Locally Advanced and Metastatic Prostate Cancer Treated with Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results from a Randomised Phase 3 Study by the South European Uroncological Group

BACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Advanced instrumentation for superheated liquid detectors in dark matter searches

Dissertação para obtenção do Grau de Doutor em Engenharia Física

Procurement strategies in the health sector: How advanced are procurement processes in Portuguese hospitals

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Purification of complex biopharmaceuticals with new processes, advanced analytics and computer-aided process design tools

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Mercury exposure and malaria prevalence among gold miners in Pará, Brazil

Economic development, including resource extraction, can cause toxic exposures that interact with endemic infectious diseases. Mercury is an immunotoxic metal used in the amalgamation of gold, resulting in both occupational exposures and environmental pollution. A cross-sectional medical survey was conducted in 1997 on 135 garimpeiros in Para, Brazil, because of their risks of both mercury exposure and malaria transmission. Mean levels of blood and urine mercury were well above non-exposed background levels. Twenty-six subjects had malaria parasitemia: Health symptoms consistent with mercury exposure were reported, but neither symptoms nor signs correlated with mercury levels in blood or urine. We did not find a dose response relationship between mercury exposure and likelihood of prevalent malaria infection, but there was a possible reduction in acquisition of immunity that may be associated with conditions in gold mining, including mercury exposure.

Advanced megaesophagus (Group III) secondary to vector-borne Chagas disease in a 20-month-old infant

The authors report the case of a female infant with Group III (or Grade III) megaesophagus secondary to vector-borne Chagas disease, resulting in severe malnutrition that reversed after surgery (Heller technique). The infant was then treated with the antiparasitic drug benznidazole, and the infection was cured, as demonstrated serologically and parasitologically. After follow-up of several years without evidence of disease, with satisfactory weight and height development, the patient had her first child at age 23, in whom serological tests for Chagas disease yielded negative results. Thirty years after the initial examination, the patient's electrocardiogram, echocardiogram, and chest radiography remained normal.

Long term (five-year) survival following radical surgical treatment plus adjuvant chemotherapy (FAM) in advanced gastric cancer: a controlled study

Several drugs and their associations are being used for adjuvant or complementary chemotherapy with the aim of improving results of gastric cancer treatment. The objective of this study was to verify the impact of these drugs on nutrition and on survival rate after radical treatment of 53 patients with gastric cancer in stage III of the TNM classification. A control group including 28 patients who had only undergone radical resection was compared to a group of 25 patients who underwent the same operative technique followed by adjuvant polychemotherapy with FAM (5-fluorouracil, Adriamycin, and mitomycin C). In this latter group, chemotherapy toxicity in relation to hepatic, renal, cardiologic, neurological, hematologic, gastrointestinal, and dermatological functions was also studied. There was no significant difference on admission between both groups in relation to gender, race, macroscopic tumoral type of tumor according to the Borrmann classification, location of the tumor in the stomach, length of the gastric resection, or response to cutaneous tests on delayed sensitivity. Chemotherapy was started on average, 2.3 months following surgical treatment. Clinical and laboratory follow-up of all patients continued for 5 years. The following conclusions were reached: 1) The nutritional status and incidence of gastrointestinal manifestation were similar in both groups; 2) There was no occurrence of cardiac, renal, neurological, or hepatic toxicity or death due to the chemotherapeutic method per se; 3) Dermatological alterations and hematological toxicity occurred exclusively in patients who underwent polychemotherapy; 4) There was no significant difference between the rate and site of tumoral recurrence, the disease-free interval, or the survival rate of both study groups; 5) Therefore, we concluded, after a 5-year follow-up, chemotherapy with the FAM regimen did not increase the survival rate.

Prognostic factors in locally advanced colon cancer treated by extended resection

The impact of clinical, pathologic, and surgical variables on the postoperative morbidity, mortality, and survival of patients undergoing extended resections of colon carcinoma were evaluated. METHODS: The medical records of 95 patients who underwent extended resections for colon carcinoma between 1953 and 1996 were reviewed. In all cases, in addition to colectomy, 1 or more organs and/or structures were resected en bloc due to a macroscopically based suspicion of tumor invasion. The clinical, pathologic, and surgical parameters were analyzed. Overall survival rates were analyzed according to the method of Kaplan and Meier. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Eighty-six patients were treated by curative surgeries and the remaining by palliative resections. Invasion of the organs and/or adjacent structures and regional lymph nodes was found microscopically in 48 and 31 patients, respectively. The median follow-up without postoperative mortality was 47.7 months. The 5-year overall survival rates was 52.6%. The 5-year overall survival rates for patients undergoing curative and palliative surgeries was 58.3% and 0%, respectively. The mean survival time in the palliative surgery group was 3.1 months. Multivariate analysis showed that Karnofsky performance status was strongly related to the risk of postoperative complications (P = .01), and postoperative deaths were associated with the type of surgery and Karnofsky performance status at the time of admission (P = .001). CONCLUSIONS: Some patients with locally advanced colon adenocarcinomas undergoing extended resections have a 5-year overall survival rates of 58.3%. Patients could benefit from palliative-intent procedures, but these measures should cautiously be indicated and avoided in patients with low Karnofsky performance status due to high rates of postoperative mortality and poor survival.

Affordable prefabricated modular houses using cement and polymer based materials and advanced design tools

By taking advantage of the appropriate use of cement and polymer based materials and advanced computational tools, a pre-fabricated affordable house was built in a modular system. Modular system refers to the complete structure that is built-up by assembling pre-fabricated sandwich panels composed of steel fibre reinforced self-compacting concrete (SFRSCC) outer layers that are connected by innovative glass fibre reinforced polymer (GFRP) connectors, resulting in a panel with adequate structural, acoustic, and thermal insulation properties. The modular house was prepared for a typical family of six members, but its living area can be easily increased by assembling other pre-fabricated elements. The speed of construction and the cost of the constructive elements make these houses competitive when compared to traditional solutions. In this paper the relevant research subjacent to this project (LEGOUSE) is briefly described, as well as the construction process of the built real scale prototype.

A description of mercury in fishes from the Madeira River Basin, Amazon, Brazil

Over the last 20 years several projects carried on the Madeira River basin in the Amazon produced a great amount data on total Hg concentration in different fish species. In this paper we discuss temporal trends in Hg contamination and its relation to body weight in some of those fishes, showing that even within similar groups, such as carnivorous and non-migratory fish, the interspecies variability in Hg accumulation is considerable.

Green composites for advanced technical applications

This paper provides an overview of properties and application of natural fibre composites. Natural fibre market, merits and demerits, surface treatment techniques, properties of some recently developed natural fibre composites and applications have been discussed.

Towards high performance and multi-functional structural membranes using advanced fibrous and textile materials

Scientific and technological advancements in the area of fibrous and textile materials have greatly enhanced their application potential in several high-end technical and industrial sectors including construction, transportation, medical, sports, aerospace engineering, electronics and so on. Excellent performance accompanied by light-weight, mechanical flexibility, tailor-ability, design flexibility, easy fabrication and relatively lower cost are the driving forces towards wide applications of these materials. Cost-effective fabrication of various advanced and functional materials for structural parts, medical devices, sensors, energy harvesting devices, capacitors, batteries, and many others has been possible using fibrous and textile materials. Structural membranes are one of the innovative applications of textile structures and these novel building skins are becoming very popular due to flexible design aesthetics, durability, lightweight and cost benefits. Current demand on high performance and multi-functional materials in structural applications has motivated to go beyond the basic textile structures used for structural membranes and to use innovative textile materials. Structural membranes with self-cleaning, thermoregulation and energy harvesting capability (using solar cells) are examples of such recently developed multi-functional membranes. Besides these, there exist enormous opportunities to develop wide varieties of multi-functional membranes using functional textile materials. Additionally, it is also possible to further enhance the performance and functionalities of structural membranes using advanced fibrous architectures such as 2D, 3D, hybrid, multi-layer and so on. In this context, the present paper gives an overview of various advanced and functional fibrous and textile materials which have enormous application potential in structural membranes.

High levels of Mercury and Lead detected by hair analysis in two Venezuelan environments

Mercury and Lead concentrations obtained by ICP-OAS analysis of human hair from riverside communities along the Orinoco river in the Amazon state (Venezuela) were compared with those from Caracas, Venezuela. Taking into account the characteristics of these two environments and the values of the average concentrations of Mercury and Lead, baselines were established suggesting that gold mining activity near the Orinoco river is responsible for the high levels of Mercury in hair from the Amazon state, whereas automobile activity is responsible for high levels of Lead in hair in Caracas.

A first evaluation on the use of Ardea albus feathers as bioindicators of mercury burden in Amazonian ecosystems

We evaluated in this study the total mercury concentration in feathers of Ardea albus collected in a colony located in the city of Belem-PA, Brazil in a prospective trial for its use as bioindicators of mercury burden in Amazonia ecosystems. An Atomic absorption spectrophotometry with gold amalgamation was used for the metal determination. The total mercury average concentration in body feathers was 2.2 ± 1.5 µg.g-1 and 1.3 ± 0.9 µg.g-1 in wing feathers. No correlation was observed between total mercury concentration and the length of body or wing feathers. Total mercury concentration was above 5 µg.g-1 dry weight in only one body feather sample.