24 research outputs found
Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice
Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice
Endometriosis node in Gynaecologic scars: A study of 17 patients and the diagnostic considerations in clinical experience in tertiary care center
Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: The pilot phase of a randomised controlled trial
Summary:
Background Preoperative (neoadjuvant) chemotherapy and radiotherapy are more eff ective than similar postoperative
treatment for oesophageal, gastric, and rectal cancers, perhaps because of more eff ective micrometastasis eradication
and reduced risk of incomplete excision and tumour cell shedding during surgery. The FOxTROT trial aims to
investigate the feasibility, safety, and effi cacy of preoperative chemotherapy for colon cancer.
Methods In the pilot stage of this randomised controlled trial, 150 patients with radiologically staged locally advanced
(T3 with ≥5 mm invasion beyond the muscularis propria or T4) tumours from 35 UK centres were randomly
assigned (2:1) to preoperative (three cycles of OxMdG [oxaliplatin 85 mg/m², l-folinic acid 175 mg, fl uorouracil
400 mg/m² bolus, then 2400 mg/m² by 46 h infusion] repeated at 2-weekly intervals followed by surgery and a
further nine cycles of OxMdG) or standard postoperative chemotherapy (12 cycles of OxMdG). Patients with KRAS
wild-type tumours were randomly assigned (1:1) to receive panitumumab (6 mg/kg; every 2 weeks with the fi rst
6 weeks of chemotherapy) or not. Treatment allocation was through a central randomisation service using a
minimised randomisation procedure including age, radiological T and N stage, site of tumour, and presence of
defunctioning colostomy as stratifi cation variables. Primary outcome measures of the pilot phase were feasibility,
safety, and tolerance of preoperative therapy, and accuracy of radiological staging. Analysis was by intention to treat.
This trial is registered, number ISRCTN 87163246.
Findings 96% (95 of 99) of patients started and 89% (85 of 95) completed preoperative chemotherapy with grade 3–4
gastrointestinal toxicity in 7% (seven of 94) of patients. All 99 tumours in the preoperative group were resected, with
no signifi cant diff erences in postoperative morbidity between the preoperative and control groups: 14% (14 of 99)
versus 12% (six of 51) had complications prolonging hospital stay (p=0·81). 98% (50 of 51) of postoperative
chemotherapy patients had T3 or more advanced tumours confi rmed at post-resection pathology compared with 91%
(90 of 99) of patients following preoperative chemotherapy (p=0·10). Preoperative therapy resulted in signifi cant
downstaging of TNM5 compared with the postoperative group (p=0·04), including two pathological complete
responses, apical node involvement (1% [one of 98] vs 20% [ten of 50], p<0·0001), resection margin involvement (4%
[ four of 99] vs 20% [ten of 50], p=0·002), and blinded centrally scored tumour regression grading: 31% (29 of 94) vs 2%
(one of 46) moderate or greater regression (p=0·0001).
Interpretation Preoperative chemotherapy for radiologically staged, locally advanced operable primary colon cancer is
feasible with acceptable toxicity and perioperative morbidity. Proceeding to the phase 3 trial, to establish whether the
encouraging pathological responses seen with preoperative therapy translates into improved long-term oncological
outcome, is appropriate
Topical L-arginine gel lowers resting anal pressure: possible treatment for anal fissure
Effect of the nitrification inhibitor dicyandiamide on microbial communities and N2O from an arable soil fertilized with ammonium sulphate
Carbon amendment and soil depth affect the distribution and abundance of denitrifiers in agricultural soils
The nitrite reductase (nirS and nirK) and nitrous oxide reductase-encoding (nosZ) genes of denitrifying populations present in an agricultural grassland soil were quantified using real-time polymerase chain reaction (PCR) assays. Samples from three separate pedological depths at the chosen site were investigated: horizon A (0–10 cm), horizon B (45–55 cm), and horizon C (120–130 cm). The effect of carbon addition (treatment 1, control; treatment 2, glucose-C; treatment 3, dissolved organic carbon (DOC)) on denitrifier gene abundance and N2O and N2 fluxes was determined. In general, denitrifier abundance correlated well with flux measurements; nirS was positively correlated with N2O, and nosZ was positively correlated with N2 (P < 0.03). Denitrifier gene copy concentrations per gram of soil (GCC) varied in response to carbon type amendment (P < 0.01). Denitrifier GCCs were high (ca. 107) and the bac:nirK, bac:nirS, bac:nirT, and bac:nosZ ratios were low (ca. 10−1/10) in horizon A in all three respective treatments. Glucose-C amendment favored partial denitrification, resulting in higher nir abundance and higher N2O fluxes compared to the control. DOC amendment, by contrast, resulted in relatively higher nosZ abundance and N2 emissions, thus favoring complete denitrification. We also noted soil depth directly affected bacterial, archaeal, and denitrifier abundance, possibly due to changes in soil carbon availability with depth. © 2016 Springer-Verlag Berlin Heidelbergclos