Role of VEGF in the differential growth between the fetal and placental ends of the umbilical cord.

INTRODUCTION: The umbilical cord (UC) is a vital structure; its alterations affect the newborn and neurological impact can be permanent. Paradoxically, factors that determine it remain unknown. We explore the differential VEGF protein expression in the UC's proximal and distal portions in relation to the hypothesis that the UC has differential growth and that VEGF plays a role in it. METHODS: An observational analytical study was performed. One UC segment was taken proximal to fetus and another distal; both were randomly processed; VEGF immunohistochemical analysis was performed; two blinded pathologists read results. RESULTS: Forty-eight newborns were included. Protein expression between the two edges of the umbilical cord, in any kind of cells, was interpreted. Endothelium, amnion, and stromal cells expressed VEGF; the first two were not different between opposite ends. Stromal cells had differential expression: higher in the proximal to the fetus portion. CONCLUSION: Knowledge of molecular factors is necessary. UC cells widely expressed VEGF, possibly contributing to UC growth. Even though stromal cell expression was different, the interaction with activity close to the fetus must be explored.

Umbilical cord and preeclampsia.

INTRODUCTION: Preeclampsia is associated with abnormalities in the umbilical cord in several ways: morphological, biochemical and functional. Alteration in blood vessels of the placenta, decidua and circulatory system of the fetus might be related to factors that cause preeclampsia and may be associated with alterations of the umbilical cord. OBJECTIVES: This study aimed to analyze the relationship between each type of umbilical cord abnormality and the different subtypes of hypertensive gestational disorders. METHODS: We conducted a prospective study on consecutive autopsies and its placentas, looking for abnormalities in the umbilical cord's features and their clinical associations. RESULTS: Umbilical cord abnormalities including length, diameter, insertion, entanglements, knots and coils were associated with maternal gestational hypertension. CONCLUSION: In women with gestational hypertension, umbilical cord abnormalities are associated with fetal and neonatal consequences.

Clinical associations to abnormal umbilical cord length in Latin American newborns.

INTRODUCTION: Umbilical cord is vital to fetal development and its alterations are related to fetal and neonatal deaths and to late neurological complications. Abnormal cord length has been recognized as the most important cord feature leading to unfavorable outcomes. We aimed to examine the relationship between fetal abnormalities and the length of umbilical cord using the ECLAMC (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas/Latin American Collaborative Study on Congenital Malformations) database. METHODS: Using ECLAMC case-control registries, we conducted an observational study on the relationship between umbilical cord length and clinical variables such as chromosomal abnormalities and neonatal malformations. RESULTS: Birth registries totaled 61820; of them 3411 had complete cord data. Abnormal length was found in 427, with 174 short (5.10%) cords and 253 long (7.41%) cords. No relation was found between abnormal cord length and gender, parity or parents' age. More abnormal length cords were found than reported in other series; unexpectedly, more long cords were observed in twin gestations. It was observed that among short cords (174), 105 were from newborns with some type of malformation and 69 with no malformation (OR = 2.92, CI (95%) 2.15-3.98, p = 0.0001); of the 253 long cords, 168 had malformation and only 85 did not (OR = 3.80, CI (95%) 2.91-4.96, p = 0.0001). CONCLUSIONS: Abnormal cord length is associated with fetal malformation. Further studies are needed to determine the clinical applicability of using this parameter in counseling during prenatal visits.

Implementation of a simple method to measure total umbilical cord length.

INTRODUCTION: Umbilical cord (UC) alterations are involved in fetal and neonatal complications, and even deaths. Abnormal length has been recognized as the most important UC feature linked to unfavorable results. However, how can the UC be accurately measured in cases in which there is an overriding need for intravenous intervention, urgent lab samples or segments for stem cell cultivation? METHODS: We performed an observational study to describe our UC length measurement method at the San Ignacio University Hospital (HUSI). RESULTS: All HUSI obstetricians and pediatricians accepted the new rapid cord measurement method; no delays were reported for either maternal or neonatal care. CONCLUSIONS: In light of the association of abnormal UC length to complications, we recommend that complete UC length data be registered. Our new and rapid method allows for any UC intervention to be performed, while at the same time, providing precise UC length data under all circumstances.

Genetic characterization of Colombian Bahman cattle using microsatellites markers.

Genetic structure and diversity of 3789 animals of the Brahman breed from 23 Colombian regions were assessed. Considering the Brahman Zebu cattle as a single population, the multilocus test based on the HW equilibrium, shows significant differences (P < 0.001). Genetic characterization made on the cattle population allowed to examine the genetic variability, calculating a H(o) = 0.6621. Brahman population in Colombia was a small subdivision within populations (F(it) = 0.045), a geographic subdivision almost non-existent or low differentiation (F(st) = 0.003) and the F(is) calculated (0.042) indicates no detriment to the variability in the population, despite the narrow mating takes place or there is a force that causes the variability is sustained without inbreeding actually affect the cattle population. The outcomes of multivariate analyses, Bayesian inferences and interindividual genetic distances suggested that there is no genetic sub-structure in the population, because of the high rate of animal migration among regions.

Molecular studies in the GJB2 gene (Cx26) among a deaf population from Bogotá, Colombia: results of a screening program.

OBJECTIVE: We conducted a pilot screening program to define the prevalence of non-syndromic deafness and establish the frequency of mutations in the GJB2 gene (Cx26) in a population of children with congenital deafness in Bogotá, Colombia. METHOD: From a cohort of 731 children in 8 institutions for the deaf, we identified 322 (44%) with presumed non-syndromic deafness. These were invited to a more detailed evaluation, but 46 chose not to participate. The remaining 276 individuals received a complete ophthalmological evaluation that was normal in 205 (74.3%) and showed salt and pepper retinopathy in 55 (19.9%) and other ocular abnormalities in 16 (5.8%). A comprehensive medical history, and a detailed physical examination were performed in the 205 children with normal ocular exam. Of these, 93 were found to have acquired deafness and/or associated anomalies and 112 (15.3% of the initial 731 children), non-syndromic deafness. The GJB2 gene was sequenced in these 112 individuals. RESULTS: Based on family history, 59.8% (67/112) of these cases had autosomal recessive non-syndromic sensorineural hearing loss and the remaining 40.2% (45/112) were sporadic, without apparent known cause. We identified three mutations in the GJB2 gene: 35delG, S199F, and 167delT, all of which have been previously reported in the literature, the variant M34T, and the polymorphism V27I. S199F was the most frequent mutation (17.9%), followed by 35delG (17.0%) and 167delT (0.4%). The mutations in the GJB2 gene were present in 50.7% of the autosomal recessive group and in 33.3% of the sporadic cases. CONCLUSIONS: Our pilot study showed that 15.3% of institutionalized deaf children in Bogotá have non-syndromic deafness and among them, the frequency of the S199F mutation was higher than reported in previous studies, whereas the frequency of the 35delG is similar to Caucasian populations. The fact that the S199F mutation was the most frequent allele in our study confirms the fact that the prevalence of GJB2 mutations depends on the ethnic origin. We emphasize the need to follow a strict protocol to identify bona fide cases of non-syndromic deafness among individuals with congenital hearing loss in order to identify the molecular basis of this condition.

Genetic counseling in Usher syndrome: linkage and mutational analysis of 10 Colombian families.

Usher Syndrome (US), an autosomal recessive disease, is characterized by retinitis pigmentosa (RP), vestibular dysfunction, and congenital sensorineural deafness. There are three recognized clinical types of the disorder. In order to improve genetic counseling for affected families, we conducted linkage analysis and DNA sequencing in 10 Colombian families with confirmed diagnosis of US (4 type I and 6 type II). Seventy-five percent of the US1 families showed linkage to locus USH1B, while the remaining 25% showed linkage to loci USH1B and USH1C. Among families showing linkage to USH1B we found two different mutations in the MYO7A gene: IVS42-26insTTGAG in exon 43 (heterozygous state) and R634X (CGA-TGA) in exon 16 (homozygous state). All six US2 families showed linkage to locus USH2A. Of them, 4 had c.2299delG mutation (1 homozygote state and 3 heterozygous); in the remaining 2 we did not identify any pathologic DNA variant. USH2A individuals with a 2299delG mutation presented a typical and homogeneous retinal phenotype with bilateral severe hearing loss, except for one individual with a heterozygous 2299delG mutation, whose hearing loss was asymmetric, but more profound than in the other cases. The study of these families adds to the genotype-phenotype characterization of the different types and subtypes of US and facilitates genetic counseling in these families. We would like to emphasize the need to perform DNA studies as a prerequisite for genetic counseling in affected families.

Deafness on the island of Providencia - Colombia: different etiology, different genetic counseling.

Providencia is a small island located in the Caribbean Ocean, northwest of Colombia with an unusually high frequency of individuals with hearing loss (5 in 1,000) is present. The hearing loss in the island was characterized as non-syndromic autosomal recessive deafness accounting for 47% (8/17) of the deaf population, Waardenburg Syndrome (deafness associated with pigmentary anomalies) for 29% (5/17), and the remaining 24% (4/17) are cases of sporadic non-syndromic deafness. For appropriate genetic counseling a complete pedigree of families with deaf individuals was constructed. The 35delG mutation in GJB2 gene, which encodes connexin 26 (Cx26), is responsible for the deafness observed in the 8 individuals with autosomal recessive non-syndromic hearing loss. The deaf individuals with Waardenburg Syndrome and the sporadic cases did not have this mutation. Therefore, we present here an atypical case of an isolated community with at least two different genetic etiologies for deafness: non-syndromic genetic deafness caused by the 35delG mutation in the GJB2 gene and deafness associated with Waardenburg Syndrome not related to GJB2. In a small and isolated population, it is feasible to assume that the deafness is caused by the same factor; however, Providencia is an atypical case. Therefore, it is extremely important to define the exact etiology of deafness in each case, since different etiologies require different genetic counseling.

Biological relationship between Central and South American Chibchan speaking populations: evidence from mtDNA.

We examined mitochondrial DNA (mtDNA) haplogroup and haplotype diversity in 188 individuals from three Chibchan (Kogi, Arsario, and Ijka) populations and one Arawak (Wayuú) group from northeast Colombia to determine the biological relationship between lower Central American and northern South American Chibchan speakers. mtDNA haplogroups were obtained for all individuals and mtDNA HVS-I sequence data were obtained for 110 samples. Resulting sequence data were compared to 16 other Caribbean, South, and Central American populations using diversity measures, neutrality test statistics, sudden and spatial mismatch models, intermatch distributions, phylogenetic networks, and a multidimensional scaling plot. Our results demonstrate the existence of a shared maternal genetic structure between Central American Chibchan, Mayan populations and northern South American Chibchan-speakers. Additionally, these results suggest an expansion of Chibchan-speakers into South America associated with a shift in subsistence strategies because of changing ecological conditions that occurred in the region between 10,000-14,000 years before present.

Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.

The people of Tumaco-La Tolita culture inhabited the borders of present-day Colombia and Ecuador. Already extinct by the time of the Spaniards arrival, they left a huge collection of pottery artifacts depicting everyday life; among these, disease representations were frequently crafted. In this article, we present the results of the personal examination of the largest collections of Tumaco-La Tolita pottery in Colombia and Ecuador; cases of Down syndrome, achondroplasia, mucopolysaccharidosis I H, mucopolysaccharidosis IV, a tumor of the face and a benign tumor in an old woman were found. We believe these to be among the earliest artistic representations of disease.

Further data on the microsatellite locus D12S67 in worldwide populations: an unusual distribution of D12S67 alleles in Native Americans.

We report the frequencies of alleles at the microsatellite locus D12S67 in 2 widely separated ethnic groups of the world: 2 populations from Sulawesi, an island in the Indonesian archipelago, and 5 Native American tribes of Colombia, South America. The allele frequencies in the Minihasans and Torajans of Sulawesi are similar to each other (but the modal class allele is different) and in general agreement with those reported in mainland Asian groups, but different from both Europeans and Chinese Han of Taiwan. The 5 Native American tribes (Arsario, Kogui, Ijka, Wayuu, and Coreguaje) display different allele frequencies from those seen in Sulawesi populations, in other groups from Europe and mainland Asia, and in Chinese Han of Taiwan. Native Americans exhibit a bimodal distribution of alleles, unlike other groups, with significant differences among the tribes. The Arsario and Kogui have no admixture with Europeans or Africans and are the most distinctive, while the Wayuu have the most admixture and show most similarity to other groups. The data suggest that nonadmixed Native Americans may be quite distinctive with respect to this marker. The most common allele varies across the 5 tribes, from 249 base pairs to 261 base pairs. All samples exhibit Hardy-Weinberg genotype proportions; heterozygosities are lowest in the 2 nonadmixed Native American tribes. Examination of all the available data indicates that some east Asian and southeast Asian groups are characterized by a high frequency of smaller sized D12S67 alleles, while other populations have a greater proportion of the larger sized alleles. The cumulative, though still highly restricted, population data on locus D12S67 demonstrate that it may be of considerable value in anthropological genetic studies of ethnic groups. Data are required on Native Americans outside Colombia before this marker can be used in admixture studies of this group.

Social, familial and medical aspects of Usher syndrome in Colombia.

A psycho-social study was performed in 19 Colombian families with 40 affected individuals with Usher syndrome, identified through our national screening program for this disease in Colombia. The study was aimed to understand their needs, kind of familial inter-relationships, and social and familial implications of the patients' double sensorial limitation, in order to provide enough information to support the importance of early diagnosis, appropriate genetic counseling, and the establishment of adequate educational and rehabilitation programs in Colombia.

Inmunohistoquimica en prurigo actinico. Observaciones con ciclosporina / Inmunohystochemistry in actinic prurigo. Observations with cyclosporin

En el estudio de 19 pacientes con Prurigo Actínico, se tomaron biopsias de piel y utilizando inmunohistoquímica se encontró un aumento de linfocitos CD3, CD4, CD8, CD45RA, CD45RO y CD45RB, así como de células de Langerhans, de moléculas DR y de las moléculas de adhesión LFA-1, ICAM-1 y ELAM-1. El análisis estadístico mostró diferencias significativas cuando se compararon los resultados entre el grupo de pacientes y el de control (p<0.05). Estos sujetos fueron luego tratados con Ciclosporina A. Para relacionar la eficacia de la droga con los marcadores inmunológicos se tomaron otras biopsias al finalizar el tratamiento, donde las células y moléculas disminuyeron significativamente. Los valores de los pacientes se normalizaron cuando se compararon con los controles, a excepción de los linfocitos CD4, de las células de Langerhans y de la expresión de las moléculas DR, lo que en parte podría explicar la cronicidad de la enfermedad y sugerir la presencia de un estímulo antigénico permanente, lo que mantiene las células y moléculas del sistema inmune activadas

Results of Expedicion Humana. I. Analysis of HLA class II (DRB1-DQA1-DPB1) alleles and DR-DQ haplotypes in nine Amerindian populations from Colombia.

HLA class II variation was analyzed in nine Native American populations of Colombia using PCR/SSOP typing methods. Under the auspices of the Expedition Humana, approximately 30 unrelated native Colombia Indian samples each from the Tule (NW Pacific Coast), Kogui (Sierra Nevada). Ijka (Sierra Nevada), Ingano (Amazonas), Coreguaje (Amazonas), Nukak (Amazonas), Waunana (Pacific), Embera (Pacific) and Sikuani (Northeastern Plains) were collected and analyzed at the DRBI, DQA1, DQB1 and DPB1 loci. The number of different DRB1, DQA1, DQB1 and DPB1 alleles in the Colombian Indians is markedly reduced in comparison with neighboring African Colombian populations, which exhibit a very high degree of class II variability, as discussed in an accompanying paper. In the Colombian Amerindian groups, DR2 (DRB1*1602), DR4 (DRB1*0407, *0404, *0403 AND *0411), DR6 (DRB1*1402) and DR8 (DRB1*0802) comprise > 95% of all DRB1 alleles. We also found an absence of DR3 in all populations, and DR1, DR7 and DR9 allelic groups were either very rare or absent. Each Colombian Amerindian population has a predominant DRB1 allele (f = approximately 0.22-0.65) and DRB1-DQA1-DQB1 haplotype. Several novel DR-DQ haplotypes were also found. At the DPB1 locus, DPB1*0402 (f = 0.28-0.82), *1401 (f = 0.03-0.45), and *3501 (f = 0.03-0.27), were the three most prevalent alleles, each population maintaining one of these three alleles as the predominant (f > 0.26) DPB1 allele. The reduction of diversity for the HLA class II alleles in the Colombian Indians is suggestive of a population bottleneck during the colonization of the Americans, with little to no subsequent admixture with neighboring African Colombian populations in the last approximately 300 years.

Neuroradiology and clinical aspects of Usher syndrome.

We describe the neurological evaluation and MRI analysis of 30 patients, belonging to 16 families with Usher syndrome (US) type I and type II (US1 and US2). In addition to the classic visual and audiological abnormalities seen in these patients, we observed abnormal gait in 88.9% of US1 and in 66.7% of US2 patients and abnormal coordination in 33.4% of US1, and in 58.3% of US2. Borderline mental retardation, depression or bipolar affective disorder were observed in 16.7% of US1 and 33.3% of US2 patients. MRI analysis showed cerebellar abnormalities in 50% of US1 and 75% of US2 patients, but no clear correlation was observed between structural abnormalities and clinical findings. A pattern for the MRI classification of US patients is suggested.