Geotrichum spp: An overlooked and fatal etiologic agent in immunocompromised patients. A case series from a referral center in Mexico.

Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.

Cross Disciplinary Role Agreement is Needed When Coordinating Long-Term Opioid Prescribing for Cancer: a Qualitative Study.

BACKGROUND: Cancer pain is highly prevalent and often managed in primary care or by oncology providers in combination with primary care providers. OBJECTIVES: To understand interdisciplinary provider experiences coordinating opioid pain management for patients with chronic cancer-related pain in a large integrated healthcare system. DESIGN: Qualitative research. PARTICIPANTS: We conducted 20 semi-structured interviews with interdisciplinary providers in two large academically affiliated VA Medical Centers and their associated community-based outpatient clinics. Participants included primary care providers (PCPs) and oncology-based personnel (OBPs). APPROACH: We deductively identified 94 examples of care coordination for cancer pain in the 20 interviews. We secondarily used an inductive open coding approach and identified themes through constant comparison coming to research team consensus. RESULTS: Theme 1: PCPs and OBPs generally believed one provider should handle all opioid prescribing for a specific patient, but did not always agree on who that prescriber should be in the context of cancer pain. Theme 2: There are special circumstances where having multiple prescribers is appropriate (e.g., a pain crisis). Theme 3: A collaborative process to opioid cancer pain management would include real-time communication and negotiation between PCPs and oncology around who will handle opioid prescribing. Theme 4: Providers identified multiple barriers in coordinating cancer pain management across disciplines. CONCLUSIONS: Our findings highlight how real-time negotiation about roles in opioid pain management is needed between interdisciplinary clinicians. Lack of cross-disciplinary role agreement may result in delays in clinically appropriate cancer pain management.

miR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome.

Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-ß2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.

Microstructure and mechanical properties of hard Acrocomia mexicana fruit shell.

Fruit and nut shells can exhibit high hardness and toughness. In the peninsula of Yucatan, Mexico, the fruit of the Cocoyol palm tree (Acrocomia mexicana) is well known to be very difficult to break. Its hardness has been documented since the 1500 s, and is even mentioned in the popular Maya legend The Dwarf of Uxmal. However, until now, no scientific studies quantifying the mechanical performance of the Cocoyol endocarp has been found in the literature to prove or disprove that this fruit shell is indeed "very hard". Here we report the mechanical properties, microstructure and hardness of this material. The mechanical measurements showed compressive strength values of up to ~150 and ~250 MPa under quasi-static and high strain rate loading conditions, respectively, and microhardness of up to ~0.36 GPa. Our findings reveal a complex hierarchical structure showing that the Cocoyol shell is a functionally graded material with distinctive layers along the radial directions. These findings demonstrate that structure-property relationships make this material hard and tough. The mechanical results and the microstructure presented herein encourage designing new types of bioinspired superior synthetic materials.

Post-glacial habitat release and incipient speciation in the genus Delphinus.

The role of ecological and changing environmental factors in the radiation of species diversity is a fundamental question in evolutionary biology. Of particular interest is the potential for these factors to determine the boundary between what we would consider differentiation among populations and incipient speciation. Dolphins in the genus Delphinus provide a useful test case, exhibiting morphological variation in beak length, coloration and body size across their wide geographic distribution, and in particular among coastal and more pelagic habitats. Two species have been proposed, D. delphis and D. capensis, but morphologically similar allopatric populations are not monophyletic, indicating that the mostly coastal 'long-beaked' D. capensis form is not a single globally distributed species. However, the sympatric populations in the Eastern North Pacific currently designated as these two species are both morphologically and genetically differentiated. Here we use microsatellite DNA and mitochondrial DNA markers to investigate the evolutionary mechanisms that led to this incipient speciation event. We used coalescent and assignment methods to investigate the timing and extent of reproductive isolation. Our data indicate that although there is some level of on-going gene flow, the putative species found in the Eastern North Pacific are reciprocally monophyletic. The timing of isolation appears to be associated with regional changes in paleoceanographic conditions within the Holocene timeframe.

Maternal exposure to floricultural work during pregnancy, PON1 Q192R polymorphisms and the risk of low birth weight.

BACKGROUND: Although there is evidence from animal studies of impaired reproductive function by exposure to organophosphates (OP), the effects on birth weight have not been sufficiently evaluated in epidemiological studies. Paraoxonase (PON1) detoxifies organophosphates by cleavage of active oxons. Some PON1 gene polymorphisms could reduce the enzyme activity and increase susceptibility to OP toxicity. OBJECTIVE: To assess the association between maternal exposure to floriculture during pregnancy and the risk of low birth weight (<2500 g) in their offspring, as well as to evaluate the interaction between this exposure and maternal genotype for PON1 Q192R polymorphisms. MATERIALS AND METHODS: A cross sectional study was carried out in two Mexican states (States of Mexico and Morelos) with high frequencies of greenhouse activity. We interviewed and collected blood samples from 264 females (floriculturists or partners of floricultural workers) who became pregnant during the 10 years prior to the interview. The questionnaire measured socioeconomic characteristics, tobacco and alcohol consumption, diseases and occupational and reproductive history. We also applied a food frequency questionnaire. Information was obtained pertaining to 467 pregnancies. DNA was extracted from white cells, and PON1 genotype was determined by Restriction Fragment Length Polymorphism for Q192R polymorphisms. Results were analyzed with generalized estimating equations models. RESULTS: After adjusting for potential confounders, we detected a statistically significant interaction between maternal exposure to flower growing work during pregnancy and PON1 Q192R polymorphisms on risk of low birth weight. The risk of having a baby with LBW is nearly six times higher if a mother is a floriculture worker during pregnancy and has PON1 192RR genotype (OR 5.93, 95% CI 1.28, 27.5). CONCLUSION: These results suggest that the interaction between maternal floriculture work during pregnancy and 192RR PON1 genotype increases the probability of having children with LBW.

Accidente cerebrovascular: la nutricion como factor patogenico y preventivo. Soporte nutricional post ACV / Cerebrovascular accident: Nutrition as a pathogenic and preventive factor. Post-CVA Nutritional support

En esta revisión valoraremos el tema en cuatro fases: 1) Prevención primaria Factores de riesgo no modificables: 1) Edad, 2) Sexo, 3) Bajo peso al nacer, 4) Raza, 5) Factores genéticos. Factores de riesgo modificables: 1) Enfermedad aterosclerótica, 2) Hipertensión arterial, 3) Diabetes mellitus, 4) Dislipemia, 5) Hábito tabáquico, 6) Consumo abusivo de alcohol, 7) Actividad física, 8) Dieta y nutrición: Las sociedades científicas recomiendan la dieta DASH (fruta, vegetales, pobre en grasas totales y saturadas) para reducir la presión arterial. La dieta rica solamente en fruta y vegetales puede disminuir el riesgo de ictus. Se recomienda reducir el consumo de sodio (≤ 2,3 g 100 mmol/día) y aumentar el de potasio (≥ 4,7 g . 120 mmol/día). para reducir la presión arterial. 9) Obesidad y distribución de la grasa corporal, 10) Hiperhomocisteinemia. 2) Tratamiento de la fase aguda La incidencia de malnutrición varían entre un 7-15% al ingreso. Después del ictus el estado nutricional se deteriora, generalmente por disfagia y déficit motores que dificultan la alimentación autónoma estando ya desnutridos el 22-35%. La presencia de malnutrición en estos pacientes condiciona de forma desfavorable su pronóstico. En caso de presentar alguna dificultad para la ingesta normal y siempre que el riesgo de aspiración sea mínimo, estar. indicado realizar modificaciones en la textura de la dieta. Si el paciente presenta fatiga o saciedad precoz será útil hacer tomas de poca cantidad pero muy frecuentes. Con mucha frecuencia nos encontramos disfagia para líquidos y deberemos espesar éstos con productos de nutrición enteral como los módulos de espesante. En pacientes con un estado nutricional deficitario o que no cubren sus requerimientos nutricionales con dieta oral los suplementos de nutrición enteral son un recurso eficaz. En pacientes con disfagia persistente, las vías para la administración de nutrición enteral m.s frecuentes son la sonda nasogástrica (SNG) y la gastrostomía endoscópica percutánea (PEG). La fórmula de elección es una polimérica, normoproteica y normocalórica y con fibra, salvo que alguna otra situación haga recomendable otro tipo diferente. En los casos de pacientes con desnutrición al ingreso o con úlceras de decúbito se recomienda una fórmula hiperprotéica. Es frecuente la hiperglucemia de estrés, que con fórmulas específicas para la diabetes mellitus se consigue controlar sin requerir tratamiento farmacológico hipoglucemiante ni control glucémico intensivo. 3) Cuidados tras el alta El desarrollo de malnutrición en este grupo de pacientes puede ser muy frecuente y se debe a míltiples factores. Si aparece disfagia, se favorece el desarrollo de infecciones por aspiración. Se debe realizar un seguimiento nutricional de los pacientes que han requerido soporte nutricional durante la fase aguda del ictus hasta su completa recuperación y un aporte de nutrientes adecuado. La nutrición enteral domiciliaria ha demostrado ser coste efectiva en este grupo de pacientes. 4) Prevención secundaria. Manejo óptimo de los factores de riesgo vascular: 1) Hipertensión arterial, 2) Diabetes mellitus, 3) Dislipemia, 4) Hábito tabáquico, 5) Sobrepeso, 6) Vitaminas (AU)

In this review we will approach the topic in four stages: 1) Primary prevention Non-modifiable risk factors: 1) Age, 2) Gender, 3) Low birth weight, 4) Ethnicity, 5) Genetic factors. Modifiable risk factors: 1) Atherosclerotic disease, 2) Arterial hypertension, 3) Diabetes mellitus, 4) Dyslipidemia, 5) Cigarette smoking, 6) Alcohol abuse, 7) Physical activity, 8) Diet and nutrition: the scientific societies recommend the DASH diet (fruits, vegetables, and low in total fat and saturated fat) in order to reduce the blood pressure. The diet rich only in fruits and vegetables may decrease the risk of ictus. Reduction in sodium intake (£ 2.3 g or 100 mmol/day) and increase of potassium (4.7 g or 120 mmol/day) are recommended to reduce arterial blood pressure. 9) Obesity and distribution of body fat, 10) Hyperhomocysteinemia. 2) Managing the acute phase The incidence of malnourishment ranges 7%-15% at admission. After the CVA the nutritional status worsens, generally due to dysphagia and motor deficits that impair autonomous feeding, 22%-35% of the patients being already malnourished. The presence of malnourishment in these patients unfavourably affects their prognosis. In the case of having some difficulty for normal feeding and whenever the risk for aspiration is low, modifying the texture of the diet is indicated. If the patient presents fatigue or early satiety, having small but frequent intakes will be useful. It is common to encounter dysphagia for liquids so that beverages should be thicken with enteral nutrition products such as thickeners. In patients with a deficient nutritional status or not meeting the nutritional requirements with an oral diet, the enteral nutrition supplements are an effective resource. In patients with persistent dysphagia, the most common routes for administrating enteral nutrition are the nasogastric tube (NGT) and percutaneous endoscopic gastrostomy (PEG). The first choice formula should be polymeric, normo-proteinic and normocaloric, with fibre, unless the recommendation is changed by some other condition. In the case of patients with hyponutrition at admission or with decubitus ulcers a hyperproteinic diet is recommended. Stress-induced hyperglycaemia is common, which may be controlled with specific diabetes mellitus formulas without needing pharmacological therapy for lowering glucose levels or intensive glycemic monitoring. 3) Care at discharge The development of malnourishment in this group of patients may be very common and is due to multiple factors. If dysphagia ensues, the occurrence of aspiration induced infections is facilitated. A nutritional follow-up should be done in the patients having required nutritional support during the acute phase of a CVA until complete recovery and appropriate nutrients intake are achieved. Home-based enteral nutrition has been shown to be cost effective in this group of patients. 4) Secondary prevention. Optimal management of vascular risk factors: 1) Arterial hypertension, 2) Diabetes mellitus, 3) Dyslipidemia, 4) Cigarette smoking, 5) Overweight, 6) Vitamins (AU)

Factores predictivos de insulinización en diabetes gestacional / Predictor factors for insulinization in gestational diabetes mellitus

Introducción: El objetivo del trabajo es valorar diferentes variables clínicas y bioquímicas con la finalidad de identificar posibles factores predictivos de insulinización, de tal manera que podamos seleccionar desde el momento del diagnóstico de diabetes gestacional (DG), grupos de pacientes con mayor predisposición para insulinización y así poder realizar un seguimiento más estrecho intentando minimizar la probabilidad de complicaciones mater-no-fetales. Sujetos: Estudiamos a 101 pacientes con DG de raza caucásica con las siguientes características globales: edad media de 33,6 ± 4,6 años, índice de masa corporal (IMC) de 25,8 ± 4,9 kg/m2, ganancia ponderal durante la gestación de 7,3 ± 4,2 kg. Antecedentes familiares de primer grado de DM 2 en el 52,6 %. El porcentaje de mujeres fumadoras durante el embarazo fue de un 30,5% y el porcentaje de insulinización global fue del 45%. Método: Identificar en primer lugar las variables con asociación estadística para posteriormente confirmarlas o descartarlas como predictoras de insulinización. Resultados: En nuestro grupo de pacientes diagnosticadas de DG se han identificado como factores predictivos de insulinización: el peso previo a la gestación (tanto el sobrepeso como la obesidad), la presencia de glucemia basal en el TSOG con 100 g superior a 85 mg/dl y tras una hora superior a 200 mg/dl y los antecedentes familiares de DM 2

ntroduction: The aim of this project is to value different clinical and biochemical variables in order to identify possible predictive factors for initiating insulin therapy in gestational diabetes, so we can select from the initial moment of the diagnosis those groups of patients with most possibilities of being treated on insulin and therefore carry out a closer follow up on them, trying to minimize the incidence of maternal and foetal complications. Subjects: 101 women with gestational diabetes of caucasian race with a medium age of 33.6 ± 4.6 years, a body mass index (BMI) of 25.8 ± 4.9 kg/m2, a weight increase during pregnancy of 7.3 ± 4.2 kg. A 52.6% of them presented a first degree familiar history of type two diabetes mellitus. A 30.5% of women smoked during pregnancy and 45% of all the group required insulin. Material and methods: To identify, in first place, the variables with statistic association as predictive of insulin treatment and thereafter confirm them or rule them out. Results: In our group of gestational diabetes diagnosed patients, we have identified as predictive factors of insulin requirement: Previous weight before pregnancy (obesity and overweight), a basal glucose level greater than 85 mg/dl in the TTOG and a 1 hour value greater than 200 mg/dl and a familiar history of type two diabetes mellitus

LMP2 and LMP7 gene polymorphism in Mexican populations: Mestizos and Amerindians.

Low molecular weight polypeptide (LMP) genes are located within the major histocompatibility complex and have been associated with autoimmune diseases such as ankylosing spondylitis. In order to define the distribution of LMP genes in Mexican populations, the LMP2 and LMP7 polymorphism was analyzed in 312 Mexican individuals (95 Mexican Mestizos, 48 Nahuas, 56 Mazatecans, 50 Teenek, and 63 Mayos) belonging to different ethnic groups. In Mexican populations both Mestizos and Amerindians presented similar distribution of LMP2 and LMP7 polymorphisms, except Nahuas and Mayos who presented the higher frequencies of LMP2-H/H and the lowest frequencies of LMP2-H/R genotypes (P < 0.05 when compared with Mexican Mestizos). The LMP7-K/K genotype was absent in Nahuas, Teenek and Mayos and only one Mazatecan individual presented this genotype. Differences with other populations were found in Mexicans. An increased frequency of LMP2-H and a decreased frequency of LMP2-R alleles were observed in Mexican Amerindians (Nahuas and Mayos) when compared with Brazilian Amerindians (Kaingang and Guarani) and Caucasians (Spaniards) (P < 0.05). All Mexican populations (Mestizos and Amerindians) presented an increased frequency of LMP7-Q allele and a decreased frequency of LMP7-K allele when compared to Brazilian Amerindians (Kaingang), Caucasians (United States) and Asian (Japan) populations (P < 0.05). Genetic distances showed that Mexican Mestizos have an important relation with Spaniards and with all Mexican Amerindians. The present data corroborate the influence of Spaniard and Amerindian genes in the Mexican Mestizo population and could help to define the true significance of LMP polymorphism as genetic and evolutive marker in the Amerindian populations.

[Alleles of the major histocompatibility system associated with susceptibility to the development of Takayasu's arteritis]. / Alelos del sistema principal de histocompatibilidad relacionados con la susceptibilidad al desarrollo de la arteritis de Takayasu.

OBJECTIVE: Since 1972, the relationship between HLA alleles and the susceptibility for Takayasu arteritis (TA) has been studied on different populations. Hence the results up to date are heterogeneous, the objective of the present review is to analyze the relationship between the presence of HLA alleles and the susceptibility for the development of TA considering the ethnic origin of the studied populations. MATERIAL AND METHODS: We carried out a bibliographic review from clinical articles of case and controls studies on different populations on which the relationship between HLA alleles and the susceptibility for TA was studied, published since 1972 until February 2000. RESULTS: We reviewed articles of studies on Asian, Arab, North-American and Mexican Mestizo populations. On Asian populations TA was associated with HLA-A31, -B52, -B39, -B5 and -DR2, on Arabs with HLA-A2, -A9, -B35 and -DR7, on North-Americans with HLA-DR4 and on Mexican Mestizo with HLA-B5, -B52 and -DR6. On the other hand, recent reports establish that several HLA-B alleles (HLA-B52 and HLA-B39) associated with the disease share some residues important on the antigen presentation. CONCLUSIONS: Hence the heterogeneity of the results obtained up to date, it stands out the increase on HLA-B52 and HLA-DR4 reported on ethnically different populations. More recent data point the possible participation of an epitope located on the peptide-binding site of the HLA-B molecule (positions 63 and 67) that seems to be shared by several alleles associated with the disease. These residues might be participating on the presentation of an unknown antigen that would unchain the disease on the genetically susceptible individuals group.

Alelos del sistema principal de histocompatibilidad relacionados con la susceptibilidad al desarrollo de la arteritis de Takayasu / Alleles of the major histocompatibility system associated with susceptibility to the development of Takayasu's arteritis

OBJECTIVE: Since 1972, the relationship between HLA alleles and the susceptibility for Takayasu arteritis (TA) has been studied on different populations. Hence the results up to date are heterogeneous, the objective of the present review is to analyze the relationship between the presence of HLA alleles and the susceptibility for the development of TA considering the ethnic origin of the studied populations. MATERIAL AND METHODS: We carried out a bibliographic review from clinical articles of case and controls studies on different populations on which the relationship between HLA alleles and the susceptibility for TA was studied, published since 1972 until February 2000. RESULTS: We reviewed articles of studies on Asian, Arab, North-American and Mexican Mestizo populations. On Asian populations TA was associated with HLA-A31, -B52, -B39, -B5 and -DR2, on Arabs with HLA-A2, -A9, -B35 and -DR7, on North-Americans with HLA-DR4 and on Mexican Mestizo with HLA-B5, -B52 and -DR6. On the other hand, recent reports establish that several HLA-B alleles (HLA-B52 and HLA-B39) associated with the disease share some residues important on the antigen presentation. CONCLUSIONS: Hence the heterogeneity of the results obtained up to date, it stands out the increase on HLA-B52 and HLA-DR4 reported on ethnically different populations. More recent data point the possible participation of an epitope located on the peptide-binding site of the HLA-B molecule (positions 63 and 67) that seems to be shared by several alleles associated with the disease. These residues might be participating on the presentation of an unknown antigen that would unchain the disease on the genetically susceptible individuals group.

Neuropatía aguda dolorosa en un paciente con diabetes tipo 2 en un paciente con diabetes tipo 2 / Acute painul neuropathy in patients with type 2 diabetes

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Heat shock protein 70 gene polymorphisms in Mexican patients with spondyloarthropathies.

OBJECTIVE: To investigate the role of HSP70 genes as contributors to genetic susceptibility of the spondyloarthropathies (SpA) in the Mexican population. METHODS: The study included 150 patients with SpA (undifferentiated spondyloarthropathy (uSpA) 68, ankylosing spondylitis (AS) 60, and reactive arthritis 22) and 158 healthy controls. HSP70-1, HSP70-2 and HSP70-hom genotypes were analysed by the polymerase chain reaction-restriction fragment length polymorphism technique. Statistical methods included the Mantel-Haenzel, chi(2), Fisher's exact test, and Woolf's method for odds ratio (OR). RESULTS: HSP70-2 B/B genotype frequency was increased in the whole group of patients with SpA (pC<0.05, OR=4.3), as well as in the different clinical subgroups (pC<0.05, OR=4.2 for AS; pC<0.05, OR=4.4 for uSpA; and pC<0.05, OR=4.1 for ReA). This frequency remained significantly increased when the patients with B27 negative SpA were analysed. On the other hand, HSP70-hom locus analysis showed significantly increased frequency of A allele in the whole group of SpA (pC<0.05, OR=3.4), as well as in the groups with AS (pC<0.05, OR=5.6) and with uSpA (pC<0.05, OR=3.1), when compared with healthy controls. In this case, also, the genotype A/A was increased in the whole group of SpA (pC<0.05, OR=4.5), as well as in patients with AS (pC<0.05, OR=6.4) and with uSpA (pC<0.05, OR=3.7). When the patients with B27 negative SpA were analysed the frequencies of HSP70-hom A allele and A/A genotype remained significantly increased in the whole group of SpA (pC<0.05, OR=3.2 for the A allele and pC<0.05, OR=4.2 for the A/A genotype) and in the uSpA subgroup (pC<0.05, OR=3.8 for the A allele and pC<0.05, OR=4.3 for the A/A genotype). CONCLUSION: In addition to the association of SpA with HLA-B27, there is a significant association of HSP70-2 and HSP70-hom alleles with SpA in Mexicans. This association seems to be independent of the susceptibility conferred by HLA-B27 in the group of patients with uSpA.

Diagnóstico diferencial de las hipoglucemias / Differential diagnosis of hypoglucemia

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Immunogenetics and clinical aspects of Takayasu's arteritis patients in a Mexican Mestizo population.

OBJECTIVE: The aim of the present work was to study the association between HLA alleles and Takayasu's arteritis in Mexican Mestizo patients. METHODS: The study included 26 Mexican Mestizo patients with Takayasu's arteritis and 99 healthy unrelated individuals. HLA-A, -B and -DR alleles were determined by polymerase chain reaction PCR-SSP RESULTS: Increased gene frequencies were demonstrated for HLA-B15(p=0.009,pC=0.020,OR=3.24,EF=11.9%) and HLA-B52 (p=0.008, pC=0.027, OR=5.16, EF=7.7%), and a decreased frequency for the HLA-A24 allele in patients compared to normal controls (p=0.035, pC=NS, PF=11.1%). When HLA typing was correlated to clinicalfeatures in 24 cases, wefound an increasedfrequencies of HLA-DR14 in patients with systemic arterial hypertension (p=0.005, pC=0.004, OR=24.6, EF=38.3%) and HLA-A2 on patients with pulmonary involvement (p=0.034, pC=0.036, OR=3.67, EF=40.4%) when compared to patients without these clinical manifestations. CONCLUSION: These data confirm HLA-B52 as a relevant susceptibility allele for Takayasu's arteritis and suggest that HLA-B15 could be important as a marker of the disease in Mexican patients. Other class I and/or class II alleles could also be relevant as markers for the clinical features present in these patients.

Polymorphism and distribution of HLA-DR2 alleles in Mexican populations.

DRB1*15/16 nucleotide polymorphism was analyzed in 68 DR2 positive individuals (18 Mexican Mestizos, 30 Mazatecans and 20 Nahuas), carrying a total of 75 DR2 haplotypes. HLA-DR2 was one of the most frequent specificities detected in Mazatecans and Nahuas with gene frequency (gf) of 0.232 and 0.141, respectively. In these populations DRB1*16 was the most frequent DR2 split (gf = 0.183 in Mazatecans and gf = 0.135 in Nahuas), whereas in Mexican Mestizos the most frequent was DRB1*15 (gf = 0.065). Four DRB1-DQB1 combinations in Mexican Mestizos, two in Mazatecans and one in Nahuas were in linkage disequilibrium. In spite of the restricted polymorphism, there were differences on DRB1*15/16 alleles found in Mexicans. DRB1*1501 a Caucasian allele was predominant in Mexican Mestizos, whereas DRB1*1602 an Amerindian allele was characteristic on Indian populations. An important difference was detected among the Amerindian populations studied since DRB1*1502 was only present in Mazatecans. This data corroborates the restricted polymorphism of DRB1*15/16 and the high frequency of DRB1*16 subtype in autochthonous American populations and suggest that the differences in gene frequencies of DRB1*15/16 alleles could be helpful in distinguishing each of these population.

Influence of the apolipoprotein E polymorphism on plasma lipoproteins in a Mexican population.

The influence of apolipoprotein E (APOE) genotypes on plasma lipid levels was determined in 278 Mexican individuals. The most frequent genotype was E3/3 (80.5%) followed by E3/4 (12.5%), E2/3 (5.0%), E2/4 (1.4%), and E4/4 (0.3%). Our data are similar to those previously described for Mexican-American and American Indian populations, which show the highest frequency worldwide of the APOE*3 and the E3/3 genotype. Compared to female carriers of the E3/3 genotype, women with the E3/4 genotype presented increased low-density lipoprotein cholesterol (117 +/- 28.0 mg/dL vs. 134.0 +/- 31.7 mg/dL, p < 0.05), and total cholesterol (179.4 +/- 33.4 mg/dL vs. 197.5 +/- 35.4 mg/dL, p < 0.01). Also, we detected increased high-density lipoprotein concentrations in women with the E2/3 genotype (53.7 +/- 19.5 mg/dL) when compared to women with the E3/3 genotype (45.2 +/- 12.0 mg/dL) (p < 0.032). Our data suggest that genetic variation at the APOE locus in the Mexican population is a genetic factor that influences plasma lipid levels. This effect was observed only in the female population. Additional studies attempting to correlate APOE polymorphism with plasma lipid profile in a large number of individuals would be helpful in establishing the true significance of this polymorphism in the Mexican population.

DNA sequencing of HLA-B alleles in Mexican patients with Takayasu arteritis.

Takayasu arteritis (TA) is characterized by a 'pulseless' condition and occurs frequently in young females from Asian and South American countries. It has been associated with Mayor Histocompatibility Complex (MHC) genes in different populations. Recent data indicate direct participation of HLA-B alleles in the susceptibility to the disease. This fact was explored in an associative study with TA to establish if some region in the exon 2, intron 2 or in the exon 3 of HLA-B alleles is common in the alleles associated with TA and at the same time to know if a specific sequence or an epitope, more than an allele, would be responsible for the susceptibility to this vasculitis. We studied HLA-B alleles of 12 Mexican patients with TA using PCR-SSP and sequencing. The analysis by PCR-SSP in 12 patients showed that five of them showed the B*15 allele, three the B*40 allele and two the B*39 allele, the remaining two presented the B*44 allele. Sequence analysis enabled us to define that the B*39 subtypes are B*3908; B*15 subtypes are B*1510, B*1515, B*1522 and B*1531; and the B*40 subtypes are B*4005 and B*4008. An individual with B*51 (B*5107) and another with B*52 (B*5201) alleles were also identified. The sequences of the intron 2 seem be heterogeneous. Analysis at the 63 and 67 positions of HLA-B alleles showed that 9 of them have similarity in some of these positions with the residues detected in the B*5201 and B*3902 alleles associated with TA in Asian populations. The results indicate that there is heterogeneity in the alleles associated with TA in Mexicans but, in spite of that heterogeneity, the alleles associates can be separated into three groups: B*39, B*15 and B*40, whose subtypes are rare and apparently of recent generation in Mexico, probably by recombination events at intron 2 level. The sequences analysis also shows that most of the alleles detected in the Mexican patients share two epitopes described in the susceptibility alleles in Asian populations, suggesting that these epitopes could be responsible for the susceptibility to develop the disease in spite of the allele in which are found.

HLA-DR4 allele frequencies on Indian and Mestizo population from Mexico.

Using PCR-SSOP and sequencing, we examined DRB1*04 nucleotide polymorphism in 137 DR4-positive Mexican healthy individuals (46 Mexican Mestizos, 64 Mazatecans, and 27 Nahuas), carrying a total of 147 DR4 haplotypes. Eleven different DRB1*04 alleles were detected in Mexican Mestizo population, whereas, in the two Indian groups a restricted polymorphism was observed (5 variants in Mazatecans and 4 in Nahuas). DRB1*0407 was the most frequent allele (gf = 0.106 in Mexican Mestizos, gf = 0.281 in Mazatecans, and gf = 0.189 in Nahuas). In spite of the restriction in polymorphism, there were differences on DRB1*04 alleles found in Mexicans mainly between Mazatecan and Nahua populations. DRB1*0403 was characteristic allele in Nahua ethnic group, whereas, 0404 and 0411 were predominant alleles in Mazatecans. This data corroborates the restricted polymorphism of DRB1*04 alleles in American populations. In spite of the restriction in this polymorphism, differences in frequencies of DRB1*04 alleles could help distinguish each population.