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1.
Nervenarzt ; 94(8): 685-693, 2023 Aug.
Article in German | MEDLINE | ID: mdl-37115255

ABSTRACT

Dysphagia is a clinically relevant problem in Parkinson's disease as well as in atypical Parkinsonian syndromes, such as multiple system atrophy and diseases from the spectrum of 4­repeat tauopathies, which affect most patients to a varying degree in the course of their disease. This results in relevant restrictions in daily life due to impaired intake of food, fluids, and medication with a subsequent reduction in quality of life. This article not only gives an overview of the pathophysiological causes of dysphagia in the various Parkinson syndromes, but also presents screening, diagnostic and treatment procedures that have been investigated for the different diseases.


Subject(s)
Deglutition Disorders , Multiple System Atrophy , Parkinson Disease , Parkinsonian Disorders , Humans , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Quality of Life , Parkinsonian Disorders/complications , Parkinsonian Disorders/diagnosis , Parkinsonian Disorders/therapy , Parkinson Disease/complications , Parkinson Disease/diagnosis , Parkinson Disease/therapy , Multiple System Atrophy/complications , Multiple System Atrophy/diagnosis , Multiple System Atrophy/therapy
2.
BMC Ecol Evol ; 21(1): 54, 2021 04 12.
Article in English | MEDLINE | ID: mdl-33845757

ABSTRACT

BACKGROUND: Placentation has evolved multiple times among both chordates and invertebrates. Although they are structurally less complex, invertebrate placentae are much more diverse in their origin, development and position. Aquatic colonial suspension-feeders from the phylum Bryozoa acquired placental analogues multiple times, representing an outstanding example of their structural diversity and evolution. Among them, the clade Cyclostomata is the only one in which placentation is associated with viviparity and polyembryony-a unique combination not present in any other invertebrate group. RESULTS: The histological and ultrastructural study of the sexual polymorphic zooids (gonozooids) in two cyclostome species, Crisia eburnea and Crisiella producta, revealed embryos embedded in a placental analogue (nutritive tissue) with a unique structure-comprising coenocytes and solitary cells-previously unknown in animals. Coenocytes originate via nuclear multiplication and cytoplasmic growth among the cells surrounding the early embryo. This process also affects cells of the membranous sac, which initially serves as a hydrostatic system but later becomes main part of the placenta. The nutritive tissue is both highly dynamic, permanently rearranging its structure, and highly integrated with its coenocytic 'elements' being interconnected via cytoplasmic bridges and various cell contacts. This tissue shows evidence of both nutrient synthesis and transport (bidirectional transcytosis), supporting the enclosed multiple progeny. Growing primary embryo produces secondary embryos (via fission) that develop into larvae; both the secondary embyos and larvae show signs of endocytosis. Interzooidal communication pores are occupied by 1‒2 specialized pore-cells probably involved in the transport of nutrients between zooids. CONCLUSIONS: Cyclostome nutritive tissue is currently the only known example of a coenocytic placental analogue, although syncytial 'elements' could potentially be formed in them too. Structurally and functionally (but not developmentally) the nutritive tissue can be compared with the syncytial placental analogues of certain invertebrates and chordates. Evolution of the cyclostome placenta, involving transformation of the hydrostatic apparatus (membranous sac) and change of its function to embryonic nourishment, is an example of exaptation that is rather widespread among matrotrophic bryozoans. We speculate that the acquisition of a highly advanced placenta providing massive nourishment might support the evolution of polyembryony in cyclostomes. In turn, massive and continuous embryonic production led to the evolution of enlarged incubating polymorphic gonozooids hosting multiple progeny.


Subject(s)
Bryozoa , Animals , Female , Fishes , Invertebrates , Placenta , Placentation , Pregnancy
3.
Parkinsons Dis ; 2016: 7489105, 2016.
Article in English | MEDLINE | ID: mdl-27073710

ABSTRACT

Lateral trunk flexion (LTF) is a common phenomenon in patients with Parkinson's disease (PD) and has recently been associated with peripheral vestibular dysfunction. Since deviation of the subjective visual vertical (SVV) is a well-recognized feature of disorders involving vestibular processing, we analyzed SVV angles in 30 PD patients with and without LTF to assess the possible role of vestibular dysfunction in the pathogenesis of LTF in PD. Quantification of SVV was obtained using a simple bedside test. PD patients with LTF had significantly greater SVV angles as compared to PD patients without LTF (median: 4.3° [range: 0.1-17.7], n = 21, versus 0.8° [0.1-1.9], n = 9; p < 0.001). 14 of 21 patients with LTF showed pathological SVV, while all 9 patients without LTF had normal SVV. Abnormal SVV was more frequent when LTF was reversible in the supine position compared to fixed LTF. In a subgroup of PD patients with LTF, pathological SVV suggests vestibular dysbalance, which might be involved in the pathophysiological mechanisms underlying LTF.

4.
Appl Opt ; 54(2): 150-6, 2015 Jan 10.
Article in English | MEDLINE | ID: mdl-25967611

ABSTRACT

In recent years thermotropic overheating protection glazings have been the focus for both solar thermal collector technology and architecture. A thermotropic glazing changes its light transmittance from highly transparent to light diffusing upon reaching a certain threshold temperature autonomously and reversibly. In thermotropic systems with fixed domains (TSFD) the scattering domains are embedded in a polymer matrix, which exhibits a sudden change of the refractive index upon reaching a threshold temperature. The aim of the present study was to comprehensively investigate the light shielding characteristics and potential of TSFD materials by applying simulation of light scattering in particle-filled layers. In random walk simulations a variety of parameters were varied systematically, and the effect on the light transmission behavior of TSFD was studied. The calculation steps of the simulation process are shown in detail. The simulations demonstrate that there is great potential for the production of functional materials with high overheating protection efficiency.

5.
Neuroscience ; 293: 67-79, 2015 May 07.
Article in English | MEDLINE | ID: mdl-25748530

ABSTRACT

Aversive experiences in early life are thought to dispose to psychopathologies such as mood or anxiety disorders. In a two-hit stress model, we assessed the effects of juvenile and/or adult stress on the 5-HT-mediated modulation of synaptic inhibition of ventral dentate gyrus granule cells. Combined but not single stress exposure led to a significant reduction in activity and increased anxiety-like behavior. Similarly, the 5-HT1A receptor-mediated inhibition of evoked inhibitory postsynaptic currents (IPSCs) of granule cells was only reduced in single stress exposed animals. This was also true for the number of granule cells responding with a 5-HT3 receptor-dependent burst of miniature IPSCs. 5-HT3 receptors are expressed on cholecystokinin (CCK)+ basket cells in the hippocampus. In fact, we observed a reduction of steady-state mRNA levels of CCK+ basket cell markers after single juvenile or adult stress and partial recovery after combined stress, thus matching the electrophysiological findings. Adaptive changes in 5-HT-mediated modulation of synaptic inhibition and CCK+ basket cells in the DG may help to maintain normal levels of anxiety after single juvenile or adult stress exposure, as indicated by the increased anxiety that accompanies the loss of this regulation upon combined stress.


Subject(s)
Dentate Gyrus/physiopathology , Neurons/physiology , Receptor, Serotonin, 5-HT1A/physiology , Receptors, Serotonin, 5-HT3/physiology , Stress, Psychological/physiopathology , Age Factors , Animals , Anxiety/physiopathology , Dentate Gyrus/drug effects , Inhibitory Postsynaptic Potentials/drug effects , Interneurons/metabolism , Male , Neural Inhibition/drug effects , Neurons/drug effects , Rats , Receptor, Serotonin, 5-HT1A/metabolism , Receptors, Serotonin, 5-HT3/metabolism , Serotonin/administration & dosage , Serotonin Receptor Agonists/administration & dosage , gamma-Aminobutyric Acid/metabolism
6.
Contraception ; 91(2): 105-12, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25453582

ABSTRACT

OBJECTIVE(S): To investigate the bleeding pattern and cycle control parameters of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a patch containing 0.6 mg EE and 6 mg norelgestromin (NGMN). STUDY DESIGN: In this phase III, open-label, randomized, parallel-group trial, healthy women aged 18-35 years (smokers aged 18-30 years) received either the EE/GSD patch (n=200) or the EE/NGMN patch (n=198). Treatment consisted of one patch per week for 3 weeks followed by a 7-day, patch-free interval for seven cycles. Bleeding control was assessed in two 90-day reference periods. RESULTS: In reference period 1, mean number of bleeding/spotting days was comparable across treatment groups (p>0.05). However, in reference period 2, there were fewer bleeding/spotting days in the EE/GSD patch group (15.7 versus 18.4; p<0.0001). Mean number of bleeding/spotting episodes was comparable across groups for both reference periods, but bleeding/spotting episodes were shorter for the EE/GSD patch than the EE/NGMN patch during reference period 1 (5.13 days versus 5.53 days, respectively; p<0.05) and reference period 2 (5.07 versus 5.66; p=0.0001). Both treatment groups showed a similar frequency of withdrawal bleeding episodes; however, across all seven cycles, the length of these episodes was consistently shorter with the EE/GSD patch (p<0.01). There were no notable treatment differences in intracyclic bleeding. CONCLUSION(S): Bleeding pattern and cycle control achieved with the EE/GSD patch was similar to that of the EE/NGMN patch. IMPLICATIONS STATEMENT: The paper presents data on the bleeding pattern and cycle control parameters of an investigational transdermal contraceptive patch containing EE and GSD compared with an approved contraceptive patch containing EE and NGMN. This descriptive study found that bleeding patterns associated with the EE/GSD patch were similar to those of an EE/NGMN patch providing higher EE exposure.


Subject(s)
Contraceptive Agents, Female/administration & dosage , Estrogens/administration & dosage , Ethinyl Estradiol/administration & dosage , Menstrual Cycle/drug effects , Norpregnenes/administration & dosage , Progestins/administration & dosage , Transdermal Patch , Adolescent , Adult , Amenorrhea/chemically induced , Amenorrhea/epidemiology , Austria/epidemiology , Contraceptive Agents, Female/adverse effects , Czech Republic/epidemiology , Drug Combinations , Estrogens/adverse effects , Ethinyl Estradiol/adverse effects , Female , Humans , Incidence , Mastodynia/chemically induced , Mastodynia/epidemiology , Menorrhagia/chemically induced , Menorrhagia/epidemiology , Metrorrhagia/chemically induced , Metrorrhagia/epidemiology , Netherlands/epidemiology , Norgestrel/administration & dosage , Norgestrel/adverse effects , Norgestrel/analogs & derivatives , Norpregnenes/adverse effects , Patient Dropouts , Progestins/adverse effects , Transdermal Patch/adverse effects , Young Adult
8.
J Neural Transm (Vienna) ; 121(10): 1303-12, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24699718

ABSTRACT

Deep brain stimulation (DBS) represents an established treatment option in a growing number of movement disorders. Recent case reports suggest beneficial effect of globus pallidus internus (GPi)-DBS in selected patients suffering from Huntington's disease with marked disabling chorea. We present a 41-year-old man with genetically confirmed HD following quadruple GPi- and subthalamic nucleus (STN)-DBS. Motor function was assessed by Abnormal Involuntary Movement Scale (AIMS) and by Unified Huntington Disease Rating Scale (UHDRS) presurgery and postsurgery for up to 4 years. Furthermore, cognitive, neuropsychiatric state and quality of life (QoL) including life satisfaction (QLS) were annually evaluated. Chorea assessed by AIMS and UHDRS subscores improved by 52 and 55 %, 45 and 60 %, 35 and 45 % and 55-66 % at 1-4 years, respectively, compared to presurgical state following GPi-STN-DBS. During these time periods bradykinesia did not increase following separate STN- and combined GPi-STN-DBS compared to presurgical state. Mood, QoL and QLS were ameliorated. However, dysexecutive symptoms increased at 4 years postsurgery. The present case report suggests that bilateral GPi- and STN-DBS may represent a new treatment avenue in selected HD patients. Clinically, GPi-DBS attenuated chorea and was associated with a larger effect-adverse effect window compared to STN-DBS. However, GPi-DBS-induced bradykinesia may emerge as one main limitation of GPi-DBS in HD. Thus, quadruple GPi-STN-DBS may be indicated, if separate GPi-DBS does not result in sufficient control of motor symptoms. Future controlled studies need to confirm if the present anecdotal observation of additive beneficial effects of GPi- and STN-DBS in a HD patient with severe generalized chorea and relatively intact cognitive and affective functions indeed represents a new therapeutic option.


Subject(s)
Deep Brain Stimulation/methods , Globus Pallidus/physiopathology , Huntington Disease/physiopathology , Huntington Disease/therapy , Subthalamic Nucleus/physiopathology , Adult , Deep Brain Stimulation/adverse effects , Globus Pallidus/pathology , Humans , Huntington Disease/pathology , Huntington Disease/psychology , Magnetic Resonance Imaging , Male , Motor Activity/physiology , Subthalamic Nucleus/pathology , Treatment Outcome
9.
Science ; 343(6166): 51-4, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24263132

ABSTRACT

Gamma-ray burst (GRB) 130427A is one of the most energetic GRBs ever observed. The initial pulse up to 2.5 seconds is possibly the brightest well-isolated pulse observed to date. A fine time resolution spectral analysis shows power-law decays of the peak energy from the onset of the pulse, consistent with models of internal synchrotron shock pulses. However, a strongly correlated power-law behavior is observed between the luminosity and the spectral peak energy that is inconsistent with curvature effects arising in the relativistic outflow. It is difficult for any of the existing models to account for all of the observed spectral and temporal behaviors simultaneously.

10.
N Engl J Med ; 368(7): 610-22, 2013 Feb 14.
Article in English | MEDLINE | ID: mdl-23406026

ABSTRACT

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).


Subject(s)
Electric Stimulation Therapy , Parkinson Disease/therapy , Quality of Life , Activities of Daily Living , Adult , Antiparkinson Agents/adverse effects , Antiparkinson Agents/therapeutic use , Combined Modality Therapy , Dopamine Agonists/adverse effects , Dopamine Agonists/therapeutic use , Dyskinesias/etiology , Electric Stimulation Therapy/adverse effects , Female , Humans , Implantable Neurostimulators/adverse effects , Intention to Treat Analysis , Male , Middle Aged , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Subthalamic Nucleus , Surveys and Questionnaires , Treatment Outcome
11.
Diabetologia ; 55(11): 3071-82, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22898767

ABSTRACT

AIMS/HYPOTHESIS: Inspired by recent speculation about the potential utility of α(2A)-antagonism in the treatment of type 2 diabetes, the study examined the contribution of α(2)-antagonism vs other mechanisms to the antihyperglycaemic activity of the imidazoline (±)-efaroxan. METHODS: Effects of the racemate and its pure enantiomers on isolated pancreatic islets and beta cells in vitro, as well as on hyperglycaemia in vivo, were investigated in a comparative manner in mice. RESULTS: In isolated perifused islets, the two enantiomers of efaroxan were equally potent in counteracting inhibition of insulin release by the ATP-dependent K(+) (K(ATP)) channel-opener diazoxide but (+)-efaroxan, the presumptive carrier of α(2)-antagonistic activity, was by far superior in counteracting inhibition of insulin release by the α(2)-agonist UK14,304. In vivo, (+)-efaroxan improved oral glucose tolerance at 100-fold lower doses than (-)-efaroxan and, in parallel with observations made in vitro, was more effective in counteracting UK14,304-induced than diazoxide-induced hyperglycaemia. The antihyperglycaemic activity of much higher doses of (-)-efaroxan was associated with an opposing pattern (i.e. with stronger counteraction of diazoxide-induced than UK14,304-induced hyperglycaemia), which implicates a different mechanism of action. CONCLUSIONS/INTERPRETATION: The antihyperglycaemic potency of (±)-efaroxan in mice is almost entirely due to α(2)-antagonism, but high doses can also lower blood glucose via another mechanism. Our findings call for reappraisal of the possible clinical utility of α(2A)-antagonistic compounds in recently identified subpopulations of patients in which a congenitally higher level of α(2A)-adrenergic activation contributes to the development and pathophysiology of type 2 diabetes.


Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Benzofurans/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Hyperglycemia/drug therapy , Imidazoles/pharmacology , Insulin-Secreting Cells/drug effects , Adrenergic alpha-2 Receptor Antagonists/pharmacology , Animals , Antihypertensive Agents/pharmacology , Brimonidine Tartrate , Calcium/metabolism , Cells, Cultured , Diabetes Mellitus, Type 2/metabolism , Diazoxide/pharmacology , Female , Hyperglycemia/metabolism , Insulin/metabolism , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/metabolism , KATP Channels/physiology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Mice, Inbred C57BL , Patch-Clamp Techniques , Quinoxalines/pharmacology , Yohimbine/pharmacology
12.
Neurology ; 73(1): 53-8, 2009 Jul 07.
Article in English | MEDLINE | ID: mdl-19564584

ABSTRACT

OBJECTIVE: High-frequency stimulation of the globus pallidus internus (GPi) is a highly effective therapy in primary dystonia. Recent reports have also demonstrated almost immediate improvement of motor symptoms in patients with tardive dystonia after pallidal deep brain stimulation (DBS). Here, we show the long-term effect of continuous bilateral GPi DBS in tardive dystonia on motor function, quality of life (QoL), and mood. METHODS: Nine consecutive patients undergoing DBS for tardive dystonia were assessed during continuous DBS at 3 time points: 1 week, 3 to 6 months, and last follow-up at the mean of 41 (range 18-80) months after surgery using established and validated movement disorder and neuropsychological scales. Clinical assessment was performed by a neurologist not blinded to the stimulation settings. RESULTS: One week and 3 to 6 months after pallidal DBS, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor scores were ameliorated by 56.4 +/- 26.7% and 74.1 +/- 15.8%, BFMDRS disability scores by 62.5 +/- 21.0% and 88.9 +/- 10.3%, and Abnormal Involuntary Movement Scale (AIMS) scores by 52.3 +/- 24.1% and 69.5 +/- 27.6%, respectively. At last follow-up, this improvement compared with the presurgical assessment was maintained as reflected by a reduction of BFMDRS motor scores by 83.0 +/- 12.2%, BFMDRS disability scores by 67.7 +/- 28.0%, and AIMS scores by 78.7 +/- 19.9%. QoL improved significantly in physical components, and there was a significant improvement in affective state. Furthermore, cognitive functions remained unchanged compared with presurgical status in the long-term follow-up. No permanent adverse effects were observed. CONCLUSION: Pallidal deep brain stimulation is a safe and effective long-term treatment in patients with medically refractory tardive dystonia.


Subject(s)
Deep Brain Stimulation/methods , Dystonic Disorders/therapy , Globus Pallidus/physiology , Adult , Affect/physiology , Aged , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Cognition Disorders/therapy , Deep Brain Stimulation/statistics & numerical data , Disability Evaluation , Dystonic Disorders/physiopathology , Dystonic Disorders/psychology , Female , Globus Pallidus/anatomy & histology , Humans , Male , Middle Aged , Mood Disorders/etiology , Mood Disorders/physiopathology , Mood Disorders/therapy , Movement/physiology , Patient Satisfaction , Quality of Life/psychology , Recovery of Function/physiology , Severity of Illness Index , Time , Treatment Outcome
13.
Appl Opt ; 48(8): 1514-9, 2009 Mar 10.
Article in English | MEDLINE | ID: mdl-19277084

ABSTRACT

Wavelength selective coatings are of common use in order to enhance the efficiency of devices heated by radiation such as solar thermal collectors. The use of suitable materials and the optimization of coating layer thicknesses are advisable ways to maximize the absorption. Further improvement is achievable by embedding particles in certain layers in order to modify material properties. We focus on optimizing the absorption behavior of a solar collector setup using copper as substrate, a layer of amorphous hydrogenated carbon with embedded titanium carbide particles (a-C:H/TiC), and an antireflection coating of amorphous silicon dioxide (aSiO(2)). For the setup utilizing homogeneous particle distribution, a relative absorption of 90.98% was found, while inhomogeneous particle embedding yielded 98.29%. These results are particularly interesting since until now, absorption of more than 95% was found only by using embedded Cr but not by using the more biocompatible Ti.

14.
J Fr Ophtalmol ; 31(1): 17-22, 2008 Jan.
Article in French | MEDLINE | ID: mdl-18401294

ABSTRACT

PURPOSE: P. Khaw has described a new trabeculectomy technique to enhance the reliability (fewer complications) and the efficacy of the classic trabeculectomy introduced by Cairns. The purpose of this study was to assess the medium-term tonometric results and complications of this new surgical procedure. MATERIAL: and methods: In a retrospective and nonrandomized study, 26 consecutive eyes of 21 patients who underwent trabeculectomy according to P. Khaw's protocol were analyzed. The surgeon conducted postoperative care for the first 2 months. The minimal follow-up was 1 year, with a mean follow-up of 16.8 months (range, 12-18 months). The criteria for success were defined as intraocular pressure (IOP) less than 16 mmHg without treatment. RESULTS: The mean IOP remained stable around 12 mmHg during the study follow-up: 12.5 mmHg+/-3.07 at 12 months and 11.8 mmHg+/-3.17 at 18 months. The success rate was 92.3% at 3 months and 84.6% at 6, 9, and 12 months. The mean IOP reduction was 44.1%+/-17.05. No failure was observed between months 6 and 18. The probability for an IOP under 16 mmHg without treatment at months 12 and 18 was 84% (Kaplan-Meier). At 1 year, 65% of the eyes had an IOP under 14 mmHg without treatment. Complications were limited and transient: one case of choroidal detachment and three cases of hyphema. No flat anterior chamber and no infection were observed during follow-up. CONCLUSION: The new trabeculectomy described by P. Khaw is a promising procedure because at the medium term it provides tonometric results matching the target pressure of glaucomatous patients without the complications of the classic trabeculectomy.


Subject(s)
Glaucoma/surgery , Intraocular Pressure , Trabeculectomy/methods , Follow-Up Studies , Humans , Manometry/methods , Retrospective Studies , Time Factors , Treatment Outcome
15.
Am J Physiol Heart Circ Physiol ; 293(5): H3008-13, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17766481

ABSTRACT

UNLABELLED: Molecular signaling pathways that regulate peripartum cardiac remodeling are not well understood. Our objectives were to study the role of mitogen-activated protein kinases (MAPKs), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) in mediating pregnancy and postpartum (PP) cardiac remodeling. METHODS: Adult female Sprague-Dawley rats were divided into nonpregnant (n = 5), 18 days pregnant (n = 5), 0 days PP (n = 7), and 14 days PP (n = 8). Rats underwent echocardiography under sedation to measure left ventricle (LV) size and function, and Western blots were performed to measure myocardial protein expression of MAPKs (p38, JNK, ERK), Akt, and eNOS. RESULTS: 1) During pregnancy, there was an increase in LV mass (0.62 +/- 0.03 to 1.1 +/- 0.04 g, P < 0.001), mass/volume ratio (0.7 +/- 0.02 to 1.28 +/- 0.02 g/ml, P < 0.0001), and ejection fraction (EF) (64 +/- 3 to 74 +/- 2%). Whereas LV mass and mass/volume ratio returned to prepregnancy values in the PP period, EF remained below normal range (53 +/- 3%, P < 0.05). 2) The expression of anti-hypertrophic factors (p38, JNK, Akt) decreased during pregnancy and normalized PP, except JNK, which increased to higher than normal levels. eNOS also increased to higher than baseline levels PP. 3) Activation of p38 and JNK was directly correlated with lower LV mass/volume ratio (r = -0.81 and -0.71, respectively; P < 0.05). CONCLUSION: Pregnancy is associated with physiological cardiac hypertrophy. There is rapid reversal of hypertrophy in the PP period while recovery of cardiac function is delayed, possibly related to PP upregulation of JNK. A dysregulation of MAPK signaling may be an important determinant of PP cardiac dysfunction.


Subject(s)
Cardiomegaly/metabolism , Pregnancy Complications, Cardiovascular/metabolism , Pregnancy, Animal/metabolism , Proteome/metabolism , Animals , Female , Pregnancy , Rats , Rats, Sprague-Dawley , Ventricular Remodeling
16.
Br J Ophthalmol ; 90(2): 158-61, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16424525

ABSTRACT

AIM: To evaluate long term results after transpupillary thermotherapy (TTT) in eyes with exudative age related macular degeneration. METHODS: In a prospective clinical study eyes with occult or predominantly occult choroidal neovascularisation and no pretreatment were scheduled to have a TTT with a power of 630 mW. Visual acuity for far and near distances as well as contrast sensitivity were evaluated 6, 12, and 24 months postoperatively and statistically analysed. RESULTS: 47 eyes fulfilled the inclusion criteria. Overall, 70% of the patients showed an improved (14%) or had unchanged (56%) ETDRS vision after 24 months. Reading vision was stabilised (51%) or better (5%) in 56% of the eyes at this time. However, the increasing number of eyes with severe deterioration resulted in a significant decrease of both parameters over time (p = 0.0002 and p = 0.0003, respectively). Contrast sensitivity could be maintained (70%) or improved (9%) in 79%. Statistical analyses indicated a trend but no significant decrease over time (p = 0.056). CONCLUSION: Although in the majority of patients far and near distance acuity could be stabilised on average a significant decrease over time after TTT was observed. Statistical comparison of months 12 and 24 showed no further deterioration.


Subject(s)
Choroidal Neovascularization/therapy , Hyperthermia, Induced/methods , Macular Degeneration/therapy , Aged , Aged, 80 and over , Angiography/methods , Choroid/blood supply , Choroid/diagnostic imaging , Choroidal Neovascularization/complications , Choroidal Neovascularization/physiopathology , Contrast Sensitivity/physiology , Female , Humans , Macular Degeneration/complications , Macular Degeneration/physiopathology , Male , Middle Aged , Prospective Studies , Reading , Regression Analysis , Tretoquinol , Visual Acuity/physiology
17.
J Neurol Neurosurg Psychiatry ; 76(12): 1713-6, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16291900

ABSTRACT

Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) alleviates symptoms in patients with dystonia but its effects on cognition, neuropsychiatric status, and quality of life have not been examined. This is a case series report of 15 consecutive patients with different forms of dystonia who underwent bilateral implantation of DBS electrodes in the GPi. The patients were evaluated preoperatively and after 3-12 months of DBS with tests of cognition (Mattis Dementia Rating Scale, Stroop Test, Trail Making Test, Phonemic and Category Word Fluency, Digit Span, Rey Auditory Verbal Learning Test, Tonic and Phasic Alertness), neuropsychiatric status (Beck Depression and Anxiety Inventories, Montgomery Asberg Depression Rating Scale, Snaith-Hamilton Pleasure Scale, Brief Psychiatric Rating Scale), quality of life, and motor functions. GPi DBS significantly improved dystonic symptoms, functional abilities, and quality of life allowing for a significant reduction of antidystonic medications. No deterioration was observed in cognitive scores and neuropsychiatric measures. The present case series report thus provides preliminary evidence for the safety of GPi DBS regarding cognitive and neuropsychiatric functions in patients with dystonia.


Subject(s)
Deep Brain Stimulation , Dystonia/therapy , Globus Pallidus/physiology , Adolescent , Adult , Affect , Aged , Cognition , Deep Brain Stimulation/adverse effects , Deep Brain Stimulation/methods , Electrodes, Implanted , Female , Functional Laterality , Humans , Male , Middle Aged , Quality of Life , Treatment Outcome
18.
Psychopharmacology (Berl) ; 178(4): 389-99, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15765254

ABSTRACT

RATIONALE: Daytime fatigue, which at the neurophysiological level is due to vigilance decrements, is a frequent complaint in postmenopausal women. OBJECTIVES: In a three-arm, 2-month, parallel group-design study, vigilance-promoting effects of a novel continuous combination (=Climodien 2/3) of estradiol valerate (EV; 2 mg) and dienogest (DNG; 3 mg) were compared with the effects of both EV alone and placebo in 55 insomniac, postmenopausal syndrome patients. METHODS: Low-resolution brain electromagnetic tomography (LORETA) was undertaken to identify the cerebral target regions of hormone replacement therapy. RESULTS: An omnibus significance test revealed Climodien to increase activity in 882 of 2,394 voxels in the alpha-2 band, followed by 733, 706, and 664 voxels in the beta-2, beta-1, and beta-3 bands, and 509 voxels in the delta band, whereas 2 mg EV alone did not produce a significant suprathreshold activity. Current density increased predominantly in the right hemisphere, which had already been described in the literature as the center of the vigilance system. In the fast alpha range, which plays a major role in the context of vigilance, increased activity was found in the right prefrontal, temporal, and superior parietal cortices, i.e., those brain areas of the right-sided fronto-parietal neuronal network that are responsible for sustained attention. A further activity increase was seen in the anterior cingulate gyrus associated with attentional control and conflict monitoring. The right temporal lobe showed increased current density in all frequency bands. CONCLUSIONS: Electroencephalographic tomography (LORETA) identified the right-hemispheric vigilance system as the target region of Climodien.


Subject(s)
Arousal/drug effects , Brain Mapping/methods , Diagnostic and Statistical Manual of Mental Disorders , Electroencephalography/methods , Estrogen Replacement Therapy/methods , Arousal/physiology , Brain Mapping/instrumentation , Data Interpretation, Statistical , Double-Blind Method , Drug Administration Schedule , Drug Combinations , Drug Synergism , Drug Therapy, Combination , Electroencephalography/drug effects , Electroencephalography/trends , Estradiol/administration & dosage , Estradiol/analogs & derivatives , Estradiol/pharmacokinetics , Estradiol/therapeutic use , Female , Humans , Middle Aged , Nandrolone/administration & dosage , Nandrolone/analogs & derivatives , Nandrolone/pharmacokinetics , Nandrolone/therapeutic use , Patient Selection , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/physiopathology , Tablets
19.
Eur J Radiol ; 51(3): 263-8, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15294335

ABSTRACT

OBJECTIVE: To determine the prevalence and clinical impact of rotator cuff tears in asymptomatic volunteers. MATERIALS AND METHODS: Sonographic examinations of the shoulder of 212 asymptomatic individuals between 18 and 85 years old were performed by a single experienced operator. The prevalence and location of complete rotator cuff tears were evaluated. The clinical assessment was based on the Constant Score. Magnetic resonance imaging (MRI) of the shoulder was obtained in those patients where US showed rotator cuff pathology. RESULTS: Ultrasound showed a complete rupture of the supraspinatus tendon in 6% of 212 patients from 56 to 83 years of age (mean: 67 years). MRI confirmed a complete rupture of the supraspinatus tendon in 90%. All patients reported no functional deficits, although strength was significantly lower in the patient group with complete supraspinatus tendon tear (P < 0.01). CONCLUSION: There is a higher prevalence in older individuals of rotator cuff tendon tears that cause no pain or decrease in activities of daily living.


Subject(s)
Rotator Cuff Injuries , Activities of Daily Living , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Bursa, Synovial/diagnostic imaging , Bursa, Synovial/pathology , Female , Humans , Humerus/diagnostic imaging , Humerus/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Muscle Contraction/physiology , Prospective Studies , Range of Motion, Articular/physiology , Rotation , Rotator Cuff/diagnostic imaging , Rotator Cuff/pathology , Rupture , Shoulder Pain/physiopathology , Ultrasonography
20.
J Fr Ophtalmol ; 26(8): 808-12, 2003 Oct.
Article in French | MEDLINE | ID: mdl-14586221

ABSTRACT

PURPOSE: To evaluate the effects of contact transscleral cyclophotocoagulation with neodymium YAG laser for refractory glaucoma. METHOD: This was a retrospective study with 36 patients (37 eyes) who were treated at the Rouen Hospital from February 1996 to February 2001. Patients had various types of glaucoma: glaucoma in pseudophakia (12), primary open-angle glaucoma (16), posttraumatic glaucoma (6), glaucoma associated with uveitis (4), neovascular glaucoma (3), and glaucoma after silicone oil (1). The Neodymium YAG laser (Alcon) was used for treatment. Energy was delivered in up 32 applications of 7-9 W for 0.7 seconds each. All patients except one 10-year-old child received retrobulbar anesthesia. Intraocular pressure was measured after 4 hours, 1 month, and 10 years. RESULTS: The mean preoperative intraocular pressure of 30.3 (+/-1.3) mmHg decreased to 19.4 (+/-2) mmHg at 1 month and to 22.2 (+/-2.4) mmHg at 1 year. Seven patients underwent a second treatment during the year, since the first one was insufficient. Treatment lowered the number of medications used to decrease intraocular pressure from a pretherapy mean of 2.7 mmHg to 1.8 mmHg at 1 month and 2.07 mmHg at 1 year. In three patients who were treated for a painful sightless eye, the treatment failed. DISCUSSION: Neodymium YAG laser necroses ciliary bodies. Treatment must be dosed to achieve the greatest efficacy without hypotonia, although hypotonia is rare, as is non-response to treatment. A few patients will be retreated during the year. The subgroup of sightless painful eyes had a high failure rate (75%), with half undergoing evisceration. We found no other differences according to the origins of refractory glaucoma. CONCLUSION: Midterm results of contact transscleral cyclophotocoagulation with Neodymium YAG laser are encouraging in the treatment of refractory glaucoma.


Subject(s)
Glaucoma/surgery , Intraocular Pressure , Laser Coagulation , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Child , Female , Follow-Up Studies , Glaucoma/etiology , Glaucoma, Neovascular/surgery , Glaucoma, Open-Angle/surgery , Humans , Laser Coagulation/methods , Male , Middle Aged , Pseudophakia/complications , Retrospective Studies , Time Factors , Treatment Outcome , Uveitis/complications
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