PHONOPHORESIS OF METHYL NICOTINATE - A PRELIMINARY-STUDY TO ELUCIDATE THE MECHANISM OF ACTION

The skin penetration enhancement effect of ultrasound (phonophoresis) on methyl nicotinate was investigated in 10 healthy volunteers in a double-blind, placebo-controlled, crossover clinical trial. Each treatment consisted of the application of ultrasound massage (3.0 MHz, 1.0 W/cm2 continuous output) or placebo massage (0 MHz) for 5 min to the forearms of the volunteers, followed by a standardized application of methyl nicotinate at intervals of 15 sec, 1 min, and 2 min postmassage. Percutaneous absorption of methyl nicotinate was monitored using laser Doppler velocimetry. Ultrasound treatment applied prior to methyl nicotinate led to enhanced percutaneous absorption of the drug, for example, ultrasound treatment data versus control data at 2 min showed significant increases (P

Do multinationals really prefer to enter culturally distant countries through greenfields rather than through acquisitions? The role of parent experience and subsidiary autonomy.

Prior research has argued that multinational enterprises (MNEs) prefer to enter culturally distant countries through greenfields rather than through acquisitions, since acquisitions in such countries are costlier to manage. This argument contains two hidden assumptions: (1) the additional costs of acquisitions in culturally distant countries are the same for all MNEs; and (2) such acquisitions have no benefits over their greenfield counterparts. In this paper we relax these two assumptions by arguing that an MNE's preference for greenfields in culturally distant countries depends on its international and host-country experience, and on the level of autonomy it plans to grant the focal subsidiary. Analyzing 171 wholly owned greenfield investments and full acquisitions made by Dutch MNEs in 35 countries, we find that these MNEs prefer to enter culturally distant countries through greenfields, but that this preference is lower when they have little international experience, or plan to grant the focal subsidiary considerable autonomy in marketing. [ABSTRACT FROM AUTHOR]

A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25 mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25 mg dapivirine and various quantities of maraviroc (50– 400 mg) were manufactured and in vitro release assessed. The 25 mg dapivirine and 100 mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing.

Monochloroacetic acid and 60% salicylic acid as a treatment for simple plantar warts:effectiveness and mode of action

Monochloroacetic acid crystals and 60% salicylic acid ointment was found to be more effective than placebo as a treatment for simple plantar warts in a double blind study on 57 patients. Nineteen (66%) patients in the active treatment group compared with five (18%) patients in the placebo group were cured after 6 weeks (P = 0.002). The active treatment was associated with a significantly higher cure rate 6 months after entry (P = 0.04). Treatments were well tolerated. IgG or IgM antibodies or both to human papilloma virus (HPV) types 1 or 2 or both were detected significantly more frequently in the actively treated group 6 weeks after entry (P = 0.0005). Twelve (50%) patients considered to be cured had no detectable secondary immune response. Our results suggest that cure does not depend primarily on the humoral system but rather on mechanical destruction of wart tissue, or occurs as a result of cell mediated immunity.

ME and Julie:a study in narrative of illness experience and therapy in a Myalgic Encephalomyelitis sufferer

This article uses what Atkinson and Walmsley (1997) refer to as an ‘autobiographical account’ to explore the themes and relationships between narrative, illness experience and therapy in a Myalgic Encephalomyelitis (ME) sufferer. Julie is a chronic ME sufferer, having lived with ME for the past 12 years. Her life-story over those years, as she presents it, casts our attention to the intrinsically personal nature of her ‘illness experience’ and to her distinctively artistic therapeutic responses to her condition. Julie’s autobiographical narrative reveals how ME has penetrated both her body and her sense of self, her limbs as well as her dreams; as though it were a parasite feeding off her fight to regain health. In terms of narrative, Julie’s ME illness progresses from past to present, but never to the future which lies beyond contemplation. Despite this denial of the future, Julie does think of ME as a liminal phase which is to be coped through. As both spatial object and temporal event, Julie conceptualises her ME variously, dealing with it on a day-to-day basis, increasingly turning to landscape painting as a form of escapism which parallels her former physical outward bound activities. This personal therapy, so this article concludes, constitutes both narrative performance and narrative text (as canvas), both of which can only cautiously be independently interpreted by the (inter)viewer.

Opening the Frontier: The Gubbio-Perugia Frontier in the Course of History.

The frontier between Gubbio (ancient Umbria) and Perugia (ancient Etruria), in the northeast part of the modern region of Umbria, was founded in the late sixth century BC. The frontier endured in different forms, most notably in the late antique and medieval periods, as well as fleetingly in 1944, and is fossilized today in the local government boundaries. Archaeological, documentary and
philological evidence are brought together to investigate different scales of time that vary from millennia to single days in the representation of a frontier that captured a watershed of geological origins. The foundation of the frontier appears to have been a product of the active agency of the Etruscans, who projected new settlements across the Tiber in the course of the sixth century BC,
protected at the outer limit of their territory by the naturally defended farmstead of Col di Marzo. The immediate environs of the ancient abbey of Montelabate have been studied intensively by targeted, systematic and geophysical survey in conjunction with excavation, work that is still in progress. An overview of the development of the frontier is presented here, employing the data currently available.

Managing state-owned enterprises in an age of crisis:An analysis of irish experience

As with all aspects of public management, the control, financing, and regulation of state-owned enterprises (SOEs) are matters subject to changing international trends and domestic political imperatives. The effects of the global financial crisis (GFC) on the ownership, financing, and role of SOEs are still unfolding, but undoubtedly will be heavily influenced by a new era of public sector reforms principally designed to reassert central political controls, as well as by fiscal pressures to balance state budgets. In this regard, the Irish experience is instructive, with the findings from two datasets being used here to examine various modes of state enterprise control and their corresponding autonomy. Significantly, there has been considerable variety within and across the SOE sector, demonstrating the need for more detailed understanding of how SOEs are managed. © 2011 Taylor & Francis.

Single course of antenatal steroids did not alter cortisol in preterm infants up to 18 months

To determine whether a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants.

Long-term neuropsychological and psychosocial outcomes of decompressive hemicraniectomy following malignant middle cerebral artery infarctions

Purpose: This study examines long-term neuropsychological and psychosocial outcomes of survivors of malignant middle cerebral artery infarction treated via decompressive hemicraniectomy. Method: A case series design facilitated a detailed analysis of the outcomes among five participants. Neuropsychological domains assessed included premorbid and current IQ, sustained, selective and divided attention, visual and auditory memory, executive functioning and visuo-spatial ability. Psychosocial domains assessed included self-rated depression, anxiety and quality of life. Participants and their main carer were asked about their retrospective view of surgery. Results: All participants showed neuropsychological impairments in multiple cognitive domains, with preserved ability in others. Effects of laterality of brain function were evident in some domains. Clinically significant depression was evident in two participants. Overall quality of life was within average limits in three of four assessed participants. Four participants retrospectively considered surgery as having been a favourable course of action. Conclusion: While neuropsychological impairments are highly likely post-surgery, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life. Results do not support the suggestion that decompressive hemicraniectomy following malignant middle cerebral artery infarction necessarily leads to unacceptable neuropsychological or psychosocial outcomes.

Decompressive hemicraniectomy following malignant middle cerebral artery infarctions:a mixed methods exploration of carer experience and level of burden

Purpose: This study explores the experiences and sense of burden of family carers of survivors of malignant middle cerebral artery infarctions who had undergone decompressive hemicraniectomy. To date, there have been no studies examining carer outcomes among this unique population. This study, taken alongside an already published study of survivor outcomes, provides a more holistic picture with regard to sequelae within the sample. Method: Six family carers completed the Sense of Competence Questionnaire and the Hospital Anxiety and Depression Scale. These results were compared with existing normative data. Carers also consented to a semi-structured interview. Interview data were examined using thematic content analysis. Consistent with the mixed methods design, quantitative and qualitative findings were integrated for further analysis. Results: While carers experienced many losses, their overall sense of burden was not outside 'Average' limits, nor did they experience clinically significant symptoms of depression. All carers identified methods of coping with the demands of caregiving. These included intrapersonal, interpersonal and practical strategies. All carers apart from one were able to identify areas of post-traumatic growth. Conclusion: Carers will benefit from information, support and care. In addition, problem solving skills are essential in managing the myriad difficulties that arise in the aftermath of stroke. [Box: see text].

Familial hypocalciuric hypercalcaemia as a differential diagnosis of hyperparathyroidism:studies in a large kindred and a review of surgical experience in the condition

We have studied 46 members of a large kindred with familial hypocalciuric hypercalcaemia (FHH) after a neck exploration failed to cure hypercalcaemia in an asymptomatic patient. Serum calcium, serum phosphate, plasma parathormone and vitamin D metabolites do not distinguish affected members from patients with hyperparathyroidism. Because of the continuing debate as to whether or not FHH is a variant of, or distinct from, hyperparathyroidism, we have carried out a review of surgical experience with subtotal parathyroidectomy in hyperparathyroidism secondary to parathyroid hyperplasia and in FHH. Whereas the procedure is successful in 90 per cent of the former cases only one case of FHH has been cured by it. This provides evidence for the two conditions being aetiologically distinct. Before patients with asymptomatic hypercalcaemia are referred for parathyroid surgery the calcium:creatinine clearance ratio should be measured using a 2 h urine sample collected after an overnight fast and a fasting blood sample. If this ratio is less than 0.01 then screening of first degree relations should be undertaken before any parathyroid surgery is performed. Unnecessary surgery can therefore be avoided.