Comparison of Amsorb®, Sodalime, and Baralyme® Degradation of Volatile Anesthetics and Formation of Carbon Monoxide and Compound A in Swine In Vivo

Background: Consequences of volatile anesthetic degradation by carbon dioxide absorbents that contain strong base include formation of compound A from sevoflurane, formation of carbon monoxide (CO) and CO toxicity from desflurane, enflurane and isoflurane, delayed inhalation induction, and increased anesthetic costs. Amsorb(R) (Armstrong Ltd., Coleraine, Northern Ireland) is a new absorbent that does not contain strong base and does not form CO or compound A in vitro. This investigation compared Amsorb(R), Baralyme(R) (Chemetron Medical Division, Allied Healthcare Products, St. Louis, MO), and sodalime effects on CO (from desflurane and isoflurane) and compound A formation, carboxyhemoglobin (COHb) concentrations, and anesthetic degradation in a clinically relevant porcine in vivo model.

Methods: Pigs were anesthetized with desflurane, isoflurane, or sevoflurane, using fresh or partially dehydrated Amsorb(R), Baralyme(R), and new and old formulations of sodalime. Anesthetic concentrations in the fresh (preabsorber), inspired (postabsorber), and end-tidal gas were measured, as were inspired CO and compound A concentrations and blood oxyhemoglobin and COHb concentrations.

Results: For desflurane and isoflurane, the order of inspired CO and COHb formation was dehydrated Baralyme(R) >> soda-lime > Amsorb(R). For desflurane and Baralyme(R), peak CO was 9,700 +/- 5,100 parts per million (ppm), and the increase in COHb was 37 +/- 14%. CO and COHb increases were undetectable with Amsorb(R). Oxyhemoglobin desaturation occurred with desflurane and Baralyme(R) but not Amsorb(R) or sodalime. The gap between inspired and end-tidal desflurane and isoflurane did not differ between the various dehydrated absorbents. Neither fresh nor dehydrated Amsorb(R) caused compound A formation from sevoflurane. In contrast, Baralyme(R) and sodalime caused 20-40 ppm compound A. The gap between inspired and end-tidal sevoflurane did not differ between fresh absorbents, but was Amsorb(R) < sodalime < Baralyme(R) with dehydrated absorbents.     

Treatment of acute antibody-mediated rejection: a single-center experience

Introduction

Acute antibody-mediated rejection (AMR) leads to graft loss. The combination of plasmapheresis (PP), intravenous immunoglobulin (IVIG), and rituximab (RTX) has been reported to be effective therapy.

Patients and methods

Between October 2005 and September 2009, 8 (4.7%) kidney transplant recipients developed AMR, diagnosed by severe acute rejection and extensive C4d staining in peritubular capillaries.

Results

All patients were treated with two to six sessions of PP with IVIG added after the last PP. In two patients, RTX was prescribed after PP and IVIG. Baseline immunosuppression was based on steroids, mycophenolate mofetil or azathioprine, and tacrolimus or cyclosporine or everolimus. The presence of subsequent significant decrease in anti-HLA class I antibodies was demonstrated in a highly sensitized patient before and after transplantation with PP treatment. An increase was observed before the diagnosis of AMR. After a mean follow-up of 10 months (range = 1-23), patient and graft survivals were 100% and 50%, respectively. Three patients lost their transplants to AMR refractory to treatment and one patient, due to interstitial fibrosis and tubular atrophy at 23 months after AMR. Finally, four patients recovered renal function, showing a mean serum creatinine of 2.2 ± 0.45 mg/dL.

Conclusions

Early diagnosis and treatment with PP, IVIG, and RTX may resolve AMR. PP before and after transplantation in high-risk patients may result in anti-HLA class I and class II antibody removal from plasma and prevention of AMR.     

The decrease in serum IL-18 levels after bariatric surgery in morbidly obese women is a time-dependent event

Background We have evaluated the impact of the reproductive status of morbidly obese women, and of the time elapsed since surgery, on the response of the proinflammatory serum cardiovascular risk marker interleukin-18 (IL-18) to the sustained and marked weight loss achieved after bariatric surgery. Methods Serum IL-18 levels were measured in 33 morbidly obese women before bariatric surgery and after losing at least 15% of the initial weight, irrespective of the time needed to achieve this goal (5 to 33 months). Results Patients lost 30.7 ± 7.8% of the initial weight, with a concomitant reduction of serum IL-18 concentrations (P < 0.001). A stepwise multiple regression analysis showed that the percentual decrease in serum IL-18 levels was determined by the interaction between the time elapsed since surgery and the percentual reduction of waist circumference (R² = 0.333, F = 15.500, β = 0.577, P < 0.001), but not by the individual effects of the time elapsed since surgery, percentual body weight loss, percentual reduction of waist circumference, menopausal status or type of surgical procedure, or by the interaction between the time elapsed since surgery with the percentual body weight loss or with menopausal status. Conclusion Serum IL-18 levels decrease after bariatric surgery in a time-dependent manner, in relation to the reduction in waist circumference. The fact that the amelioration of the obesity-associated inflammatory process requires time and not only weight loss, might contribute to explain early non-surgical cardiovascular complications of bariatric surgery.     

Health outcomes of midlife and older Latina and black American mothers of children with developmental disabilities

The impact of caring for a child with a developmental disability on the physical and mental health of Latina and Black American women was examined. We used the National Health Interview Survey to compare the health of older mothers who were co-residing with a child who had a developmental disability to the health of same age mothers without caregiving responsibilities. Findings show that for both groups, older adult caregivers were more likely to report having limitations from arthritis than their noncaregiving counterparts. Caregiving was associated with more depressive symptoms for Latinas, but this relationship was not found for Black American women. Findings suggest that physical and mental health of caregivers need more attention in research and practice.     

Disruption of hepatocyte growth factor/c-Met signaling enhances pancreatic beta-cell death and accelerates the onset of diabetes

OBJECTIVE

To determine the role of hepatocyte growth factor (HGF)/c-Met on β-cell survival in diabetogenic conditions in vivo and in response to cytokines in vitro.

RESEARCH DESIGN AND METHODS

We generated pancreas-specific c-Met-null (PancMet KO) mice and characterized their response to diabetes induced by multiple low-dose streptozotocin (MLDS) administration. We also analyzed the effect of HGF/c-Met signaling in vitro on cytokine-induced β-cell death in mouse and human islets, specifically examining the role of nuclear factor (NF)-κB.

RESULTS

Islets exposed in vitro to cytokines or from MLDS-treated mice displayed significantly increased HGF and c-Met levels, suggesting a potential role for HGF/c-Met in β-cell survival against diabetogenic agents. Adult PancMet KO mice displayed normal glucose and β-cell homeostasis, indicating that pancreatic c-Met loss is not detrimental for β-cell growth and function under basal conditions. However, PancMet KO mice were more susceptible to MLDS-induced diabetes. They displayed higher blood glucose levels, marked hypoinsulinemia, and reduced β-cell mass compared with wild-type littermates. PancMet KO mice showed enhanced intraislet infiltration, islet nitric oxide (NO) and chemokine production, and β-cell apoptosis. c-Met-null β-cells were more sensitive to cytokine-induced cell death in vitro, an effect mediated by NF-κB activation and NO production. Conversely, HGF treatment decreased p65/NF-κB activation and fully protected mouse and, more important, human β-cells against cytokines.

CONCLUSIONS

These results show that HGF/c-Met is critical for β-cell survival by attenuating NF-κB signaling and suggest that activation of the HGF/c-Met signaling pathway represents a novel strategy for enhancing β-cell protection.Type I diabetes is an autoimmune disease that results from cellular cytotoxicity leading to selective and progressive destruction of insulin-secreting cells (1–3). Many growth factors known to control cell growth and survival in physiologic and pathologic conditions are expressed in the pancreas and could potentially participate in an autocrine/paracrine fashion in the final fate of β-cells in an autoimmune environment. Overexpression of IGF-1, transforming growth factor-β, or granulocyte macrophage-colony stimulating factor ameliorates islet infiltration and β-cell death in mouse models of increased islet inflammation and diabetes (4–6). However, the role of endogenous pancreatic growth factors in type I diabetes has not been examined. Because growth factors can locally affect β-cell survival, neogenesis, and regeneration, and modulate chemokine production and immune responses, alterations in the level/activation of growth factor signaling pathways might contribute to the delay/acceleration of the onset of diabetes.Hepatocyte growth factor (HGF)/c-Met signaling pathway participates in the control of multiple biological functions, including development, proliferation, survival, regeneration, and branching morphogenesis (7). HGF binds with high affinity to, and induces the dimerization of, c-Met, its transmembrane tyrosine kinase receptor (8). Deletion of exon 16 of the c-Met gene, which encodes Lys¹¹⁰⁸ (ATP binding site), essential for the kinase activity of this receptor, in knockout mice results in embryonic lethality (9). These mice display a phenotype identical to HGF knockout mice (10). Both HGF and c-Met are expressed in the pancreas; HGF localizes to endothelial, islet, and mesenchymal cells, and c-Met is expressed in islet, ductal, and pancreatic progenitor cells (11–14). Conditional ablation of the c-Met gene in mouse β-cells using RIP-Cre and lox-c-Met mice leads to deficient insulin secretion without alteration of β-cell mass (12,13). On the other hand, HGF overexpression in the β-cell of transgenic mice increases β-cell replication, mass, and function (15,16). Furthermore, HGF improves islet graft survival in animal models of diabetes (17–19). HGF positively influences autoimmune responses, reducing the severity of autoimmune myocarditis and arthritis (20,21). HGF also downregulates airway and kidney inflammation, and inflammatory bowel disease (22–24). Whether HGF plays a role in autoimmune diabetes is unknown.To address the function of c-Met in the development, growth, and maintenance of β-cells under physiologic conditions, as well as its role in β-cell survival and response to injury in vivo, we generated pancreas-specific c-Met-null (PancMet KO) mice. We report that although c-Met is dispensable for normal β-cell growth and function under basal conditions, it is critically important for β-cell survival in diabetogenic conditions. β-Cell survival is dramatically worsened in the absence of HGF/c-Met signaling, resulting in accelerated diabetes onset. These observations also apply to human β-cells, underscoring a therapeutic opportunity for the HGF/c-Met signaling pathway in human diabetes.     

Effect of various trophic factors on bacterial translocation in experimental short bowel syndrome

Massive bowel resection triggers an adaptive process in the remaining intestine in spite of which, bacterial translocation (BT) is frequent under these conditions. Several trophic factors, including growth hormone (GH), epidermal growth factor (EGF) and insuline (INS) are involved in the process of adaptation in short bowel syndrome (SBS). However, the effect of GH, EGF or INS on BT has not been investigated experimentally. The aim of the study was to test the hypothesis that GH, EGF or INS administration prevents BT in rats with SBS receiving only parenteral nutrition (PN). Thirty-seven adult Wistar rats underwent central venous cannulation and were randomly assigned to one of two groups receiving for ten days four treatment regimes: PN group (N = 10) fasting, all-in-one PN solution (300 mL/kg/24 h, 280 kcal/kg/24 h), 80% gut resection including ileo-cecal valve. GH group (N = 9) fasting, same PN regime and resection plus GH (1 mg/kg/d, s.c.). EGF group (N = 9): same PN regime and resection plus EGF (150 microgr/24 h, e.v.) INS group(N = 9): same PN regime and resection plus INS (1 U.I./100 g/24 h s.c.) At the end of the experiment the rats were exanguinated and mesenteric lymph nodes and samples of systemic and portal blood were obtained and cultured. Several samples of full-thickness jejunal wall were taken for measuring cell proliferation index (PCNA) and mucosal thickness. Jejunal mucosal thickness increased by 30%, 28% and 29% and PCNA index by 21%, 20% and 25% in GH, EGF and INS, treated rats respectively in comparison with those treated with PN alone. However, contrary to our expectations, BT expressed by positive culture of intestinal germs in systemic blood was demonstrated respectively in 44%, 40% and 28% of GH, EGF and INS animals, respectively, and in 0% of PN-only rats. Although exogenous GH, EGF or INS improves gut mucosal structure in rats with SBS treated with PN, it seems to increase rather than decrease mucosal permeability to intestinal germs in them.     

NMP 22, BTA stat test and cytology in the diagnosis of bladder cancer: a comparative study

OBJECTIVE: To evaluate the usefulness of the NMP 22 and BTA stat test in the diagnosis and follow-up of bladder cancer and to compare these tests to cytology and cystoscopy, routine diagnostic methods. METHODS: 150 patients followed up for bladder cancer or symptoms suggestive of bladder cancer underwent cystoscopy after cytology, NMP 22 and BTA stat test using a recently voided urine sample. In suspect cases, TUR and histopathological analysis were performed. RESULTS: Bladder cancer was proven in 76 patients and excluded in 74. For NMP 22 we have used the cutoff value recommended by the manufacturer (10 U/ml) and that obtained by our receiver-operating characteristic curve (6 U/ml). Sensitivity was 84.21% for NMP 22 at the cutoff value of 6 U/ml and 76.32% with 10 U/ml; 72.37% for BTA stat test; 69.74% for cytology, and 100% for cystoscopy. Specificity was 86.49% for NMP 22 at a cutoff value of 6 U/ml and 90.54% at 10 U/ml; 89.19% for the BTA stat test; 93.24% for cytology and 89.19% for cystoscopy. NMP 22 sensitivity for grades 1, 2, and 3 was 68.75, 75.86 and 100%, respectively, at a cutoff value of 6 U/ml, and 50, 68.97 and 96.77%, respectively, at a cutoff level of 10 U/ml; for BTA stat the sensitivity was 56.25% in G1, 62.07% in G2 and 90.32% in G3, and for cytology the sensitivity was 43.75, 62.07 and 90.32%, respectively. The sensitivity of NMP 22 was 68.75% in stage Ta, 84.78% in T1 and 100% in T2-T4 at a cutoff level of 6 U/ml and 50, 80.43 and 92.86%, respectively, at a cutoff level of 10 U/ml; BTA stat sensitivity was 50% in Ta, 73.91% in T1 and 92.86% in T2-T4; and in cytology the results were 37.50, 73.91 and 85.71%, respectively. Using the McNemar test, there was only a significant difference between the sensitivity of NMP 22 at a cutoff level of 6 U/ml and cytology in the overall sample. CONCLUSIONS: The high sensitivity of the NMP 22 and BTA stat test in combination with the data obtained from the parameters used for the evaluation of the test demonstrate their usefulness in the diagnosis and follow-up of bladder cancer. NMP 22 at a cutoff value of 6 U/ml is significantly more sensitive than cytology and consequently a thoroughly valid diagnostic tool in the diagnosis of bladder cancer which may substitute voided urine cytology.     

Myocardial and Coronary Effects of Propofol in Rabbits with Compensated Cardiac Hypertrophy

Background: Myocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts.

Methods: The effects of propofol (10-1,000 [mu]m) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts from rabbits with pressure overload-induced left ventricular hypertrophy (LVH group, n = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM group, n = 10), using an isolated and erythrocyte-perfused heart model. In addition, to assess the myocardial and coronary effects of propofol in more severe LVH, hearts with a degree of hypertrophy greater than 140% were selected (severe LVH group, n = 7).

Results: The cardiac hypertrophy model induced significant left ventricular hypertrophy (136 +/- 21%, P < 0.05). The pressure-volume relation showed normal systolic function but an altered diastolic compliance in hypertrophic hearts. Propofol only decreased myocardial contractility and relaxation at supratherapeutic concentrations (>= 300 [mu]m) in SHAM and LVH groups. The decrease in myocardial performances was not significantly different in SHAM and LVH groups. Propofol induced a significant increase in coronary blood flow which was not significantly different between groups. In severe LVH group, the degree of hypertrophy reached to 157 +/- 23%. Similarly, the effects of concentrations of propofol were not significantly different from the SHAM group.     

Activation of Coagulation and Fibrinolysis during Coronary Surgery: On-pump versus Off-pump Techniques

Background : The authors studied the changes in selected hemostatic variables in patients undergoing coronary surgery with on-pump coronary artery bypass grafting (CABG) or off-pump coronary artery bypass surgery (OPCAB) techniques.

Methods : Platelet counts and plasma concentrations of antithrombin, fibrinogen, D dimer, [alpha]2 antiplasmin, and plasminogen were measured preoperatively, 5 min after administration of heparin, 10 min after arrival in the intensive care unit, and 24 h after surgery in patients scheduled to undergo OPCAB (n = 15) or CABG (n = 15). To correct for dilution, hemostatic variables and platelet counts were adjusted for the changes in immunoglobulin G plasma concentrations and hematocrit, respectively.

Results : Adjusting for dilution, antithrombin and fibrinogen concentrations decreased to a similar extent in patients undergoing OPCAB or CABG (pooled means and 95% confidence limits of the mean: 95.5% of baseline, 93-98%, P = 0.002, and 91.7% of baseline, 88-95%, P = 0.0001), respectively, whereas [alpha]2-antiplasmin concentrations were unchanged. Only CABG was associated with a reduction in platelet counts (76% of baseline, 66-85%, P = 0.0001), plasminogen concentrations (96% of baseline, 91-99%, P = 0.011), and increased D-dimer formation (476%, 309-741%, P = 0.004). Twenty-four hours after surgery, platelet counts were still lower in patients undergoing CABG (P = 0.049), but all the investigated variables adjusted for dilution were similar in the two groups.