Kindling-like convulsive activities in the isolated ileum of the guinea pig. I. Electrical stimulation

A kindling-like convulsive activity model produced by subthreshold, iterative electrical stimulation of the isolated male guinea pig ileum is described. In this model, the mechanical activity of the longitudinal muscular fibers of the ileum was systematically quantified in terms of the basic frequency, tonus, amplitude, and transient amplitude increments (A, n spikes/20 min) of "normal" contractions and presence of high-amplitude, paroxysmal, "epileptiform" contractures (B, n spikes/20 min). Changes in these parameters were statistically compared through consecutive stages of the same stimulated male ileum (I = initial activation, II = initial inhibition. IIIA = late activation, and IV = late inhibition) and equivalent stages of stimulated female and nonstimulated male ilea where "kindling-like" activities were only occasionally observed. Basic tonus, amplitude, and number of A spikes showed significant changes through consecutive stimulated male ileum "kindling" stages: increased from baseline to stage I, decreased from I to II, increased from II to III and from III to IIIA, and decreased from IIIA to IV. The number of B spikes significantly increased from II to III, III to IIIA, and IIIA to IV. No significant changes in baseline frequency were found through all stages nor in tonus, amplitude, A and B spikes between stage IV and the self-sustained activity observed 120 min after stimulation. In addition, there were significant correlations between B spikes vs. basic tonus and amplitude and A spikes when the stimulated male ileum shifted from stage II to IIIA (positive correlations) and from IIIA to IV (negative correlations). Basic tonus during stage I, basic amplitude during IIIA, A spikes during self-sustained activity and B spikes during III, IIIA, IV, and self-sustained activity were in the stimulated male ileum larger than those in both the stimulated female and the nonstimulated male ilea. Tonus and A spikes during III and IIIA in the stimulated male ileum were larger than in the nonstimulated, whereas tonus during IV and self-sustaining activity and amplitude during II in the stimulated male ileum were smaller than in the female stimulated ileum.     

Subcellular compartmentalization of a potassium channel (Kv1.4): preferential distribution in dendrites and dendritic spines of neurons in the dorsal cochlear nucleus

Voltage-dependent ion channels have specific patterns of distribution along the neuronal plasma membrane of dendrites, cell bodies and axons, which need to be unravelled in order to understand their contribution to neuronal excitability and firing patterns. We have investigated the subcellular compartmentalization of Kv1.4, a transient, fast-inactivating potassium channel, in fusiform cells and related interneurons of the rat dorsal cochlear nucleus. A polyclonal antibody which binds to a region near the N-terminus domain of a Kv1.4 channel was raised in rabbits. Using a high-resolution combination of immunocytochemical methods, Kv1.4 was localized mainly in the apical dendritic trunks and cell bodies of fusiform cells, as well as in dendrites and cell bodies of interneurons of the dorsal cochlear nucleus, likely cartwheel cells. Quantitative immunogold immunocytochemistry revealed a pronounced distal to proximal gradient in the dendrosomatic distribution of Kv1. 4. In plasma membrane localizations, Kv1.4 was preferentially present in dendritic spines, either in the spine neck or in perisynaptic locations, always away from the postsynaptic density. These findings indicate that Kv1.4 is largely distributed in dendritic compartments of fusiform and cartwheel cells of the dorsal cochlear nucleus. Its preferential localization in dendritic spines, where granule cell axons make powerful excitatory synapses, suggests a role for this voltage-dependent ion channel in the regulation of dendritic excitability and excitatory inputs.     

Titration of Mechanical Insufflation–Exsufflation Optimal Pressure Combinations in Neuromuscular Diseases by Flow/Pressure Waveform Analysis

IntroductionThe aim of this study was to assess several air-pressure settings for MI–E to determine their effect on peak cough flow (PCF), and to compare the best pressures with those are more common used in the literature (±40 cmH₂O) in patients with neuromuscular disorders (NMD).MethodsAdults with NMD in whom MI–E was indicated were recruited. Assisted PCF was measured by an external pneumotachograph. The protocol included 9 PCF measures per patient: 1 baseline (non-assisted), 4 with increasing inspiratory pressures without negative pressure (10, 20, 30 and 40 cmH₂O or maximum tolerated), and then 4 adding expiratory pressures (?10, ?20, ?30 and ?40 cmH₂O or maximum tolerated) with maximum inspiratory pressure previously achieved.ResultsTwenty one patients were included, 61% with amyotrophic lateral sclerosis (ALS). Mean PCFs with recommended pressures (±40 cmH₂O) were lower than the scored in the individualized steps of the titration protocol (197.7 ± 67 l/min vs 214.2 ± 60 l/min, p < 0.05). Regarding subgroups, mean PCF_max values in ALS patients with bulbar symptoms were significantly higher than those achieved with recommended pressures (163.6 ± 80 vs 189 ± 66 l/min, p < 0.05).ConclusionThe PCF_max obtained with the protocol did not always match the recommended settings. It may be advisable to perform MI–E titration assessed by non-invasive PCF monitoring in patients with NMD, especially in ALS with bulbar involvement to improve the therapy detecting airway collapse induced by high pressures.     

Nestin and vimentin colocalization affects the subcellular location of glucocorticoid receptor in cutaneous melanoma

Aims: Nestin (a neuronal stem cell/progenitor cell marker of central nervous system development), vimentin (which is ubiquitously expressed in mesenchymal cells), and the glucocorticoid receptor (GR, which is involved in the immune response, cell proliferation, and apoptosis) have been shown to interact in embryonic and undifferentiated tissues in modulating cell proliferation. The aim of this study was to analyse nestin, vimentin and GR expression in tumour tissue (melanoma), and their association with clinicopathological variables, to evaluate any effect on tumour progression. Methods and results: Immunohistochemistry, double‐label immunofluorescence and confocal laser scanning microscopy were performed on biopsy specimens of cutaneous melanoma from 81 patients. Fisher’s and Pearson’s tests showed a correlation between nestin, vimentin and subcellular GR location (P = 0.008). Their concomitant expression also correlated with Clark level and thickness (P = 0.02 and P = 0.029, respectively). Kaplan–Meier analysis revealed a poorer outcome for stage III and IV patients with associated expression of nestin, vimentin and cytoplasmic GR in tumour tissue (P = 0.02). Conclusions: These results suggest the presence in melanoma of growth mechanisms involving nestin, vimentin, and GR, similarly to that occurring in embryonic and undifferentiated cells, and may help in understanding tumour biology to provide a molecular basis for clinical therapies.     

Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

Background:  Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol-induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D₁ receptors in these effects.
Methods:  Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D₁ receptor antagonist, SCH 39166 (SCH) (50 μg/kg), was administered 10 minutes before ethanol (1 g/kg).
Results:  Quantitative microscopic examination showed that ethanol, dose-dependently increased phospho-ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied.
Conclusions:  The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D₁ receptor-mediated mechanism. Overall, these results suggest that the D₁ receptors/ERK pathway may play a critical role in the motivational properties of ethanol.     

Should we try to determine the specific cause of cardiac tamponade?

INTRODUCTION: The causes of cardiac tamponade vary and it has been suggested that underlying causes should be sought in all cases. The purpose of this study was to determine the causes of cardiac tamponade in our environment, distinguishing between specific and idiopathic causes, and analyzing the proportion and causes in the subgroup of patients with relapsing tamponade. PATIENTS AND METHOD: We retrospectively studied all patients who underwent therapeutic pericardiocentesis between 1985 and 2001. The clinical and radiographic features and macroscopic characteristics of the pericardial fluid were analyzed. The final diagnosis in each patient was based on the clinical history, follow-up, pericardial fluid cytology, and pericardial biopsy, if available. RESULTS: Ninety-six patients were included (52 men/44 women), mean age 56.1 16.1 years. The cause of pericardial effusion was neoplasm in 50 patients (52.1%), 14 idiopathic pericarditis (14.6%), 12 renal failure (12.5%), 7 iatrogenic cases (7.3%), 4 mechanical tamponades (4.2%), 2 tuberculosis (2.1%), and 7 other causes (7.3%). Thirty-five patients had relapsing tamponade; only 2 of them had idiopathic pericarditis (5.7%). We found no significant differences in age, development time, extracted volume or fluid features between tamponade of specific or idiopathic origin. CONCLUSIONS: Most of the cardiac tamponades in our series had a specific cause. This made it necessary to identify a specific underlying cause in each case, especially in relapsing effusions. However, we did not find any variable suggestive of the cause of the disease.     

Neoadjuvant radiation and chemotherapy in rectal cancer does not increase postoperative complications

Background and aims Neoadjuvant radiation and chemotherapy in rectal cancer reduces local recurrences and increases the rate of conservative sphincter surgery. However, an increase in postoperative morbidity and mortality has also been observed. This study analyzed the operative difficulty and postoperative complications in patients with this treatment.Patients and methods Retrospective review of 103 patients with rectal cancer, divided into two groups: group A, 53 patients undergoing preoperative radiotherapy with 45 Gy combined with chemotherapy, and group B, 50 patients with rectal cancer who received surgery after diagnosis. Both groups were homogeneous. The two groups were compared for both technical difficulty, using intraoperative data and rate of complications.Results There were no statistically significant differences between the two groups with regard to intraoperative or postoperative data. In group A there were 20 complications in 17 patients (32%) and in group B 22 complications in 19 patients (38%). The rates of perineal wound infection were similar. The percentage of anastomotic leaks was higher in group A. A greater number of anterior resections was performed in group A.Conclusion Preoperative radiation and chemotherapy in rectal cancer does not increase postoperative complications and increases the rate of sphincter-preserving surgery.An invited commentary on this paper is available at