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1.
J Intensive Care Med ; : 8850666241253213, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839250

RESUMO

OBJECTIVE: Elevation of Troponin I (TnI) in spontaneous subarachnoid hemorrhage (SAH) patients is a well-known phenomenon and associated with cardiopulmonary complications and poor outcome. The present study was conducted to investigate the association of the TnI value on admission, and the occurrence of cerebral vasospam in SAH patients. PATIENTS AND METHODS: A total of 142 patients with SAH, who were admitted to the neurosurgical intensive care unit (ICU) between December 2014 and January 2021 were evaluated. Blood samples were drawn on admission to determine TnI value. Each patient's demographic, radiological and medical data on admission, the modified Ranking Scale score at discharge as well as continuous measurements of transcranial Doppler sonography were analyzed. A maximum mean flow velocity (MMFV) > 120 cm/sec was defined as any vasospasm. These were stratified into severe vasospasms, which were defined as at least two measurements of MMFVs > 200 cm/sec or an increase of MMFV > 50 cm/sec/24 h over two consecutive days or a new neurological deterioration and mild vasospasm defined as MMFVs > 120 cm/sec in absence of severe vasospasm criteria. The total study population was dichotomized into patients with an initially elevated TnI (>0.05 µg/L) and without elevated TnI (≤0.05 µg/L). RESULTS: A total of 52 patients (36.6%) had an elevated TnI level upon admission, which was significantly associated with lower GCS score (p < 0.001), higher WFNS score (p < 0.001) and higher Fisher grade (p = 0.01) on admission. In this context a higher rate of ischemic brain lesions (p = 0.02), a higher modified Rankin Scale score (p > 0.001) and increased mortality (p = 0.02) at discharge were observed in this group. In addition, TnI was identified as an independent predictor for the occurrence of any vasospasm and severe vasospasm. CONCLUSION: An initially elevated TnI level is an independent predictor for the occurrence of any and severe vasospasm in patients with SAH.

2.
Ultrasound Obstet Gynecol ; 57(1): 113-118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32510722

RESUMO

OBJECTIVE: This observational study reports on the postnatal mortality and 30-month outcome of children who underwent fully percutaneous fetoscopic repair of myelomeningocele (MMC) at a single center in Giessen, Germany. METHODS: Between October 2010 and August 2014, a total of 72 patients underwent fully percutaneous fetoscopic MMC closure at 21 + 0 to 29 + 1 (mean, 23 + 5) weeks' gestation. Of these, 52 (72%) participated in this study; however, 30-month mortality data are available for all 72 children. Children were examined at four timepoints: shortly after birth and at 3 months, 12 months and 30 months of corrected age. The patients underwent age-specific standardized neurological examinations and assessment of leg movements and ambulation at all timepoints. Cognitive and motor development were assessed using the Bayley Scales of Infant Development, second edition (BSID-II), at 30 months. RESULTS: All 72 children survived the intrauterine procedure, however, four (5.6%) infants died postnatally (including two of the 52 comprising the study cohort). Of the 52 patients included in the study, 11.5% were delivered before the 30th week of gestation (mean, 33 + 1 weeks) and, of the survivors, 48.1% had ventriculoperitoneal shunt placement. Of the 50 infants that were alive at 30 months, independent ambulation, without orthosis, was feasible for 46%. At 30 months of follow-up, 46% of children presented with a functional level that was at least two segments better than the anatomical level of the lesion. At 30 months, 70% of the children presented with BSID-II psychomotor development index score of ≥ 70 and 80% with BSID-II mental development index score of ≥ 70. CONCLUSION: Intrauterine repair of MMC by percutaneous fetoscopy shows largely similar outcomes to those reported for open repair, with respect to mortality, prematurity, shunt-placement rates, motor and mental development and free ambulation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Doenças Fetais/cirurgia , Fetoscopia/mortalidade , Meningomielocele/cirurgia , Pré-Escolar , Fetoscopia/métodos , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Meningomielocele/embriologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Desempenho Físico Funcional , Derivação Ventriculoperitoneal/métodos
3.
J Intensive Care Med ; 35(11): 1173-1179, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30913956

RESUMO

OBJECTIVE: Cardiopulmonary complications/stress are well-known phenomena in patients after aneurysmal subarachnoid hemorrhage (aSAH) and might be associated with an elevated serum troponin I (TNI) level. Since the glucocorticoid hormone cortisol is released during stress situations, the present study was conducted to investigate the influence of serum cortisol (SC) on cardiac and pulmonary parameters in patients after aSAH within the first 24 hours of intensive care unit (ICU) treatment. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 104 patients with aSAH admitted to our emergency department between January 2008 and April 2017. Blood samples were taken to determine SC and TNI. Demographics, initial Glasgow Coma Scale (GCS) score, World Federation of Neurosurgical Societies (WFNS) score, and Fisher grade were evaluated retrospectively. Mean norepinephrine application rate (NAR) in µg/kg/min and mean inspiratory oxygen fraction (OF) within the first 24 hours were defined as cardiopulmonary parameters. RESULTS: An elevated SC value was found in 44 (42%) patients, and 27 (26%) patients showed an increased TNI value. In patients with initially increased SC value, a significant higher NAR (P = .04) was needed. Furthermore, patients with initially elevated TNI value had a lower GCS score (P = .0013) and a higher WFNS score (P = .003) on admission and required a higher NAR (P = .02) as well as OF (P = .0008) within the first 24 hours of ICU treatment. CONCLUSIONS: In the current study, initially elevated SC values were associated with a higher need of NAR within the first 24 hours of ICU treatment after aSAH. Moreover, patients with initially elevated TNI values required an increased NAR and a higher OF so that these biomarkers could be useful to improve ICU treatment.


Assuntos
Hidrocortisona , Hemorragia Subaracnóidea , Biomarcadores , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações
4.
Ultrasound Obstet Gynecol ; 47(2): 158-61, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26138563

RESUMO

OBJECTIVE: To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA). METHODS: This was a retrospective analysis of a cohort of 71 fetuses which underwent minimally invasive fetoscopic patch coverage of SBA between 21 + 0 and 29 + 1 weeks of gestation. Postnatal neurosurgical procedures were classified into two types: re-coverage of the SBA within the first 3 months following birth, and shunt placement as treatment of associated hydrocephalus within the first year. RESULTS: Location of the SBA was lumbosacral in 59 cases, lumbar in seven, thoracic in three and sacral in two. In total, 20/71 (28%) patients underwent early postnatal neurosurgical intervention by means of re-coverage of the SBA. This was performed because of cerebrospinal fluid leakage in seven (35%), adhesions with functional deterioration in three (15%), incomplete coverage in five (25%) and skin defect in five (25%) cases. Ventriculoperitoneal shunt placement within 1 year was required in 32 (45%) cases and was preceded by ventriculostomy in two. Three (4%) infants needed Chiari decompression surgery in the first 12 months following birth, because of syringomyelia or gait disturbance. CONCLUSIONS: Fetoscopic patch coverage of SBA may require postnatal re-coverage in some cases. In most cases, conservative wound treatment shows good results, without requiring neurosurgical intervention. The low 1-year-shunt rate is comparable to data of the Management of Myelomeningocele Study and lower compared with published data of patients with postnatal only coverage of SBA.


Assuntos
Fetoscopia/efeitos adversos , Feto/cirurgia , Procedimentos Neurocirúrgicos/métodos , Espinha Bífida Cística/cirurgia , Feminino , Fetoscopia/métodos , Idade Gestacional , Humanos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Região Lombossacral/embriologia , Região Lombossacral/cirurgia , Cuidado Pós-Natal/métodos , Gravidez , Reoperação/métodos , Estudos Retrospectivos , Espinha Bífida Cística/complicações , Espinha Bífida Cística/embriologia , Derivação Ventriculoperitoneal
5.
Vet Pathol ; 52(4): 681-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25358536

RESUMO

Four healthy adult dogs (Golden Retrievers aged 6 years and 9 years, Dalmatian aged 13 years, and Mastiff aged 5 years) developed clinical signs of acute respiratory disease and died within 2 to 7 days of onset of clinical signs. The lungs of the 3 dogs submitted for necropsy were diffusely and severely reddened due to hyperemia and hemorrhage. Microscopic lesions in all dogs were suggestive of acute viral or toxic respiratory damage and varied from acute severe fibrinonecrotic or hemorrhagic bronchopneumonia to fibrinous or necrotizing bronchointerstitial pneumonia. Necropsied dogs also had hemorrhagic rhinitis and tracheitis with necrosis. Virus isolation, transmission electron microscopy, and polymerase chain reaction were used to confirm the presence of canid herpesvirus 1 (CaHV-1) in the lung samples of these dogs. Lung tissues were negative for influenza A virus, canine distemper virus, canine parainfluenza virus, canine respiratory coronavirus, and canine adenovirus 2. Canid herpesvirus 1 has been isolated from cases of acute infectious respiratory disease in dogs but has only rarely been associated with fatal primary viral pneumonia in adult dogs. The cases in the current report document lesions observed in association with CaHV-1 in 4 cases of fatal canine herpesvirus pneumonia in adult dogs.


Assuntos
Doenças do Cão/patologia , Infecções por Herpesviridae/veterinária , Herpesvirus Canídeo 1/isolamento & purificação , Pneumonia Viral/veterinária , Infecções Respiratórias/veterinária , Animais , Cães , Evolução Fatal , Feminino , Infecções por Herpesviridae/patologia , Pulmão/patologia , Masculino , Pneumonia Viral/patologia , Reação em Cadeia da Polimerase/veterinária , Infecções Respiratórias/patologia
6.
Vet Pathol ; 49(3): 453-61, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22075774

RESUMO

Borrelia burgdorferi is the causative agent of Lyme disease, which is mainly characterized by lameness in dogs. More than 95% of naturally infected dogs are asymptomatic or subclinical; however, in experimental studies, histologic synovial lesions are consistently observed in asymptomatic dogs inoculated with B. burdgorferi. This study investigates the ability of a synovial histopathologic scoring system, clinicopathologic data, and polymerase chain reaction (PCR) testing to differentiate between B. burgdorferi-infected and uninfected dogs. Eighteen 18-week-old beagles were subject to challenge with B. burgdorferi-infected wild-caught ticks (Ixodes scapularis), and 4 uninfected dogs served as controls. Infection was confirmed by serology (ELISA) and PCR amplification of B. burgdorferi-specific DNA of skin biopsies taken at the tick attachment site. A synovial scoring system from human medicine was adapted and implemented on postmortem synovial samples to discriminate infected and noninfected animals. Application of this system to elbows and stifles with a cumulative joint score cutoff  > 4 showed a sensitivity of 88.2% and a specificity of 100%, with a positive likelihood ratio of infinity and a negative likelihood ratio of 0.12. Complete blood count, serum biochemistry, urinalysis, urine protein:creatinine, urine PCR, synovial and lymph node cytology, and synovial PCR were evaluated but were not reliable indicators of clinical disease.


Assuntos
Borrelia burgdorferi , Doenças do Cão/diagnóstico , Doenças do Cão/microbiologia , Ixodes/microbiologia , Doença de Lyme/veterinária , Membrana Sinovial/patologia , Animais , Contagem de Células Sanguíneas/veterinária , Creatina/urina , Doenças do Cão/patologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Técnicas Histológicas/veterinária , Funções Verossimilhança , Doença de Lyme/diagnóstico , Doença de Lyme/patologia , Reação em Cadeia da Polimerase/veterinária , Membrana Sinovial/microbiologia
7.
Acta Neurochir Suppl ; 109: 163-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20960337

RESUMO

Intraoperative computed tomography (iCT) has gained increasing impact among modern neurosurgical techniques. Multislice CT with a sliding gantry in the OR provides excellent diagnostic image quality in the visualization of vascular lesions as well as bony structures including skull base and spine. Due to short acquisition times and a high spatial and temporal resolution, various modalities such as iCT-angiography, iCT-cerebral perfusion and the integration of intraoperative navigation with automatic re-registration after scanning can be performed. This allows a variety of applications, e.g. intraoperative angiography, intraoperative cerebral perfusion studies, update of cerebral and spinal navigation, stereotactic procedures as well as resection control in tumour surgery. Its versatility promotes its use in a multidisciplinary setting. Radiation exposure is comparable to standard CT systems outside the OR. For neurosurgical purposes, however, new hardware components (e.g. a radiolucent headholder system) had to be developed. Having a different range of applications compared to intraoperative MRI, it is an attractive modality for intraoperative imaging being comparatively easy to install and cost efficient.


Assuntos
Neuronavegação/métodos , Procedimentos Neurocirúrgicos/métodos , Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X/métodos , Doenças Vasculares/cirurgia , Artérias Cerebrais/patologia , Artérias Cerebrais/ultraestrutura , Humanos , Coluna Vertebral/diagnóstico por imagem , Doenças Vasculares/diagnóstico por imagem
8.
Vet Pathol ; 47(6): 1021-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20817891

RESUMO

Weanling Brown Norway (BN) rats are susceptible to persistent steroid-responsive pulmonary abnormalities following resolution of an acute respiratory virus infection. In contrast, Fischer 344 (F344) rats recover without complications. Previous studies determined that NF-κB activation and subunit composition were markedly different between these 2 rat strains. This study examined whether viral infection also resulted in altered pulmonary expression of IκBα and IκBß, 2 inhibitory regulators of NF-κB. Western blot analyses of total pulmonary protein extracted from BN and F344 rats at 7, 10, and 14 days after inoculation (n = 5 per group) did not reveal virus-induced differences in IκBß expression. In contrast, a lower molecular weight form of IκBα appeared in the BN rats at 14 days postinfection, and it was still present at 21 days after infection (n = 5 per group). The change in IκBα expression observed in the susceptible BN but not the resistant F344 animals occurs when the epithelium is proliferating during the repair phase, and it correlates with the development of the persistent virus-induced airway inflammation and pulmonary functional abnormalities. These results further implicate differential regulation of NF-κB in the pathogenesis of virus-induced asthma.


Assuntos
Asma/virologia , NF-kappa B/antagonistas & inibidores , Animais , Asma/metabolismo , Asma/fisiopatologia , Western Blotting , Bromodesoxiuridina/metabolismo , Eletroforese em Gel Bidimensional , Proteínas I-kappa B , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Inibidor de NF-kappaB alfa , Ratos , Ratos Endogâmicos BN/metabolismo , Ratos Endogâmicos BN/virologia , Ratos Endogâmicos F344/metabolismo , Ratos Endogâmicos F344/virologia , Infecções por Respirovirus/complicações , Infecções por Respirovirus/metabolismo , Vírus Sendai/metabolismo , Especificidade da Espécie
9.
Int J Oncol ; 57(4): 1039-1046, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945397

RESUMO

Sphingosine­1­phosphate (S1P) plays a key role in cell survival, growth, migration, and in angiogenesis. In glioma, it triggers the activity of the S1P­receptor 1 and of the sphingosine kinase 1; thus influencing the survival rate of patients. The aim of the present study was to investigate the anti­proliferative effect of the S1P analogue FTY720 (fingolimod) in glioblastoma (GBM) cells. A172, G28, and U87 cells were incubated with micromolar concentrations of FTY720 or temozolomide (TMZ) for 24 to 72 h. Proliferation and half maximal inhibitory concentration (IC50) were determined by using the xCELLigence system. FACS analysis was performed to check the cell cycle distribution of the cells after a 72­h incubation with FTY720. This was then compared to TMZ­incubated and to untreated cells. Gene expression was detected by RT­qPCR in A172, G28, U87 and three primary GBM­derived cell lines. FTY720 was able to reduce the number of viable cells. The IC50 value was 4.6 µM in A172 cells, 17.3 µM in G28 cells, and 25.2 µM in U87 cells. FTY720 caused a significant arrest of the cell cycle in all cells and stabilized or over­expressed the level of AKT1, MAPK1, PKCE, RAC1, and ROCK1 transcripts. The TP53 transcript level remained stable or was downregulated after treatment with FTY720. FTY720 may be a promising target drug for the treatment of GBM, as it has a strong anti­proliferative effect on GBM cells.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Cloridrato de Fingolimode/farmacologia , Glioblastoma/tratamento farmacológico , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacologia , Quinases Associadas a rho/metabolismo , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Transdução de Sinais , Temozolomida/farmacologia
10.
Acta Neurochir (Wien) ; 151(5): 519-27; discussion 527, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19337684

RESUMO

BACKGROUND: The strongest evidence in medical clinical literature is represented by randomized controlled trials (RCTs). This study was designed to evaluate neurosurgically relevant RCTs published recently by neurosurgeons. METHOD: A literature search in MEDLINE and EMBASE included all clinical studies published up to 30 June 2006. RCTs with neurosurgical relevance published by at least one author with affiliation to a neurosurgical department were selected. The number and characteristics of individual trials were recorded, and the quality of the trials with regard to study design, quality of reporting, and relevance for clinical practice was assessed by two different investigators using a modification of the Scottish Intercollegiate Guidelines Network methodology checklist. Changes of RCT quality over time as well as factors influencing the quality were analyzed. FINDINGS: From the initial search results (MEDLINE n = 3,860, EMBASE n = 3,113 articles), 159 RCTs published by neurosurgeons were extracted for final evaluation. Of the RCTs, 62% have been published since 1995; 52% came from the USA, UK, and Germany. The median RCT sample size was 78 patients and the median follow-up 35.7 weeks. Fifty-two percent of all RCTs were of good, 37% of moderate, and 11% of bad quality, with an improvement over time. RCTs with financial funding and RCTs with a sample size of >78 patients were of significantly better quality. There were no major differences in the rating of the studies between the two investigators. CONCLUSIONS: Only a fraction of neurosurgically relevant literature consists of RCTs, but the quality is satisfying and has significantly improved over the last years. An adequate sample size and sufficient financial support seem to be of substantial importance with regard to the quality of the study. Our data also show that by using a standardized checklist, the quality of trials can be reliably assessed by observers of different experience and educational levels.


Assuntos
Neurocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/classificação , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Medicina Baseada em Evidências , Humanos , Controle de Qualidade , Projetos de Pesquisa
11.
J Clin Neurosci ; 61: 205-209, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30396817

RESUMO

Decompressive craniectomy (DC) is an accepted surgical technique for reducing life-threatening levels of intracranial pressure. Remodelling the cranial vault following DC can constitute a reconstructive challenge and is known to carry significant morbidity. The aim of our study was to evaluate acrylic versus autologous cranioplasty with regard to specific complication rates. A retrospective analysis was conducted of 286 consecutive adult patients who underwent cranioplasty following supratentorial decompressive craniectomy at our institution between January 2003 and June 2013. The patients were followed based on medical records, operative reports, imaging and outpatient contacts in the postoperative course. A total of 221/286 patients in our series received an autologous bone flap. 65/286 cranioplasty procedures were carried out using acrylic (PMMA) implants to cover uni- or bilateral defects. Within the follow-up period a total of 100 operative revisions were performed. 33.3% patients in the autologous bone group and 40.6% of patients in the acrylic group developed complications requiring surgical attention. The main reason for revision was infection with a total of 37 revisions necessary to treat disturbed wound healing. Postoperative sub- and epidural hematomas requiring revision were more frequent in the acrylic group. Resorption of the autologous bone flap requiring operative revision was seen in 8/222 (3.6%) cases. Other complications included loosening of the implant or dislocation. From our data it can be concluded that cranioplasty procedures using autologous bone-flaps and acrylic implants carry signifikant morbidity, but that both are justifiable techniques for cranioplasty in adult patients.


Assuntos
Substitutos Ósseos , Transplante Ósseo/métodos , Craniotomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Idoso , Transplante Ósseo/efeitos adversos , Craniotomia/efeitos adversos , Craniectomia Descompressiva/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimetil Metacrilato , Próteses e Implantes , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Crânio/cirurgia , Retalhos Cirúrgicos , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos
12.
Vet J ; 253: 105376, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31685134

RESUMO

While recent work demonstrated that enrofloxacin and ciprofloxacin reach the fetoplacental unit without causing obvious lesions in the 9-month-old equine fetus or resulting foal, many practitioners still hesitate to prescribe a fluoroquinolone during pregnancy. Since early gestation is a critical time for fetal skeletal development, if fluoroquinolones are chondrotoxic to the fetus at any point during gestation, this period would be important. The aim of this study was to assess the effects of 2 weeks' exposure to enrofloxacin on the equine fetus between 46 and 60 days gestation. Twelve pregnancies from nine healthy mares were allocated into two groups: untreated (n=7), or treatment (7.5mg/kg enrofloxacin, PO×14days, n=6). Abortion was induced with prostaglandin 24h after the last enrofloxacin dose, or on the equivalent day of gestation for untreated mares. Four of nine mares were rebred for a second cycle and were assigned to the opposite treatment to serve as their own controls. Fetal fluids from treated mares were analysed for enrofloxacin and ciprofloxacin concentrations. Fetal organs (heart, lungs, spleen, kidney, and liver) and limbs were examined histopathologically. Enrofloxacin and ciprofloxacin diffused to the fetal fluids during early gestation and did not result in detectable abnormalities in the fetus after 14 days of treatment. While current research does not determine long-term foal outcomes, enrofloxacin may be useful for select bacterial infections in pregnant mares.


Assuntos
Anti-Infecciosos/farmacologia , Enrofloxacina/farmacologia , Feto/efeitos dos fármacos , Doenças dos Cavalos/tratamento farmacológico , Aborto Animal , Alantoide/metabolismo , Líquido Amniótico/metabolismo , Animais , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/toxicidade , Enrofloxacina/farmacocinética , Enrofloxacina/toxicidade , Feminino , Doenças dos Cavalos/patologia , Cavalos , Gravidez
13.
Exp Clin Endocrinol Diabetes ; 116(3): 152-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18205092

RESUMO

The angiogenic growth factor Vascular Endothelial Growth Factor-C (VEGF-C) and its receptor VEGFR-3 are also known to be implicated in the development of lymphatic vessels. We assessed the expression of VEGF-C and VEGFR-3, together with blood and lymphatic vessel extents and proliferation index (PI) values, by immunohistochemistry (IHC) in 6 normal human pituitary glands and 53 pituitary adenomas of different tumour grade, on consecutive tissue sections. VEGF-C was detected in around 10% of the endocrine cells in normal pituitary tissue, while this gland was devoid of lymphatic vascularization and showed very few vessels positive for VEGFR-3. Concerning tumour tissue, most of the adenomas showing VEGF-C immunoreactivity (21/47) were positive in 60% of the tumour cells and the ones positive for VEGFR-3 showed a number of immunostained vessels higher than those observed in the normal pituitary. Most of the tumours positive for VEGFR-3 did not show any LYVE-1 positive vessels (18/53), suggesting that at least in these cases, VEGFR-3 is expressed on blood vessels. Nevertheless, we observed a significant association between low expression of VEGFR-3 and low lymphatic vessel number, suggesting that VEGFR-3 might be involved in the starting of DE NOVO lymphangiogenesis in this tumour type. Moreover, tumours bearing lymphatic vessels showed the tendency to shift towards a more aggressive behaviour (high tumour grade and high PI). In conclusion, the VEGF-C/VEGFR-3 system might be involved in controlling tumour angiogenesis in the pituitary adenomas lacking lymphatic vessels, but may also play a role in starting the process of tumour lymphangiogenesis.


Assuntos
Adenoma/metabolismo , Vasos Linfáticos/metabolismo , Neoplasias Hipofisárias/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adenoma/patologia , Humanos , Imuno-Histoquímica , Linfangiogênese/fisiologia , Neovascularização Patológica/patologia , Neoplasias Hipofisárias/patologia , Valores de Referência
14.
Technol Health Care ; 26(2): 209-221, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28968251

RESUMO

BACKGROUND: Previous studies revealed evidence that induced hypothermia attenuates ischemic organ injuries after severe trauma. In the present study, the effect of hypothermia on liver damage was investigated in a porcine long term model of multi-system injury, consisting of blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shockMETHODS: In 30 pigs, a standardized polytrauma including blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shock of 45% of total blood volume was induced. Following trauma, hypothermia of 33∘C was induced for 12 h and intensive care treatment was evaluated for 48 h. As outcome parameters, we assessed liver function and serum transaminase levels as well as a histopathological analysis of tissue samples. A further 10 animals served as controls. RESULTS: Serum transaminase levels were increased at the end of the observation period following hypothermia without reaching statistical significance compared to normothermic groups. Liver function was preserved (p⩽ 0.05) after the rewarming period in hypothermic animals but showed no difference at the end of the observation period. In H&E staining, cell death was slightly increased hypothermic animals and caspase-3 staining displayed tendency towards more apoptosis in hypothermic group as well. CONCLUSIONS: Induction of hypothermia could not significantly improve hepatic damage during the first 48 h following major trauma. Further studies focusing on multi-organ failure including a longer observation period are required to illuminate the impact of hypothermia on hepatic function in multiple trauma patients.


Assuntos
Hipotermia Induzida/métodos , Unidades de Terapia Intensiva , Hepatopatias/prevenção & controle , Traumatismo Múltiplo/terapia , Traumatismos Abdominais/terapia , Animais , Modelos Animais de Doenças , Testes de Função Hepática , Masculino , Distribuição Aleatória , Choque Hemorrágico/terapia , Suínos , Traumatismos Torácicos/terapia , Índices de Gravidade do Trauma , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/terapia
15.
J Clin Invest ; 108(8): 1123-31, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11602619

RESUMO

Cushing syndrome is caused by an excess of adrenocorticotropic hormone (ACTH) production by neuroendocrine tumors, which subsequently results in chronic glucocorticoid excess. We found that retinoic acid inhibits the transcriptional activity of AP-1 and the orphan receptors Nur77 and Nurr1 in ACTH-secreting tumor cells. Retinoic acid treatment resulted in reduced pro-opiomelanocortin transcription and ACTH production. ACTH inhibition was also observed in human pituitary ACTH-secreting tumor cells and a small-cell lung cancer cell line, but not in normal cells. This correlated with the expression of the orphan receptor COUP-TFI, which was found in normal corticotrophs but not in pituitary Cushing tumors. COUP-TFI expression in ACTH-secreting tumor cells blocked retinoic acid action. Retinoic acid also inhibited cell proliferation and, after prolonged treatment, increased caspase-3 activity and induced cell death in ACTH-secreting cells. In adrenal cortex cells, retinoic acid inhibited corticosterone production and cell proliferation. The antiproliferative action and the inhibition of ACTH and corticosterone produced by retinoic acid were confirmed in vivo in experimental ACTH-secreting tumors in nude mice. Thus, we conclude that the effects of retinoic acid combine in vivo to reverse the endocrine alterations and symptoms observed in experimental Cushing syndrome.


Assuntos
Síndrome de Cushing/prevenção & controle , Tretinoína/farmacologia , Hormônio Adrenocorticotrópico/biossíntese , Animais , Fator I de Transcrição COUP , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Síndrome de Cushing/etiologia , Síndrome de Cushing/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Pró-Opiomelanocortina/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transplante Heterólogo , Células Tumorais Cultivadas
16.
J Clin Invest ; 96(4): 2017-25, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7560095

RESUMO

In addition to its well-known homoeostatic actions in the cardiovascular system, ET-1 has been shown to constitute a potent growth regulatory peptide in various tissues. We have studied the expression of ET-1 and its receptors (ET-Ar and ET-Br) in human meningiomas (n = 35) as well as their involvement in cellular growth. By PCR of reverse-transcribed RNA we detected ET-1 mRNA in 91% (32 of 35), ET-Ar mRNA in 82% (29 of 35), and ET-Br mRNA in 42% (15 of 35) of human meningiomas examined. The localization of ET-1 mRNA, ET-Ar mRNA, and ET-1 peptide in tumoral cells was observed by in situ hybridization and immunohistochemistry, whereas ET-Br mRNA was expressed at low level only in cells belonging to blood vessels. In addition, we found that ET-1 stimulated [3H] thymidine incorporation in primary cell cultures of 20 meningiomas and that this effect could be blocked by BQ-123, a specific antagonist for ET-Ar. In contrast, RES-701-3, an antagonist of ET-Br, did not block the proliferative effect of ET-1. In conclusion, our data provide evidence that ET-1 constitutes an important growth factor for meningiomas acting via ET-Ar. We can hypothesize that ET-1, acting in concert with other growth factors and cytokines, is involved in the meningioma tumorigenesis.


Assuntos
Endotelinas/análise , Neoplasias Meníngeas/química , Meningioma/química , Receptores de Endotelina/análise , Adulto , Idoso , Sequência de Bases , DNA/biossíntese , Endotelinas/genética , Endotelinas/fisiologia , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meninges/química , Meningioma/patologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Receptores de Endotelina/fisiologia , Células Tumorais Cultivadas
19.
MMW Fortschr Med ; 148(43): 26-8, 2006 Oct 26.
Artigo em Alemão | MEDLINE | ID: mdl-17619419

RESUMO

The diagnosis is established through neurological examinations, laboratory and imaging diagnostics. Conservative treatment such as a neck brace, drug and physical therapies could bring relief. Manifest or progressing deficiency symptoms associated with sensory or motoric deficit, bladder, rectal or erectile disorder are indications for early surgery.


Assuntos
Vértebras Cervicais/cirurgia , Compressão da Medula Espinal/cirurgia , Osteofitose Vertebral/cirurgia , Estenose Espinal/cirurgia , Idoso , Diagnóstico Diferencial , Humanos , Laminectomia , Imageamento por Ressonância Magnética , Exame Neurológico , Prognóstico , Compressão da Medula Espinal/diagnóstico , Fusão Vertebral , Osteofitose Vertebral/diagnóstico , Estenose Espinal/diagnóstico
20.
MMW Fortschr Med ; 148(43): 29-32, 2006 Oct 26.
Artigo em Alemão | MEDLINE | ID: mdl-17619420

RESUMO

Lumbar spinal stenosis is one of the most frequent causes of spinal surgical interventions in over 60-year olds. The exact relationship between degenerative changes and the resulting symptoms is unclear since imaging shows stenotic changes in the spines of many symptom-free patients. The concurrence of imaging findings, the symptoms described and manifestations is crucial for the indication of surgical decompression. Nevertheless, spinal claudication that is refractory to conservative therapy is the most frequent indication for surgery. The success rate two years after OP is approximately 80% in over 75-year olds. Five years after surgical intervention, an improvement in the symptoms is still recognizable in 50% of these patients.


Assuntos
Dor nas Costas/etiologia , Vértebras Lombares , Transtornos de Sensação/etiologia , Compressão da Medula Espinal/diagnóstico , Osteofitose Vertebral/diagnóstico , Estenose Espinal/diagnóstico , Diagnóstico Diferencial , Seguimentos , Humanos , Laminectomia , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Exame Neurológico , Radiculopatia/diagnóstico , Radiculopatia/etiologia , Compressão da Medula Espinal/cirurgia , Fusão Vertebral , Osteofitose Vertebral/cirurgia , Estenose Espinal/cirurgia , Tomografia Computadorizada por Raios X
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