Biomedical subjects

Eduardo Ramos

Publications and source records attributed to Eduardo Ramos.

5 recordsLinked to original sources

PubMed2025

Novel Insights into the Clinical Features, Genetic Spectrum and Clonal Evolution of Patients Carrying NLRP3 Mosaicism.

NLRP3 mosaicism is a well-established mechanism causing the monogenic autoinflammatory disease named cryopyrin-associated periodic syndromes (CAPS). The number of reported patients with NLRP3 mosaicism is small, and the knowledge about the long-term disease behavior is limited. Herein we assembled the largest cohort of individuals with NLRP3 mosaicism reported to date to obtain additional evidence that strengthens the understanding of this disease. The novel genetic data were obtained by using Sanger and next-generation sequencing methods, whereas in vitro analyses determined the functional consequences of detected variants. A total of seventeen individuals with NLRP3 mosaicism were enrolled, with 16/17 experiencing different CAPS phenotypes. An overrepresentation of late-onset forms was detected (37.5%). Overall, clinical manifestations, analytical results, and outcomes of treatments were markedly similar to those detected in patients with germline variants. A large mutational diversity was identified, with 16 different variants among 17 individuals. Two main patterns of mosaicism (extended vs. myeloid-restricted) were detected, with the last one overrepresented in the late-onset group. The evaluation of mosaicism over time identified three different patterns, being the group with stable mosaicism the largest one. Collected evidence supports the marked similarities among patients carrying somatic or germline NLRP3 variants. The overrepresentation of NLRP3 mosaicism in late-onset forms should be considered in patients with inflammatory manifestations starting in adulthood. Analysis of mosaicism at the biological level confirms the two known patterns of corporal distribution and reveals that mosaicism remains stable over time in most patients, but it may also vary during the course of the disease.

Humans↗

PubMed2004

Complex dynamics in simple systems with periodic parameter oscillations.

We study systems with periodically oscillating parameters that can give way to complex periodic or nonperiodic orbits. Performing the long time limit, we can define ergodic averages such as Lyapunov exponents, where a negative maximal Lyapunov exponent corresponds to a stable periodic orbit. By this, extremely complicated periodic orbits composed of contracting and expanding phases appear in a natural way. Employing the technique of epsilon-uncertain points, we find that values of the control parameters supporting such periodic motion are densely embedded in a set of values for which the motion is chaotic. When a tiny amount of noise is coupled to the system, dynamics with positive and with negative nontrivial Lyapunov exponents are indistinguishable. We discuss two physical systems, an oscillatory flow inside a duct and a dripping faucet with variable water supply, where such a mechanism seems to be responsible for a complicated alternation of laminar and turbulent phases.

Adaptation, Physiological↗

PubMed2004

Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.

OBJECTIVE: To investigate the involvement of the CIAS1/PYPAF1/NALP3 gene in 7 unrelated Spanish families with recurrent autoinflammatory diseases characterized by early onset, recurrent fever, and a chronic urticarial rash, in whom a clinical diagnosis of cryopyrin-associated periodic syndromes (CAPS) is suspected. METHODS: Clinical symptoms, results of laboratory analyses, and data on previous treatments in members of the 7 families were recorded on a questionnaire specific for hereditary autoinflammatory diseases. All coding regions and intronic flanking boundaries of the CIAS1/PYPAF1/NALP3 gene were amplified by polymerase chain reaction and sequenced. RESULTS: Five different missense mutations, including 2 de novo and 1 previously unreported mutation (R488K), were identified in exon 3 of the CIAS1/PYPAF1/NALP3 gene in 5 of the 7 affected families. Expanded genetic analysis among the healthy individuals identified incomplete penetrance in 2 families. No mutations were found in 2 of the 3 patients with chronic infantile neurologic, cutaneous, articular (CINCA) syndrome/neonatal-onset multisystem inflammatory disease (NOMID). CONCLUSION: The clinical data suggested a diagnosis of familial cold-induced autoinflammatory syndrome in 3 families, CINCA/NOMID syndrome in 3 others, and a possible Muckle-Wells syndrome, whereas mutational analysis showed different CIAS1/PYPAF1/NALP3 missense mutations in 5 families. These data are consistent with a common molecular basis of these diseases and highlights the phenotypic heterogeneity among CIAS1/PYPAF1/NALP3 gene-associated syndromes. The previously unreported mutation and the incomplete penetrance found in 2 families expand the genetic basis underlying these autoinflammatory syndromes. These findings should alert clinicians to the possible genetic basis of these conditions, even in the absence of a family history, in their attempts to establish an accurate diagnosis and the optimal therapeutic approach.

Autoimmune Diseases↗

PubMed2003

Noise-induced fluctuations of period lengths of stable periodic orbits.

We discuss a class of one-dimensional maps, which possesses a globally attracting stable periodic orbit. Despite a strongly negative Lyapunov exponent, a small amount of noise can introduce fluctuations of the period length. It is shown that this is a reasonable model for the observed dynamics of a bubble formation experiment in a heated capillary embedded in boiling water.

Journal Article↗

PubMed2003

Limitations of probiotic therapy in acute, severe dehydrating diarrhea.

BACKGROUND: Recent studies have shown that probiotics, most commonly, may be useful in treating acute gastroenteritis. However, beneficial effects appear to be limited to a modest decrease in the duration of diarrhea. No studies have evaluated this therapy in moderate to severe dehydrating diarrhea in a metabolic facility. METHODS: Male children less than 2 years of age were admitted to a metabolic unit of the Department of Pediatrics at the Federal University of Bahia, Brazil, with moderate dehydration and were randomized in a double-blind, placebo-controlled fashion. Oral rehydration solution (ORS) was administered per protocol and either placebo or was given in combination with the ORS. Output of urine, stool, and vomitus was recorded along with stool weight, nude body weight, and standard laboratory assessments for hydration. RESULTS: There was no significant reduction in diarrhea duration and stool output in the group. However, Kaplan-Meier survival analysis demonstrated that, even in moderate to severe diarrhea, resolution of the illness occurred so rapidly, that statistically significant benefits of probiotic therapy could not be demonstrated. CONCLUSION: Our data implies that colonization must occur before benefits of probiotics can be realized. Probiotics are, therefore, likely to be of limited benefit in treating diarrheal illnesses of short duration such as viral enteritis. The beneficial effects of probiotics may be limited to prophylactic usage in high-risk populations.

Acute Disease↗