Renal physiology. Laparoscopic considerations

Oliguria is a recognized component of the physiologic effect of increased intra-abdominal or retroperitoneal pressure. The cause is multifactorial, emanating from vascular and parenchymal compression, and is associated with systemic hormonal effects. Ureteral obstruction does not play a significant role. These changes are pressure-dependent and are usually not apparent until pressures reach 15 mm Hg or more. This effect is not associated with any histologic pathology or evidence of renal tubular damage. After the release of the pneumoperitoneum or pneumoretroperitoneum, the renal function and urine output return to normal with no long-term sequelae, even in patients with pre-existing renal disease. The entire operative team must understand the physiologic effects of CO2 insufflation, which allows appropriate intraoperative monitoring and management and minimizes intraoperative and postoperative complications.     

Differential expression of the PSD-95 gene family in electrosensory neurons

The PSD-95 family of membrane-associated guanylate kinase (MAGUK) proteins are involved in the assembly and organization of neurotransmitter receptors at excitatory synapses in the vertebrate nervous system. We have isolated partial cDNAs for five PSD-95 family members from Apteronotus leptorhynchus brain RNA using a degenerate PCR method. The amino acid sequences deduced indicate that A. leptorhynchus neurons express homologues of the mammalian PSD-93, SAP-97, and SAP-102 MAGUKs and two homologues of mammalian PSD-95. In situ hybridization experiments have been carried out to localize the cellular expression of all five MAGUK mRNAs in the central nervous system of A. leptorhynchus. In the cerebellum the expression patterns are highly similar to patterns reported for mammalian cerebellum, suggesting an evolutionary conservation of the functional roles in this gene family. Cellular levels of expression of the PSD-95 MAGUK mRNAs and the NMDAR-1 mRNA were highly correlated in neurons of the dorsal forebrain but were not correlated in neurons of the electrosensory lateral line lobe (ELL) or the cerebellum. These results suggest that the expression of PSD-95 MAGUK genes in forebrain neurons may provide mechanisms for synaptic organization that are not shared by neurons in the ELL and cerebellum.     

Effect of hyperventilation on brain tissue oxygenation and cerebrovenous PO2 in rats

Previous studies have shown that cortical tissue oxygenation is impaired during hyperventilation. However, it is important to quantify the effect of hyperventilation on brain tissue PO(2) and cerebrovenous PO(2) simultaneously especially since cerebral venous oxygenation is often used to assess brain tissue oxygenation. The present study was designed to measure the sagittal sinus PO(2) (PvO(2)), brain tissue PO(2) in the thalamus (PtO(2)), and brain temperature (Bt) simultaneously during acute hyperventilation. Isoflurane-anesthetized rats were hyperventilated for 10 min during which time the arterial carbon dioxide tension (PaCO(2)) dropped from 40.3+4.9 mmHg to 23.5+2.8 mmHg. PtO(2) declined from 26.0+/-4.2 mmHg to 14.8+/-5.2 mmHg (P=0.004) while brain temperature decreased from 36.5+0.3 degrees C to 36.2+0.3 degrees C (P=0.02). However, PvO(2) and arterial blood pressure (BP) did not change during hyperventilation. The maintenance of PvO(2) when perfusion is thought to decline and PtO(2) decreases suggests that there may be a diffusion limitation, possibly due to selective perfusion. Therefore, cerebrovenous PO(2) may not give a good assessment of brain tissue oxygenation especially in conditions of acute hyperventilation, and deeper brain regions other than the cortex also show impaired tissue oxygenation following hyperventilation.     

Physiology of the lateral decubitus position and one-lung ventilation

OLV is most frequently utilized to provide a quiet field for the performance of many different surgical procedures. In some patients, severe hypoxemia may result, mandating the implementation of other therapies to provide adequate oxygenation. This paper has reviewed the physiological consequences of the lateral position that may contribute to the hypoxemia and the techniques we utilize at our institution for establishing OLV, maintaining OLV, and treating hypoxemia during OLV. Our technique is performed with the goal of maintaining adequate gas exchange and protecting the ventilated lung from potential overdistension and injury. It remains for future study to determine if the use of a lung protective strategy during intraoperative OLV offers any benefit to patients at risk for postoperative lung injury, such as those undergoing major lung resections.     

Long-term outcomes among localized prostate cancer survivors: health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy.

PURPOSE: We sought to elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a well-characterized cohort of prostate cancer (PC) survivors 4 to 8 years after primary treatment. PATIENTS AND METHODS: Patients who had been evaluated previously at a median of 2.6 years after radical prostatectomy (RP), external radiation (three-dimensional conformal radiation therapy [3-D CRT]), or brachytherapy (BT) were recontacted at a median of 6.2 years after treatment. The clinical relevance of long-term HRQOL impairment among survivors was established by comparison with controls of similar age. Factors associated with HRQOL changes during this interval were evaluated. RESULTS: Of the 964 eligible men, 709 (73.5%) completed measurable questionnaires. In four domains (urinary irritative-obstructive, urinary incontinence, bowel, and sexual), significant HRQOL differences were detected for at least one of the therapy groups, compared with controls (all P < .05). During the 4-year interval, significant improvement was observed for the urinary irritative-obstructive (P < .0001) and bowel (P < .0001) domains among BT patients, whereas urinary incontinence HRQOL worsened for both the BT (P = .0017) and 3-D CRT (P = .0008) treatment groups. Overall sexual HRQOL deteriorated for the 3-D CRT cohort (P = .0017), as well as for controls (P = .0136). Among RP patients, significant HRQOL changes were not observed. CONCLUSION: During a 4-year interval from earlier to longer-term phases of PC treatment survivorship, sexual, urinary, and bowel dysfunction remain significant concerns among early-stage PC treatment survivors, compared with control men. Although postprostatectomy HRQOL remains relatively stable during this interval, disease-specific HRQOL continues to evolve among men treated with BT and 3-D CRT.     

Evaluation by computerized axial tomography of eclamptic women with seizures refractory to magnesium sulfate therapy

Over a 1-year period, seven eclamptic patients with repetitive seizures while receiving therapeutic levels of intravenous magnesium sulfate were evaluated by computerized axial tomography. In five patients brain abnormalities were identified, which included diffuse cerebral edema (one), cerebral venous thrombosis (two), and low density white matter (two). Clinical management of eclamptic women on the basis of structural central nervous system abnormalities documented by computerized tomography appears to warrant further investigation.     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。     

Analysis of the metabolic footprint and tissue metabolome of placental villous explants cultured at different oxygen tensions reveals novel redox biomarkers

Pre-eclampsia (PE) is a multi-system disorder of pregnancy hypothesised to arise from circulating factors derived from an unhealthy placenta. Some changes in placental phenotype seen in PE can be reproduced by culture in altered oxygen (O(2)) tension. Currently, these circulating factors are unidentified, partly due to the complexity of maternal plasma. Investigation of factors released from placental tissue provides a potential method to identify bioactive compounds. Experimental strategies to study compounds present in a biological system have expanded greatly in recent years. Metabolomics can detect and identify endogenous and secreted metabolites. We aimed to determine whether metabolites could be identified in placental cultures with acceptable experimental variability and to determine whether altered O(2) tension affects the composition of the placental metabolome. In this study we used gas-chromatography-mass spectroscopy to determine the presence of metabolites in conditioned culture medium (CCM) and tissue lysates of placental villous explants cultured in 1, 6 and 20% atmospheric O(2) for 96h. This experimental strategy had an intra-assay variation of 6.1-11.6%. Intra and inter-placental variability were 15.7-35.8% and 44.8-46.2% respectively. Metabolic differences were identified between samples cultured in 1, 6 and 20% O(2) in both CCM and tissue lysate. Differentially expressed metabolites included: 2-deoxyribose, threitol or erythritol and hexadecanoic acid. We conclude that metabolomic strategies offer a novel approach to investigate placental function. When conducted under carefully controlled conditions, with appropriate statistical analysis, metabolic differences can be identified in placental explants in response to altered O(2) tension. Metabolomics could be used to identify changes in conditions associated with placental pathology.     

A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.