Noninvasive Estimation of Blood Alcohol Concentrations: Ethanol Vapor Above the Eye

The present study describes, in animals, a novel approach to the in vivo, noninvasive determination of alcohol in the body. The concentration of ethanol in vapor above the lacrimal fluid in the eye was analyzed in situ by the use of a fast (1-min) gas sensor method developed previously for biological liquids. After an oral dose of 1 g/kg to 11 animals, eye vapor measurements and blood samples were obtained over 4 hr. The correlation of 61 blood ethanol concentrations obtained by the two methods yielded a correlation coefficient of 0.92 and a slope of 0.99. The metabolic rates of ethanol determined by gas chromatographic analysis of blood and by ethanol eye vapor analysis are virtually identical. The data suggest that ethanol eye vapor analysis may be an attractive, noninvasive method for the determination of ethanol in animals. The method is not subject to false high readings due to alcohol in the buccal cavity and thus might constitute an alternative to breath analysis in the human. In a separate series, ethanol was determined by head space gas chromatography in samples of blood and lacrimal fluid while the animals were under ketamine anesthesia. The correlation of ethanol concentrations in blood and lacrimal fluid (r = 0.99) shows that ethanol is distributed in lacrimal fluid which comprises part of total body water.     

CLOTBUST: Design of a Randomized Trial of Ultrasound-Enhanced Thrombolysis for Acute Ischemic Stroke

BACKGROUND: Intravenous tissue plasminogen activator (TPA) therapy can be monitored with 2 MHz transcranial Doppler (TCD). This article describes the design of CLOTBUST (combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA), the first prospective international multicenter randomized clinical trial of noninvasive externally applied ultrasound to enhance systemic thrombolysis in human stroke. SUBJECTS: Patients with acute ischemic stroke eligible for intravenous TPA therapy within 3 hours of symptom onset who have detectable middle cerebral artery occlusion on a prebolus TCD are included in this trial. All patients receive standard 0.9 mg/kg TPA therapy. Patients are randomized (1:1) to either 2 hours of continuous monitoring with TCD or placebo monitoring. FDA-approved portable diagnostic TCD equipment and standard headframes (Marc series, Spencer Technologies, Seattle, WA) are used. Output of TCD units is set at 100% power achievable at depths of insonation that display the worst TIBI flow grade signals. METHODS AND END-POINTS: Acute MCA occlusion on prebolus TCD is defined as thrombolysis in brain ischemia (TIBI) flow grades 0-3. Treating physicians are blinded to randomization assignment, and certified scorers measure stroke severity using the National Institute of Health Stroke Scale (NIHSS). Safety of continuous TCD monitoring is determined by rates of symptomatic (NIHSS score increase by 4+ points) intracerebral hemorrhage within 72 hours after initial symptom onset. Potential enhancement of TPA therapy will be determined using combined primary end-point of early complete recanalization on TCD (TIBI flow grades 4-5), dramatic recovery (NIHSS < or = 3 points), or decline in the NIHSS > or = 10 points repeatedly measured every 30 minutes within 2 hours after TPA bolus. Other end-points include recovery at 24 hours and 3 months, modified Rankin scores (mRS) are obtained at 90 days, and favorable outcome is determined as NIHSS or mRS scores 0-1. CONCLUSIONS: The aim of phase II CLOTBUST trial is to determine the rates of early complete recanalization and dramatic/early clinical recovery in TPA + TCD and TPA groups. The sample size is set at 126 patients since a medium effect size (.50) is anticipated for TPA + TCD group vs TPA alone to achieve combined primary end-point.     

'Not everything that can be counted counts and not everything that counts can be counted'– towards a critical exploration of modes of satisfaction measurement in sheltered housing

This paper reflects on a research project funded by a consortium of leading sheltered housing (SH) providers and their regulatory body, the Housing Corporation. The project aimed to ascertain which aspects of SH older people perceived to be central to their satisfaction and the methods they judged most appropriate to measuring this. We outline key policy developments of importance to SH (specifically the development of performance measurement regimes), and changes in the nature of SH, which are driving providers to re‐evaluate how they measure user satisfaction. We discuss the aims of the project, our methodology and findings, and conclude by raising critical questions about the process of measuring satisfaction within an increasingly managerialised housing system. We argue that this favours standardised methods of information gathering (such as questionnaires) rather than engage with clients in order to develop methods and systems capable of eliciting qualitative issues of concern to them. Our conclusions are, we believe, applicable to health and social care provision, where similar tensions exist around performance measurement and user satisfaction.     

Combined Excimer Laser and Topical Tacrolimus for the Treatment of Vitiligo: A Pilot Study

Background. Vitiligo is an acquired skin disorder that is characterized by well-defined, often symmetric white patches. Although current therapeutic modalities are directed toward increasing melanocyte melanin production, few treatment modalities address the immunologic nature of the disease.
Objective. To determine whether excimer laser, a known therapeutic modality, in combination with tacrolimus, a topical immunomodulator, accelerate response time and/or improve the degree of response in patients with this disorder.
Methods. Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board–approved double-blind, placebo-controlled study. Twenty-four symmetric vitiliginous patches (elbows, knees) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks. Additionally, topical tacrolimus 0.1% ointment (Protopic) and placebo (Aquaphor) were applied to randomized patches (left or right) twice daily throughout the length of the trial. Vitiliginous patches were monitored with photographs at baseline, every 2 weeks, and 6 months after treatment. Biopsies were performed on subjects with significant results.
Results. Twenty vitiliginous patches from six subjects qualified for evaluation. Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response (75% repigmentation) compared with 20% for the placebo group. Subjects who responded successfully repigmented faster (19%) with combination therapy compared with excimer laser alone. Additionally, three subjects experienced transient hyperpigmentation in lesions treated with combination therapy.
Conclusion. Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease.     

Les plantes transgéniques (OGM végétaux) : connaissances et inconnues sur les risques d'allergénicité…

Much attention is now being focused on foods from genetically modified plants because of the risk of allergenicity. No such risk has been reported for the first generation of GM plants made resistant to herbicides and insect larvae. Current experiments with hypoallergenic GM plants are reported and discussed in the present paper. The second generation of GM plants will improve the nutritional aspects of natural foods. Transgenic proteins could reach from 4 up to 8% of the total protein content in these foods. Any potential difference in allergenicity between second generation GM plants and the natural varieties must be examined with respect to the risk for food allergy caused by food products made from these plants and the risk for respiratory allergies in the people living near the crops caused by airborne pollen originating from the plants. WHO–FAO directives as well as the Codex Alimentarius proposals and the European Food Safety Authority (EFSA) guidelines recommend that transgenic proteins be screened for homology (by in silico study) and cross-reactivity with known allergens, as well as being examined carefully for modifications of host-plant proteomes. In vivo animal studies are also to be carried out to assess any potential immunogenicity. Lacking adequate safety data, the absence of potential allergenicity of transgenic plants cannot be ruled out. This is why data that do not meet the recommended safety criteria required for commercialization of GM plants do not allow us to rule out absolutely the risk that may be associated with products that are going to be commercialized. Therefore, it is essential that commercialized GM plants be monitored. We propose the establishment of public reference serum banks based on up-to-date WHO–FAO recommendations concerning the selection of sera according to precise criteria. We also propose establishing a system of allergovigilance linking national and European health and food safety agencies and a network of university hospital-based clinical and laboratory reference centres, together with a network of clinical allergists, responsible for the creation of the serum banks. Allergists working through these networks would be able to identify new sensitizations to transgenic foods in the population, just as they now identify new types of food allergies, which, in this case, would be GM foods. Such a project is now being established in France.