RESUMO
BACKGROUND: The precise role of total body (18) F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) in the clinical management of patients with cutaneous malignant melanoma (CMM) is not well established. OBJECTIVE: The purpose of this study was to investigate the diagnostic accuracy of PET/CT in early- and late-stage patients with high-risk CMM. METHODS: We retrospectively analysed various imaging, histopathological and clinical data from 97 patients also examined by PET/CT during a 5-year period (2007-2011). Three groups were assessed: stage I/II, resected stage III and unresectable stage III/stage IV. RESULTS: The median follow-up time of living patients was 43.48 ± 19.67 (15-142) months. We observed a high diagnostic accuracy in all stages (91.3%, 92.5% and 96.2% respectively). PET/CT appeared to be reliable diagnostic tool even for the detection of small lymph node metastases. PET/CT was informative in 14 of 19 cases wherein another imaging examination provided inconclusive results regarding lesion dignity. However, PET/CT was less suitable for properly evaluating the dignity of a lung lesion. A true positive scan was twice as likely in clinically negative patients with resected stage III disease than in patients with stage I/II disease (35.9% and 14.5%, P = 0.007). CONCLUSIONS: These results confirm that PET/CT is an important diagnostic tool in the management of patients with high-risk CMM, but it cannot replace the standard of care examinations. More accurate clinicopathological and timing criteria must be defined to best utilize the advantages of this imaging method.
Assuntos
Melanoma/diagnóstico por imagem , Melanoma/secundário , Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Fluordesoxiglucose F18 , Humanos , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.
Assuntos
Hidradenite Supurativa/etiologia , Hidradenite Supurativa/terapia , Guias de Prática Clínica como Assunto , Europa (Continente) , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/epidemiologia , HumanosRESUMO
Pemphigus vulgaris is an autoimmune blistering disease that is induced by binding of antibodies to a 130/85-kD protein complex on epidermal keratinocytes. An in vivo experimental model of this disease was developed by reconstituting severe combined immunodeficiency (SCID) mice with 1-10 x 10(7) PBL from patients with naturally occurring pemphigus vulgaris. Of 49 reconstituted mice, 34 (69%) produced human IgG levels of > 0.1 mg/ml. Circulating anti-pemphigus antibodies were found in 20 of the 34 successfully reconstituted mice; 44% of these animals had deposits of human IgG in their own skin after it was traumatized by either heat or cold. Spontaneous pemphigus vulgaris-like blisters associated with human IgG deposits were rarely found in mouse skin. By contrast, allogeneic human skin grafted to 10 to 12 mice before reconstitution with patients' PBL developed pemphigus vulgaris-like lesions containing human IgG deposits. These results demonstrate that SCID mice can serve as a model of an antibody-mediated human autoimmune skin disease.
Assuntos
Transfusão de Linfócitos , Camundongos SCID/imunologia , Pênfigo/imunologia , Transplante de Pele/imunologia , Adulto , Animais , Autoanticorpos/sangue , Vesícula/imunologia , Vesícula/patologia , Humanos , Imunoglobulinas/biossíntese , Recém-Nascido , Camundongos , Pênfigo/patologia , Especificidade da EspécieRESUMO
The ability of circulating white blood cells to enter inflamed tissues is mediated by specific cell adhesion molecules thought to be expressed in a programmed and sequential manner to form an "adhesion cascade." Because of the complexity of this process, it is becoming increasingly important to develop in vivo models. Two major problems have limited the utility of current animal models. The first is the inability of many of the antibodies developed against cell adhesion molecules in human cell culture models to cross-react in animals. The second is the uncertainty in extrapolating animal (particularly rodent) findings to humans. To circumvent these problems, full thickness human skin grafts were transplanted onto immunodeficient (severe combined immunodeficient) mice. After 4-6 wk, the transplanted skin grafts closely resembled normal skin histologically and maintained their human vasculature as determined by immunohistochemical staining with human-specific endothelial cell markers. Intradermal injection of tumor necrosis factor-alpha resulted in the reversible upregulation of the leukocyte-endothelial adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1, and in an active inflammatory reaction with migration of murine leukocytes into cytokine-injected areas. These results indicate that the severe combined immunodeficient mouse/human skin transplant model provides a useful in vivo system in which to study human endothelium during the process of inflammation.
Assuntos
Moléculas de Adesão Celular/metabolismo , Transplante de Pele/fisiologia , Adulto , Animais , Antígenos de Diferenciação Mielomonocítica/metabolismo , Moléculas de Adesão Celular/análise , Quimera , Selectina E , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Molécula 1 de Adesão Intercelular , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Masculino , Camundongos , Camundongos SCID , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Transplante de Pele/imunologia , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula VascularRESUMO
New experimental models of human neoplastic diseases attempt to mimic the human environment that fostered the development of disease in cancer patients. The aim of the present study was to establish a human lymphocyte-engrafted, severe combined immunodeficient (hu-PBL-SCID) mouse model to investigate thyroid cancer and to evaluate the potential use of this model for cancer immunotherapy. Thyroid neoplastic tissues were obtained from ten patients (one follicular adenoma, five papillary, one follicular, one anaplastic and two medullary cancers). One 8 x 4 x 3 millimeter sample from each tumor was cut into two pieces of identical size and transplanted into two SCID mice. In each case, one of the two mice was injected intraperitoneally with lymphocytes from the same tumor patient for the reconstitution of the human immune system (Group A), while the other animal received no lymphocytes (Group B). The engraftment of the tumors was successful in all cases. The growth rate was highly dependent on the histological type. When histologies were compared before implantation and after the removal of the implants, the characters of the tumors proved to be unchanged, except one case where an anaplastic cancer arose from a papillary tumor. Macrophages were present in all but one papillary cancer. All differentiated thyroid cancers were infiltrated by T and B lymphocytes. Lymphocytes and macrophages disappeared from 19/20 grafts by week 16. However, in one case from group A lymphocytes were detected four months after the transplantation. In another case from group A, one papillary cancer spontaneously decreased in size and disappeared. Before implantation, HLA-DR expression was detected in every papillary cancer. HLA-DR expression in the grafts was not seen in 3/5 cases by week 16. In conclusion, an animal model has been established for the investigation of human thyroid cancer, by which the analysis of anti-tumor immunity, as a postulate of immune therapy, may be possible.
Assuntos
Modelos Animais de Doenças , Linfócitos/imunologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Animais , Antígenos CD/sangue , Antígenos CD/imunologia , Feminino , Antígenos HLA-DR/sangue , Humanos , Imunoglobulina M/sangue , Imuno-Histoquímica , Imunoterapia , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Transplante de Neoplasias , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/terapia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Diurnal rhythm of plasma beta endorphin was established with the highest level in the morning and the lowest one at midnight in normotensive subjects and also in patients with essential hypertension. Clonidine (300 micrograms daily) significantly increased plasma beta endorphin concentrations only in the hypertensive patients. The significant linear correlation between the increase in plasma beta endorphin concentration and the decrease in blood pressure (both systolic and diastolic) in these patients may point to the role of this endogenous opioid in the antihypertensive action of clonidine.
Assuntos
Ritmo Circadiano , Clonidina/uso terapêutico , Endorfinas/sangue , Hipertensão/sangue , Clonidina/farmacologia , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , beta-EndorfinaRESUMO
The epidermal repopulation of Langerhans cells (LCs) during wound healing was examined using a human skin severe combined immunodeficient (SCID) mouse model. The experiments, were carried out after proving the human origin of keratinocytes repopulating the wound beds using the W6/32 monoclonal antibody. It was shown that CD1a- and HLA-DR-positive dendritic cells (mostly LCs) are already detectable 2 days after injury within the newly formed epithelium. In the excisional wounds investigated, neither HLA-DR nor ICAM-1 expression of human keratinocytes was observed. Our present data suggest that LC repopulation is an early event in the process of re-epithelization.
Assuntos
Células de Langerhans/patologia , Pele/lesões , Cicatrização/fisiologia , Animais , Modelos Animais de Doenças , Epitélio/patologia , Antígenos HLA-DR/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Células de Langerhans/imunologia , Camundongos , Camundongos SCID , Pele/imunologia , Pele/patologia , Transplante de Pele , Fatores de Tempo , Transplante Heterólogo , Cicatrização/imunologiaRESUMO
Histamine is produced by many cells expressing histidine decarboxylase (HDC), the enzyme responsible for the synthesis of histamine. Since melanoma cells and tissue contain relatively large amounts of histamine, the functional significance of histamine was examined using specific antihistamines in vitro and in vivo in the human melanoma cell line HT168 and severe combined immunodeficiency (SCID) mice. It was shown that the H2 receptor antagonist cimetidine when combined with N, N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine-HCl (DPPE), a tamoxifen derivate, inhibits the proliferation of HT168 cells. Furthermore, it is suggested that there is a factor(s) that interferes with the exponential growth of HT168 cells xenografted to immunodeficient mice, and cimetidine and DPPE together significantly influence this factor(s). This combination of antihistamines also increases the survival of human melanoma-grafted mice. These changes are accompanied by enhanced infiltration of interferon-gamma- producing mouse macrophages into the tumour tissue. These findings suggest that two different mechanisms are probably acting concordantly: direct inhibition of tumour cell proliferation by the H2 receptor antagonists, and activation of the local immune response characterized by interferon-gamma production. These findings may help to elucidate the possibility of a rationally designed antihistamine strategy in melanoma therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Animais , Comunicação Autócrina/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Cimetidina/administração & dosagem , Sistema Enzimático do Citocromo P-450/metabolismo , Sinergismo Farmacológico , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Histidina Descarboxilase/metabolismo , Humanos , Interferon gama/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Melanoma/enzimologia , Melanoma/patologia , Melanoma Experimental/enzimologia , Melanoma Experimental/prevenção & controle , Camundongos , Camundongos SCID , Proteínas de Neoplasias/metabolismo , Éteres Fenílicos/administração & dosagem , RNA Mensageiro/análise , RNA Neoplásico/análise , Receptores Histamínicos H2/genética , Receptores Histamínicos H2/metabolismo , Células Tumorais Cultivadas/transplante , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Using a human skin/severe combined immunodeficient (SCID) chimeric mouse model, we examined the keratinocyte expression of the thrombospondin receptor (CD36) and its ligand thrombospondin-1 (TSP1) in acute uninflamed wounds. Positive suprabasal keratinocyte expression of CD36 was observed as early as 30 minutes after wounding in the adjacent, intact epidermis; it disappeared 4 days later. Keratinocytes of the freshly re-epithelised wounds and those of the surrounding epidermis remained TSP1-negative throughout the whole observation period of 7 days. Our results indicate that CD36-positive keratinocytes, probably in connection with activated, TSP1-positive thrombocytes, may play an important role in the early phase of wound healing.
Assuntos
Antígenos CD36/metabolismo , Queratinócitos/imunologia , Pele/lesões , Animais , Humanos , Imuno-Histoquímica , Queratinócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos SCID , Modelos Biológicos , Pele/metabolismo , Trombospondinas , CicatrizaçãoRESUMO
During the last 10 years the authors operated upon 8 patients with illnesses beginning with different lung alterations. In all cases the basic illness was a papillary or papillo-follicular cancer of the thyroid gland which later was found indirectly after other operation and histologic examination. By evaluation of clinical symptoms, operative and morphologic findings conclusions as well as the results of reexamination the authors draw conclusions as to the biological attributes of this tumor type. They recognize that the carcinomas of the thyroid gland cause metastases of regional lymph nodes or distant lung metastases approaching the TO stage. Lung metastases appeared in different shapes and were in all cases the fist clinical sign of the basic illness. Considering the biological attributes of this tumor the authors emphasize that it is not inoperable or untreatable.
Assuntos
Neoplasias da Glândula Tireoide/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Erros de Diagnóstico , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
The literature on the incidence of chronic and acute renal insufficiency is reviewed and the results of own investigations in an area with a population of 1,560,000 are presented. Data were collected in questionnaires. The yearly incidence of patients with chronic uraemia requiring active therapy was estimated at 33 per 1 million population. The number of acute cases was 45 per million. The necessity of increasing the dialysis capacity is stressed. The importance of peritoneal dialysis in the therapy of uraemia cases which do not meet the requirements of the acute and chronic dialysis programmes is emphasized.
Assuntos
Injúria Renal Aguda/epidemiologia , Falência Renal Crônica/epidemiologia , Humanos , Hungria , Diálise Peritoneal , Diálise Renal , Uremia/epidemiologiaRESUMO
The functional importance of renal TxB2 generation in the maintenance of elevated arterial blood pressure in essential hypertension was followed in 22 patients, using the method of sustained blood pressure decrease by i.v. sodium nitroprusside infusion. Linear correlation between urinary excretion of TxB2, urine flow, and sodium excretion could be established in both control and hypotensive periods. Presumably, changes in urinary excretion of TxB2 reflect a secondary intrarenal counterregulatory response.
Assuntos
Hipotensão/urina , Renina/sangue , Sódio/urina , Tromboxano A2/urina , Urodinâmica , Adulto , Pressão Sanguínea , Diurese , Humanos , Hipotensão/sangue , Pessoa de Meia-IdadeRESUMO
PURPOSE: The aim of this study was to investigate the possibility of quantitative classification in intervertebral disc degeneration using spin-spin relaxation time (T2) cut-off values with regard to morphological classifications. METHODS: Lumbar magnetic resonance (MR) imaging was performed on 21 subjects (a total of 104 lumbar disks). The T2 relaxation time was measured in the nucleus pulposus using a sagittal multi-echo spin-echo sequence. The morphological classification of disc degeneration was assessed independently by three experienced neuroradiologists according to the Pfirrmann and Schneiderman classifications. Receiver operating characteristic analysis was performed among grades to determine T2 cut-off values in each classification. Intra- and interobserver differences were calculated using kappa statistics. RESULTS: Moderate overall interobserver agreement was found between observers in both the Pfirrmann and Schneiderman classification schemes (kappa 0.46 and 0.51), while intraobserver reliability was substantial to almost perfect. The interobserver reliability was only fair in Pfirrmann grades III and IV (kappa 0.33 and 0.36), but the T2 cut-off values still indicated a significant difference between grades (p<0.05). CONCLUSIONS: Interobserver agreement of MR evaluation in patients with intervertebral disc degeneration was only fair to moderate on the classification of more severe disc degeneration in the Pfirrmann and Schneiderman schemes. Based on our results, quantitative T2 cut-off values seem to be a more reliable method to define the degree of disc degeneration, which may help staging intervertebral disc degeneration (IVDD) even if the interobserver reliability is low.
Assuntos
Interpretação Estatística de Dados , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Degeneração do Disco Intervertebral/patologia , Vértebras Lombares/patologia , Modelos Estatísticos , Adolescente , Adulto , Algoritmos , Simulação por Computador , Estudos de Viabilidade , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
A clinical investigation to determine the effectiveness of Zn-hyaluronan gel for the treatment of partial thickness burns was carried out. 60 patients were enrolled in the study with an average of 3% TBSA burn. Exudation lasted 3 days, no infectious complications were observed. By day 14 the wounds of 52 patients have healed, average complete healing time was 10,5 days. An overall 93,3% healing rate was achieved within the planned observation period. Reduction of spontaneous and movementrelated pain was reduced to less than half of the initial values by day 5,5 and 6,3 respectively. Development of a thin, elastic, well tolerable and protective membrane-like layer was noted. This kept the wounds moist while clean during wound-healing, and was spontaneously shed as epithelisation proceeded. Zn-hyaluronan gel is a novel topical wound care product that has proven to be suitable for the treatment of partial thickness burns.
RESUMO
Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the implants was 185 cm(2). Among those, 15 implant sites of 14 patients were assessed at an average of 50 months after surgery. The scar function was assessed by using the modified Vancouver Scar Scale. We have found that the overall scar quality and function was significantly better over the implanted areas than over the surrounding skin. Also these areas received a better score for scar height and pliability. Our findings suggest that acellular dermal implants are especially useful tools in the treatment of full-thickness burns as well as postburn scar contractures.