Effects of isoflurane on glutamate and taurine releases, brain swelling and injury during transient ischemia and reperfusion

The volatile anesthetic agent isoflurane was thought to provide neuroprotection against ischemic damage; however, this effect remains controversial. Using the middle cerebral artery occlusion model and intracerebral microdialysis, the authors monitored the variations of glutamate and taurine concentrations in the extra-cellular space in male rats anesthetized with pentobarbital or isoflurane. Brain injury and edema were evaluated 24 h after ischemia. Isoflurane prevented the ischemia-induced efflux of glutamate and reduced the release of taurine. No difference in the size of the brain lesions was observed with both anesthetics, and isoflurane induced the formation of a bigger brain edema and reduced taurine release. These results suggest that inhibiting glutamate release during ischemia may not be sufficient to improve brain outcome after transient ischemia.     

Neural correlates of antinociception in borderline personality disorder

CONTEXT: A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. OBJECTIVE: To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. DESIGN: Case-control study. SETTING: A university hospital. PARTICIPANTS: Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. INTERVENTIONS: Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. RESULTS: Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. CONCLUSION: The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.     

Risk Factors and Outcomes for Anastomotic Leakage in Colorectal Surgery: A Single-Institution Analysis of 1576 Patients

Background  

Anastomotic leakage is associated with high mortality, high reoperation rate, and increased hospital length of stay. Although many studies have examined the risk factors for anastomotic leak, large prospective series that report on long-term survival rates are lacking.     

Tubulocystic renal carcinoma: a clinical perspective

Introduction

Tubulocystic renal carcinoma (TCRC) is a recently described neoplastic entity. To date, clinicopathological features on less than hundred cases of these rare tumours have been characterized exclusively in the pathological literature. Herein, we present five additional cases emphasizing clinical aspects on these rare renal neoplasms.

Material and method

Cases diagnosed as TCRC were retrieved and reviewed from the routine and consultation files of the Pilsen tumour registry comprising over 20,000 cases of renal tumours.

Results

All patients were men, mean age 56 years (range 29–70). Features on computed tomography (CT) were in two cases Bosniak III, one IV and two were solid tumours. In four patients, nephrectomy was performed, and one patient underwent resection. At the time of surgery, two patients had metastases. In one case, both primary tumour and metastases were active on FDG positron emission tomography (PET)/CT. Both patients with metastatic disease were treated with sunitinib with partial response. One patient died 26 months postoperatively and the other patient is alive 5 months after surgery. Three patients with localized tumours are without evidence of disease 31, 28 and 7 months after surgery. In one case, the resected tumour was histologically combined with a papillary renal cell carcinoma (PRCC).

Conclusion

TCRC occurs predominantly in men with a wide age range. TCRC frequently displays a cystic component which may render a radiological classification of Bosniak III or IV. FDG PET/CT is helpful in the detection of metastases. TCRC has definitive malignant potential. Our findings support a possible relationship to PRCC. The tyrosine kinase inhibitor sunitinib may be used a therapeutical agent with partial response and temporary effect.     

Interactions of 16α-[F]-fluoroestradiol (FES) with sex steroid binding protein (SBP)

Fluorine-18 16alpha-Fluoroestradiol ([18F]-FES) is a positron-emitting tracer for the estrogen receptor that is used for positron emission tomography (PET) studies of tumor tissues rich in the estrogen receptor. The role of the sex steroid binding protein (SBP or SHBG) in the transport of the [18F]-FES to the estrogen-receptor-rich tissue in breast cancer patients in vivo was investigated. To determine the extent to which [18F]-FES is bound to SBP in the blood, we performed a series of studies using blood samples obtained from patients undergoing [18F]-FES PET scans. The binding of [18F]-FES to the SBP was measured using a simple protein precipitation assay. The binding of [18F]-FES metabolites to SBP was also measured. These measurements showed that the tracer was distributed between albumin and SBP, and the binding capacity of SBP was sufficient to ensure that the protein was not saturated when the tracer was fully mixed with the plasma; however, local saturation of SBP may occur when [18F]-FES is administered intravenously. Typically about 45% of [18F]-FES in circulating plasma was bound to SBP, but this fraction was dependent on the concentration of SBP in plasma. The transfer of the tracer between the two proteins was rapid, complete in less than 20 s at 0 degrees C, suggesting that the equilibrium was maintained under most circumstances and that local saturation resolved quickly when blood from the injection site entered the central circulation. These data suggest that SBP binding of [18F]-FES is significant and will affect the input function of the tracer for any model that is used for the quantitative evaluation of [18F]-FES uptake in PET studies. Estimates of equilibrium binding in blood samples are sufficient to characterize [18F]-FES binding to SBP in the circulation.     

Accuracy of pedicle screw insertion in the cervical spine for internal fixation using frameless stereotactic guidance

OBJECT: Although transpedicular fixation is a biomechanically superior technique, it is not routinely used in the cervical spine. The risk of neurovascular injury in this region is considered high because the diameter of cervical pedicles is very small and their angle of insertion into the vertebral body varies. This study was conducted to analyze the clinical accuracy of stereotactically guided transpedicular screw insertion into the cervical spine. METHODS: Twenty-seven patients underwent posterior stabilization of the cervical spine for degenerative instability resulting from myelopathy, fracture/dislocation, tumor, rheumatoid arthritis, and pyogenic spondylitis. Fixation included 1-6 motion segments (mean 2.2 segments). Transpedicular screws (3.5-mm diameter) were placed using 1 of 2 computer-assisted guidance systems and lateral fluoroscopic control. The intraoperative mean deviation of frameless stereotaxy was < 1.9 mm for all procedures. RESULTS: No neurovascular complications resulted from screw insertion. Postoperative computed tomography (CT) scans revealed satisfactory positioning in 104 (90%) of 116 cervical pedicles and in all 12 thoracic pedicles. A noncritical lateral or inferior cortical breach was seen with 7 screws (6%). Critical malplacement (4%) was always lateral: 5 screws encroached into the vertebral artery foramen by 40-60% of its diameter; Doppler sonographic controls revealed no vascular compromise. Screw malplacement was mostly due to a small pedicle diameter that required a steep trajectory angle, which could not be achieved because of anatomical limitation in the exposure of the surgical field. CONCLUSIONS: Despite the use of frameless stereotaxy, there remains some risk of critical transpedicular screw malpositioning in the subaxial cervical spine. Results may be improved by the use of intraoperative CT scanning and navigated percutaneous screw insertion, which allow optimization of the transpedicular trajectory.     

Brain death induces inflammation in the donor intestine

BACKGROUND: Brain death donors are frequently used for transplantation. Previous studies showed that brain death (BD) negatively affects the immunological and inflammatory status of both liver and kidney. Because the intestine is increasingly used as a donor organ and no information on effects of BD on small intestine is available we performed this study. METHODS: We studied the inflammatory and apoptotic changes in donor intestine after BD induction. Brain death was induced in rats by inflation of a balloon catheter. Three groups (n=6) were compared: 1-hr BD, 4-hr BD, and sham-operated controls. RESULTS: An increased polymorphonuclear cell influx in ileum, as a measure of inflammation, was observed in 1- and 4-hr BD group compared with controls. Jejunum showed a significant increase at the 4-hr BD group compared with the control group. Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and interleukin-6 were upregulated after 1- and 4-hr BD. Caspase-3 positive cells were found in jejunum and ileum after 4-hr BD on the top of the villi. Serum interleukin-6 was severely elevated in the 1- and 4-hr brain dead rats. CONCLUSION: These data show the early occurrence of intestinal inflammation and apoptosis after BD induction. These events may ultimately have a negative influence on the outcome of intestinal transplantation.     

Static cold storage preservation of ischemically damaged kidneys. a comparison between IGL-1 and UW solution.

Especially in damaged organs, adequate organ preservation is critically important to maintain viability. Institut Georges Lopez-1 (IGL-1) is a new preservation solution, with an extracellular sodium/potassium ratio and polyethylene glycol as a colloid. The influence of warm and cold ischemia was evaluated in a rat Lewis-Lewis transplant model with a follow up of 14 days. Eight groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0 and 15 min followed by 0- or 24-h cold storage (CS) preservation in IGL-1 or UW-CSS. Blood was collected daily during the first week and at day 14. Recipients were placed in metabolic cages at day 4 and 14 after transplantation allowing urine collection and adequate measurement of glomerular filtration rate. Focussing on inflammation, reactive oxygen species production, proximal tubule damage, proteinuria, histology, and renal function after transplantation we could not show any relevant difference between IGL-1 and UW-CSS. Furthermore, the combination of 15-min warm ischemia and by 24-h cold ischemia did not result in life sustaining kidney function after transplantation, irrespective of the used solution. In the present experiment, static CS preservation of ischemically damaged rat kidneys in either IGL-1 or UW-CSS rendered equal results after transplantation.     

Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.

We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling.     

Restoration of cardiomyocyte functional properties by angiotensin II receptor blockade in diabetic rats

Recent evidence suggests that blockade of the renin-angiotensin system ameliorates diabetes-induced cardiac dysfunction, but the mechanisms involved in this process remain elusive. We investigated the effect of treatment with an angiotensin II receptor blocker, losartan, on the metabolic and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 20 mg x kg(-1) x day(-1) losartan for 8 weeks. Insulin and beta-adrenergic stimulation failed to increase the glucose uptake rate in STZ cardiomyocytes, whereas the alpha-adrenergic effect persisted. Concurrently, a typical prolongation of action potential duration (APD) and a decrease of transient outward current (I(to)) were recorded in patch-clamped STZ myocytes. Treatment with losartan did not affect body weight or glycemia of diabetic or control animals. However, in losartan-treated STZ-induced diabetic rats, beta-adrenergic-mediated enhancement of glucose uptake was completely recovered. APD and I(to) were similar to those measured in losartan-treated control rats. A significant (P < 0.0001) correlation between metabolic and electrophysiological parameters was found in control, diabetic, and losartan-treated diabetic rats. Thus, angiotensin receptor blockade protects the heart from the development of cellular alterations typically associated with diabetes. These data suggest that angiotensin receptor blockers may represent a new therapeutic strategy for diabetic cardiomyopathy.