Limb-kinetic apraxia affects activities of daily living in Parkinson's disease: a multi-center study.

BACKGROUND AND PURPOSE: Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb-kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger and hand movements, may contribute to impaired dexterity even more than bradykinesia per se. However, the impact of limb-kinetic apraxia on ADL remains controversial. Our aim was to identify the strongest predictor of buttoning and unbuttoning in PD. It was hypothesized that coin rotation (a surrogate of limb-kinetic apraxia) represents the most important determinant. METHODS: Sixty-four right-handed, early to moderate PD patients were recruited from three movement disorder centers (Hoehn andYahr stages 1-3). Buttoning, unbuttoning and coin rotation (right and left hand) represented the target tasks. Motor impairment was assessed according to the Unified Parkinson's Disease Rating Scale. RESULTS: Multiple linear regression analysis showed that coin rotation with the right hand was the only significant predictor of buttoning (P < 0.001) and unbuttoning (P = 0.002). Notably, measures of bradykinesia or overall motor impairment did not represent significant predictors. CONCLUSIONS: Constituting the novel key finding, limb-kinetic apraxia seems to be particularly relevant for ADL requiring dexterity skills in PD, even at early to moderate disease stages. Our results prompt research into the pathophysiological background and therapeutic options to treat limb-kinetic apraxia. The simple coin rotation test provides valuable information about ADL-related dexterity skills.

Temporal macrodynamics and microdynamics of the postoperative impedance at the tissue-electrode interface in deep brain stimulation patients.

OBJECTIVE: To study the temporal dynamics of tissue impedance after deep brain stimulation (DBS). BACKGROUND: DBS therapy commonly employs a constant voltage approach, and current delivery to the tissue is a function of electrode-tissue impedance. It is presumed that impedance fluctuates early postimplantation, with implications for variations in current delivery and therapeutic efficacy. We hypothesised that the largest variation will be recorded early after surgery, followed by stabilisation. METHODS: Review of impedance checks of implanted DBS systems at standard parameters during the first five months postimplantation. All measurement time points were binned into 1-week periods, and we used repeated measures analysis of variance with Tukey pairwise multiple comparisons correction. The analysis was repeated after normalising impedance values for each subject to that patient's baseline value. RESULTS: There was an initial (non-significant) drop in impedance at week 1, followed by significant increase at week 3 (p=0.0002). There were no further significant differences in impedance values at subsequent time points. Analysis of normalised data showed a significant difference between the initial measurement in postoperative week 1 (normalised value 1) and week 3 (normalised value 1.73, p<0.0001), with no further difference among the subsequent weekly points during the 5-month follow-up. No significant hourly variations were found at any time points. CONCLUSIONS: We found major changes in impedance within the first month postimplantation, with no further variation. This is an important confirmation in patients of this temporal dynamics of the impedance of implanted DBS hardware, with potential therapeutic implications.

Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy.

BACKGROUND AND PURPOSE: Injectable botulinum neurotoxin (BoNT) is the principal effective treatment for blepharospasm (BSP). This trial explores the safety and efficacy of topical acetyl hexapeptide-8 (AH8), a competitive SNAP25 inhibitor, as a potential new therapy in BSP. METHODS: Double-blind, placebo-controlled, randomized trial of daily topical application of AH8 in 24 patients with BSP. The primary outcome was time to return to baseline Jankovic Blepharospasm Rating Scale (JBRS) after a BoNT injection simultaneously with the initiation of AH8. Patients displaying a strictly regular pattern of response to 3-monthly injections of BoNT were included. RESULTS: There were no significant adverse events. There was a trend for longer time until return to baseline JBRS after injection in the active group compared to placebo (3.7 months vs. 3.0 months), and for better scores in the active group. One-third (4/12) of the patients in the active group had a considerable extension of symptom control after BoNT (range: 3.3-7.1 months). CONCLUSIONS: Topical AH8 is safe and promising for extending the duration of action of BoNT therapy for BSP.

Mathematical structural descriptors and mutagenicity assessment: a study with congeneric and diverse datasets$.

Quantitative bioactivity and toxicity assessment of chemical compounds plays a central role in drug discovery as it saves a substantial amount of resources. To this end, high-performance computing has enabled researchers and practitioners to leverage hundreds, or even thousands, of computed molecular descriptors for the activity prediction of candidate compounds. In this paper, we evaluate the utility of two large groups of chemical descriptors by such predictive modelling, as well as chemical structure discovery, through empirical analysis. We use a suite of commercially available and in-house software to calculate molecular descriptors for two sets of chemical mutagens - a homogeneous set of 95 amines, and a diverse set of 508 chemicals. Using calculated descriptors, we model the mutagenic activity of these compounds using a number of methods from the statistics and machine-learning literature, and use robust principal component analysis to investigate the low-dimensional subspaces that characterize these chemicals. Our results suggest that combining different sets of descriptors is likely to result in a better predictive model - but that depends on the compounds being modelled and the modelling technique being used.

Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance.

Diabetes Mellitus leads to pain neuropathy and cardiovascular complications which remain resistant to current therapies involving the control of glycaemia. This study aims at defining the contribution of kinin B(1) receptor (B(1)R) and the oxidative stress on sensory abnormalities and arterial hypertension in a rat model of insulin resistance. Rats were fed with 10% d-glucose for a chronic period of 12-14 weeks and the impact of a diet supplemented with alpha-lipoic acid, a potent antioxidant, was determined on tactile and cold allodynia, arterial hypertension and the expression of kinin B(1)R (real-time PCR and autoradiography) in several tissues. Acute effects of brain penetrant (LF22-0542) and peripherally acting (R-715) B(1)R antagonists were also assessed. Glucose-fed rats exhibited tactile and cold allodynia along with increases in systolic blood pressure between 4 and 12 weeks; these alterations were alleviated by alpha-lipoic acid. The latter regimen also decreased significantly increased plasma levels of insulin and glucose and insulin resistance (HOMA index) at 14 weeks. B(1)R mRNA was virtually absent in liver, aorta, lung, kidney and spinal cord isolated from control rats, yet B(1)R mRNA was markedly increased in all tissues in glucose-fed rats. Up-regulated B(1)R mRNA and B(1)R binding sites (spinal cord) were significantly reduced by alpha-lipoic acid in glucose-fed rats. LF22-0542 reduced tactile and cold allodynia (3h) and reversed arterial hypertension (3-48h) in glucose-fed rats. R-715 abolished tactile and cold allodynia but had not effect on blood pressure. Data suggest that the oxidative stress contributes to the induction and up-regulation of B(1)R in the model of insulin resistance induced by glucose feeding. The over expressed B(1)R contributes centrally to arterial hypertension and in the periphery to sensory abnormalities.

Heritability, correlations and in silico mapping of locomotor behavior and neurochemistry in inbred strains of mice.

The midbrain dopamine system mediates normal and pathologic behaviors related to motor activity, attention, motivation/reward and cognition. These are complex, quantitative traits whose variation among individuals is modulated by genetic, epigenetic and environmental factors. Conventional genetic methods have identified several genes important to this system, but the majority of factors contributing to the variation remain unknown. To understand these genetic and environmental factors, we initiated a study measuring 21 behavioral and neurochemical traits in 15 common inbred mouse strains. We report trait data, heritabilities and genetic and non-genetic correlations between pheno-types. In general, the behavioral traits were more heritable than neurochemical traits, and both genetic and non-genetic correlations within these trait sets were high. Surprisingly, there were few significant correlations between the behavioral and the individual neurochemical traits. However, striatal serotonin and one measure of dopamine turnover (DOPAC/DA) were highly correlated with most behavioral measures. The variable accounting for the most variation in behavior was mouse strain and not a specific neurochemical measure, suggesting that additional genetic factors remain to be determined to account for these behavioral differences. We also report the prospective use of the in silico method of quantitative trait loci (QTL) analysis and demonstrate difficulties in the use of this method, which failed to detect significant QTLs for the majority of these traits. These data serve as a framework for further studies of correlations between different midbrain dopamine traits and as a guide for experimental cross designs to identify QTLs and genes that contribute to these traits.

The effect of the plasma needle on tumoral cell lines apoptosis.

In this paper, we present the effect of the plasma needle on tumor cell surface. The plasma is generated at the tip of a metal needle by using a radio-frequency generator of 13.56 MHz, 100's V amplitude. In our study we investigated the interaction of non-thermal plasma (plasma needle) with living monolayer tumour cells in culture medium. We applied short needle to sample distance (1 mm) at temperature of 25 degrees C, 30 degrees C and 37 degrees C, respectively. Our data sugest that the plasma needle reduces the viability and induces apoptosis of tumour cells. These activities may be very useful in dermatology, where a part of the tissue must be removed with high-precision, without damage to the adjacent cells and without inflammatory reaction.

Adenosine's role in hypercapnia-evoked cerebral vasodilation in the rat.

Carbon dioxide induces a rapid dilation of cerebral arterioles, enabling local blood flow to match increasing metabolic requirements of tissue. Amongst the vasodilatory substances released by cortical tissue in response to CO2 are adenosine and nitric oxide. Here we report that selective adenosine A(2A) receptor antagonists, applied topically using a rat cortical window technique, significantly depressed the CO2-evoked increase in arteriolar diameter, measured using video microscopy, as well as attenuating the CO2 and pH reactivity of the cortical arterioles. Two non-selective inhibitors of nitric oxide synthase also significantly depressed the hypercapnia-evoked increase in arteriolar diameter.

The effect of moisture on the adsorption of xenon by activated carbon.

The following procedure was used to determine the effect of moisture on the adsorption of xenon from air onto activated carbon: A known amount of water is added to a sample of dried activated carbon and allowed to equilibrate. This activated carbon is then split between two cylindrical beds placed in a temperature controlled water bath, and air is passed through the beds sequentially. Because the beds contain pre-moistened activated carbon from the same sample, the first bed acts as a buffer, maintaining a constant humidity in the second. The mean holdup time of a pulse of 133Xe injected into the second bed is used to determine the adsorption coefficient for xenon under these conditions. Measurements were made for three carbons activated to 35, 40, and 59%, respectively, at temperatures of 25 degrees C and 55 degrees C. The effect of moisture on the same activated carbon at these two temperatures shows an affine relationship that could be helpful in extending these results to other temperatures. At low moisture uptakes, a plot of the log(adsorption coefficient) vs. moisture uptake gives a straight line.

[Intraoperative ultrasonography, dissection with ultra-shears and trans-cystic choledochoscopy during laparoscopic approach in obstructive lithiasis icterus case]. / Ecografie intraoperatorie, disectie cu foarfeca cu ultrasunete si coledocoscopie transcistica într-un caz de icter mecanic litiazic rezolvat pe cale laparoscopica.

The authors present the case of a 48 years old male with lithiasis obstructive icterus who was operated by laparoscopic transcystic approach with choledochoscopy. This minimally invasive technique was very spectacular trough the using of laparoscopic ultrasonography, dissection with Ultra-Shears device and transcystic choledochoscopy. Careful watching of abdominal laparoscopic view and transcystic choledochoscopic view is the particularity of laparoscopic transcystic management of choledocholithiasis. This metod don't let us to explore the biliary tract before the junction between common bile duct and cystic duct.

[Intraoperative ultrasonography during laparoscopic surgery]. / Ecografia intraoperatorie în chirurgia laparoscopica.

AIM: Of this study is the introduction and the results evaluation of laparoscopic ultrasonography performed. MATERIAL AND METHOD: We realize a prospective study about laparoscopic ultrasonography performed in 37 cases with laparoscopic surgical treatment. The Aloka SSD 2000 mobile scanner is used. This system make possible the use of an linear-array transducer, with mechanical flexibility and availability of Doppler analysis. Most frequently we used intraoperative ultrasonography in laparoscopic cholecystectomy as an alternative for cholangiography to exclude CBD pathology. Because of various surgical pathology with laparoscopic approach, the laparoscopic ultrasonography utilization range was vastly. RESULTS: In all the cases we could performed the laparoscopic ultrasonography. In 6 of 27 cases with laparoscopic cholecystectomy we found pathological disorders of bile ducts. CBD with diameter found between 5-12 mm. We properly saw the distal segment of CBD in 23 cases (89.2%), and common hepatic duct in 26 cases (97.3%). The quality of visualization was very good in 21 cases (83.8%) and moderate in 6 cases (16.2%). We easy identify CBD stones and we successfully used Doppler color mode in differentiating vascular from non-vascular from non-vascular structures. Laparoscopic ultrasonography performed in a case with left colon cancer excluded liver metastasis and lymph nodes metastasis. CONCLUSIONS: 1. Laparoscopic ultrasonography combines the advantages of diagnostic laparoscopy and intraoperative contact ultrasonography; 2. Laparoscopic ultrasonography is a simple and very efficient intraoperative examination procedure; 3. Laparoscopic ultrasonography is the technique to choose in CBD intraoperative exploration; 4. Laparoscopic ultrasonography improve abdominal malignancy exploration, thus modifying therapeutic decisions; 5. Color Doppler mode guides the surgeon's steps in difficult directions.

[Cortico-suprarenal carcinoma]. / Carcinom de glanda corticosuprarenala.

The authors show the case of a 69 years old male with a large corticosuprarenalian tumor that was detected on an random abdominal echographic examination. The patient was operated in the General Surgery Department. of Prof. Agrippa Ionescu Hospital, Bucharest. We performed ablation of the large left suprarenalian gland malign tumor with left nephrectomy, splenectomy and partial pancreatectomy. The hystopathological examination reveals a diffuse corticosuprenalian carcinoma. The case is interesting because of low incidence of this kind of malign tumor and also of the unusual tumor evolution in a long time up to its large size (12 cm in diameter).

Short and valid assessment of apraxia in Parkinson's disease.

BACKGROUND: Valid assessment of apraxia in usually non-apraxic Parkinson's disease helps to delineate atypical parkinsonism frequently associated with apraxia. Furthermore, in a subgroup of late Parkinson's disease apraxia, typically the ideomotor subtype, may gradually superimpose onto parkinsonian motor symptoms contributing to defective manual skill. Here we evaluate the utility of a brief, standardized test, the apraxia screen of TULIA (AST). METHODS: Seventy five Parkinson's disease patients were tested with the AST. Parkinsonian motor deficits were measured using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III and difficulties in activities of daily living (ADL) by modified MDS-UPDRS part II (eating, dressing, personal hygiene, and writing). RESULTS: No association was found between the AST and MDS-UPDRS part III, indicating that AST discriminates well (discriminative validity) between apraxia and parkinsonism. Furthermore, AST was associated with ADL and Hoehn & Yahr stage (convergent validity). CONCLUSIONS: AST is a short and valid test to rule out or detect apraxia in Parkinson's disease.

Employers' expectations of knowledge and skills of master's-trained industrial hygienists.

Certified industrial hygienists with recent hiring experience were surveyed about their expectations of competencies when hiring entry-level master's-trained industrial hygienists. Results were used to affirm educational objectives and program outcomes required by new program accreditation criteria. We received 129 completed surveys from 179 eligible participants agreeing to participate. Most of the respondents were employed in very large companies (>500 employees) and were evenly distributed in manufacturing, services, and public administration. More than 70% of respondents identified essential knowledge and skills in 11 topic areas that fall entirely within the categories of recognition, evaluation, and control. Environmental and management topics were identified as essential by less than 25% of the respondents. Nineteen competencies identified as essential by 60% of the respondents were entirely in the categories of recognition, evaluation, control, and communication. Less than 50% of the respondents thought competencies in the management area were useful but not essential. Air sampling pumps, sound level meters, noise dosimeters, and direct-reading instruments were the mostfrequently listed equipment with which industrial hygienists should be familiar. These survey results represent the first systematic input from employers on their expectations for competencies of master's-trained industrial hygienists.

Hemovigilance: clinical tolerance of solvent-detergent treated plasma.

OBJECTIVE: This study was conducted to assess retrospectively the clinical tolerance of SD treated plasma and to compare it to other labile blood products (red blood cell and platelet concentrates). METHODS: Adverse events (AEs) related to the use of blood products at the Blood Transfusion Center (BTC) are routinely collected through a formalised system of hemovigilance. All AEs reported are entered into a safety data base which was used for the study. All AEs reported during a one-year period to the BTC were retrospectively re-assessed and descriptive statistics calculated. RESULTS: 5064 units of SD treated plasma were transfused to 894 recipients during the study period at the occasion of 1553 transfusions. No AE associated to SD treatment plasma was reported during that period. In contrast, during the same period, 485 AEs associated with the use of red blood cell concentrates (RBCC) were reported in 251 patients at the occasion of 262 transfusions. 2.1% (251/11,748) of the patients transfused with RBCC experienced one or more AEs. The incidence of AEs per unit transfused was 1.3% (485/37,332), and 2.4% (485/20,460) of RBCC transfusions were associated with one or more AEs. 142 AEs associated with the use of platelet concentrate (PC) were observed in 69 patients at the occasion of 73 transfusions. 4.2% (69/1645) of patients transfused with PC experienced one or more AEs. The incidence of AEs per unit transfused was 1.1% (142/12,772), and 2.8% (142/5034) of PC transfusions were associated with one or more AEs. All reported AEs were classified and non serious. The most frequently observed AEs were fever, chills and rashes which accounted for roughly 64% of all reported AEs. CONCLUSION: As for the overall clinical tolerance of red cell and platelet concentrates, the results of this study are in complete agreement with the published literature. The study also confirms the extremely good tolerability of SD treated plasma in comparison with other labile blood products.