[The compulsory isolation of Hansen's disease patients: memories of the elderly].

From 1924 to 1962, Brazil used compulsory internment of Hansen's disease patients as one of the ways of controlling the disease in the community. After this policy ended, many patients continued to live in these units. The former Asilo Pirapitingui, now the Hospital Dr.

Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation.

In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, alpha-iodinated naphthofuranquinone (NPPN-3223), beta-iodinated naphthofuranquinone (NPPN-3222) and beta-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate-lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced to their seminaphthofuranquinone radical by the liver NADPH-P450 reductase system, as detected by ESR measurements.

Epicardial real-time 3-dimensional echocardiography with the use of a pediatric transthoracic probe: a technical approach.

Objective: The aim of the present study was to suggest a simple and comprehensive method for performing real-time 3-dimensional (3D) epicardial echocardiography with a pediatric probe small enough for the surgical field. Intraoperative echocardiography is a necessary tool for planning and performing cardiac surgery. Although epicardial intraoperative echocardiography is intended for few patients, it is a part of an exhaustive approach to intraoperative echocardiography.

Clinical and epidemiological characteristics of refractory hypertension in renal transplant patients.

Hypertension is common following renal transplantation, affecting up to 80% of recipients. It is generally accepted that hypertension is associated with poor graft survival and reduced life expectancy, contributing to increased cardiovascular risk factors and mortality rates. The prevalence of refractory hypertension among renal transplant patients is unknown; it may be associated with a worse prognosis.

In vitro analyses of the effect of aromatic diamidines upon Trypanosoma cruzi.

Objectives: Aromatic diamidines (ADs) have been recognized as promising antiparasitic agents. Therefore, in the present work, the in vitro trypanocidal effect of 11 ADs upon the relevant clinical forms of Trypanosoma cruzi was evaluated, as well as determining their toxicity to mammalian cells and their subcellular localization.

Methods: The trypanocidal effect upon trypomastigotes and amastigotes was evaluated by light microscopy through the determination of the IC(50) values.

Evaluating routine diagnostic imaging in acute appendicitis.

Aim: To evaluate the impact of selective imaging on clinical management of patients who present with symptoms suggesting acute appendicitis.

Materials And Methods: During a two-and-half year period, 941 consecutive patients with right lower quadrant pain were analyzed. Patients who underwent selective imaging were compared to those treated without further imaging.

Intracranial compound odontome.

An exceedingly rare case of an extragnathic odontome is described arising within the brain. A 10-year-old boy complained of progressive frontal headache for 5 years. Axial computerized tomography the head revealed a solid, calcified lesion with well-defined borders localized in the sellar and suprasellar region composed of multiple calcified structures resembling teeth.

Comparison of eight echocardiographic methods for determining the prevalence of mechanical dyssynchrony and site of latest mechanical contraction in patients scheduled for cardiac resynchronization therapy.

Prevalence of echocardiographically assessed mechanical dyssynchrony and consistency in detection of the latest mechanical left ventricular (LV) contracting region when different echocardiographic methods are used in the same patient remains ill-defined. The objectives of this study were to evaluate (1) the prevalence of intraventricular mechanical dyssynchrony and (2) consistency of latest mechanical LV contraction using a multiparametric approach derived from tissue Doppler imaging (TDI), 3-dimensional (3D) echocardiography, and speckle tracking in patients scheduled for cardiac resynchronization therapy (CRT). In 63 patients with heart failure scheduled for CRT, 2D echocardiography, TDI, 3D echocardiography, and speckle tracking were prospectively collected and analyzed.

The effects on Trypanosoma cruzi of novel synthetic naphthoquinones are mediated by mitochondrial dysfunction.

Despite ongoing efforts, the current treatment for Chagas disease is still unsatisfactory, mainly because of the severe side effects and variable efficacy of the available nitroheterocycles. Our group has been assaying natural quinones isolated from Brazilian flora, and their derivatives, as alternative chemotherapeutic agents against Trypanosoma cruzi. From C-allyl lawsone three naphthofuranquinones were synthesized, which were active against trypomastigotes and epimastigotes.

Relation between coronary atherosclerotic plaques and traditional risk factors in people with no history of cardiovascular disease undergoing multi-detector computed coronary angiography.

Aims: To prospectively investigate the prevalence of coronary artery plaques (CAP) as detected by computed tomography-based angiography in a large number of consecutive individuals with no history of coronary artery disease (CAD) or acute coronary syndrome; to evaluate whether traditional risk factors are related to prevalence of CAP and to the expected 10-year risk of first major or fatal cardiovascular event (CVE).

Design: Prospective, single-centre, cross-sectional study.

Setting: The division of Cardiology at Fondazione Cardiocentro Ticino Lugano, Switzerland.

Evaluation of POSSUM for patients undergoing pancreatoduodenectomy.

Background: Comparison of operative morbidity rates after pancreatoduodenectomy between units may be misleading because it does not take into account the physiological variable of the condition of the patients. The aim of the present study was to evaluate the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) for pancreatoduodenectomy patients and to look for risk factors associated with morbidity in a high-volume center.

Methods: Between January 1993 and April 2006, 652 patients underwent a pancreatoduodenectomy, 502 of them for malignant disease.

Novel 2- and 4-substituted 1H-imidazo[4,5-c]quinolin-4-amine derivatives as allosteric modulators of the A3 adenosine receptor.

4-Arylamino and 2- cycloalkyl (including amino substitution) modifications were made in a series of 1H-imidazo[4,5-c]quinolin-4-amine derivatives as allosteric modulators of the human A(3) adenosine receptor (AR). In addition to allosteric modulation of the maximum functional efficacy (in [(35)S]GTPgammaS G protein binding assay) of the A(3)AR agonist Cl-IB-MECA (15), some analogues also weakly inhibited equilibrium radioligand binding at ARs. 4-(3,5-Dichlorophenylamino) (6) or 2-(1-adamantyl) (20) substitution produced allosteric enhancement (twice the maximal agonist efficacy), with minimal inhibition of orthosteric AR binding.

Validation of a nomogram for predicting survival after resection for adenocarcinoma of the pancreas.

Background: Nomograms are statistical tools providing the overall probability of a specific outcome; they have shown better individual discrimination than the tumour node metastasis staging system in several cancers. The pancreatic nomogram, originally developed in the Memorial Sloan-Kettering Cancer Center (MSKCC) in the USA, combines clinicopathological and operative data to predict disease-specific survival at 1, 2 and 3 years from initial resection.

Methods: An external patient cohort from a retrospective pancreatic adenocarcinoma database at the Academic Medical Centre in Amsterdam was used to test the validity of the pancreatic adenocarcinoma nomogram.

Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi.

In a screening of 65 derivatives of natural quinones using bloodstream trypomastigotes of Trypanosoma cruzi, the 3 naphthoimidazoles derived from beta-lapachone - N1, N2 and N3--were selected as the most active. Investigation of their mode of action led to the characterization of mitochondrion, reservosomes and DNA as their main targets, and stimulated further studies on death pathways. Ultrastructural analysis revealed both autophagic (autophagosomes) and apoptotic-like (membrane blebbing) phenotypes.

Electron microscopy in antiparasitic chemotherapy: a (close) view to a kill.

Electron microscopy may be useful in chemotherapy studies at distinct levels, such as the identification of subcellular targets in the parasites and the elucidation of the ultimate drug mechanism of action, inferred by the alterations induced by antiparasitic compounds. In this review we present data obtained by electron microscopy approaches of different parasitic protozoa, such as Trypanosoma cruzi, Leishmania spp., Giardia lamblia and trichomonads, under the action of drugs, demonstrating that the cell architecture organization is only determined in detail at the ultrastructural level.

4-Benzyloxy-gamma-sultone derivatives: discovery of a novel family of non-nucleoside inhibitors of human cytomegalovirus and varicella zoster virus.

We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the 4-keto-1,2-oxathiole-2,2-dioxide (beta-keto-gamma-sultone) heterocyclic system. Several 4- and 5-substituted-5H-1,2-oxathiole-2,2-dioxide derivatives were found to have a selective inhibitory activity against human cytomegalovirus (HCMV) and varicella zoster virus (VZV) replication in vitro, being inactive against a variety of other DNA and RNA viruses. A structure-activity relationship (SAR) study showed that the presence of a benzyl at the 5 position and a benzyloxy substituent at the 4 position are a prerequisite for anti-HCMV and VZV activity.

Brazilian Green Propolis: Effects In Vitro and In Vivo on Trypanosoma cruzi.

The composition of a Brazilian green propolis ethanolic extract (Et-Bra) and its effect on Trypanosoma cruzi trypomastigotes and other pathogenic microorganisms have already been reported. Here, we further investigated Et-Bra targets in T. cruzi and its effect on experimental infection of mice.

Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous inherited disorder arising from dysmotility of motile cilia and sperm. This is associated with a variety of ultrastructural defects of the cilia and sperm axoneme that affect movement, leading to clinical consequences on respiratory-tract mucociliary clearance and lung function, fertility, and left-right body-axis determination. We performed whole-genome SNP-based linkage analysis in seven consanguineous families with PCD and central-microtubular-pair abnormalities.

Synthesis and characterization of [76Br]-labeled high-affinity A3 adenosine receptor ligands for positron emission tomography.

Introduction: Bromine-76-radiolabeled analogues of previously reported high-affinity A(3) adenosine receptor (A(3)AR) nucleoside ligands have been prepared as potential radiotracers for positron emission tomography.

Methods: The radiosyntheses were accomplished by oxidative radiobromination on the N(6)-benzyl moiety of trimethyltin precursors. Biodistribution studies of the kinetics of uptake were conducted in awake rats.

POSSUM predicts survival in patients with unresectable pancreatic cancer.

Background: The aim of this study was to evaluate the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) for patients with unresectable pancreatic cancer and to analyze whether POSSUM can predict the long-term outcome in these patients. Such a scoring system could be useful to aid in the decision between surgical and endoscopic palliation.

Methods: Between January 1993 and December 2004, 241 patients were found to have unresectable pancreatic cancer during exploratory laparotomy and underwent a double bypass procedure consisting of a gastrojejunostomy and a hepaticojejunostomy.

Trypanosoma cruzi targets for new chemotherapeutic approaches.

Background: Strategies for development of anti-parasite chemotherapy involve identification of active principles of plants, investigation of drugs already licensed for other pathologies, or validation of specific targets identified within key metabolic pathways.

Objective: To review the state of the art of drug targets against Trypanosoma cruzi with emphasis on sterol metabolism, kinetoplast DNA (kDNA) sites, trypanothione reductase, cysteine proteinase, hypoxanthine-guanine phosphoribosyltransferase, dihydrofolate reductase and glyceraldehyde-3-phosphate dehydrogenase.

Methods: Current knowledge, accumulated over the last three decades, on targets for design and development of new trypanocidal compounds is described.

Different cell death pathways induced by drugs in Trypanosoma cruzi: an ultrastructural study.

Electron microscopy has proven to be a reliable and essential tool to determine morphological alterations and target organelles in the investigation of new drugs for Chagas disease. In this review, we focused on evaluating different agents that induce death of Trypanosoma cruzi, i.e.

Pancreas-preserving total duodenectomy versus standard pancreatoduodenectomy for patients with familial adenomatous polyposis and polyps in the duodenum.

Background: Pancreas-preserving total duodenectomy (PPTD) was introduced as a replacement for pancreatoduodenectomy (PD) for familial adenomatous polyposis (FAP). This study analysed the results of PPTD in the Netherlands and reviewed the relevant literature.

Methods: All 26 patients who underwent PPTD for FAP in four centres in the Netherlands between January 2000 and January 2007 were compared with a group of 77 patients who had PD for ampulla of Vater adenocarcinoma at one centre during the same interval.