Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women.

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15-85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan-Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman's age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3.

Identification of a 6-cM minimal deletion at 11q23.1-23.2 and exclusion of PPP2R1B gene as a deletion target in cervical cancer.

Previous functional and deletion mapping studies on cervical cancer (CC) have implicated one or more tumor suppressor genes (TSGs) on chromosome 11 at q13 and q22-24 regions. Of these, the 11q22-24 region exhibits frequent allelic deletions in a variety of solid tumor types, suggesting the presence of critical genes for tumor suppression in this region. However, the precise region of deletion on 11q is not clearly defined in CC. In an attempt to accurately map the deleted region, we performed an extensive loss of heterozygosity (LOH) mapping in 58 tumors using 25 polymorphic loci on both the short and long arms. The pattern of LOH identified three sites of deletions, two on 11p (p15.11-p15.3 and p12-13), and one on 11q (q23.1-q23.2). The 11q23.1-q23.2 exhibited highest frequency (60.6%) of deletions, suggesting that this could be the site of a candidate TSG in CC. The minimal deletion at 11q23.1-23.2 was restricted to a 6-cM region between 123.5 and 129.5 cM genetic distance on chromosome 11, identifying the site of a potential TSG important in the pathogenesis of CC. At least five known genes and 28 UniGene clusters were mapped to the present commonly deleted region. In addition, we have excluded a previously known TSG PPP2R1B at 11q23 as a deletion target in CC. The definition of the minimal deletion and the availability of expressed sequence resources should facilitate the identification of the candidate TSG.

Mapping the sites of putative tumor suppressor genes at 6p25 and 6p21.3 in cervical carcinoma: occurrence of allelic deletions in precancerous lesions.

Allelic deletions on the short arm of chromosome 6 (6p) are one of the common, possibly early, genetic changes that occur in the pathogenesis of cervical carcinoma (CC). Previous loss of heterozygosity (LOH) studies in CC identified a number of critical regions of deletions on 6p. However, the precise location of minimally deleted regions and their role in precancerous lesions have not been well characterized. To address these questions, we first performed a detailed LOH analysis on 6p in 59 cases of invasive CC. The pattern of LOH identified two minimal regions of deletions, one spanning a 5 cM genetic distance at 6p25 and a second site of 10.3 cM deletion mapping to 6p21.3. The 6p21.3 minimal deletion spans HLA class I genes. To understand the role of 6p genetic alterations in the development of CC, we also investigated 12 high-grade and 4 low-grade cases of cervical intraepithelial neoplasia (CIN) for LOH after laser microdissection. The high-grade CINs exhibited 91.7% LOH, and low-grade CINs had 50% LOH. These findings implicate the presence of at least two tumor suppressor genes on 6p relevant to CC and suggest that these genetic alterations occur very early in CC development. This study should therefore facilitate the identification of tumor suppressor genes on 6p and may identify which CINs are at high risk of progressing to invasive CC.

Changes in normal lipid profile of menopausal women with combined hormone replacement therapy. Comparative clinical trial of two hormonal combinations (conjugated estrogens/medroxyprogesterone acetate versus estradiol valerate/cyproterone acetate).

OBJECTIVES: To compare the effect on plasma lipids of conjugated estrogens/medroxyprogesterone acetate (CE/MPA) and estradiol valerate/cyproterone acetate (EV/CPA) in healthy peri and postmenopausal women during 1 year. METHODS: Multicentric, controlled, single blinded Phase III clinical trial. Women were randomized to two treatment groups: Group A (n = 49 women): CE 0.625 mg/day for 21 days and MPA 5 mg from day 12 to 21. Group B (n = 55 women): EV 2 mg/day for 21 days and CPA 1 mg from day 12 to 21. Total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C), triglycerides, aminotransferases and alkaline phosphatase were measured before starting therapy, and after 3, 6, 9 and 12 months of hormone replacement therapy (HRT). TC/HDL-C and LDL-C/HDL-C ratios were determined. RESULTS: There were no changes in TC levels. HDL-C increased and LDL-C decreased significantly, with no differences between groups but within each group. Triglycerides increased significantly but remained within normal values, with no differences between groups. TC/HDL-C ratio showed a slight and steady decrease in both groups. LDL-C/HDL-C ratio decreased in both treatment groups. CONCLUSION: Both cyclic sequential preparations used in HRT showed a favorable effect on plasma lipids in healthy peri and postmenopausal women, with an increase in HDL-C and a decrease in LDL-C levels, as well as in the LDL-C/HDL-C and TC/HDL-C ratios. Our study confirms the positive effect of estrogens on lipids, which does not seem to be adversely affected by the addition of progestogens derived from pregnanes.

Prevalence and determinants of HPV infection among Colombian women with normal cytology.

Human papillomavirus is the principal risk factor associated with cervical cancer, the most common malignancy among women in Colombia. We conducted a survey, aiming to report type specific prevalence and determinants of human papillomavirus infection in women with normal cytology. A total of 1859 women from Bogota, Colombia were interviewed and tested for human papillomavirus using a general primer GP5+/GP6+ mediated PCR-EIA. The overall HPV DNA prevalence was 14.8%; 9% of the women were infected by high risk types, 3.1% by low risk types, 2.3% by both high risk/low risk types and 0.4% by uncharacterized types (human papillomavirus X). Thirty-two different human papillomavirus types were detected, being human papillomavirus 16, 58, 56, 81(CP8304) and 18 the most common types. The human papillomavirus prevalence was 26.1% among women younger than 20 years, 2.3% in women aged 45-54 years, and 13.2% in women aged 55 years or more. For low risk types the highest peak of prevalence was observed in women aged 55 years or more. Compared to women aged 35-44 years, women aged less than 20 years had a 10-fold increased risk of having multiple infections. Besides age, there was a positive association between the risk of human papillomavirus infection and number of regular sexual partners and oral contraceptive use. In women aged below 25 years, high educational level and having had casual sexual partners predicted infection risk. In conclusion, there was a broad diversity of human papillomavirus infections with high risk types being the most common types detected. In this population multiplicity of sexual partners and, among young women, high educational level and casual sexual partners seem to determine risk.

Low grade squamous intra-epithelial lesions and human papillomavirus infection in Colombian women.

Low grade squamous intra-epithelial lesions could be considered as a manifestation of human papillomavirus exposition, however the discrepancy between rates of infection with human papillomavirus and development of low grade squamous intra-epithelial lesions is notable. Here we report a cross-sectional three-armed case-control study in the Colombian population, to compare the risk factors of women with low grade squamous intra-epithelial lesions with that of human papillomavirus DNA-negative and positive women with normal cytology.

Prevalence and determinants of Chlamydia trachomatis infections in women from Bogota, Colombia.

OBJECTIVES: Chlamydia trachomatis infection in the cervix and uterus has been hypothesised to be a co-factor for cervical cancer. We performed a cross sectional study in Bogota, Colombia, where cervical cancer rates are high, to determine the prevalence and determinants of C trachomatis infection, and in particular its association with human papillomavirus (HPV). METHODS: 1829 low income sexually active women were interviewed and tested for C trachomatis, using an endogenous plasmid PCR-EIA, and for 37 HPV types, using a general primer GP5+/6+ mediated PCR-EIA. RESULTS: The overall prevalence of C trachomatis was 5.0%, and it did not differ substantially between women with normal (5.0%) and those with abnormal (5.2%) cervical cytology. Women infected with any HPV type (15.1%) had a slightly increased risk of being simultaneously infected with C trachomatis (adjusted OR 1.3, 95% CI: 0.8 to 2.4). This association was stronger when multiple HPV infections (adjusted OR 2.5, 95% CI: 1.1 to 5.9) were present. No other lifestyle or reproductive characteristics were clearly associated with risk of C trachomatis infection. CONCLUSIONS: HPV infected women, particularly women with multiple HPV infections, are at increased risk of being infected with C trachomatis.

Efectos de la terapia hormonal de reemplazo transdermica- 1 vez por semana (Climaderm) vs dos veces por semana (Estraderm) sobre los lipidos y lipoproteinas en mujeres postmenopausicas / Effects of transdermal hormonal replacement therapy-once a week (Climaderm) Vs twice a week (Estraderm) on lipids and lipoproteins in postmenopausal women

Objetivo: Evaluar el comportamiento de pruebas bioquímicas, funcionales hepáticas y lipídicas en dos regímenes de terapia hormonal de reemplazo del 17-b-estradioluna vez por semana (Climaderm) vs dos veces por semana (Estraderm), durante un año en mujeres postmenopáusicas. Métodos: Es parte de un estudio multicéntrico, Fase III abierto, aleatorizado en 19 mujeres postmenopáusicas durante un año, con criterios de inclusión y exclusión preestablecidos. Se dividieron en dos grupos; A =11 ( 1 vez por semana) y B = 8 (dos veces por semana) Se determinaron el índice de masa corporal (IMC), T. Arterial, cuadro hemático, Glicemia billirrubinas, proteínastotales y diferenciales al inicio y al final del estudio, El Colesterol, HDL, LDL, Triglicéridos, Apolipoproteína (A)4Lpa), Apolipoproteína (B) (Lpb), al inicio ,6 meses y al año. Como pruebas de significancia se utilizo la T de Student, prueba exacta de Fischer y la prueba apareada de t. Resultados: No hay modificaciones en el IMC en ambos grupos (23.7 vs 24.7), Existe una disminución significativa del pulso (p<0.001) en el grupo A (78-75 x min. vs 79-76 x min.). No hay modificaciones en la Presión Media Diastólica (PMD) al inicio y final de estudio (84.5-96.6 vs 94.7-95.4). No hay modificaciones en el cuadro hemático ni en las pruebas funcionales hepáticas en ambos grupos. La glicemia disminuye significativamente (p<0.001) en el grupo A ( 94.8-86.7 vs 96.4-86.3 mg/dl). El Colesterol Total disminuye en un -9 por ciento en ambos grupos, las LDL disminuyen -9.37 vs -13.37 por ciento ). La Lp(a) -0.34 por ciento vs -9.4 por ciento y la Lp(b) -018 vs +10.39. La HDL no se modifica con tendencia a disminuir -1.19 por ciento vs-6.75 por ciento . Conclusiones: Al comparar la vía transdérmica una vez por semana vs dos veces por semana no modifica los parámetros bioquímicos en las pruebas funcionales hepáticas en mujeres postmenopáusicas. La vía transdérmica una vez por semana produce una disminución significativa en el pulso, la glicemia, colesterol total, LDL y Lp(a)

Densidad Mineral osea medida por densiometria de energia dual de Rx en mujeres climatericas de Santafé de Bogotá / Mineral density so measure for densiometria of energia dual of Rx in women climaterics of Santafé de Bogotá

Se realizan 1.971 densitometrías por la técnica de doble fotón dual (DPA) en mujeres climatéricas de la ciudad de Santa Fe de Bogotá, que consultaron por diferente sintomatología o simplemente para control, en el Instituto Materno Infantil, Medicina propagada o medicina particular durante el período de 1993 y 31 de diciembre de 1994. Se excluyeron las pacientes que estaban ingiriendo algún tipo de medicación hormonal. La edad estuvo comprendida entre los 40 y 75 años. El índice de Masa corporal estuvo dentro de límites normales (IMC=23) pero con diferencias significativas entre los grupos etarios. La densidad mineral ósea medida en gr/cm2 mostró que el 70 por ciento estaban dentro de los límites normales para el promedio asignado al instrumento (tabla del Brasil), con 1 DS por encima o por debajo (ostopenia) fue del 15 por ciento y 2 DS 1 por ciento . Estos datos sugieren que la ostopenia es menor de la reportada por otros países y se plantea la necesidad de hacer estudio piloto para Colombia y con una población blanco. Se establecen valores de referencia de la densidad mineral ósea en mujeres pre y postmenopáusicas

Correlacion entre el indice de masa corporal y densidad mineral osea / Correlation between body mass index and bone mineral density

Objetivos: Conocer si el aumento de peso modifica la densidad mineral ósea (DM0). Material y métodos: 5e tomaron 797; pacientes pre y postmenopáusica que fueron remitidas para practicar de rutina una densitometría ósea. Las pacientes se dividieron en dos grupos de acuerdo a su estado socioeconómico Grupo 1 > de 2 salarios mínimos, grupo 2 < de 2 salarios mínimos. Se utilizó para la medición un aparato de absorciometría de rayos X de doble fotón (DEXA) con los standares de un equipo Lunar DPX. Las pacientes se clasificaron de acuerdo al índice de masa corporal (IMC) en 4 categorías; < 20 delgadas, normales 20-24, sobrepeso 25-29 y obesas > de 30.Resultados: De acuerdo al índice de Masa Corporal, se encontró que el 70 por ciento de /as mujeres eran delgadas, normales 64 por ciento, sobrepeso 20.4 por ciento y obesas 5.2 por ciento . La DM0 promedio en las pacientes delgadas a nivel de columna Lumbar fue 950.52 g-m2 y de las obesas de 912.82 g-m2 sin ser significativa esta diferencia. Cuando la DM0 fue comparada entre los dos grupos socioeconómicos, se encontró diferencia significativa a nivel de la columna lumbar en las mujeres con sobrepeso (p< 0.03). En la misma forma se encontraron niveles de DM0 significativamente más altos en el Grupo 2 a nivel de la columna y el fémur en las pacientes normales y con sobre peso (p < 0.003 y p < 0.001 respectivamente) Conclusión: El presente estudio demuestra cómo la DM0 se modifica con el IMC y muestra diferencias significativas según el estudio socioeconómico a nivel y fémur

Determinacion de niveles de vitamina D y su relacion con la densidad mineral osea (DMO) en mujeres perimenopausicas / Vitamin D and Bone mineral density of perimenopause women

Objetivos. Conocer en nuestro medio los niveles de vitamina D en mujeres durante el climaterio y su diferencia en los casos de osteopenia / osteoporosis confirmados por osteodensitometría. Muestra. Se tomaron 27 pacientes que consultaron por síndrome climaterio a la Clínica de Climaterio del Instituto Materno Infantil (IMI) de Bogotá durante 1999: 3 osteoporóticas, 12 osteopénicas y 12 normales por osteodensitometría de acuerdo a los parámetros establecidos por la Asociación Internacional de Osteoporosis.Metodología. Se utilizó la técnica de radioinmunoanálisis para la determinación cuantitativa de 1,25 (OH)2D2 en plasma humano, utilizando el kit Gamma b1, 25 dihydroxyvitamin de la casa IDS, por medio de inmunoextracción. Sensibilidad - 2 Desviaciones estándar de 10 replicas del calibrador cero (5 pmol/L). Valor de referencia 46- 110 pmol/L. Estos datos se compararon con la Densidad Mineral Osea (DM0) medida por densitometría a nivel de columna lumbar (L4) y fémur, considerando como osteoporosis un T-score de -2.5. Para el cálculo de la muestra se utilizó la prueba de T (22 grados de libertad), asumiendo igualdad de varianzas. Resultados: El promedio para el grupo es 81.7 +18.9 pmol/L. El 68 por ciento de la muestra se encuentra entre 62.7 y 100.6 pmol/L dentro del promedio de lo esperado. El promedio de las mujeres normales es de 100.4 + 13.56 pmol/L y las osteopénicas de 66.96 + 9.5 pmol/L estos valores representan una disminución del 33 por ciento cuando se comparan las mujeres normales frente a las osteopénicas. Existe una diferencia significativa p< 0.001 entre las de DM0 normales y las osteopénicas