Environmental risk of severely Pb-contaminated riverbank sediment as a consequence of hydrometeorological perturbation.

Metal mining activities have resulted in the widespread metal pollution of soils and sediments and are a worldwide health concern. Pb is often prolific in metal-mining impacted systems and has acute and chronic toxic effects. Environmental factors controlling diffuse pollution from contaminated riverbank sediment are currently seen as a "black box" from a process perspective. This limits our ability to accurately predict and model releases of dissolved Pb. Previous work by the authors uncovered key mechanisms responsible for the mobilisation of dissolved Zn. The current study identifies key mechanisms controlling the mobilisation of dissolved Pb, and the environmental risk these releases pose, in response to various sequences of "riverbank" inundation/drainage. Mesocosm experiments designed to mimic the riverbank environment were run using sediment severely contaminated with Pb, from a mining-impacted site. Results indicated that, although Pb is generally reported as less mobile than Zn, high concentrations of dissolved Pb are released in response to longer or more frequent flood events. Furthermore, the geochemical mechanisms of release for Zn and Pb were different. For Zn, mechanisms were related to reductive dissolution of Mn (hydr)oxides with higher concentrations released, at depth, over prolonged flood periods. For Pb, key mechanisms of release were related to the solubility of anglesite and the oxidation of primary mineral galena, where periodic drainage events serve to keep sediments oxic, particularly at the surface. The results are concerning because climate projections for the UK indicate a rise in the occurrence of localized heavy rainfall events that could increase flood frequency and/or duration. This study is unique in that it is the first to uncover key mechanisms responsible for dissolved Pb mobilisation from riverbank sediments. The mineralogy at the mining-impacted site is common to many sites worldwide and it is likely the mechanisms identified in this study are widespread.

A polymorphism of the interleukin-1 beta gene influences survival in pancreatic cancer.

Pro-inflammatory cytokines contribute to the cachexia associated with pancreatic cancer and stimulate the acute phase response which has been associated with shortened survival in such patients. Polymorphisms of cytokine genes may influence their production. The present study examined the effect of a polymorphism of the interleukin (IL)-1b gene upon the inflammatory state and survival in pancreatic cancer. Genomic DNA was obtained from 64 patients with pancreatic cancer and 101 healthy controls. Using the polymerase chain reaction and subsequent TaqI restriction enzyme digestion the subject's genotype for a diallelic polymorphism of the interleukin-1b gene was established. IL-1b production by peripheral blood mononuclear cells and serum C-reactive protein (CRP) levels from patients were also examined and survival noted. Patients homozygous for allele 2 of the IL-1b gene had significantly shorter survival than other groups (P = 0.0001). These patients also exhibited higher IL-1b production (P = 0.022). Possession of allele 2 was also associated with significantly shorter survival (median 144 vs 256 days, P = 0.034) and significantly higher CRP level (P = 0.0003). The possession of a genotype resulting in increased IL-1b production was associated with shortened survival and increased serum CRP level. This may reflect the role of IL-1b in inducing an acute phase protein response and cachexia in cancer or may be related to changes in tumour phenotype.

Two polymorphisms of the tumour necrosis factor gene do not influence survival in pancreatic cancer.

Polymorphisms of the tumour necrosis factor (TNF) gene have been related to TNF production and outcome in a variety of inflammatory and malignant diseases. Proinflammatory cytokines and the inflammatory state appear to affect outcome in pancreatic cancer. Thus, the present study examined the TNFB and TNF-308 polymorphisms for their relationship to the inflammatory state and survival in pancreatic cancer. Sixty-four patients with advanced pancreatic cancer and 101 healthy subjects were genotyped for each polymorphism. Serum concentrations of the two TNF receptors and C-reactive protein (CRP) were measured in 45 of the cancer patients with no evidence of infection or jaundice, 1 month after surgical intervention. There was no difference in distribution of genotypes between the patient and control groups. There was no association between any genotype and concentrations of any of the measured inflammatory mediators. While those with an elevated CRP concentration had significantly poorer survival, there was no association between either TNF genotype and survival. This study found no association between TNF genotype and the inflammatory state or survival in advanced pancreatic cancer. Other cytokines may be more important than TNF in determining the inflammatory state and disease progress in pancreatic cancer.

Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group.

OBJECTIVE: To examine the safety and efficacy of transurethral pharmacotherapy for erectile dysfunction, involving the use of a novel therapeutic system to administer alprostadil (prostaglandin E1) to the urethral mucosa in a double-blind, randomized, parallel, placebo-controlled study conducted in five countries in Europe. PATIENTS AND METHODS: In an outpatient setting, patients with primarily organic erectile dysfunction of at least 3 months' duration were treated with transurethral alprostadil, in an open-label, dose-escalating study. Testing stopped when the dose provided an erection sufficient for intercourse, as assessed by the patient and the investigator. Patients who achieved a sufficient response were then randomized to either active medication at the selected dose or to placebo for use at home for 3 months. After each home administration, patients recorded in diaries whether or not sexual intercourse occurred and any adverse reactions to the drug. RESULTS: A total of 249 patients were treated in an outpatient setting; of these patients, 159 (64%) achieved an erection sufficient for intercourse and were randomized (1:1) to either active medication or placebo for home treatment. Of the patients randomized to alprostadil for home treatment, 69% reported intercourse at least once, compared with 11% of patients randomized to placebo (P < 0.001). The most common adverse reaction, urethral pain/burning, was reported by 7% of patients in the clinic. Most patients (83%) graded transurethral alprostadil as causing minimal or no discomfort in the clinic. No patient reported priapism or developed penile fibrosis. CONCLUSION: Alprostadil delivered transurethrally by this system was well tolerated and effective in treating erectile dysfunction.

The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. MUSE Study Group.

OBJECTIVE: To evaluate the impact of treatment for erectile dysfunction on the quality of life of men and their partners. PATIENTS AND METHODS: The study included 249 men with organic erectile dysfunction of more than 3 months' duration who self-administered transurethral alprostadil in an open-label, dose-escalating manner in an outpatient medical setting. Patients with a sufficient response (159) were randomly assigned in a double-blind protocol to either active medication or placebo for 3 months at home. Patients and partners each completed quality-of-life questionnaires before and after treatment. RESULTS: In the clinic 159 of the 249 men (64%) had an erection sufficient for intercourse when using transurethral alprostadil. At home, 46 of 67 men (69%) reported intercourse at least once on transurethral alprostadil, compared with eight of 73 (11%) on placebo (P < 0.001). Patients on alprostadil showed a 34% improvement in their 'relationship with partner', a 5% improvement in 'personal wellness', and a 71% improvement in 'quality of erection' domains, compared with a decline of 11%, 8% and 1%, respectively, in patients on placebo (P < 0.005 for each comparison). Partners of patients on alprostadil showed a 35% improvement in the 'relationship with partner' domain, compared with a 12% improvement in the placebo group (P = 0.028). There was a trend toward improvement in other partner domains. Urogenital pain was reported by 14% of patients during home treatment. CONCLUSION: The resumption of sexual intercourse with the use of transurethral alprostadil was accompanied by an improvement in several important quality-of-life domains in patients and their partners.