Gender identity in patients with 5-alpha reductase deficiency raised as females.

BACKGROUND AND OBJECTIVE: 5-Alpha reductase type 2 deficiency (5-ARD) is a rare disorder of sex development. The lack of 5-alpha reductase, an enzyme that converts testosterone into dihydrotestosterone, results in external genitalia that may appear female, or predominantly male, albeit undervirilized, or, more often, ambiguous. METHODS: This study describes a series of patients with 5-ARD raised as female, focusing on aspects related to gender identity. Following a retrospective chart review, patients with 5-ARD were invited to return to the clinic to enable their gender identity to be assessed using an 11-item structured in-house questionnaire. The Golombok-Rust Inventory of Sexual Satisfaction was applied to patients who had initiated their sexual life. RESULTS: Six patients aged >15 years with 5-ARD and raised as female were included. Most patients were diagnosed late: two before and four after puberty. The mean length of the phallus was 2.8 cm (0.5-5.0). Reasons for seeing a doctor included genital appearance (n = 3), amenorrhea/absence of breast development (n = 2), and changes in gender role attitudes (n = 1). According to the gender identity assessment, 4 patients identified as female, 1 as male, and 1 as both genders. Only the patient identified as male requested gender re-assignment. Of the two patients who had initiated their sexual life, sexual satisfaction was found to be good in one and poor in the other due to vaginal discomfort during intercourse. CONCLUSION: In the present series, the majority of undervirilized patients with a diagnosis of 5-ARD raised as female were in complete conformation with being female and described themselves as heterosexual. The more virilized patients were those least in conformity with their female-assigned gender.

Long term outcomes in 46, XX adult patients with congenital adrenal hyperplasia reared as males.

Patients with Congenital Adrenal Hyperplasia (CAH) owing to 21-hydroxylase deficiency and whose karyotype is 46, XX are usually assigned to the female gender. Reported herein are the long term outcomes in three patients with CAH whose karyotype is 46, XX and who were reared as males. A retrospective review of three CAH patients with a 46, XX karyotype who were reared as males was conducted. Gender assignment, clinical and biochemical data, pre and post-genitoplasty genital examinations were reviewed. Gender identity was tested by an extensive questionnaire. Gender role, sexual preference, marital status and sexual satisfaction were evaluated by interview. The three patients were genotyped for the CYP21A2 gene confirming the diagnosis of CAH. Owing to genital virilization, cultural preferences for male gender and the lack of newborn screening programs the three patients reported herein were assigned to the male gender at birth before the diagnosis of CAH was established. In adulthood the patients remained significantly virilized. Thorough psychosexual assessments in adulthood revealed well established male gender identities compatible with their male gender assignments at birth. In all three patients, gender role and behavior were consistent with male gender identity including sexual intercourse with female partners. The three patients reported herein revealed that male gender assignment to CAH patients with a 46, XX karyotype may have a successful outcome providing there is strong parental support and expert endocrine care. No standard guidelines have been published for the gender assignment of CAH patients with a 46, XX karyotype and genital ambiguity. More studies concerning gender assignment in CAH patients with a 46, XX karyotype reared as males are needed.

Association between the thrombophilic polymorphisms MTHFR C677T, Factor V Leiden, and prothrombin G20210A and recurrent miscarriage in Brazilian women.

Some cases of recurrent first trimester miscarriage have a thrombotic etiology. The aim of this study was to investigate the prevalence of the most common thrombophilic mutations - factor V (FV) Leiden G1691A (FVL), prothrombin (FII) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T - in women with recurrent miscarriages. In this case-control study, we included 137 women with two or more consecutive first-trimester miscarriages (£12 weeks of gestation) and 100 healthy women with no history of pregnancy loss, and with at least one living child. DNA was extracted from the patient samples, and the relevant genes (FVL, FII, and MTHFR) were amplified by PCR, followed by restriction fragment length polymorphism, to assess the polymorphisms in these genes. The allelic frequencies of polymorphisms were not significantly different between the case and control groups. Polymorphisms in the MTHFR, FVL, and FII genes were not associated with recurrent miscarriage during the first trimester of pregnancy in Brazilian women (P = 0.479; P = 0.491 and P = 0.107, respectively). However, the etiologic identification of genetic factors is important for genetic counseling.

n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in hepatitis C virus infected patients: a randomised controlled trial.

BACKGROUND: Insulin resistance promotes liver disease progression and may be associated with a lower response rate in treated hepatitis C virus (HCV) infected patients. n-3 polyunsaturated fatty acid (PUFA) supplementation may reduce insulin resistance. The present study aimed to evaluate the effect of n-3 PUFA supplementation on insulin resistance in these patients. METHODS: In a randomised, double-blind clinical trial, 154 patients were screened. After applying inclusion criteria, 52 patients [homeostasis model assessment index of insulin resistance (HOMA-IR ≥2.5)] were randomly divided into two groups: n-3 PUFA (n = 25/6000 mg day(-1) of fish oil) or control (n = 27/6000 mg day(-1) of soybean oil). Both groups were supplemented for 12 weeks and underwent monthly nutritional consultation. Biochemical tests were performed at baseline and after intervention. Statistical analysis was performed using the Wilcoxon Mann-Whitney test for comparisons and the Wilcoxon test for paired data. Statistical package r, version 3.02 (The R Project for Statistical Computing) was used and P < 0.05 (two-tailed) was considered statistically significant. RESULTS: Comparisons between groups showed that n-3 PUFA supplementation was more effective than the control for reducing HOMA-IR (P = 0.015) and serum insulin (P = 0.016). The n-3 PUFA group not only showed a significant reduction in HOMA-IR 3.8 (3.2-5.0) versus 2.4 (1.8-3.3) (P = 0.002); serum insulin 17.1 (13.8-20.6) µIU mL(-1) versus 10.9 (8.6-14.6) µIU mL(-1) (P = 0.001); and glycated haemoglobin 5.4% (5.0-5.7%) versus 5.1% (4.8-5.6%) (P = 0.011), but also presented an increase in interleukin-1 97.5 (0.0-199.8) pg mL(-1) versus 192.4 (102.2-266.8) pg mL(-1) (P = 0.003) and tumour necrosis factor 121.2 (0.0-171.3) pg mL(-1) versus 185.7 (98.0-246.9) pg mL(-1) (P = 0.003). CONCLUSIONS: n-3 PUFA supplementation reduces insulin resistance in genotype 1 HCV infected patients.

New studies of second and fourth digit ratio as a morphogenetic trait in subjects with congenital adrenal hyperplasia.

OBJECTIVES: Congenital adrenal hyperplasia (CAH) is a disease that occurs during fetal development and can lead to virilization in females or death in newborn males if not discovered early in life. Because of this there is a need to seek morphological markers in order to help diagnose the disease. In order to test the hypothesis that prenatal hormones can affect the sexual dimorphic pattern 2D:4D digit ratio in individual with CAH, the aim of this study was to compare the digit ratio in female and male patients with CAH and control subjects. METHODS: The 2D:4D ratios in both hands of 40 patients (31 females-46, XX, and 9 males-46, XY) were compared with the measures of control individuals without CAH (100 males and 100 females). RESULTS: Females with CAH showed 2D:4D ratios typical of male controls (0.950 and 0.947) in both hands (P < 0.001). In CAH males the left hand 2D:4D ratio (0.983) was statistically different from that of male controls (P < 0.05). CONCLUSIONS: These finding support the idea that sexual dimorphism in skeletal development in early fetal life is associated with differences between the exposure to androgens in males and females, and significant differences associated with adrenal hyperplasia. Although the effects of prenatal androgens on skeletal developmental are supported by numerous studies, further investigation is yet required to clarify the disease and establish the digit ratio as a biomarker for CAH.

Huntington disease and Huntington disease-like in a case series from Brazil.

The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

Evaluation of panoramic radiomorphometric indices related to low bone density in sickle cell disease.

SUMMARY: In sickle cell disease, erythroid hyperplasia causes trabecular destruction leading to low bone density. This condition could be suspected by the radiomorphometric indices and your diagnosis becomes relevant in a multidisciplinary context of health care for sickle cell subjects, providing prognostics and contributing to determine adequate therapeutic and preventive actions. INTRODUCTION: The aim of this study was to assess the risk of low bone density in subjects with sickle cell disease (SCD) through analysis of panoramic radiographic exams by radiomorphometric indices. METHODS: Seventy-eight Brazilian subjects with SCD took part in this study and were subdivided into four groups: (I) 31 SCD subjects aged under 40 years; (II) 13 SCD subjects aged 40 years or more; (III) 12 normal subjects aged under 40 years; and (IV) 22 normal subjects aged 40 years or more. In the panoramic radiographs, the mandibular cortical index (MCI) classification, increased spacing of the trabecular bone, panoramic mandibular index (PMI), and mental index (MI) were evaluated. Exact Fisher's test was used to compare age between the different groups. Descriptive analysis of the data was performed to evaluate the simple visual estimation of low bone density (increased bone trabecular space and MCI), and a one-way analysis of variance (Bonferroni criteria) was used to compare the means of the quantitative indices (PMI and MI). The significance level was p < 0.05. RESULTS: In the MCI classification, C2 was more prevalent, especially in groups I and IV. Increased spacing of the trabecular bone was more frequent in groups I and II. MI did not show a statistically significant difference among the groups. PMI showed a statistically significant difference only between groups III and IV. CONCLUSIONS: The radiomorphometric indices applied in the present study can be used on panoramic radiographs to detect the presence of low bone density in SCD subjects.

The use of medicinal plants by an indigenous Pataxó community in NE Brazil / O uso de plantas medicinais por uma comunidade indígena Pataxó no NE do Brasil

We identified and classified 48 medicinal plants used by the Pataxó Indians in south Bahia, Brazil. The location is an ecologically threatened area designated by UNESCO as a World Heritage Site. The aim of this paper is to document phytotherapeutic practices in the indigenous community of Mata Medonha. We conducted interviews with the 25 families present at the area. Of the 48 medicinal species identified, only 14 (29%) had been examined for mechanism of action or isolation of biochemical compounds, according to bibliographic research. The plants were deposited at the Alexandre Leal Costa Herbarium of the Federal University of Bahia. We gathered information about the preparation and uses of the plants. The species are used for a variety of maladies, including flu, congestion, bronchitis and headaches, pain, snake bites, and some were only used for women's disorders. The Pataxó ethnopharmacological knowledge is under pressure from the economic outmigration of the community and threats to the biodiversity from logging, mining, and tourism. The plants studied here include important drug candidates. Additional research on the molecular aspects of the species cited should be performed.

Foram identificadas e classificadas 48 plantas medicinais usadas por Índios Pataxós no sul da Bahia. A região é área de risco ecológico designada pela UNESCO como Sítio do Patrimônio Mundial. O objetivo deste estudo foi de documentar as práticas fitoterápicas na comunidade indígena da Mata Medonha. Foram conduzidas entrevistas com as 25 famílias presentes no local. Dentre as 48 espécies identificadas, apenas 14 (29%) foram avaliadas quanto ao mecanismo de ação ou isolamento de compostos químicos, de acordo com levantamento bibliográfico. As plantas foram depositadas no Herbário Alexandre Leal Costa da Universidade Federal da Bahia. Foram registradas informações sobre o preparo e uso das plantas citadas. As espécies são usadas para uma variedade de doenças incluindo gripe, congestão, bronquite, dores em geral, picadas de cobra e algumas apenas para doenças femininas. O conhecimento etnofarmacológico Pataxó está sobre pressão pelas migrações para fora da comuindade e ameaças à biodiversidade por desmatamento, mineração e turismo. As plantas estudadas incluem importantes candidatos a fármacos. Pesquisas adicionais sobre os aspectos moleculares devem ser realizadas.

[The role of the human histocompatibility antigens in the pathogenesis of neurological disorders]. / Papel del sistema de histocompatibilidad humano en la patogénesis de las enfermedades neurológicas.

INTRODUCTION: Several studies have been trying to define genetic markers of neurological disorders. Among them, antigens and alleles of the HLA (human leukocyte antigens) system are distinguished. The HLA exerts genetic influence on the susceptibility, clinical aspects and severity of many diseases. The discovery of new molecular methods to typify HLA alleles and the recent nomenclature updates have been contributing to a better understanding of this system. Unfortunately, this information has not been adequately published in the clinical literature. AIM: To review the structure, function, nomenclature and methods of detection of the HLA polymorphism and its associations with common neurological disorders. DEVELOPMENT: Articles that were published between 1990 and 2004 were searched in the MEDLINE and LILACS databases. This review demonstrated that although the HLA association is well established for some neurological disorders (e.g., HLA-DQB1*0602 with multiple sclerosis and narcolepsy; HLA-B7 e HLA-A2 with Alzheimer's disease; HLA-DR3-DR8 with Lamber-Eaton syndrome; and HLA class II Parkinson's disease and amyotrophic lateral sclerosis), these associations are not consistent and vary in different ethnic groups. CONCLUSIONS: It is necessary to study populations from different ethnic backgrounds to identify new associations or to strength the ones already identified. This knowledge will contribute in the evaluation of the risk that a person carrying a particular allele or haplotype has to develop a neurological disease and therefore contribute towards a better understanding of its pathogenesis.

Papel del sistema de histocompatibilidad humano en la patogénesis de las enfermedades neurológicas / The role of the human histocompatibility antigens in the pathogenesis of neurological disorders

Introducción. Numerosos estudios intentan definir los marcadores genéticos de las enfermedades neurológicas. Entre ellos, destacan los antígenos y los alelos del sistema mayor de histocompatibilidad humano. El sistema HLA (human leukocyte antigens) ejerce una influencia genética sobre la susceptibililidad, la manifestación clínica y la gravedad de varias enfermedades. Nuevos métodos moleculares para realizar la tipificación de los alelos del HLA y las constantes actualizaciones de su nomenclatura han contribuido en el mejor entendimiento de ese sistema. Lamentablemente, esas informaciones no se han introducido de manera adecuada en la literatura clínica. Objetivo. Revisar la estructura, la función, la nomenclatura y los métodos de detección del polimorfismo del HLA, y explicar sus asociaciones con enfermedades neurológicas comunes en la práctica clínica. Desarrollo. Se buscaron artículos publicados entre los años 1990 y 2004 en las bases de datos MEDLINE y LILACS. Esa revisión mostró que aunque el HLA esté asociado a algunas enfermedades neurológicas (por ejemplo, HLADQB1* 0602 con la esclerosis múltiple y la narcolepsia, HLA-B7 y HLA-A2 con la enfermedad de Alzheimer, HLA-DR3-DR8 con el síndrome de Lamber-Eaton, y los antígenos HLA de clase II con la enfermedad de Parkinson y la esclerosis lateral amiotrófica), esas asociaciones no son muy consistentes y muestran variaciones en las diferentes etnias debido a su marcado polimorfismo. Conclusiones. Es necesario llevar a cabo investigaciones en poblaciones de diferentes etnias para identificar nuevas asociaciones o reforzar las ya existentes. Las asociaciones más consistentes pueden permitir el uso del sistema HLA para evaluar el riesgo de que una persona portadora de un alelo o haplotipo en particular pueda llegar a desarrollar una determinada enfermedad, lo que podría contribuir a un mejor entendimiento de su patogenia

Introduction. Several studies have been trying to define genetic markers of neurological disorders. Among them, antigens and alleles of the HLA (human leukocyte antigens) system are distinguished. The HLA exerts genetic influence on the susceptibility, clinical aspects and severity of many diseases. The discovery of new molecular methods to typify HLA alleles and the recent nomenclature updates have been contributing to a better understanding of this system. Unfortunately, this information has not been adequately published in the clinical literature. Aim. To review the structure, function, nomenclature and methods of detection of the HLA polymorphism and its associations with common neurological disorders. Development. Articles that were published between 1990 and 2004 were searched in the MEDLINE and LILACS databases. This review demonstrated that although the HLA association is well established for some neurological disorders (e.g., HLA-DQB1*0602 with multiple sclerosis and narcolepsy; HLA-B7 e HLA-A2 with Alzheimer’s disease; HLA-DR3-DR8 with Lamber-Eaton syndrome; and HLA class II Parkinson’s disease and amyotrophic lateral sclerosis), these associations are not consistent and vary in different ethnic groups. Conclusions. It is necessary to study populations from different ethnic backgrounds to identify new associations or to strength the ones already identified. This knowledge will contribute in the evaluation of the risk that a person carrying a particular allele or haplotype has to develop a neurological disease and therefore contribute towards a better understanding of its pathogenesis