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Background: Autoinflammation and phospholipase Cγ2‐associated antibody deficiency and immune dysregulation (APLAID) is an exceedingly rare monogenic autoinflammatory disease. To date, only five cases have been reported with four distinct pathogenic mutations. Objectives: We present a novel case of APLAID, corroborated by molecular analysis, with newly described clinical findings including central nervous system vasculitis (CNSV); and distinctive histopathological characteristics that may expand our knowledge of this rare disease′s phenotype. Methods: This is a case report presentation of a 3‐year‐old boy, seen at a reference paediatric hospital in Mexico. His parents authorized the use of his clinical information and photographs. Results: A 3‐day‐old boy presented to the emergency department with a vesiculo‐pustular rash that resolved within 1 week. Two months later, he developed widespread papules and pseudovesicles that evolved into infiltrated plaques. He also had periodical flares of conjunctivitis, diarrhoea and erythematous blistering acral plaques triggered by upper respiratory infections. By the age of 10 months, he experienced seizures and CNSV. Laboratory work‐up showed mild neutropenia, decreased serum levels of immunoglobulins and B‐cell lymphopenia. A skin biopsy revealed a dense, perivascular and interstitial histiocytic and granulomatous infiltrate, with palisading granulomas, and leucocytoclastic vasculitis with karyorrhexis. APLAID syndrome was confirmed by Sanger sequencing of PLCG2 gene [heterozygous genotype LRG_376t1:c.2543T>C or p.(Leu848Pro)]. Conclusions: Presence of CNSV has not been previously described in APLAID, however as the number of reported patients with APLAID is very small, it is possible that the overall spectrum of clinical manifestations has not been completely elucidated. The herein identified p.(Leu848Pro) variant was also documented in a Portuguese patient, suggesting that it could be a PLCG2 gene 'hot‐spot'. [ABSTRACT FROM AUTHOR]

[Display omitted] • Stenocereus huastecorum fruit contains betalains and phenolic compounds. • Kidney protection observed by pitaya juice concentrate attenuated renal dysfunction and structural damage. • Pitaya administration had antioxidant and antiapoptotic effects. • Pitaya juice concentrate had changes in the nitric oxide and tumor necrosis factor-alpha pathway. Cisplatin (CP) is an antineoplastic agent used to treat solid tumors, that has high nephrotoxicity caused by physiologic, hemodynamic, and biochemical alterations. Some studies have shown that naturally derived bioactive compounds in CP-induced nephrotoxicity reduce the side effects of this antineoplastic drug. Pitaya is an endemic fruit from Mexico with a high bioactive compound content, including betalains and phenolic compounds, with reports of antioxidant and anti-inflammatory properties. In this study, the aim was to establish the effect of a pitaya juice concentrate (PJC) on CP-induced nephrotoxicity in Wistar male rats through the identification of metabolites, determination of its chemical composition and antioxidant activity, and evaluation of the protective effect of a PJC on CP-induced nephrotoxicity in rats. The PJC showed a high content of betanins with antioxidant activity by an oxygen radical absorbance capacity assay (1299.6 ± 2.80 Trolox equivalents/g). PJC was administered daily (400 mg day−1, p. o.) for 3 days before CP administration until the end of the experiment. On day four, rats were administered a single injection of CP (6 mg kg, i.p.-1) and sacrificed 72 h later. We observed that CP provoked renal dysfunction (1.0 ± 0.1 vs. 0.4 ± 0.07 serum creatinine levels), oxidative stress, a decrease in nitrate and nitrite (NO 2 ¯/NO 3 ¯) levels (0.1 ± 0.08 vs. 0.4 ± 0.3) and activation of apoptosis and immune responses in kidney tissue. In addition, CP treatment induced tubular damage threefold. PJC administration prevented renal dysfunction (0.5 ± 0.06 vs. 1.0 ± 0.1), normalized degenerative structural damage prevented the increase in lipoperoxidation levels (0.04 ± 0.01 vs. 0.2 ± 0.1) and reduced the apoptosis index by 2.5 in kidney tissue. However, it did not modify the immune response caused by CP. Furthermore, PJC treatment increased nuclear factor erythroid two related factors two protein levels two times and NO 2 ¯/NO 3 ¯ levels 22 times in kidney tissue, which may play a role in the renoprotective effect. In conclusion, the renoprotective effect of PJC on CP-induced nephrotoxicity was associated with the attenuation of dysfunction, structural damage, apoptosis activation, and oxidative stress and was related to changes in the tumor necrosis factor-alpha and renal nitric oxide (NO) pathways. The changes in the NO pathway may be involved in renal hemodynamics. Pitaya could be used as a functional food and therapeutic coadjuvant during CP treatments due to its high bioactive levels and renoprotective compounds. [ABSTRACT FROM AUTHOR]

Background: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking., Methods: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed., Results: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms., Conclusions: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country., Competing Interests: The authors declared no conflict of interest.

Objective: To estimate the frequency of detection and levels of aflatoxin B 1 -lysine adduct (AFB 1 -lys), an important hepatocellular carcinoma (HCC) risk factor, in eastern and southern Mexico., Materials and Methods: We determined serum AFB 1 -lys using mass spectrometry in a representative sample of 952 adults (weighted n = 7,493,354) from five states (Campeche, Chiapas, Tamaulipas, Veracruz and Yucatán) in 2018. We calculated overall and subgroup-specific frequency of detection and 95% confidence intervals (95%CI) and median AFB 1 -lys levels and quartiles., Results: The overall frequency of detection of AFB 1 -lys was 91.9% (95%CI 88.6, 94.3). The median AFB 1 -lys level was 0.172 pg/μL (Q1-Q3, 0.060-0.582). Levels differed geographically (median pg/μL, 0.361 for Veracruz and 0.061 for Yucatan) and were higher among men and older individuals. Levels were almost three times higher in rural relative to urban areas (0.317 vs. 0.123 pg/μL). We observed higher AFB 1 -lys exposure in lower socioeconomic status (SES) level populations., Conclusion: AFB 1 -lys frequency of detection was very high and exposure levels were highest in Veracruz, men, rural areas, and among persons of lower SES. Understanding modifiable HCC risk factors in populations with unique epidemiological patterns could inform preventative interventions., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objective: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center., Materials and Methods: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center., Results: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/μL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1., Conclusion: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Introduction: Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe SARS-CoV-2 infection, the reported impact of COVID-19 in these patients has been reassuring, while the differential susceptibility of distinct types of IEI remains unclear., Objective: We aimed to describe the findings and outcomes of our known patients with IEI who were diagnosed with COVID-19., Methods: In a retrospective study from March 2020 to February 2021, four centers in Mexico collected clinical, laboratory, and genetic data from pediatric and adult patients with known diagnoses of IEI who presented with COVID-19, based on compatible symptoms and positive SARS-CoV-2 testing or known household exposure., Results: We report 31 patients with known IEI from Mexico who presented with SARS-CoV-2 infection. Seventy-four percent were male, 52% were pediatric, and 81% survived. Their ages ranged from 5 months to 56 years, with a median of 17 years. Sixty-five percent had predominant antibody deficiencies, 48% were hospitalized, and 26% required ICU. Pediatric patients had a higher hospital admission rate than adults. Inpatient mortality was 40%, and ICU mortality rate was 63%. Forty-eight percent developed pneumonia, while 36% had evidence of hyperinflammation (4 adults and 7 children). Predominant laboratory features were lymphopenia and thrombocytopenia, seen in 70 and 44% of patients, respectively. The serum D-dimer median value was 2.6 (0.5-20.6) μg/mL, and the median highest ferritin value was 1015 (32-10,303) ng/mL. Intravenous immunoglobulin was used in 80% of patients. Other treatments included macrolides (39%) and corticosteroids (29%). Six patients died from secondary infection or uncontrolled systemic inflammation., Discussion: Although impaired immunity due to IEI may be a predisposing factor for severe COVID-19, most of our patients with IEI who acquired the SARS-CoV-2 infection developed a well-tolerated infection and survived, as have more than 80% of worldwide reported patients to date. An impaired immune or inflammatory response may be a predisposing factor for some and a protective factor for others. A systematic review of the literature could help identify those patients at risk of severe disease and complications. Healthcare-associated infections should be aggressively prevented., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mutations in recombinase activating genes 1 and 2 (RAG1/2) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS). A group of previously unrecognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here, we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two variants that had not been associated with immunodeficiency. This study represents the first case series of RAG1- or RAG2-deficient patients from Mexico and Latin America., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: In newborns, dramatic changes occur in the blood and bone marrow during the first hours; there are rapid fluctuations in the quantities of leukocytes populations. In this work, we investigated leukocytes subsets counts in two types of blood samples (cord blood and capillary blood) extracted from healthy newborns., Methods: Blood samples from Mexican neonates were collected by Instituto Nacional de Pediatría with written informed consent. For all samples we determined leukocytes populations; neutrophils, monocytes, total lymphocytes, and populations: T CD3+ cells, TCD4+ cells, T CD8+ cells, B CD19+ cells and NK CD16+56 cells by flow cytometry. We used the Mann-Whitney U test to compare leukocytes of cord and capillary blood; also to analyze the differences between gender and we obtained reference values of the cord and capillary blood in neonates., Results: We observed higher absolute counts and frequencies of total lymphocyte in capillary blood compared with cord blood. In absolute numbers, the capillary blood showed significant differences in neutrophils, monocytes, lymphocytes, T CD3+ cells, T CD4+ cells, T CD8+ cells, B CD19+ cells, and NK cells; no significant differences were observed between genders., Discussion: Our data contribute to newborn Mexican reference values for all these populations of leukocytes. We found that the dispersal range differs between the two types of blood, suggesting a different fate in the immune response. Immunophenotyping of the blood cell population to identify these cells is an essential tool in the diagnosis and follow-up of neonates with immunodeficiencies and other immune disorders., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.

Background: The use of osteoclast inhibitors in metastatic bone disease, increase bone mineral density and reduce the risk of fracture, patients with osteonecrosis have been reported after the chronic use of these inhibitors. In our country, the use of osteoclast inhibitors is in the context of osteoporosis and bone metastases, so it is important to describe the incidence of this complication in Mexican population., Objective: To describe the incidence of osteonecrosis of the jaws at the Centro Médico Nacional 20 de Noviembre, during the period from January 1st, 2010 to June 1st, 2016., Methods: This is a retrospective cohort study developed at the Centro Medico Nacional 20 Noviembre, ISSSTE, Mexico. We included all patients who received bisphosphonates or denosumab in the context of metastatic bone disease due to solid tumors and who had osteonecrosis of the jaw., Results: A 802 patients who used bisphosphonates or denosumab in metastatic bone disease (699 bisphosphonates and 103 denosumab). Of these, 28 (3.5%) patients presented osteonecrosis. The median use of zoledronic acid for the presence of osteonecrosis was 25 months (15-49 months) and for Denosumab it was 16 months (11-35 months), without finding significant differences between the use of drugs p = 0.511 and the risk of osteonecrosis., Conclusions: Drug-induced osteonecrosis has a low incidence in Mexican population, denosumab does not show a greater number of cases of osteonecrosis compared to bisphosphonates; no association was found between functional status, number of metastatic bone sites, nor use of antigenic or tyrosine kinase inhibitors as factor associated with osteonecrosis of the jaws., (Copyright: © 2019 Permanyer.)

Background: Patients with proximal forearm and arm transplantation have obtained and/or maintained function of the elbow joint and full active range of motion of the extrinsic muscles of the hand, but with diminished protective sensibility and a lack of good function of the intrinsic muscles. These patients have improved function, as measured by the Disabilities of the Arm, Shoulder and Hand questionnaire., Methods: We report the case of a 52-year-old man who suffered a high-voltage electrical burn requiring amputation of his upper limbs. He underwent bilateral proximal forearm transplantation in Mexico City in May 2012., Results: At 2-year follow-up, immunosuppressive treatment has not led to metabolic, oncologic, or infectious complications. Keloid scars developed at the graft-recipient interface. There have been 4 acute rejections: the fourth was treated with methylprednisolone, rituximab, and immunoglobulin. Chronic rejection has not been detected. The extrinsic muscles of the wrist and digits have good function. Although the intrinsic muscles demonstrated electrical activity 15 months postoperatively, clinically, they are nonuseful. After 2 years, hand function is sufficient to allow the patient to grasp lightweight and medium-sized objects. The patient's Disabilities of the Arm, Shoulder and Hand questionnaire score improved from 50.00 points to 30.83 points, and his Hand Transplantation Score System rating is good, at 69/73 (right/left) of 100. The patient and his family are very satisfied with the functional and aesthetic outcomes., Conclusions: Upper arm or proximal forearm transplantation is a reconstructive option for patients who have experienced amputation because of trauma.

Background: There are two inheritance patterns, the X-linked recessive (XL) pattern and the autosomal recessive pattern. There is no information on the predominant inheritance pattern of male patients with chronic granulomatous disease (CGD) in Mexico., Objective: The aim of this study was to determine the inheritance pattern in a cohort of Mexican male patients with CGD by means of the detection of an XL status carrier among their female relatives, and to describe the frequency of discoid lupus (DL) among carriers., Methods: We detected the female relatives within the families of male patients with CGD, and carried out the 123 dihydrorhodamine (DHR) assay in all female participants. All carriers were questioned for current or past established DL diagnosis., Results: We detected 33 families with one or more CGD male patients; we found an XL-CGD in 79% of the relatives from at least one female relative with a bimodal pattern. For the remaining seven relatives we were not able to confirm a carrier status by means of a DHR assay. Moreover, we detected one mother with CGD secondary to skewed X-chromosome inactivation. We also found 47 carriers, and only one carrier with DL among them., Conclusion: We concluded that XL-CGD is the most frequent form of CGD in a cohort of CGD male patients in Mexico. DHR assay is a fast and practical tool to determine the CGD form in the Latin-American countries. Finally, DL frequency in Mexico is lower than that reported in the literature for other regions of the world., (Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.)

Background: Common variable immunodeficiency (CVID) is characterised by hypogammaglobulinaemia and a broad clinical spectrum, mainly showing recurrent bacterial infections accompanied sometimes by increased susceptibility to chronic lung disease, autoimmunity, and neoplastic diseases., Objectives: To evaluate the clinical and immunological characteristics of patients with CVID in Mexico., Methods: This is a retrospective analysis of 43 patients with CVID from the Immunology Division of seven different reference centres in Mexico. Patients were diagnosed according to the diagnostic criteria of the European Society for Immunodeficiency Diseases. We collected demographics, clinical and immunological data from each patient and a statistical analysis was performed., Results: There were 23 (53.5%) male and 20 (46.5%) female patients. Median age at onset of disease was 13.7 years, and median age at diagnosis was 19 years. Average delay in diagnosis was 12.5 years. The median total serum levels of IgG, IgM, and IgA at diagnosis were 175, 18, and 17.8mg/dL, respectively. The mean percentage of CD19+ B cells was 8.15%. Sinusitis (83%), pneumonia (83%), gastrointestinal infection (70%), and acute otitis media (49%) were the most common manifestations. Bronchiectasis was present in 51% of the patients, 44% manifested non-infectious chronic diarrhoea, and 70% experienced weight loss. Autoimmunity was present in 23% of the patients; haemolytic anaemia and autoimmune thrombocytopenic purpura were the most common presentations. Allergy was present in 30.2% of patients, with allergic rhinitis and asthma being the most frequent types. Two patients developed malignancy. All the patients received Intravenous immunoglobulin (IVIG) as a fundamental part of the treatment at a mean dose of 408mg/kg., Conclusion: This is the first cohort of CVID reported in Mexico We found that infection diseases were the most frequent presentations at onset. Moreover, patients had an average diagnosis delay of twelve years and thus a major prevalence of bronchiectasis. We suggest performing an extended analysis of patients with CVID patients in other Latin American countries., (Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.)

Background: Although epidemiologic and socioeconomic criteria and biomedical risk factors indicate high-priority for tuberculosis (TB) control in Mexico, molecular epidemiology studies of the disease in the country are scarce., Methods: Complete sociodemographic and clinical data were obtained from 248 of the 432 pulmonary TB (PTB) cases confirmed from 2006 to 2010 on the population under epidemiological surveillance in the state of San Luis Potosí, México. From most PTB cases with complete data Mycobacterium tuberculosis complex (MTC) isolates were recovered and their spoligotypes, lineages and families, geographic distribution and drug resistance determined., Results: Pulmonary tuberculosis incidence ranged from 2.4 to 33.4 (cases per 100,000 inhabitants) in the six state sanitary jurisdictions that were grouped in regions of low (jurisdictions I-II-III), intermediate (jurisdictions IV-V) and high incidence (jurisdiction VI) with 6.2, 17.3 and 33.4 rates, respectively. Most patients were poor, 50-years-median-age males and housewives. Among the 237 MTC spoligotyped isolates, 232 corresponded to M. tuberculosis (104 spoligotypes in 24 clusters) and five to M. bovis. The predominant Euro-American lineage was distributed all over the state, the East-Asian lineage (Beijing family) in the capital city, the Indo-Oceanic (Manila family) in eastern localities, and M. bovis in rural localities., Conclusions: In San Luis Potosí TB affects mainly poor male adults and is caused by M. tuberculosis and to a minor extent by M. bovis. There is great genotypic diversity among M. tuberculosis strains, the Euro-American lineage being much more prevalent than the Indo-Oceanic and East-Asian lineages. The frequency of resistant strains is relatively low and not associated to any particular lineage.

Background: Over the past three decades, there has been a remarkable improvement in the outcome of children diagnosed with systemic lupus erythematosus (SLE). In general, paediatric-onset SLE has been associated with higher mortality rates and more disease damage than adults with SLE. The objective was to determinate the impact of clinical, laboratory, and electroencephalographic findings on survival amongst patients with paediatric-onset SLE., Methods: Charts of Mexican patients with paediatric-onset SLE diagnosed between 1970 and 2001 were analysed retrospectively; univariate and multivariate analyses were used for analysing associations between clinical and laboratory features and death; Kaplan-Meier tests were used to estimate survival curves., Results: 159 patients were included, 105 were female, with a median age of 12.7 years at diagnosis and a median duration of symptoms prior to diagnosis of 8.4 months. Univariate analysis showed that haematuria, leukocyturia, proteinuria, presence of urine cast, <60% glomerular filtration rate, haemolytic anaemia, and abnormal electroencephalogram, were all poor prognostic factors (p<0.05). Multivariate analysis showed that the presence of proteinuria and abnormal electroencephalograms (p<0.05) were independent factors associated with death. The overall survival rate was 82.9% at five years and 77.4% at ten years upon follow-up. Infection and high disease activity were the most common causes of death., Conclusions: Survival of paediatric-onset SLE patients was lower compared to that reported for patients in wealthier countries. Amongst the patients who died, the presence of proteinuria and abnormal electroencephalograms were found to be determinant for survival. Infection and activity were the most common causes of death., (Copyright © 2011 SEICAP. Published by Elsevier Espana. All rights reserved.)

The angiotensinogen gene locus has been associated with essential hypertension in most populations analyzed to date. Increased plasma angiotensinogen levels have been proposed as an underlying cause of essential hypertension in whites; however, differences in the genetic regulation of plasma angiotensinogen levels have also been reported for other populations. The aim of this study was to analyze the relationship between angiotensinogen gene polymorphisms and haplotypes with plasma angiotensinogen levels and the risk of essential hypertension in the Mexican population. We genotyped 9 angiotensinogen gene polymorphisms in 706 individuals. Four polymorphisms, A-6, C4072, C6309, and G12775, were associated with increased risk, and the strongest association was found for the C6309 allele (χ(2)=23.9; P=0.0000009), which resulted in an odds ratio of 3.0 (95% CI: 1.8-4.9; P=0.000006) in the recessive model. Two polymorphisms, A-20C (P=0.003) and C3389T (P=0.0001), were associated with increased plasma angiotensinogen levels but did not show association with essential hypertension. The haplotypes H1 (χ(2)=8.1; P=0.004) and H5 (χ(2)=5.1; P=0.02) were associated with essential hypertension. Using phylogenetic analysis, we found that haplotypes 1 and 5 are the human ancestral haplotypes. Our results suggest that the positive association between angiotensinogen gene polymorphisms and haplotypes with essential hypertension is not simply explained by an increase in plasma angiotensinogen concentration. Complex interactions between risk alleles suggest that these haplotypes act as "superalleles."

Introduction: The plasmatic angiotensinogen (AGT) level has been associated with essential hypertension. Linkage analysis has found a relationship between the AGT gene locus and hypertension in the Mexican-American population, but studies have failed to identify genetic variants associated with hypertension or plasma AGT levels. This study analyzes the relationship between polymorphisms in the AGT gene and plasmatic AGT levels in Mexican population., Methods: Nine polymorphisms in AGT gene were genotyped, and plasma AGT level was determined by enzyme-linked immunosorbent assay., Results: Differences in AGT plasma levels were associated with 2 polymorphisms: T-20G, TT = 25.3 ± 8.3 versus TG + GG = 21.6 ± 8.8 μg/mL; P = 0.008 and C3389T (T174M), CC = 25.8 ± 9.9 versus TC + TT = 20.5 ± 5.4 μg/mL; P = 0.0002. Haplotype 2 was associated with low plasma AGT (-5.1 μg/mL [95% confidence interval: -8.6 to -1.6], P = 0.004) and Haplotype 8 was associated with high plasma AGT (6.5 μg/mL [95% confidence interval: 2.5 to 10.6], P = 0.001). This association remained after adjustment for covariates. A Likelihood Ratio Test for haplotype-phenotype association adjusted for covariates resulted in χ = 38.9, P = 0.0005. The total effect of the haplotypes on plasma AGT level variance was 19.5%. No association was identified between haplotypes and quantitative traits of blood pressure., Conclusions: Two polymorphisms (T-20G and C3389T) and 2 haplotypes (H2 and H8) showed an association with plasma AGT levels in Mexican population.

Aim: The CYP2D6 enzyme participates in the metabolism of commonly prescribed drugs: antidepressants, antipsychotics and antihypertensives. The CYP2D6 gene shows a high degree of interindividual and interethnic variability that influences its expression and function. Mexican Mestizos are a recently admixed population resulting from the combination of Amerindian, European and, to a lesser extent, African populations. This study aimed to comprehensively characterize the CYP2D6 gene in Mexican Mestizos., Materials & Methods: We performed linkage disequilibrium and network analyses in resequencing data of 96 individuals from two regions within Mexico with a different history of admixture and particular population dynamics, the Northwestern state of Sonora and the Central-Pacific state of Guerrero., Results & Conclusion: We identified 64 polymorphisms, including 14 novel variants: 13 SNPs and a CYP2D7 exon 2 conversion, that was assigned CYP2D6*82 by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Three novel SNPs were predicted to have functional effects. For CYP2D6*82 we hypothesize an Amerindian origin that is supported by its identification in three Mexican Amerindian groups (Mayas, Tepehuanos and Mixtecos). Frequencies of CYP2D6*1, *2, *4, *5, *10, *29, *53, *82 and its duplications were 50.0, 25.5, 14.1, 2.0, 2.6, 1.0, 0.5, 2.1 and 3.6%, respectively. We found significant frequency differences in CYP2D6*1 and *2 between Mexican Mestizos and in CYP2D6*1, *2, *4, *5, *10 and *29 between Mexicans and at least one other population. We observed strong linkage disequilibrium and phylogenetic relationships between haplotypes. To our knowledge, this study is the first comprehensive resequencing analysis of CYP2D6 in Mexicans or any other Latin American population, providing information about genetic diversity relevant in the development of pharmacogenomics in this region.

Thirty rumens were examined every month from May 1989 to April 1992 to establish seasonal trends of infection and their relationship to the climatic factors caused by Paramphistomum cervi in cattle. The cattle were chosen from three municipalities of the Sierra region in Tabasco: Jalapa, Tacotalpa and Teapa. P. cervi was found throughout the year with prevalence between 3.33 and 96.67%, and with a yearly average of 39.10%. The major period of infection was shown in Jalapa. However, the maximum mean intensity was found in Teapa. The prevalence of the infection in all three sites was similar, showing the regional trend of P. cervi infection. Cattle were infected mainly throughout the rainy and windy seasons, during summer, autumn and at the beginning of winter.

A cross-sectional survey of the seroprevalence of hepatitis B virus (HBV) markers among healthy people was conducted in San Juanito, a rural community in the northern state of Chihuahua, Mexico. The overall prevalence in 970 people was 6.6% for antibody to hepatitis B core antigen. There was an age effect on the prevalence of HBV infection, and a gradual increase in prevalence was observed in patients up to the age of 40 years. Those subjects with a history of dental procedures had a 2-fold higher risk for HBV infection (odds ratio [OR], 2.4; 95% confidence intervals [CI], 1.01-5.86), and there was a 74% increased risk for each blood product transfusion (OR, 1.74; 95% CI, 1.09-2.77). Horizontal transmission seems to be the major source of endemicity in San Juanito because no woman was a chronic carrier. To lower HBV transmission rate, an adequate active screening program for blood donors should be implemented, together with a universal infant immunization program.

Air pollution is a serious health problem in major cities in Mexico. The concentrations of monitored criteria pollutants have been above the US National Ambient Air Quality Standards for the last decade. To determine whether the number of primary malignant nasal and paranasal neoplasms has increased, we surveyed 256 such cases admitted to a major adult oncology hospital located in metropolitan Mexico City (MMC) for the period from 1976-1997 and to a tertiary hospital in Monterrey, an industrial city, for the period from 1993-1998. The clinical histories and histopathologic material were reviewed, and a brief clinical summary was written for each case. In the MMC hospital the number of newly diagnosed nasal and paranasal neoplasms per year for the period from 1976-1986 averaged 5.1, whereas for the next 11 years it increased to 12.5. The maximal increase was observed in 1995-1997, with an average of 20.3 new cases per year (P = 0.0006). The predominant neoplasms in these series were non-Hodgkin's lymphoma, squamous cell carcinoma, melanoma, adenocarcinoma, Schneiderian carcinoma, and nasopharyngeal carcinoma. In the Monterrey hospital a 2-fold increase in the numbers of newly diagnosed nasal and paranasal neoplasms was recorded between 1993 and 1998. The predominant MMC neoplasm in this series, namely nasal T-cell/natural killer cell non-Hodgkin's lymphoma, is potentially Epstein-Barr virus related. Nasal and paranasal malignant neoplasms are generally rare. Environmental causative factors include exposure in industries such as nickel refining, leather, and wood furniture manufacturing. Although epidemiologic studies have not addressed the relationship between outdoor air pollution and sinonasal malignant neoplasms, there is strong evidence for the nasal and paranasal carcinogenic effect of occupational aerosol complex chemical mixtures. General practitioners and ear, nose, and throat physicians working in highly polluted cities should be aware of the clinical presentations of these patients. Identification of this apparent increase in sinonasal malignant neoplasms in two urban Mexican polluted cities warrants further mechanistic and epidemiologic studies.

Objective: To evaluate the change of knowledge in nurses attending an eighteen-hour lactation course at the General Hospital of Mexico., Material and Methods: The study was conducted from May 1996 to May 1997 and consisted of a breastfeeding training course and pre and post-test course evaluations of nurse participants. One-hundred-and-forty out of 152 nurses were trained and evaluated. Statistical analysis consisted of a paired t-test and analysis of variance., Results: Of 152 nurses attending the course, 140 (92%) completed pre and post-course evaluations. Global results of pre and post-tests were 5.39 +/- 1.37 and 7.74 +/- 0.79, (p < 0.001). The difference was still significant after we compared the instruction level of participants. There was a trend towards a higher level of instruction among those with higher knowledge on lactation in the post-course evaluation (p = 0.004)., Conclusions: An 18-hour course given to nurses significantly increased in knowledge on lactation.

To establish seasonal trends in infection and maturity of Fasciola hepatica in cattle in relation to macroclimatic factors, 2730 condemned livers were examined from March 1989 to February 1992. Livestock came from Jalapa, Tacotalpa and Teapa, all municipalities in Tabasco State. Flukes were collected monthly and separated into three different maturation stages. Mean numbers of flukes collected were determined. The analysis of the maturation stages detected in cattle showed: (a) F. hepatica matured throughout the year at all three sites; (b) the greatest mean fluke's burdens were found in Jalapa and the lowest in Teapa; large parasite populations were significantly higher from February to September than in July and/or August; (c) persistence of mature, gravid F. hepatica indicated that parasite eggs are shed throughout the year; (d) recruitment of F. hepatica occurred throughout the year with two major periods of infection, the first and main period during the dry season (from February to June), and a second minor infection period, during the rainy season (from August to October); (e) a close relationship was observed between the seasonal infection pattern in cattle and the seasonal infection pattern in snails, as well as fluctuations in the snail population according to rainfall and temperature variation.

A chloramphenicol resistant strain of S. typhi which caused a very large epidemic of typhoid fever in Mexico in 1972-73 survived in opened bottles of one carbonated drink with a pH of 4.6 for two weeks and in another such drink with a pH of 5.1 for six months. Bottled beverages are potential sources of large outbreaks of enteric disease, and deserve the same type of standards sand monitoring as comparable fluids such as milk.