Effects of a Shortage of Imiglucerase on Three Patients with Type I Gaucher Disease

Background: Children with Gaucher disease type I (GD1) are usually treated with enzyme replacement therapy (ERT) at a dose of 30-60U/Kg/2W. Recently, due to an acute shortage supply of imiglucerase, a reduced dose or a reduced infusion frequency was recommended. Objective: To evaluate the effects of a reduced infusion frequency of imiglucerase over 15 months of follow-up. Patients and Methods: Three patients (1M:2F) were treated with ERT since a median age of 7 years (range 5-12). Only one had bone crisis and Erlenmeyer deformations. Median duration of treatment before dose reduction was 3 years (range 1-8). ERT resulted in total regression of symptoms, normalization of hematological parameters and progressive improvement of chitotriosidase in all patients. In August 2009 infusion schedule was changed from a media 45U/Kg every two weeks to every four weeks. Results: All patients remained asymptomatic and with no major change on hematological parameters except for the patient with bone crisis who presented subnormal platelet count. All patients showed an upward trend in chitotriosidase values. Comments: Although a longer follow-up is needed, is probable that even children completely stabilized can probably not be kept on lower doses even though the reduction of frequency of the infusions represent a lower social burden.

Lagochilascaris minor Leiper, 1909 (Nematoda: Ascarididae) in Mexico: three clinical cases from the Peninsula of Yucatan

Human lagochilascariasis (HL) is a parasite produced by Lagochilascaris minor Leiper 1909 that also can be found in cats and dogs. HL is considered an emerging zoonosis in the Americas, spreading from Mexico to Argentina, and the Caribbean Islands. The present paper describes three HL cases from the Peninsula of Yucatan, Mexico, recorded in the last decade. It describes the characteristics of the lesions and discusses the route of transmission in humans and particularly in the observed patients.

Detection of Bartonella henselae DNA in clinical samples including peripheral blood of immune competent and immune compromised patients by three nested amplifications

Bacteria of the genus Bartonella are emerging pathogens detected in lymph node biopsies and aspirates probably caused by increased concentration of bacteria. Twenty-three samples of 18 patients with clinical, laboratory and/or epidemiological data suggesting bartonellosis were subjected to three nested amplifications targeting a fragment of the 60-kDa heat shock protein (HSP), the internal transcribed spacer 16S-23S rRNA (ITS) and the cell division (FtsZ) of Bartonella henselae, in order to improve detection in clinical samples. In the first amplification 01, 04 and 05 samples, were positive by HSP (4.3%), FtsZ (17.4%) and ITS (21.7%), respectively. After the second round six positive samples were identified by nested-HSP (26%), eight by nested-ITS (34.8%) and 18 by nested-FtsZ (78.2%), corresponding to 10 peripheral blood samples, five lymph node biopsies, two skin biopsies and one lymph node aspirate. The nested-FtsZ was more sensitive than nested-HSP and nested-ITS (p < 0.0001), enabling the detection of Bartonella henselae DNA in 15 of 18 patients (83.3%). In this study, three nested-PCR that should be specific for Bartonella henselae amplification were developed, but only the nested-FtsZ did not amplify DNA from Bartonella quintana. We conclude that nested amplifications increased detection of B. henselae DNA, and that the nested-FtsZ was the most sensitive and the only specific to B. henselae in different biological samples. As all samples detected by nested-HSP and nested-ITS, were also by nested-FtsZ, we infer that in our series infections were caused by Bartonella henselae. The high number of positive blood samples draws attention to the use of this biological material in the investigation of bartonellosis, regardless of the immune status of patients. This fact is important in the case of critically ill patients and young children to avoid more invasive procedures such as lymph nodes biopsies and aspirates.

Evaluation of three different DNA extraction methods from blood samples collected in dried filter paper in Plasmodium subpatent infections from the Amazon region in Brazil

Asymptomatic Plasmodium infection is a new challenge for public health in the American region. The polymerase chain reaction (PCR) is the best method for diagnosing subpatent parasitemias. In endemic areas, blood collection is hampered by geographical distances and deficient transport and storage conditions of the samples. Because DNA extraction from blood collected on filter paper is an efficient method for molecular studies in high parasitemic individuals, we investigated whether the technique could be an alternative for Plasmodium diagnosis among asymptomatic and pauciparasitemic subjects. In this report we compared three different methods (Chelex®-saponin, methanol and TRIS-EDTA) of DNA extraction from blood collected on filter paper from asymptomatic Plasmodium-infected individuals. Polymerase chain reaction assays for detection of Plasmodium species showed the best results when the Chelex®-saponin method was used. Even though the sensitivity of detection was approximately 66% and 31% for P. falciparum and P. vivax, respectively, this method did not show the effectiveness in DNA extraction required for molecular diagnosis of Plasmodium. The development of better methods for extracting DNA from blood collected on filter paper is important for the diagnosis of subpatent malarial infections in remote areas and would contribute to establishing the epidemiology of this form of infection.

Three transducers for one photodetector: essays for optical communications

Dissertation presented to obtain the PhD degree in Electrical and Computer Engineering - Electronics

Economic analysis in health care regulation : three essays

ABSTRACT - It is the purpose of the present thesis to emphasize, through a series of examples, the need and value of appropriate pre-analysis of the impact of health care regulation. Specifically, the thesis presents three papers on the theme of regulation in different aspects of health care provision and financing. The first two consist of economic analyses of the impact of health care regulation and the third comprises the creation of an instrument for supporting economic analysis of health care regulation, namely in the field of evaluation of health care programs. The first paper develops a model of health plan competition and pricing in order to understand the dynamics of health plan entry and exit in the presence of switching costs and alternative health premium payment systems. We build an explicit model of death spirals, in which profitmaximizing competing health plans find it optimal to adopt a pattern of increasing relative prices culminating in health plan exit. We find the steady-state numerical solution for the price sequence and the plan’s optimal length of life through simulation and do some comparative statics. This allows us to show that using risk adjusted premiums and imposing price floors are effective at reducing death spirals and switching costs, while having employees pay a fixed share of the premium enhances death spirals and increases switching costs. Price regulation of pharmaceuticals is one of the cost control measures adopted by the Portuguese government, as in many European countries. When such regulation decreases the products’ real price over time, it may create an incentive for product turnover. Using panel data for the period of 1997 through 2003 on drug packages sold in Portuguese pharmacies, the second paper addresses the question of whether price control policies create an incentive for product withdrawal. Our work builds the product survival literature by accounting for unobservable product characteristics and heterogeneity among consumers when constructing quality, price control and competition indexes. These indexes are then used as covariates in a Cox proportional hazard model. We find that, indeed, price control measures increase the probability of exit, and that such effect is not verified in OTC market where no such price regulation measures exist. We also find quality to have a significant positive impact on product survival. In the third paper, we develop a microsimulation discrete events model (MSDEM) for costeffectiveness analysis of Human Immunodeficiency Virus treatment, simulating individual paths from antiretroviral therapy (ART) initiation to death. Four driving forces determine the course of events: CD4+ cell count, viral load resistance and adherence. A novel feature of the model with respect to the previous MSDEMs is that distributions of time to event depend on individuals’ characteristics and past history. Time to event was modeled using parametric survival analysis. Events modeled include: viral suppression, regimen switch due virological failure, regimen switch due to other reasons, resistance development, hospitalization, AIDS events, and death. Disease progression is structured according to therapy lines and the model is parameterized with cohort Portuguese observational data. An application of the model is presented comparing the cost-effectiveness ART initiation with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus one non-nucleoside reverse transcriptase inhibitor(NNRTI) to two NRTI plus boosted protease inhibitor (PI/r) in HIV- 1 infected individuals. We find 2NRTI+NNRTI to be a dominant strategy. Results predicted by the model reproduce those of the data used for parameterization and are in line with those published in the literature.

Diagnosic Classification: Results from a Clinical Experience of Three Years with DC: 0–3

Infancy and early childhood are characterized by a dynamic and ever changing process. Since the beginning of their clinical work at the Infancy Unit, the authors were concerned with individual assessment and the questions about the role played by parents as well as by babies in pathology and intervention.In this article, the authors begin with a description of the path that led them to the selection of DC 0–3 as a diagnostic classification system and how this has been instrumental in helping them to better define infant psychopathology and guide them in treatment orientations. Next, they present the results of the applicationof Axis I and II of DC: 0–3 in their clinical population in the years 1997, 1998, and 1999. The objectives of this study were to learn more about the distribution of mental disorders in a clinical population up tofour years of age. The authors attempted to separate infants at risk for developing psychic disorders from those presenting current psychopathology as well as the possible influence of demographic features on this distribution, to define a target population and design adapted therapeutic measures. The identification of these objectives provides the rationale for the use of a diagnostic tool, like DC: 0–3, which is essential to plan clinical activity, to evaluate therapeutic efficacy, and to develop specific programs.

Three essays in risky behaviors

A PhD Dissertation, presented as part of the requirements for the Degree of Doctor of Philosophy from the NOVA - School of Business and Economics

Business plan for “Three Generations”

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

Comparison of vigilance methods in three houses with different Triatoma infestans densities

Através da prova de 7 dias foi estudado o grau de resistência do Plasmodium falciparum à cloroquina, amodiaquina e sulfadoxina-pirimetamina em Porto Velho, Estado de Rondônia, Brasil. Não se observaram diferenças significativas nas médias de parasitas nos dias de seguimento e nas proporções de resistência entre os três medicamentos testados, fazendo com que os autores recomendem a manutenção das 4-aminoquinoleínas como drogas a serem usadas atualmente em infecções não graves por P. falciparum na área de Porto Velho.

Pattern of acquisition of rotavirus antibody in children followed up from birth to the age of three years

Nine hundred and forty-eight serum samples from 83 children living in Belem, Brazil, collected'within their first three years of life, were testedfor the presence of group- specific rotavirus-antibody by an enzyme-linked immunosorbent assay (ELISA) blocking-test. Passively transferred maternal antibody lasted about two and half months; subsequentely, low levels of rotavirus antibody started to appear at seven months, reaching a peak at eleven months of age. From one year onwards positivity gradually increased, reaching highest values at 34 months of life. Individual responses were examined in sera from 61 children who were followed up since birth to three years of age: 38 (62,3%) ofthem developed a long-term immunity following first infection; eleven (18.0%) children developed a short-term immunity after first infection by rotavirus; seven (11.5%) had no antibody response within their first three years of life; and 5 (8.2%) showed positive antibody response from birth to three years old.

Three essays on the term structure of interest rates

A PhD Dissertation, presented as part of the requirements for the Degree of Doctor of Philosophy from the NOVA - School of Business and Economics