Pathological laughter and crying in patients with multiple system atrophy-cerebellar type.

In the cerebellar type of multiple system atrophy (MSA-C), the burden of pathological changes involves the cerebellum and its associated brainstem structures in the basis pontis and the inferior olivary nucleus, and as a result, the clinical phenotype is dominated early on by the cerebellar dysfunction. We report our clinical and post mortem findings in a patient with MSA-C who exhibited pathological laughter in the absence of any congruent changes of mood. A review of the clinical notes of 27 other patients with MSA-C revealed a problem with pathological laughter, or crying, or both in 9 more patients. Our finding of about 36% occurrence suggests that the problem of dysregulation of emotional expression is more prevalent in MSA-C than the paucity of reports in the literature suggests. Our findings are consistent with the view that the cerebellum and its interconnected structures may be involved in the regulation of emotional expression.     

Aktuelle und effektive bildgebende Diagnostik von Sprunggelenk und Fuß

Projection radiographic techniques have been used in a standardized manner for decades for the diagnosis of conditions of the foot and ankle; the indications for them and the pattern of findings useful in the initial diagnosis and monitoring of the course are generally known to clinical radiology staff. Computed tomography has been introduced as an extension of the basic procedures performed for diagnosis in the ankle and the hindfoot. In the case of complex fractures, however, specialist experience is essential. CT is an easily accessible investigative procedure and is meanwhile economical and very powerful. Magnetic resonance imaging supplements the range of investigations in special cases when there are particular problems. Microfractures, findings indicative of inflammation and/or dystrophy and, in particular questions concerning the musculoligamentous support system are the situations in which such investigations are needed. Ultrasound has an additive value vis-à-vis magnetic resonance imaging and is an easily accessible and highly effective examination procedure both for the primary diagnosis and for serial monitoring. Financial constraints in the healthcare sector are increasingly limiting purely medical indications. Regardless of this development, the retention of projection radiography, computer tomography, and magnetic resonance imaging must be demanded for the initial diagnosis in the care of foot and ankle injuries. The earliest possible implementation of all these techniques for the initial diagnosis is the first step towards effective treatment. Cafrefully chosen and, if appropriate, complementary strategies are needed for monitoring of the course and for assessment.     

Quantitative evaluation of adhesive properties and drug-adhesive interactions for transdermal drug delivery formulations using linear solvation energy relationships.

This paper describes the results of the application of linear solvation energy relationships (LSERs) to quantitatively characterize the properties of adhesives and to evaluate the degree of drug-adhesive interaction in transdermal drug delivery formulations. Probe solutions were prepared in acetonitrile (ACN) for a set of probe compounds with different physicochemical properties, and were used to swell the adhesives for subsequent probe molecule-adhesive interactions. The degree of the interactions was measured by the 'sorbed' amount of probe molecules. Based on LSERs, the 'sorbed' amounts were linearly correlated with their properties. The corresponding coefficients reflect the differential interactions of these molecules with the adhesive and ACN, and are quantitative indications of the adhesive properties. Two different transdermal acrylate adhesives (isooctyl acrylate/acrylamide/vinyl acetate in the weight ratios of 75/5/20 and isooctyl acrylate/2-hydroxyethyl acrylate/vinyl acetate in the weight ratios of 58/20/18) were selected for the evaluation of the methodology. It is concluded that the first adhesive is more basic and hydrophobic, which is consistent with the use of acrylamide monomer and significant amount of isooctyl acrylate. The second adhesive is more acidic and polarizable due to a relatively high amount of the 2-hydroxyethyl acrylate. Additionally, the 'sorbed' amount can be regarded as an interaction parameter or index between a drug molecule and the adhesive. Finally, this parameter is expected to correlate with the thermodynamic properties of transdermal formulations such as drug solubility, diffusion coefficient, release rate, and maybe skin permeation rate.     

Cost–Utility Analysis of Paclitaxel in Combination with Cisplatin for Patients with Advanced Ovarian Cancer

The standard treatment for patients with advanced ovarian cancer (AOC) has been cyclophosphamide and cisplatin (CP). Recently, the results of a large randomized comparative trial demonstrated that the combination of paclitaxel and cisplatin (TP) provided a progression-free survival benefit of 5 months. In this study, a cost–utility analysis was performed from a Canadian health care system perspective to estimate the incremental cost-effectiveness of the TP combination. Twelve AOC patients who received treatment with TP were matched for age and disease stage on a 1-to-2 basis with a CP control. Total hospital resource consumption was then collected for all patients. Treatment preferences were estimated from a cohort of 20 patients and 40 healthy female volunteers using the time trade-off technique. The outcomes were then generated through a decision-analytic model. First-line treatment costs with TP were approximately fourfold greater on a per-cycle basis than the CP alternative (Can$1911 vs Can$459). When progression-free survival benefit and patient treatment preferences were incorporated into the analysis, the results of the decision model revealed an incremental cost between Can$12,000 and Can$24,000 per quality-adjusted progression-free year with the TP protocol. Even though the TP combination has a considerably higher drug acquisition cost, the results of the current analysis suggest that this new chemotherapy regimen does provide patients with substantial quality-adjusted progression-free survival benefit at a reasonable cost to the Canadian health care system.     

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.