Item Response Model Adaptation for Analyzing Data from Different Versions of Parkinson’s Disease Rating Scales

Pharmaceutical Research - Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique delivering drugs into the abdominal cavity as an aerosol under high pressure. It is...     

Nordic OCD & Related Disorders Consortium: Rationale,design, and methods

Obsessive‐compulsive disorder (OCD) is a debilitating psychiatric disorder, yet its etiology is unknown and treatment outcomes could be improved if biological targets could be identified. Unfortunately, genetic findings for OCD are lagging behind other psychiatric disorders. Thus, there is a pressing need to understand the causal mechanisms implicated in OCD in order to improve clinical outcomes and to reduce morbidity and societal costs. Specifically, there is a need for a large‐scale, etiologically informative genetic study integrating genetic and environmental factors that presumably interact to cause the condition. The Nordic countries provide fertile ground for such a study, given their detailed population registers, national healthcare systems and active specialist clinics for OCD. We thus formed the Nordic OCD and Related Disorders Consortium (NORDiC, www.crowleylab.org/nordic ), and with the support of NIMH and the Swedish Research Council, have begun to collect a large, richly phenotyped and genotyped sample of OCD cases. Our specific aims are geared toward answering a number of key questions regarding the biology, etiology, and treatment of OCD. This article describes and discusses the rationale, design, and methodology of NORDiC, including details on clinical measures and planned genomic analyses.     

Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma

Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.     

Compositional Effects on Indentation Mechanical Properties of Chemically Strengthened TiO2-Doped Soda Lime Silicate Glasses

TiO₂ is an important oxide for property modifications in the conventional soda lime silicate glass family. It offers interesting optical and mechanical properties, for instance, by substituting heavy metals such as lead in consumer glasses. The compositional effects on the hardness, reduced elastic modulus and crack resistance as determined by indentation of chemically strengthened (CS) TiO₂-doped soda lime silicate glass was studied in the current paper. The CS, which was performed by a K⁺ for Na⁺ ion exchange in a molten KNO₃ salt bath at 450 °C for 15 h, yielded significant changes in the indentation mechanical properties. The hardness of the glass samples increased, and this was notably dependent on the SiO₂, CaO and TiO₂ content. The reduced elastic modulus was less affected by the CS but showed decrease for most samples. The crack resistance, an important property in many applications where glasses are subjected to contact damage, showed very different behaviors among the series. Only one of the series did significantly improve the crack resistance where low CaO content, high TiO₂ content, high molar volume and increased elastic deformation favored an increased crack resistance.     

The influences of muscle fibre proportions and areas upon EMG during maximal dynamic knee extensions

This study is an investigation of the relationship between muscle morphology and surface electromyographic (EMG) parameters [mean frequency of the power spectrum (MNF), signal amplitude (root mean square, RMS) and the signal amplitude ratio (SAR; i.e. the ratio between the RMS level during the passive part of the contraction cycle and the RMS level during the active part of the contraction cycle)] during 100 maximal dynamic knee extensions at 90° · s⁻¹. Each contraction cycle comprised of 1 s of active knee extension and 1 s of passive knee flexion. The surface EMG was recorded from the vastus lateralis muscle. Twenty clinically healthy subjects participated in the study, and muscle biopsy samples of the vastus lateralis were obtained from 19 of those subjects. The relationships between muscle morphology and EMG were investigated at three stages of the test: initially, during the fatigue phase (initial 40 contractions), and at the endurance level (the final 50 contractions). Major findings on correlations are that SAR and MNF tended to correlate positively with the proportion of type 1 fibres, and RMS correlated positively with the proportion of type 2 muscle fibres. The muscle fibre areas showed little correlation with the EMG variables under investigation. The results of the present study showed that the three EMG variables of a dynamic endurance test that were investigated (RMS, MNF and SAR) were clearly correlated with the proportions of the different fibre types, but only to a small extent with fibre areas. These findings contradict some of the theoretical models of the EMG, especially for parameters in the frequency domain. Accepted: 17 June 1999     

The treatment of primary intraocular malignancy

This paper will summarize much of the information derived in an association between The Department of Radiation Oncology of Hahnemann University Hospital and the Oncology Service of Wills Eye Hospital of Thomas Jefferson University, a collaborative effort for the treatment of primary intraocular malignancies that has spanned the last dozen years. In that time we have treated malignant intraocular melanoma by radioactive eyeplaque brachytherapy and have begun to develop a similar program for treatment of recurring retinoblastoma. These experiences will be described.     

Insulin and glucagon secretion in swimming mice: effects of adrenalectomy and chemical sympathectomy

Swimming-stress is known to inhibit glucose-stimulated insulin secretion and stimulate glucagon secretion. In the present study, in mice, we investigated the relative contribution of sympathetic nerves and the adrenals to these effects. Mice were pretreated either with adrenalectomy or chemical sympathectomy induced by i.v. injection of 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve terminals. Two days later, the mice were injected i.v. with either glucose (5.6 mmol/kg) or saline, immediately before being subjected to 2 min swimming-stress or 2 min resting. Directly thereafter, blood was sampled. In normal controls, swimming inhibited glucose-stimulated insulin secretion and elevated plasma glucagon levels (P less than 0.01). Both these responses were absent both in adrenalectomized and in chemically sympathectomized mice. We also found that in resting animals, adrenalectomy reduced plasma levels of glucagon (P less than 0.05) and glucose (P less than 0.01), and that in adrenalectomized mice, swimming lowered basal plasma insulin levels (P less than 0.05). Furthermore, 6-OHDA-treatment elevated basal plasma glucagon levels (P less than 0.01). Thus, we show that, in the mouse, the inhibition of glucose-stimulated insulin secretion and the stimulation of glucagon secretion that occur during swimming-stress are both dependent on mechanisms requiring both the adrenals and intact sympathetic nerve terminals.     

Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group.

Two hundred five men, 40 to 70 years of age, admitted to the coronary care unit with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction), were randomized to double-blind placebo-controlled treatment with an intravenous infusion of recombinant tissue-type plasminogen activator (rTPA), 1 mg/kg body weight (maximum 100 mg) during 4 hours, in addition to aspirin, heparin, and beta-blockade. No severe complications occurred. Myocardial ischemia, defined as myocardial infarction, incapacitating angina despite medication, or signs of ischemia at the exercise test, was reduced by treatment with rTPA compared with placebo both at discharge, 53% compared with 70% (p = 0.02), and at 1 month, 61% compared with 80% (p = 0.005). Signs of myocardial ischemia during the exercise test were reduced at discharge 51.0% compared with 68% (p = 0.03) and at 1 month 48% compared with 62% (p = 0.09). Coronary angiography after 1 month showed no difference in major coronary lesions between the groups, nor was there any reduction in the number of performed coronary revascularization procedures. In conclusion, treatment with rTPA in unstable coronary artery disease in men reduced myocardial ischemia but did not significantly reduce the need for revascularization in long-term follow-up.