Valproic acid intensifies epileptiform activity in the hippocampal pyramidal neurons

The effects of large concentrations of valproic acid (VPA) on veratridine-induced epileptiform activity (veratridine model) were investigated in rat hippocampal CA1 pyramidal neurons. Studies were performed on the veratridine model in rat brain slices using conventional electrophysiological intracellular techniques. Large concentrations of VPA (5 mM or more) enhanced rather than inhibited epileptiform activity induced by veratridine. During the proepileptic phase of VPA, a membrane depolarization accompanied by a decrease in membrane input resistance were evident. The voltage-dependent proepileptic effect of VPA was blocked by tetrodotoxin (TTX; 100 nM) but not by the calcium channel blockers, diltiazem (5 microM) or omega-conotoxin GVIA (5 microM). VPA did not induce a proepileptic effect when it was superfused at high concentration (0.5-10 mM) on sodium channel-independent models such as the bicuculline or magnesium-free artificial cerebrospinal fluid. Large concentrations of VPA had no significant effect on untreated neurons. The VPA-enhanced veratridine bursting is probably related to the reported proepileptic activities observed in patients taking high doses of this drug. These data also suggest the involvement of sodium channels in the proepileptic effect of VPA.     

An examination of the effects of isoenergetic intragastric infusions of pure macronutrients on cold pain perception in healthy human volunteers

Our previous study demonstrated that meals, particularly when rich in fat, significantly reduced the pain induced by the cold pressor stimulus in healthy human subjects. To determine the mechanisms involved, the aim of this study was to bypass the taste and cognitive component of food and to investigate the scope of these analgesic effects with direct intragastric infusion of pure macronutrients in a group of 16 healthy human volunteers (eight male and eight female) on the response to cold-induced pain. All subjects underwent the cold pressor test (CPT) on three occasions in a counterbalanced order: before and after intragastric intubation and infusion of isoenergetic fat (10% intralipid), carbohydrate (CHO-maltodextrin), and a control infusion of isotonic saline. All solutions were of equal volume and administered at room temperature. The CPT was carried out four times on each test day, once before intubation, and 0.5, 1.5, and 2.5 h after intragastric infusion. Radial pulse and blood pressure measurements and visual analogue scales of mood/emotional state were carried out before and after each CPT. There were no significant differences in pain scores between the three test conditions, suggesting that by bypassing the cognitive and taste component of eating, the trigger for any postingestive analgesic effects of food are lost.     

Reactive microgliosis

Damage to the central nervous system (CNS) elicits the activation of both astrocytes and microglia. This review is focused on the principal features that characterize the activation of microglia after CNS injury. It provides a critical discussion of concepts regarding microglial biology that include the relationship between microglia and macrophages, as well as the role of microglia as immunocompetent cells of the CNS. Mechanistic and functional aspects of microgliosis are discussed primarily in the context of microglial neuronal interactions. The controversial issue of whether reactive microgliosis is a beneficial or a harmful process is addressed, and a resolution of this dilemma is offered by suggesting different interpretations of the term 'activated microglia' depending on its usage during in vivo or in vitro experimentation.     

The hospitalist: the new addition to the inpatient management team

To coordinate care and manage costs, physicians are being added to the inpatient management team. To assist the chief nurse executive in assimilating this new team member into the patient care provider group, the authors describe the role of the hospitalist, the goals of the organization in using the new role, questions to ask and steps to take to ensure success for the whole-care team and the organization.     

Transhiatal approach to total gastrectomy for adenocarcinoma of the gastric cardia

BACKGROUND: A thoracoabdominal approach has traditionally been described for the resection of tumours of the gastric cardia. The aim of this study was to evaluate a transhiatal approach for resection of cancers of the gastric cardia. METHODS: Twenty consecutive patients undergoing transhiatal gastro-oesophagectomy for cancer of the gastric cardia were studied. Data were collected prospectively with regard to operating time, operative blood loss, intensive care unit (ICU) stay, analgesia use, duration of hospital stay, and pathological details of resection margin clearance and lymph node yield. Results were compared with those of the 20 preceding patients for whom the same prospective information had been recorded following resection via the standard thoracoabdominal approach. RESULTS: The transhiatal approach required a shorter operating time (median 190 (range 105-255) versus 280 (225-330) min; P = 0.004). It resulted in less blood loss (median 405 (180-2000) versus 1000 (420-3200) ml; P = 0.03) and fewer days in the ICU (median 0 (0-31) versus 2 (1-8) days; P = 0.005) despite being performed in an older patient population (median 71 (43-78) versus 63 (59-70) years; P = 0.016). There was no difference in either the lymph node harvest or length or involvement of upper resection margins. CONCLUSION: The transhiatal approach to the resection of tumours at the gastric cardia is a valid and safe alternative to the standard thoracoabdominal technique. This technique avoids thoracotomy and its associated morbidity and is accompanied by reduced blood loss, decreased operating time and a shorter ICU stay.     

Intermediate expansions of a GAA repeat in the frataxin gene are not associated with type 2 diabetes or altered glucose-induced beta-cell function in Danish Caucasians

A variable expansion of a GAA repeat is present in the first intron of the frataxin gene, also termed FRDA1 or X25. Long repeat lengths (>66 repeats) are present in patients with Friedreich's ataxia, while an intermediate expansion (10-66 repeats) has recently been reported to be highly associated with type 2 diabetes. Using a polymerase chain reaction-based assay, we found that 32.4% (95%CI 29.9-34.9) of 636 Danish Caucasian type 2 diabetic patients were carriers of an intermediate expansion, whereas the frequency was 30.4% (26.4-34.4) among 224 matched glucose-tolerant control subjects (P = 0.6). In the control subjects, the values of serum insulin and C-peptide responses during an oral glucose tolerance test were similar between the 69 carriers and 155 noncarriers. Furthermore, we investigated a possible relationship between expansions of the FRDA1 gene and glucose-induced beta-cell function in 338 young Caucasians (33.7% [30.1-37.3] carriers) and in 215 glucose-tolerant subjects (31.0% [26.6-35.4] carriers) with a type 2 diabetic parent. In neither population did the carriers differ from noncarriers according to values of fasting plasma glucose, serum insulin, or C-peptide, acute serum insulin, or C-peptide responses after intravenous glucose. In conclusion, intermediate expansion of the frataxin trinucleotide repeat is not associated with type 2 diabetes or altered glucose-induced insulin secretion in Danish Caucasians.