Assessing the performance of environmental management in academic research laboratories.

Managing environmental risk is essential to ensure organisations minimise their impact on the environment, comply with environmental legislation and maintain their reputation in an increasingly environmentally aware society. Organisations frequently use management systems to plan and execute routine environmental assessments, however environmental impacts may still arise from routine activities or accidents that could be avoided by effective environmental management. Currently there is no method for an organisation to assess the level of awareness their employees have of activities that may lead to an environmental impact, or the level of uptake of environmental management processes. Therefore, the Environmental Management Performance Assessment (EMPA) process was developed to enable organisations to self-assess existing environmental management processes by survey of their employees. The EMPA process was aligned to key phases of the Deming Cycle and involves development and distribution of a survey to organisation employees. The responses are then used to recognise areas for improvement by progression through a bespoke flow chart integrated with the initial survey. This enables demonstration of how particular hazards arise from insufficient awareness at different stages in the Deming Cycle and how these hazards can have wider, reputational, economic, and legislative consequences. The process was trialled by surveying academic researchers on the environmental management processes in their laboratories as a sample set.

Are insulin resistance and non-alcoholic fatty liver disease associated with Peyronie's disease? A pilot study.

Risk factors for Peyronie's disease (PD) are serum lipid abnormalities, hypertension and type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation are key-players in the pathogenesis of arterial diseases, leading to insulin resistance (IR), which is a major determinant of non-alcoholic fatty liver disease (NAFLD). We studied the potential relationship between PD, IR, and NAFLD. Forty-nine male patients were enrolled, fulfilling the well-accepted diagnostic criteria of stable PD. Fifty male individuals without PD, well-matched for age and BMI, were selected as the control group. Comorbidities (T2DM and hypertension), as well as the lipid profile and the glucometabolic asset, were evaluated. The triglycerides/HDL ratio (TG/HDL-C ratio) with a cut-off of ≥3 and the triglycerides-glucose index (TyG) with an optimal cut-point of 8.5 were used for diagnosis of IR and NAFLD, respectively. NAFLD diagnosis was confirmed by the presence of bright liver at ultrasonography. Hypertension was found more frequently in PD patients than in no-PD subjects (P=0.017), independently of age (P=0.99). Both IR and NAFLD were significantly associated with the presence of PD in our population of men (P=0.043 and 0.0001, respectively), no matter how old (P=0.11 and 0.74, respectively). At logistic regression, NAFLD was the only predictor of the PD presence (p=0.021). The AUROC of TyG to predict PD was 0.7437 (sensitivity 67.35% and specificity 80%) with a percentage of correctly classified patients of 73.74%. Oxidative stress markers were significantly associated with NAFLD. Testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses. Both factors, i.e., oxidative stress and hypogonadism, are central to PD pathogenesis. In conclusion, NAFLD and IR are strongly associated with PD. The pathogenic link between these conditions and the underlying mechanisms are only hypothetical and thoroughly summarized in the discussion.

Natural orifices transluminal endoscopic surgery (NOTES): an overview of technical challenges and complications of transgastric procedures in anesthetized pigs.

AIM: Natural orifice transluminal endoscopic surgery (NOTES) is a new reality that is progressively gaining popularity in the scientific community. The aim of this study was to report the authors' experience with various peroral transgastric procedures performed on the porcine model. The technical difficulties and challenges that arose were also analyzed. METHODS: Ten anesthetized pigs, divided into an acute (3) and a survival group (7) underwent the following procedures using a double channel endoscope: peritoneoscopy (10), cholecystectomy (6),splenectomy (3), and gastrojejunostomy (3). RESULTS: All the procedures were completed successfully. There was one complication related to the gastric wall incision. In the survival experiment group all pigs (4) submitted to biliare procedures made an uncomplicated recovery after a follow-up period of 2 weeks. Gastrojejunostomies (3) were instead graved by one technical failure (anastomosis disruption at post-mortem examination) and one case of mortality (premature euthanasia for evidences of sepsis). Complete gastric cleansing was impossible to achieve and overinflation was a common problem. The creation of gastro-enteric anastomoses was technically difficult with the current available devices. CONCLUSION: Transgastric endoscopic surgery is technically feasible in a porcine model. A new instrumentation is needed and could strongly help to overcome the technical difficulties highlighted. More extensive animal studies are mandatory in order to evaluate the benefits and the limitations of this new technique.

Nonlocal properties of dynamical three-body Casimir-Polder forces.

We consider the three-body Casimir-Polder interaction between three atoms during their dynamical self-dressing. We show that the time-dependent three-body Casimir-Polder interaction energy displays nonlocal features related to quantum properties of the electromagnetic field and to the nonlocality of spatial field correlations. We discuss the measurability of this intriguing phenomenon and its relation with the usual concept of stationary three-body forces.

Carotid endarterectomy under local anesthesia in elderly: is it worthwhile?

Carotid endarterectomy (CEA) has a positive effect on stroke free survival in patients with either symptomatic or asymptomatic severe carotid bifurcation stenosis. However, most trials have excluded elder patients. In addition, concerns have arisen regarding the benefits of CEA in the elderly population, especially in women. In this study, we performed an outcome analysis in patients undergoing CEA comparing those eighty and older to their younger counterparts. A total of 262 carotid operations were performed under local anaesthesia between 1998 and 2004; 76 (34%) were carotid reconstructions in 70 patients over 75 yr of age. Twenty patients (26%) presented with asymptomatic critical stenosis. Transient ischemic symptoms were the reason for presentation in 35 patients (46%). Progressive stroke was documented in two patients (3%) and a stroke with persisting neurological deficit was demonstrated in 19 cases (25%). Coronary artery disease was present in 47 patients (38%) and arterial hypertension in 55 (72%). Fifty-nine patients (84%) were classified as ASA group 3. Seventy-one thromboendarterectomies of the carotid bifurcation with direct closure were performed. Five patients had other types of reconstruction. Postoperative complications occurred in three patients. One had a transient neurological deficit and another a lethal stroke; the third patient died from myocardial infarction. The in-hospital mortality was 2.9%, which was not significantly higher than the results of the reconstructions in younger patients (1.5%). Surgery for carotid artery occlusive disease under local anaesthesia can be safely performed in selected patients of more than 75 yr of age.

[Ultrasound-guided endoscopic drainage, without radiological examination, in patients with neoplastic biliary obstruction. Preliminary results]. / Sulla possibilità di drenaggio endoscopico, sotto guida ecografica, senza controllo radiologico, in pazienti con stenosi neoplastiche della via biliare principale. Risultati preliminari.

AIM: Endoscopic stent insertion has become the preferred method for palliation of malignant biliary obstruction. Currently, endoscopic stent placement involves the use of contrast media and radiological equipment to achieve direct opacification of the biliary duct systems, and to determine the location and the extension of biliary obstruction. This report proposes a new combination of ultrasonography and biliary endoscopy, with endoscopic stent placement entirely performed under US-guidance. METHODS: US-guided stent placement was carried out in 8 patients. A guide-wire and a guiding-catheter were endoscopically introduced and identified, by US, the common bile duct across the stricture. Hydromer-coated polyurethane angled stents (10F) were finally inserted over the guide-wire/guiding-catheter by a pusher tube system. RESULTS: Successful stent insertion was achieved in all patients. There were no complications. Successful drainage, with substantial reduction in bilirubin level, was achieved in all patients (14.2+/-9.5 vs 4.2+/-2.9 mg/dl at 1 week). CONCLUSION: Endoscopic stent placement performed under US-guidance, is safe and effective. Further studies in a larger series, including more proximal strictures are suggested.

Ultrasonography-guided endoscopic stent placement for malignant biliary obstruction: a preliminary report of four cases.

We present a new combination of transabdominal ultrasound (US) and biliary endoscopy, with endoscopic stent placement carried out under US guidance. Four patients (two men, two women; average age 66.2 years) underwent US-guided stent placement for palliation of ampullary carcinoma (n = 3) or pancreatic cancer (n = 1). A guide wire and a guiding catheter were endoscopically introduced and identified, by US in the common bile duct across the stricture. Hydromer-coated polyurethane angled stents (10 Fr) were finally inserted over the guide wire/guiding catheter by a pusher tube system. Successful drainage, with substantial reduction in bilirubin level, was achieved in all patients (14.2 +/- 9.5 vs. 4.2 +/- 2.9 mg/dl at 1 week). The present case series shows that endoscopic stent placement performed under US guidance is safe and effective. Further studies of larger series, including more proximal strictures, are warranted.

[Endoscopic palliative treatment of the common bile duct at the hepatic hilum. Results in 583 patients treated in a single center over a 10-year period]. / Trattamento palliativo per via endoscopica delle stenosi della via biliare principale all'ilo epatico. Risultati in 583 pazienti trattati in un singolo Centro in 10 anni.

BACKGROUND: The outcomes of endoscopic biliary drainage for malignant stenoses at the hepatic hilum were retrospectively evaluated. METHODS: From January 1990 to June 2001, 583 patients, 368 males, average age 69+/-18.5 years, were recruited. Endoscopic procedure consisted of insertion of 1 ore multiple stents, plastic or metallic, across the stricture, under mild sedation. RESULTS: Successful stent insertion was achieved in 518/583 (88.8%) patients and successful drainage in 474 (81.3%) patients. Early complications were observed in 101 (17.3%) patients with related-mortality of 17 (2.9%) patients. Late complications occurred in 39.9% of patients. Survival was of 189 days, on average. CONCLUSIONS: Endoscopic palliation should be the initial management of choice for malignant biliary stenoses at the hepatic hilum.

Role of surgery in thymic disorders.

Thymomas are relatively slow-growing neoplasms that should be considered malignant tumours. When treated in the early stages, however, they have an excellent prognosis for long-term survival. Surgery, radiation therapy and chemotherapy all play a role in the management of these neoplasms. Surgery is the treatment of choice in thymoma patients and has become an increasingly accepted procedure in the treatment of myasthenia gravis (MG) since 1936, when thymectomy was performed for this disease for the first time. Improvement in myasthenic symptoms is nearly always observed following thymectomy, but the rates of complete remission vary from 7% to 63%. We have studied the potential preoperative factors predicting the evolution of MG.

Benzothiazole hydroxy ureas as inhibitors of 5-lipoxygenase: use of the hydroxyurea moiety as a replacement for hydroxamic acid.

A novel series of N-[(2-benzothiazolylthio)alkyl]-N'-hydroxyurea derivatives (9-25) was synthesized and evaluated for biological activity as inhibitors of 5-lipoxygenase both in vivo (mouse zymosan peritonitis assay) and in vitro (Ca2+ ionophore-stimulated human peripheral blood leukocyte model). The compounds of this series were based on the corresponding hydroxamic acid derivatives (1, 3, 4, and 5) which were moderately active in vitro but inactive in vivo. A number of compounds in the hydroxyurea series exhibited oral activity for 5-lipoxygenase inhibition. Results of studies relating structure to in vivo and in vitro 5-lipoxygenase activity are reported.

Enhancement of in vitro lipopolysaccharide-stimulated interleukin-1 production by levamisole.

The production of interleukin-1 (IL-1) by the P388D1 mouse macrophage cell line and by adherent peritoneal exudate cells (PMs) was examined. In vitro IL-1 production by P388D1 cells treated with lipopolysaccharide (LPS) was enhanced by coculture with levamisole (0.1 to 10 microM). Oral administration of levamisole (3 mg/kg) to mice also resulted in potentiation of in vitro IL-1 production by thioglycollate-elicited peritoneal macrophages in response to in vitro LPS stimulation. Potentiation was approximately twofold. IL-1 production in the absence of LPS by either the P388D1 cells or the PMs was nil, and levamisole did not directly stimulate IL-1 production in these cases. IL-1 activity in the culture supernatants was measured by thymocyte comitogenic assays. The immunochemical identify of the thymocyte comitogenic activity as IL-1 alpha was confirmed by neutralization with a specific goat anti-mouse IL-1 alpha antiserum. These results suggest that one mechanism by which levamisole acts to normalize and restore immune responses may be enhancing the signals which enable activated macrophages to secrete IL-1.

Antinociceptive action of McN-5195 in rodents: a structurally novel (indolizine) analgesic with a nonopioid mechanism of action.

McN-5195 [(+/-)-trans-3-(2-bromophenyl)-octahydroindolizine] inhibited at nontoxic doses the nociceptive response in tail-pinch, tail-flick and 48 degrees C hot-plate tests of mice, with ED50 values of 38.2, 33.9 and 30.9 mg/kg i.p., respectively, and of rats, with ED50 values (i.p.) of 33.2 mg/kg (tail-flick) and 33.3 mg/kg (hot-plate). The compound was p.o. active in the acetylcholine-induced irritant test (ED50 = 20.1 mg/kg) in mice and the air-induced irritant test (ED50 = 33.2 mg/kg) in rats. McN-5195 blocked thalamic activity (multiunit recordings from the ventral posterolateral nucleus) evoked by noxious stimulation of the contralateral hindlimb of anesthetized rats, but did not alter thalamic activity during non-noxious stimulation. The antinociceptive action of McN-5195 was not blocked by naloxone and was not diminished in morphine-tolerant animals. McN-5195 did not affect arachidonate metabolism and was not active against carrageenan-induced paw edema or in an adjuvant arthritis test in rats. McN-5195 did not bind to opiate, serotonin S1 or S2, dopamine D2, alpha-1, alpha-2, beta adrenergic or gamma-aminobutyric acid-A receptors and did not inhibit the synaptic uptake of norepinephrine, serotonin, dopamine or gamma-aminobutyric acid. McN-5195-induced antinociception was not affected by reserpine or phentolamine pretreatment and was not reduced in clonidine-tolerant animals. Ketanserin and yohimbine inhibited McN-5195-induced antinociception by an indirect mechanism. Tolerance did not develop to chronic administration of McN-5195 (120 mg/kg 3 times per day for 10 days). We conclude that McN-5195 is a structurally novel (indolizine) antinociceptive agent that produces its analgesic action via a nonopioid mechanism, not involving products of arachidonate metabolism.

Effect of tolmetin glycine amide (McN-4366), a prodrug of tolmetin sodium, on adjuvant arthritis in the rat.

The glycine amide of tolmetin sodium (TGA) functions as a prodrug and was demonstrated to be more potent than the parent compound as an inhibitor of developing and established adjuvant arthritis in the female Lewis rat. In contrast, the glycine amide of indomethacin was less potent than indomethacin. The superiority of TGA relative to tolmetin sodium in alleviating this condition was demonstrated by inhibition of paw swelling and reduction of the degenerative bone changes that are associated with the progression of this chronic animal model of rheumatoid arthritis in humans. These properties were not evident when equimolar mixtures of tolmetin sodium and glycine were administered concurrently. Pharmacokinetic analyses revealed that TGA was absorbed completely and hydrolyzed to tolmetin in the female adjuvant arthritic rat. The combined effects of absorption, distribution and hydrolysis of TGA produced lower peak plasma tolmetin levels than an equivalent dose of tolmetin sodium, but plasma concentrations were sustained for a longer period of time contributing to an apparent increase in potency. Furthermore, TGA displayed a decreased propensity to cause gastrointestinal irritation compared to tolmetin sodium. Several additional amino acid amides of tolmetin were similar to the glycine amide in exhibiting increased potency and reduced gastrointestinal toxicity in comparison to equivalent doses of tolmetin sodium.