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81.
Arno?M.?JanssenEmail authorView authors OrcID profile Moniek?A.?M.?Munneke Jorik?Nonnekes Thomas?van der?Kraan Alice?Nieuwboer Ivan?Toni Anke?H.?Snijders Bastiaan?R.?Bloem Dick?F.?Stegeman 《Journal of neurology》2017,264(5):963-972
Freezing of gait (FOG) in Parkinson’s disease (PD) likely results from dysfunction within a complex neural gait circuitry involving multiple brain regions. Herein, cerebellar activity is increased in patients compared to healthy subjects. This cerebellar involvement has been proposed to be compensatory. We hypothesized that patients with FOG would have a reduced ability to recruit the cerebellum to compensate for dysfunction in other brain areas. In this study cerebellar activity was modified unilaterally by either excitatory or inhibitory theta burst stimulation (TBS), applied during two separate sessions. The ipsilateral cerebellar hemisphere, corresponding to the body side most affected by PD, was stimulated. Seventeen patients with PD showing ‘off’ state FOG participated. The presence of FOG was verified objectively upon inclusion. We monitored gait and bimanual rhythmic upper limb movements before and directly after TBS. Gait was evaluated with a FOG-provoking protocol, including rapid 360° turns and a 10-m walking test with small fast steps. Upper limb movement performance was evaluated with a repetitive finger flexion–extension task. TBS did not affect the amount of freezing during walking or finger tapping. However, TBS did increase gait speed when walking with small steps, and decreased gait speed when walking as fast as possible with a normal step size. The changes in gait speed were not accompanied by changes in corticospinal excitability of M1. Unilateral cerebellar TBS did not improve FOG. However, changes in gait speed were found which suggests a role of the cerebellum in PD. 相似文献
82.
SA Tannu LM Renzetti N Tare JD Ventre D Lavelle TA Lin A Morschauser J Paciorek DR Bolin H Michel L Singer M Hargaden ID Knowles P Gardiner M Cazzola L Calzetta MG Matera A Hicks 《British journal of pharmacology》2010,161(6):1329-1342
BACKGROUND AND PURPOSE
Vasoactive intestinal peptide is expressed in the respiratory tract and induces its effects via its receptors, VPAC1 and VPAC2. RO5024118 is a selective VPAC2 receptor agonist derived via chemical modification of an earlier VPAC2 agonist, RO0251553. In the present studies, we characterized the pharmacological activity of RO5024118.EXPERIMENTAL APPROACH
Stability of RO5024118 to human neutrophil elastase was assessed. Bronchodilatory activity of RO5024118 was investigated in guinea pig and human isolated airway smooth muscle preparations and in a guinea pig bronchoconstriction model. Pulmonary anti-inflammatory activity of RO5024118 was investigated in a lipopolysaccharide mouse model and in a porcine pancreatic elastase (PPE) rat model.KEY RESULTS
RO5024118 demonstrated increased stability to neutrophil elastase compared with RO0251553. In human and guinea pig isolated airway preparations, RO5024118 induced bronchodilatory effects comparable with RO0251553 and the long-acting β-agonist salmeterol and was significantly more potent than native vasoactive intestinal peptide and the short-acting β-agonist salbutamol. In 5-HT-induced bronchoconstriction in guinea pigs, RO5024118 exhibited inhibitory activity with similar efficacy as, and longer duration than, RO0251553. In a lipopolysaccharide-mouse model, RO5024118 inhibited neutrophil and CD8+ cells and myeloperoxidase levels. In rats, intratracheal instillation of PPE induced airway neutrophilia that was resistant to dexamethasone. Pretreatment with RO5024118 significantly inhibited PPE-induced neutrophil accumulation.CONCLUSIONS AND IMPLICATIONS
These results demonstrate that RO5024118 induces dual bronchodilatory and pulmonary anti-inflammatory activity and may be beneficial in treating airway obstructive and inflammatory diseases. 相似文献83.
Robert?ArmbrustEmail authorView authors OrcID profile Klaus-Dieter?Wernecke Jalid?Sehouli Matthias?David 《Archives of gynecology and obstetrics》2018,297(1):131-137
Purpose
Until now there are no systematic studies about the long-term course of myoma growth. Therefore, the aims of the present study were: (1) ultrasound monitoring of the natural course of growth of uterine leiomyomas; (2) assessment of whether the growth of myomas depends on the age of the patients, the location, or the initial size (possible co-factors/predictor criteria for increase of growth); influence of oral contraceptives (OC).Methods
Patient records (2010–May 2016) were retrospectively and systematically evaluated in regards to their growth and clinical course. The patients received a follow-up questionnaire by mail about the further history. Linear regression analysis and generalized regression analysis were performed to determine the influence of various factors on the growth of myomas.Results
Overall, 152 met the further inclusion criteria. Most of the myomas increased in size but 10% of the myomas became smaller without therapy. There is a significant dependency between the initial myoma size, and the first and second measurements, but not between those measures and myoma localization. In regression analysis, there was also a significant association between the growth of the myomas and the initial size but no association with age, complaint symptoms, and use of OC. However, the use of OC waas significantly associated with myoma growth in GEE.Conclusions
The course of growth of myomas has large variance, so this should not be taken as a sign for a malignant event (sarcoma or the so-called STUMP). The growth takes place with considerable individual variability and ultimately is not predictable.84.
Meg?E.?FluhartyEmail authorView authors OrcID profile Jon?Heron Marcus?R.?Munafò 《European child & adolescent psychiatry》2018,27(6):739-752
Substance use is associated with impaired social cognition. Experimental studies have shown that acute intoxication of alcohol, tobacco, and cannabis decreases the performance in non-verbal, social communication and theory of mind tasks. However, in epidemiological studies the temporal direction of this association has gone relatively unstudied. We investigated both directions of association within an adolescent birth cohort: the association of social cognition with subsequent substance use, and the association of early substance use with subsequent social cognition. We used data from the Avon Longitudinal Study of Parents and Children, a UK birth cohort. Logistic regression indicated that poor childhood non-verbal communication was associated with decreased odds of adolescent alcohol (OR 0.70, 95% 0.54–0.91), tobacco (OR 0.62, 95% CI 0.47–0.83), and cannabis use (OR 0.62, 95% CI 0.46–0.83). Early adolescent substance use was associated with increased odds of poor social communication (alcohol: OR 1.46, 95% CI 0.99–2.14; tobacco: OR 1.95, 95% CI 1.33–2.86) and poor social reciprocity (alcohol: OR 1.57, 95% CI 1.18–2.09; tobacco: OR 1.92, 95% CI 1.43–2.58; cannabis: OR 1.54, 95% CI 1.16–2.05). Overall, the relationship between social cognition and substance use was different in each temporal direction. Poor non-verbal communication in childhood appeared protective against later substance use, while adolescent substance use was associated with decreased social cognitive performance. 相似文献
85.
86.
Avdienko VG Kosmiadi GA Baenskiĭ AV Averbakh MM Kapina MA Kalinina OA Dem'ianenko NV Kondratiuk NA Gergert VIa 《Problemy tuberkuleza》2002,(2):30-33
It is widely accepted that protection against tuberculosis is provided by the formation of type 1 immune response, which is characterized by the production of IFN-gamma and IL-2. However, type 2 antimycobacterial immune response is also present: specific IgE antibodies that are IL-4 dependent, are usually found in tuberculosis patients. There is elevated production of type 2 cytokines in some cases. Thus, both types of an immune response can simultaneously develop, probably counteracting with each other. It is unknown which of mycobacterial antigens are capable of inducing a preferential type 2 response. To detect these antigens, the authors studied tuberculosis IgE antibodies in the sera of 500 tuberculosis patients by using the ELISA assay with ultrasonic disintegrated M. Tuberculosis H37Rv (sonicate). Antigens recognized by IgE antibodies were found to be localized in the cell wall of mycobacteria. The IgE-response was specific since the sera did not react with the antigens of atypical mycobacteria and other bacterial species. 相似文献
87.
RATIONALE AND OBJECTIVES: This study was designed to (1) compare the effects of ionic (ioxaglate) and nonionic (iodixanol and iohexol) iodinated low-osmolar contrast media (CM) on platelet function in human whole blood by using the new PFA-100trade mark, a "platelet function analyzer"; (2) determine the animal species closest to human with regard to platelet reactivity to CM; and (3) evaluate which element of the ioxaglate solution supports this activity. METHODS: For all studies, platelet adhesion and aggregation were measured using the PFA-100trade mark system with adenosine diphosphate-primed collagen membrane cartridges. Results are shown as the membrane closure time (MCT; the longer the MCT, the greater the antiaggregatory effect) and given as medians. Citrated whole-blood samples from six healthy volunteers were mixed for 1 minute with a 10% (vol/vol) solution of ioxaglate, iodixanol, or iohexol or their respective ionic and nonionic controls (isotonic saline and mannitol). The test solution/control solution ratio for the MCT was calculated for the blood of humans, guinea pigs, rabbits, dogs, and rats. Isotonic saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), and sodium ioxaglate (600 mOsm/kg) were tested under similar conditions. RESULTS: All three CM caused significant prolongation of MCT when compared with their respective controls (ioxaglate: 300 seconds, ie, "no closure" on the PFA-100trade mark system; iodixanol: 179 seconds; iohexol: 171 seconds; saline: 115 seconds; mannitol: 118 seconds). The antiplatelet effect of ioxaglate was higher than that of iodixanol and iohexol (P < 0.05). The animal species tested did not differ significantly from the human species with regard to an effect of their blood on MCT. Both ioxaglic acid salts caused a higher prolongation of MCT when compared with saline (sodium salt: 259 seconds; meglumine salt: 212 seconds; P < 0.05 vs. saline) but not versus the ioxaglate commercial solution. Conversely, both iso- and hyperosmolar solutions of meglumine hydrochloride (108 and 128 seconds, respectively) did not lengthen MCT versus saline, but their MCTs were shorter than that of the commercial solution of ioxaglate (P < 0.05). CONCLUSIONS: The ionic CM ioxaglate displayed a greater antiaggregatory effect on human platelets than did both iso-osmolar (iodixanol) and hyperosmolar (iohexol) nonionic CM. This effect seems to be linked to the ioxaglic moiety, because neither osmolality nor sodium or meglumine appeared to play a significant role. 相似文献
88.
In Tari, in the southern highlands of Papua New Guinea, each child experienced, on average, two acute lower respiratory tract infections (ALRTI) between birth and age 5 years. The yearly mortality rate from ALRTI was 30 per 1000 in infants, and 4 per 1000 in children aged between 1 and 4 years. A double-blind trial of a 14-valent pneumococcal polysaccharide vaccine was carried out on 871 children from this community who were aged between 6 months and 5 years. Morbidity from ALRTI was lower (by 37%) in children given the vaccine provided they were at least 17 months of age at the time of immunisation. There were 8 deaths from ALRTI in the placebo group, but only 1 death in the vaccine group. 相似文献
89.
90.
Gianluca?TognonEmail authorView authors OrcID profile Elisabet?Rothenberg Martina?Petrolo Valter?Sundh Lauren?Lissner 《European journal of nutrition》2018,57(8):2869-2876