A reexamination of the cytochrome P-450-catalyzed free radical production from a dihydropyridine. Evidence of trace transition metal catalysis.

Radical production from 3,5-bis(ethoxycarbonyl)-4-ethyl-2,6-dimethyl-1,4- dihydropyridine (DDEP) in rat liver microsomes has been attributed to one-electron oxidation via cytochrome P-450 followed by extrusion of an ethyl radical. In the presence of the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN), this radical was detected as the 4-POBN/ethyl radical adduct by electron paramagnetic resonance spectroscopy. The addition of catalase resulted in over a 50% decrease in radical production. The concentration of the 4-POBN/ethyl radical adduct increased about 9-fold in the presence of EDTA and approximately 2-fold in the presence of either diethylenetriaminepentaacetic acid (DTPA) or deferoxamine mesylate. When DDEP was incubated with deferoxamine mesylate-washed microsomes and NADPH in Chelex-treated incubation buffer, much less 4-POBN/ethyl radical formation occurred. Addition of either DTPA, EDTA, or the ferric complexes of these chelators greatly stimulated production of the 4-POBN/ethyl radical adduct in this system. These results suggest that the ethyl radicals produced from DDEP in a microsomal system arise via trace transition metal-catalyzed reactions

Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

Fatigue Intervention by Nurses Evaluation - The FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]

Background: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis and serious personal and economic consequences. Evidence for the effectiveness of any treatment for CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to be successful in improving fatigue and physical functioning in patients in secondary care. The treatment involves providing patients with a readily understandable explanation of their symptoms, from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic rehabilitation when delivered by specially trained general nurses in primary care. We selected a client-centred counselling intervention, called supportive listening, as a comparison treatment. Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in primary care, is more readily available, and controls for supportive therapist contact time. Our control condition is treatment as usual by the general practitioner (GP). Methods and design: This study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained nurse-therapists in patients' homes, compared with nurse-therapist delivered supportive listening and treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried out alongside the clinical trial. Three adult general nurses were trained over a six month period to deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat basis. A qualitative study will examine the interventions' mechanisms of change, and also GPs' drivers and barriers towards referral

Hepatic Sarcoidosis Mimicking Hilar Cholangiocarcinoma: Case Report and Review of the Literature

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Hepatic involvement was reported in about 11% of patients with sarcoidosis. However, cases of sarcoidosis in which the granuloma is solitary and limited in the liver are very rare. A 51-year-old woman with tumors in the liver underwent extended left lobectomy with caudate lobectomy and bile duct resection. The tumor was located between segment 4 and the hilar region. Some daughter nodules were found in the left lobe, which were regarded as intrahepatic metastasis. Our case displayed clinical and radiologically distinct findings, which are very similar to those of hilar cholangiocarcinoma restricted to the liver. This report demonstrates that sarcoidosis can show solitary hepatic involvement in the absence of thoracic lymphadenopathy. In such a case, it is difficult to distinguish the diagnosis from other malignant neoplasms. In conclusion, the diagnosis of hepatic sarcoidosis has to be made through prudent and comprehensive investigations that include a full clinical history of sarcoidosis in other organs. Despite utilizing several detailed diagnostic modalities, the definitive diagnosis of cases of solitary sarcoidosis may remain difficult. In these cases, surgical treatment including liver resection should be considered in order to avoid missing a suitable opportunity for treatment

Learner control in animated multimedia instructions

The interactivity principle in multimedia learning states that giving learners control over pace and order of instructions decreases cognitive load and increases transfer performance. We tested this guideline by comparing a learner-paced instruction with a system-paced instruction. Time-on-task and interactive behavior were logged, and were also related to interest, prior knowledge, and cognitive involvement. We successfully replicated the interactivity principle in terms of better transfer. However, this coincided with a large increase in time-on-task. Also, large individual differences existed in the use of learner control options, which were mostly unrelated to the other variables. Thus, the benefits of introducing learner control in multimedia learning are at the expense of learning efficiency, and it remains unclear for whom the interactivity principle works best

Of cattle, sand flies and men : a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination

Background: Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. Methods and Principal Findings: To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kalaazar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peridomestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Conclusions: Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed

Could dental school teaching clinics provide better care than regular private practices?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149321/1/jicd12329.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149321/2/jicd12329_am.pd

Substance abuse and intimate partner violence: treatment considerations

Given the increased use of marital- and family-based treatments as part of treatment for alcoholism and other drug disorders, providers are increasingly faced with the challenge of addressing intimate partner violence among their patients and their intimate partners. Yet, effective options for clinicians who confront this issue are extremely limited. While the typical response of providers is to refer these cases to some form of batterers' treatment, three fundamental concerns make this strategy problematic: (1) most of the agencies that provide batterers' treatment only accept individuals who are legally mandated to complete their programs; (2) among programs that do accept nonmandated patients, most substance-abusing patients do not accept such referrals or drop out early in the treatment process; and (3) available evidence suggests these programs may not be effective in reducing intimate partner violence. Given these very significant concerns with the current referral approach, coupled with the high incidence of IPV among individuals entering substance abuse treatment, providers need to develop strategies for addressing IPV that can be incorporated and integrated into their base intervention packages