doppler flowmetry; P<0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.     

Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies.

BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues experimentally. OBJECTIVES: To experimentally address the controversies concerning the correct way to record MAPs or calculate ARIs. METHODS: Left ventricular local electrograms were recorded in isolated pig hearts with an exploring electrode grid, with a KCl reference electrode on the left ventricular myocardium, the aortic root, or the left atrium. Local activation was determined from calculated Laplacian electrograms. RESULTS: With the KCl electrode on the aortic root, local electrograms represented local activation. However, with the KCl electrode on the myocardium remote from the exploring electrode, a combined electrogram emerged consisting of local activation recorded from the grid and remote activation recorded from the reference electrode. The remote, inverted monophasic component did not show propagation and did not correlate with the Laplacian complex. When the KCl electrode was placed on the atrium during AV block, remote atrial monophasic components were completely dissociated from local, ventricular deflections. At left ventricular sites with a positive T wave, the Laplacian signal showed that the end of the T wave was caused by remote repolarization. During cooling-induced regional action potential prolongation, the T wave became negative, whereby the positive flank of the T wave remained correlated with repolarization (recorded with a MAP at the same site). CONCLUSIONS: MAPs are recorded from the depolarizing electrode. In both negative and positive T waves, the moment of maximum dV/dt corresponds to local repolarization.     

Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy.

PURPOSE: To retrospectively review our experience with VNS in pediatric patients with pharmacoresistant epilepsy and examine the seizure-frequency outcome and rates of discontinuation in two age groups: adolescent and pre-adolescent children. RESULTS: Complete pre- and post-VNS data were available for 46/49 patients. Median age at implantation was 12.1 (range 2.3-17.9) and median duration of epilepsy 8.0 (1.9-16.9) years. Twenty-one patients (45.6%) were under 12 years at the time of surgery. Median follow-up was 2 years; follow-up exceeded 4 years in 9/46 patients. As compared to baseline, median seizure-frequency reduction in the setting of declining numbers was 56% at 3 months, 50% at 6, 63% at 12, 83% at 24 and 74% at 36 months. When a last observation carried forward analysis was employed median seizure-frequency reduction in the range of 60% was observed at 1, 2 and 3 years post-VNS. Twenty patients (43.5%) had >75% seizure-frequency reduction. No response (increase or <50% reduction) was observed in 19/46 (41.3%). Five patients (10.1%) were seizure-free for more than 6 months by their last follow-up. There was no difference in the number of AEDs used before and after VNS. The long-term discontinuation rate was 21.7% and reflected a lack of clinical response or infection. CONCLUSIONS: In this series VNS was well-tolerated and effective as add-on therapy for refractory seizures in children of all ages. Response was even more favorable in the younger group (<12 years at implantation). Infection and lack of efficacy were the most common reasons for discontinuation of long-term VNS therapy in this group.     

Bacillus Calmette-Guérin treatment and vesicorenal reflux

14 patients with radiologically documented vesicorenal reflux (5 bilateral, 7 unilateral, 2 unilateral double-J stents) received intravesical immunotherapy with bacillus Calmette-Guérin (BCG) after treatment of their superficial urothelial tumors. 1 patient with a double-J stent suffered a highly febrile attack following obstruction of the indwelling ureteral catheter. The other patients tolerated 1 or 2 (6 of 14 patients) courses of BCG without an increase in side effects. Topical intravesical therapy with BCG in patients with vesicorenal reflux seems to be indicated in view of the multicentricity of urothelial carcinoma and can be performed without an increased risk of complications.     

Reduced genital sensitivity in female patients with multiple system atrophy of parkinsonian type.

According to the consensus statement on the diagnosis of multiple system atrophy (MSA), erectile dysfunction is required for male patients to fulfil the urinary incontinence criterion. However, there is no equivalent item for female patients. We questioned 19 female patients with MSA of the parkinsonian type (MSA-P), 28 female patients with Parkinson's disease (PD), and 27 healthy controls on their genital sensitivity. A total of 47% of the MSA patients but only 4% of the PD patients and 4% of the control group admitted to reduced genital sensitivity, a highly significant difference (P < 0.001). Moreover, the appearance of reduced genital sensitivity in female MSA patients showed a close temporal relation to the onset of the disease. If these preliminary results can be confirmed and further specified in a larger sample, a historical item of reduced genital sensitivity in female patients might become a diagnostic feature for MSA, comparable to erectile dysfunction in male patients.     

Three-dimensional reconstruction of magnetic resonance images of the temporomandibular joint by I-DEAS.

Evaluation of the temporomandibular joint has been limited by the inability of current technology to image complex morphology and motion in three dimensions. An engineering design program, I-DEAS, has been used to construct solid models from magnetic resonance images. A dried skull with an acrylic resin temporomandibular disc replica, immersed in water, provided sagittal and coronal MR images. Linear dimensions and disc volumes obtained from the models were compared with the original and found to be consistent, within the limits imposed by the slice thickness. We have applied the method to the living joint in an asymptomatic volunteer, and report our initial experience in demonstrating the spatial relationships and motion of the joint components.     

Fusion and failure following anterior cervical plating with dynamic or rigid plates: 6-months results of a multi-centric, prospective, randomized, controlled study

Anterior cervical plate fixation is an approved surgical technique for cervical spine stabilization in the presence of anterior cervical instability. Rigid plate design with screws rigidly locked to the plate is widely used and is thought to provide a better fixation for the treated spinal segment than a dynamic design in which the screws may slide when the graft is settling. Recent biomechanical studies showed that dynamic anterior plates provide a better graft loading possibly leading to accelerated spinal fusion with a lower incidence of implant complications. This, however, was investigated in vitro and does not necessarily mean to be the case in vivo, as well. Thus, the two major aspects of this study were to compare the speed of bone fusion and the rate of implant complications using either rigid- or dynamic plates. The study design is prospective, randomized, controlled, and multi-centric, having been approved by respective ethic committees of all participating sites. One hundred and thirty-two patients were included in this study and randomly assigned to one of the two groups, both undergoing routine level-1- or level-2 anterior cervical discectomy with autograft fusion receiving either a dynamic plate with screws being locked in ap - position (ABC, Aesculap, Germany), or a rigid plate (CSLP, Synthes, Switzerland). Segmental mobility and implant complications were compared after 3- and 6 months, respectively. All measurements were performed by an independent radiologist. Mobility results after 6 months were available for 77 patients (43 ABC/34 CSLP). Mean segmental mobility for the ABC group was 1.7 mm at the time of discharge, 1.4 mm after 3 months, and 0.8 mm after 6 months. For the CSLP- group the measurements were 1.0, 1.8, and 1.7 mm, respectively. The differences of mean segmental mobility were statistically significant between both groups after 6 months (P = 0.02). Four patients of the CSLP-group demonstrated surgical hardware complications, whereas no implant complications were observed within the ABC-group (P = 0.0375). Dynamic plate designs provided a faster fusion of the cervical spine compared with rigid plate designs after prior spinal surgery. Moreover, the rate of implant complications was lower within the group of patients receiving a dynamic plate. These interim results refer to a follow-up period of 6 months after prior spinal surgery. Further investigations will be performed 2 years postoperatively.