Acute vagus nerve stimulation does not suppress spike and wave discharges in genetic absence epilepsy rats from Strasbourg

We evaluated the efficacy of vagus nerve stimulation (VNS) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a validated model for absence epilepsy. In the first experiment, we investigated whether VNS applied at seizure onset can interrupt spike and wave discharges (SWD). In the second experiment, we investigated whether SWD are suppressed or shortened in duration when VNS is applied several hours per day. Both control and VNS groups underwent EEG and VNS electrode implantation. For the first experiment, a randomized crossover design was used. Stimuli (amplitude: 3 V; frequency: 30 Hz; pulse duration: 500 micros) were given when an SWD occurred on the EEG. The experiment was repeated the next day. In the second experiment, treated animals were stimulated (amplitude: 1.5 mA; frequency: 30 Hz; pulse duration: 500 micros; on/off time cycle: 30 s / 5 min) for 3h per day, during five consecutive days. In the first experiment, the duration of the SWD was increased on day 1, (P < 0.05). There was no difference in SWD duration on Day 2. In the second experiment, no significant differences could be found in number, duration and EEG frequency of SWD. VNS applied at the onset of an SWD can prolong the duration of SWD in GAERS. As a 5-day stimulation protocol had no effect, long-term VNS might be necessary to affect SWD.     

Contribution of sex differences in the acute stress response to sex differences in water maze performance in the rat

Male rats outperform females in spatial tasks, such as the water maze (WM). Female rats are known to have higher basal serum corticosterone (CORT) levels and to manifest a more rapid and stronger CORT response to novel stressors. Sex differences in stress responses to the handling and forced swimming in the WM task might contribute to the sex difference in WM performance. In Experiment 1, naive females were found to be impaired relative to naive males in swimming to a visible platform in a WM pool due to strongly thigmotaxic swimming by females. In Experiment 2, serum CORT, a physiological measure of stress, was highly elevated during and after WM training, with female > male values and strong inverse correlations between CORT and measures of WM performance in females. Familiarization with the WM pool and test procedures by strategies pretraining prior to spatial training reduced or eliminated the sex differences in the stress response and WM performance. In Experiment 3, adrenalectomy to eliminate the stress response eliminated sex differences in WM performance. Taken together, the results suggest that male and female rats may harbor brain circuitry that is equally capable of accurate spatial navigation and memory in the WM but which may be impaired to different degrees by the differential stress responses triggered by WM testing.     

The radiologic appearance of intercostal muscle flap

Background

The intercostal muscle flap (ICMF) is commonly used in airway and esophageal surgery to reinforce an anastomosis or site of closure. These flaps undergo heterotopic ossification that may result in stenosis of adjacent airways or the esophagus. We evaluated the computer tomography (CT) scan, technetium-99m-methylene diphosphonate bone scan and positron emission tomography with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG-PET) findings of ICMF and the frequency of airway or esophageal stenosis.

Methods

A retrospective review was made of the radiologic records of 23 patients (9 women, 14 men) who underwent ICMF. The CT scans were obtained a mean of 36 months (range, 1 week to 58 months) after surgery and the size, morphology, and density of the ICMFs were recorded. Correlative bone scan in 13 patients and FDG-PET scans in 11 patients were reviewed.

Results

A discontinuous, thin, linear calcified stripe or parallel stripes (mean thickness, 4 mm; mean density, 430 Houndsfield unit [HU]) were present in all patients on CT. The flap contained fat density (mean, −59 HU) in 18 patients and soft tissue density (mean, 41 HU) in 8 patients and measured about 1 cm in thickness. The appearance of ICMF is characteristic when the ossification extends from the posterolateral chest wall to an adjacent bronchial stump. There was no increased uptake on bone scan or FDG-PET scan. None of the patients had airway or esophageal stenosis.

Conclusions

The ICMF manifests on CT as a thin, linear calcified stripe or parallel stripes with central fat or soft tissue density. Airway stenosis due to ICMF is likely quite rare. We did not detect any airway stenosis.     

Needle EMG of abductor hallucis and peroneus tertius in normal subjects

Normal values for standard concentric-needle electromyography (EMG) of the abductor hallucis (AH) and peroneus tertius (PT) muscles have not been established to date, yet both are potentially useful muscles in the diagnosis of length-dependent peripheral nerve disorders. Forty-three normal asymptomatic subjects stratified by age underwent a standard set of nerve conduction studies and concentric-needle examination to exclude asymptomatic disease and develop normal values for the AH and the PT for various EMG parameters. Fibrillation potentials were observed in the AH in 21% of normal subjects (10% < 60 years old, 30% > 60 years old); 19% of subjects were unable to voluntarily activate the AH. All subjects could activate the PT regardless of age. No fibrillation potentials were observed in subjects < 60 years of age, whereas 9% of those older than 60 years had mild fibrillation potentials in the PT. The PT is a useful muscle in the evaluation of length-dependent peripheral neuropathy and other peripheral nerve disorders of the lower extremities, on the basis of ease of motor unit potential activation and analysis, and relative infrequency of fibrillation potentials in normal subjects.     

Neurostimulation for refractory epilepsy

Neurostimulation is an emerging treatment for refractory epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond to such a treatment and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing vagus nerve stimulation (VNS). Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Deep brain stimulation (DBS) for epilepsy has regained interest. Central nervous system structures known to play a key role in the epileptogenic network such as the thalamus and subthalamic nucleus have been targeted. Another approach is to target the ictal onset zone such as the medial temporal lobe. At Ghent University Hospital 10 patients have been treated with long-term amygdalohippocampal DBS. Several hypotheses have been raised for the mechanism of action of DBS for refractory seizures. Seizure reduction may be due to a microlesion caused by electrode insertion or by provoking a reversible functional lesion due to the effect of electrical current on hyperexcitable tissue. Neurophysiological techniques such as evoked potentials monitoring and intraoperative single unit potential recordings may guide correct electrode placement, individual DBS titration and elucidation of the mechanims of action of DBS for epilepsy.     

Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report

Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3 protein combined with a fixed dose of the immunological adjuvant SBAS-2, which contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.) injections at 3-week intervals. Patients whose tumour stabilised or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The vaccine was generally well tolerated. Among the 33 melanoma patients who were evaluable for tumour response, we observed 2 partial responses, 2 mixed responses and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29 months. In addition, a partial response lasting 10 months was observed in 1 of the 3 metastatic bladder cancer patients included. None of the tumour responses described above involved visceral metastases. Immunological responses to the vaccine will be reported separately.     

Expression of mage genes in transitional-cell carcinomas of the urinary bladder

Human genes MAGE-1 and MAGE-3 code for distinct antigens, which are recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). These antigens may constitute useful targets for anti-cancer immunotherapy, since no expression of MAGE genes has been observed in normal tissues other than testis. Out of 57 samples of primary transitional-cell carcinomas of the bladder, 12 (21%) expressed MAGE-1 and 20 (35%) expressed MAGE-3. All but one of the tumors expressing MAGE-1 also expressed MAGE-3. Genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3, were expressed by 30% and 33% of the tumors respectively. MAGE expression was more frequent in advanced tumor stages: 61% of the invasive tumors (stage ± T2) were positive for expression of at least one of the four genes, whereas only 28% of the superficial tumors (stages Ta and Tl) expressed these genes. © 1995 Wiley-Liss, Inc.     

Prognostic factors in localised prostate cancer with emphasis on the application of molecular techniques

Prostate cancer is the most prevalent malignancy in males in the Western world and the second leading cause of male cancer death. Prostate specific antigen (PSA) based screening and case finding leads to identification of early stage prostate cancer. It is often difficult to discriminate between patients that need curative treatment and those that can be managed conservatively. Prognostic factors are used to make this clinical decision.Based on the classification proposed by the American College of Pathologists and the World Health Organisation, selected prognostic factors in prostate cancer are described. Clinical applicable factors are stage, grade and serum PSA. Prognostic factors that are not routinely used (for various reasons) are ploidy, histological type and cancer volume in needle biopsies. All other factors (including circulating tumour cells, angiogenesis, growth factors, proliferation rate, apoptosis, nuclear morphometry, neuroendocrine differentiation, loss of chromosomal regions, tumour suppresser genes and adhesion molecules) are promising as prognostic factor although currently their use in clinical decisions is not recommended. The role of these factors in prostate cancer growth and their predictive value are discussed.The rapid developments in molecular techniques allow assessment of structure or function of thousands of genes in a prostate biopsy sample. We expect that molecular characterisation of tumour material will become a clinically important tool to predict prognosis in patients with localised prostate cancer.     

Diagnostic value of simultaneous non-invasive continuous,ambulatory finger blood pressure and electrocardiogram monitoring in a patient with hypertrophic obstructive cardiomyopathy

BACKGROUND: The pathophysiology of hypertrophic obstructive cardiomyopathy (HOCM) is complex and heterogeneous, and it may be difficult to disentangle the various pathophysiologic properties leading to complaints. OBJECTIVES: To elucidate the sequence of acute pathophysiologic changes leading to complaints in a patient with HOCM. METHODS: Cardiopres measurements [the combination of non-invasive, continuous finger artery blood pressure monitoring, and three-lead electrocardiogram (ECG) recordings] were performed during physiologic, supine exercise--before and after replacement of metoprolol by verapamil. Within 24 h of the Cardiopres measurement standard Doppler echocardiography was performed. Finger artery pressure wave was analysed using Beatscope software (BMI-TNO, Amsterdam, The Netherlands), ST analysis was performed with H-Scribe (Mortara Instrument, Bilt, The Netherlands). RESULTS: Exercise under metoprolol: finger BP decreased from 130/65 mmHg to 90/60 mmHg, heart rate increased from 65 bpm to 100 bpm and ST analysis revealed significant ST depression in all leads. The occurrence of ST depression preceded the hypotension. Echocardiography showed a dynamic gradient of 70 mmHg. Exercise under verapamil: the patient had less complaints, BP increased from 125/60 mmHg to 165/65 mmHg, heart rate increased from 75 bpm to 107 bpm and ST analysis showed no ST depression > 1 mm. Echocardiography showed no change. CONCLUSIONS: The use of the Cardiopres during a physiological stimulus showed improvement in exercise capacity in a patient with HOCM, while the standard test, stress-echocardiography, showed no correlation with clinical status. The Cardiopres is a useful diagnostic and research tool, allowing non-invasive, ambulatory monitoring of blood pressure and ECG changes.