Association Between Diaphragmatic Paralysis and Ipsilateral Cervical Spondylosis on MRI

Lung - Diaphragmatic paralysis (DP) is an important cause of dyspnea with many underlying etiologies; however, frequently no cause is identified despite extensive investigation. We hypothesized...     

In vitro/in vivo functionality of Catapres-TTS

The in vitro and in vivo functionality of Catapres-TTS, a transdermal therapeutic system that delivers the alpha adrenergic receptor agonist clonidine, is discussed in terms of the drug transport kinetics and resultant plasma drug concentration profiles. The design of Catapres-TTS is presented as an optimization by which the best combination of system performance characteristics is obtained within the inherent limitations of the transdermal drug transport properties and the known pharmacokinetic and pharmacodynamic properties of the drug. Clonidine is a potent antihypertensive agent with a relatively low therapeutic index. For Catapres-TTS, the majority of control over the drug input rate resides within the system, rather than within the skin, which significantly reduces the variability in drug input rate and resulting plasma drug concentration both within and between patients. Moreover, the presence of a rate-control element in the system allows for patterning of the drug release rate. An initial bolus of drug is placed in the contact adhesive layer, where its transport into the skin is not inhibited by the rate control element in the system, for reduction in the time needed to achieve steady state drug input. The selection of the loading dose of drug is described as an optimization between the minimization of the lag time and the maintenance of constant plasma drug concentrations during the crossover period between system applications in chronic therapy.     

Epstein-barr virus in multiple sclerosis

Recent seroepidemiologic and pathologic evidence suggests that prior infection with Epstein-Barr virus (EBV) may be necessary for the development of multiple sclerosis (MS). EBV infects more than 90% of all humans, most of whom remain healthy. In contrast, 99% of MS patients have evidence of prior infection with EBV. EBV infects resting B lymphocytes, immortalizing them into long-lived memory B cells that survive largely undetected by the immune system in the peripheral circulation. MS patients show elevated titers to EBV years before developing any neurologic symptoms. Postmortem pathologic analysis of brains of patients with MS has revealed diffuse EBV-associated B-cell dysregulation in all forms of MS. Theories of pathogenesis of EBV in MS include antigenic mimicry, immortalization of B-cell clones, and cytotoxic T-cell dysfunction against virally infected B cells. This article reviews the existing evidence of the relationship between EBV and MS and considers the therapeutic implication of this evidence.     

Evaluation of the legal risk of a ‘missed’ cancer in two breastscreen services

Variation in opinions of medical experts is a problem for both the legal and medical profession. This is particularly relevant in breast imaging. BreastScreen Queensland and New South Wales have developed a review protocol to assess ‘reasonableness’ of radiological opinions. It is hoped that the protocol will be acceptable to the courts and will result in a fair outcome for all parties involved in a medico-legal dispute.     

The effect of substance P and other tachykinins on inositol phospholipid hydrolysis in rabbit retina, superior colliculus and retinal cultures

Substance P and eledoisin stimulate the accumulation of inositol phosphates in a dose-dependent manner in retinal and superior colliculus slices of the rabbit. The EC50 values for substance P and eledoisin in both tissues were of the same order (1.5-4.9 microM), suggesting that the receptors in the two tissues were alike with characteristics of the SP-P subtype rather than the SP-E subtype. These data suggest that the SP-immunoreactive material in the retinal ganglion and amacrine cells is identical. The effectiveness for a number of tachykinin substances at 10(-5) M for stimulating inositol phosphates accumulation was as follows: Substance P greater than eledoisin greater than neurokinin A greater than neurokinin B greater than substance P (octapeptide) greater than substance P (pentapeptide). Spantide [(D-Arg1, D-Try7.9, Leu11) substance P] and (D-Pro2, D-Try7.9) substance P did not stimulate inositol phospholipid hydrolysis. However, spantide, at a concentration of 10(-6) M, was an antagonist of the effect produced by substance P, but had no action on the effect produced by neurokinin A or neurokinin B. Substance P and other tachykinins were also effective in stimulating inositol phosphates accumulation in 3-5-day-old rabbit retinal cultures but did not elicit a response in the older (25-30-day-old) cultures which lacked neurones but contained Müller cells. Furthermore, substance P was only active in the younger cultures in stimulating an increase in internal calcium levels. It is therefore concluded that retinal tachykinin receptors linked to phosphoinositide turnover and calcium mobilisation are associated exclusively with neurones and not with Müller cells.