Innovation in clinical method: diabetes care and negotiating skills

The development of a method to facilitate clinical negotiationwith diabetic patients is described. The principles of the methodincorporate patient centredness, an assessment of readinessto change and some elements of motivational interviewing. Asimple low cost technology is part of the innovative method.Details of the method and its application are published beforethe results of a randomized controlled trial to ensure thatthe techniques are in the public domain before the outcome ofthe trial is known.     

Leucocytoclastic vasculitis associated with hepatitis C virus antibodies

The actiopathogenesis of leucocytoclastic vasculitis is still unknown, but recently hepatitis C virus (HCV) has been suggested as trigger of autoimmunity. We report a case of a 26-yr-old patient with purpura due to leucocytoclastic vasculitis associated with hepatitis C virus infection. Laboratory findings showed AST, ALT, gamma GT within normal limits, positive antibodies to HCV (IIF and Riba II) and polymerase chain reaction for HCV RNA. Anti-nuclear antibodies, IgG and IgM anti- cardiolipin antibodies, anti-platelet antibodies and anti-neutrophil cytoplasmic antibodies with perinuclear pattern were also present. A skin biopsy specimen of a purpuric lesion showed leucocytoclastic vasculitis with small vessel thrombosis and perivascular deposition of IgM and fibrinogen on immunofluorescence study. This case shows a role of HCV in leucocytoclastic vasculitis; it is possible that this HCV can induce autoimmunity independently of cryoglobulins and liver involvement.      

Central thrombi in pulmonary arterial hypertension detected by MR imaging

Differentiation of thrombi from slow flow in the pulmonary arteries, sometimes observed in the presence of pulmonary arterial hypertension, can be equivocal. Magnetic resonance (MR) imaging was performed in a patient with chronic pulmonary thromboembolism and pulmonary arterial hypertension using an electrocardiographically gated technique that allowed visualization of the pulmonary arteries at the end of diastole and multiple times during systole. These images were compared with those of a patient with primary pulmonary hypertension and those of healthy subjects. Thrombi were discrete structures, seen throughout the cardiac cycle on both the first and second spin-echo images, and decreased in signal intensity on the second image. Slow flow increased in signal intensity and changed in structure during the cardiac cycle and was seen best on the second image. MR may play an important role in excluding large central thrombi as the cause of pulmonary arterial hypertension. It is a noninvasive method for defining pulmonary arterial wall thickness and for direct visualization of chronic pulmonary thrombus.     

Nonlinear oral pharmacokinetics of the alpha-antagonist 4-amino-5-(4-fluorophenyl)-6,7-dimethoxy-2-[4-(morpholinocarbonyl)-perhydro-1,4-diazepin-1-yl]quinoline in humans: use of preclinical data to rationalize clinical observations.

4-amino-5-(4-fluorophenyl)-6,7-dimethoxy-2-[4-(morpholinocarbonyl)-perhydro-1,4-diazepin-1-yl]quinoline (UK-294,315) is an antagonist of the human alpha1-adrenoceptor and exhibits nonlinear oral pharmacokinetics in humans. Superproportional increases in Cmax occur (220-fold, over a 1- to 50-mg dose range), area under the curve increases linearly, but time to maximum concentration decreases with dose, suggesting variation in rate but not extent of absorption. Oral absorption in humans is extensive, with only 14% of an orally administered (20 mg) radiolabeled dose excreted unchanged in the feces. In rats and dogs, UK-294,315 is partially eliminated as unchanged drug in feces (29 and 14% of an intravenous dose, respectively). Oral bioavailability is low in rats (11%) and high in dogs (71%), in keeping with systemic clearance. Fecal elimination of unchanged drug was 60% after oral administration to rats, indicating incomplete absorption in this species, whereas absorption in dogs is complete. UK-294,315 is a P-glycoprotein (P-gp) substrate (Km, 15 microM) exhibiting polarized flux in Caco-2 cell monolayers, saturable across a concentration range of 5 to 200 microM. Furthermore, the observations in vitro occurred at similar concentrations to those estimated in the gut lumen in clinical trials (dose range, 1-100 mg). It is considered that P-gp acts as a saturable absorption barrier to UK-294,315, slowing the rate of absorption at low doses, and is responsible for the observed nonlinearity in oral disposition in humans. Rat and dog pharmacokinetic studies offered limited insight into the process(es) driving nonlinear pharmacokinetics in humans. Our current understanding of the functional effects of P-gp in the human intestine, in combination with in vitro studies at clinically relevant concentrations, has helped rationalize the clinical data for UK-294,315.     

Dendritic cells and skin sensitisation hazard assessment.

Allergic contact dermatitis is an important occupational and environmental health disease. There is a need, therefore, to identify skin sensitisation hazard, and to assess accurately likely risks to human health. During the past 15 years very significant advances have been made in our understanding of the cellular and molecular mechanisms that serve to initiate and regulate cutaneous immune responses, including the acquisition of skin sensitisation. This has facilitated parallel advances in the identification and characterisation of skin sensitising chemicals and the development of more robust approaches to risk assessment. It is relevant to consider whether advances in immunobiology provide opportunities also for the design of alternative approaches to the toxicological evaluation of skin sensitisation, including the development of in vitro methods. Here we review the potential use of strategies based on analysis of responses induced in Langerhans cells and dendritic cells; professional antigen processing and presenting cells that are known to play pivotal roles during the induction phase of adaptive immune responses.     

Primary classic Kaposi''s sarcoma of the penis: report of a case and review

Kaposi's sarcoma is a vascular tumour of multifocal origin occurring primarily on the extremities. The case of a 45-year-old HIV negative and HHV-8 positive man with an asymptomatic reddish macular lesion on the inner layer of the prepuce is described. Although primary penile Kaposi's sarcoma is a relatively uncommon disorder in HIV negative men, dermatologists and venereologists should consider this possibility when treating non-specific penile lesions. A minimal penile lesion with non-distinctive clinical features may sometimes be the exclusive manifestation of Kaposi's sarcoma, making histologic evaluation necessary to establish the diagnosis.     

Epileptic seizures induced by sexual abuse. Pathogenic and pathoplastic factors

Previous sexual abuse is now thought to be a common cause of non-epileptic seizures (pseudoseizures). However, since sexual abuse is common, a previous history of sexual abuse may also occur in people with actual epilepsy. We present six patients in all of whom sexual abuse may, by acting as a stressor in the already predisposed, have precipitated epilepsy and in some of whom the abuse may have affected the actual experiences of the epilepsy itself: all but one of the patients had partial seizures.