Angular bundle kindling is accelerated in rats with a genetic predisposition to acoustic stimulus-induced seizures

Limbic kindling was examined in genetically epilepsy-prone (GEPR) and non-epileptic control rats. The early stage of kindling development was accelerated in both groups of GEPR rats compared to controls. Later stages of kindling were accelerated in GEPR-9 but not GEPR-3 rats. These results indicate that GEPR rats have an enhanced susceptibility to limbic kindling and suggest that limbic brain alterations may contribute to acceleration of the early stage kindling development in GEPR rats.     

Robotic-assisted heller myotomy versus laparoscopic heller myotomy for the treatment of esophageal achalasia: multicenter study

Laparoscopic Heller myotomy (LHM) has become the standard treatment option for achalasia. The incidence of esophageal perforation reported is about 5%–10%. Robotically assisted Heller myotomy (RAHM) is emerging as a safe alternative to LHM. Data comparing the two approaches are scant. The aim of this study was to compare RAHM with LHM in terms of efficacy and safety for treatment of achalasia. A total of 121 patients underwent surgical treatment of achalasia at three institutions. A retrospective review of prospectively collected perioperative data was performed. Patients were divided into two groups: group A (RAHM), 59 patients, and group B (LHM), 62 patients. All the operations were completed using minimally invasive techniques. There were 63 women and 58 men, with a mean age of 45 ±19 years (14–82 years). Fifty-one percent of patients in group A and 95% of patients in group B reported weight loss. Duration of symptoms was equal for both groups. Dysphagia was the main complaint in both groups (P = NS). There was no difference in preoperative endoscopic treatment in both groups (44% versus 27%, P = NS). Operative time was significantly shorter for LHM in the first half of the experience (141 ± 49 versus 122 ± 44 minutes, P < .05). However, in the last 30 cases there was no difference in operative time between the groups (P = NS). Intraoperative complications (esophageal perforation) were more frequent in group B (16% versus 0%). The incidence of postoperative heartburn did not differ by group. There were no deaths. At 18 and 22 months, 92% and 90% of patients had relief of their dysphagia. This study suggests that RAHM is safer than LHM, because it decreases the incidence of esophageal perforation to 0%, even in patients who had previous treatment. At short-term follow-up, relief of dysphagia was equally achieved in both groups. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). This study was supported in part by a grant provided by Intuitive Surgical, Inc. and Ethicon Endo-Surgery, Inc.     

In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

Improvement of endoneurial lipid abnormalities in experimental diabetic neuropathy by oxygen modification

Endoneurial hypoxia and a high frequency of closed capillaries have been found in chronic experimental diabetes and human diabetic sural nerve, respectively. These findings have led to the hypothesis that the pathogenesis of diabetic neuropathy is due to endoneurial hypoxia. To evaluate the role of endoneurial hypoxia in experimental diabetic neuropathy, the effects of supplementation and deprivation of oxygen on peripheral nerve lipid biosynthesis were studied in normal control and streptozotocin-induced diabetic rats. Defective lipid biosynthesis in diabetic nerve was partially prevented by oxygen supplementation. When normal rats were placed in a hypoxic chamber, lipid abnormalities similar to those observed in diabetic nerves were demonstrated in the absence of changes in nerve free sugars. These findings suggest that endoneurial hypoxia may underlie some key biochemical abnormalities encountered in experimental diabetic neuropathy.     

Health Behavior Correlates of Depression in a Sample of High School Students

Frequency of symptoms of depression and selected health-related practices and events were measured in a sample of 219 high school students. Students reported numerous symptoms of depression. Relative proportions of boys and girls reporting symptoms of depression were not significantly different. However, girls reported experiencing more severe depression than their male counterparts. Depression correlated significantly with several of the 22 health practices and states of affect examined. Both the determinants and manifestations of depression in adolescent cohorts require in-depth investigation. Possible implications for school health personnel are discussed.     

Middle-Down Fragmentation for the Identification and Quantitation of Site-Specific Methionine Oxidation in an IgG1 Molecule

A middle-down LC/MS approach, for the rapid quantitation and characterization of site-specific methionine oxidation in a recombinant monoclonal IgG1 molecule, is described. An IgG1 antibody was digested with endoprotease LysC under limited proteolytic conditions to produce two major components; an antigen binding fragment (Fab) and a crystallizable fraction (Fc). These fractions were then reduced to produce three major species; light chain (LC), Fc/2 which is the C terminal region of the heavy chain (HC) and the N-terminal heavy chain region (Fd). These three fragments were separated by reversed-phase HPLC using a diphenyl column. The diphenyl column resolved site-specific methionine oxidation in all three subunits. Middle- down N-terminal sequencing with a LCT premier mass spectrometer was used to identify the sites of oxidation in the LC. Sites of oxidation in the Fc/2 were identified using middle-down collision-induced dissociation (CID) on a Qtof premier. This method allowed for the rapid quantitation and identification of oxidation on each methionine residue in an IgG1 molecule.     

Comparison of novel computer detectors and human performance for spike detection in intracranial EEG.

OBJECTIVE: Interictal spikes in intracranial EEG (iEEG) may correlate with epileptogenic cortex, but review of interictal iEEG is labor intensive. Accurate automated spike detectors are necessary for understanding the role of spikes in epileptogenesis. METHODS: The sensitivity, accuracy and reproducibility of three automated iEEG spike detectors were compared against two human EEG readers using iEEG segments from eight patients. A consensus set of detections was generated for detector calibration. Spike verification was calculated after both human EEG readers independently reviewed all detections. RESULTS: Humans and two of the three automated detectors demonstrated comparable accuracy. In four patients, automated spike detection sensitivity was >70% and accuracy was >50%. In the remaining four patients, EEG background morphology resulted in poorer performance. Blinded human verification accuracy was 76.7+/-6.6% for computer-detected spikes, and 84.5+/-4.1% for human-detected spikes. CONCLUSIONS: Automated iEEG spike detectors perform comparably to humans, but sensitivity and accuracy are patient dependent. Humans verified the majority of computer-detected spikes. SIGNIFICANCE: In some patients automated detectors may be used for mapping spike occurrences in epileptic networks. This may reveal associations between spike distribution, seizure onset, and pathology.     

A preliminary study of serotonergic antidepressants in treatment of dysthymia

Rosenthal, Jesse et al. A Preliminary Study of Serotonergic Antidepressants in the Treatment of Dysthymia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 933–941.

1. 1. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents.

2. 2. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone.

3. 3. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on followup at five months.

4. 4. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.