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1.
J Chem Phys ; 156(23): 234106, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35732515

RESUMO

Dispersion interactions are one of the components of van der Waals (vdW) forces that play a key role in the understanding of intermolecular interactions in many physical, chemical, and biological processes. The theory of dispersion forces was developed by London in the early years of quantum mechanics. However, it was only in the 1960s that it was recognized that for molecules lacking an inversion center, such as chiral and helical molecules, there are chirality-sensitive corrections to the dispersion forces proportional to the rotatory power known from the theory of circular dichroism and with the same distance scaling law R-6 as the London energy. The discovery of the chirality-induced spin selectivity effect in recent years has led to an additional twist in the study of chiral molecular systems, showing a close relation between spin and molecular geometry. Motivated by it, we propose in this investigation to describe the mutual induction of charge and spin-density fluctuations in a pair A-B of chiral molecules by a simple physical model. The model assumes that the same fluctuating electric fields responsible for vdW forces can induce a magnetic response via a Rashba-like term so that a spin-orbit field acting on molecule B is generated by the electric field arising from charge density fluctuations in molecule A (and vice versa). Within a second-order perturbative approach, these contributions manifest as an effective intermolecular exchange interaction. Although expected to be weaker than the standard London forces, these interactions display the same R-6 distance scaling.


Assuntos
Teoria Quântica , Londres , Estereoisomerismo
2.
Oper Orthop Traumatol ; 32(2): 171-178, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-31690973

RESUMO

OBJECTIVE: Treatment of a persistently painful snapping triceps and possibly snapping ulnar nerve. INDICATION: Snapping triceps. CONTRAINDICATIONS: General surgical risks. SURGICAL TECHNIQUE: Following the anterior transposition of the ulnar nerve (subcutaneously or submuscular), the snapping portion of the triceps tendon is transsected and reinforced, and transposition of the medial triceps margin into the central triceps portion is carried out. POSTOPERATIVE MANAGEMENT: Cast for 5-7 days; for a total of 6 weeks functional exercise without maximum flexion and resistance exercise of the triceps. Weight loading after 3 months. RESULTS: In the case presented, complaints were absent after 3 months. Full load exercise, e.g., push-ups, was achieved 4 months after surgery. There was no recurrent snapping within the first year. The results of this case are in agreement with the 25 patients previously reported in the PubMed literature. Recurrence, gross restrictions of movement, and complications were not observed in patients who underwent surgery.


Assuntos
Músculo Esquelético , Humanos , Amplitude de Movimento Articular , Tendões , Resultado do Tratamento , Nervo Ulnar
3.
Herz ; 44(7): 574-585, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31555893

RESUMO

Severe mitral regurgitation (MR) is associated with increased morbidity and mortality. Thus, the correct evaluation of the underlying etiology, pathomechanism and severity is crucial for optimal treatment. Echocardiography is the predominant diagnostic modality in the clinical routine as it enables grading of mitral regurgitation, which can frequently be achieved by readily available qualitative parameters. Additionally, echocardiography provides several methods to quantify the hemodynamic significance of MR. The effective regurgitation orifice area (EROA) is the quantitative parameter best correlated with clinical events. American and European imaging guidelines both recommend the use of quantitative parameters even though they disagree on the cut-off values for secondary MR. The evaluation of MR should always include an assessment of the adjacent heart chambers in order to be able to assess the impact of volume overload on size and function of the left ventricle and left atrium. The final interpretation of the quantitative parameters requires knowledge of left ventricular volume and ejection fraction. Newer 3D-echocardiographic approaches to quantify MR are less dependent on mathematical assumptions and have shown convincing results in several studies but still lack sufficient clinical validation. As an alternative to echocardiography, for specific indications cardiac magnetic resonance imaging (MRI) has proven to be a systematic and observer-independent method for quantification of MR.


Assuntos
Ecocardiografia Tridimensional , Insuficiência da Valva Mitral , Ecocardiografia Doppler em Cores , Ventrículos do Coração , Humanos , Insuficiência da Valva Mitral/diagnóstico por imagem , Índice de Gravidade de Doença
4.
Curr Rheumatol Rev ; 14(2): 98-107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28782470

RESUMO

Osteoarthritis represents the most frequently diagnosed condition of the musculoskeletal system and accounts for a high amount of direct and indirect socioeconomic costs worldwide. While for rheumatoid arthritis much progress has been made in the past decades both in understanding its pathogenesis and in creating novel therapies, the pathophysiology of osteoarthritis still holds several secrets to be unraveled in the near future in order to also allow for the development of effective novel pharmacotherapeutical options. Though first categorized as a joint disorder being primarily non-inflammatory in nature for a long period of time with research focused on biomechanic aspects and imbalanced wear and tear, recent evidence including immunological processes helped to refine disease interpretation. Thus, showing true inflammatory characteristics that clinically emerge as synovitis, osteoarthritis is nowadays recognized to include signs of inflammation that at least histologically may sometimes be indistinguishable from rheumatoid synovial infiltration. Although this was known already more than 25 years ago, efforts made in solving pathophysiologic key issues did not succeed sufficiently. This review is thought to summarize elementary pathogenic aspects including genetic predisposition and epigenetic regulation and highlights important central innate but also putative adaptive immunological mechanisms today generally accepted to drive inflammation and tissue destruction in osteoarthritis.


Assuntos
Osteoartrite/patologia , Osteoartrite/fisiopatologia , Humanos
5.
Psychopharmacology (Berl) ; 234(9-10): 1573-1586, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28243714

RESUMO

RATIONALE: Smoking is the leading cause of preventable death in the USA, but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. OBJECTIVES: We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the five-choice continuous performance test (5C-CPT). METHODS: Mice were trained in the 5C-CPT prior to osmotic minipump implantation containing saline or nicotine. Experiment 1 used 40 mg kg-1 day-1 nicotine treatment and tested C57BL/6 mice 4, 28, and 52 h after pump removal. Experiment 2 used 14 and 40 mg kg-1 day-1 nicotine treatment in α7 nAChR knockout (KO) and wildtype (WT) littermates tested 4 h after pump removal. Subsets of WT mice were killed before and after pump removal to assess changes in receptor expression associated with nicotine administration and withdrawal. RESULTS: Nicotine withdrawal impaired attention in the 5C-CPT, driven by response inhibition and target detection deficits. The overall attentional deficit was absent in α7 nAChR KO mice despite response disinhibition in these mice. Synaptosomal glutamate mGluR5 and dopamine D4 receptor expression were reduced during chronic nicotine but increased during withdrawal, potentially contributing to cognitive deficits. CONCLUSIONS: The α7 nAChR may underlie nicotine withdrawal-induced deficits in target detection but is not required for response disinhibition deficits. Alterations to the glutamatergic and dopaminergic pathways may also contribute to withdrawal-induced attentional deficits, providing novel targets to alleviate the cognitive symptoms of withdrawal during quit attempts.


Assuntos
Atenção/fisiologia , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Desempenho Psicomotor/fisiologia , Síndrome de Abstinência a Substâncias/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/deficiência , Animais , Atenção/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Desempenho Psicomotor/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/psicologia , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/agonistas
6.
Orthopade ; 46(3): 222-226, 2017 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-27904932

RESUMO

BACKGROUND: Reverse shoulder arthroplasty (RSA) has become a frequently used and established treatment for patients with cuff tear arthropathy, increasingly also for patients with fracture sequelae (FS), failed rotator cuff reconstruction and omarthrosis with cuff insufficiency. Since 2007 new generation prostheses, for example Delta Xtend (Depuy, Warsaw, USA), have been used, but few mid-term results have been published. OBJECTIVES: The aim of this study is to report on the outcome after RSA after a mean follow-up of 68 months (range 63-75), to verify the already published, encouraging early results and to learn about the function and pain situation after RSA in the mid-term period. METHODS: 60 patients underwent RSA with the Depuy Delta Xtend prosthesis in the years 2007 and 2008, performed by the senior author of this study. 39 of these patients were available for follow up and were asked to complete a questionnaire (msCS, modified subjective Constant Score). In addition, 28 patients agreed to a clinical examination. With these patients, in addition, the constant score, age and gender-adjusted constant score and range of motion were evaluated. RESULTS: The mean msCS of preoperative 39.15 points (range 12-69) improved to 71.74 points (range 44-100) after 5 years. The mean CS at 5 years was 65.79 points (range 21-93) and the mean age and gender-adjusted constant score was 92%. The mean active anterior elevation was 139° (range 70-180°), the mean abduction was 135° (range 50-170°) and the mean active external rotation was 17° (range -20-40°). CONCLUSION: This study confirms good early results after RSA after more than 5 years. We see very good outcomes in patients with CTA and omarthrosis, whilst the rate of complication is low.


Assuntos
Artroplastia do Ombro/instrumentação , Artroplastia do Ombro/métodos , Satisfação do Paciente , Amplitude de Movimento Articular , Lesões do Manguito Rotador/diagnóstico , Lesões do Manguito Rotador/terapia , Prótese de Ombro , Idoso , Idoso de 80 Anos ou mais , Análise de Falha de Equipamento , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Resultado do Tratamento
7.
Oper Orthop Traumatol ; 28(1): 78-89, 2016 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-25900829

RESUMO

OBJECTIVE: Safe and cost-effective rotator-cuff repair. INDICATION: All types of rotator cuff lesions. CONTRAINDICATIONS: Frozen shoulder, rotator cuff mass defect, defect arthropathy. SURGICAL TECHNIQUE: Extensive four-point fixation on the bony footprint is performed using the double-row lateral augmentation screw anchor (LASA-DR) with high biomechanical stability. Following mobilization of the tendons, these are refixed in the desired configuration first medially and then laterally. To this end, two drilling channels (footprint and lateral tubercle) are created for each screw. Using the shuttle technique, a suture anchor screw is reinforced with up to four pairs of threads. The medial row is then pierced and tied, and the sutures that have been left long are tied laterally around the screw heads (double row). POSTOPERATIVE MANAGEMENT: 4 Weeks abduction pillow, resulting in passive physiotherapy, followed by initiation of active assisted physiotherapy. Full weight-bearing after 4-6 months. RESULTS: Prospective analysis of 35 consecutive Bateman-III lesions with excellent results and low rerupture rate (6%).


Assuntos
Parafusos Ósseos , Procedimentos Cirúrgicos Reconstrutivos/instrumentação , Procedimentos Cirúrgicos Reconstrutivos/métodos , Lesões do Manguito Rotador/cirurgia , Âncoras de Sutura , Técnicas de Sutura , Adulto , Idoso , Análise de Falha de Equipamento , Humanos , Pessoa de Meia-Idade , Desenho de Prótese , Lesões do Manguito Rotador/diagnóstico , Resultado do Tratamento
8.
Z Orthop Unfall ; 153(4): 399-407, 2015 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-26274558

RESUMO

BACKGROUND: The double-row rotator cuff repair is discussed controversially. Despite improved biomechanical properties, reduced re-tear rates and higher costs, no significant difference compared to single-row fixation in the clinical results is found. Mid-term results of an open double-row fixation with titanium anchor screws are presented. MATERIAL AND METHODS: 237 patients (m = 142, f = 95, median age: 56.3 years) were operated in 2007 with this technique by the senior author (M. G.). Preoperatively, 2 years and 4,5 years postoperatively a subjective shoulder score (SSG) with follow-up rates of 86, 87 and 83 %, was evaluated. 5.1 years postoperatively an objective evaluation of 131 patients using the Constant-Murley scores (CS), the simple shoulder tests (SST), Gerber's shoulder value and the evaluation with school grades followed. The integrity of the cuff was checked with ultrasound. The absolute (re-tears and partial re-tears) and the relative (re-tears, partial re-tears, thinning and thickening of the cuff) re-tear rates were evaluated. RESULTS: In SSG a highly significant improvement from 51 to 83 points was found (p < 0.001). In CS 80 points (min.: 18; max.: 100), and in SST 11 points (min.: 2; max.: 12) were achieved. The shoulder value of Gerber increased significantly from preoperative 28.1 to 84.5 % 5.1 years postoperative (p < 0.001).The absolute re-tear rate, evaluated in ultrasound was 7.6 %, the relative re-tear rate 17.6 %. For primary rotator cuff reconstructions a higher CS with 82 points and a lower relative re-tear rate with 10.5 % were found. The patient's age had no significant influence on the clinical outcome. The rupture size showed a significant impact on the re-tear rate and the scores (p < 0.05). Between the operated and healthy shoulder neither strength nor mobility were found to be significantly different. Men reached a highly significant better strength than women (p < 0.001) which also resulted in a significantly better outcome in the CS (p < 0.01). The costs for open titanium transfixation technique with 330 € per case are markedly less than for arthroscopic suture bridge technique with 600 to 1000 € per case. CONCLUSION: Open double-row cuff repair with titanium screws is a safe and cost effective technique with a low re-tear rate with comparable clinical results regarding open and arthroscopic procedures.


Assuntos
Parafusos Ósseos , Procedimentos Cirúrgicos Reconstrutivos/instrumentação , Lesões do Manguito Rotador , Manguito Rotador/cirurgia , Âncoras de Sutura , Titânio/química , Análise de Falha de Equipamento , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Procedimentos Cirúrgicos Reconstrutivos/métodos , Estudos Retrospectivos , Manguito Rotador/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia
9.
Psychoneuroendocrinology ; 51: 495-505, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25444643

RESUMO

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is a major public health concern, especially given the recent wars in Iraq and Afghanistan. Nevertheless, despite a sharp increase in the incidence of psychiatric disorders in returning veterans, empirically based prevention strategies are still lacking. To develop effective prevention and treatment strategies, it is necessary to understand the underlying biological mechanisms contributing to PTSD and other trauma related symptoms. METHODS: The "Marine Resiliency Study II" (MRS-II; October 2011-October 2013) Neurocognition project is an investigation of neurocognitive performance in Marines about to be deployed to Afghanistan. As part of this investigation, 1195 Marines and Navy corpsmen underwent a fear conditioning and extinction paradigm and psychiatric symptom assessment prior to deployment. The current study assesses (1) the effectiveness of the fear potentiated startle paradigm in producing fear learning and extinction and (2) the association of performance in the paradigm with baseline psychiatric symptom classes (healthy: n=923, PTSD symptoms: n=42, anxiety symptoms: n=37, and depression symptoms: n=12). RESULTS: Results suggest that the task was effective in producing differential fear learning and fear extinction in this cohort. Further, distinct patterns emerged differentiating the PTSD and anxiety symptom classes from both healthy and depression classes. During fear acquisition, the PTSD symptom group was the only group to show deficient discrimination between the conditioned stimulus (CS+) and safety cue (CS-), exhibiting larger startle responses during the safety cue compared to the healthy group. During extinction learning, the PTSD symptom group showed significantly less reduction in their CS+ responding over time compared to the healthy group, as well as reduced extinction of self-reported anxiety to the CS+ by the end of the extinction session. Conversely, the anxiety symptom group showed normal safety signal discrimination and extinction of conditioned fear, but exhibited increased baseline startle reactivity and potentiated startle to CS+, as well as higher self-reported anxiety to both cues. The depression symptom group showed similar physiological and self-report measures as the healthy group. DISCUSSION: These data are consistent with the idea that safety signal discrimination is a relatively specific marker of PTSD symptoms compared to general anxiety and depression symptoms. Further research is needed to determine if deficits in fear inhibition vs. exaggerated fear responding are separate biological "domains" across anxiety disorders that may predict differential biological mechanisms and possibly treatment needs. Future longitudinal analyses will examine whether poor learning of safety signals provides a marker of vulnerability to develop PTSD or is specific to symptom state.


Assuntos
Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/psicologia , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Ansiedade/psicologia , Depressão/psicologia , Medo/fisiologia , Humanos , Aprendizagem/fisiologia , Acontecimentos que Mudam a Vida , Masculino , Reflexo de Sobressalto/fisiologia , Resiliência Psicológica , Adulto Jovem
10.
J Psychopharmacol ; 29(2): 178-96, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25516372

RESUMO

Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. While antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult, however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition.


Assuntos
Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Animais , Humanos
11.
Curr Top Behav Neurosci ; 21: 157-83, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25158622

RESUMO

Posttraumatic stress disorder (PTSD) is a major public health concern, which has been seeing increased recent attention partly due to the wars in Iraq and Afghanistan. Historically, research attempting to understand the etiology and treatment of PTSD has made frequent use of psychophysiological measures of arousal as they provide a number of advantages in providing objective, non-self-report outcomes that are closely related to proposed neurobiological mechanisms and provide opportunity for cross-species translation. Further, the ongoing shift in classification of psychiatric illness based on symptom clusters to specific biological, physiological, and behavioral constructs, as outlined in the US National Institute of Mental Health (NIMH) Research Domain Criteria project (RDoC), promises that psychophysiological research will continue to play a prominent role in research on trauma-related illnesses. This review focuses on the current state of the knowledge regarding psychophysiological measures and PTSD with a focus on physiological markers associated with current PTSD symptoms, as well as markers of constructs thought to be relevant to PTSD symptomatology (safety signal learning, fear extinction), and psychophysiological markers of risk for developing PTSD following trauma. Future directions and issues for the psychophysiological study of trauma including traumatic brain injury (TBI), treatment outcome studies, and new wearable physiological monitoring technologies are also discussed.

12.
Philos Trans A Math Phys Eng Sci ; 372(2017): 20130309, 2014 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-24797137

RESUMO

Postharvest technologies have allowed horticultural industries to meet the global demands of local and large-scale production and intercontinental distribution of fresh produce that have high nutritional and sensory quality. Harvested products are metabolically active, undergoing ripening and senescence processes that must be controlled to prolong postharvest quality. Inadequate management of these processes can result in major losses in nutritional and quality attributes, outbreaks of foodborne pathogens and financial loss for all players along the supply chain, from growers to consumers. Optimal postharvest treatments for fresh produce seek to slow down physiological processes of senescence and maturation, reduce/inhibit development of physiological disorders and minimize the risk of microbial growth and contamination. In addition to basic postharvest technologies of temperature management, an array of others have been developed including various physical (heat, irradiation and edible coatings), chemical (antimicrobials, antioxidants and anti-browning) and gaseous treatments. This article examines the current status on postharvest treatments of fresh produce and emerging technologies, such as plasma and ozone, that can be used to maintain quality, reduce losses and waste of fresh produce. It also highlights further research needed to increase our understanding of the dynamic response of fresh produce to various postharvest treatments.


Assuntos
Abastecimento de Alimentos , Frutas , Verduras , Microbiologia de Alimentos , Armazenamento de Alimentos
13.
Bone Marrow Transplant ; 49(7): 913-20, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24797180

RESUMO

BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with ~85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, fludarabine 180 mg/m(2), alemtuzumab 54 mg/m(2) (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3-20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II-IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.


Assuntos
Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Irmãos , Doadores de Tecidos , Quimeras de Transplante , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados , Adulto Jovem
14.
Z Rheumatol ; 73(2): 149-60; quiz 161-2, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-24659151

RESUMO

Capillaroscopy is performed to evaluate the morphology, frequency and blood flow of nailfold capillaries as well as relevant extracapillary changes in rheumatic conditions. The main indication is the differentiation between primary and secondary Raynaud's phenomenon. Various rheumatic conditions show different and partially typical pathognomonic alterations of the microcirculation or capillary patterns. This simple, noninvasive, inexpensive and effective technique is well suited for early diagnosis, especially of connective tissue diseases. The specific significance is highest for systemic sclerosis which is the most frequently evaluated entity. The corresponding microscopic alterations allow stage-adapted conclusions concerning the acuity of inflammation to be formed. That is not the only reason why capillaroscopy represents an important tool in follow-up controls and together with other techniques, such as flow measurement by laser Doppler, further conclusions can be drawn.


Assuntos
Capilares/fisiopatologia , Angioscopia Microscópica/métodos , Unhas/irrigação sanguínea , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/fisiopatologia , Velocidade do Fluxo Sanguíneo , Medicina Baseada em Evidências , Humanos , Unhas/fisiopatologia
15.
Transl Psychiatry ; 3: e324, 2013 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-24217494

RESUMO

Attentional dysfunction in schizophrenia (SZ) is a core deficit that contributes to multiple cognitive deficits and the resulting functional disability. However, developing procognitive therapeutics for neuropsychiatric disorders have been limited by a 'translational gap'--a lack of cognitive paradigms having cross-species translational validity and relevance. The present study was designed to perform an initial validation of the cross-species homology of the 5-choice Continuous Performance Test (5C-CPT) in healthy nonpsychiatric comparison subjects (NCS), SZ patients and mice under pharmacologic challenge. The 5C-CPT performance in SZ patients (n=20) was compared with age-matched NCS (n=23). The effects of the general muscarinic receptor antagonist scopolamine on mice (n=21) performing the 5C-CPT were also assessed. SZ subjects exhibited significantly impaired attention in the 5C-CPT, driven by reduced target detection over time and nonsignificantly increased impulsive responding. Similarly, scopolamine significantly impaired attention in mice, driven by reduced target detection and nonsignificantly increased impulsive responding. Scopolamine also negatively affected accuracy and speed of responding in mice, although these measures failed to differentiate SZ vs. NCS. Thus, mice treated with scopolamine exhibited similar impairments in vigilance as seen in SZ, although the differences between the behavioral profiles warrant further study. The availability of rodent and human versions of this paradigm provides an opportunity to: (1) investigate the neuroanatomic, neurochemical and genomic architecture of abnormalities in attention observed in clinical populations such as SZ; (2) develop and refine animal models of cognitive impairments; and (3) improve cross-species translational testing for the development of treatments for these impairments.


Assuntos
Atenção , Transtornos Cognitivos/induzido quimicamente , Modelos Animais de Doenças , Camundongos , Antagonistas Muscarínicos/farmacologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Escopolamina/farmacologia , Adulto , Animais , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tempo de Reação , Adulto Jovem
16.
Bone Marrow Transplant ; 48(1): 19-25, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22684047

RESUMO

Intravenous BU divided four times daily (q6 h) has been shown to be safe and effective in pediatric allo-SCT recipients. Though less frequent dosing is desirable, pharmacokinetic (PK) data on twice daily (q12 h) i.v. BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving i.v. BU q12 h as part of conditioning before allo-SCT. BU levels were obtained after the first dose of conditioning. PK parameter analysis (n=49) yielded the following 95% confidence intervals (CI95): weight-normalized volume of distribution: 0.65-0.73 L/kg; t(1/2): 122-147 min; weight-normalized clearance (CL(n)): 3.4-4.3 mL/min/kg; and area under the curve: 1835-2180 mmol × min/L. From these results, a steady state concentration was calculated with CI95 between 628-746 ng/mL. Comparison between recipients ≤4 vs >4 years old revealed significant differences in t(1/2) (mean: 115 vs 146 min, P=0.008) and CL(n) (mean: 4.4 vs 3.5 mL/min/kg, P=0.038). Intravenous BU q12 h had a comparable PK to i.v. BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to i.v. q6h dosing.


Assuntos
Antineoplásicos Alquilantes/farmacocinética , Bussulfano/farmacocinética , Agonistas Mieloablativos/farmacocinética , Transplante de Células-Tronco/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Fatores Etários , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/sangue , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/sangue , Criança , Pré-Escolar , Estudos de Coortes , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Sobrevivência de Enxerto/efeitos dos fármacos , Meia-Vida , Humanos , Lactente , Infusões Intravenosas , Masculino , Taxa de Depuração Metabólica , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Agonistas Mieloablativos/sangue , Transplante Homólogo
17.
Clin Neurophysiol ; 124(5): 1025-30, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23200315

RESUMO

OBJECTIVE: This study was to investigate the utility of motor evoked potential monitoring elicited by transcranial electrical stimulation (tcMEP) during CEA in addition to the established median nerve somatosensory evoked potentials (mSSEPs). METHODS: We retrospectively reviewed data from 600 patients undergoing CEA under general anesthesia with monitoring of mSSEPs and tcMEPs in a multicenter study. MSSEP and tcMEP parameters were recorded during internal carotid artery (ICA) cross clamping and compared with the postoperative motor outcome, demographic and patient history data. RESULTS: The intraoperative monitoring of tcMEPs was successful in 594 of the patients (99%) and selective shunt was performed in 29 of them (4.83%). Nine of the patients showed a transient contralateral loss of tcMEPs, without changes in mSSEPs and required intervention (1.5% "false-negative"). Three of them showed postoperative motor deficits. The time period from tcMEP loss to intervention was significantly longer (p = 0.01) in this group compared to the patients without postoperative motor deficit. CONCLUSION: TcMEPs during CEA may be an adjunct to mSSEP monitoring to avoid "false-negative" mSSEP results, as mSSEPs seem to lack specificity for detecting isolated ischemia of corticospinal pathway. SIGNIFICANCE: TcMEPs seem to improve postoperative outcome, especially in case of a timely correction of cerebral ischemia.


Assuntos
Isquemia Encefálica/cirurgia , Endarterectomia das Carótidas , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Monitorização Intraoperatória , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/métodos , Artéria Carótida Interna/fisiopatologia , Endarterectomia das Carótidas/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Estudos Retrospectivos
19.
Diagn Ther Endosc ; 2012: 692532, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23055655

RESUMO

Available evidence suggests that the use of CO(2) insufflation in endoscopy is more comfortable for the patient. The safety of CO(2) use in colonoscopy remains contentious, particularly in sedated patients. The objective of the present prospective trial was to assess the safety of CO(2) colonoscopies. Methods. 109 patients from our previous randomized CO(2) colonoscopy study and an additional 238 subsequent consecutive unselected patients who had a routine colonoscopy performed in a private practice were enrolled from April 2008 through September 2008. All but 2 patients were sedated. All patients were routinely monitored with transcutaneous CO(2) measurement. Volumes of CO(2) administered were correlated with capnographic measurements from transcutaneous monitoring. Results. Of the 347 patients examined, 57% were women; mean (SD) age of participants was of 60.2 years (12.8). Mean propofol dosage was 136 mg (64 mg). Mean CO(2) values were 34.7 mm Hg (5.3) at baseline, 38.9 mm Hg (5.5) upon reaching the ileum, and 36.9 mm Hg (5.0) at examination's end. Mean maximum increase of CO(2) was 4.5 mm Hg (3.6). No correlation was observed between volume of CO(2) administered and increase in level of CO(2) (correlation coefficient: 0.01; P value: 0.84). No complications were observed. Conclusions. The present prospective study, which was based on one of the largest sedated patient sample reported to date in this setting, provides compelling evidence that CO(2) insufflation in colonoscopy is safe and unassociated with relevant increases in transcutaneously measured levels of CO(2).

20.
Z Rheumatol ; 71(6): 460-7, 2012 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-22875571

RESUMO

Even though biologics, frequently combined with conventional DMARD therapy, represent a significant advance in the treatment of rheumatic diseases, they have disadvantages such as high costs of production and parenteral administration. Therefore, oral small-molecule drugs are a potential alternative. Major targets for such small-molecule therapeutics are intracellular signaling molecules. This article will briefly discuss potential intracellular targets for therapeutics in the field of rheumatic diseases. How therapeutic signaling inhibitors will be used in clinical practice will depend on a number of factors: their overall effectiveness, their effectiveness in patients who did not or insufficiently respond to conventional DMARD therapy and/or treatment with biologics, their effectiveness when combined with other therapeutics, their side effects, and their cost-benefit ratio.The English full-text version of this article is available at SpringerLink (under "Supplemental").


Assuntos
Antirreumáticos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Espaço Intracelular/metabolismo , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Espaço Intracelular/efeitos dos fármacos
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