Ethical and social issues in the use of biomarkers in epidemiological research

The use of biomarkers in epidemiological research may raise ethical and social issues. These issues stem from the belief that research participants have 'rights' to appropriate information before, during and after studies so that they can make informed decisions. Ethical issues can arise during protocol development, obtaining participation, and in the interpretation and notification of text and study results. Additionally, there are ethical considerations concerning the use of biological specimens collected and stored for one purpose and subsequently used for other research purposes. A major ethical issue is the maintenance of participants' privacy and the confidentiality of their test and study results. Ethics committees need to be well-informed about the scope, limitations and expectations of biomarker research in order to be able to respond to social and scientific developments in the use of biomarkers.     

High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome

Activation of endothelin receptors on the vasculature can produce a variety of responses from potent vasoconstriction to mild vasodilation, depending on the receptor complement within the tissue. To elucidate the potential role of endothelin analogues as tumour blood flow modifiers, we have evaluated the effect of the ET(B) receptor agonist, IRL 1620 ([Suc-(Glu9, Ala(11,15))-ET-1(8-21)]) in CBH/CBi rats bearing an HSN fibrosarcoma. Tissue blood flow and vascular resistance were determined, 20 min following administration of IRL 1620 (bolus intravenous), using the uptake of radiolabelled iodoantipyrine (125I-IAP). Blood flow was unchanged in most tissues. However, at doses > or = 1.0 nmol kg(-1) IRL 1620, blood flow in the brain and heart was increased, whereas in the small intestine it was reduced. Blood flow in the skeletal muscle was reduced at 1.0 nmol kg(-1) only. Tumour blood flow was significantly reduced at 3.0 and 5.0 nmol kg(-1). Vascular resistance was unchanged in most tissues although it was increased in the skeletal muscle at 1.0 nmol kg(-1), in the kidney at 1.0 and 3.0 nmol kg(-1) and in the brain and heart, it was reduced at 5.0 nmol kg(-1) IRL 1620. Vascular resistance was significantly increased in the tumour and the small intestine at doses > or = 1 nmol kg(-1) IRL 1620. Pretreatment of rats with BQ-788, an ET(B) receptor antagonist, selectively attenuated the tumour vascular response to 3 nmol kg(-1) IRL 1620 with no changes observed in the normal tissue responses. Our results demonstrate that the HSN tumour vasculature is selectively responsive to IRL 1620 at doses > 1 nmol kg(-1) compared with the majority of normal tissues with the exception of the small intestine, and that only the tumour response is highly sensitive to BQ-788 antagonism, under the experimental dosing regime investigated. These differences may be exploitable for therapeutic benefit.     

Measuring human brain GABA in vivo: effects of GABA-transaminase inhibition with vigabatrin

Gamma-aminobutyric acid (GABA) plays a pivotal role in suppressing the origin and spread of seizure activity. Low occipital lobe GABA was associated with poor seizure control in patients with complex partial seizures. Vigabatrin irreversibly inhibits GABA-transaminase, raising brain and cerebrospinal fluid (CSF) GABA concentrations. The effect of vigabatrin on occipital lobe GABA concentrations was measured by in vivo nuclear magnetic-resonance spectroscopy. Using a single oral dose of vigabatrin, the rate of GABA synthesis in human brain was estimated at 17% of the Krebs cycle rate. As the daily dose of vigabatrin was increased to up to 3 g, the fractional elevation of brain GABA was similar to CSF increase. Doubling the daily dose from 3 to 6 g failed to increase brain GABA further. Increased GABA concentrations appear to reduce GABA synthesis in humans as it does in animals. With traditional antiepileptic drugs, remission of the seizure disorder was associated with normal GABA levels. With vigabatrin, elevated CSF and brain GABA was associated with improved seizure control. Vigabatrin enhances the vesicular and nonvesicular release of GABA. The release of GABA during seizures may be mediated in part by transporter reversal that may serve as an important protective mechanism. During a seizure, this mechanism may be critical in stopping the seizure or preventing its spread.     

Intravascular ultrasound-guided optimized stent deployment. Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study)

OBJECTIVES: A study was set up to validate the safety and feasibility of intravascular ultrasound-guided stenting without subsequent anticoagulation, and its impact on the 6 months restenosis rate. METHODS: The study was designed to be multicentred, prospective, and observational. RESULTS: One hundred and sixty-one patients with stable angina and a de novo coronary artery lesion were enrolled. In four patients, the implantation of a Palmaz-Schatz (with spiral bridge) stent had failed. One of these four patients died 3 days following bypass surgery. In two other patients, intravascular ultrasound assessment was not performed. One hundred and twenty-five of the remaining 155 patients (81%) were treated with aspirin (100 mg x day(-1)), because all three criteria for optimized stent expansion were met. Twenty-two of the remaining 38 patients (25%), in whom at least one criterion was not met were treated with aspirin and acenocoumarol (3 months, INR 2.5-3.5), while 16 patients only received aspirin. Stent thrombosis was documented in two patients (1.3%) for which repeat angioplasty was performed. During the hospital stay, there were no deaths or Q-wave myocardial infarctions. Five patients (3.2%) sustained a non-Q-wave myocardial infarction. During the follow-up period (198+/-38 days, complete for all patients, except one), one patient (0.6%) sustained a Q-wave myocardial infarction, one (0.6%) underwent bypass surgery, and repeat angioplasty was performed in nine patients (5.7%). In two of the nine patients, repeat angioplasty involved another lesion. Therefore, the target lesion revascularization rate during follow-up was 4.5% (seven patients). At quantitative coronary angiography, the minimal lumen diameter (mean+/-SD) increased from 1.12+/-0.34 mm before to 2.89+/-0.35 mm after stenting. Repeat angiography at 6 months was performed in 144 patients (92%). The minimal lumen diameter at follow-up was 2.12+/-0.67 mm. Restenosis (diameter stenosis of 50% or more) was documented in 12 patients or 8.3%. When the two patients with documented stent thrombosis are included, the restenosis rate amounts to 97%. CONCLUSIONS: These data confirm that, in selected patients, stents can safely be implanted without the use of systemic anticoagulation, provided optimal stent expansion is achieved. The exact role of intravascular ultrasound in the achievement of these results needs to be established by appropriately designed studies. In the meantime, intravascular ultrasound coupled with the Palmaz-Schatz stent incorporating a spiral bridge, may have contributed considerably to the immediate angiographic outcome, which in turn may explain the favourable clinical and angiographic outcome at 6 months.     

A v-SNARE implicated in intra-Golgi transport

We report the identification of a putative v-SNARE (GOS-28), localized primarily to transport vesicles at the terminal rims of Golgi stacks. In vitro, GOS-28, A Golgi SNARE of 28 kD, is efficiently packaged into Golgi-derived vesicles, which are most likely COPI coated. Antibodies directed against GOS-28 block its ability to bind alpha-SNAP, partially inhibit transport from the cis to the medial cisternae, and do not inhibit budding of COP-coated vesicles, but do accumulate docked uncoated vesicles.     

The socioecological model of procommunity action: The benefits of residential stability.

The authors conducted 3 studies to test a socioecological model of procommunity action. Study 1 showed that residents of stable communities purchased a "critical habitat" license plate to support preservation of the environment in their home state more often than did residents of mobile communities. Study 2 demonstrated that home game baseball attendance was less dependent on the team's record in stable cities than in mobile cities. Study 3, an experiment, showed that residential stability had a causal impact on procommunity behavior. Moreover, the effect of stability was partially mediated by identification with the "community." Together, these studies indicate that residential stability can lead to stronger identification with one's community, which, in turn, leads to more procommunity behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immediate weightbearing after uncemented total hip arthroplasty

Radiographic subsidence of the femoral prosthesis and clinical results after unilateral and simultaneous bilateral uncemented total hip arthroplasty were compared. Patients who had bilateral total hip arthroplasty began weight-bearing as tolerated on both lower extremities the day after surgery. Patients who had undergone unilateral total hip arthroplasty were maintained at 10% weightbearing on the operative limb for 6 weeks after surgery. Patients in both groups were matched for age, gender, and weight. Minimal followup was 2 years. There was no difference between the two groups in terms of clinical results. Radiographic assessments were performed immediately after surgery, 6 weeks after surgery, and again at 2 years after surgery. Radiographs were reviewed by a single observer and analyzed with a digitized data recorder. Increased subsidence of the femoral prosthesis within the bilateral group was found at 6 weeks. The mean subsidence of the femoral prosthesis at 6 weeks for the bilateral total hip arthroplasty group was 0.86 mm (range, 0.18-2.60 mm) and for the unilateral group was 0.39 mm (range, 0.07-1.46 mm). However, subsidence occurring between 6 weeks and 2 years averaged 0.50 mm (range, 0.09-1.10 mm) for the bilateral group and 0.54 mm (range, 0.03-0.99 mm) for the unilateral group. This difference was not significant. At the 2-year followup, all femoral prostheses in both groups appeared radiographically stable with evidence of bone ingrowth and no indications of loosening. Thus, immediate weightbearing after bilateral total hip arthroplasty in this study resulted in more initial subsidence (during the first 6 weeks after surgery) of the femoral prosthesis but did not preclude the prosthesis from becoming stable and achieving bone ingrowth. Patients in both groups obtained satisfactory clinical results. Because initial stability and bone ingrowth are factors influenced by prosthesis design, the results of this study may not be applicable to all implants.