Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion.

The new treatment strategy for Peritoneal Surface Malignancy combines a cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cytoreduction removes all macroscopic tumor. Intraperitoneal chemotherapy avoids implantation of microscopic residual tumor cells on intra-abdominal surfaces when it is administered intraoperatively and/or early in the postoperative period. Delivering cytotoxic drugs directly into the peritoneal cavity maximizes dose intensity and minimizes systemic toxicity. Hyperthermia is selectively cytotoxic for malignant cells and potentiates the effect of chemotherapy. Implementation of this procedure makes the perioperative personnel to face a risk of exposure to cytotoxic agents. Furthermore, peritonectomies and electro-evaporation of tumor nodules are performed with high voltage electrocautery, generating a large amount of surgical smoke during several hours. Inhalation of these fumes may be also a risk for healthcare workers. In this article, we analyse in depth these new risks of the operating room personnel, we review the literature, and we give guidelines for secure performance of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy, as well as for early postoperative intraperitoneal chemotherapy administration. These new procedures are safe techniques for patients and healthcare workers provided adequate policies are adopted to avoid occupational exposure.     

Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

Neuropeptides in idiopathic chronic constipation (slow transit constipation)

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.     

How to assess fetal metabolic acidosis from cord samples.

The degree of metabolic acidosis at birth has been calculated in cord artery and vein samples from 21 term fetuses with cord artery pH less than 7.20. The aim of the study was to compare base deficit values calculated from either Siggaard-Andersen alignment nomogram (BD blood) or the Acid-Base chart (BD extra cellular fluid, BDecf). BDblood was found to be consistently higher in the cord artery as compared with BDecf, 13.2 +/- 3.5 and 9.9 +/- 2.9 mmol/l (Mean +/- SD), respectively. A significant correlation was found between cord artery PCO2 and BDblood whereas BDecf appeared unaffected by PCO2. In cases with cord entanglement BDecf a-v differences were increased to 3.4 +/- 2.3 mmol/l as compared with the small a-v difference noted in acidotic cases without cord entanglement, 1.1 +/- 1.25 mmol/l. It is speculated that with acutely emerging, intermittent asphyxia due to cord compression, a cord artery and vein difference in metabolic acidosis may exist and where the vein captures the basal level and the artery the acute changes. It is concluded that BDecf in both cord artery and vein add valuable information on the mechanisms behind metabolic acidosis.     

Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey

BACKGROUND: The role of atopy in the evolution to chronic obstructive disease remains controversial. AIM: We aimed to assess the association between individual sensitization to common allergens and lung function. METHOD: We analysed data from 12,687 subjects aged 20 to 44 years, from 34 centres in 15 countries participating in the European Community Respiratory Health Survey (ECRHS). Participants performed a blood test, lung function test, methacholine challenge, and answered an administered questionnaire. The relationships between specific IgE, FEV1 and FEV1/FVC ratio were assessed for each study centre stratified by sex, followed by random effects meta-analysis. RESULTS: Asthmatics sensitized to house dust mite had a lower FEV1 (-119 mL in women and -112 mL in men) and FEV1/FVC ratio (-1.95%, and -2.48%) than asthmatics without sensitization. Asthmatics sensitized to cat had a lower FEV1 (statistically significant for women only) and a lower FEV1/FVC ratio. Asthmatic women sensitized to grass had a lower FEV1 and a lower ratio, and those sensitized to Cladosporium had a lower FEV1. A weak association was found with sensitization to cat and to Cladosporium among non-asthmatic women, which disappeared after adjusting for BHR. CONCLUSION: We conclude that atopy was related to a lower lung function, which was only apparent among asthmatics. This relationship was explained by specific sensitization to cat and to house dust mite, the latter being homogeneous across areas.     

Dexamethasone inhibits food intake suppression induced by low doses of interleukin-1 beta administered intracerebroventricularly.

Intracerebroventricular (ICV) microinfusion of recombinant human interleukin-1 beta (rhIL-1 beta, 0.125 to 2.0 ng/rat) dose-dependently suppressed 2 h and nighttime food intake in rats. The following daytime food intake did not change or increased. ICV infusion of bovine serum albumin (BSA), or heat-treated rhIL-1 beta had no effect on food intake. Pretreatment with dexamethasone (200 micrograms/rat, intraperitoneal) blocked the food intake suppression induced by low doses of rhIL-1 beta. This ability of dexamethasone, a synthetic corticosteroid, may have potential therapeutic implications in acute and chronic pathological processes associated with increased levels of IL-1 and appetite suppression.     

Effects of galanin on insulin and glucagon secretion in the rat

Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80 pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets was dose-dependently suppressed by galanin (10^-6-10^-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower dose levels, the peptide also inhibits basal glucagon release.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.