Is serial determination of inspiratory muscle strength a useful prognostic marker in chronic heart failure?

BACKGROUND: Little data exists on the prognostic role of inspiratory muscle strength (PImax) in chronic heart failure (CHF). Training studies, however, frequently use it as a therapeutic target and surrogate marker for prognosis. The prognostic value of changes of PImax that allow this extrapolation is unknown. DESIGN: Patients with stable CHF were prospectively included and 1-year and all-time event rates recorded for endpoint analysis. METHODS: In 158 patients (85% men; New York Heart Association functional class: 2.4+/-0.6), PImax was measured along with clinical evaluations at two visits, the initial visit and the second visit, 6.4+/-1.4 months apart. The mean follow-up was 59+/-34 months. RESULTS: Overall, 59 patients (37%) reached the primary endpoint of death or hospitalization (endpoint positive), and overall mortality rate (secondary endpoint) was 26% (42 patients). PImax did not differ between endpoint-negative and endpoint-positive patients, both at the initial and at the second visit (8.3+/-5.6 vs. 7.3+/-3.4 kPa and 8.8+/-6.0 vs. 7.9+/-3.6 kPa, respectively; P=NS), and both groups showed increased PImax (0.6+/-2.6 vs. 0.6+/-2.8 kPa; P=NS). Cox analyses found neither the absolute nor the relative change of PImax to be significant predictors for the primary and secondary endpoints (P=NS for both), both for the 1-year and for the all-time event rates. Endpoint rates did not differ between patients showing increasing or decreasing PImax (P=NS; relative risk (RR): 0.77; 95% confidence interval: 0.47-1.27). CONCLUSION: Trials focusing on inspiratory muscle function should use the actual levels of PImax as a surrogate marker to represent prognostic information, rather than relative or absolute changes. This is the first study to investigate the prognostic information of the changes of PImax over time, regarding both short-term and long-term morbidity and mortality in patients with stable CHF.     

Essential role of p21/waf1 in the mediation of the anti-proliferative effects of GHRH antagonist JMR-132

GHRH, besides its neuroendocrine action in controlling the release of GH from the pituitary, stimulates the growth of various cancers in vivo and in vitro by direct mechanism(s). However, the molecular mechanism that mediates these proliferative effects of GHRH in extrapituitary tissues remains poorly characterized. In the present study, we investigated whether the tumor suppressor p21/waf1 is involved in the mediation of the proliferative effects of GHRH in A549 human lung cancer epithelial cells. Exposure of A549 cells to the GHRH antagonist JMR-132 caused a significant inhibition in the rate of cell proliferation. In A549 cells, GHRH suppressed while JMR-132 increased the levels of p21 expression in a dose-dependent manner. This suggests that GHRH could regulate p21 levels. We then evaluated whether p21 is required in A549 cells for the regulation of cell proliferation by GHRH. To this end, we knocked-down p21 expression in A549 cells by siRNA and assessed the effects of antagonist JMR-132 on cell proliferation. We found that the loss of p21 expression abolished the anti-proliferative effects of JMR-132. Suppression of p21 expression by siRNA in human HT29 colon cancer cells and non-transformed mouse osteoblasts KS483 also blocked the anti-proliferative effects of JMR-132 suggesting that the regulation of cell proliferation by GHRH is p21 dependent. These results shed light on the molecular mechanism of action of GHRH antagonists in tumor tissues and suggest that the antineoplastic activity of GHRH antagonists could be considered for the treatment of cancers expressing p21.     

Complete mesocolic excision and extended (D3) lymphadenectomy for colonic cancer: is it worth that extra effort? A review of the literature

Purpose

Recent interest in complete mesocolic excision (CME) with central vascular ligation (CVL) or extended (D3) lymphadenectomy (EL) for curative resection of colon cancer has been driven by published series from experienced practitioners showing excellent survival outcomes and low recurrence rates. In this article, we attempt to clarify the role of CME or EL in modern colorectal surgery.

Methods

A narrative review of the evidence for CME and EL in the curative treatment of colon cancer.

Results

The principal of CME surgery, similar to total mesorectal excision (TME) for rectal cancer, is the removal of all lymphatic, vascular, and neural tissue in the drainage area of the tumour in a complete mesocolic envelope with intact mesentery, peritoneum and encasing fascia. Extended (D3) lymphadenectomy (EL) is based on similar principles. Sound anatomical and oncological arguments are made to support the principles of removing the tumor contained within an intact mesocolic facial envelope together with an extended lymph node harvest. Excellent oncological outcomes with minimal morbidity and mortality have been reported. This has led to calls for the standardisation of surgery for colon cancer using CME. However, there is conflicting evidence regarding the prognostic benefit of greater lymph node harvests and the evidence for an oncological benefit of CME is limited by methodology flaws and several potential confounding factors.

Conclusions

Although there is a reasonable anatomical and oncological basis for these techniques, there are no randomised controlled trials from which to draw confident conclusions and there is insufficient consistent high quality evidence to recommend widespread adoption of CME.

     

Germinal center B (GCB) and non-GCB cell-like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation

Patients with germinal center B cell-like (GCB) and non-GCB diffuse large B cell lymphomas (DLBCL) receiving first line therapy have distinct prognosis. We explored the differences in outcome following salvage autologous hematopoietic stem cell (HSC) transplantation between patients with GCB and non-GCB DLBCL. Forty-four patients with relapsed and 15 patients with primary refractory chemosensitive disease undergoing BEAM (BCNU [carmustine], etoposide, cytarabine, melphalan) conditioning and autologous HSC were included. Immunohistochemical analysis was performed for CD10, BCL-6, MUM1 (allowing classification into GCB and non-GCB-like DLBCL) and BCL-2. Median follow-up of survivors was 25 months; median age at the time of transplantation was 60 years (range 17–77). Thirty-two patients (54%) were classified as having GCB and 27 (46%) as having non-GCB-like DLBCL. Patients with GCB and non-GCB DLBCL did not differ in the risk of progression after HSC transplant ( P  = 0·78) or overall survival ( P  = 0·48). In multivariate analysis, only time to progression after initial treatment impacted overall survival. We conclude that patients with relapsed or primary refractory chemosensitive GCB and non-GCB-like DLBCL derive similar benefit from autologous HSC transplant.     

Fetal lamb coagulation system during birth asphyxia

Levels of many coagulation factors are low in the healthy infant and even lower in the asphyxiated premature infant. We investigated whether a brief exposure to asphyxia at the time of birth causes the activation and consumption of coagulation factors. Following delivery by caesarean section, premature lambs were asphyxiated by occluding the endotracheal tube for 10 min and then resuscitated. Blood was obtained prior to and following birth for measurement of blood gases and the coagulation system. Birth asphyxia in the premature lamb resulted in thrombin generation and rapid consumption of specific coagulation factors.     

Abnormalities of pulmonary artery wedge pressures in sleep-induced apnea

Six patients with sleep apnea syndrome were studied with continuous hemodynamic monitoring during sleep. Sleep apnea had been previously documented with an average number of apneas per hour of sleep ranging from 23 to 93 (mean 63). There was a significant decrease in heart rate during sleep (82 ± 5 to 69 ± 6, P < 0.01). There was a significant rise in systemic blood pressure (103 ± 2 mm Hg to 116 ± 6 mm Hg, P < 0.05) and pulmonary artery pressure (20 ± 1 mm Hg to 32 ± 5 mm Hg) during sleep. In addition, pulmonary artery wedge pressure increased (12 ± 2 mm Hg to 20 ± 3 mm Hg, P < 0.05) during sleep and 5 of the 6 patients developed an abnormal pulmonary wedge pressure. There was a significant decrease in P_O2 during sleep (71 ± 3 mm Hg to 49 ± 2 mm Hg, P < 0.005). These findings suggest that increases in pulmonary wedge pressures may be contributing to increase in pulmonary artery pressures in these patients during sleep.     

A randomized,double-blind,placebo-controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome

Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.     

Acute pancreatitis in patients on chronic peritoneal dialysis: an increased risk?

OBJECTIVES: The primary aim of this study is to determine if patients with end-stage renal disease (ESRD) on peritoneal dialysis (PD) have a higher risk of developing acute pancreatitis (AP) than patients on hemodialysis (HD). The secondary aim is to compare the outcomes of AP between the two groups. METHOD: This is a retrospective case-control study. The study groups consisted of all patients initiated on HD and PD between January 1, 1998 and August 1, 2003. AP was identified using ICD-9 codes. Statistical analysis was carried out using Poisson regression, Kaplan-Meier curve, log-rank test, and Cox regression. RESULTS: One thousand two hundred and thirty-three and 160 eligible patients were identified in the HD and PD groups, respectively. Twenty-eight patients had AP. Eight patients were excluded as they had identifiable etiologies for AP. Of the remaining 20 patients with AP, 14 were in the HD group and 6 were in the PD group (p= 0.009). Incidence of AP was 18.4 per 1,000 person-years in the PD group and 6.5 per 1,000 person-years in the HD group (p= 0.033). Kaplan-Meier curves showed a significant difference in AP-free survival between the two groups (log-rank p= 0.026). Using time-dependent analysis, the hazard ratio for AP in PD patients after adjustment for age and sex was 3.94 (p= 0.006). There was no observed difference in length of hospital stay and ICU stay. All cases of AP were interstitial. There were no complications or deaths related to AP. CONCLUSION: PD is a risk factor for AP. There is no statistical difference in AP-related mortality and morbidity between HD and PD.     

Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars

The Mars Organic Analyzer (MOA), a microfabricated capillary electrophoresis (CE) instrument for sensitive amino acid biomarker analysis, has been developed and evaluated. The microdevice consists of a four-wafer sandwich combining glass CE separation channels, microfabricated pneumatic membrane valves and pumps, and a nanoliter fluidic network. The portable MOA instrument integrates high voltage CE power supplies, pneumatic controls, and fluorescence detection optics necessary for field operation. The amino acid concentration sensitivities range from micromolar to 0.1 nM, corresponding to part-per-trillion sensitivity. The MOA was first used in the lab to analyze soil extracts from the Atacama Desert, Chile, detecting amino acids ranging from 10-600 parts per billion. Field tests of the MOA in the Panoche Valley, CA, successfully detected amino acids at 70 parts per trillion to 100 parts per billion in jarosite, a sulfate-rich mineral associated with liquid water that was recently detected on Mars. These results demonstrate the feasibility of using the MOA to perform sensitive in situ amino acid biomarker analysis on soil samples representative of a Mars-like environment.     

Prospective assessment of magnetic resonance cholangiopancreatography for noninvasive imaging of the biliary tree.

BACKGROUND: Traditionally, ERCP has been the only reliable method for imaging the biliary tree, but it is invasive and carries a risk of complications. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method for imaging the biliary tree. The aim of this study was to prospectively assess the accuracy of MRCP in a large number of patients. METHODS: Consecutive patients referred to a teaching hospital for ERCP were eligible for study entry. MRCP was performed within 24 hours before ERCP. MRCP findings were compared with ERCP findings or, when the initial ERCP was unsuccessful, with results of repeat ERCP, percutaneous transhepatic cholangiography, or surgery. RESULTS: One hundred forty-six patients underwent 149 ERCP/MRCP procedures, of which 129 were evaluable with successful MRCP and ERCP or an ERCP-equivalent study. Diagnoses included choledocholithiasis in 46 and biliary stricture in 12 patients. The sensitivity, specificity, positive, and negative predictive values for MRCP in the diagnosis of choledocholithiasis were 97.9%, 89.0%, 83.6%, and 98.6%, respectively. All 12 strictures were diagnosed by MRCP (sensitivity 100%, specificity 99.1%). CONCLUSIONS: MRCP is an accurate, noninvasive alternative to ERCP for imaging the biliary tree. Choledocholithiasis and biliary strictures can be reliably diagnosed or excluded by MRCP. MRCP should be used increasingly in patients with suspected biliary obstruction to select those who require a therapeutic procedure.