RESUMO
A rare finding of primary cutaneous CD4+ small to medium-sized Tcell lymphoma (SMPTCL) in a fifteen-year-old patient is reported. This is a rare tumor entity for which there is currently no standardized treatment recommendation. At the interdisciplinary tumor board, the decision was made to resect the tumor and reconstruct the defect with a nasolabial advancement flap in a two-stage process. Follow-up examinations, currently over 3 years, have shown the patient to be free of recurrences.
Assuntos
Linfoma Cutâneo de Células T , Linfoma de Células T , Neoplasias Cutâneas , Adolescente , Linfócitos T CD4-Positivos , Humanos , Linfoma de Células T/diagnóstico , Linfoma de Células T/cirurgia , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/cirurgia , Recidiva Local de Neoplasia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgiaRESUMO
Experimental models of Graves' hyperthyroid disease accompanied by Graves' orbitopathy (GO) can be induced efficiently in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. In this study, we report on the development of a bona fide murine model of autoimmune Graves' disease induced with homologous mouse TSHR A-subunit plasmid. Autoimmune thyroid disease in the self-antigen model was accompanied by GO and characterized by histopathology of hyperplastic glands with large thyroid follicular cells. Examination of orbital tissues showed significant inflammation in extra-ocular muscle with accumulation of T cells and macrophages together with substantial deposition of adipose tissue. Notably, increased levels of brown adipose tissue were present in the orbital tissue of animals undergoing experimental GO. Further analysis of inflammatory loci by 19 F-magnetic resonance imaging showed inflammation to be confined to orbital muscle and optic nerve, but orbital fat showed no difference in inflammatory signs in comparison to control ß-Gal-immunized animals. Pathogenic antibodies induced to mouse TSHR were specific for the self-antigen, with minimal cross-reactivity to human TSHR. Moreover, compared to other self-antigen models of murine Graves' disease induced in TSHR knock-out mice, the repertoire of autoantibodies to mouse TSHR generated following the breakdown of thymic self-tolerance is different to those that arise when tolerance is not breached immunologically, as in the knock-out models. Overall, we show that mouse TSHR A-subunit plasmid immunization by electroporation overcomes tolerance to self-antigen to provide a faithful model of Graves' disease and GO.
Assuntos
Autoantígenos/imunologia , Doença de Graves/imunologia , Oftalmopatia de Graves/imunologia , Inflamação/imunologia , Nervo Óptico/imunologia , Receptores da Tireotropina/imunologia , Tireoidite Autoimune/imunologia , Animais , Autoanticorpos/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Miosite Orbital , Plasmídeos/imunologia , Receptores da Tireotropina/genética , Tolerância a Antígenos PrópriosRESUMO
BACKGROUND: The aim of the present study is to examine the impact of kV-CBCT-based online adaptive radiation therapy (ART) on dosimetric parameters in comparison to image-guided-radiotherapy (IGRT) in consecutive patients with tumors in the head and neck region from a prospective registry. METHODS: The study comprises all consecutive patients with tumors in the head and neck area who were treated with kV-CBCT-based online ART or IGRT-modus at the linear-accelerator ETHOS™. As a measure of effectiveness, the equivalent-uniform-dose was calculated for the CTV (EUDCTV) and organs-at-risk (EUDOAR) and normalized to the prescribed dose. As an important determinant for the need of ART the interfractional shifts of anatomic landmarks related to the tongue were analyzed and compared to the intrafractional shifts. The latter determine the performance of the adapted dose distribution on the verification CBCT2 postadaptation. RESULTS: Altogether 59 consecutive patients with tumors in the head-and-neck-area were treated from 01.12.2021 to 31.01.2023. Ten of all 59 patients (10/59; 16.9%) received at least one phase within a treatment course with ART. Of 46 fractions in the adaptive mode, irradiation was conducted in 65.2% of fractions with the adaptive-plan, the scheduled-plan in the remaining. The dispersion of the distributions of EUDCTV-values from the 46 dose fractions differed significantly between the scheduled and adaptive plans (Ansari-Bradley-Test, p = 0.0158). Thus, the 2.5th percentile of the EUDCTV-values by the adaptive plans amounted 97.1% (95% CI 96.6-99.5%) and by the scheduled plans 78.1% (95% CI 61.8-88.7%). While the EUDCTV for the accumulated dose distributions stayed above 95% at PTV-margins of ≥ 3 mm for all 8 analyzed treatment phases the scheduled plans did for margins ≥ 5 mm. The intrafractional anatomic shifts of all 8 measured anatomic landmarks were smaller than the interfractional with overall median values of 8.5 mm and 5.5 mm (p < 0.0001 for five and p < 0.05 for all parameters, pairwise comparisons, signed-rank-test). The EUDOAR-values for the larynx and the parotid gland were significantly lower for the adaptive compared with the scheduled plans (Wilcoxon-test, p < 0.001). CONCLUSIONS: The mobile tongue and tongue base showed considerable interfractional variations. While PTV-margins of 5 mm were sufficient for IGRT, ART showed the potential of decreasing PTV-margins and spare dose to the organs-at-risk.
Assuntos
Neoplasias de Cabeça e Pescoço , Radioterapia Guiada por Imagem , Humanos , Planejamento da Radioterapia Assistida por Computador , Neoplasias de Cabeça e Pescoço/radioterapia , Cabeça , PescoçoRESUMO
Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. However, the mechanisms of bone loss caused by androgen deficiency are still unclear. In the present study, we sequentially investigated the skeletal and hormonal effects of androgen deficiency in aged orchiectomized (ORX) rats over a time period of 9 months. One hundred seventy 13-month-old male Fischer-344 rats were either ORX or sham-operated (SHAM). Eight rats served as baseline controls. After in vivo fluorochrome labeling, groups of 8-15 SHAM and ORX rats each were killed at 2 weeks and at 1, 2, 3, 4, 6, and 9 months postsurgery. As expected, ORX induced a fall in serum total and free testosterone levels, but also reduced serum estradiol concentrations. Cancellous bone area (BAr) in the proximal tibia but not in the first lumbar vertebral body showed an age-dependent decline in SHAM rats. Relative to SHAM controls, ORX rats had significantly reduced cancellous BAr after 2 weeks post-ORX in the tibia and after 2 months post-ORX in the vertebral body. Thereafter, vertebral and tibial cancellous BAr continued to decline in ORX animals throughout the study. Osteoclast number (NOc), osteoblast surface, bone formation rate (BFR), and activation frequency were increased in ORX animals from 1 month postsurgery until the end of the trial. Moreover, in close temporal association with the histomorphometric findings, serum osteocalcin and urinary excretion of collagen cross-links and calcium were elevated in ORX rats. In a stepwise model of multiple regression analysis using estradiol and free and total testosterone as independent variables, estradiol was the only significant predictor of histomorphometric indices of bone formation and bone resorption in SHAM and ORX rats. These data show that androgen deficiency induces substantial loss of cancellous bone in the axial and appendicular skeleton of aged male rats and that this osteopenia is associated with a sustained increase in bone turnover. Thus, the skeletal effects of androgen withdrawal in aged male rats appear to resemble those induced by estrogen withdrawal in female rats. Furthermore, our study suggests that estradiol may act as a physiological suppressor of bone remodeling in aged male rats.
Assuntos
Envelhecimento/metabolismo , Androgênios/deficiência , Doenças Ósseas Metabólicas/etiologia , Envelhecimento/sangue , Envelhecimento/patologia , Fosfatase Alcalina/sangue , Animais , Peso Corporal , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/metabolismo , Di-Hidrotestosterona/sangue , Ingestão de Alimentos , Estradiol/sangue , Modelos Lineares , Vértebras Lombares/patologia , Masculino , Orquiectomia , Tamanho do Órgão , Osteocalcina/sangue , Ratos , Ratos Endogâmicos F344 , Glândulas Seminais , Testosterona/sangue , Tíbia/patologiaRESUMO
Bone-marrow changes in infectious diseases due to feline infectious peritonitis virus (FIPV), feline immunodeficiency virus (FIV), parvovirus (PV, canine and feline) and canine distemper virus (CDV), and in the lymphohaemopoietic neoplasias (LHNs) usually associated with feline leukaemia virus infection were studied in samples obtained from 204 cats and 82 dogs at necropsy. The study demonstrated (1) no changes, (2) non-specific reactive changes, and (3) disease-specific changes (similar to those occurring in extramedullary sites) in: 51.2, 48.8 and 9.7% of 41 cases of FIPV infection, respectively; 0, 100 and 0% of nine cases of FIV infection, respectively; 1.3, 0 and 92% of 75 cases of canine PV infection, respectively; 5.3, 3.9 and 84% of 76 cases of feline PV infection, respectively; 71.4, 28.6 and 0% of seven cases of CDV infection, respectively; and 35.9, 52.6 and 11.5% of 78 cases of LHN, respectively. The distribution of the disease-specific bone-marrow changes was either diffuse or focal; diffuse changes were frequently found in cases of feline and canine PV infection, and focal changes were found inconsistently in FIPV infections and feline LHN. To the extent that the bone marrow showed any changes in FIV and CDV infections, they were mostly reactive and not pathognomonic.
Assuntos
Medula Óssea/patologia , Doenças do Gato/patologia , Doenças do Cão/patologia , Transtornos Linfoproliferativos/veterinária , Viroses/veterinária , Animais , Gatos , Cinomose/patologia , Cães , Peritonite Infecciosa Felina/patologia , Panleucopenia Felina/patologia , Feminino , Vírus da Imunodeficiência Felina , Infecções por Lentivirus/patologia , Infecções por Lentivirus/veterinária , Leucemia de Mastócitos/patologia , Leucemia de Mastócitos/veterinária , Linfoma/patologia , Linfoma/veterinária , Transtornos Linfoproliferativos/patologia , Masculino , Infecções por Parvoviridae/patologia , Infecções por Parvoviridae/veterinária , Parvovirus Canino , Estudos Retrospectivos , Viroses/patologiaRESUMO
A competitive bradykinin enzymeimmunoassay (BK-EIA) for the determination of urinary kinins was developed. The BK-EIA was based on a stable BK-peroxidase conjugate and a BK-antirabbit-antiserum. Compared with a healthy control group, a significantly lower mean kinin excretion was found in patients with essential hypertension.
Assuntos
Hipertensão/urina , Cininas/urina , Adolescente , Adulto , Idoso , Bradicinina , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-IdadeRESUMO
Bone loss and long-term persistence of osteoporosis with increased fracture risk are common after liver transplantation. It is unknown whether transplantation-induced disruption of hepatic nerves, serving numerous regulatory metabolic and sensory functions, is herein involved. To test this possibility, we measured bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and studied dynamic histomorphometry, radiocalcium kinetics, and biochemical parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra and total BMD of the femoral diaphysis were decreased by 13% and 6%, respectively, 9 months postsurgery. The breaking force of the femur was significantly lower by 21%. However, bone mass in the femoral and tibial metaphysis was preserved as evidenced by pQCT measurements and histomorphometry. Trabecular width and wall thickness were significantly decreased in vertebral cancellous bone, whereas indices of bone formation and resorption were normal or slightly reduced. Serum minerals, mineral balance, fractional and net absorption of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of 45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone resorption remained unchanged. We conclude that liver transplantation-related denervation causes cancellous and cortical bone loss in well-innervated bone sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss in TX rats is due to an impairment of osteoblast team performance and subsequent trabecular thinning. The mechanism uncovered by our study may contribute to long-term bone loss after liver transplantation.
Assuntos
Doenças Ósseas Metabólicas/etiologia , Osso e Ossos/metabolismo , Denervação/efeitos adversos , Transplante de Fígado/efeitos adversos , Fígado/cirurgia , Animais , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/patologia , Osso e Ossos/fisiopatologia , Fraturas do Fêmur/fisiopatologia , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Fêmur/patologia , Fígado/inervação , Transplante de Fígado/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Masculino , Complicações Pós-Operatórias , Radiografia , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Estresse Mecânico , Tíbia/diagnóstico por imagem , Tíbia/metabolismo , Tíbia/patologiaRESUMO
The effects of colectomy on acid-base status, extra-osseous and bone minerals, calciotropic hormones and bone morphology have not yet been studied. To rectify this, groups of normally fed male rats were subjected to distal (n=11), proximal (n=12) or total (n=12) colectomy. Sham-operated rats (n=12) served as controls. At 112 (+/-2) days after colectomy the following changes were noted: (1) weight gain was delayed; (2) faecal excretion of calcium and phosphorus was normal, whereas that of magnesium was increased; (3) intestinal calcium secretion and absorption of calcium and phosphorus were normal, but magnesium absorption was decreased; (4) urinary excretion of magnesium was also decreased, that of phosphorus was increased, and that of pyridinium and deoxypyridinium tended to be high; (5) the serum levels of ionized magnesium, total calcium, 25-hydroxyvitamin D and parathyroid hormone were normal, while that of 1,25-dihydroxyvitamin D was markedly elevated; and (6) bone magnesium and phosphorus content were decreased, but bone calcium was normal, and thus the bone calcium/phosphorus ratio was high. These abnormalities were associated with moderate metabolic acidosis, as reflected by high urinary ammonium, low citrate and low total CO(2), but normal blood gases. Significant structural abnormalities of bone were not detectable, but trabecular bone tended to show rarefication. Distal colectomy had the least effect, whereas proximal and total colectomies had a distinct effect, on these parameters. It is concluded that colectomy in the rat causes: (1) a syndrome of magnesium deficiency of intestinal origin, compensated metabolic acidosis, urinary phosphorus loss, and high circulating 1,25-dihydroxyvitamin D levels, with the degree depending on the extent of surgical resection; and (2) brittle bones, a feature characteristic of low bone magnesium and more generalized magnesium deficiency. The mechanisms leading to this syndrome are unknown, but altered tissue levels of magnesium and phosphorus may play a key role.
Assuntos
Equilíbrio Ácido-Base , Doenças Ósseas/metabolismo , Colectomia/efeitos adversos , Deficiência de Magnésio/metabolismo , Minerais/metabolismo , Animais , Biomarcadores/análise , Doenças Ósseas/etiologia , Osso e Ossos/metabolismo , Calcitriol/sangue , Cálcio/metabolismo , Colectomia/métodos , Absorção Intestinal/fisiologia , Masculino , Hormônio Paratireóideo/sangue , Distúrbios do Metabolismo do Fósforo/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
To examine the role of the estrogen receptor-alpha (ERalpha) during male skeletal development, bone density and structure of aged ERalphaKO mice and wild-type (WT) littermates were analyzed and skeletal changes in response to sex steroid deficiency and replacement were also studied. In comparison to WT, ERalphaKO mice had smaller and thinner bones, arguing for a direct role of ERalpha to obtain full skeletal size in male mice. However, male ERalphaKO mice had significantly more trabecular bone as assessed both by pQCT and histomorphometry, indicating that ERalpha is not essential to maintain cancellous bone mass. Six weeks following orchidectomy (ORX), both WT and ERalphaKO mice showed high-turnover osteoporosis as revealed by increases in serum osteocalcin and decreases in trabecular (-38% and -58% in WT and ERalphaKO, respectively) and cortical bone density (-5% and -4% in WT and ERalphaKO, respectively). Administration of testosterone propionate (T, 5 mg/kg/day) completely prevented bone loss both in ERalphaKO and in WT mice. As expected, estradiol (E2, 60 microg/kg/day) replacement did not prevent cancellous bone loss in ORX ERalphaKO mice. However, E2 stimulated bone formation at the endocortical surface in ORX ERalphaKO, suggesting that osteoblasts may respond to nonERalpha-mediated estrogen action. In conclusion, although functional ERalpha may play a significant role during male skeletal development, this receptor does not seem essential for androgen-mediated skeletal maintenance in older male mice.