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1.
J Mater Sci Mater Med ; 33(11): 76, 2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36264396

RESUMEN

Fractures of the paranasal sinuses often require surgical intervention. Persisting bone defects lead to permanent visible deformities of the facial contours. Bone substitutes for reconstruction of defects with simultaneous induction of new bone formation are not commercially available for the paranasal sinus. New materials are urgently needed and have to be tested in their future area of application. For this purpose critical size defect models for the paranasal sinus have to be developed. A ≥2.4 cm large bilateral circular defect was created in the anterior wall of the maxillary sinus in six sheep via an extraoral approach. The defect was filled with two types of an osteoconductive titanium scaffold (empty scaffold vs. scaffold filled with a calcium phosphate bone cement paste) or covered with a titanium mesh either. Sheep were euthanized after four months. All animals performed well, no postoperative complications occured. Meshes and scaffolds were safely covered with soft tissue at the end of the study. The initial defect size of ≥2.4 cm only shrunk minimally during the investigation period confirming a critical size defect. No ingrowth of bone into any of the scaffolds was observed. The anterior wall of the maxillary sinus is a region with low complication rate for performing critical size defect experiments in sheep. We recommend this region for experiments with future scaffold materials whose intended use is not only limited to the paranasal sinus, as the defect is challenging even for bone graft substitutes with proven osteoconductivity. Graphical abstract.


Asunto(s)
Sustitutos de Huesos , Ovinos , Animales , Cementos para Huesos , Titanio , Maxilar/cirugía , Fosfatos de Calcio , Regeneración Ósea , Seno Maxilar/cirugía
2.
Biomater Adv ; 136: 212754, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35929289

RESUMEN

Current alloplastic materials such as PMMA, titanium or PEEK don't show relevant bone ingrowth into the implant when used for cranioplasty, ceramic implants have the drawback being brittle. New materials and implant designs are urgently needed being biocompatible, stable enough for cranioplasty and stimulating bone formation. In an in vivo critical size sheep model circular cranial defects (>2.4 cm) were covered with three different types of a 3D-printed porous titanium scaffolds with multidirectional, stochastically distributed architecture (uncoated scaffold, hydroxyapatite-coated scaffold, uncoated scaffold filled with a calcium phosphate bone cement paste containing ß-TCP granules). An empty titanium mesh served as control. Among the different investigated setups the hydroxyapatite-coated scaffolds showed a surprisingly favourable performance. Push-out tests revealed a 2.9 fold higher force needed in the hydroxyapatite-coated scaffolds compared to the mesh group. Mean CT density at five different points inside the scaffold was 2385HU in the hydroxyapatite-coated group compared to 1978HU in the uncoated scaffold at nine months. Average lateral bone ingrowth after four months in the hydroxyapatite-coated scaffold group was up to the implant center, 12.1 mm on average, compared to 2.8 mm in the control group covered with mesh only. These properties make the investigated scaffold with multidirectional, stochastically distributed structure superior to all products currently on the market. The study gives a good idea of what future materials for cranioplasty might look like.


Asunto(s)
Prótesis e Implantes , Titanio , Animales , Cementos para Huesos , Durapatita/farmacología , Impresión Tridimensional , Ovinos , Cráneo/diagnóstico por imagen , Titanio/química
3.
J Oral Biol Craniofac Res ; 11(4): 601-607, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34567964

RESUMEN

Skull base surgery remains one of the challenging areas in the field of cranio-maxillofacial surgery, otolaryngology and neurosurgery. Subsequent reconstruction of bone and soft tissue are an essential component to restore function and appearance after ablative surgery. Establishment of interdisciplinary tumor boards with presentation of the individual patient cases have become standard. Multiplanar reconstruction using MRI or CT imaging techniques combined with virtual 3D planning allow precise planning of the procedures. Intraoperative navigation helps for complete resection of malignant findings with safety margins; surgical approaches provide a good overview of the surgical site. Reconstruction using local flaps have a low complication rate with equally reliable results in reconstruction of small tissue defects. Free flap surgery makes reconstruction of large tissue defects possible. Alloplastic materials are alternatively used for reconstruction of bone defects. Based on selected patients, treatment algorithms and standard surgical procedures in extracerebral skull base surgery will be illustrated. Current techniques and new approaches will be discussed with emphasize on hard and soft tissue reconstruction.

4.
J Intern Med ; 289(2): 193-205, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32654192

RESUMEN

BACKGROUND: Extracellular fluid volume (ECF) is independently associated with chronic kidney disease (CKD) progression and mortality in patients with CKD, but the prognostic value of the trajectory of ECF over time beyond that of baseline value is unknown. OBJECTIVES: To characterize ECF trajectory and evaluate its association with the risks of end-stage kidney disease (ESKD) and mortality. METHODS: From the prospective tricentric NephroTest cohort, we included 1588 patients with baseline measured glomerular filtration rate (mGFR) ≥15 mL min-1 /1.73 m2 and ECF measurement. ECF and GFR were measured repeatedly using the distribution volume and clearance of 51 Cr-EDTA, respectively. ESKD and mortality were traced through record linkage with the national registries. Adjusted shared random-effect joint models were used to analyse the association between the trajectory of ECF over time and the two competing outcomes. RESULTS: Patients were mean age 58.7 years, 66.7% men, mean mGFR of 43.6 ± 18.6 mL min-1 /1.73 m2 and mean ECF of 16.1 ± 3.6 L. Over a median follow-up of 5.3 [IQR: 3.0;7.4] years, ECF increased by 136 [95%CI 106;167] mL per year on average, whilst diuretic prescription and 24-hour urinary sodium excretion remained stable. ESKD occurred in 324 (20.4%) patients, and 185 (11.6%) patients died before ESKD. A higher current value of ECF was associated with increased hazards of ESKD (adjusted hazard ratio [aHR]: 1.12 [95%CI 1.06;1.18]; P < 0.001 per 1 L increase in ECF), and death before ESKD (aHR: 1.10 [95%CI 1.04;1.17]; P = 0.002). CONCLUSIONS: The current value of ECF was associated with the risks of ESKD and mortality, independent of multiple potential confounders, including kidney function decline. This highlights the need for a close monitoring and adjustment of treatment to avoid fluid overload in CKD patients.


Asunto(s)
Líquido Extracelular/metabolismo , Fallo Renal Crónico/mortalidad , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo
5.
Int J Oral Maxillofac Surg ; 50(4): 511-515, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32847710

RESUMEN

A 71-year-old woman was referred to the clinic with extensive medication-related osteonecrosis of the jaw (MRONJ) involving the mandible. She had received 7 years of zoledronate therapy. On cone beam computed tomography, the MRONJ presented as a large sequestrum spanning from the left to the right condylar process, surrounded by thick sub-periosteal bone. The sequestrum was excised via an intraoral approach, leaving the newly formed sub-periosteal bone as a neo-mandible. The patient recovered well from the operation and was discharged 5 days after surgery. She healed completely without complications. This case report presents an alternative surgical treatment that may be considered if there is clinically stable sub-periosteal bone surrounding extensive MRONJ.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Osteonecrosis , Anciano , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico por imagen , Osteonecrosis de los Maxilares Asociada a Difosfonatos/cirugía , Conservadores de la Densidad Ósea/efectos adversos , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Mandíbula , Ácido Zoledrónico
6.
J Craniomaxillofac Surg ; 47(12): 1973-1979, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31810844

RESUMEN

The Cook-Swartz-Doppler probe is an easy to handle and reliable tool for free flap monitoring. In the head and neck region different confounders can affect the read out. We therefore analyzed the use of the Doppler probe regarding these potential difficulties and to compare the diagnostic accuracy in arterial or venous monitoring of free flaps in the head and neck region. A retrospective study was performed in which all patients were included who underwent free flap surgery in the head and neck region in the Department of Plastic Surgery and the Department of Maxillofacial Surgery of our institution between 2010 and 2018 and were monitored with an implanted Doppler probe. 147 free tissue transfers were included. No significance was found for arterial and venous placement of the Doppler probe for sensitivity (artery 83.3%; vein 84.6%; p = 0.87), specificity (artery 89.2%; vein 96.1%; p = 0.17) and negative predictive value (artery 96.7%; vein 94.2%; p = 0.55). A better positive predictive value for placing the Doppler probe around the artery (82.7%) than the vein (61.1%) was found in our study (p = 0.056). The better positive predictive value in arterial monitoring suggests that this is the more reliable measuring method to assess flap perfusion in the head and neck region.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello/cirugía , Monitoreo Ambulatorio/métodos , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Colgajos Tisulares Libres/irrigación sanguínea , Colgajos Tisulares Libres/fisiología , Neoplasias de Cabeza y Cuello/patología , Humanos , Flujometría por Láser-Doppler/instrumentación , Microcirugia/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos
7.
J Med Case Rep ; 13(1): 247, 2019 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-31395094

RESUMEN

BACKGROUND: Cervical lymph node swelling is quite a common symptom mainly caused by infections in the face or as metastasis of a malignant tumor. In infection cases in particular, rare diseases should never be overlooked. With an incidence of 120 cases in the United States of America (USA) and approximately 25 cases in Germany per year, infection with the pathogen Francisella tularensis is one of these rare diseases that can cause massive lymph node swellings and might even be fatal. CASE PRESENTATION: The example of a healthy 67-year-old German woman who was treated at our university hospital presents a typical progression of a localized form of tularemia. The pathogen could be identified in a universal 16S ribosomal deoxyribonucleic acid (DNA) polymerase chain reaction. Pathogen-specific treatment with lymph node abscess incision, daily rinsing of the abscess cavity, and orally administered antibiotic therapy with doxycycline could cure our patient completely without any remaining complications. CONCLUSION: In patients with cervical lymph node swelling caused by infection it is indispensable to perform specific identification of the pathogen for further local and specific antibiotic treatment. Possible infections with atypical bacteria like Francisella tularensis should never be ignored. Universal polymerase chain reactions are a suitable method for early detection of such rare pathogens.


Asunto(s)
Absceso/etiología , Linfadenopatía/etiología , Tularemia/complicaciones , Absceso/patología , Absceso/terapia , Anciano , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Drenaje/métodos , Femenino , Francisella tularensis/aislamiento & purificación , Humanos , Linfadenopatía/diagnóstico , Linfadenopatía/patología , Linfadenopatía/terapia , Cuello , Tomografía Computarizada por Rayos X , Extracción Dental , Tularemia/diagnóstico
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 3927-3930, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31946731

RESUMEN

The next generation of flexible, electrically active implants, such as brain implants or retina chips require a flexible, biostable as well as biocompatible passivation, ensuring a degradation-free usage for long time periods on the order of several years. Until today, these passivations are prepared mostly by polyimides or parylene, both of which are water vapor permeable to a certain degree. To remedy this deficiency, Atomic Layer Deposited (ALD) thin films are characterized regarding their electrical passivating features under conditions of accelerated aging, such as elevated temperatures in a liquid environment. The initial electrical passivation by various ALD deposited multilayers, combining alternating thin Al2O3 and TiO2 layers is the goal of this research as well as the stability of these layers under induced degradation. Such layers, in combination with a parylene passivation, would ensure a water vapor impermeable and biocompatible coating.


Asunto(s)
Óxido de Aluminio , Materiales Biocompatibles Revestidos , Prótesis e Implantes , Electricidad
9.
Diabetes Metab ; 45(2): 175-183, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-29706470

RESUMEN

AIM: To describe current practices of glucose-lowering treatments in people with diabetes and chronic kidney disease (CKD), the associated glucose control and hypoglycaemic symptoms, with an emphasis on sex differences. METHODS: Among the 3033 patients with CKD stages 3-5 recruited into the French CKD-REIN study, 645 men and 288 women had type 2 diabetes and were treated by glucose-lowering drugs. RESULTS: Overall, 31% were treated only with insulin, 28% with combinations of insulin and another drug, 42% with non-insulin glucose-lowering drugs. In CKD stage 3, 40% of patients used metformin, 12% at stages 4&5, similar for men and women; in CKD stage 3, 53% used insulin, similar for men and women, but at stages 4&5, 59% of men and 77% of women used insulin. Patients were reasonably well controlled, with a median HbA1c of 7.1% (54mmol/mol) in men, 7.4% (57mmol/mol) in women (P=0.0003). Hypoglycaemic symptoms were reported by 40% of men and 59% of women; they were not associated with the estimated glomerular filtration rate, nor with albuminuria or with HbA1c in multivariable analyses, but they were more frequent in people treated with insulin, particularly with fast-acting and pre-mixed insulins. CONCLUSION: Glucose-lowering treatment, HbA1c and hypoglycaemic symptoms were sex dependent. Metformin use was similar in men and women, but unexpectedly low in CKD stage 3; its use could be encouraged rather than resorting to insulin. Hypoglycaemic symptoms were frequent and need to be more closely monitored, with appropriate patient-education, especially in women.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemiantes/clasificación , Hipoglucemiantes/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/epidemiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/estadística & datos numéricos , Femenino , Francia/epidemiología , Humanos , Servicios de Información , Masculino , Insuficiencia Renal Crónica/complicaciones , Factores Sexuales
10.
Mol Psychiatry ; 23(3): 533-543, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28696432

RESUMEN

Single-nucleotide polymorphisms (SNPs) in CACNA1C, the α1C subunit of the voltage-gated L-type calcium channel Cav1.2, rank among the most consistent and replicable genetics findings in psychiatry and have been associated with schizophrenia, bipolar disorder and major depression. However, genetic variants of complex diseases often only confer a marginal increase in disease risk, which is additionally influenced by the environment. Here we show that embryonic deletion of Cacna1c in forebrain glutamatergic neurons promotes the manifestation of endophenotypes related to psychiatric disorders including cognitive decline, impaired synaptic plasticity, reduced sociability, hyperactivity and increased anxiety. Additional analyses revealed that depletion of Cacna1c during embryonic development also increases the susceptibility to chronic stress, which suggest that Cav1.2 interacts with the environment to shape disease vulnerability. Remarkably, this was not observed when Cacna1c was deleted in glutamatergic neurons during adulthood, where the later deletion even improved cognitive flexibility, strengthened synaptic plasticity and induced stress resilience. In a parallel gene × environment design in humans, we additionally demonstrate that SNPs in CACNA1C significantly interact with adverse life events to alter the risk to develop symptoms of psychiatric disorders. Overall, our results further validate Cacna1c as a cross-disorder risk gene in mice and humans, and additionally suggest a differential role for Cav1.2 during development and adulthood in shaping cognition, sociability, emotional behavior and stress susceptibility. This may prompt the consideration for pharmacological manipulation of Cav1.2 in neuropsychiatric disorders with developmental and/or stress-related origins.


Asunto(s)
Canales de Calcio Tipo L/genética , Canales de Calcio Tipo L/fisiología , Trastornos Mentales/genética , Adulto , Negro o Afroamericano , Animales , Trastorno Bipolar/genética , Canales de Calcio/genética , Trastorno Depresivo Mayor/genética , Modelos Animales de Enfermedad , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Humanos , Masculino , Ratones/embriología , Ratones Transgénicos/genética , Neuronas/metabolismo , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética
11.
Head Face Med ; 13(1): 19, 2017 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-29116013

RESUMEN

BACKGROUND: Orthognathic surgery is associated with considerable swelling and neurosensory disturbances. Serious swelling can lead to great physical and psychological strain. A randomized, prospective, controlled clinical trial was realized in order to evaluate the effect of a preoperative intravenous dexamethasone injection of 40 mg on postoperative swelling and neurosensory disturbances after orthognathic surgery. METHODS: Thirty-eight patients (27 male and 11 female) patients, all with the indication for an orthognathic surgery, were enrolled in this study (mean age: 27.63 years, range: 16-61 years) and randomly divided into two groups (study group/ control group). Both groups underwent either maxillary and/or mandibular osteotomies, resulting in three subgroups according to surgical technique (A: LeFort I osteotomy, B: bilateral sagittal split osteotomy (BSSO), C: bimaxillary osteotomy). The study group received a single preoperative intravenous injection of 40 mg dexamethasone. Facial edema was measured by 3D surface scans on the 1st, 2nd, 5th, 14th and 90th postoperative day. Furthermore, neurosensory disturbances on the 2nd, 5th, 14th and 90th postoperative day were investigated by thermal stimulation. RESULTS: Facial edema after LeFort I osteotomy, BSSO and bimaxillary osteotomy showed a significant decrease in the study group compared to the control group (P = 0.048, P = 0.045, P < 0.001). The influence of dexamethasone on neurosensory disturbances was not significant for the inferior alveolar nerve (P = 0.746) or the infraorbital nerve (P = 0.465). CONCLUSIONS: Patients undergoing orthognathic surgery should receive a preoperative injection of dexamethasone in order to control and reduce edema. However, there was no influence of dexamethasone on reduction of neurosensory disturbances. TRIAL REGISTRATION: DRKS00009033 .


Asunto(s)
Dexametasona/administración & dosificación , Edema/prevención & control , Procedimientos Quirúrgicos Ortognáticos/efectos adversos , Osteotomía Sagital de Rama Mandibular/efectos adversos , Trastornos Somatosensoriales/prevención & control , Adolescente , Adulto , Edema/etiología , Femenino , Estudios de Seguimiento , Alemania , Humanos , Hiperalgesia/etiología , Hiperalgesia/prevención & control , Inyecciones Intravenosas , Masculino , Maxilar/cirugía , Persona de Mediana Edad , Procedimientos Quirúrgicos Ortognáticos/métodos , Osteotomía Sagital de Rama Mandibular/métodos , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo , Umbral Sensorial , Trastornos Somatosensoriales/etiología , Resultado del Tratamiento , Adulto Joven
12.
Support Care Cancer ; 25(11): 3425-3435, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28597252

RESUMEN

PURPOSE: The study's purpose was to develop practical guidelines for assessment and management of refusal of treatment by adults afflicted with cancer. METHODS: The French Association for Supportive Care in Cancer and the French Society for Psycho-oncology gathered a task force that applied a consensus methodology to draft guidelines studied predisposing situations, the diagnosis, regulatory aspects, and the management of refusal of treatment by adults afflicted with cancer. RESULTS: We propose five guidelines: (1) be aware of the conditions/profiles of patients most often associated with refusal of treatment so as to adequately underpin the care and support measures; (2) understand the complexity of the process of refusal and knowing how to accurately identify the type and the modalities of the refused treatments; (3) apply a way to systematically analyze refusal, thereby promoting progression from a situation of disaccord toward a consensual decision; (4) devise procedures, according to the legal context, to address refusal of treatment that safeguards the stakeholders in situations of sustained disaccord; and (5) know the indications for ethical collective decision-making. CONCLUSION: The quality of the relationship between patients and health professionals, and the communication between them are essential components involved in reaching a point of consent or refusal of treatment. A process of systematic analysis of refusal is recommended as the only way to ensure that all of the physiological, psychological, and contextual elements that are potentially involved are taken into account.


Asunto(s)
Directrices para la Planificación en Salud , Neoplasias/terapia , Psicooncología/métodos , Negativa del Paciente al Tratamiento/psicología , Adulto , Francia , Humanos , Psicooncología/normas , Adulto Joven
13.
Ann Oncol ; 28(2): 386-392, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28426102

RESUMEN

Background: Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking. Patients and methods: We evaluated infection-related complications that were grade ≥3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period. Results: Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n = 389), followed by ear (n = 151), bloodstream (n = 147), and gastrointestinal tract (n = 145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n = 4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1-9.9 years at diagnosis was associated with febrile neutropenia (P = 0.002) during induction and febrile neutropenia and documented infection (both P < 0.001) during later continuation. White race was associated with documented infection (P = 0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P < 0.001) and documented infections (P = 0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P < 0.001). Conclusions: The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/mortalidad , Neutropenia Febril Inducida por Quimioterapia/terapia , Niño , Preescolar , Dexametasona/administración & dosificación , Femenino , Humanos , Lactante , Recuento de Leucocitos , Masculino , Neutrófilos/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Infecciones del Sistema Respiratorio/inducido químicamente , Infecciones del Sistema Respiratorio/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Vincristina/administración & dosificación
14.
Clin Pharmacol Ther ; 101(3): 373-381, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27564568

RESUMEN

We performed a genomewide association study (GWAS) of primary erythrocyte thiopurine S-methyltransferase (TPMT) activity in children with leukemia (n = 1,026). Adjusting for age and ancestry, TPMT was the only gene that reached genomewide significance (top hit rs1142345 or 719A>G; P = 8.6 × 10-61 ). Additional genetic variants (in addition to the three single-nucleotide polymorphisms [SNPs], rs1800462, rs1800460, and rs1142345, defining TPMT clinical genotype) did not significantly improve classification accuracy for TPMT phenotype. Clinical mercaptopurine tolerability in 839 patients was related to TPMT clinical genotype (P = 2.4 × 10-11 ). Using 177 lymphoblastoid cell lines (LCLs), there were 251 SNPs ranked higher than the top TPMT SNP (rs1142345; P = 6.8 × 10-5 ), revealing a limitation of LCLs for pharmacogenomic discovery. In a GWAS, TPMT activity in patients behaves as a monogenic trait, further bolstering the utility of TPMT genetic testing in the clinic.


Asunto(s)
Antimetabolitos Antineoplásicos/farmacocinética , Leucemia/tratamiento farmacológico , Mercaptopurina/farmacocinética , Metiltransferasas/genética , Antimetabolitos Antineoplásicos/administración & dosificación , Niño , Relación Dosis-Respuesta a Droga , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Mercaptopurina/administración & dosificación , Farmacogenética , Polimorfismo de Nucleótido Simple
15.
Osteoporos Int ; 28(3): 909-915, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27900426

RESUMEN

We evaluated the influence of degenerative disease and fractured vertebra on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) in 1500 women aged 50-80 years. TBS was not affected by a degenerative disease. While BMD increases after 62.5 years, TBS continues to decline. TBS should play a leading role in lumbar spine evaluation. INTRODUCTION: After menopause, lumbar spine (LS) BMD and TBS values decrease. Degenerative disease (DD) increases with age and affect LS BMD. The aim of this study was to measure changes in LS BMD and TBS in women 50 to 80 years old, taking into account the impact of fractured vertebrae and DD. METHODS: LS BMD, TBS, and vertebral fracture assessment were evaluated in the OsteoLaus cohort (1500 women, 50-80 years old). The exams were analyzed following ISCD guidelines to identify vertebrae with fractures or DD (Vex). RESULTS: 1443 women were enrolled: mean age 66.7 ± 11.7 years, BMI 25.7 ± 4.4. LS BMD and TBS were weakly correlated (r2 = 0.16). The correlation (Vex excluded) between age and BMD was +0.03, between age and TBS -0.34. According to age group, LS BMD was 1.2 to 3.2% higher before excluding Vex (p < 0.001). TBS had an insignificant change of <1% after excluding Vex. LS BMD (Vex) decreased by 4.6% between 52.5 and 62.5 years, and increased by 2.6% between 62.5 and 77.5 years. TBS (Vex excluded) values decreased steadily with age with an overall loss of 8.99% between 52.5 and 77.5 years. Spine TBS, femoral neck, and total hip BMD gradually decreased with age, reaching one SD between the oldest and youngest group. CONCLUSIONS: TBS is not affected by DD. While BMD increases after 62.5 years, TBS continues to decline. For lumbar spine evaluation, in view of its independence from DD, TBS should play a leading role in the diagnosis in complement to BMD.


Asunto(s)
Densidad Ósea/fisiología , Hueso Esponjoso/fisiopatología , Vértebras Lumbares/fisiopatología , Osteoporosis Posmenopáusica/fisiopatología , Enfermedades de la Columna Vertebral/fisiopatología , Absorciometría de Fotón , Distribución por Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Cuello Femoral/fisiopatología , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/diagnóstico , Fracturas Osteoporóticas/diagnóstico , Fracturas Osteoporóticas/fisiopatología , Fracturas de la Columna Vertebral/fisiopatología
16.
J Biomed Nanotechnol ; 12(7): 1527-43, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-29337492

RESUMEN

The induction of effective T cell-mediated immune responses is the main objective of vaccination against cancer. T cell responses are initiated by dendritic cells (DCs) as the most potent antigen-presenting cells. Designing vaccines for efficient delivery of tumor antigens to these cells in immunogenic fashion is, therefore, a major task in tumor immunology. In this human-based in vitro study we investigated the suitability of different polymeric nanoparticles (NPs) for delivering the tumor-associated antigen Her2/neu to DCs for induction of T cell responses by mucosal vaccination. The natural polymer chitosan and novel functionalized PLGA-based polymers were used for NP production. All NPs were efficiently taken up by DCs. Her2/neu delivered by NPs was more efficiently processed and presented by DCs than the soluble protein and induced more vigorous CD4+ and CD8+ T cell proliferation, and cytotoxic T cells. Testing the suitability of this platform for mucosal vaccination, NPs were applied to the apical side of an intestinal epithelium model and found to be efficiently transported across the epithelial layer to become available to basolateral DCs. Thus, chitosan and PLGA-based NPs are efficient carriers for delivery of antigens to DCs for induction of T cell-based immunity, and suitable for mucosal vaccine formulations.


Asunto(s)
Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Células Dendríticas/inmunología , Inmunidad Mucosa/inmunología , Nanopartículas/química , Antígenos de Neoplasias/química , Células CACO-2 , Vacunas contra el Cáncer/química , Células Cultivadas , Quitosano/química , Portadores de Fármacos/química , Humanos , Receptor ErbB-2/química , Receptor ErbB-2/inmunología , Linfocitos T/inmunología
17.
Int J Oral Maxillofac Surg ; 44(12): 1468-73, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26265065

RESUMEN

Communication between the surgeon and the radiation oncologist is improved with the use of virtual models of the final tumour resection, combining three-dimensional imaging and conventional clip marking with computer-aided navigation. This investigation was designed to determine the deviation of virtual marking procedures compared to conventional marking by titanium ligature clips in oral cancer with different localizations. Seventeen patients with surgically placed clips and virtual landmarks on the resection margin after complete tumour ablation were evaluated. To determine whether the virtual landmarks remain predictive of the resection margin, the deviation of the virtual points from their corresponding clips was analyzed by measuring the distance between their centres of gravity. In total, 189 clips were evaluated. Metric analyses of the deviation between the virtual points and clips showed a deviation of 2.3 ± 0.6mm for tumours with a maxilla localization, 7.2 ± 2.5mm for tumours with a mandible localization, and 12.6 ± 3.8mm for tumours with a tongue localization. A significant statistical relationship was demonstrated in the virtual point-clip deviation as a function of tumour localization. Virtual marking of maxillary tumour resection margins allows accurate definition of the former tumour bed and could lead to novel adjuvant treatment strategies.


Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Planificación de la Radioterapia Asistida por Computador , Cirugía Asistida por Computador , Instrumentos Quirúrgicos , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Marcadores Fiduciales , Humanos , Masculino , Persona de Mediana Edad , Titanio , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
18.
J Craniomaxillofac Surg ; 43(7): 1309-13, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26116970

RESUMEN

OBJECTIVE: Little information is available as to whether recurrences of oral squamous cell carcinoma (OSCC) show different histopathological grades than the primary tumor and whether postoperative radiotherapy (PORT) influences the grade of differentiation in the case of recurrence. The objective of this study was the evaluation of recurrence rates and change in differentiation. MATERIAL AND METHODS: This retrospective, single-institution cohort study included surgically treated OSCC patients over a 13-year period (2000-2013). The relationship among tumor size, lymph node metastases, and recurrence rate of OSCC was investigated. Primary tumor differentiation was compared with differentiation of recurrence. RESULTS: A total of 429 patients (277 men and 152 women) were included in this study. Of these, 124 (28.9%) received PORT. The incidence of primary cervical metastases increased significantly with tumor size (p < 0.001). Recurrence developed in 82 patients (19.1%). Stage T1/T2 showed a significantly lower recurrence rate than stage T3/T4 (16.3% vs. 30.2%) (p < 0.01). A total of 23 (30.7%) patients with recurrence showed a change in differentiation. CONCLUSION: Increasing primary tumor size correlates with incidence of cervical metastases and recurrence rate. Initial cervical metastases show no effect on recurrence rates. Differentiation of primary tumor does not correlate with the recurrence rate. The majority of recurrences show consistent histopathological grading.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Adulto , Anciano , Anciano de 80 o más Años , Diferenciación Celular , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Adulto Joven
19.
J Craniomaxillofac Surg ; 43(7): 1284-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26116971

RESUMEN

INTRODUCTION: Cone-Beam Computed Tomography (CBCT) has become widely used in dentistry and maxillofacial surgery. Accuracy, sensitivity and specificity of thin bony structures below 0.5 mm have been subject of some in vitro studies. This prospective in vivo study investigates the correlation between preoperative CBCT-imaging and intraoperative clinical examination of thin bony structures. We hereby present results from daily clinical routine. METHODS: A total number of 80 sites in 64 patients has been examined to differentiate between preoperative 3D imaging and clinical measurements on cystic lesions in maxilla and mandible. Different CBCT-devices with a voxel size ranging from 0.08 mm to 0.4 mm were used. RESULTS: Overall-specificity found for detecting thin bony structures of the human jaw is 13.89%, overall sensitivity is 100%, positive predictive value (PPV) is 58.67% and negative predictive value (NPV) is 100%. DISCUSSION: Image quality is the key to make use of additional information CBCT provides and depends on spatial, temporal and contrast resolution. CBCT does not depict reliably thin bony structures of the jaw, even if high voxel resolution is used. CONCLUSION: In selected cases using high resolution protocols should be considered despite affecting the patient with higher doses of radiation.


Asunto(s)
Tomografía Computarizada de Haz Cónico/métodos , Cirugía Bucal/métodos , Femenino , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y Especificidad
20.
J Craniomaxillofac Surg ; 43(5): 705-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25937474

RESUMEN

OBJECTIVE: The present study evaluates the morbidity after iliac crest harvesting from the anterior iliac rim for oral onlay grafting and identifies influential factors. MATERIAL AND METHODS: Twenty partially edentulous or edentulous patients (15 females and 5 males) with a mean age of 54.25 years (range 20-78 years, SD 13.86 years, remaining bone height <5 mm of the alveolar ridge) underwent iliac onlay bone grafting. The postoperative clinical morbidity was classified in minor and major complications and was evaluated with respect to body mass index (BMI). RESULTS: The grafting procedure was successfully performed in all patients with a mean BMI of 23.34 (range 18-29, SD 3.36). A significant difference between BMI and walking aid necessity (p = 0.018) was demonstrated, but no difference between BMI and hip pain, duration of disturbance, gait disturbance, complication rate, and sensory loss was identified (p > 0.05). Between hip pain and scar length, age and hip/jaw pain did not demonstrate a significant difference (p > 0.05). Postoperative complications were minor and consisted of hematoma, seroma, and transient sensory disturbance. CONCLUSION: Patients undergoing bone harvest from the anterior superior iliac crest with oral grafting show a low minor complication rate and a high overall satisfaction of 95%.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Trasplante Óseo/métodos , Ilion/cirugía , Complicaciones Posoperatorias , Recolección de Tejidos y Órganos/métodos , Sitio Donante de Trasplante/cirugía , Adulto , Anciano , Índice de Masa Corporal , Cicatriz/etiología , Femenino , Estudios de Seguimiento , Ataxia de la Marcha/etiología , Hematoma/etiología , Humanos , Arcada Edéntula/cirugía , Arcada Parcialmente Edéntula/cirugía , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Dolor Postoperatorio/etiología , Satisfacción del Paciente , Estudios Prospectivos , Seroma/etiología , Recolección de Tejidos y Órganos/efectos adversos , Caminata/fisiología , Adulto Joven
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