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1.
Strahlenther Onkol ; 198(1): 1-11, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34786605

RESUMEN

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.


Asunto(s)
Docentes Médicos , Oncología por Radiación , Competencia Clínica , Curriculum , Alemania , Humanos , Oncología por Radiación/educación
2.
Strahlenther Onkol ; 197(5): 385-395, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33410959

RESUMEN

BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Carga Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica , Estudios Retrospectivos , Resultado del Tratamiento , Carga Tumoral/efectos de la radiación
3.
Strahlenther Onkol ; 196(8): 699-704, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32367455

RESUMEN

PURPOSE: Medical students' knowledge of radiation oncology (RO) is of increasing importance with a rising prevalence of malignancies. However, RO teaching in medical schools is heterogeneous and has not been analyzed at a federal level yet. Therefore, the following survey aims to provide a national overview of RO teaching in Germany. METHODS: A questionnaire containing multiple-choice and free-text questions covering the extent and topics of RO teaching was sent to RO departments of all university hospitals in Germany and was answered by the heads of department/main lecturers. RESULTS: 24/35 (68.6%) RO departments returned completed forms. Most faculties employ lectures (91.7%), seminars (87.5%), and practical/bedside training (75.0%), whereas training in radiation biology and medical physics are rare (25% and 33.3%, respectively). Main topics covered are general RO (100%), radiation biology (91.7%), and side effects (87.5%). Regarding RO techniques and concepts, image-guided and intensity-modulated radiotherapy are taught at all faculties, followed by palliative and stereotactic techniques (87.5% each). Notably, all departments offered at least a partial rotation in RO in conjunction with radiology and/or nuclear medicine departments in the last year of medical school, while only 70.8% provided a complete rotation in RO. In addition, 57.1% of the departments have taken measures concerning the upcoming National Competence-Based Learning Objectives Catalogue (NKLM) for medical education. CONCLUSION: RO plays an integral but underrepresented role in clinical medical education in Germany, but faces new challenges in the development of practical and competence-based education, which will require further innovative and interdisciplinary concepts.


Asunto(s)
Oncología por Radiación/educación , Encuestas y Cuestionarios , Curriculum , Docentes Médicos , Alemania , Hospitales Universitarios , Humanos , Revisión por Expertos de la Atención de Salud , Sociedades Médicas , Enseñanza
4.
Strahlenther Onkol ; 196(5): 457-464, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32016497

RESUMEN

PURPOSE: Purpose of this study was to investigate outcome and toxicity of re-irradiation for recurrent primary glioblastoma (rGBM). We evaluated a group of patients with rGBM and identical primary treatment comprising adjuvant radiotherapy (30â€¯× 2 Gy) with concurrent temozolomide (TMZ). METHODS: In this retrospective study of 46 patients, all received adjuvant or definitive normofractionated radiotherapy to a pretreated area, some with concurrent chemotherapy. Impact of different clinical, histological, or epidemiological factors on survival and radiation toxicity was reviewed. RESULTS: Of 46 patients, 40 completed the intended therapy. Overall survival (OS) was 20 months (range 6-72 months). Overall survival and progression-free survival after re-irradiation (OS2 and PFS2) were 9.5 and 3.4 months (range 2-40 and 0.7-44 months). Simultaneous systemic therapy improved PFS2 and OS2 (4.3 vs. 2.0, p < 0.001 and 12 vs. 4 months, p = 0.13, respectively). Therapy with TMZ or bevacizumab improved PFS2 vs. nitrosureas (6.6 vs. 2.9, p = 0.03 and 5.1 vs. 2.9 months, p = 0.035, respectively). TMZ also improved PFS2 and OS2 vs. all other systemic therapies (6.6 vs. 4, p < 0.001 and 17 vs. 10 months, p = 0.1). In a subgroup analysis for patients with methylation of the MGMT promoter, doses of >36 Gy as well as TMZ vs. no systemic therapy improved PFS2 (p = 0.045 and p = 0.03, respectively). 27.5% of all patients had no acute toxicity. Three patients with acute and four patients with late grade 3 toxicities were reported. CONCLUSION: Normofractionated radiotherapy is a feasible option for rGBM with a good toxicity profile. Simultaneously applied systemic therapy was associated with improved outcome. For MGMT promoter-methylated histology, higher radiation doses improved survival.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Reirradiación/métodos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/mortalidad , Terapia Combinada , Estudios de Factibilidad , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Dosificación Radioterapéutica , Reirradiación/efectos adversos , Estudios Retrospectivos , Tasa de Supervivencia
5.
Strahlenther Onkol ; 196(12): 1096-1102, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33125504

RESUMEN

PURPOSE: The coronavirus pandemic is affecting global health systems, endangering daily patient care. Hemato-oncological patients are particularly vulnerable to infection, requiring decisive recommendations on treatment and triage. The aim of this survey amongst experts on radiation therapy (RT) for lymphoma and leukemia is to delineate typical clinical scenarios and to provide counsel for high-quality care. METHODS: A multi-item questionnaire containing multiple-choice and free-text questions was developed in a peer-reviewed process and sent to members of the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance. Answers were assessed online and analyzed centrally. RESULTS: Omission of RT was only considered in a minority of cases if alternative treatment options were available. Hypofractionated regimens and reduced dosages may be used for indolent lymphoma and fractures due to multiple myeloma. Overall, there was a tendency to shorten RT rather than to postpone or omit it. Even in case of critical resource shortage, panelists agreed to start emergency RT for typical indications (intracranial pressure, spinal compression, superior vena cava syndrome) within 24 h. Possible criteria to consider for patient triage are the availability of (systemic) options, the underlying disease dynamic, and the treatment rationale (curative/palliative). CONCLUSION: RT for hemato-oncological patients receives high-priority and should be maintained even in later stages of the pandemic. Hypofractionation and shortened treatment schedules are feasible options for well-defined constellations, but have to be discussed in the clinical context.


Asunto(s)
COVID-19/epidemiología , Linfoma/radioterapia , Mieloma Múltiple/radioterapia , Pandemias , Oncología por Radiación/normas , SARS-CoV-2/aislamiento & purificación , Triaje/normas , Citas y Horarios , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/prevención & control , Prueba de COVID-19 , Infección Hospitalaria/prevención & control , Diagnóstico Diferencial , Fraccionamiento de la Dosis de Radiación , Humanos , Higiene/normas , Control de Infecciones/métodos , Control de Infecciones/normas , Linfoma/complicaciones , Linfoma/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Osteólisis/etiología , Osteólisis/radioterapia , Equipo de Protección Personal , Oncología por Radiación/métodos , Neumonitis por Radiación/diagnóstico , Síndrome de la Vena Cava Superior/etiología , Síndrome de la Vena Cava Superior/radioterapia , Encuestas y Cuestionarios , Tiempo de Tratamiento , Irradiación Corporal Total
7.
J Neurosurg Sci ; 55(3): 179-87, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21968582

RESUMEN

AIM: Electrophysiological monitoring (EM) is still controversial in the prediction of outcome after subarachnoid hemorrhage (SAH). The absence of evoked potentials (EP) is a good predictor for unfavorable, whereas the prediction of favorable outcome may be less useful. Aim of this study was to evaluate, if multimodal EM provides significant information about the patients' outcome or if this method might be dispensable. METHODS: Multimodal EP data were recorded sequentially in 51 SAH-patients. The following data were recorded: World Federation of Neurological Surgeons (WFNS-) grade, Fisher grading score, endovascular versus neurosurgical treatment, aneurysm location and clinical outcome according to the Glasgow Outcome Scale (GOS). Multimodal electrophysiological monitoring included median nerve somatosensory evoked potential (M-SSEP), tibial nerve somatosensory evoked potential (T-SSEP), flash-visual evoked potential (f-VEP), brainstem auditory evoked potential (BAEP) and central conduction time (CCT) of M-SSEP. EP data were recorded sequentially; the first and last studies were evaluated. RESULTS: No correlation was found between initial and last M-SSEP, T-SSEP, BAEP and initial f-VEP and the patients' outcome. An 'unfavorable' outcome was in conjunction with an initial delayed CCT (>6 ms, P=0.03) and the final f-VEP correlated well with the patients' outcome (P=0.03). CONCLUSION: In conclusion, neither T-SSEP, f-VEP, BAEP nor CCT can be used as valid predictor for outcome after SAH. The patient's initial clinical grading still provides the only satisfying predictor, independent of the patient's clinical course.


Asunto(s)
Cuidados Críticos/métodos , Potenciales Evocados Somatosensoriales , Potenciales Evocados Visuales , Monitoreo Fisiológico/métodos , Hemorragia Subaracnoidea/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Hemorragia Subaracnoidea/terapia , Resultado del Tratamiento , Adulto Joven
9.
Parkinsonism Relat Disord ; 64: 118-123, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30935828

RESUMEN

BACKGROUND: Pallidal deep brain stimulation (DBS) has shown to be beneficial in patients with advanced levodopa-responsive Parkinson's disease (PD) in several short-term studies. However, reported long-term outcomes of pallidal DBS for PD are limited and contradictory. METHODS: Eighteen consecutive PD patients were treated with unilateral or bilateral stimulation of the internal part of the globus pallidus (GPi). Assessments were carried out before and six months after neurosurgery, and annually thereafter for up to 16 years (mean follow-up time: 6 years). Primary outcomes included motor signs (Unified PD Rating Scale [UPDRS]-III), activities of daily living (ADL, UPDRS-II), and levodopa-induced motor complications (UPDRS-IV). RESULTS: The results show that GPi stimulation improves levodopa-responsive PD motor signs (UPDRS-III), levodopa-induced motor complications (UPDRS-IV), and ADL (UPDRS-II) in advanced PD. Among motor signs, tremor showed the best response to pallidal stimulation. Levodopa-induced motor complications and tremor showed improvements for more than 10 years after neurosurgery. CONCLUSIONS: The overall findings in our cohort demonstrate that pallidal stimulation is effective in reducing parkinsonian motor signs (UPDRS-III), particularly in the 'off'-medication state. Although the beneficial effects on bradykinesia, rigidity and ADL may be limited to 5-6 years, the follow up results indicate that the improvements of levodopa-induced motor complications (UPDRS-IV) and tremor can be sustained for more than 10 years.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Globo Pálido , Enfermedad de Parkinson/terapia , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tiempo , Resultado del Tratamiento
10.
Radiat Oncol ; 13(1): 185, 2018 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-30241556

RESUMEN

BACKGROUND: Prostate cancer (PCA) is the most-prevalent non-skin cancer in men worldwide. Nevertheless, the treatment of oligometastatic, especially lymph-node (ln) recurrent, PCA remains elusive. The aim of our study was to provide insights in radiotherapy (RT)-treatment of recurrent PCA exhibiting ln- or osseous (oss)-oligometastases. METHODS: Between April 2012 and April 2017, 27 oligometastatic PCA patients (19 ln and 8 single oss) were treated with RT at our institution. RESULTS: The metastasis-free survival (MFS) was 24.8 m (22.0-36.0 m) and 25.4 m (23.9-28.1 m) for the ln- and oss-subgroup resulting in 1-year MFS of 75.4 and 100% and 2-year MFS of 58.7 and 83.3% for ln- and oss-metastatic patients, respectively. Of notice, none of the recurrences for ln-patients was in the RT-field, constituting a local control of 100%. Within the ln-group, pre-RT median-PSA was 2.6 ng/ml, median post-RT PSA was 0.3 ng/ml, which was significant (p = 0.003). Median biochemical-free survival (bfS) was 12.2 m. PCA that was initially confined to the prostate had a better bfS (p < 0.001) and MFS (p = 0.013). The oss-group had a median PSA of 4.9 ng/ml pre-treatment which dropped to a median value of 0.14 ng/ml (p = 0.004). Toxicities were moderate, with only 1 case of III° toxicity. There were no deaths in the ln-group, thus overall survial was 100% here. CONCLUSION: Our study points out the feasibility of RT as a treatment option in recurrent PCA and demonstrates an excellent local control with a low-toxicity profile.


Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Recurrencia Local de Neoplasia/radioterapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Anciano , Estudios de Factibilidad , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/cirugía , Terapia Recuperativa/métodos , Resultado del Tratamiento
11.
Biochim Biophys Acta ; 1489(2-3): 345-53, 1999 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-10673035

RESUMEN

TFF-peptides (formerly P-domain peptides, trefoil factors) represent major secretory products of mucous epithelia in mammals and amphibia. The nucleotide sequence of a large portion of a gene encoding the TFF-peptide xP4.1 from Xenopus laevis and its genomic organization were determined in the present study. The peptide xP4.1 containing four TFF-domains is thought to represent the functional frog homolog of human TFF2 (formerly hSP). The xP4.1 gene analyzed spans a region of about 7 kb and consists of six exons. Each TFF-domain is encoded by a single exon flanked by type 1 introns typical of shuffled modules. The 5'-upstream region contains a TATA-box, and potential binding sites for hepatocyte nuclear factor 3 and AP-1. Furthermore, the cDNA sequence of a transcript named xP4.2 with 91% similarity to xP4.1 is presented. RT-PCR analysis revealed that xP4.1 and xP4.2 genes are differentially expressed. xP4.1 transcripts are detectable only in the stomach, but not in the esophagus, whereas xP4.2 transcripts are found both in the esophagus and in the stomach with a descending gradient from fundus to antrum.


Asunto(s)
Regulación de la Expresión Génica , Sustancias de Crecimiento/genética , Péptidos y Proteínas de Señalización Intercelular , Isoformas de Proteínas/genética , Proteínas de Xenopus , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario , Humanos , Datos de Secuencia Molecular , ARN Mensajero/genética , Factor Trefoil-2 , Xenopus laevis
12.
Am J Clin Nutr ; 57(2 Suppl): 313S-314S, 1993 02.
Artículo en Inglés | MEDLINE | ID: mdl-8427211

RESUMEN

Selenite concentration regulates activity and expression of the p27 substrate-binding subunit of type I 5'deiodinase (5'-D) and of a protein labeled with bromoacetylthyroxin (BrAcT4), or p30, with yet unknown function in a porcine-kidney epithelial cell line (LLC-PK1) cultured in serum-free medium. p27 is metabolically labeled by 75-selenite and affinity labeled by BrAc[125I]T4. Compared with glutathione peroxidase, expression of the p27 5'D subunit (5'-DI) is observed at 10-fold-lower concentrations of selenium in the growth medium, suggesting an intracellular hierarchy of selenite utilization. Selenium deficiency retards cell growth and prevents 5'-DI expression and may thus impair thyroid hormone action in vivo.


Asunto(s)
Yoduro Peroxidasa/metabolismo , Selenio/farmacología , Marcadores de Afinidad , Animales , Línea Celular , Glutatión Peroxidasa/metabolismo , Riñón , Radioisótopos de Selenio , Porcinos , Tiroxina/análogos & derivados , Tiroxina/metabolismo
13.
Transplantation ; 72(1): 116-22, 2001 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-11468545

RESUMEN

BACKGROUND: The cytolytic attack of natural killer (NK) cells is blocked by recognition of the idiotypic phenotype of certain polymorphisms in HLA class I molecules, specifically by HLA-C alleles (Asn77, Lys80 or Ser77, Asn80) or HLA-Bw4 allotypes. Because liver allograft rejection is associated closer with mismatch in HLA class I than class II, we investigated the role of NK cells in acute hepatic allograft rejection in vivo/in vitro. METHODS: The HLA pattern was typed with serological and polymerase chain reaction (PCR) techniques. In 31 liver transplantations, mononuclear cells from donor spleen and peripheral blood of recipients (before/after transplantation) were cultured in mixed lymphocyte cultures (MLC). MLC-derived effector cells were analyzed by flow cytometry and tested in 51Cr-release assays. RESULTS: Patients with NK allospecific constellations tended to have higher numbers of NK cells in peripheral blood during the first 4 weeks after transplantation, and patients' lymphocytes stimulated with donor cells had a significantly higher cytotoxic activity on days 14 and 21 compared with patients without NK allospecificity. However, acute rejection occurred with similar frequency in both groups (31% with allospecific constellations vs. 40% without). Moreover, acute rejection episodes were not associated with an increase in NK cells in vivo or enhanced cytotoxicity of NK cells to donor target cells. CONCLUSIONS: Under standard immunosuppressive therapy, NK allospecific constellations did not seem play a major role in acute hepatic allograft rejection. Strategies to prevent or treat NK allospecific constellations after liver transplantation are not likely to reduce the incidence or severity of acute allograft rejection.


Asunto(s)
Isoanticuerpos/análisis , Células Asesinas Naturales/inmunología , Trasplante de Hígado/inmunología , Enfermedad Aguda , Adolescente , Adulto , Células Cultivadas , Citotoxicidad Inmunológica , Femenino , Rechazo de Injerto/inmunología , Humanos , Células Asesinas Naturales/patología , Recuento de Leucocitos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Persona de Mediana Edad , Trasplante Homólogo
14.
Cancer Lett ; 165(1): 71-9, 2001 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-11248421

RESUMEN

Normal cells differ from malignant tumor cells in the transcription levels of many different genes. Two colorectal tumor cell lines were compared with a normal colorectal cell line by differential display reverse transcription PCR to screen for tumor cell specific differentially transcribed genes. By this strategy the upregulation of a novel gene was detected designated as 'upregulated in colorectal cancer gene-1' (UCC1). The UCC1 gene transcript level is increased in cultured tumor cells and in two out of three analyzed colorectal tumor tissue specimens compared to normal cultured cells and to corresponding normal tissue samples. Remarkably, the UCC1 protein shows significant sequence similarity to the highly divergent piscine glycoproteins termed ependymins which are synthesized by leptomeningeal fibroblasts and secreted into the cerebrospinal fluid.


Asunto(s)
Neoplasias Colorrectales/genética , Proteínas de Neoplasias/genética , Proteínas del Tejido Nervioso/química , Secuencia de Aminoácidos , Células Cultivadas , Clonación Molecular , Colon/citología , Colon/fisiología , Neoplasias Colorrectales/patología , Humanos , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/genética , ARN Mensajero/análisis , Homología de Secuencia de Aminoácido
15.
J Neurosurg ; 95(2): 222-32, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11780891

RESUMEN

OBJECT: Contemporary management of head-injured patients is based on assumptions about CO2 reactivity, pressure autoregulation (PA), and vascular reactivity to pharmacological metabolic suppression. In this study, serial assessments of vasoreactivity of the middle cerebral artery (MCA) were performed using bilateral transcranial Doppler (TCD) ultrasonography. METHODS: Twenty-eight patients (mean age 33 +/- 13 years, median Glasgow Coma Scale score of 7) underwent a total of 61 testing sessions during postinjury Days 0 to 13. The CO2 reactivity (58 studies in 28 patients), PA (51 studies in 23 patients), and metabolic suppression reactivity (35 studies in 16 patients) were quantified for each cerebral hemisphere by measuring changes in MCA velocity in response to transient hyperventilation, arterial blood pressure elevation, or propofol-induced burst suppression, respectively. One or both hemispheres registered below normal vasoreactivity scores in 40%, 69%, and 97% of study sessions for CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.0001), respectively. Intracranial hypertension, classified as intracranial pressure (ICP) greater than 20 mm Hg at the time of testing, was associated with global impairment of CO2 reactivity, PA, and metabolic suppression reactivity (p < 0.05). A low baseline cerebral perfusion pressure (CPP) was also predictive of impaired CO2 reactivity and PA (p < 0.01). Early postinjury hypotension or hypoxia was also associated with impaired CO2 reactivity (p < 0.05), and hemorrhagic brain lesions in or overlying the MCA territory were predictive of impaired metabolic suppression reactivity (p < 0.01). The 6-month Glasgow Outcome Scale score correlated with the overall degree of impaired vasoreactivity (p < 0.05). CONCLUSIONS: During the first 2 weeks after moderate or severe head injury, CO2 reactivity remains relatively intact, PA is variably impaired, and metabolic suppression reactivity remains severely impaired. Elevated ICP appears to affect all three components of vasoreactivity that were tested, whereas other clinical factors such as CPP, hypotensive and hypoxic insults, and hemorrhagic brain lesions have distinctly different impacts on the state of vasoreactivity. Incorporation of TCD ultrasonography-derived vasoreactivity data may facilitate more injury- and time-specific therapies for head-injured patients.


Asunto(s)
Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/fisiopatología , Dióxido de Carbono/fisiología , Homeostasis/fisiología , Presión Intracraneal/fisiología , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/fisiopatología , Ultrasonografía Doppler Transcraneal , Vasodilatación/fisiología , Adolescente , Adulto , Velocidad del Flujo Sanguíneo/fisiología , Circulación Cerebrovascular/fisiología , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Valor Predictivo de las Pruebas
16.
Am J Health Syst Pharm ; 55(19): 1979-86, 1998 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-9784784

RESUMEN

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of anagrelide are reviewed. Anagrelide is a selective thrombocytopenic agent with FDA-approved labeling for the treatment of essential thrombocythemia. Clinical trials have shown that the drug may have a role in the treatment of other chronic myeloproliferative disorders, including polycythemia vera, chronic myeloid leukemia, and agnogenic myeloid metaplasia. The mechanism by which anagrelide reduces platelet count is not yet clear. The current hypothesis is that anagrelide affects the late (postmitotic) phases of megakaryocyte development. Anagrelide has a large volume of distribution and is extensively metabolized; less than 1% is recovered unchanged in the urine. Plasma half-life after a 0.5-mg dose is 1.3 hours. Anagrelide's efficacy and safety have been evaluated in open-label, noncomparative trials, in which the response rate was 60-93%. Adverse effects include headache, diarrhea, edema, palpitations, and abdominal pain. Patients with renal or hepatic dysfunction need to be closely monitored for signs of toxicity. The recommended starting dosage is 0.5 mg four times a day or 1 mg twice a day, with dosage adjustment to the lowest effective amount required to reduce and maintain platelet count below 600 x 10(9)/L. The wholesale acquisition price for 0.5-mg capsules is $350 per 100. Whether anagrelide will replace hydroxyurea as first-line therapy in some or all patients remains to be determined. Anagrelide is effective in the treatment of essential thrombocythemia and may have a role in the treatment of other myeloproliferative disorders.


Asunto(s)
Inhibidores de Agregación Plaquetaria/uso terapéutico , Quinazolinas/uso terapéutico , Trombocitemia Esencial/tratamiento farmacológico , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/farmacocinética , Quinazolinas/efectos adversos , Quinazolinas/economía , Quinazolinas/farmacocinética
17.
Acta Neurochir Suppl ; 81: 69-70, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12168359

RESUMEN

Thirty years after its first description metabolic suppressive therapy is still controversial in patients with intractable intracranial hypertension. In this study high dose propofol was used to induce metabolic suppression. The effects on intracranial pressure (ICP) and the cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlc) are reported. A total of 28 studies were performed on 14 head injured patients. A Xenon133 cerebral blood flow (CBF) and a CO2-reactivity (CO2R) test were performed prior to induction of metabolic suppression. The following parameters were continuously monitored: EEG, etCO2, SjvO2, ICP, MAP and bilateral MCA flow velocity (VMCA). PCO2 was obtained before and during propofol-induced EEG burst-suppression in arterial and jugular-venous blood. CMRO2, CMRGlc and Metabolic Ratio (MR = CMRO2/CMRGlc) were calculated. MR < 0.6 was defined as relative hyperglycolysis. ICP decreased by 24.1 +/- 29.0% during burst-suppression. Arterial, jugular-venous and etCO2 also decreased. Multiple regression analysis revealed that CO2 was the strongest predictor for ICP. Lower baseline ICP and normal CO2 reactivity were predictors for normal metabolic suppression reactivity. In studies with normal metabolic ratio, ICP reduction was associated with a reduction in CMRO2. In studies with hyperglycolysis, ICP reduction was poor but CMRGlc decreased significantly. In conclusion, intact CO2R, normal or only moderately elevated ICP and normal MR are predictive of ICP reduction with high dose propofol after head injury.


Asunto(s)
Lesiones Encefálicas/cirugía , Circulación Cerebrovascular/fisiología , Hipertensión Intracraneal/terapia , Anticonvulsivantes/uso terapéutico , Biomarcadores/sangre , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/fisiopatología , Dióxido de Carbono/sangre , Humanos , Hipertensión Intracraneal/etiología , Oxígeno/sangre , Propofol/uso terapéutico
18.
Acta Neurochir Suppl ; 81: 67-8, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12168358

RESUMEN

Induced blood pressure elevation has become a popular treatment for intracranial hypertension. However, there remains a concern that in some patients blood pressure elevation will further elevate ICP. This study was conducted to test the hypothesis that increasing MAP decreases ICP. A total of 47 studies were performed on 23 intubated patients with head injury. MAP and SjvO2 were continuously monitored. MAP was raised significantly by 13.8 (5.9) mmHg (t-test; p < 0.0001) using phenylephrine infusion. The percent change ICP per mmHg increase in MAP (% delta ICP/mm Hg MAP) was calculated. Pearson correlation coefficient, t-test and logistic regression analysis were used for statistical evaluation. Increasing MAP resulted in a decrease in ICP in 38.3% and in an increase in ICP in 61.7% out of 47 studies. The following characteristics were seen in patients in whom a decrease in ICP was associated with an increase in MAP: High GCS (r = -0.61; p = 0.004) and low SjvO2 ((2 = 4.89; p = 0.027). In patients with lower GCS and high SjvO2 an increase in MAP resulted in an increase in ICP. We concluded that in the majority of studies increasing MAP was followed by an increase in ICP. CPP therapy has a selective indication in patients with high GCS, low SjvO2 and increased ICP.


Asunto(s)
Lesiones Encefálicas/cirugía , Hipertensión Intracraneal/terapia , Presión Intracraneal/fisiología , Anticonvulsivantes/uso terapéutico , Presión Sanguínea , Humanos , Hipertensión Intracraneal/etiología , Monitoreo Intraoperatorio , Piperazinas/uso terapéutico
19.
Acta Neurochir Suppl ; 81: 71-2, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12168361

RESUMEN

Gosling's pulsatility index (PI) is generally thought to reflect cerebrovascular resistance. Hyperventilation and increased intracranial pressure (ICP) usually increase PI. In this study, the effect of hyperventilation on PI was assessed in head injured patients with and without elevated ICP. A total of 73 hyperventilation studies were conducted on 20 intubated TBI patients. EtCO2, ICP, MCA flow velocity and MCA PI bilaterally were recorded simultaneously. Hemispheric CO2-Reactivity (hCO2R) was calculated. Only studies with a baseline ICP < 15 or > 30 mm Hg were included for analysis. With hyperventilation pCO2 decreased on average from 33.54.2 to 26.84.8 mmHg. PI increased significantly in patients with baseline ICP < 15 mmHg (11.8%; p < 0.0001) but decreased significantly if baseline ICP was > 30 mm Hg (12.21%; p = 0.0013). High baseline ICP, low initial GCS and impaired hCO2R were associated with the decrease of PI. Hyperventilation unexpectedly reduced PI in patients with high ICP. Because decreased PI suggests decreased CVR, it is postulated that hyperventilation in the setting of raised ICP improves cerebral microcirculation.


Asunto(s)
Dióxido de Carbono/sangre , Circulación Cerebrovascular/fisiología , Traumatismos Craneocerebrales/fisiopatología , Hiperventilación , Hipertensión Intracraneal/terapia , Microcirculación/fisiología , Adulto , Velocidad del Flujo Sanguíneo , Traumatismos Craneocerebrales/terapia , Diástole , Femenino , Humanos , Hipertensión Intracraneal/etiología , Presión Intracraneal/fisiología , Masculino
20.
Pediatr Nurs ; 22(6): 525-8, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-9087091

RESUMEN

Respiratory syncytial virus immune globulin has been shown to prevent or attenuate RSV lower respiratory tract infection in infants under 24 months of age with BPD or who were born prematurely (< or = 35 weeks gestation). The use of RSV-IG is expensive. The estimated average cost of prophylaxis for a season is $4,000 to $5,000 per infant. Because of the cost of RSV-IG, and because viral transmission is possible when any blood product is administered, careful consideration of which children should receive RSV-IG is warranted.


Asunto(s)
Inmunoglobulinas Intravenosas/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/terapia , Preescolar , Interacciones Farmacológicas , Humanos , Lactante , Recién Nacido
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