A semantically aware platform for the authoring and secure enactment of bioinformatics workflows.

Recent advances in the field of bioinformatics present a number of challenges in the secure and efficient management and analysis of biological data resources. Workflow technologies aim to assist scientists and domain experts in the design of complex, long running, data and computing intensive experiments that involve many data processing and analysis tasks with the objective of generating new knowledge or formulate new hypothesis. In this paper we present a bioinformatics workflow authoring and execution environment that intends to greatly facilitate the whole lifecycle of such experiments. Emphasis is given on the security and ethical requirements of these scenarios and the corresponding technological response. In addition we present our semantic framework used for supporting specific user-requirements related to the reasoning and inference capabilities of the environment.

First-line intra-arterial chemotherapy (IAC) with epirubicin and mitoxantrone in locally advanced breast cancer.

BACKGROUND: Approximately 20% of patients with breast cancer present with locally advanced disease without distant metastases. This phase II double-center trial aimed at investigating the activity of epirubicin (Farmorubicin)--mitoxantrone (Onkotrone/Novantrone) combination as first-line intra-arterial chemotherapy (IAC) in locally advanced breast cancer patients. PATIENTS AND METHODS: Thirty-six patients with locally advanced disease and no prior exposure to anthracyclines received the following regimen: epirubicin (Farmorubicin) 30 mg/mq and mitoxantrone (Onkotrone/Novantrone) 10 mg/mq by IAC short infusion on day 1, every 3 weeks for up to six cycles. Prior to IAC an arteriogram of subclavian, internal mammary and lateral thoracic arteries was obtained in all patients, followed by infusion of a blue dye solution into the arteries to determine the most appropriate vessel that supplies the tumor area. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 25 patients (70%; 95%CI, 62% to 80%): 3 CR, 22 PR. Although three of the patients showed complete tumor regression, operative removal or toilet mastectomy became feasible in 25 patients since tumor shrinkage ranged over 75%. A total of 25 mastectomies were carried out for 36 patients. Four patients had bulky tumors (> 13 cm tumor diameter), while 8 patients had ulcerated tumors, two of which presented with complete infiltration of normal breast tissue. The median time to progression and median overall survival were 11 and 27 months, respectively. The time to local response was 3 weeks and time to mastectomy was 9 weeks. Transient neurological disorders developed in six patients and skin chemical burns with painful inflammatory reactions were encountered in ten patients. No systemic toxicity was observed in terms of bone marrow depression and hair loss. No cardiotoxicity was observed. In all specimens necrosis was reported (complete 3 cases, partial 16 and minimal 6). CONCLUSION: A combination of epirubicin (Farmorubicin) and mitoxantrone (Onkotrone/Novantrone) as IAC appears to be a safe and well tolerated treatment for locally advanced breast cancer without clinical evidence of distant metastases. When combined with surgery it offers interesting results in terms of local control and allows a high rate of mastectomies in otherwise inoperable cases.

Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in healthy subjects.

BACKGROUND: Acute hyperglycemia has been associated with delayed gastric emptying of solid foods in healthy control subjects. Erythromycin has been found to be a gastrointestinal prokinetic agent in humans. We examined whether acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of a solid meal after a fasted state in healthy subjects. METHODS: Twelve healthy subjects ate standard solid meals that had been radiolabeled. Gastric emptying was measured by scintigraphy during normoglycemia (5-8.9 mmol/L glucose) and hyperglycemia induced by intravenous glucose (16-19 mmol/L glucose) after administration of placebo or 200 mg of erythromycin intravenously. Emptying was measured randomly on 4 different days. RESULTS: Administration of erythromycin during normoglycemia or induced hyperglycemia compared with placebo accelerated the gastric emptying of the solid meal but did not completely normalize the delay caused by hyperglycemia versus normoglycemia (p < 0.001). In both conditions, erythromycin versus placebo significantly reduced the lag-phase duration (9.7 +/- 2.3 min and 22.0 +/- 3.9 min vs. 38.3 +/- 5.7 min and 49.5 +/- 6.0 min, respectively; p < 0.001), gastric emptying of the half meal (39.2 +/- 4.0 min and 52.0 +/- 7.1 min vs. 75.7 +/- 11.8 min and 94.0 +/- 13.4 min, respectively; p < 0.001), and the percentage of meal retained in the stomach 120 min postprandially (p < 0.001). CONCLUSION: The erythromycin-induced acceleration effect on gastric emptying was related to the plasma glucose level. Hyperglycemia might have chosen a cholinergic antagonist pathway that delayed gastric emptying of solids. Even though induced hyperglycemia inhibited gastric emptying, erythromycin accelerated the gastric emptying rate through two distinct pathways: cholinergic and noncholinergic.

New perspectives in the management of sigmoid diverticulitis.

The sigmoid colon is the part of the large intestine, which most commonly involved in diverticular disease due to its anatomical properties. Diverticular disease of the colon is being seen with increasing frequency mostly in western countries. Diverticulitis results from inflammation and subsequent perforation of a colonic diverticulum. Mild forms of diverticulitis usually present with gradually increasing symptoms from the lower left quadrant of the abdomen, whereas acute complicated disease is characterised by dramatic onset of abdominal pain, followed by fever within a few hours. The standard treatment for uncomplicated diverticulitis is bowel rest, with liquid diet or intravenous fluids in combination with antibiotics. Prophylactic resection is not to be recommended for patients with diverticular disease, but a high-fibre diet may afford protection by preventing further complications. Patients not responding to conservative treatment within the first 24 hours require further evaluation by computed tomography or ultrasonography. Fistula formation and intestinal obstruction are indications for surgical intervention, although the frequent recurrent attacks, which commonly afflict these patients, are seldom associated with severe complications. Laparoscopic approach has been introduced in the diagnosis and definitive treatment of uncomplicated diverticulitis, with less morbidity and mortality rates, and hospitalisation of the patients and in these terms could be promising in the future.