RESUMO
BACKGROUND: The rare inversa subtype of recessive dystrophic epidermolysis bullosa (RDEB-I) is characterized by predominant intertriginous skin blistering and marked mucosal involvement. Specific recessive missense mutations in the collagen VII triple helix are implicated in the disease. To date, otological complications have been reported infrequently in this patient group. METHODS: We conducted an observational, retrospective, double institution case record review of patients with RDEB-I who presented with otological complications between January 2000 and June 2020. Diagnosis was established on the basis of clinical features, family history and mutation analysis of the COL7A1 gene. RESULTS: In total, 11 (44%) of 25 patients with RDEB-I in our database (2 paediatric, 9 adult; mean age 40.9 years, range 8-72 years) experienced otological complications. Of these 11 patients, 10 (90.9%) had recurrent otitis externa, 7 (63.6%) had meatal stenosis and 7 (63.6%) had recurrent blistering of the external auditory canals. All 11 patients reported hearing difficulties, with conductive hearing loss confirmed by audiology testing in 6 (54.5%) of these. Of the 11 patients, 3 (27.3%) went on to have implantable hearing aids [2 bone-anchored hearing aids (BAHA) and 1 middle ear implant (MEI)] fitted with favourable outcome, while a fourth paediatric patient presented with a cholesteatoma that was surgically managed. DISCUSSION: We observed a higher prevalence of otological morbidity in RDEB-I than previously reported, and present the first case of cholesteatoma in epidermolysis bullosa (EB). Our data indicate that BAHA and MEI are safe and effective treatment options for hearing loss in EB. Clinicians should be vigilant in screening for ear symptoms in RDEB-I and consider early referral to an Ear, Nose and Throat specialist.
Assuntos
Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Adolescente , Adulto , Idoso , Criança , Colágeno Tipo VII/genética , Epidermólise Bolhosa/genética , Epidermólise Bolhosa Distrófica/complicações , Epidermólise Bolhosa Distrófica/genética , Genes Recessivos , Humanos , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Due to a large variety in treatment outcomes reported in therapeutic trials and lacking patient-relevant outcomes, it is hard to adequately compare and improve current therapies for patients with capillary malformations (CMs). The Core Outcome Set for Capillary Malformations (COSCAM) project aims to develop a core outcome set (COS) for use in future CM trials, in which we will first develop a core outcome (sub)domain set (CDS). Here, we describe the methods for the development of a CDS and present the results of the first development stage. METHODS: The COSCAM project is carried out according to the recommendations of the Cochrane Skin Core OUtcomes Set INitiative (CS-COUSIN) and the Core Outcome Measures in Effectiveness Trials (COMET) initiative. During the first stage, we identified all potentially relevant outcome subdomains based on a systematic review, two focus group sessions and input from patient representatives of Dutch patient organizations and the COSCAM-founding group. In stage two, we will present the subdomains in a three-round e-Delphi study and online consensus meeting, in which CM patients, parents/caregivers and CM experts worldwide rate the importance of the proposed subdomains, hereby finalizing the core outcome (sub)domains of the CDS. RESULTS: A total of 67 potential outcome subdomains were included; sixteen were previously used in the literature, 20 were proposed by Dutch patients and their parents/caregivers (n = 13) in focus group sessions and 38 were suggested by the experts of the COSCAM-founding group. Seven were excluded because of overlap. CONCLUSION: The final CDS may serve as a minimum standard in future CM trials, thereby facilitating adequate comparison of treatment outcomes. After this CDS development, we will select appropriate outcome measurement instruments to measure the core outcome subdomains.
Assuntos
Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Capilares/anormalidades , Técnica Delphi , Determinação de Ponto Final , Humanos , Revisões Sistemáticas como Assunto , Resultado do Tratamento , Malformações VascularesAssuntos
Displasia Ectodérmica/genética , Integrina alfa6/genética , Integrina beta4/genética , Enteropatias Perdedoras de Proteínas/terapia , Adolescente , Adulto , Autopsia/métodos , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Insuficiência de Crescimento/diagnóstico , Insuficiência de Crescimento/etiologia , Insuficiência de Crescimento/genética , Feminino , Genótipo , Humanos , Lactente , Líbano/epidemiologia , Masculino , Microscopia Eletrônica/métodos , Doenças da Unha/patologia , Doenças da Unha/cirurgia , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/etiologia , Sepse/diagnóstico , Sepse/etiologia , IrmãosAssuntos
Epidermólise Bolhosa/diagnóstico , Testes Genéticos/estatística & dados numéricos , Pele/patologia , Biópsia/estatística & dados numéricos , Criança , Pré-Escolar , Epidermólise Bolhosa/genética , Epidermólise Bolhosa/patologia , Imunofluorescência/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Microscopia Eletrônica/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Inflammatory bowel disease (IBD) etiology involves genetic susceptibility, environmental triggers, and the gut microbiome. Antibiotic exposure is associated with IBD, both in early life and adulthood. Here, we investigated whether Nod2-deficiency influenced response of the gut microbiota to antibiotics and subsequent colitis susceptibility. Wild-type and Nod2-/- littermate mice were treated with amoxicillin as adults or neonates, and fecal samples were collected for 16S rRNA sequencing. Five weeks after antibiotic exposure, dextran sulfate sodium (DSS) colitis was induced. Antibiotic treatment altered the microbiota of adult WT and Nod2-/- mice, but recovery was delayed in Nod2-/- mice. Neonatal antibiotic treatment significantly changed the microbiota at weaning in WT and Nod2-/- littermates; however, Nod2-/- mice maintained reduced microbial diversity 14 days after cessation of antibiotics. Although treatment of adult mice did not influence susceptibility to colitis, neonatally treated Nod2-/- mice developed a more severe colitis. Moreover, the colitis phenotype was transferable through fecal transplantation into germ-free Nod2-/- recipients, and was associated with changes in intestinal T cells and the cytokine milieu following inflammation. These data demonstrate that neonatal antibiotic exposure has long-lasting influence on the microbiota and mucosal immunity, and may explain how NOD2 contributes to the risk of intestinal inflammation.
Assuntos
Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Colite/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças Inflamatórias Intestinais/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Amoxicilina/administração & dosagem , Animais , Animais Recém-Nascidos , Antibacterianos/administração & dosagem , Colite/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Interação Gene-Ambiente , Humanos , Doenças Inflamatórias Intestinais/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Adaptadora de Sinalização NOD2/genética , RiscoRESUMO
Aims Physical activity has been proposed to be an effective non-pharmacological method of reducing systemic inflammation and therefore may prove particularly efficacious for women with polycystic ovary syndrome (PCOS) who have been shown to have high levels of inflammation and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Therefore, the aim of the present study was to assess whether modest changes in daily step count could significantly reduce levels of inflammatory markers in women with PCOS. Subjects and Methods Sixty-five women with PCOS were assessed at baseline and again at 6 months. All had been provided with an accelerometer and encouraged to increase activity levels. Multivariate linear regression analyses (adjusted for age, ethnicity, baseline step count, change in BMI and change in accelerometer wear-time) were used to assess changes in daily step count against clinical and research biomarkers of inflammation, CVD and T2DM. Results Mean step count/day at baseline was 6337 (±270). An increase in step count (by 1000 steps) was associated with a 13% reduction in IL6 (ß: -0.81 ng/L; 95% CI, -1.37, -0.25, P = 0.005) and a 13% reduction in CRP (ß: -0.68 mg/L; 95% CI, -1.30, -0.06, P = 0.033). Additionally, there was a modest decrease in BMI (ß: 0.20 kg/m2; 95% CI, -0.38, -0.01, P = 0.038). Clinical markers of T2DM and CVD were not affected by increased step count. Conclusions Modest increases in step count/day can reduce levels of inflammatory markers in women with PCOS, which may reduce the future risk of T2DM and CVD.
Assuntos
Alopecia em Áreas/tratamento farmacológico , Dermatite Atópica/tratamento farmacológico , Piperidinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Vitiligo/tratamento farmacológico , Adulto , Alopecia em Áreas/imunologia , Dermatite Atópica/imunologia , Humanos , Inibidores de Janus Quinases/farmacologia , Masculino , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Resultado do Tratamento , Vitiligo/imunologiaRESUMO
Herein we detail the cases of three patients transferred on veno-arterial extracorporeal membrane oxygenation (VA ECMO) from a tertiary referral hospital to an ECMO centre. We highlight the benefits of such a transfer and offer this as a model of care for unwell patients likely to require a prolonged period of ECMO support.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Transferência de Pacientes , Adulto , Austrália , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Fatores de TempoAssuntos
Capilares/patologia , Eritema/diagnóstico , Pele/patologia , Nádegas , Criança , Diagnóstico Diferencial , Feminino , Humanos , Coxa da PernaRESUMO
This article summarizes recommendations reached following a systematic literature review and expert consensus on the diagnosis and management of cutaneous squamous cell carcinomas in people with epidermolysis bullosa. The guidelines are intended to help inform decision making by clinicians dealing with this complex complication of a devastating disease.
Assuntos
Carcinoma de Células Escamosas/terapia , Epidermólise Bolhosa/complicações , Neoplasias Cutâneas/terapia , Amputação Cirúrgica/métodos , Membros Artificiais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/prevenção & controle , Consenso , Humanos , Metástase Linfática , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Dor/prevenção & controle , Guias de Prática Clínica como Assunto , Psicoterapia/métodos , Retinoides/uso terapêutico , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/prevenção & controle , Assistência Terminal/métodos , Técnicas de Fechamento de FerimentosRESUMO
We describe the challenging case of a patient presenting with extensive, eruptive mid-facial squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) consequent to radiotherapy. Our patient had a personal and family history of multiple KAs and SCCs. Multiple self-healing squamous epithelioma, otherwise known as Ferguson-Smith disease, was diagnosed. This case presented a therapeutic challenge to preserve tissue and avoid severe facial disfigurement. We found oral acitretin to be the treatment of choice.
Assuntos
Acitretina/uso terapêutico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Faciais/radioterapia , Ceratoacantoma/radioterapia , Neoplasias Primárias Múltiplas/radioterapia , Neoplasias Cutâneas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias Faciais/tratamento farmacológico , Neoplasias Faciais/patologia , Humanos , Ceratoacantoma/tratamento farmacológico , Ceratoacantoma/patologia , Ceratolíticos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Induzidas por Radiação/tratamento farmacológico , Síndromes Neoplásicas Hereditárias/tratamento farmacológico , Síndromes Neoplásicas Hereditárias/patologia , Síndromes Neoplásicas Hereditárias/radioterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaAssuntos
Líquen Plano/patologia , Parede Abdominal/patologia , Adulto , Feminino , Humanos , RecidivaRESUMO
The role of the canonical NF-kappaB pathway in mammary tumorigenesis was investigated using a transgenic (TG) mouse expressing a dominant-negative inhibitor of kappaB (IkappaBalpha(SR (S32A/S36A))) in the mammary gland under the control of the mouse mammary tumor virus promoter (MMTV). TG and control mice were subjected to a chemical carcinogenesis protocol. Hyperkeratinized squamous metaplasias (cytokeratin-6+/p63+) sometimes with a basaloid island component, were found in both TG and control mice whereas luminal (cytokeratin-19+/MUC1+) ErbB2+ papillary and adenomatous lesions developed almost exclusively in control mice. p65/RelA- and NF-kappaB DNA-binding activity were detected in mammary luminal lesions, but rarely in squamous metaplasias. Analysis of NF-kappaB family proteins and target genes using microarray data from a cohort of human mammary tumors revealed the expression of a canonical NF-kappaB pathway, but not non-canonical pathway proteins in HER2+ luminal cancers. HER2+ tumors also showed differential regulation of specific NF-kappaB target genes relative to basal and ER+ luminal cancers. Isolation of mammary cell populations enriched for stem and progenitor cell characteristics from an NF-kappaB-EGFP reporter mouse by fluorescence-activated cell sorting demonstrated that luminal progenitors contain activated NF-kappaB whereas the mammary stem cell-enriched population, does not. Together these data suggest that the canonical NF-kappaB pathway is active in normal luminal progenitor cells before transformation and is required for the formation of mammary luminal-type epithelial neoplasias.
Assuntos
Neoplasias Mamárias Experimentais/etiologia , NF-kappa B/fisiologia , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais/fisiologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Neoplasias da Mama/etiologia , Antígeno CD24/análise , Humanos , Quinase I-kappa B/análise , Integrina alfa6/análise , Vírus do Tumor Mamário do Camundongo/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptor ErbB-2/análise , Fator de Transcrição RelA/análiseRESUMO
Lagophthalmos is a well known complication in leprosy due to the involvement of seventh cranial nerve resulting in incomplete closure of the eyelids. The real magnitude of ocular morbidity as a consequence of lagophthalmos is unknown, as several ocular complications can occur independently due to involvement of the fifth (trigeminal) nerve or due to secondary infection. Therefore, a study was designed to carefully examine the eyes of 100 consecutive leprosy patients with lagophthalmos seeking treatment at a leprosy referral centre in Delhi. Among the eyes examined, 145 had lagophthalmos. The symptomatology and anterior-posterior chamber morbidity in eyes with lagophthalmos were significantly higher as compared to unaffected eyes. Significantly, higher morbidity was seen regardless of sex or type of leprosy or deformity. Capacity building of the health professionals regarding ocular morbidity and increased emphasis on the importance of self care among patients can significantly reduce ocular morbidity.
Assuntos
Doenças Palpebrais/microbiologia , Hanseníase Multibacilar/complicações , Hanseníase Paucibacilar/complicações , Estudos Transversais , Doenças Palpebrais/patologia , Feminino , Humanos , Índia , Hanseníase Multibacilar/microbiologia , Hanseníase Multibacilar/patologia , Hanseníase Paucibacilar/microbiologia , Hanseníase Paucibacilar/patologia , Masculino , Morbidade , Mycobacterium leprae , Acuidade VisualRESUMO
AIMS: To investigate the reactivity for oestrogen and progesterone receptors (ER and PR) in renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). MATERIALS AND METHODS: Thirty-eight RO, 25 CHRCC, 20 papillary RCC with oncocytic cytoplasm and 10 clear cell RCC with dominant eosinophilic cytoplasm were submitted for immunohistochemistry for ER, PR, CD117 and RCC. RESULTS: All cases of RO and CHRCC displayed moderately positive reactivity for PR. The nuclear reactivity ranged from 60% to 90% in RO and from occasional cells to 70% in CHRCC. In CHRCC, reactivity tended to be more prevalent in areas of tumour cells with eosinophilic cytoplasm. Progesterone reactivity was focal in areas. All RO and most CHRCC were reactive for CD117 and neither RO nor CHRCC was reactive for RCC. CD117 reactivity tended to be more intense in CHRCC than in RO. Negative reactivity for CD117 and positive reactivity for RCC were observed in almost all RCC, as reported in the literature. CONCLUSIONS: PR can be used in combination with CD117 and RCC in the differential diagnosis of RO and eosinophilic variant of CHRCC with other RCC with oncocytic or eosinophilic cytoplasm.
Assuntos
Adenoma Oxífilo/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Receptores de Progesterona/metabolismo , Adenoma Oxífilo/cirurgia , Carcinoma de Células Renais/cirurgia , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Diagnóstico Diferencial , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Renais/cirurgia , Masculino , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores de Estrogênio/metabolismoRESUMO
BACKGROUND: Type 2 diabetes is characterised by a progressive decline in HbA1c control over time. Early combination therapy, rather than sequential introduction of individual oral glucose-lowering agents, has been proposed to prevent this gradual rise in HbA1c. This observational study assessed the effect of early dual combination oral glucose-lowering therapies within 6 months of diagnosis in newly diagnosed, drug-naïve patients with type 2 diabetes. PATIENTS AND METHODS: This was an observational, open-label, non-randomised study in newly diagnosed patients with type 2 diabetes, aged 35-70 years, with HbA1c levels > 8.0% at diagnosis or > 7.0% at the 3-6-month follow-up. Patients were allocated to dietary management alone if the HbA1c level was 7.0-8.0% at diagnosis. Metformin combined with gliclazide, repaglinide, or pioglitazone was given at diagnosis if the HbA1c was > 8.0%. Similar treatments were introduced at 3-6 months if the HbA1c was > 7.0%. Over a 3-year period, HbA1c was measured at 3-monthly intervals. All patients underwent regular dietetic review. Target HbA1c was < or = 7.0%. RESULTS: 416 patients were considered eligible for inclusion, with a mean (+/- SD) age of 54.1 +/- 9.2 years, BMI of 33.5 +/- 6.1 kg/m2, and baseline HbA1c of 8.6 +/- 1.7%. A mixed model analysis of variance on the 178 patients who started with combination therapy, either immediately or after a 3-6 month period on diet, showed that metformin plus gliclazide, repaglinide, or pioglitazone was associated with a gradual increase in HbA1c values. Amongst those patients treated with the metformin/pioglitazone combination there was an estimated 0.1% increase in HbA1c/year. This was much less pronounced than the rises seen in HbA1c/year of 0.5% with the metformin/gliclazide and metformin/repaglinide combinations. CONCLUSIONS: This preliminary analysis of an observational, non-randomised, open-label ongoing study has shown that early use of combination therapy at time of diagnosis or within the first 3-6 months following diagnosis with metformin plus pioglitazone in newly diagnosed type 2 diabetes results in a slower deterioration in glycaemic control than that with metformin combined with either gliclazide or repaglinide. This may be due to the beta-cell protective properties of pioglitazone. These results need to be confirmed by further studies with a more robust design and methodology.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Adulto , Glicemia/análise , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Pioglitazona , Tiazolidinedionas/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Although physical irritant contact dermatitis (PICD) is a common occupational dermatosis, it is one of the least well understood because of its multiple types, lack of diagnostic test, and the many mechanisms involved in its production. OBJECTIVES: To characterize the materials and mechanisms of physical irritation of the skin. METHODS: We did a retrospective analysis over the past 20 years of all patients with a diagnosis of PICD at St John's Institute of Dermatology Contact Dermatitis Clinic. RESULTS: Of the 29,000 patients who attended the clinic over the study period, 392 patients were diagnosed with PICD and of these, 335 files were analysed. CONCLUSIONS: Our findings show that PICD accounted for 1.15% of all patients attending the contact clinic over the study period. Diverse occupations and materials were implicated. The most common cause of PICD was low humidity due to air-conditioning, which caused dermatitis of the face and neck in office workers due to drying out of the skin.
Assuntos
Dermatite de Contato/etiologia , Dermatite Ocupacional/etiologia , Passatempos , Irritantes/efeitos adversos , Adolescente , Adulto , Idoso , Ar Condicionado/efeitos adversos , Criança , Pré-Escolar , Poeira/efeitos adversos , Feminino , Traumatismos da Mão/complicações , Auxiliares de Audição/efeitos adversos , Temperatura Alta/efeitos adversos , Humanos , Umidade , Lactente , Masculino , Metais/efeitos adversos , Pessoa de Meia-Idade , Papel , Plásticos/efeitos adversos , Próteses e Implantes/efeitos adversos , Roupa de Proteção/efeitos adversos , Estudos Retrospectivos , Borracha/efeitos adversos , MadeiraRESUMO
Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.
Assuntos
Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Neoplasias das Glândulas Suprarrenais/classificação , Neoplasias das Glândulas Suprarrenais/mortalidade , Idoso , Neoplasias Ósseas/classificação , Neoplasias Ósseas/mortalidade , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/mortalidade , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Técnicas Imunoenzimáticas , Queratinas/análise , Neoplasias Renais/classificação , Neoplasias Renais/mortalidade , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Vimentina/análiseRESUMO
Over the past two years, ATP has clearly been shown to act as a co-transmitter with GABA, glycine and probably glutamate in the central nervous system. Our understanding of the ATP-gated P2X receptors is progressing rapidly, and the pharmacology, stoichiometry and subunit combinations of heteropolymeric P2X channels has been substantially elucidated.
Assuntos
Proteínas do Tecido Nervoso/fisiologia , Receptores Purinérgicos P2/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Trifosfato de Adenosina/fisiologia , Animais , Encéfalo/fisiologia , Previsões , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/fisiologia , Canais Iônicos/fisiologia , Mamíferos/fisiologia , Modelos Neurológicos , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/imunologia , Neuroglia/efeitos dos fármacos , Neuroglia/fisiologia , Proteína Quinase C/fisiologia , Subunidades Proteicas , Agonistas do Receptor Purinérgico P2 , Ratos , Receptores de GABA/fisiologia , Receptores Pré-Sinápticos/efeitos dos fármacos , Receptores Pré-Sinápticos/fisiologia , Receptores Purinérgicos P2/química , Receptores Purinérgicos P2/imunologia , Proteínas Recombinantes de Fusão/fisiologia , Relação Estrutura-AtividadeRESUMO
PURPOSE: Accurate spatial representation of tumor clearance after conformal radiotherapy is an endpoint of clinical importance. Magnetic resonance spectroscopy (MRS) can diagnose malignancy in the untreated prostate gland through measurements of cellular metabolites. In this study we sought to describe spectral metabolic changes in prostatic tissue after radiotherapy and validate a multivariate analytic strategy (based on MRS) that could identify viable tumor. METHODS AND MATERIALS: Transrectal ultrasound-guided prostate biopsies from 35 patients were obtained 18-36 months after external beam radiotherapy. One hundred sixteen tissue specimens were subjected to 1H MRS, submitted to histopathology, and analyzed for correlation with a multivariate strategy specifically developed for biomedical spectra. RESULTS: The sensitivity and specificity of MRS in identifying a malignant biopsy were 88.9% and 92% respectively, with an overall classification accuracy of 91.4%. The diagnostic spectral regions identified by our algorithm included those due to choline, creatine, glutamine, and lipid. Citrate, an important discriminating resonance in the untreated prostate gland, was invisible in all spectra, regardless of histology. CONCLUSIONS: Although the spectral features of prostate tissue markedly change after radiotherapy, MRS combined with multivariate methods of analysis can accurately identify histologically malignant biopsies. MRS shows promise as a modality that could integrate three-dimensional measures of tumor response.