Cystathionine ß-synthase and methylenetetrahydrofolate reductase mutations in Mexican individuals with hyperhomocysteinemia.

BACKGROUND: Hyperhomocysteinemia, a thrombotic risk factor, may have several causes. Among the genetic causes of hyperhomocysteinemia, there are polymorphisms in the enzymes methylenetetrahydrofolate reductase (C677T) and cystathionine ß-synthase (C699T, C1080T, and 844ins68). Although the frequency of hyperhomocysteinemia in our country is high, there is no evidence about the frequencies of these polymorphisms. METHODS: We analyzed 80 healthy individuals from several regions in our country. We evaluated the fasting and post-oral methionine load plasma Hcy and the genotypes in order to obtain the allele frequencies of the polymorphisms C677T of methylenetetrahydrofolate reductase and C699T, C1080T, and 844ins68 of the cystathionine ß-synthase. RESULTS: No individual had deficiency of folic acid, vitamins B12, or B6, but 80% had post-oral methionine load hyperhomocysteinemia. We found a significant increase in the Hcy plasma concentration associated with age and gender. Only the polymorphism C1080T was significantly associated with hyperhomocysteinemia. CONCLUSION: There is an association between fasting and post-oral methionine load plasma Hcy concentrations with the allelic frequencies of the polymorphisms C669T, 844ins68, and C1080T of the cystathionine ß-synthase and C667T of the methylenetetrahydrofolate reductase in healthy Mexican individuals. As compared with individuals with normal fasting or post-oral methionine load Hcy plasma levels, only C1080T was significantly associated with hyperhomocysteinemia.

Eosinophilic gastroenteritis / Gastroenteritis eosinofílica

The eosinophilic gastroenteritis is a disease of unknown etiopathogenesis and rare presentation, with several clinical symptoms, ranging from mild episodes until nonspecific abdominal acute episodes of intestinal obstruction, which some times make it necessary urgent surgical treatment. This wide symptomatic range seems to be conditioned by the degree of eosinophilic infiltration of the intestinal wall and the number of layers involved. This paper reports the case of a patient who, due to the diagnosis difficulties, illustrates in a single patient the intestinal and respiratory anatomo-clinical diversity and the evolution of the eosinophilia both intestinal and peripheral. Patient was sent to our service with diagnoses of bronchial asthma, chronic allergic rhinitis and chronic anemia.

La gastroenteritis eosinofílica es una enfermedad de etiopatogenia no aclarada y manifestación poco frecuente, con síntomas clínicos diversos, abarca desde cuadros leves abdominales inespecíficos hasta episodios agudos de obstrucción intestinal que en ocasiones hacen preciso el tratamiento quirúrgico urgente. Este amplio abanico sintomático parece estar condicionado por el grado de infiltración eosinofílica de la pared intestinal y el número de capas afectadas. Comunicamos un caso que por la dificultad diagnóstica ilustra, en un solo paciente, la diversidad anatomoclínica del cuadro intestinal y respiratorio y la evolución de la eosinofilia intestinal y periférica. La paciente fue enviada a nuestro servicio con los diagnósticos de asma bronquial, rinitis crónica alérgica y anemia crónica persistente.

Safety of the oral methionine load test: effects on the clinical performance and laboratory tests.

INTRODUCTION: Hyperhomocysteinemia is a prothrombotic risk factor. Homocysteine is evaluated during fasting and after an oral methionine load (OML). AIM: To determine the safety of the OML test according to the general performance status and clinical laboratory tests. We studied healthy nonsmoking volunteers and patients with several thrombotic conditions. Before and after receiving an OML, blood samples were obtained to perform several laboratory tests. We also evaluated acute and subacute adverse effects and 30-day associated morbidity and mortality. Of 353 individuals, three were eliminated because they did not tolerate the OML. We studied 175 healthy individuals and 175 patients without age differences. After OML, mild to moderate clinical abnormalities were recorded in 78 subjects (22.1%): nausea (n = 69; 88.5%), dizziness (n = 13; 16.7%) and decreased or increased blood pressure (n = 8; 10.2%). Nausea always disappeared after breakfast in affected individuals. Prevalence of complications was similar in patients and controls. No patient required hospitalization and there was no mortality during the 30-day study period. In conclusion, OML test had no significant undesirable effects on the clinical status or the general laboratory tests of patients and healthy controls. Some mild and moderate symptoms associated with OML tests were observed, and OML test did not negatively affect general laboratory tests. OML test is a safe diagnostic procedure in patients with previous thrombotic events (and with the consequent associated risk factors such as diabetes mellitus or dyslipidemia) and in healthy subjects.

[Levels of CD4+ and FOXP3+ lymphocytes in patients with allergic rhinitis]. / Concentraciones de linfocitos T CD4+ y FOXP3+ en pacientes con rinitis alérgica.

BACKGROUND: Allergic rinitis is the more common allergic disease, affecting to 25% of general population. Otitis media, sinusitis and other complications result from not controlled allergic rinitis. It has been reported that a low expression of FOXP3 marker on lymphocytes is associated with allergic diseases, and that allergen immunotherapy increases its synthesis. OBJECTIVE: To compare CD4+ FOXP3+ T cell levels in patients with allergic rhinitis, with and without allergen immunotherapy. METHODS: In this cross-sectional, observational and comparative study were included adult patients with allergic rinitis in two groups: one group with 29 patients under allergen immunotherapy for six months, and other group with 30 patients without immunotherapy. Lymphocyte markers CD3, CD4, CD8 y FOXP3 were determined in both groups, as well as serum immunoglobulins. RESULTS: In the group treated with immunotherapy the mean age was 36.4 years, and 72% of them were women. In the other group the age average was 40.4 years and 63% were women. There were no significant differences in immunoglobulin levels among both groups; IgG4 had higher levels, but not significant, in the immunotherapy group (82.1 vs 72.4 mg/dL, p=0.67). Patients from the group without immunotherapy had higher number of FOXP3+ lymphocytes, but not significant (8.2 vs 7.9, p=0.57). CONCLUSIONS: Patients treated with allergen immunotherapy had lower FOXP3+ lymphocytes number than those not treated. More studies are needed for considering FOXP3+ lymphocyte molecule as a useful marker in the follow-up of patients under immunotherapy.

Effect of highly active antiretroviral therapy on homocysteine plasma concentrations in HIV-1-infected patients.

OBJECTIVE: To analyze the effect of antiretroviral therapy on homocysteine levels in HIV-1-infected patients. DESIGN: Observational, prospective study of patients with AIDS. METHODS: We included patients with HIV-1 infection naive for antiretroviral drugs. Before and after 6 months of treatment, we evaluated fasting and postoral methionine load plasma homocysteine, serum vitamins B6 and B12, and intraerythrocyte folate levels. RESULTS: We studied 69 patients who began therapy for a 6-month period. Fasting and postoral methionine load plasma homocysteine levels increased significantly after 6 months of antiretroviral therapy with respect to basal values (P < 0.001). Fasting hyperhomocysteinemia was present in 7.3% of patients before treatment and in 89.9% after 6 months of therapy (P = 0.0001). Postoral methionine load hyperhomocysteinemia was found in 4.5% of subjects before therapy vs. 98.5% at the end of study period (P = 0.001). These results were not associated with folate or vitamins B6 or B12 levels. CONCLUSIONS: In patients with HIV-1 infection, fasting and postoral methionine load plasma homocysteine levels increased after 6 months of antiretroviral treatment. Nutritional abnormalities were not responsible for hyperhomocysteinemia, suggesting that enzymatic disturbances in the metabolic pathways of homocysteine may occur.

[An overview of primary immunodeficiency in Mexico]. / Panorama epidemiológico de las inmunodeficiencias primarias en México.

Primary immunodeficiencies are rare immunologic diseases whose main characteristics are recurrent infections. These diseases are frequently unsuspected and the delayed diagnosis makes complications irreversible with the consequent poor quality of life. In Mexico, primary immunodeficiencies have a low prevalence, which is secondary to under-diagnosis and the lack of specialized laboratory studies in most hospitals. Since there is a registration of primary immunodeficiency cases in Europe and other developed countries, it is possible to estimate the incidence of primary immunodeficiencies and to elaborate guidelines of diagnosis and treatment. In our country we do not have any epidemiological registry; however, from 1998 to 2004 the number of cases of primary immunodeficiency has increased; the minimal incidence calculated is 0.16 to 0.24 per 100,000 births for chronic granulomatous disease, severe combined immunodeficiency and X linked agammaglobulinemia, this data is still very low compared to other international registries. We present an epidemiological review of primary immunodeficiency prevalence in Mexico compared to some international reports.

[Factor VIII activity among young Mexican patients with acute myocardial infarction]. / Actividad del factor VIII en jóvenes mexicanos con infarto agudo del miocardio.

BACKGROUND: Atherothrombotic disease is the leading cause of death worldwide. Most casualties are due to acute myocardial infarction (AMI). Patients younger than 45 years account for 5-10% of AMI cases. These patients generally do not display typical atherothrombotic risk factors. METHODS: Our cross-sectional study included adult patients under 45; men and women with AMI were included. A control group of healthy individuals matched for age, sex, and blood group was included to determine the role of several atherothrombotic risk factors on AMI. One hundred and sixty patients were included, the control group was comprised by 77 males (m) and 83 females (f) RESULTS: Our results indicate that 25% of patients (23 m and 18 f) had increased FVIII compared with 8.8% of control subjects. Mean FVIII activity for patients and controls was 134 mg/dl (95%CI=114) vs. 118 mg/dl (95%CI=128-140), respectively (p=0.001). Prevalence of elevated FVIII was higher than the one found for hypertension or diabetes mellitus. HDL cholesterol was higher among patients than controls. Quantitative variables associated with AMI were high FVIII activity, blood monocyte count and HDL cholesterol. CONCLUSIONS: Classical atherothrombotic risk factors do not fully explain AMI events in the young. High levels of FVIII activity is a moderate but common risk factor in young people suffering AMI.

Actividad del factor VIII en jóvenes mexicanos con infarto agudo del miocardio / Factor VIII activity among young Mexican patients with acute myocardial infarction

Antecedentes: La enfermedad aterotrombótica es la causa de muerte más frecuente y la mayoría corresponde a infarto agudo del miocardio (IAM). Los menores de 45 años representan 5 a 10% de los IAM y es común que no sean portadores de factores de riesgo aterotrombótico clásicos. Métodos: Este estudio transversal analítico incluyó pacientes menores de 45 años con IAM, de uno y otro sexo, pareados por edad, sexo y grupo sanguíneo con sus respectivos controles, para analizar el impacto de diferentes factores de riesgo aterotrombótico sobre el IAM. Incluimos 160 casos y controles, 77 hombres y 83 mujeres. Resultados: El 25% de los pacientes tuvo aumento del factor VIII de la hemostasia (FVIII) vs. 8.8% en los controles. El FVIII promedio para pacientes y controles fue 134 mg/dl (IC 95%=114) vs. 118 mg/dl (IC 95%=128-140), respectivamente (p=0.001). La prevalencia de actividad alta del FVIII fue mayor que la de diabetes mellitus o hipertensión arterial. Paradójicamente, el colesterol HDL fue mayor en los pacientes que en los controles. Las únicas variables cuantitativas asociadas a IAM fueron la actividad alta del FVIII, la cuenta de monocitos en sangre periférica y el colesterol HDL. Conclusiones: Los factores de riesgo aterotrombótico clásicos no explican totalmente el IAM en jóvenes. El aumento de FVIII es un factor de riesgo moderado pero frecuente en la población joven con IAM.

BACKGROUND: Atherothrombotic disease is the leading cause of death worldwide. Most casualties are due to acute myocardial infarction (AMI). Patients younger than 45 years account for 5-10% of AMI cases. These patients generally do not display typical atherothrombotic risk factors. METHODS: Our cross-sectional study included adult patients under 45; men and women with AMI were included. A control group of healthy individuals matched for age, sex, and blood group was included to determine the role of several atherothrombotic risk factors on AMI. One hundred and sixty patients were included, the control group was comprised by 77 males (m) and 83 females (f) RESULTS: Our results indicate that 25% of patients (23 m and 18 f) had increased FVIII compared with 8.8% of control subjects. Mean FVIII activity for patients and controls was 134 mg/dl (95%CI=114) vs. 118 mg/dl (95%CI=128-140), respectively (p=0.001). Prevalence of elevated FVIII was higher than the one found for hypertension or diabetes mellitus. HDL cholesterol was higher among patients than controls. Quantitative variables associated with AMI were high FVIII activity, blood monocyte count and HDL cholesterol. CONCLUSIONS: Classical atherothrombotic risk factors do not fully explain AMI events in the young. High levels of FVIII activity is a moderate but common risk factor in young people suffering AMI.

Effect of combined administration of clopidogrel and lysine acetylsalicylate versus clopidogrel and aspirin on platelet aggregation and activated GPIIb/IIIa expression in healthy volunteers.

Platelet activation contributes to thrombotic events in cardiovascular disease. Acetylsalicylic acid (ASA) is used in combination with clopidogrel to reduce cardiovascular events. Lysine acetylsalicylate (L-ASA), also inhibits platelet activation with fewer gastrointestinal side effects than ASA. Dual therapy with L-ASA and clopidogrel may result in an antiplatelet effect with fewer side effects. We compared the antiplatelet effect of combined ASA/clopidogrel versus L-ASA/clopidogrel in healthy subjects. Fourteen volunteers (seven men and seven women, aged 25-45 years) received antiplatelet therapy during 14-day periods in the following sequence: 75 mg ASA; 160 mg L-ASA; 75 mg clopidogrel; 160 mg L-ASA plus 75 mg clopidogrel, and 75 mg ASA plus 75 mg clopidogrel. We evaluated platelet aggregation and glycoprotein IIb/IIIa activation. Our results show that administration of L-ASA/clopidogrel is as effective as ASA/clopidogrel combination.