Disease burden for patients with primary immunodeficiency diseases identified at reference hospitals in Guanajuato, Mexico.

BACKGROUND: In addition to the deleterious effect on health, there is considerable economic and psychosocial morbidity associated with primary immunodeficiency diseases (PID). Also, the cost of a late diagnosis frequently results in a heavy disease burden on the patient. The objective of this study was to collect and analyze data on patients with PID in the state of Guanajuato in Mexico, to indirectly estimate the burden of the disease. METHODS: An observational, longitudinal, and comparative study was conducted. A total of 44 patients were included and grouped according to the updated classification of PID. RESULTS: The median time elapsed from the onset of symptoms to the reference and diagnosis by a tertiary hospital was of 2.17 (IQR = 6.44) years. Before diagnosis, the number of hospitalizations/year per patient was 0.86 (IQR = 2.28), the number of visit to emergency room/year per patient was 0.92 (IQR = 1.77), the number of doctor's visits/year per patient was 15 (IQR = 11.25), whereas the school/work absence days per patient were reported in 52.72 (IQR = 56.35) days per year. After diagnosis, 20 patients (45.45%) received IVIG replacement therapy, and all of them presented a significant improvement (p <0.05) in all the mentioned variables. Characteristically, even when patients with PID received IVIG, there was still an important disease burden when comparing them against healthy controls. Complications secondary to PID were detected in 19 patients (43.18%). The reported overall mortality rate was 6.82% (n = 3). CONCLUSIONS: We were able to indirectly estimate an important disease burden in patients with PID; which is considered to be preventable, at least in part, with effective interventions like health planning, research, collaboration with primary care providers, and generation of policies and practices, in order to improve the quality of life and care of families with PID.

[Hemophagocytic syndrome associated to hepatitis]. / Síndrome hemofagocítico asociado con hepatitis.

Hemophagocytic syndrome is characterized by increased proliferation and activation of antigen presenting cells (histiocytes) in bone marrow and other organs of the reticuloendothelial system as well as CD8+ T cells that threatens life of patients. The predominant clinical manifestations such as fever, cytopenia, hepatitis, coagulopathy, neurological symptoms and multiple organ failure are related to systemic inflammation. We report the case of an infant who started with jaundice, abdominal pain, vomiting and malaise, at admission, hepatomegaly, splenomegaly and biochemically with features suggestive of hepatocellular inflammation and progressive cholestasis with poor outcome, it was added persistent fever, seizures, anemia, thrombocytopenia, leukopenia, elevated ferritin and hypertriglyceridemia integrating hemophagocytic syndrome with fatal outcome despite immunosuppressive therapy.

El síndrome hemofagocítico se distingue por la proliferación y activación de células presentadoras de antígeno en la médula ósea y otros órganos del sistema retículo endotelial, así como de linfocitos T CD8+ que ponen en peligro la vida de los pacientes. Las manifestaciones clínicas predominantes, como fiebre, citopenias, hepatitis, coagulopatía, síntomas neurológicos e insuficiencia orgánica múltiple están relacionadas con inflamación sistémica. Comunicamos el caso de un lactante que inició su padecimiento con ictericia, dolor abdominal, vómito, ataque al estado general, hepatomegalia, esplenomegalia y características bioquímicas sugerentes de inflamación hepatocelular y colestasis progresiva con mala evolución clínica; al cuadro se agregó fiebre persistente, crisis convulsivas, anemia, trombocitopenia, leucopenia, ferritina y triglicéridos elevados, que integraron síndrome hemofagocítico con desenlace fatal a pesar de recibir tratamiento inmunosupresor.

[Disseminated Tuberculosis in an Infant with IFNg-IL-12/IL 23 Axis Defect]. / Tuberculosis diseminada en un lactante con defecto innato del eje IFNg-IL 12/IL 23.

BCG vaccine contains low virulence Mycobacterium bovis bacillus. In Mexico it is given at birth with few reported adverse reactions in immunocompetent children; however, in immuno-compromised patients it can cause serious local or systemic adverse reactions. The most frequent related diseases include chronic granulomatous disease (CGD), human immunodeficiency virus infection (HIV), severe combined immunodeficiency (SCID) and mendelian susceptibility to mycobacterial disease (MSMD). At this time, the innate defect of the IFN-?/IL-12/IL-23 axis constitutes the main implied alteration in patients with MSMD. We present the case of an infant with disseminated mycobacterial infection and history of BCG given at birth and documentation of an altered functional study of the IFN-?/IL12/IL-23 axis, specifically at the IL-12 pathway, which is susceptible to improve with exogenous IFN-? administration. Treatment was started with antituberculous drugs plus subcutaneous IFN-?, with a marked clinical improvement. In children with disseminated infection by weakly virulent intracellular microorganisms, such as the species included in BCG vaccine, primary or secondary underlying immunodeficiency should be ruled out.

Reduction in rate of epilepsy from neurocysticercosis by community interventions: the Salamá, Honduras study.

PURPOSE: Epilepsy is highly prevalent in developing countries like Honduras, with few studies evaluating this finding. This population-based study evaluated the impact of an 8-year public health and educational intervention program in reducing symptomatic epilepsies in rural Salamá, Honduras. METHODS: We used the capture and recapture method including review of charts, previous databases, key informants from the community, and a second house-to-house survey for epilepsy. Epilepsy incidence and prevalence day after the interventions was May 5, 2005. Residents with active epilepsy with onset after May 1997 were offered neurologic evaluation, electroencephalography, and brain tomography. New data over 8 years were compared to preintervention data from the initial baseline 1997 study utilizing prevalence ratios and confidence intervals. Other calculations utilized chi square or Fisher's exact tests. KEY FINDINGS: Thirty-three of 36 patients with onset of active epilepsy after 1997 accepted evaluations to determine etiology. Symptomatic etiology was found in 58.3%. Neurocysticercosis (NCC) was again the most frequent cause (13.9%), followed by perinatal insults (11.1%). Epilepsy secondary to NCC was significantly reduced from 36.9% in 1997 (p = 0.02). The incidence (35.7/100,000) and prevalence (11.8/1,000) of active epilepsy were not significantly reduced when compared to the incidence (92.7/100,000) and prevalence (15.4/1,000) of active epilepsy in 1997. SIGNIFICANCE: Our cohort appears to indicate that health and educational community interventions can reduce preventable epilepsy from NCC in a hyperendemic population in a low-resource, developing country. Plans are underway for the Honduran Government to institute this rural model countrywide.

Comparative bioavailability of propafenone after administration of a magistral suspension vs. commercial tablets in healthy volunteers.

Propafenone (CAS 34183-22-7) is an effective antiarrhythmic drug used in children, although in some countries no specific pediatric formulation is available. The aim of this study is to compare the relative bioavailability of a magistral (MAG) preparation of propafenone versus its commercial (COM) presentation in a group of 16 Mexican healthy volunteers. Bioavailability was determined after crossover administration of the drugs, through a randomized two-phase trial. All volunteers had normal hepatic and renal functions, determined clinically at the beginning of the study, and received 150 mg of either COM (tablets) or MAG (suspension). Blood samples were drawn for a 24-h post-dose analysis by HPLC to measure plasma levels of propafenone. Subjects (mean 25.9 +/- 5.3 years and 66.1 +/- 12.4 kg) had the following pharmacokinetic parameters: Cmax 189.9 +/- 20.92 ng/mL, Tmax 1.5 h, AUC 322.4 +/- 36.28 ng x ml(-1) x h for COM. Values for MAG were Cmax 225.8 +/- 24.38 ng/mL, Tmax 1.7 h and AUC 359.3 +/- 27.90 ng x ml(-1) x h. These values yielded a relative bioavailability of 111.42% for MAG compared with COM. No electrocardiographic changes were recorded in any subject with respect to the baseline value, in both treatment schemes. Therefore, propafenone suspension prepared as a magistral formulation may be used as an alternative drug in pediatric patients.

Extemporaneous suspension of propafenone: attending lack of pediatric formulations in Mexico.

BACKGROUND: Physicians have frequently encountered difficulties when prescribing drugs not available in doses suitable for pediatric age groups. Furthermore, children have difficulty swallowing tablets. This study aimed to determine the stability of an oral propafenone suspension made from commercial tablets with a syrup vehicle and to establish its reliable use with children. METHODS: An extemporaneous suspension of propafenone 1.5 mg/ml was prepared with commercial tablets. Its physicochemical and microbiologic stability was established by constant monitoring during 90 days at room temperature (15 +/- 5 degrees C) and at refrigeration (3-5 degrees C). Plasma levels of propafenona were measured in two children with supraventricular tachycardia at steady state. RESULTS: The suspension was stable, maintaining its original physicochemical and microbiologic properties. Moreover, no apparent changes in color or odor were observed. Plasma levels of propafenone in patients demonstrated therapeutic concentrations after they had taken the suspension, with no unwanted outcome. CONCLUSIONS: The conservation of both physicochemical and microbiologic stability of the suspension represents an option for the administration of propafenone to children.

Evaluación del efecto antiarrítmico de propafenona en niños con taquicardia paroxística supraventricular / Evaluation of anti-arrhythmic effect of propafenone in children with supraventricular paroxistic tachycardia

Introducción. Las taquicardias supraventriculares (TSV) son arritmias tratadas con propafenona, debido a su utilidad en población pediátrica. Objetivo: evaluar el efecto antiarrítmico de propafenona, así como su farmacocinética en niños con TSV. Métodos. Se trata de un estudio prospectivo donde se incluyeron niños del servicio de cardiología con diagnóstico de TSV. La evolución clínica de los pacientes fue evaluada mediante monitoreo electrocardiográfico; además, se hizo un estudio farmacocinético de propafenona, utilizando un método de cromatografía de líquidos de alta resolución con detección por fluorescencia. Resultados. Se revisaron los expedientes de 85 niños con diagnóstico de TSV durante el período de 2000 a 2007; actualmente existen 11 pacientes que son tratados con propafenona, y en 3 de ellos se hizo el estudio farmacocinético. El estudio electrocardiográfico mostró trazos normales después del tratamiento con propafenona. Los parámetros farmacocinéticos del medicamento fueron similares a los reportados en estudios previos. Conclusiones. En los pacientes incluidos se observó remisión de la arritmia; además, sus parámetros farmacocinéticos fueron semejantes a los reportados en la literatura, por lo que el uso del medicamento puede ser considerado en niños con dicho padecimiento.

Introduction. Supraventricular tachycardia (SVT) involves arrhythmias treated with propafenone in children due to its utility. The aim of this study was to evaluate the anti-arrhythmic effect of propafenone as well as its pharmacokinetics in children with SVT. Methods. A prospective study was conducted in children with SVT. The evolution of their treatment with propafenone was followed by EKG monitoring. A pharmacokinetic study was carried out by using HPLC with fluorescence detection. Results. The files of 85 children with SVT from 2000 to 2007 were reviewed; currently 11 patients are treated with propafenone, Pharmacokinetics study was performed in 3 of the current patients. The EKG study showed regular registers after propafenone treatment. Propafenone pharmacokinetic parameters were similar to those reported previously. Conclusions. The patients included showed an arrhythmia remission, and their pharmacokinetic parameters were similar to those reported in the literature. Thus, the use of propafenone may be considered appropriate for SVT treatment in children.

Effects of active site mutations in haemoglobin I from Lucina pectinata: a molecular dynamic study.

Haemoglobin I from Lucina pectinata is a monomeric protein consisting of 142 amino acids. Its active site contains a peculiar arrangement of phenylalanine residues (PheB10, PheCD1 and PheE11) and a distal Gln at position E7. Active site mutations at positions B10, E7 and E11 were performed in deoxy haemoglobin I (HbI), followed by 10 ns molecular dynamic simulations. The results showed that the mutations induced changes in domains far from the active site producing more flexible structures than the native HbI. Distance analyses revealed that the heme pocket amino acids at positions E7 and B10 are extremely sensitive to any heme pocket residue mutation. The high flexibility observed by the E7 position suggests an important role in the ligand binding kinetics in ferrous HbI, while both positions play a major role in the ligand stabilisation processes. Furthermore, our results showed that E11Phe plays a pivotal role in protein stability.

Molecular dynamics of surfactant protein C: from single molecule to heptameric aggregates.

Surfactant protein C (SP-C) is a membrane-associated protein essential for normal respiration. It has been found that the alpha-helix form of SP-C can undergo, under certain conditions, a transformation from an alpha-helix to a beta-strand conformation that closely resembles amyloid fibrils, which are possible contributors to the pathogenesis of pulmonary alveolar proteinosis. Molecular dynamics simulations using the NAMD2 package were performed for systems containing from one to seven SP-C molecules to study their behavior in water. The results of our simulations show that unfolding of the protein occurs at the amino terminal, and despite this unfolding, no transition from alpha-helix to beta-strand was observed.