Progression of the load of waterborne and intestinal parasitic diseases in the State of Amazonas

In the State of Amazonas, Brazil, urban expansion together with precarious basic sanitation conditions and human settlement on river banks has contributed to the persistence of waterborne and intestinal parasitic diseases. Time series of the recorded cases of cholera, typhoid fever, hepatitis A and leptospirosis are described, using data from different levels of the surveillance systems. The sources for intestinal parasitosis prevalence data (non-compulsory reporting in Brazil) were Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana (LILACS) and the annals of major scientific meetings. Relevant papers and abstracts in all languages were accessed by two independent reviewers. The references cited by each relevant paper were scrutinized to locate additional papers. Despite its initial dissemination across the entire State of Amazonas, cholera was controlled in 1998. The magnitude of typhoid fever has decreased; however, a pattern characterized by eventual outbreaks still remains. Leptospirosis is an increasing cause of concern in association with the annual floods. The overall prevalence of intestinal parasites is high regardless of the municipality and the characteristics of areas and populations. The incidence of hepatitis A has decreased over the past decade. A comparison of older and recent surveys shows that the prevalence of intestinal parasitic diseases has remained constant. The load of waterborne and intestinal parasitic diseases ranks high among the health problems present in the State of Amazonas. Interventions aiming at basic sanitation and vaccination for hepatitis A were formulated and implemented, but assessment of their effectiveness in the targeted populations is still needed.

Laparoscopic treatment of retroperitoneal fibrosis: report of two cases and review of the literature

OBJECTIVES: We present the results of treatment by laparoscopy of two patients with retroperitoneal fibrosis and review the literature since 1992, when the first case of this disease that was treated using laparoscopy was published. We also discuss the contemporary alternatives of clinical treatment with corticosteroids and tamoxifen. CASE REPORT: Two female patients, one with idiopathic retroperitoneal fibrosis, and other with retroperitoneal fibrosis associated with Riedel's thyroiditis, were treated using laparoscopic surgery. Both cases had bilateral pelvic ureteral obstruction and were treated using the same technique: transperitoneal laparoscopy, medial mobilization of both colons, liberation of both ureters from the fibrosis, and intraperitonealisation of the ureters. Double-J catheters were inserted before the operations and removed 3 weeks after the procedures. The first patient underwent intraperitonealisation of both ureters in a single procedure. The other had 2 different surgical procedures because of technical difficulties during the first operation. Both patients were followed for more than 1 year and recovered completely from the renal insufficiency. One of them still has occasional vague lumbar pain. There were no abnormalities in the intravenous pyelography in either case. CONCLUSIONS: Surgical correction of retroperitoneal fibrosis, when indicated, should be attempted using laparoscopy. If possible, bilateral ureterolysis and intraperitonealisation of both ureters should be performed in the same operation.

Correlation between osteochondral changes depicted by magnetic resonance imaging and disease progression

PURPOSE: To determine the consequences of the chronic use of systemic corticosteroids in children with juvenile rheumatoid arthritis by means of evaluating osteochondral effects depicted by magnetic resonance imaging. PATIENTS AND METHODS: We reviewed clinical and magnetic resonance imaging findings in 69 children (72 knees) with juvenile rheumatoid arthritis. Two groups were studied. Group I: 34 (49.3%) children had previous or current use of systemic corticotherapy (22 girls; 12 boys; mean age: 11.3 years; mean disease duration: 5.9 years; mean corticotherapy duration: 2.9 years; mean cumulative dose of previous corticosteroids: 5000 mg); Group II: 35 (50.7%) children had no previous use of corticosteroids (27 girls; 8 boys; mean age: 11.7 years; mean disease duration: 5.3 years). The groups were compared statistically. RESULTS: In the group that had received corticotherapy (Group I), osteochondral abnormalities were significantly correlated to long-standing disease (>3.5 years; p<0.001). This correlation was not found in the group that had no previous history of corticotherapy (Group II). No correlations were established between median dose of corticosteroids and magnetic resonance imaging findings. CONCLUSION: It is important to further investigate the long-term intra-articular effects of systemic corticotherapy to ensure that the side effects of the aggressive therapy will not be more harmful for the joints than the symptoms suffered over the natural course of the disease.

Cystic fibrosis with normal sweat chloride concentration: case report

Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy

Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula. PURPOSE: To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula. METHOD: Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each) and their respective controls (sham-operated controls - Sh), Sh4 and Sh8 (8 rats each). Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up. RESULT: Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg), used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 ± 4.1) than in Sh8 (100.8 ± 1.3), but comparable between aortocaval fistula 4 (50.0 ± 8.9) and Sh4 (84.8 ± 2.3). Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r² = .86, P <.001), whereas left ventricular systolic pressure (r² = 0.73, P = .004) and end-diastolic pressure (r² = 0.55, P = 012) correlated positively and independently with interstitial fibrosis. CONCLUSION: Coronary driving pressure falls and ventricular pressures increase early after aortocaval fistula and are associated with subsequent myocardial fibrosis deposition.

The reasons behind the progression in PISA scores: An education production function approach using semi-parametric techniques

Research Masters

Strategies to regulate myopia progression with contact lenses: a review

Purpose: Higher myopic refractive errors are associated with serious ocular complications that can put visual function at risk. There is respective interest in slowing and if possible stopping myopia progression before it reaches a level associated with increased risk of secondary pathology. The purpose of this report was to review our understanding of the rationale(s) and success of contact lenses (CLs) used to reduce myopia progression. Methods: A review commenced by searching the PubMed database. The inclusion criteria stipulated publications of clinical trials evaluating the efficacy of CLs in regulating myopia progression based on the primary endpoint of changes in axial length measurements and published in peerreviewed journals. Other publications from conference proceedings or patents were exceptionally considered when no peer-review articles were available. Results: The mechanisms that presently support myopia regulation with CLs are based on the change of relative peripheral defocus and changing the foveal image quality signal to potentially interfere with the accommodative system. Ten clinical trials addressing myopia regulation with CLs were reviewed, including corneal refractive therapy (orthokeratology), peripheral gradient lenses, and bifocal (dual-focus) and multifocal lenses. Conclusions: CLs were reported to be well accepted, consistent, and safe methods to address myopia regulation in children. Corneal refractive therapy (orthokeratology) is so far the method with the largest demonstrated efficacy in myopia regulation across different ethnic groups. However, factors such as patient convenience, the degree of initial myopia, and non-CL treatments may also be considered. The combination of different strategies (i.e., central defocus, peripheral defocus, spectral filters, pharmaceutical delivery, and active lens-borne illumination) in a single device will present further testable hypotheses exploring how different mechanisms can reinforce or compete with each other to improve or reduce myopia regulation with CLs.

Pseudomonas aeruginosa diversification during infection development in cystic fibrosis lungs

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Urothelial bladder cancer progression: lessons learned from the bench

Urothelial bladder carcinoma (UBC) is an intricate malignancy with a variable natural history and clinical behavior. Despite developments in diagnosis/prognosis refinement and treatment modalities, the recurrence rate is high, and progression from non-muscle to muscle invasive UBC commonly leads to metastasis. Moreover, patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment, and overall survival rates are poor. Thus, UBC remains a challenge in the oncology field, representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence, progression, and chemo-refractoriness. However, progress toward personalized medicine has been hampered by the unique genetic complexity of UBC. Recent genome-wide expression and sequencing studies have brought new insights into its molecular features, pathogenesis and clinical diversity, revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups. Hence, it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation. In this review, we have summarized ours and others' research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer: tumor neovascularization, invasion and metastasis, and energy metabolism reprogramming of the tumor microenvironment.

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for Monocarboxylate Transporters as metabolic targets for therapy.

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.

Transmission and progression to disease of Mycobacterium tuberculosis phylogenetic lineages in The Netherlands

The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.

Real-time monitoring of progression towards renal failure in primary care patients

First published online: December 16, 2014.

Mitral valve disease with rheumatic appearance in the presence of left ventricular endomyocardial fibrosis

This is a report of a nine-year-old boy with both mitral stenosis and regurgitation and extensive endomyocardial fibrosis of the left ventricle. Focus is given to the singularity of the fibrotic process, with an emphasis on the etiopathogenic aspects.

Endomyocardial fibrosis associated with massive calcification of the left ventricle

This is the report of a rare case of endomyocardial fibrosis associated with massive calcification of the left ventricle in a male patient with dyspnea on great exertion, which began 5 years earlier and rapidly evolved. Due to lack of information and the absence of clinical signs that could characterize impairment of other organs, the case was initially managed as a disease with a pulmonary origin. With the evolution of the disease and in the presence of radiological images of heterogeneous opacification in the projection of the left ventricle, the diagnostic hypothesis of endomyocardial disease was established. This hypothesis was later confirmed on chest computed tomography. The patient died on the 16th day of the hospital stay, probably because of lack of myocardial reserve, with clinical findings of refractory heart failure, possibly aggravated by pulmonary infection. This shows that a rare disease such as endomyocardial fibrosis associated with massive calcification of the left ventricle may be suspected on a simple chest X-ray and confirmed by computed tomography.

Clinical Meaning of Ascites in Patients with Endomyocardial Fibrosis

OBJECTIVE: To evaluate the clinical meaning of ascites and the main features of patients with ascites and endomyocardial fibrosis. METHODS: We studied 166 patients with endomyocardial fibrosis (mean age 37 years, 114 women) treated over the last 20 years. Ventriculography findings, surgery or necropsy confirmed the diagnosis in all patients. Most patients belonged to New York Heart Association Functional Class III/IV (134, 83.7%). Eighty-one (50.6%) had biventricular, 28 (17.5%) had right ventricular, and 51 (31.8%) had left ventricular involvement. During follow-up, 56 patients died. RESULTS: Ascites was present in 67 (41.8%) patients, and right ventricular involvement was present in 59 (88%). In the comparison between patients with or without ascites, those with ascites had higher mortality (49.2% and 24.7%, respectively). Patients with ascites had a higher incidence of edema (95% vs. 43%), hepatomegaly (5.8cm vs. 4.1cm), mean right atrium pressure (19.3 vs. 12mmHg), and final right ventricle diastolic pressure (18.7 vs. 12.9mmHg). Also, patients with ascites had a longer history of illness (5.1 and 3.9 years, respectively) and had atrial fibrillation more frequently (44.7% vs. 30.1%). CONCLUSION: Ascites was observed in less than 50% of cases of endomyocardial fibrosis and was associated with greater involvement of the right ventricle and with a longer duration of the disease, thus being a characteristic of a worse prognosis.