Incidence, clinical spectrum, diagnostic features, treatment and predictors of paradoxical reactions during antibiotic treatment of Mycobacterium ulcerans infections

Background: Paradoxical reactions from antibiotic treatment of Mycobacterium ulcerans have recently been recognized. Data is lacking regarding their incidence, clinical and diagnostic features, treatment, outcomes and risk factors in an Australian population.

Methods: Data was collected prospectively on all confirmed cases of M. ulcerans infection managed at Barwon Health Services, Australia, from 1/1/1998-31/12/2011. Paradoxical reactions were defined on clinical and histological criteria and cases were determined by retrospectively reviewing the clinical history and histology of excised lesions. A Poisson regression model was used to examine associations with paradoxical reactions.

Results: Thirty-two of 156 (21%) patients developed paradoxical reactions a median 39 days (IQR 20-73 days) from antibiotic initiation. Forty-two paradoxical episodes occurred with 26 (81%) patients experiencing one and 6 (19%) multiple episodes. Thirty-two (76%) episodes occurred during antibiotic treatment and 10 (24%) episodes occurred a median 37 days after antibiotic treatment. The reaction site involved the original lesion (wound) in 23 (55%), was separate to but within 3 cm of the original lesion (local) in 11 (26%) and was more than 3 cm from the original lesion (distant) in 8 (19%) episodes. Mycobacterial cultures were negative in 33/33 (100%) paradoxical episodes. Post-February 2009 treatment involved more cases with no antibiotic modifications (12/15 compared with 11/27, OR 5.82, 95% CI 1.12-34.07, p&thinsp;=&thinsp;0.02) and no further surgery (9/15 compared with 2/27, OR 18.75, 95% CI 2.62-172.73, p&thinsp;<&thinsp;0.001). Six severe cases received prednisone with marked clinical improvement. On multivariable analysis, age ≥ 60 years (RR 2.84, 95% CI 1.12-7.17, p&thinsp;=&thinsp;0.03), an oedematous lesion (RR 3.44, 95% CI 1.11-10.70, p=0.03) and use of amikacin in the initial antibiotic regimen (RR 6.33, 95% CI 2.09-19.18, p&thinsp;<&thinsp;0.01) were associated with an increased incidence of paradoxical reactions.

Conclusions: Paradoxical reactions occur frequently during or after antibiotic treatment of M. ulcerans infections in an Australian population and may be increased in older adults, oedematous disease forms, and in those treated with amikacin. Recognition of paradoxical reactions led to changes in management with less surgery, fewer antibiotic modifications and use of prednisolone for severe reactions.

A tectônica meso-cenozóica de parte da borda nordeste da Bacia do Paraná: traços de fissão em apatita

The possible development of thermal events in the central portion of São Paulo state was described based on apatite fission track analysis. Using apatites of sedimentary rocks of the Paraná Basin, modeling the thermal history was made possible due to the homogeneity of the data. Every thermal history begins with a total annealing of fission tracks, related to the Serra Geral magmatism, evolving into a cooling period. In addition to cooling after the magmatism (Early Cretaceous) two other periods of cooling were also detected, registered in the Late Cretaceous/ Paleocene and Eocene, driven as much by uplift with tectonic denudation as by faulting. The nearest portion of the edge of the basin (external to the Dome of Pitanga), registered a period of warming over the Paleocene that can be attributed to the increase in the geothermal gradient. The periods of cooling have a regional and temporal relationship with the tectonic events that occurred in the southeastern Brazil and were described in the crystalline basement. The period of warming, registered in the Late Cretaceous/ Paleocene, has local occurrence and can be found only in the southern portion of the studied area.

Evolution of the South Atlantic passive continental margin in southern Brazil derived from zircon and apatite (U-Th-Sm)/He and fission-track data

The area between São Paulo and Porto Alegre in southeastern Brazil plays a key area to understand and quantify the evolution of the South Atlantic passive continental margin (SAPCM) in Brazil. In this contribution, we present new thermochronological data attained by fission-track and (U-Th-Sm)/He analysis on apatites and zircons from metamorphic, sedimentary and intrusive rocks. The zircon fission-track ages range between 108.4 (15.0) and 539.9 (68.4). Ma, the zircon (U-Th-Sm)/He ages between 72.9 (5.8) and 525.1(2.4). Ma, whereas the apatite fission-track ages range between 40.0 (5.3) and 134.7 (8.0). Ma, and the apatite (U-Th-Sm)/He ages between 32.1 (1.5) and 93.0 (2.5). Ma. The spatial distribution of these ages shows three distinct blocks with a different evolution cut by old fracture zones. While the central block exhibits an old stable block, the Northern and especially the Southern block underwent complex post-rift exhumation. The sample of the Northern block shows two distinct cooling phases in the Upper Cretaceous and the Paleogene to Neogene. After sedimentation of the Permian sandstones the samples of the Central block were never heated up over 100. °C with a following moderate to fast cooling phase in Cretaceous to Eocene time and a fast cooling between Oligocene to Miocene. The five thermal models obtained in the Southern block indicate a complex evolution with three cooling phases. The exhumation events of the three blocks correspond with the Paraná-Etendekka event, the alkaline intrusions due to the Trinidad hotspot, and the evolution of the continental rift basins in SE Brazil and are, therefore, most likely to be the major force for the post-rift evolution of the passive continental margin in SE Brazil, which therefore corresponds to the three main phases of the Andean orogeny. © 2013 Elsevier B.V.

Dinâmica do relevo: quantificação de processos formadores

Pós-graduação em Geologia Regional - IGCE

Evaluation of a novel photography-based home assessment protocol for identification of environmental risk factors for falls in elderly persons

PRINCIPLES To evaluate the validity and feasibility of a novel photography-based home assessment (PhoHA) protocol, as a possible substitute for on-site home assessment (OsHA). METHODS A total of 20 patients aged ≥65 years who were hospitalised in a rehabilitation centre for musculoskeletal disorders affecting mobility participated in this prospective validation study. For PhoHA, occupational therapists rated photographs and measurements of patients' homes provided by patients' confidants. For OsHA, occupational therapists conducted a conventional home visit. RESULTS Information obtained by PhoHA was 79.1% complete (1,120 environmental factors identified by PhoHA vs 1416 by OsHA). Of the 1,120 factors, 749 had dichotomous (potential hazards) and 371 continuous scores (measurements with tape measure). Validity of PhoHA to potential hazards was good (sensitivity 78.9%, specificity 84.9%), except for two subdomains (pathways, slippery surfaces). Pearson's correlation coefficient for the validity of measurements was 0.87 (95% confidence interval [CI 0.80-0.92, p <0.001). Agreement between methods was 0.52 (95%CI 0.34-0.67, p <0.001, Cohen's kappa coefficient) for dichotomous and 0.86 (95%CI 0.79-0.91, p <0.001, intraclass correlation coefficient) for continuous scores. Costs of PhoHA were 53.0% lower than those of OsHA (p <0.001). CONCLUSIONS PhoHA has good concurrent validity for environmental assessment if instructions for confidants are improved. PhoHA is potentially a cost-effective method for environmental assessment.

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and associate with increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes mellitus and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (p=2.4*10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. SNPs at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in average UACR per minor allele was 21% for HS6ST1 and 13% for RAB38/CTSC (p=6.3*10(-7) and 5.8*10(-7), respectively). Experiments using streptozotocin-treated diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout vs. control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared to controls. The loci identified here confirm known and highlight novel pathways influencing albuminuria.