Differential actions of NPY on seizure modulation via Y1 and Y2 receptors: evidence from receptor knockout mice

PURPOSE: Neuropeptide Y (NPY) has been shown to modulate seizure activities. To provide further understanding of the involvement of two of the most abundantly expressed NPY receptors, Y1 and Y2, we assessed the effect of Y1 and Y2 gene deletion on systemic kainic acid-induced seizures. We also examined the effect of rAAV-mediated hippocampal NPY overexpression on seizure susceptibility in these receptor knockout mice. METHODS: Recombinant adeno-associated viral vector overexpressing NPY (rAAV-NPY) or an empty vector control (rAAV-Empty) was injected into the hippocampus of adult C57BL/6-129/SvJ wild-type male mice and mice deficient of Y1 or Y2 receptors on the same background. Four weeks after vector injection, mice were subjected to systemic kainic acid-induced seizures, and the seizure behaviors were scored. RESULTS: The rAAV-mediated hippocampal overexpression of NPY led to a twofold reduction in seizures induced by systemic kainic acid in wild-type mice and Y1 receptor knockout mice but not in mice deficient of Y2 receptors. A differential action by the receptors was observed in the seizure-induced mortality rate, with increased fatality in Y2-/- mice. In addition, although NPY overexpression did not significantly affect the mortality rate in Y2-/- and wild-type mice, it abolished KA-induced mortality in Y1-/-mice. CONCLUSIONS: This study shows for the first time an altered susceptibility to chemically induced seizures in Y1 and Y2 knockout mice and demonstrates a differential seizure modulation mediated by these receptors via a genetic approach.     

Experimental blunt chest trauma impairs fracture healing in rats

In poly‐traumatic patients a blunt chest trauma is an important trigger of the posttraumatic systemic inflammatory response. There is clinical evidence that fracture healing is delayed in such patients, however, experimental data are lacking. Therefore, we investigated the influence of a thoracic trauma on fracture healing in a rat model. Male Wistar rats received either a blunt chest trauma combined with a femur osteotomy or an isolated osteotomy. A more rigid or a more flexible external fixator was used for fracture stabilization to analyze whether the thoracic trauma influences regular healing and mechanically induced delayed bone healing differently. The blunt chest trauma induced a significant increase of IL‐6 serum levels after 6 and 24 h, suggesting the induction of a systemic inflammation, whereas the isolated fracture had no effect. Under a more rigid fixation the thoracic trauma considerably impaired fracture healing after 35 days, reflected by a significantly reduced flexural rigidity (three‐point‐bending test), as well as a significantly diminished callus volume, moment of inertia, and relative bone surface (µCT analysis). In confirming the clinical evidence, this study reports for the first time that a blunt chest trauma considerably impaired bone healing, possibly via the interaction of the induced systemic inflammation with local inflammatory processes. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:734–739, 2011     

Anatomy of the psoas muscle and lumbar plexus with respect to the surgical approach for lateral transpsoas interbody fusion

Lateral transpsoas interbody fusion (LTIF) is a minimally invasive technique that permits interbody fusion utilizing cages placed via a direct lateral retroperitoneal approach. We sought to describe the locations of relevant neurovascular structures based on MRI with respect to this novel surgical approach. We retrospectively reviewed consecutive lumbosacral spine MRI scans in 43 skeletally mature adults. MRI scans were independently reviewed by two readers to identify the location of the psoas muscle, lumbar plexus, femoral nerve, inferior vena cava and right iliac vein. Structures potentially at risk for injury were identified by: a distance from the anterior aspect of the adjacent vertebral bodies of <20 mm, representing the minimum retraction necessary for cage placement, and extension of vascular structures posterior to the anterior vertebral body, requiring anterior retraction. The percentage of patients with neurovascular structures at risk for left-sided approaches was 2.3% at L1–2, 7.0% at L2–3, 4.7% at L3–4 and 20.9% at L4–5. For right-sided approaches, this rose to 7.0% at L1–2, 7.0% at L2–3, 9.3% at L3–4 and 44.2% at L4–5, largely because of the relatively posterior right-sided vasculature. A relationship between the position of psoas muscle and lumbar plexus is described which allows use of the psoas position as a proxy for lumbar plexus position to identify patients who may be at risk, particularly at the L4–5 level. Further study will establish the clinical relevance of these measurements and the ability of neurovascular structures to be retracted without significant injury.     

Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has proven useful in the differentiation of various tumour entities, including breast cancer. In patients with primary breast cancer we performed a 3-h imaging protocol to examine possible improvements in tumour detectability and image contrast. Twenty-nine patients with primary breast cancer with a diameter of ≥2 cm that was demonstrated to be malignant by biopsy or surgery were injected with 370–740 MBq ¹⁸F-FDG and scanned in the prone position. Data were acquired 0–40 min, 1.5 h and 3.0 h after injection. After correction for measured attenuation, decay and scatter and iterative reconstruction, standardised uptake values (SUVs) and tumour-to-non-tumour and tumour-to-organ ratios were calculated. Visual analysis was performed using transverse, sagittal and coronal slices as well as 3D reprojection images. Tumour-to-non-tumour and tumour-to-organ ratios were significantly higher for the 3-h images than for the 1.5-h images. SUVs did not increase to the same extent. Lesion detectability was 83% in 1.5-h images compared to 93% in 3-h images. We conclude that tumour contrast in breast cancer is improved by starting the PET acquisition at 3 h p.i. rather than at 1.5 h p.i. Received 17 October and in revised form 8 December 1998     

Sudden cardiac death and dialysis patients

Dialysis patients have extraordinarily high mortality rates. The death rate for all US dialysis patients in 2004 was 230 per 1000 patient-years. Cardiac disease is the major cause of death in dialysis patients and accounts for 43% of all-cause mortality. In the United States Renal Data System database 62% of cardiac deaths (or 27% of all deaths) are attributable to arrhythmic mechanisms. The estimated rate of sudden cardiac death in US dialysis patients in 2002 was 7% per year. There are several plausible explanations for the special vulnerability of dialysis patients to sustaining sudden cardiac death. Obstructive coronary artery disease, coupled with diminished tolerance to myocardial ischemia (in the setting of myocardial fibrosis and left ventricular hypertrophy), rapid electrolyte shifts in hemodialysis patients, and derangements in autonomic function may all contribute to this heightened risk of sudden cardiac death. This review focuses on the epidemiology of sudden cardiac death in dialysis patients, underlying mechanisms of sudden death, and potential interventions to reduce the risk of sudden cardiac death in dialysis patients (including medical therapy and defibrillators). It is unlikely that one single therapeutic intervention will prevent sudden cardiac death in dialysis patients; but a more modest (and attainable) goal is the implementation of multiple strategies to reduce the risk of sudden cardiac death in this special high-risk population.     

Continuous hyperthermic peritoneal perfusion for desmoplastic small round cell tumor

Desmoplastic small round cell tumor (DSRCT) is a rare disease of children, adolescents, and young adults that begins and spreads on the peritoneal surfaces. Desmoplastic small round cell tumor usually presents with diffuse abdominal metastatic disease similar in gross appearance to carcinomatosis. To date, very aggressive treatment programs have yielded dismal outcomes. Here we present 2 cases of DSRCT that were treated with aggressive surgical excision followed by intraoperative continuous hyperthermic peritoneal perfusion using cisplatin. These are the first pediatric case reports of DSRCT being treated with continuous hyperthermic peritoneal perfusion, a procedure usually used in treatment of adult carcinomatosis.     

Totally endoscopic coronary artery bypass graft: initial experience with an additional instrument arm and an advanced camera system

Background Robotically enhanced telemanipulation for totally endoscopic coronary artery bypass does not provide adequate tactile feedback, traction, or counter-traction. The exposition of coronary target sites is difficult, the visual field is limited, and the epicardial stabilization may be troublesome. A fourth robotic arm for endothoracic instrumentation has been added to the da Vinci surgical system to facilitate totally endoscopic operations. The stereoendoscope was upgraded with a wide-angle feature. Methods The procedure was performed in five patients. Four of these patients had left internal thoracic artery (LITA) to left anterior descending artery (LAD) grafting on the beating heart and the fifth had sequential bypass grafting (LITA to diagnonal branch and LAD) on an arrested heart. The additional effector arm of the da Vinci surgical system was brought into the operative field beneath the operating table and used as a second right arm. The wide-angle view was activated by either the console or the patient side surgeon. Results The mean operative, port placement, and anastomotic times for a beating-heart totally endoscopic coronary artery bypass were 195±58, 25±10, and 18±5 min, respectively. All procedures were free of morbidity and mortality, with satisfactory angiographic control. The sequential arterial bypass grafting procedure was fully completed in totally endoscopic technique. Conclusions The additional instrumentation arm and wide-angle visualization are useful technical improvements of the da Vinci surgical system, solving the problem of traction, countertraction, and facilitated exposition of target sites as well as visualization of the surgical field. They provide potential for wider acceptance of totally endoscopic coronary artery bypass grafting in a larger surgical community. Online publication: 13 October 2004     

The comparison of 2-18F-2-deoxyglucose and 15-(ortho-123I-phenyl)-pentadecanoic acid uptake in persisting defects on thallium-201 tomography in myocardial infarction

The myocardial uptake of glucose and fatty acids into 201Tl redistribution defects were studied in 32 patients with myocardial infarction by tomography using 2-18F-2-deoxyglucose (FDG) and 15-(ortho-123I-phenyl)-pentadecanoic acid (oPPA). A total of 1153 segments were analyzed, 408 (35%) of which showed a persistent thallium-defect in stress-redistribution images. Of the segments with a decreased 201Tl uptake in these redistribution tomograms, 50.5% had a decreased uptake of both FDG and oPPA; in 21.8% FDG as well as oPPA uptake was within normal range. Normal FDG uptake but decreased oPPA uptake was detected in 17.4%, whereas 10.3% of the segments had normal oPPA uptake but decreased FDG uptake (chi-square test, p less than 0.001). A significant correlation of FDG and oPPA uptake (r = 0.51) was found in the segments with persistent 201Tl defect. Thus, a substantial fraction of persistent thallium-defects after healed myocardial infarction exhibit FDG as well as oPPA uptake, probably due to residual fatty acid metabolism in partially ischemic regions.     

New abdominal CT angiography protocol on a 16 detector-row CT scanner - first results

Purpose. Purpose of this study was the implementation of a new abdominal CT angiography protocol on a 16 detector-row CT scanner and the comparison to selective catheter angiography. Methods. 76 patients with various vascular disorders underwent abdominal CT angiography on a recently developed 16 detector-row CT scanner using submillimeter slice collimation (16×0.75 mm). Results were compared with mesenteric and/or hepatic angiography in 17 patients performed during tumor embolization. Opacification was provided using individually tailored contrast application with a test bolus setting. To evaluate the contrast injection protocol density measurements within the vessel lumen were performed. Results. Diagnostic image quality was achieved in all patients with angiographic comparison (n = 17). Within the hepatic and mesenteric vasculature up to 4th generation vessels could be identified. Compared to selctive angiography CT angiography provided equivalent morphologic information up to the detectable vessel generation. With the applied contrast application regimen there were no significant differences in vessel enhancement along the abdominal aorta and iliac arteries. Conclusion. 16 detector-row CT enables whole abdominal angiographic studies with submillimeter resolution in a single breath-hold. The improved spatial resolution enables for high quality 3D visualization. Compared to invasive angiography, 16 detector-row CT reveals equivalent morphologic information.