The surgical bed after BCNU polymer wafer placement for recurrent glioma: serial assessment on CT and MR imaging

OBJECTIVE: The objective of our study was to describe the CT and MR imaging appearances of the surgical bed in the brains of patients receiving biodegradable polymers impregnated with N, N'1, 3-Bis-(2-chloroethyl)-N-nitrosourea (BCNU) for recurrent glioma and to determine whether patients receiving placebos could be differentiated from those receiving BCNU based on the pattern and growth kinetics of tumor recurrence. MATERIALS AND METHODS: The CT and MR images of 20 patients who underwent surgery for resection of recurrent high-grade gliomas and placement of intratumoral wafers (11 received BCNU polymer wafers, nine received control wafers) were analyzed for wafer appearance, volume of gas in the tumor bed, and volume of enhancement on serial scans. RESULTS: Wafers appeared as linear hyperdense structures on CT and as linear low-signal-intensity structures on MR imaging and caused no significant enhancement. In the BCNU polymer group, gas volume was 4.0 +/- 3.4 cm(3) (mean +/- SD), whereas gas volume was 1.6 +/- 3.0 cm(3) for the placebo group (Mann-Whitney test, p = 0.03). A trend toward linear rather than exponential recurrent tumor growth was identified for the BCNU polymer group but not for the placebo group. CONCLUSION: BCNU polymer wafers have a specific appearance on CT and MR imaging with which radiologists should be familiar: gas in the surgical bed is an expected transient finding, and tumor regrowth in patients receiving BCNU polymer wafers appeared to occur at a slower rate than in those receiving the placebo.     

Oxygenation using tidal volume breathing after maximal exhalation

We compared, in volunteers, the oxygenation achieved by tidal volume breathing (TVB) over a 3-min period after maximal exhalation with that achieved by TVB alone. Twenty-three healthy volunteers underwent the two breathing techniques in a randomized order. A circle absorber system with an oxygen flow of 10 L/min was used. The end-expiratory oxygen concentration (EEO(2)) was monitored at 15-s intervals up to 3 min. TVB after maximal exhalation produced EEO(2) values of 68% +/- 5%, 75% +/- 5%, and 79% +/- 4% at 30, 45, and 60 s, respectively, which were significantly larger (P < 0.05) than the corresponding values obtained with TVB alone (58% +/- 5%, 66% +/- 6%, and 71% +/- 5%, respectively). In both techniques, the EEO(2) increased exponentially, with time constants of 35 s during TVB after maximal exhalation versus 58 s during TVB without prior maximal exhalation. In conclusion, maximal exhalation before TVB can hasten preoxygenation by decreasing the nitrogen content of the functional residual capacity, with a consequent increase of EEO(2) to approximately 70% in 30 s and 80% in 60 s. IMPLICATIONS: Oxygenation by using maximal exhalation before tidal volume breathing produced a significantly faster increase in end-expiratory oxygen concentration than oxygenation with tidal volume breathing alone.     

Quinacrine induces cytochrome c-dependent apoptotic signaling in human cervical carcinoma cells

Quinacrine (QU), a phospholipase-A2 (PLA-2) inhibitor has been used clinically as a chemotherapeutic adjuvant. To understand the mechanisms leading to its chemotherapeutic effect, we have investigated QU-induced apoptotic signaling pathways in human cervical squamous carcinoma HeLa cells. In this study, we found that QU induced cytochrome c-dependent apoptotic signaling. The release of pro-apoptotic cytochrome c was QU concentration- and time-dependent, and preceded activation of caspase-9 and -3. Flow cytometric FACScan analysis using fluorescence intensities of DiOC6 demonstrated that QU-induced cytochrome c release was independent of mitochondrial permeability transition (MPT), since the concentrations of QU that induced cytochrome c release did not alter mitochondrial membrane potential (delta pai(m)). Moreover, kinetic analysis of caspase activities showed that cytochrome c release led to the activation of caspase-9 and downstream death effector, caspase-3. Caspase-3 inhibitor (Ac-DEVD-CHO) partially blocked QU-induced apoptosis, suggesting the importance of caspase-3 in this apoptotic signaling mechanism. Supplementation with arachidonic acid (AA) sustained caspase-3 activation induced by QU. Using inhibitors against cellular arachidonate metabolism of lipooxygenase (Nordihydroxyguaiaretic Acid, NDGA) and cyclooxygenase (5,8,11,14-Eicosatetraynoic Acid, ETYA) demonstrated that QU-induced apoptotic signaling may be dependent on its role as a PLA-2 inhibitor. Interestingly, NDGA attenuated QU-induced cytochrome c release, caspase activity as well as apoptotic cell death. The blockade of cytochrome c release by NDGA was much more effective than that attained with cyclosporin A (CsA), a MPT inhibitor. ETYA was not effective in blocking cytochrome c release, except under very high concentrations. Caspase inhibitor z-VAD blocked the release of cytochrome c suggesting that this signaling event is caspase dependent, and caspase-8 activation may be upstream of the mitochondrial events. In summary, we report that QU induced cytochrome c-dependent apoptotic signaling cascade, which may be dependent on its role as a PLA-2 inhibitor. This apoptotic mechanism induced by QU may contribute to its known chemotherapeutic effects.     

Perioperative and Intraoperative Pain and Anesthetic Care of the Chronic Pain and Cancer Pain Patient Receiving Chronic Opioid Therapy

Abstract:   The expanding role of the anesthesiologist as a "perioperative physician" places ever-increasing demands upon his or her clinical skills and knowledge. One area of growing concern for the anesthesiologist involves the perioperative assessment and management of the opioid-tolerant chronic pain patient. Opioids occupy a position of unsurpassed clinical utility for the treatment of many types of painful conditions. Coupled with noticeable shifts in physician attitudes that have occurred in recent years regarding the use of opioids for the treatment of benign and malignancy-related pain, many more patients are presenting for surgical procedures who are opioid tolerant. It is important therefore that the practicing anesthesiologist become familiar with the currently available opioid formulations, including drug interactions and side effects, in order to better plan the patient's perioperative anesthetic needs and management. Unfortunately, there is a lack of scientifically rigorous studies in this important area, and most of the information must be derived from anecdotal reports and personal experience of anesthesiologists working in this field. In this review, we shall discuss some aspects of current chronic pain management, the newer forms of opioid administration which may be unfamiliar to the anesthesiologist, as well as clinical aspects of opioid use and tolerance including the impact it may have on perioperative anesthetic management.     

Nonstandard Lumbar Region in Predicting Fracture Risk

Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine (LS) BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1–L2 BMD with standard L2–L4 BMD and assess whether the addition of either LS site could improve fracture prediction over FN BMD. This study comprised a prospective cohort of 3016 women and men over 60?yr from the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to measure BMD at L1–L2, L2–L4, and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using receiver operating characteristic curve analyses. There were 565 women and 179 men with a minimal trauma fracture during a mean of 11?±?7?yr. L1–L2 BMD T-score was significantly lower than L2–L4 T-score in both genders (p?<?0.0001). L1–L2 and L2–L4 BMD models had a similar fracture predictive ability. LS BMD was better than FN BMD in predicting vertebral fracture risk in women [area under the curve 0.73 (95% confidence interval, 0.68–0.79) vs 0.68 (95% confidence interval, 0.62–0.74), but FN was superior for hip fractures prediction in both women and men. The addition of L1–L2 or L2–L4 to FN BMD in women increased overall and vertebral predictive power compared with FN BMD alone by 1% and 4%, respectively (p?<?0.05). In an elderly population, L1–L2 is as good as but not better than L2–L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in individuals with spinal degenerative disease are needed.     

Peri-operative management of Cushing’s disease

Management of patients with ACTH producing pituitary adenoma remains to be challenging. Removal of the pituitary adenoma through transsphenoidal surgery is the main stay of treatment. Complete resection of the adenoma is followed by the development of ACTH deficiency since the normal corticotrophs are suppressed by the pre-existing hypercortisolemia. The concern for ACTH deficiency has led many centers to advocate the use glucocorticoids before, during and after surgery. We provide evidence that such coverage with glucocorticoids is unnecessary until clinical or biochemical documentation of need is established. Given that patients are closely monitored, they are immediately treated with glucocorticoids once they exhibit any clinical and/or biochemical evidence of adrenal insufficiency. Defining remission in the immediate postoperative period has been rather difficult despite using different biochemical markers. Serum cortisol continues to be the best determinant of disease activity after surgical adenomectomy. However it needs to be interpreted with caution as a biochemical marker of remission in patients given glucocorticoids during and after surgery. Other biochemical markers are also used in the peri-operative period to determine the possibility of remission. These include the dexamethasone suppression test, CRH stimulation without dexamethasone, urinary free cortisol measurements, desmopressin stimulation test, the determination of salivary cortisol and / or plasma ACTH concentrations. Each test has its own advantages and limitations. The simplest and most informative approach is to measure serum cortisol levels repeatedly after surgery without the administration of exogenous glucocorticoids. Low serum cortisol levels (less than 2 ug/dL) in the peri-operative period are highly indicative of surgical success and a high likelihood for clinical remission. Higher serum cortisol levels require careful interpretation and further planning and discussions between the patient and the management team.     

Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases

Certain selective serotonin reuptake inhibitors (SSRIs) induce the clinical and biochemical manifestations of a metabolic syndrome by as yet unknown mechanism. Here we demonstrate that incubation (1 h) of rat hepatoma Fao cells with the SSRIs paroxetine and sertraline, but not with the atypical antipsychotic drug olanzapine, inhibited the insulin-stimulated Tyr phosphorylation of the insulin receptor substrate-1 (IRS-1) with half-maximal effects at approximately 10 microM. This inhibition correlated with a rapid phosphorylation and activation of a number of Ser/Thr IRS-1 kinases including JNK, S6K1, ERK and p38 MAPK, but not PKB (Akt). JNK appears as a key player activated by SSRIs because specific JNK inhibitors partially eliminated the effects of these drugs. The SSRIs induced the phosphorylation of IRS-1 on S307 and S408, which inhibits IRS-1 function and insulin signaling. These results implicate selected SSRIs as inhibitors of insulin signaling and as potential inducers of cellular insulin resistance.     

Relation of habitual cocoa consumption to aortic stiffness and wave reflections, and to central hemodynamics in healthy individuals

The effect of habitual cocoa consumption on arterial stiffness and wave reflection indexes, as well as on peripheral and central blood pressure, was assessed in 198 healthy subjects. In conclusion, higher cocoa intake was an independent determinant of low arterial stiffness and wave reflection indexes and was also independently associated with significantly lower central (aortic) pulse pressure.     

Surgical management of primary and metastatic sarcoma of the mobile spine

OBJECT: Sarcomas of the spine are a challenging problem due to their frequent and extensive involvement of multiple spinal segments and high recurrence rates. Gross-total resection to negative margins, with preservation of neurological function and palliation of pain, is the surgical goal and may be achieved using either intralesional resection or en bloc excision. The authors report outcomes of surgery for primary and metastatic sarcomas of the mobile spine in a large patient series. METHODS: A retrospective review of patients undergoing resection for sarcomas of the mobile spine between 1993 and 2005 was undertaken. Sarcomas were classified by histology study results and as either primary or metastatic. Details of the surgical approach, levels of involvement, and operative complications were recorded. Outcome measures included neurological function, palliation of pain, local recurrence, and overall survival. RESULTS: Eighty patients underwent 110 resections of either primary or metastatic sarcomas of the mobile spine. Twenty-nine lesions were primary sarcomas (36%) and 51 were metastatic sarcomas (64%). Intralesional resections were performed in 98 surgeries (89%) and en bloc resections were performed in 12 (11%). Median survival from surgery for all patients was 20.6 months. Median survival for patients with a primary sarcoma of the spine was 40.2 months and was 17.3 months for patients with a metastatic sarcoma. Predictors of improved survival included a chondrosarcoma histological type and a better preoperative functional status, whereas osteosarcoma and a high-grade tumor were negative influences on survival. Multivariate analysis showed that only a high-grade tumor was an independent predictor of shorter overall survival. American Spinal Injury Association scale grades were maintained or improved in 97% of patients postoperatively, and there was a significant decrease in pain scores postoperatively. No significant differences in survival or local recurrence rates between intralesional or en bloc resections for either primary or metastatic spine sarcomas were found. CONCLUSIONS: Surgery for primary or metastatic sarcoma of the spine is associated with an improvement in neurological function and palliation of pain. The results of this study show a significant difference in patient survival for primary versus metastatic spine sarcomas. The results do not show a statistically significant benefit in survival or local recurrence rates for en bloc versus intralesional resections for either metastatic or primary sarcomas of the spine, but this may be due to the small number of patients undergoing en bloc resections.