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1.
J Med Imaging Radiat Oncol ; 63(1): 142-150, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30461207

RESUMO

INTRODUCTION: The role of the radioprotector amifostine in ameliorating radiotherapy side effects in head and neck squamous cell carcinoma (HNSCC) is controversial. This trial aimed to determine whether pretreatment with amifostine reduced the incidence of Radiation Therapy Oncology Group grade ≥2 acute and late xerostomia in patients receiving definitive or adjuvant radiotherapy for HNSCC, without reducing tumour control or survival. METHODS: Between 14 September 2001 and 8 November 2004, 44 Royal Adelaide Hospital patients were randomized double-blind to receive amifostine (200 mg/m2 IV) or placebo (normal saline IV) 5 days/week, prior to standard radiotherapy (60-70 Gy), each having ≥75% of the parotids treated to ≥40 Gy. Side effects were assessed weekly during treatment, at 3 and 5 months after radiotherapy, then every 6 months until disease progression or death. RESULTS: The accrual target was 200 patients over 4-5 years, but the trial closed prematurely when only 44 patients had been randomized after 3 years. Of 41 evaluable patients, 80% (16/20) in the amifostine arm had grade ≥2 acute radiation salivary toxicity versus 76% (16/21) in the placebo arm (P = 1.00). The rate of grade ≥2 late radiation salivary toxicity at 12 months was 66% in the amifostine arm and 82% in the placebo arm (estimated hazard ratio 1.61, 95% confidence interval 0.74-3.49, P = 0.22). Other toxicities tended to be worse in the amifostine arm: acute grade 3-4 skin 35% vs 5% and mucous membrane 40% vs 5%; grade ≥2 vomiting 35% vs 5%, hypocalcaemia 25% vs 5% and fatigue 85% vs 33%, with only the latter retaining statistical significance after adjusting for multiple comparisons. There were no significant differences in failure-free (P = 0.70) or overall survival (P = 0.86), with estimated 4-year rates of 48% vs 54% and 49% vs 59% for the amifostine vs placebo arms respectively. CONCLUSION: There was no clear evidence that pretreatment with amifostine made any difference to the incidence of grade ≥2 acute or late xerostomia. Other toxicity tended to be more severe with amifostine. There was no effect on failure-free or overall survival. Acknowledging the low statistical power, these results do not support the use of IV amifostine pre-radiotherapy in HNSCC.


Assuntos
Amifostina/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Protetores contra Radiação/uso terapêutico , Xerostomia/etiologia , Xerostomia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Austrália do Sul , Taxa de Sobrevida , Resultado do Tratamento
2.
Forensic Sci Med Pathol ; 14(2): 236-240, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29572623

RESUMO

A 61-year-old female died in hospital with multiple organ failure 4 weeks following presentation with acute kidney injury, hemolytic anemia and methemoglobinemia. At autopsy, brown to black discoloration of cartilages was observed. Histology revealed brown pigmentation of the hyaline cartilage, with focal full-thickness erosion of the articular hyaline cartilage, characteristic of alkaptonuria (ochronosis). Although alkaptonuria is rarely fatal, this case illustrates a rare acute fatal complication. Accumulation of circulating homgentisic acid secondary to acute derangement of renal function is believed to have overwhelmed the endogenous antioxidant processes, resulting in hemolysis and methemoglobinemia, which were refractory to treatment. Small numbers of cases have previously been reported in the literature in patients known to suffer with the disease, all of which were preceded by acute kidney injury. Whilst the clinical diagnosis of alkaptonuria may be challenging, the autopsy findings of this rare condition are striking and this case illustrates the utility of the autopsy, albeit retrospectively, in arriving at a diagnosis. To our knowledge this is the first reported case where previously undiagnosed alkaptonuria has presented with methemoglobinemia.


Assuntos
Alcaptonúria/diagnóstico , Hemólise , Metemoglobinemia/etiologia , Ocronose/patologia , Injúria Renal Aguda/etiologia , Anemia Hemolítica/etiologia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia
3.
J Med Imaging Radiat Oncol ; 59(2): 255-64, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25345594

RESUMO

INTRODUCTION: The purpose of this retrospective review was to evaluate concordance with evidence-based quality indicator guidelines for prostate cancer patients treated radically in a 'generalist' (as distinct from 'sub-specialist') centre. We were concerned that the quality of treatment may be lower in a generalist centre. If so, the findings could have relevance for many radiotherapy departments that treat prostate cancer. METHODS: Two hundred fifteen consecutive patients received external beam radiotherapy (EBRT) and/or brachytherapy between 1.10.11 and 30.9.12. Treatment was deemed to be in line with evidence-based guidelines if the dose was: (i) 73.8-81 Gy at 1.8-2.0 Gy/fraction for EBRT alone (eviQ guidelines); (ii) 40-50 Gy (EBRT) for EBRT plus high-dose rate (HDR) brachytherapy boost (National Comprehensive Cancer Network (NCCN) guidelines); and (iii) 145 Gy for low dose rate (LDR) I-125 monotherapy (NCCN). Additionally, EBRT beam energy should be ≥6 MV using three-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT), and high-risk patients should receive neo-adjuvant androgen-deprivation therapy (ADT) (eviQ/NCCN). Treatment of pelvic nodes was also assessed. RESULTS: One hundred four high-risk, 84 intermediate-risk and 27 low-risk patients (NCCN criteria) were managed by eight of nine radiation oncologists. Concordance with guideline doses was confirmed in: (i) 125 of 136 patients (92%) treated with EBRT alone; (ii) 32 of 34 patients (94%) treated with EBRT + HDR BRT boost; and (iii) 45 of 45 patients (100%) treated with LDR BRT alone. All EBRT patients were treated with ≥6 MV beams using 3D-CRT (78%) or IMRT (22%). 84%, 21% and 0% of high-risk, intermediate-risk and low-risk patients received ADT, respectively. Overall treatment modality choice (including ADT use and duration where assessable) was concordant with guidelines for 176/207 (85%) of patients. CONCLUSION: The vast majority of patients were treated concordant with evidence-based guidelines suggesting that, within the limits of the selected criteria, prostate cancer patients are unlikely to be disadvantaged by receiving radiotherapy in this 'generalist' centre.


Assuntos
Institutos de Câncer/estatística & dados numéricos , Institutos de Câncer/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitais Gerais/estatística & dados numéricos , Neoplasias da Próstata/radioterapia , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Hospitais Gerais/normas , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Garantia da Qualidade dos Cuidados de Saúde/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Radioterapia/normas , Radioterapia/estatística & dados numéricos , Resultado do Tratamento
4.
Clin Vaccine Immunol ; 17(6): 954-65, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20410328

RESUMO

Cryptosporidium infection is commonly observed among children and immunocompromised individuals in developing countries, but large-scale outbreaks of disease among adults have not been reported. In contrast, outbreaks of cryptosporidiosis in the United States and Canada are increasingly common among patients of all ages. Thus, it seems likely that residents of regions where Cryptosporidium is highly endemic acquire some level of immunity, while residents of the developed world do not. A new immunodominant Cryptosporidium parvum antigen in the 15- to 17-kDa size range was identified as the Cryptosporidium parvum 60S acidic ribosomal protein P2 (CpP2). We developed a recombinant protein-based enzyme-linked immunosorbent assay for serologic population surveillance for antibodies that was 89% sensitive and 92% specific relative to the results of the large-format Western blot assay. The human IgG response is directed almost exclusively toward the highly conserved, carboxy-terminal 15 amino acids of the protein. Although IgG antibody cross-reactivity was documented with sera from patients with acute babesiosis, the development of an anti-CpP2 antibody response in our Peru study population correlated better with Cryptosporidium infection than with infection by any other parasitic protozoan. In Haiti, the prevalence of antibodies to CpP2 plateaus at 11 to 20 years of age. Because anti-CpP2 IgG antibodies were found only among residents of countries in the developing world where Cryptosporidium infection occurs early and often, we propose that this response may be a proxy for the intensity of infection and for acquired immunity.


Assuntos
Anticorpos Antiprotozoários/sangue , Clonagem Molecular , Cryptosporidium parvum/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/imunologia , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/administração & dosagem , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/metabolismo , Criança , Pré-Escolar , Cryptosporidium parvum/genética , Cryptosporidium parvum/imunologia , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Haiti , Humanos , Imunização , Epitopos Imunodominantes , Dados de Sequência Molecular , Peru , Fosfoproteínas/administração & dosagem , Fosfoproteínas/metabolismo , Coelhos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Ribossômicas/administração & dosagem , Proteínas Ribossômicas/metabolismo , Sensibilidade e Especificidade
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