RESUMEN
The impact of oral pathogens onto the generation and variability of oral tumors has only recently been investigated. To get further insights, oral cancer cells were treated with pathogens and additionally, as a result of this bacterial cellular infection, with human defensins, which are as anti-microbial peptide members of the innate immune system. After cell stimulation, proliferation behavior, expression analysis of oncogenic relevant defensin genes, and effects on EGFR signaling were investigated. The expression of oncogenic relevant anti-microbial peptides was analyzed with real-time PCR and immunohistochemistry. Cell culture experiments were performed to examine cellular impacts caused by stimulation, i.e., altered gene expression, proliferation rate, and EGF receptor-dependent signaling. Incubation of oral tumor cells with an oral pathogen (Porphyromonas gingivalis) and human α-defensins led to an increase in cell proliferation. In contrast, another oral bacterium used, Aggregatibacter actinomycetemcomitans, enhanced cell death. The bacteria and anti-microbial peptides exhibited diverse effects on the transcript levels of oncogenic relevant defensin genes and epidermal growth factor receptor signaling. These two oral pathogens exhibited opposite primary effects on the proliferation behavior of oral tumor cells. Nevertheless, both microbe species led to similar secondary impacts on the proliferation rate by modifying expression levels of oncogenic relevant α-defensin genes. In this respect, oral pathogens exerted multiplying effects on tumor cell proliferation. Additionally, human defensins were shown to differently influence epidermal growth factor receptor signaling, supporting the hypothesis that these anti-microbial peptides serve as ligands of EGFR, thus modifying the proliferation behavior of oral tumor cells.
Asunto(s)
Aggregatibacter actinomycetemcomitans/crecimiento & desarrollo , Proliferación Celular/efectos de los fármacos , Defensinas/farmacología , Encía/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de la Boca/patología , Porphyromonas gingivalis/crecimiento & desarrollo , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Secuencia de Aminoácidos , Antiinfecciosos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/microbiología , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Encía/efectos de los fármacos , Encía/metabolismo , Encía/microbiología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/microbiología , Humanos , Técnicas para Inmunoenzimas , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/genética , Neoplasias de la Boca/microbiología , Invasividad Neoplásica , Estadificación de Neoplasias , Porphyromonas gingivalis/efectos de los fármacos , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Transducción de Señal/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
INTRODUCTION: Focal pressure-related changes in brain perfusion and metabolism are discussed in single-suture craniosynostosis and brachycephalic cases (bicoronal synostosis). Raised intracranial pressure levels could be measured in some cases. In order to find possible loco-regional brain tissue changes during plastic surgery, we investigated oxygenation and perfusion parameters using non-invasive near-infrared spectroscopy (NIRS) probes. METHODS: Twenty-two consecutively operated cases (mean age 7 months) with single-suture craniosynostosis were prospectively investigated using a NIRS probe (LEA(©), O2C, white light 500-800 nm, laser NIR). Measurements for oxygen saturation (SO(2)), relative quantity of hemoglobin (rHb), blood flow, and blood flow velocity of the bilateral frontal, temporal, and parietal cortices were taken transosseously (prior to decompression) and epidurally directly after decompression as well as 15 and 30 min after decompression and before closure. RESULTS: Twenty-two patients with scaphocephaly (11), trigonocephaly (6), anterior plagiocephaly (3), and brachycephaly (2) were investigated. SO(2) was improving in all patient subgroups, showing the highest levels in the fronto-temporal region; rHb improved in scaphocephalic, trigonocephalic, and brachycephalic children. Again, the highest values were found not only in the temporal but also in the frontal region and in brachycephalic patients also in the parietal cortex. CONCLUSION: These preliminary results of a new technology for brain tissue oxygenation and blood flow measurements suggest a regional compromise of cortical metabolism and circulation in patients with craniosynostosis.
Asunto(s)
Corteza Cerebral/metabolismo , Craneosinostosis/patología , Craneosinostosis/cirugía , Hemodinámica , Oxihemoglobinas/metabolismo , Procedimientos de Cirugía Plástica/métodos , Circulación Cerebrovascular/fisiología , Craneosinostosis/clasificación , Femenino , Humanos , Lactante , Masculino , Espectroscopía Infrarroja CortaRESUMEN
Purpose of this study was to investigate whether human ß-defensins (hBDs) affect maturation and proliferation of osteoblast-like MG63 cells in vitro. Osteoblast-like MG63 cells were stimulated with hBD-1, -2, and -3 under control conditions and with hBD-2 during experimental inflammation (induced by interleukin-1ß, tumor necrosis factor-α, toll-like receptor-2 and -4 agonists). Expression of different osteogenic markers and hBDs were analyzed by real-time PCR, immunohistochemistry, and enzyme-linked immunosorbent assay. In addition, alkaline phosphatase (ALP) enzyme activity and biomineralization as markers for differentiation were monitored. All tested hBDs were expressed on mRNA and protein level in MG63 cells. Only stimulation with hBD-2 elevated the proliferation rate. hBD-2 and hBD-3 positively affected the differentiation of osteoblast-like cells provided by increased transcript levels of osteogenic markers, up-regulated ALP enzyme activity and enhanced mineralized nodule formation. All pro-inflammatory stimuli enhanced interleukin-6 and hBD-2 expression and down-regulated markers of osteoblastic differentiation. In accordance, inflammation increased transcript level of Notch-1 (an inhibitor of osteoblastic differentiation). hBD-2 was not able to revert effects of inflammation on differentiation. In bone cells human ß-defensins exhibit further functions than antimicrobial peptide activity. These include stimulation of proliferation and differentiation. Differentiation arrest due to inflammation could not be overcome by hBD-2 alone.
Asunto(s)
Proteína Morfogenética Ósea 2/fisiología , Proteína Morfogenética Ósea 4/fisiología , Calcificación Fisiológica/fisiología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/fisiología , Osteoblastos/citología , Osteoblastos/fisiología , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/fisiología , Proteína Morfogenética Ósea 2/genética , Proteína Morfogenética Ósea 4/genética , Diferenciación Celular/fisiología , Línea Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Humanos , Osteoblastos/metabolismo , Osteogénesis/genética , Osteogénesis/fisiología , beta-Defensinas/genética , beta-Defensinas/metabolismo , beta-Defensinas/fisiologíaRESUMEN
This study investigated the IGF-1-influence on oncological relevant genes in pleomorphic adenomas. Therefore A64-tumor cells were stimulated by recombinant IGF-1. After RNA-extraction, transcript levels of hBD-1, hBD-2, hBD-3, DEFA1/3, DEFA4, S100A4, Psoriasin, DOC-1, EGF, EGFR, and IGFR were analyzed by qRT-PCR at t = 0, 4, 8, 24, 48, and 72 hr. The gene-products were visualized by immunostaining. A64-tumor-cells were deficient for hBD-1 and IGF-1. IGF-1 downregulates hBD-2 and hBD-3 without influencing hBD-1-expression. IGF-1 only slightly affects DEFA1/3-, DEFA4-, S100A4-, Psoriasin-, DOC-1-, EGF-, EGFR-, and IGFR-gene-expression. IGF-1-deficiency combined with low basic hBD-2-gene-expression and hBD-3-gene-expression might counteract, whereas hBD-1-deficiency promotes malignant transformation in pleomorphic adenomas.
Asunto(s)
Adenoma Pleomórfico/genética , Transformación Celular Neoplásica/genética , Factor I del Crecimiento Similar a la Insulina/deficiencia , Neoplasias de las Glándulas Salivales/genética , beta-Defensinas/genética , Adenoma Pleomórfico/metabolismo , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Transformación Celular Neoplásica/metabolismo , Expresión Génica , Humanos , Inmunohistoquímica , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacología , Neoplasias de las Glándulas Salivales/metabolismo , beta-Defensinas/biosíntesis , beta-Defensinas/metabolismoRESUMEN
BACKGROUND: Most local oral vaccine strategies use the sublingual region for drug application. Only little is known about the cytokine micromilieu, the nature of T cell subtypes and expression of target structures for adjuvants at different oral mucosal regions (OMR). However, targeting the optimal OMR might ensure highest efficiency of drug uptake and lowest risk for adverse effects. METHODS: Expression of TGF-ß1, IL10 as well as Th1, Th2 and Th17 cytokines and transcription factors was investigated at different OMR and skin by quantitative real-time PCR, immunohistochemistry or flow cytometry. RESULTS: Highest number of T cells was located in vestibular/buccal region (VBR). In contrast to skin (SK), OMR T cells produced TGF-ß1, IL-10, IFN-γ and IL-17. Significantly higher TGF-ß1 mRNA expression in the VBR compared with the sublingual region (SLR) and skin could be detected, while equal transcripts of IL-10 and regulatory T cell-associated transcription factor FoxP3 could be demonstrated. Expression of Th17-associated IL-17A, IL-17F, IL-22 and IL-26 mRNA could be demonstrated in VBR and SLR but not in SK. Interestingly, compared to SK, significantly higher expression of TGF-ß1 and IFN-γ could be detected in OMR. Moreover, expression of toll-like receptor (TLR) 2 and TLR4 was highest in VBR with significant expression on dendritic cells in OMR. CONCLUSION: From this data, we conclude that (i) VBR and SLR represent a protolerogenic micromilieu, (ii) both regions form a Th1 cytokine-predominated microenvironment, but also express mRNA for Th17 cytokines and (iii) TLRs detectable in VBR and SLR might serve as a target structures for adjuvants.
Asunto(s)
Citocinas/inmunología , Células Dendríticas/inmunología , Inmunidad Mucosa/inmunología , Mucosa Bucal/inmunología , Subgrupos de Linfocitos T/inmunología , Anciano , Separación Celular , Células Dendríticas/citología , Femenino , Citometría de Flujo , Humanos , Tolerancia Inmunológica , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mucosa Bucal/citología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Subgrupos de Linfocitos T/citología , Células TH1/citología , Células TH1/inmunología , Células Th17/citología , Células Th17/inmunología , Receptor Toll-Like 2/biosíntesis , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 4/biosíntesis , Receptor Toll-Like 4/inmunologíaRESUMEN
OBJECTIVE: To analyze the prenatal ultrasound findings of the craniofacial and extracephalic anatomy, the postnatal pathological findings, and the genetic anomalies in 51 cases of holoprosencephaly (HPE). MATERIALS AND METHODS: Between 1990 and 2005, a collective of 51 fetuses with tentative ultrasound diagnosis of HPE was recruited at two tertiary referral centers for prenatal ultrasound diagnostics via the Pia Fetal Database (GEMedical Systems, Webling, Germany). Cephalic as well as extracephalic anomalies were investigated, and all cases were subdivided into the subgroups lobar, a lobar, and semilobar HPE. In addition to the ultrasound investigation, 45 fetuses were analyzed for genetic anomalies and 21 fetuses underwent an autopsy. RESULTS: The average age at diagnosis was 21.9 weeks of gestation. There was a greater number of female fetuses, with an overall ratio of 2.67:1. In 61% of all cases, there was a reduction of growth in comparison with healthy fetuses of the same age. Within the second trimenon, the cephalic anomalies became evident when investigating the diameter of the fetal head (second trimenon: 71%below the fifth percentile; third trimenon: 92% below the fifth percentile). In 82%of the cases, extracephalic anomalies were diagnosed additionally. In 63%, the diagnosis of holoprosencephaly led to a termination of pregnancy. Ten percent of the fetuses were born alive. In 81% of the cases, the diagnosis of HPE was confirmed postnatally. The remaining 19% showed other severe cephalic and extracephalic anomalies. Chromosomal anomalies were detected in 79% of the fetuses, most frequently trisomy 13 (59%). DISCUSSION: Because of recent advances in the development and improvement of high-resolution ultrasound, early diagnosis of congenital anomalies such as HPE is now possible. In this study, which represents the largest collection of prenatally diagnosed HPE reported in the literature to date, the average age at diagnosis was earlier than in other studies. The ultrasound devices of today provide excellent images of the fetus that allow an exact diagnosis of craniomaxillofacial anomalies as well as extracephalic anomalies. Apart from a very few cases, the diagnosis of HPE is incompatible with life.
Asunto(s)
Holoprosencefalia/diagnóstico por imagen , Ultrasonografía Prenatal , Adolescente , Adulto , Trastornos de los Cromosomas/diagnóstico por imagen , Trastornos de los Cromosomas/genética , Anomalías Congénitas/diagnóstico por imagen , Anomalías Congénitas/genética , Anomalías Craneofaciales/diagnóstico por imagen , Anomalías Craneofaciales/genética , Femenino , Alemania , Holoprosencefalia/genética , Humanos , Recién Nacido , Cariotipificación , Masculino , Embarazo , Segundo Trimestre del Embarazo , Adulto JovenRESUMEN
OBJECTIVE: To determine the relationship between trisomies 13, 18, and 21 and craniofacial malformations detected by prenatal sonography. DESIGN: During a 29-year period (1976 through 2004), prenatal sonographic findings of 69 fetuses with trisomy 13; 171 fetuses with trisomy 18; 302 fetuses with trisomy 21; and 17 fetuses with other trisomies were evaluated retrospectively, after fetal karyotype identification. Sonographic findings were compared with autopsy results in 209 patients (trisomy 13, n=39; trisomy 18, n=64; and trisomy 21, n=106). RESULTS: For trisomy 13, cleft deformities were detected prenatally in 65.2%, and of the 39 cases with pathological information, 76.9% were found to have a cleft deformity. Ocular and orbital abnormalities were found in 28%. Malformations of the jaws and abnormal profiles were more frequently diagnosed postnatally than prenatally. For trisomy 18, abnormal profiles (41.5%) and ear abnormalities (5.3%) were the most noticeable ultrasound markers, next to abnormalities of the neurocranium (36.8%) and cranial bone configuration (21.6%). Dysmorphisms of the eye, ear, or nose were detected more frequently in autopsy cases. For trisomy 21, ultrasound showed an aberrant shape of the skull in 14.2% of fetuses. In general, the ocular-orbital and nasal abnormalities in fetuses with trisomy 18 or 21 were more evident in pathological examination than in prenatal ultrasound imaging. CONCLUSIONS: Facial anomalies are common in the major trisomies, and their prenatal sonographic identification should be improved. The above-mentioned facial anomalies provide sufficient reason to consider performing cytogenic evaluation.
Asunto(s)
Cromosomas Humanos 13-15/genética , Cromosomas Humanos 16-18/genética , Cromosomas Humanos 21-22 e Y/genética , Anomalías Craneofaciales/diagnóstico por imagen , Anomalías Craneofaciales/genética , Anomalías Maxilofaciales/diagnóstico por imagen , Anomalías Maxilofaciales/genética , Trisomía/patología , Ultrasonografía Prenatal , Adulto , Amniocentesis , Autopsia , Cromosomas Humanos 13-15/diagnóstico por imagen , Cromosomas Humanos 16-18/diagnóstico por imagen , Cromosomas Humanos 21-22 e Y/diagnóstico por imagen , Anomalías Craneofaciales/patología , Femenino , Marcadores Genéticos , Edad Gestacional , Humanos , Recién Nacido , Cariotipificación , Masculino , Edad Materna , Anomalías Maxilofaciales/patología , Fenotipo , Estudios Retrospectivos , Cráneo/anomalíasRESUMEN
BACKGROUND: Whereas the antimicrobial peptides hBD-2 and -3 are related to inflammation, the constitutively expressed hBD-1 might function as 8p tumour suppressor gene and thus play a key role in control of transcription and induction of apoptosis in malignant epithelial tumours. Therefore this study was conducted to characterise proteins involved in cell cycle control and host defence in different benign and malignant salivary gland tumours in comparison with healthy salivary gland tissue. METHODS: 21 paraffin-embedded tissue samples of benign (n = 7), and malignant (n = 7) salivary gland tumours as well as healthy (n = 7) salivary glands were examined immunohistochemically for the expression of p53, bcl-2, and hBD-1, -2, -3. RESULTS: HBD-1 was distributed in the cytoplasm of healthy salivary glands and benign salivary gland tumours but seems to migrate into the nucleus of malignant salivary gland tumours. Pleomorphic adenomas showed cytoplasmic as well as weak nuclear hBD-1 staining. CONCLUSION: HBD-1, 2 and 3 are traceable in healthy salivary gland tissue as well as in benign and malignant salivary gland tumours. As hBD-1 is shifted from the cytoplasm to the nucleus in malignant salivary gland tumours, we hypothesize that it might play a role in the oncogenesis of these tumours. In pleomorphic adenomas hBD-1 might be connected to their biologic behaviour of recurrence and malignant transformation.
Asunto(s)
Núcleo Celular/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , beta-Defensinas/metabolismo , Adenoma Pleomórfico/metabolismo , Carcinoma Adenoide Quístico/metabolismo , Estudios de Casos y Controles , Citoplasma/metabolismo , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The aim of this study was to investigate the gene expression of human beta-defensin-1, -2, -3 (hBD-1, -2, -3), interleukin-1beta, tumour necrosis factor-alpha and cyclooxygenase-2 in oral squamous cell carcinoma (OSCC) compared to benign and premalignant lesions as well as healthy controls. Biopsies of healthy gingiva (n=5), irritation fibroma (n=5), leukoplakia (n=5) and OSCC (n=5) were obtained during routine surgical procedures. RNA was extracted according to standard protocols and transcripts of hBD-1, -2, -3, interleukin-1beta, tumour necrosis factor-alpha and cyclooxygenase-2 were analysed by real-time polymerase chain reaction. The expression of hBD-1 was reduced in all lesions (5-fold in irritation fibroma and 2.5-fold in leukoplakia), but most significantly (50-fold) in OSCC. hBD-1 appears to play a role in the development of OSCC. The loss of its function might contribute to the malignant progression of these tumours.
Asunto(s)
Antiinfecciosos/análisis , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , beta-Defensinas/análisis , Carcinoma de Células Escamosas/genética , Ciclooxigenasa 2/análisis , Progresión de la Enfermedad , Fibroma/genética , Fibroma/patología , Regulación Neoplásica de la Expresión Génica/genética , Encía/anatomía & histología , Humanos , Interleucina-1beta/análisis , Leucoplasia Bucal/genética , Leucoplasia Bucal/patología , Neoplasias de la Boca/genética , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/análisisRESUMEN
The present in vitro study examines molecular processes that are relevant during bone homeostasis after Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infection with a focus on the differentiation level of osteoblasts. Regenerative processes are often hindered by the recurrence of bacterial infections, which can ultimately provoke a severe destruction of bone tissue. To obtain more detailed insights into such a complex scenario, we have used undifferentiated MG63 osteoblast-like cells as an experimental paradigm to examine the impact of two oral pathogens, A. actinomycetemcomitans and P. gingivalis, on proliferation, cytotoxicity and osteogenic differentiation. Cell culture experiments were performed to analyze cellular behavior. The level of genes interfering with bone tissue integrity (matrix metalloproteinases and their tissue inhibitors) and osteogenic markers (alkaline phosphatase, Runx2, human ß-defensin-2) was compared in undifferentiated versus differentiated MG63 cells using real-time polymerase chain reaction. Functional activity of matrix metalloproteinases was quantified by zymography. Western blot analysis was used to verify the phosphorylation state of mitogen-activated protein kinases p38 and extracellular-signal-regulated kinases 1/2. When co-cultured with undifferentiated MG63 cells, oral pathogens provoked distinct cellular effects. Only A. actinomycetemcomitans reduced cell proliferation, increased cell death, and induced osteogenic differentiation. A comparison of matrix metalloproteinase network stability in the presence of oral pathogens revealed a partial sensitivity towards P. gingivalis but not A. actinomycetemcomitans. So, beside the proof of concept that MG63 cells co-cultured with oral pathogens can serve as an in vitro model for mimicking destructive and regenerative events after bacterial infections, our data indicate that double infections might counterbalance otherwise positive effects.
Asunto(s)
Aggregatibacter actinomycetemcomitans/patogenicidad , Diferenciación Celular , Osteoblastos/metabolismo , Osteoblastos/microbiología , Porphyromonas gingivalis/patogenicidad , Fosfatasa Alcalina/metabolismo , Técnicas de Cultivo de Célula , Muerte Celular , Proliferación Celular , Técnicas de Cocultivo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/fisiología , Humanos , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Osteogénesis/genética , Osteogénesis/fisiología , Inhibidores Tisulares de Metaloproteinasas/genética , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Células Tumorales Cultivadas , beta-Defensinas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The trans-sinusoidal maxillary distractor (TS-MD) was used to achieve maxillary advancement in three patients with repaired cleft lip and palate. After preoperative computer-aided planning of the distraction vectors, each TS-MD was bent on a stereolithographic model of the maxilla of the patient. The devices were intraoperatively positioned using a methyl-methacrylate template. After standard Le Fort I osteotomy the devices were intraorally activated. After distraction the devices remained in situ for 3 months as rigid internal fixation of the maxilla. All patients were successfully distracted according to protocol. Maxillary advancement was 12, 8 and 11 mm. In two patients, additional maxillary widening of 6 and 8 mm was achieved by choosing divergent distraction vectors. After distraction a clockwise rotation of the maxilla was observed in two patients. There was no relapse during the 3 months of consolidation and 12-month follow-up. The TS-MD allows not only distraction but also rigid internal fixation after distraction. It was easy to apply but difficult to remove. Owing to preoperative 3D planning of the distraction vectors, the results were predictable, but clockwise rotation of the maxilla during distraction should be considered in planning. The distractor did not interfere with function or social activities during distraction and retention periods. After removal it left no extraoral scars.
Asunto(s)
Fisura del Paladar/cirugía , Seno Maxilar/cirugía , Osteogénesis por Distracción/métodos , Osteotomía Le Fort/métodos , Adolescente , Adulto , Tornillos Óseos , Fisura del Paladar/diagnóstico por imagen , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Seno Maxilar/diagnóstico por imagen , Osteogénesis por Distracción/instrumentación , Osteotomía Le Fort/instrumentación , Planificación de Atención al Paciente , Radiografía , Resultado del TratamientoRESUMEN
PURPOSE: In order to evaluate complication rates of dentoalveolar surgery in patients with congenital bleeding disorders, a retrospective case-control study was performed. METHODS: A collective of patients with congenital bleeding disorders (n = 69), who received common oral surgery procedures in combination with intense perioperative monitoring and coagulation factor substitution at the University Hospital of Bonn between 1992 and 2011, was matched with patients without bleeding disorders by age, sex, and type of surgery. In addition to the rates of perioperative bleeding and other complications, the duration of surgery and the use of local hemostatic agents were compared between both cohorts. RESULTS: There were no significant differences between the two groups regarding the rate of postoperative bleeding (2.9 vs. 1.4%, patients with congenital bleeding disorders vs controls) and the rate of other complications (7.2 vs. 21.7%). Furthermore, no significant difference in operation time (54 min in patients with congenital bleeding disorders vs 45 min in controls) was observed. However, there was a significant difference (p < 0.001) regarding the use of local hemostatic measures, which were applied in all patients with hereditary bleeding disorders but in only one of the controls. All patients with bleeding disorders were inpatients, while all controls were treated in an outpatient setting. CONCLUSIONS: If adequate measures are taken, the complication rate following oral surgery in patients with hereditary bleeding disorders can be reduced to that of patients without bleeding disorders. However, these results are reached at significant costs due to coagulation factor replacement and inpatient treatment.
Asunto(s)
Trastornos de la Coagulación Sanguínea Heredados/complicaciones , Trastornos de la Coagulación Sanguínea Heredados/tratamiento farmacológico , Factores de Coagulación Sanguínea/administración & dosificación , Hemostasis Quirúrgica/métodos , Procedimientos Quirúrgicos Orales , Atención Perioperativa/métodos , Hemorragia Posoperatoria/prevención & control , Adolescente , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Niño , Preescolar , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Adulto JovenRESUMEN
AIMS: Stability of orthodontic miniscrew implants is prerequisite to their success and durability in orthodontic treatment. As investigations revealed a positive correlation of miniscrew stability to periimplant bone quality, it has been the aim of this study to analyze the bone structure of resection preparations of human mandibles histologically by investigating the samples according to age, gender and exposure to radiotherapy. METHODS: Inflammation- and tumor-free alveolar bone sections from human mandibles (n = 31) with previously diagnosed carcinoma, chronic osteomyelitis or cysts were analyzed histomorphologically and histomorphometrically as to the dimension of trabeculae in cancellous areas. Group A investigated the impact of a history of radiation therapy, group B of gender and group C contrasted biopsies from individuals aging under 60 or over 60 years. Statistics were performed using the Kruskal-Wallis-test. RESULTS: Radiation, gender and age did not significantly influence bone density. The mean bone density averaged 40.7 ± 15.0% of spongiosa for the total collective with a median age of 58.4 years ± 14.7 years. CONCLUSIONS: Our findings provide new information on bone quality, thus contributing to a more precise evaluation of the parameters affecting and those not affecting miniscrew implant stability. On the basis of these results, the formulation of clinical guidelines for risk assessment of therapeutic approaches in patients prior to insertion of orthodontic skeletal anchorage devices seems to be conceivable.
Asunto(s)
Huesos/efectos de la radiación , Implantes Dentales , Mandíbula/efectos de la radiación , Métodos de Anclaje en Ortodoncia/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Biopsia , Médula Ósea/anatomía & histología , Neoplasias Óseas/radioterapia , Tornillos Óseos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia/efectos adversos , Caracteres Sexuales , Adulto JovenRESUMEN
The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with "glioblastoma multiforme." We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as "short-term" for TTP of less than 6 months (n = 54), and "long-term" for TTP of more than 12 months (n = 52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastoma multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n = 7) or anaplastic oligoastrocytoma (WHO grade III, n = 2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only prognostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy.
Asunto(s)
Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Glioblastoma/mortalidad , Glioblastoma/patología , Adulto , Anciano , Errores Diagnósticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: The aim of this study was to investigate the expression pattern of oncogenes, antimicrobial peptides, and genes involved in inflammation in leukoplakia of the oral cavity compared with healthy gingiva. STUDY DESIGN: Biopsies of healthy gingiva (n=20) and leukoplakia (n=20), were obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of alpha-defensin (DEFA) 1/3, DEFA-4, S100-A7, deleted-in-oral-cancer (Doc) 1, interleukin (IL) 1beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF) alpha, cyclooxygenase (Cox) 2, epidermal growth factor (EGF), keratinocyte growth factor (KGF), transforming growth factor (TGF) beta1, TGF-alpha, collagen-IA1 (Col-1), and tenascin-c were analyzed by real-time reverse-transcription polymerase chain reaction. The proteins encoded by the different genes were visualized by immunostaining. RESULTS: Compared with healthy gingiva (set as 1), there was an increased gene expression of DEFA-4 (179.2-fold), S100-A7 (25.4-fold), EGF (24.8-fold), TGF-beta1 (25.2-fold), and tenascin-c (34.3-fold) in oral leukoplakia. The expression of IL-1beta and Doc-1 was decreased (0.01-fold and 0.2-fold, respectively). CONCLUSIONS: The combination of an increased expression of the antimicrobial peptide DEFA-4, the oncogene S100-A7, EGF, and tenascin-c, and a decreased Doc-1 expression in oral leukoplakia might characterize its potency of malignant transformation. Chronic inflammation seems not to be involved in the development of this lesion.
Asunto(s)
Transformación Celular Neoplásica/metabolismo , Perfilación de la Expresión Génica , Encía/metabolismo , Leucoplasia Bucal/metabolismo , Estudios de Casos y Controles , Diferenciación Celular/fisiología , Transformación Celular Neoplásica/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Factor de Crecimiento Epidérmico/genética , Factor de Crecimiento Epidérmico/metabolismo , Factor 7 de Crecimiento de Fibroblastos/genética , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Encía/inmunología , Humanos , Inmunohistoquímica , Interleucinas/genética , Interleucinas/metabolismo , Leucoplasia Bucal/inmunología , ARN/análisis , Valores de Referencia , Proteína A7 de Unión a Calcio de la Familia S100 , Proteínas S100/genética , Proteínas S100/metabolismo , Tenascina/genética , Tenascina/metabolismo , Factor de Crecimiento Transformador alfa/genética , Factor de Crecimiento Transformador alfa/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , alfa-Defensinas/genética , alfa-Defensinas/metabolismoRESUMEN
STUDY GOAL: As it is an unusual and infrequent clinical entity, hyperplasia of the coronoid process is often overlooked or diagnosed too late. The aim of this study was to characterize the morphology, etiology, and clinical picture of coronoid hyperplasia as well as to discuss its diagnosis and treatment. MATERIALS AND METHODS: All cases of histologically confirmed hyperplasia of the coronoid process treated in our center between 1995 and 2004 were analyzed. Patient data were evaluated with respect to age, gender, clinical symptoms, diagnostic work-up, and treatment. The extracted data were compared to those found in the literature. RESULTS: The study included 14 new cases and 101 cases already published: 96 with bilateral and 19 with unilateral hyperplasia. At the time of diagnosis, the subjects' mean age was 23.7 years. The patients in Bonn were all treated by coronoidectomy and appropriate physiotherapy. An improvement in mouth opening could be achieved in 86% of our patients. CONCLUSIONS: In comparison to the somewhat disappointing results of previously published studies with regard to mouth opening and mandibular mobility, our treatment concept seems to offer the possibility for improvement. Our study emphasizes the significance of three-dimensional CT techniques for diagnosis and surgical planning, the superiority of coronoidectomy over coronoidotomy, and the importance of dynamic physiotherapy to prevent postoperative scar formation.
Asunto(s)
Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Cóndilo Mandibular/patología , Radiografía Panorámica , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Femenino , Humanos , Hiperplasia/diagnóstico por imagen , Hiperplasia/cirugía , Masculino , Cóndilo Mandibular/diagnóstico por imagen , Cóndilo Mandibular/cirugía , Modalidades de Fisioterapia , Cuidados Posoperatorios , Rango del Movimiento Articular/fisiología , Trastornos de la Articulación Temporomandibular/cirugíaRESUMEN
Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain tumor with a median survival of less than one year despite multimodal treatment regimens. However, a small subgroup of GBM patients has a better clinical outcome, with a small number of patients surviving several years. Apoptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signaling pathways, cancer cells may escape apoptosis, despite carrying irreversible DNA damage. In the present study, we have analyzed tumors of two age-matched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs. The percentage of alterations in genes/proteins involved in the apoptotic pathway investigated here was virtually identical in the two groups of clinically different GBM patients. Thus, our data imply that none of these alterations investigated per se has a strong impact on the overall survival of GBM patients.