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1.
Herz ; 45(7): 626-631, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32572500

RESUMO

Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.


Assuntos
Cardiologia , Neoplasias , Cardiotoxicidade , Humanos , Oncologia , Neoplasias/diagnóstico , Neoplasias/terapia
2.
Internist (Berl) ; 61(11): 1132-1139, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33034675

RESUMO

BACKGROUND: Oncological therapies show a number of undesired adverse effects on the cardiovascular system. In particular, the side effects of recently established oncological therapies are incompletely understood and clinical data are lacking in the interpretation of novel cardiac complications. OBJECTIVE: This article provides a short overview of the mechanisms of cardiac side effects of certain oncological therapies. MATERIAL AND METHODS: The review is mainly based on data from preclinical studies. RESULTS: Numerous toxic side effects have already been described and investigated in preclinical models. For certain groups of drugs (e.g. anthracyclines, tyrosine kinase inhibitors and immune checkpoint inhibitors) the underlying molecular mechanisms are still not fully understood. CONCLUSION: An improved understanding of the molecular mechanism involved in cardiotoxicity might help improve the quality of clinical decisions. Additionally, it will provide new insights into the pathophysiology of cardiac diseases. The aim is to use the results of translational research and to clinically implement them in suitable cardio-oncology units.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade , Cardiopatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Humanos , Oncologia
3.
Opt Express ; 26(6): 7098-7106, 2018 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-29609396

RESUMO

In this paper, we report on a novel method to control the coherence behavior in a sum frequency generation interferometer powered by two independent pump lines. At the output of the interferometer, the two incoherent fringe patterns must be superimposed to maximize the contrast. The first step consists in canceling the differential group delay. The second one uses the phase control on one pump to synchronize the fringe patterns. This innovative method is experimentally demonstrated with a setup involving a 1544 nm signal and two pump lines around 1064 nm leading to a converted signal around 630 nm. It can be easily extended to a greater number of pump lines.

4.
Arch Toxicol ; 92(9): 2703-2748, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30132047

RESUMO

Isoflavones are secondary plant constituents of certain foods and feeds such as soy, linseeds, and red clover. Furthermore, isoflavone-containing preparations are marketed as food supplements and so-called dietary food for special medical purposes to alleviate health complaints of peri- and postmenopausal women. Based on the bioactivity of isoflavones, especially their hormonal properties, there is an ongoing discussion regarding their potential adverse effects on human health. This review evaluates and summarises the evidence from interventional and observational studies addressing potential unintended effects of isoflavones on the female breast in healthy women as well as in breast cancer patients and on the thyroid hormone system. In addition, evidence from animal and in vitro studies considered relevant in this context was taken into account along with their strengths and limitations. Key factors influencing the biological effects of isoflavones, e.g., bioavailability, plasma and tissue concentrations, metabolism, temporality (pre- vs. postmenopausal women), and duration of isoflavone exposure, were also addressed. Final conclusions on the safety of isoflavones are guided by the aim of precautionary consumer protection.


Assuntos
Mama/efeitos dos fármacos , Isoflavonas/efeitos adversos , Isoflavonas/farmacologia , Hormônios Tireóideos/metabolismo , Animais , Mama/metabolismo , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Feminino , Humanos , Isoflavonas/farmacocinética , Glycine max/química , Distribuição Tecidual
5.
Orthopade ; 47(2): 148-157, 2018 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-29318329

RESUMO

In recent years, the understanding of shoulder fractures has changed due to the progress of arthroscopy. In addition to the cosmetic result, the access morbidity, particularly the integrity of the subscapularis muscle in glenoid and scapular fractures, must be mentioned as an advantage of a minimally invasive approach. Furthermore, necessary secondary interventions, e. g. hook plate removal, can be prevented or minimized by modern implants and arthroscopic techniques.However, the available data and publications are almost exclusively limited to technical notes or small case series, so statements about faster recreation or potential reduction of infection risk cannot be made. Whether addressing concomitant injuries has an effect on the clinical and functional outcome is also unclear at the present time.


Assuntos
Artroscopia/métodos , Fixação Interna de Fraturas/métodos , Fraturas do Ombro/cirurgia , Placas Ósseas , Clavícula/diagnóstico por imagem , Clavícula/lesões , Clavícula/cirurgia , Cavidade Glenoide/diagnóstico por imagem , Cavidade Glenoide/cirurgia , Humanos , Ligamentos Articulares/diagnóstico por imagem , Ligamentos Articulares/lesões , Ligamentos Articulares/cirurgia , Cuidados Pós-Operatórios/métodos , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Luxação do Ombro/classificação , Luxação do Ombro/diagnóstico por imagem , Luxação do Ombro/cirurgia , Fraturas do Ombro/classificação , Fraturas do Ombro/diagnóstico por imagem
6.
Diabet Med ; 34(2): 189-196, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27589252

RESUMO

AIM: To investigate the safety and efficacy of insulin degludec/liraglutide (IDegLira), a novel combination product, as add-on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy. METHODS: In this 26-week, double-blind trial, adults with Type 2 diabetes [HbA1c 53-75 mmol/mol (7.0-9.0%)] were randomized to IDegLira (n = 289) or placebo (n = 146) as add-on to pre-trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0-6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). RESULTS: The mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference -11 mmol/mol (95% CI -13; -10) or -1.02% (95% CI -1.18; -0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (<7%) was achieved by 79.2% of participants in the IDegLira group vs 28.8% in the placebo group [estimated odds ratio 11.95 (95% CI 7.22; 19.77); P < 0.001]. Mean weight change was +0.5 kg with IDegLira vs -1.0 kg with placebo [estimated treatment difference 1.48 kg (95% CI 0.90; 2.06); P < 0.001]. Confirmed hypoglycaemia occurred in 41.7 and 17.1% of IDegLira- and placebo-treated participants, respectively, with rates of 3.5 vs 1.4 events/patient-years of exposure [estimated rate ratio 3.74 (95% CI 2.28; 6.13); P < 0.001]. IDegLira was generally well tolerated. The rates of serious adverse events were 20.3 and 8.0 per 100 patient-years of exposure with IDegLira and placebo, respectively, without obvious patterns in the type of events. CONCLUSIONS: IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Liraglutida/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade
7.
J Helminthol ; 91(5): 534-538, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27411883

RESUMO

Toxoplasmosis causes complications during pregnancy that have serious effects on fetal development. Thus far, toxocariasis has been reported to spread only via vertical transmission. Nonetheless, the population of pregnant women is also exposed to this infection. Co-infection with both Toxoplasma gondii and Toxocara spp. has been reported in children, but there are no reports of co-infection in the population of pregnant women. The aim of this study was to determine the prevalence of co-infection with T. gondii and Toxocara spp. in pregnant women at a university hospital in southern Brazil, and to identify the risk factors associated with infection by both parasites. Two hundred pregnant women were tested for the presence of anti-T. gondii and anti-Toxocara spp. antibodies and were asked to complete an epidemiological questionnaire. In this study, the co-infection rate observed in the total population of pregnant women was 8%. In addition, women with a positive result for a serology test for Toxocara spp. were at increased risk of infection by T. gondii (P = 0.019). Co-infection with both parasites in pregnant women was associated with low birth weights in neonates. The similar modes of transmission of both parasites could explain the co-infection. Only a few previous studies have investigated this phenomenon. The findings of the present study emphasize the importance of serological diagnosis during prenatal care and further research in this area to identify risk factors associated with this co-infection, and the possible implications of this co-infection during pregnancy and on the health of newborns.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Coinfecção/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Toxocaríase/epidemiologia , Toxoplasmose/epidemiologia , Animais , Brasil/epidemiologia , Coinfecção/parasitologia , Feminino , Hospitais Universitários , Humanos , Recém-Nascido de Baixo Peso , Transmissão Vertical de Doenças Infecciosas , Gravidez , Resultado da Gravidez , Prevalência , Medição de Risco , Inquéritos e Questionários , Toxocara/imunologia , Toxoplasma/imunologia
8.
Clin Genet ; 89(2): 228-34, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26080898

RESUMO

Although the integration of whole genome sequencing (WGS) into standard medical practice is rapidly becoming feasible, physicians may be unprepared to use it. Primary care physicians (PCPs) and cardiologists enrolled in a randomized clinical trial of WGS received genomics education before completing semi-structured interviews. Themes about preparedness were identified in transcripts through team-based consensus-coding. Data from 11 PCPs and 9 cardiologists suggested that physicians enrolled in the trial primarily to prepare themselves for widespread use of WGS in the future. PCPs were concerned about their general genomic knowledge, while cardiologists were concerned about how to interpret specific types of results and secondary findings. Both cohorts anticipated preparing extensively before disclosing results to patients by using educational resources with which they were already familiar, and both cohorts anticipated making referrals to genetics specialists as needed. A lack of laboratory guidance, time pressures, and a lack of standards contributed to feeling unprepared. Physicians had specialty-specific concerns about their preparedness to use WGS. Findings identify specific policy changes that could help physicians feel more prepared, and highlight how providers of all types will need to become familiar with interpreting WGS results.


Assuntos
Genoma Humano , Médicos , Análise de Sequência de DNA/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação
9.
J Evol Biol ; 27(10): 2272-82, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25146161

RESUMO

The weak selection approximation of population genetics has made possible the analysis of social evolution under a considerable variety of biological scenarios. Despite its extensive usage, the accuracy of weak selection in predicting the emergence of altruism under limited dispersal when selection intensity increases remains unclear. Here, we derive the condition for the spread of an altruistic mutant in the infinite island model of dispersal under a Moran reproductive process and arbitrary strength of selection. The simplicity of the model allows us to compare weak and strong selection regimes analytically. Our results demonstrate that the weak selection approximation is robust to moderate increases in selection intensity and therefore provides a good approximation to understand the invasion of altruism in spatially structured population. In particular, we find that the weak selection approximation is excellent even if selection is very strong, when either migration is much stronger than selection or when patches are large. Importantly, we emphasize that the weak selection approximation provides the ideal condition for the invasion of altruism, and increasing selection intensity will impede the emergence of altruism. We discuss that this should also hold for more complicated life cycles and for culturally transmitted altruism. Using the weak selection approximation is therefore unlikely to miss out on any demographic scenario that lead to the evolution of altruism under limited dispersal.


Assuntos
Altruísmo , Evolução Biológica , Genética Populacional/métodos , Modelos Genéticos , Seleção Genética , Alelos , Aptidão Genética
10.
Unfallchirurgie (Heidelb) ; 127(1): 69-78, 2024 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-38175216

RESUMO

Scapular fractures are rare injuries that require different treatment strategies. Nondisplaced fractures and the majority of scapular body fractures can be treated conservatively, while surgical treatment should be considered for displaced fractures involving the glenoid. Displaced glenoid fractures of appropriate size and intra-articular step formation should be treated surgically. Different classification systems for scapular fractures can support the treatment decision. Postoperative and posttraumatic management should include early mobilization to achieve a good functional outcome. Clear recommendations and treatment algorithms at the evidence level are not available and long-term outcomes of scapular fractures are the subject of further investigation. The results published so far show good to excellent results for surgical and conservative treatment, depending on the type of fracture. Individual patient factors should be considered when planning treatment.


Assuntos
Fraturas do Ombro , Humanos , Resultado do Tratamento , Escápula/diagnóstico por imagem
11.
Bioorg Med Chem ; 21(21): 6634-41, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24012376

RESUMO

The objective of this study was to synthesize and evaluate a novel fluorine-18 labeled deuterium substituted analogue of rasagiline (9, [(18)F]fluororasagiline-D2) as a potential PET radioligand for studies of monoamine oxidase B (MAO-B). The precursor compound (6) and reference standard (7) were synthesized in multi-step syntheses. Radiolabeling of 9 was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulfamidate group. The incorporation radiochemical yield from fluorine-18 fluoride was higher than 30%, the radiochemical purity was >99% and the specific radioactivity was >160GBq/µmol at the time of administration. In vitro compound 7 inhibited the MAO-B activity with an IC50 of 173.0±13.6nM. The MAO-A activity was inhibited with an IC50 of 9.9±1.1µM. The fluorine-18 version 9 was characterized in the cynomolgus monkey brain where a high brain uptake was found (275% SUV at 4min). There was a higher uptake in the striatum and thalamus compared to the cortex and cerebellum. A pronounced blocking effect (50% decrease) was observed in the specific brain regions after administration of l-deprenyl (0.5mg/kg) 30min prior to the administration of 9. Radiometabolite studies demonstrated 40% of unchanged radioligand at 90min post injection. An efficient radiolabeling of 9 was successfully established and in the monkey brain 9 binds to MAO-B rich regions and its binding is blocked by the selective MAO-B compound l-deprenyl. The radioligand 9 is a potential candidate for human PET studies.


Assuntos
Indanos/química , Inibidores da Monoaminoxidase/química , Monoaminoxidase/química , Compostos Radiofarmacêuticos/química , Animais , Encéfalo/diagnóstico por imagem , Córtex Cerebral/metabolismo , Deutério/química , Radioisótopos de Flúor/química , Humanos , Indanos/metabolismo , Macaca fascicularis/metabolismo , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/metabolismo , Tomografia por Emissão de Pósitrons , Ligação Proteica , Compostos Radiofarmacêuticos/metabolismo , Tálamo/metabolismo
12.
Bioorg Med Chem ; 21(1): 186-95, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23211968

RESUMO

The aim of this project was to synthesize and evaluate three novel fluorine-18 labeled derivatives of propargyl amine as potential PET radioligands to visualize monoamine oxidase B (MAO-B) activity. The three fluorinated derivatives of propargyl amine ((S)-1-fluoro-N,4-dimethyl-N-(prop-2-ynyl)-pent-4-en-2-amine (5), (S)-N-(1-fluoro-3-(furan-2-yl)propan-2-yl)-N-methylprop-2-yn-1-amine (10) and (S)-1-fluoro-N,4-dimethyl-N-(prop-2-ynyl)pentan-2-amine (15)) were synthesized in multi-step organic syntheses. IC(50) values for inhibition were determined for compounds 5, 10 and 15 in order to determine their specificity for binding to MAO-B. Compound 5 inhibited MAO-B with an IC(50) of 664 ± 48.08 nM. No further investigation was carried out with this compound. Compound 10 inhibited MAO-B with an IC(50) of 208.5 ± 13.44 nM and compound 15 featured an IC(50) of 131.5 ± 0.71 nM for its MAO-B inhibitory activity. None of the compounds inhibited MAO-A activity (IC(50) > 2 µM). The fluorine-18 labeled analogues of the two higher binding affinity compounds (10 and 15) (S)-N-(1-[(18)F]fluoro-3-(furan-2-yl)propan-2-yl)-N-methylprop-2-yn-1-amine (16) and (S)-1-[(18)F]fluoro-N,4-dimethyl-N-(prop-2-ynyl)pentan-2-amine (18) were both prepared from the corresponding precursors 9A, 9B and 14A, 14B by a one-step fluorine-18 nucleophilic substitution reaction. Autoradiography experiments on human postmortem brain tissue sections were performed with 16 and 18. Only compound 18 demonstrated a high selectivity for MAO-B over MAO-A and was, therefore, chosen for further examination by PET in a cynomolgus monkey. The initial uptake of 18 in the monkey brain was 250% SUV at 4 min post injection. The highest uptake of radioactivity was observed in the striatum and thalamus, regions with high MAO-B activity, whereas lower levels of radioactivity were detected in the cortex and cerebellum. The percentage of unchanged radioligand 18 was 30% in plasma at 90min post injection. In conclusion, compound 18 is a selective inhibitor of MAO-B in vitro and demonstrated a MAO-B specific binding pattern in vivo by PET in monkey. It can, therefore, be considered as a candidate for further investigation in human by PET.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/enzimologia , Radioisótopos de Flúor/análise , Monoaminoxidase/metabolismo , Pargilina/análogos & derivados , Propilaminas/análise , Animais , Autorradiografia , Radioisótopos de Flúor/metabolismo , Radioisótopos de Flúor/farmacocinética , Humanos , Macaca fascicularis , Pargilina/análise , Pargilina/metabolismo , Pargilina/farmacocinética , Tomografia por Emissão de Pósitrons , Propilaminas/metabolismo , Propilaminas/farmacocinética , Radiografia
13.
Skeletal Radiol ; 42(3): 411-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22923156

RESUMO

INTRODUCTION: Magnetic resonance imaging (MRI) is the standard of reference for the non-invasive evaluation of ligament injuries of the knee. The development of dual-energy CT (DE-CT) made it possible to differentiate between tissues of different density by two simultaneous CT measurements with different tube voltages. This approach enables DE-CT to discriminate ligament structures without intra-articular contrast media injection. The aims of this study were on the one hand to determine the delineation of the anterior cruciate ligament (ACL) and on the other hand to assess the diagnostic value of DE-CT and MRI in the detection of iatrogenically induced injury of the ACL in a porcine knee joint model. MATERIALS AND METHODS: Twenty porcine hind legs, which were placed in a preformed cast in order to achieve a standardized position, were scanned using DE-CT. Thereafter, a 1.5-T MRI using a standard protocol was performed. The imaging procedures were repeated with the same parameters after inducing defined lesions (total or partial incision) on the ACL arthroscopically. After post-processing, two radiologists and two orthopedic surgeons first analyzed the delineation of the ACL and then, using a consensus approach, the iatrogenically induced lesions. The result of the arthrotomy was defined as the standard of reference. RESULTS: The ACL could be visualized both on DE-CT and MRI in 100% of the cases. As for the MRI, the sensitivity and specificity of detecting the cruciate ligament lesion respectively compared with the defined arthrotomy was 66.7% and 78.6% for intact cruciate ligaments, 100% and 75% in the case of a complete lesion, 33.3% and 78.6% for lesions of the anteromedial bundle, and 0% and 100% for lesions of the posterolateral bundle. In comparison, DE-CT demonstrated a sensitivity and specificity of 66.7% and 71.4% in the case of intact cruciate ligaments, 75% and 68.8% in the case of completely discontinued ACLs, 0% and 92.9% in the case of lesions of the anteromedial bundle, and 25% and 87.5% in the case of lesions of the posterolateral bundle. CONCLUSIONS: The present ex vivo experiment shows that both study modalities (DE-CT and MRI) are equal with regard to the delineation of the ACL, while MRI achieved higher sensitivity and specificity regarding iatrogenically induced complete ACL lesions. DE-CT could be a possible alternative to MRI for certain indications in the diagnosis of a knee ligament injury.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho/diagnóstico , Imageamento por Ressonância Magnética/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Animais , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/patologia , Técnicas In Vitro , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos
14.
Acta Chir Orthop Traumatol Cech ; 80(2): 125-30, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23562256

RESUMO

PURPOSE OF THE STUDY: Especially in such complex salvage procedures as latissimus dorsi transfer for irreparable rotator cuff tears there is a need for valid prognostic prediction parameters. Parameters such as osteoarthritis, acromiohumeral distance, subscapularis, or teres minor insufficiency are controversial. The aim of this study is to present our data and to evaluate the literature regarding such parameters. METHODS: Fifty-seven patients with a follow-up of 3 years (range, 18-72 months, n = 57) were selected for this study. Average age of patients at the time of surgery was 64.9 years. Patients were evaluated using the age and gender adjusted scoring system according to Constant and Murley score (CS). Standard radiography was attempted containing a true-ap, outlet, and axillary view. The acromio-humeral distance was measured in the true ap view. The grade of glenohumeral osteoarthritis and cuff tear arthropathy was detected using the classification of Hamada et al. Differences in CS were compared for each of the PPP. RESULTS: Mean Constant score increased significantly (p < 0.0001) 3 years postoperatively from initially 22.7 points to 66.0 points (adjusted CS 80.3%). We found a major difference in the Constant score in patients with or without previous surgery (80.4% vs, 65.2%). CONCLUSION: Latissimus dorsi transfer is an excellent option in the treatment of irreparable postero-superior tears of the rotator cuff in well-selected patients. The literature remains ambiguous with regard to valid prognostic predictive parameters for complex salvage procedures, owing to the consistent use of small study samples. Thus, there is an overwhelming need for a multicenter study.


Assuntos
Lesões do Manguito Rotador , Transferência Tendinosa/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Manguito Rotador/cirurgia , Resultado do Tratamento
15.
Obere Extrem ; 18(1): 30-36, 2023.
Artigo em Alemão | MEDLINE | ID: mdl-36627888

RESUMO

Locked dislocations of the glenohumeral joint are rare but often painful and are associated with limited range of motion in the shoulder. In patients of advanced age, arthroplasty is increasingly indicated as a surgical treatment option. Preoperatively, the direction of dislocation, the presence and extent of a glenoid defect, and the soft tissue situation (rotator cuff status, joint capsule) should be analyzed in a differentiated manner. Based on the above factors, we recommend the subclassification of type 2 according to Boileau: posterior locked dislocation (2a), anterior locked dislocation without glenoid defect (2b), and anterior locked dislocation with glenoid defect (2c). In the case of dorsally locked dislocation, a good clinical result can be achieved by using an anatomical endoprosthesis. For ventrally locked dislocations, we recommend using an inverse total endoprosthesis with, if necessary, bony glenoid reconstruction and transfer of the pectoralis major muscle.Level of evidence: IV.

16.
Bioorg Med Chem ; 20(9): 3065-71, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22436387

RESUMO

The aim of this study was to synthesize and evaluate a novel fluorine-18 labeled analogue of rasagiline (6) as a PET radioligand for monoamine oxidase B (MAO-B). The corresponding non-radioactive fluorine-19 ligand, (1S,2S)-2-fluoro-N-(prop-2-yn-1-yl)indan-1-amine (4), was characterized in in vitro assays. The precursor compound (3aS,8aR)-3-(prop-2-yn-1-yl)-3,3a,8,8a-tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide (3) and reference standard 4 were synthesized in multi-step syntheses. Recombinant human MAO-B and MAO-A enzyme preparations were used in order to determine IC(50) values for compound 4 by use of an enzymatic assay employing kynuramine as substrate. Radiolabeling was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulphamidate group. Human whole hemisphere autoradiography (ARG) was performed with [(18)F]fluororasagiline. Blocking experiments with pirlindole (MAO-A), L-deprenyl and rasagiline (MAO-B) were conducted to demonstrate the specificity of the binding. A positron emission tomography (PET) study was carried out in a cynomolgus monkey where time activity curves for whole brain and regions with high and low MAO-B activity were recorded. Radiometabolites were measured in monkey plasma using gradient HPLC. Compound 4 inhibited MAO-B with an IC(50) of 27 nM and MAO-A with an IC(50) of 2.3 µM. Radiolabeling of precursor 3 and subsequent hydrolysis of the protecting group towards (1S,2S)-2-[(18)F]fluoro-N-(prop-2-yn-1-yl)indan-1-amine (6) was successfully accomplished with an radiochemical yield of 40-70%, a radiochemical purity higher than 99% and a specific radioactivity higher than 200GBq/µmol. ARG demonstrated selective binding for [(18)F]fluororasagiline (6) to MAO-B containing brain regions, for example, striatum. The initial uptake in the monkey brain was 250% SUV at 4 min post injection. The highest amounts of radioactivity were observed in the striatum and thalamus as expected whereas in the cortex and cerebellum lower levels were observed. Metabolite studies demonstrated 30% unchanged radioligand at 90 min post injection. Our investigations demonstrated that the new ligand [(18)F]fluororasagiline (6) binds specifically to MAO-B in vitro and has a MAO-B specific binding pattern in vivo. Thus, it could serve as a novel potential candidate for human PET studies.


Assuntos
Indanos/química , Ligantes , Monoaminoxidase/química , Compostos Radiofarmacêuticos/síntese química , Animais , Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor/química , Humanos , Indanos/metabolismo , Macaca fascicularis , Monoaminoxidase/genética , Monoaminoxidase/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
17.
Unfallchirurgie (Heidelb) ; 125(9): 671-680, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-35833976

RESUMO

Proximal humeral fractures (PHF) are the third most common fracture in humans and the incidence is increasing. There are basically three treatment strategies: conservative, joint-preserving reconstructive or joint-replacing procedures. In addition to fracture morphology, patient-specific and surgeon-specific factors are particularly important when deciding on treatment. The experience and training of the surgeon also play a decisive role. In the case of joint-preserving treatment, the risk of osteosynthesis failure and of sequelae of the fracture must always be assessed. If conservative or reconstructive treatment methods are not promising, the joint-replacing procedure is the treatment of choice. The anatomical fracture prosthesis is only indicated, if at all, for young patients with a destroyed humeral head with a preserved rotator cuff and large fragments of the tuberosities. In advanced age, the implantation of a reverse endoprosthesis is increasingly used for dislocated, multifragmentary PHF. In both procedures, the anatomical healing of the tuberosities has a significant impact on the functional outcome.


Assuntos
Artroplastia de Substituição , Prótese Articular , Fraturas do Ombro , Artroplastia de Substituição/métodos , Fixação Interna de Fraturas/métodos , Humanos , Cabeça do Úmero/cirurgia , Fraturas do Ombro/diagnóstico por imagem
18.
Oper Orthop Traumatol ; 34(1): 55-70, 2022 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-35119483

RESUMO

OBJECTIVE: Latissimus dorsi transfer aims to reduce pain and improve function for irreparable tears of the posterosuperior rotator cuff by restoring the transversal force couple to improve external rotation and delaying superior migration of the humeral head. INDICATIONS: Surgery is advocated in patients with unbearable shoulder pain and limited external rotation caused by an irreparable posterosuperior rotator cuff tear. Usually, a latissimus transfer is recommended in the presence of superior migration of the humeral head, higher grade fatty infiltration of the rotator cuff and a restriction of range of motion and strength for abduction and external rotation. Advantages of the arthroscopically assisted technique are the missing need of detaching the deltoid from its origin, smaller incisions and therapy of concomitant intraarticular lesions. CONTRAINDICATIONS: Little pain and sufficient shoulder function in massive posterosuperior rotator cuff tears do not necessitate latissimus transfer. In the presence of subscapularis tears, osteoarthritis and deltoid dysfunction as well as shoulder stiffness tendon transfer are associated with inferior clinical outcomes. SURGICAL TECHNIQUE: Surgery is performed in prone position. The incision is made about 5 cm caudal of the posterolateral corner of the acromion and extends over 6 cm at the inferior border of the deltoid muscle. After exploration and protection of the axillary and radial nerve the latissimus tendon is peeled off of the humerus. The medial part of the latissimus is then mobilized to gain length for the later transfer. Afterwards the footprint of the infraspinatus is visualized and debrided. Two or three suture anchors are placed into the posterosuperior aspect of the greater tuberosity. The sutures are stitched through the tendon in a horizontal mattress stitch configuration and the tendon tied onto the bone. In arthroscopic advancement, the patient is placed in an upright beach-chair position with the arm attached to an arm holder. After debridement of the supraspinatus and infraspinatus footprint, arthroscopic preparation at the anterior border of the subscapularis tendon is performed. The latissimus tendon is visualized and detached with electrocautery. Afterwards the interval between posterior rotator cuff and deltoid muscle is prepared to allow the transfer of the latissimus tendon to the posterosuperior footprint. This marks the transition to the open approach, in which the arm is placed in a flexed and internally rotated position. POSTOPERATIVE MANAGEMENT: Immobilization in a shoulder sling for 3 weeks. Early passive range of motion (ROM: flexion 30°, internal rotation 60°, abduction 0°, external rotation 0°) was immediately allowed. After 3 weeks, passive ROM was increased to 90° of flexion, 60° of abduction, whereas external rotation was still restricted. After 7 weeks, free passive ROM and after 8 weeks active ROM (assisted) were allowed. RESULTS: In all, 67 patients (mean age 63 years) were examined 54 months (±â€¯28) after open transfer of the latissimus dorsi tendon. Constant score improved from 24 (±â€¯6) points to 68 (±â€¯17) points. Active flexion increased from 83° (±â€¯47°) to 144° (±â€¯35°), abduction from 69° (±â€¯33°) to 134° (±â€¯42°) and external rotation from 24° (±â€¯18°) to 35° (±â€¯21°). The VAS score decreased from 6.3 (±â€¯1.1) to 1.8 (±â€¯2). However, osteoarthritis worsened over time and the Hamada-Fukuda stage increased from 1.4 to 2.1 and the acromihumeral distance decreased from 7.9 (±â€¯2.6) to 5.1 (±â€¯2.2) at final follow-up.


Assuntos
Lesões do Manguito Rotador , Músculos Superficiais do Dorso , Humanos , Pessoa de Meia-Idade , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Transferência Tendinosa , Resultado do Tratamento
19.
J Evol Biol ; 23(11): 2356-69, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20825551

RESUMO

When individuals in a population can acquire traits through learning, each individual may express a certain number of distinct cultural traits. These traits may have been either invented by the individual himself or acquired from others in the population. Here, we develop a game theoretic model for the accumulation of cultural traits through individual and social learning. We explore how the rates of innovation, decay, and transmission of cultural traits affect the evolutionary stable (ES) levels of individual and social learning and the number of cultural traits expressed by an individual when cultural dynamics are at a steady-state. We explore the evolution of these phenotypes in both panmictic and structured population settings. Our results suggest that in panmictic populations, the ES level of learning and number of traits tend to be independent of the social transmission rate of cultural traits and is mainly affected by the innovation and decay rates. By contrast, in structured populations, where interactions occur between relatives, the ES level of learning and the number of traits per individual can be increased (relative to the panmictic case) and may then markedly depend on the transmission rate of cultural traits. This suggests that kin selection may be one additional solution to Rogers's paradox of nonadaptive culture.


Assuntos
Características Culturais , Evolução Cultural , Aprendizagem/fisiologia , Modelos Biológicos , Simulação por Computador , Fertilidade/fisiologia , Teoria dos Jogos , Humanos
20.
Plant Biol (Stuttg) ; 21(4): 738-744, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30773824

RESUMO

Most angiosperms rely on animal pollination for reproduction, but the dependence on specific pollinator groups varies greatly between species and localities. Notably, such dependence may be influenced by both floral traits and environmental conditions. Despite its importance, their joint contribution has rarely been studied at the assemblage level. At two elevations on the Caribbean island of Dominica, we measured the floral traits and the relative contributions of insects versus hummingbirds as pollinators of plants in the Rubiaceae family. Pollinator importance was measured as visitation rate (VR) and single visit pollen deposition (SVD), which were combined to assess overall pollinator effectiveness (PE). In the wet and cool Dominican highland, we found that hummingbirds were relatively more frequent and effective pollinators than insects, whereas insects and hummingbirds were equally frequent and effective pollinators at the warmer and less rainy midelevation. Furthermore, floral traits correlated independently of environment with the relative importance of pollinators, hummingbirds being more important in plant species having flowers with long and wide corollas producing higher volumes of dilute nectar. Our findings show that both environmental conditions and floral traits influence whether insects or hummingbirds are the most important pollinators of plants in the Rubiaceae family, highlighting the complexity of plant-pollinator systems.


Assuntos
Aves , Insetos , Polinização , Rubiaceae/fisiologia , Altitude , Animais , Aves/fisiologia , Dominica , Flores/anatomia & histologia , Flores/fisiologia , Umidade , Insetos/fisiologia , Néctar de Plantas/fisiologia , Rubiaceae/anatomia & histologia , Temperatura
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