Ana Rosa Pinto Quidute

Contaminantes ambientais e os interferentes endócrinos

The toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reduction of its possible damages.

Preventive medicine for von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Tumores testiculares bilaterais por hiperplasia congênita de restos adrenais

OBJECTIVES Testicular tumors are a rare condition associated with congenital adrenal hyperplasia (CAH), originated from intratesticular adrenal rest tumors, and they are rarely associated with malignant tumors. Their histological differentiation from Leydig-cell tumors is quite difficult, which would lead to inappropriate orchiectomies. Thus the objective of this report was to present this diagnostic dilemma. METHODS Reported the case of 16-yr-old boy with previous diagnosis of CAH with bilateral testicular enlargement who was recommended to be submitted to a bilateral orchiectomy. RESULTS Considering this findings, it was decided to treat conventionally with prednisone with significant reduction of testicular volume, and normalization of androgens levels. CONCLUSION This case shows the importance of intratesticular adrenal rest tumors in the differential diagnosis of testicular tumors. Cautious approach during investigation and treatment are recommended to avoid inappropriate orchiectomies.

Pharmacotherapeutic follow-up of patients with Chagas disease using benznidazole: drug-related problems and pharmaceutical interventions

INTRODUCTION Benznidazole (BNZ) is a drug available for the etiological treatment of Chagas disease. However, this drug is toxic and has a limited effectiveness on the chronic phase of this disease, often leading to poor treatment adherence. METHODS: This is a descriptive and exploratory study conducted at the Pharmaceutical Care Service for Chagas disease patients of the Federal University of Ceará. Drug-related problems (DRPs) and pharmaceutical interventions (PIs) were classified according to the Second Consensus of Granada. RESULTS: The average age of patients with Chagas disease was 62 years, with the majority residing in the Ceará countryside (86.7%), and having low education levels (63.3% with elementary school education). Regarding family income, most patients belonged to a household that earned ≤1-2 times the minimum wage per month. Approximately 73% of these patients complied with the BNZ treatment, and nearly 7% underwent therapy interruption after medical evaluation. A total of 189 DRPs were identified, of which 51.9% (n=98) were classified as potential, and 48.1% (n=91) as actual. The most frequent DRPs were related to safety (qualitative safety; n=70; 37%), necessity (non-adherence; n=52; 27.5%), and effectiveness (qualitative effectiveness/non-optimal drug selection; n=45; 23.8%). Among the 216 PIs conducted, the majority were related to patient education (n=168; 77.8%) and pharmacological strategy (n=42; 19.4%). CONCLUSIONS: This study indicates the need for pharmacotherapeutic monitoring in patients with Chagas because of the high number of therapeutic interventions, DRPs (approximately 3 DRPs/patient), BNZ adherence, and polypharmacy.

Who Are the Super-Responders to Cardiac Resynchronization Therapy?

Fundamento: Pacientes submetidos a ressincronizacao cardiaca podem evoluir com padroes de resposta acima do esperado, com normalizacao dos parâmetros clinicos e ecocardiograficos. Objetivo: Analisar as caracteristicas clinicas e ecocardiograficas desta populacao de super-respondedores, comparando-as com os demais pacientes submetidos a terapia de ressincronizacao cardiaca. Metodos: Estudo de coorte observacional, prospectivo, envolvendo 146 pacientes, consecutivamente submetidos a implantes de ressincronizador cardiaco. Para comparacao das variaveis, foram realizados o teste exato de Fisher e o teste de Mann-Whitney. Foram considerados super-respondedores os pacientes com fracao de ejecao > 50 % e classe funcional I/II (New York Heart Association) apos 6 meses da terapia de ressincronizacao cardiaca. Resultados: A idade media foi de 64,8 ± 11,1 anos, sendo 69,8% do sexo masculino, com mediana da fracao de ejecao de 29%, sendo 71,5% com bloqueio de ramo esquerdo, 12% com bloqueio de ramo direito associado a bloqueios divisionais; 16,3% com marca-passo cardiaco definitivo, 29,3% com miocardiopatia isquemica, 59,4% com miocardiopatia dilatada e 11,2% com miocardiopatia chagasica. Foram observados 24 (16,4%) super-respondedores, sendo que 13 (8,9%) apresentaram normalizacao da fracao de ejecao, dos diâmetros diastolicos do ventriculo esquerdo e da classe funcional. Quando comparados com os pacientes nao super-respondedores, em relacao as caracteristicas pre-implante, os super-respondedores apresentaram-se mais no sexo feminino (58,3% vs. 22,8%; p = 0,002), maior indice de massa corporal (26,8 vs. 25,5; p = 0,013), maior fracao de ejecao basal (31,0 vs. 26,9; p = 0,0003) e menores diâmetros diastolicos do ventriculo esquerdo (65,9 mm vs. 72,6 mm; p = 0,0032). Dez pacientes (41,6% dos super-respondedores) com bloqueio de ramo direito e bloqueio divisional evoluiram como super-respondedores, entretanto apenas um paciente com doenca de Chagas e apenas na primeira avaliacao. Conclusoes: Os super-respondedores apresentaram cardiopatia de base menos avancada e sem diferencas em relacao ao tipo de disturbio de conducao basal. Pacientes com bloqueio de ramo direito e bloqueio divisional, mas sem cardiopatia chagasica podem tambem evoluir como super-respondedores.

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.

Development and Validation of Predictive Models of Cardiac Mortality and Transplantation in Resynchronization Therapy

Background 30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes. Objective This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx) at different stages of cardiac resynchronization therapy (CRT). Methods Prospective observational study of 116 patients aged 64.8 ± 11.1 years, 68.1% of whom had functional class (FC) III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves. Results The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 ± 17.9 months. Prior to implantation, right ventricular dysfunction (RVD), ejection fraction < 25% and use of high doses of diuretics (HDD) increased the risk of cardiac death and Tx by 3.9-, 4.8-, and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping. Conclusion We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT.

Echocardiographic Predictors of Worse Outcome After Cardiac Resynchronization Therapy

Background Cardiac resynchronization therapy (CRT) is the recommended treatment by leading global guidelines. However, 30%-40% of selected patients are non-responders. Objective To develop an echocardiographic model to predict cardiac death or transplantation (Tx) 1 year after CRT. Method Observational, prospective study, with the inclusion of 116 patients, aged 64.89 ± 11.18 years, 69.8% male, 68,1% in NYHA FC III and 31,9% in FC IV, 71.55% with left bundle-branch block, and median ejection fraction (EF) of 29%. Evaluations were made in the pre-implantation period and 6-12 months after that, and correlated with cardiac mortality/Tx at the end of follow-up. Cox and logistic regression analyses were performed with ROC and Kaplan-Meier curves. The model was internally validated by bootstrapping. Results There were 29 (25%) deaths/Tx during follow-up of 34.09 ± 17.9 months. Cardiac mortality/Tx was 16.3%. In the multivariate Cox model, EF < 30%, grade III/IV diastolic dysfunction and grade III mitral regurgitation at 6-12 months were independently related to increased cardiac mortality or Tx, with hazard ratios of 3.1, 4.63 and 7.11, respectively. The area under the ROC curve was 0.78. Conclusion EF lower than 30%, severe diastolic dysfunction and severe mitral regurgitation indicate poor prognosis 1 year after CRT. The combination of two of those variables indicate the need for other treatment options.

Perfil microbiológico e desfechos clinicos de úlceras em pés de diabéticos internados - doi:10.5020/18061230.2010.p231

Objectives: To describe the microbiological profile and clinical outcomes of diabetic foot ulcers of inpatients of a tertiary university hospital, at Ceara, Brazil. Methods: We conducted a retrospective analysis of medical charts data of all diabetic inpatients of the Endocrine and Diabetes Unit of Walter Cantidio University Hospital (Federal University of Ceara), admitted from January, 2006 to June, 2007 for severe foot ulcers (minimum of grade 2 of Wagner`s classification), which were refractory to ambulatory treatment. Clinical data from each patient were recorded (sex, age, diabetes duration, and comorbidities) as well as microbiological characteristics of foot ulcers and surgical (amputations) material. Results: We identified 17 diabetic patients, all type 2, aged 58.11 ± 10.8 years and 12.4 ± 8.4 years of disease, 58.8% male. Of ulcers, 41.1% were grade 2; 35.2% grade 3; 11.7% grade 4 and 11.7% grade 5 of Wagner; 64.7% with less than 3 months of evolution. Debridement was performed in 82.3% of patients and amputation in 47%; osteomyelitis was identified in 47% of cases. All patients started empiric antibiotic therapy, where ciprofloxacin/metronidazole was the most used scheme (76.5%). Cultures were negative in 12.5% of the patients. In the positive ones, the most prevalent bacterial pathogens detected in the culture materials were: S. aureus (57.1%); S. viridans (28.7%); P. aeruginosas (28.7%); M. morganii (28.7%). The majority (75%) of isolated S. aureus were methicillin-resistant, but were sensitive to vacomicin. Conclusion: We observed the presence of polymicrobial flora with a large number of multiresistant pathogens and high prevalence of osteomyelitis and amputations in diabetic patients with severe ulcers, neuropathy and peripheral vascular disease.

Projeto sala de espera: uma proposta para a educação em diabetes - doi:10.5020/18061230.2006.p197

Education is an essential aspect of diabetic care. For this, many strategies have been searched. The objectives of the present study were to describe “The Waiting Room Project”, a proposal based on using the time in which the patient waits for individual attendance, to promote Diabetes Education; and to evaluate the clinical and epidemiological profile of diabetic participants of this project. Twenty meetings were conducted from March to October 2006, with 350 patients followed-up at the Diabetes Clinics of Walter Cantidio University Hospital-UFC, and their companions. Of these, 76 randomly assigned patients were interviewed. The meetings occurred on each Friday, in 2 sessions of approximately half hour, which were coordinated by a multidisciplinary team, and took into account 25 patients each. At the end, a breakfast was served and used for nutritional education. Among the interviewed participants, women prevailed (85.5%), with mean age of 60.4±9.1 years, and average time of diagnosis of 10.6±5.9 years. In relation to treatment, 40.7% used insulin, 63.1% used oral anti-diabetics and 9.2% only adopted life style changes. Drugs compliance was present in only 47.8% of the participants and the majority (67.1%) did not practice physical activities. Regarding to the diet, only 31.5% fully adhered to it. More than 75% of the participants could read and write, and earned a minimum wage or less. From the observations derived from practice, one may perceive: a greater motivation of the patients after each meeting, a more active participation in doctor’s appointments and an increasing interest on their disease and care. To provide the participation of diabetic patients in their treatments, stimulating self-care, is a challenge to be reached by all health units, and that can be favored by strategies like this described.