A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Effects of Intermittent Femoral Nerve Injections of Bupivacaine, Levobupivacaine, and Ropivacaine on Mitochondrial Energy Metabolism and Intracellular Calcium Homeostasis in Rat Psoas Muscle

Background: Long-acting local anesthetics cause muscle damage. Moreover, long-acting local anesthetics act as uncoupler of oxidative phosphorylation in isolated mitochondria and enhance sarcoplasmic reticulum Ca2+ release. The aim of the study was to evaluate effects of perineural injections of local anesthetics on mitochondrial energetic metabolism and intracellular calcium homeostasis in vivo.

Methods: Femoral nerve block catheters were inserted in adult male Wistar rats. Rats were randomized and received seven injections (1 ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle was quickly dissected from next to the femoral nerve. Local anesthetic concentrations in muscle were determined. Oxidative capacity was measured in saponin-skinned fibers. Oxygen consumption rates were measured, and mitochondrial adenosine triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial respiratory chain complexes were evaluated. Local calcium release events (calcium sparks) were analyzed as well as sarcoplasmic reticulum calcium content in saponin-skinned fibers.

Results: Eight hours after the last injection, psoas muscle concentration of local anesthetics was less than 0.3 [mu]g/g tissue. Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were significantly decreased in the muscle of rats treated with local anesthetics. A global decrease (around 50%) in all of the enzyme activities of the respiratory chain was observed. Levobupivacaine increased the amplitude and frequency of the calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.     

Does age worsen EEG slowing and attention deficits in obstructive sleep apnea syndrome?

OBJECTIVE: The aim of this study was to determine whether EEG slowing is more pronounced in older than younger OSAS patients and to verify whether this cortical slowing is correlated to daytime performance, respiratory perturbation and sleep fragmentation. METHODS: Twelve young OSAS patients (mean age 38.2+/-2.0 y) and 13 older OSAS patients (mean age 62.2+/-1.9 y) along with 13 young controls (mean age 35.8+/-2.0 y) and 14 older controls (mean age 60.2+/-2.0 y) underwent a polysomnographic evaluation followed by a waking EEG recording. As a global index of cortical slowing, a ratio of slow-to-fast frequencies was calculated in all cortical regions. Daytime performance was assessed using the four choice reaction time test. RESULTS: Differences in waking EEG and in daytime performance were analyzed by ANOVAs with Group and Age as factors. Waking EEG did not yield a Group by Age interaction. OSAS patients had higher ratios across all regions than controls. Similarly, daytime performance revealed no Group by Age interaction. However, OSAS patients showed more lapses than controls and older subjects were slower than younger subjects. CONCLUSIONS: Our results indicate that age does not interact with OSAS to worsen the severity of cortical slowing, but age can add to the OSAS effect to worsen daytime performance deficits in OSAS patients. SIGNIFICANCE: The daytime performance deficits observed particularly in elderly OSAS patients warrant a careful clinical assessment of these patients to prevent accidents and injuries.     

Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.     

Influence of time elapsed between myocardial infarction and coronary artery bypass grafting surgery on operative mortality.

OBJECTIVE: Optimal timing for CABG surgery after myocardial infarction (MI) remains controversial. We examined the influence of patient age and time elapsed between MI and isolated CABG surgery on operative mortality. METHODS: Perioperative data of 13,545 patients who underwent isolated CABG surgery from 1991 to 2005 were reviewed. A previous MI was found in 7219 patients, classified among groups A-E whether they underwent surgery less than 6h (A, n=26), between 6 and 24h (B, n=51), between 1 and 7 days (C, n=313), between 8 and 30 days (D, n=917), or more than 30 days (E, n=5912) after the event. Crude percentages and odds ratio estimates of operative mortality were calculated. RESULTS: In patients who had no history of MI, the mortality rate was 1.7%, while it was, respectively, 19.2, 9.8, 8.6, 3.2, and 2.4% in patients from groups A to E. Among 6589 patients over 65 years of age, 3027 had no history of MI. Their mortality was 2.4%, compared to, respectively, 35.7, 13.8, 11.3, 5.1, and 3.9% for those belonging to groups A-E. Overall odds ratio estimates of operative mortality were 3.92 (p=0.19), 5.08 (p=0.002), 4.33 (p=0.0001), 1.50 (p=0.08), and 1.18 (p=0.24) for groups A-E, respectively. CONCLUSIONS: Operative mortality is not influenced by a history of MI sustained more than 30 days prior to isolated CABG surgery, but is highly and most significantly increased between 6h and 1 week after MI, especially in older patients. That critical period should be avoided whenever possible.     

In vitro behavior of human nonfertile semen in isoosmotic and hyperosmotic media

High-ionic-strength media are known to favor rapid capacitation and acrosome reaction of spermatozoa in vitro. The influence of isoosmolar (N-BWW) and hyperosmolar (H-BWW) media on the percent motility, forward progression, and zona-free hamster egg penetration has been investigated for 148 semen from patients consulting for male or idiopathic sterility. After 15 h of incubation, the hyperosmotic medium had no significant detrimental effect on the percent motility of spermatozoa, although the forward progression was better maintained in the isoosmolar medium. In general egg penetration was increased when spermatozoa were treated with the hypertonic medium, and in particular 5 patients whose semen showed no penetration when treated with N-BWW scored greater than 12% when treated with H-BWW. For the 23 subjects who had an IVF at the same period, a good agreement with zona-free egg penetration was found in 70% of the cases.     

Sclerosed liver hemangioma mimicking malignant tumor at MR imaging: Pathologic correlation

This case report illustrates atypical magnetic resonance (MR) imaging findings in a liver hemangioma mimicking a malignant lesion—lower signal intensity than cerebrospinal fluid on T2-weighted spin-echo images and lack of early enhancement on dynamic contrast material—enhanced gradient-echo images. Pathologic analysis demonstrated nearly total replacement of the vascular cavities by dense fibrous tissue. In this rare, sclerosed form, this lesion could not be defined as a hemangioma with MR imaging.     

Platelet receptor expression on three human megakaryoblast-like cell lines.

Platelets, the progeny of bone marrow megakaryocytes, are nonnucleated cells; many platelet proteins, including platelet membrane receptors, are believed to be derived from megakaryocytes. Several hematopoietic cell lines that exhibit megakaryocytic characteristics have been established as models for the study of megakaryocyte biology. We report here the screening of platelet receptor expression, in terms of functional coupling with the formation of two second messengers, calcium and cAMP, in three cell lines exhibiting megakaryoblastic properties: HEL, MEG-01, and DAMI. We show that all these cell lines respond to thrombin, ADP, epinephrine, and prostaglandin E1 (PGE1). However, transmembrane signaling pathways appear partly different from those present in mature platelets, because the action of thrombin was found to be positively coupled with the cAMP pathway, in addition to that of calcium, and because PGE1, which interacts with the cAMP pathway, also raises intracellular calcium levels in the three cell lines studied. Furthermore, an endothelin-1-induced increase in intracellular calcium level was observed in MEG-01 cells, strongly suggesting the expression of endothelin receptors on platelet precursors cells, whereas the presence of such receptors is controversial on platelets. These cell lines should prove useful in further studies of the expression and molecular pharmacology of platelet receptors on platelet precursor cells, as well as for the investigation of functional roles for platelet receptors on megakaryoblastic cells.     

Benzo(a)pyrene inhibits epidermal growth factor binding and receptor autophosphorylation in human placental cell cultures

Studies investigated the effects of benzo(a)pyrene (BP) treatment on epidermal growth factor (EGF) receptor binding and kinase activity in human placental cell cultures. Specific binding of 125I-EGF to cells from early gestation placentae was significantly decreased by 37 and 60% following exposure to 1 and 10 microM BP, respectively, for 24 hr. In contrast, cells cultured from term placentae showed no inhibitory effect of either concentration of BP. Specific binding of 125I-labeled insulin and insulin-like growth factors-I and -II to early gestation cells was decreased only 15-18% at 10 microM BP, which indicates that loss of membrane receptors appears to be selective for EGF. Scatchard analysis of early gestation cells revealed that BP was associated with a dose-dependent loss in the number of high affinity EGF binding sites. Evidence from cross-linking and autophosphorylation experiments confirmed that the Mr 170,000 binding protein was decreased in a dose-dependent manner following BP treatment. In comparison, term placental cells exhibit a 26% loss of EGF receptor autophosphorylation without alteration in binding following exposure to 10 microM BP. Thus, early gestation cells exhibit a BP-related down-regulation of EGF receptors, whereas term placental cells show receptor desensitization. No adverse effect of BP treatment was observed on the incorporation of [35S] methionine into proteins secreted by early gestation cells. Further experiments compared the effects of BP with the related poly-cyclic compounds beta-naphthoflavone, alpha-naphthoflavone, and 3-methylcholanthrene. In early gestation cells, EGF binding and receptor autophosphorylation were measurably decreased at 10 microM concentrations of these polycyclic compounds, but to a lesser extent than observed with BP. In term placental cells, however, EGF binding was unchanged or increased, whereas receptor autophosphorylation was decreased 10-26%. Thus, exposure of term placental cells to these polycyclic compounds leads to a dissociation between EGF binding and receptor protein kinase activity. Finally, aryl hydrocarbon hydroxylase activity was induced 20- to 200-fold in early placental cells exposed to BP, beta-naphthoflavone, and 3-methylcholanthrene. In summary, the direct effects of BP and related compounds observed on placental EGF receptors may indicate altered function of EGF in the regulation of cell growth and differentiation in the human placenta.