Human papillomavirus infection, centrosome aberration, and genetic stability in cervical lesions.

DNA replication and centrosome duplication have to be strictly synchronized to guarantee genomic stability. p53, pRb, cyclin E, and cyclin A are reported to be involved in the synchronizing process. We investigated the relationship between papillomavirus infection, centrosome aberration and aneuploidy during genesis of cervical carcinoma. The number of centrosomes found in cells from normal cervical epithelium (n = 5), condyloma acuminata (n = 5), cervical intraepithelial neoplasia (CIN) I, II, and III (n = 14) and invasive cervical carcinoma (n = 5) was analyzed by gamma tubulin immunofluorescence staining. The nuclear DNA content was investigated by image cytometry and human papillomavirus (HPV) infection was determined by polymerase chain reaction. Normal epithelia and condyloma acuminata showed cells with one or two centrosomes, whereas CIN lesions showed cells with an increasing number of centrosomes. This abnormality was found to be lowest in CIN I lesions, increased with advancing grade of CIN and was highest in lesions of invasive carcinomas. In parallel, an increasing number of cells with aberrant DNA content was seen. All carcinomas and all except one of the CIN III lesions showed aneuploidy. Three CIN II cases were aneuploid and two cases with CIN I were tetraploid. Normal epithelia and condyloma acuminata showed diploidy. All invasive carcinomas and lesions with CIN were positive for high-risk HPV types 16, 18, or 31, except one invasive carcinoma and one CIN II lesion positive for universal primers only. Three condyloma acuminata were HPV 16-positive and one HPV 6-positive. The results suggest that high-risk HPV infection is correlated to a progressive numerical disturbance of centrosome replication followed by progressive chromosomal aberrations in CIN lesions and invasive carcinomas.

Turner's syndrome and hearing disorders in women aged 16-34.

Forty women with Turner's syndrome aged 16-34 years were tested clinically and audiometrically according to their ear problems and hearing. A high incidence of middle-ear infections was demonstrated. A mid-frequency sensorineural hearing loss was frequently diagnosed and could be correlated to the karyotype. The dip showed a progression with age. Middle-ear problems were more common among women with a dip. An early high-frequency hearing loss could be noted in the present group among the older women. In some cases this had already led to social hearing problems and use of hearing aids. When comparing these women with a group of elderly Turner women the dip was not as deep, the maximum peak was seen in the 2 kHz region and social hearing problems and hearing aids were not as frequent. If no dip was found no major hearing problems could be detected or expected in future life. The data emphasize the importance of early audiological evaluation and information about predisposition to hearing impairment in Turner's syndrome.

Bone mineral density in middle-aged women with Turner's syndrome.

Bone mineral density (BMD), bone mineral content and body composition were determined in 47 middle-aged (mean age 47.9 +/- 1.1 years) women with Turner's syndrome. Bone mineral density was measured in the forearm, femoral neck and total body. The women investigated had a BMD lower than the normal mean. When expressed as Z scores (individual values compared to normal reference data matched for age, weight and sex), the median Z score of the total body was -1.23. When comparing women with the karyotype 45,X and mosaic women, the latter showed a higher BMD in all sites of measurement. Duration of hormonal replacement therapy (HRT) differed significantly between the mosaic and the 45,X women, with a longer duration in the mosaic group (20.7 +/- 2 vs 12.1 +/- 2.6 years; p < 0.01). The duration of HRT was found to be the more important factor to maintain bone mass, not the karyotype. Bone mineral density increased with years of HRT but not until after > 20 years of HRT could a significant difference be shown between the women with HRT < or = 20 years and those with HRT > 20 years. No correlation was found between BMD and body weight, body fat or percentage body fat. Whether the osteopenia found in women with Turner's syndrome is similar to that found postmenopausally or is a specific form related to the chromosome aberration remains to be investigated further. The present data support a relation to estrogen deficiency.

Ear and hearing problems in 44 middle-aged women with Turner's syndrome.

The present study has investigated ear and hearing problems in 44 women with Turner's syndrome (median age 45.5 years). Social hearing problems were common after the age of 40 and 27% were fitted with hearing aids. Audiograms revealed a hearing loss > 20 dB hearing level (HL) in 91% leading to clinically significant hearing problems in 60%. A distinct dip in the 1.5 kHz frequency range, with a mean value of 46 dB was found in 30 women. The occurrence of the dip was correlated to the karyotype. All women with the karyotype 45,X and 45,X/46,X,i(Xq) demonstrated this dip while in the 45,X/46,XX group it was found in 31%. No dips were found among 45,X/46,XY and 45,X/46,XX/47,XXX women. With increasing age a progressive high frequency hearing loss was added to the dip leading to severe hearing problems earlier in the Turner women than age-matched controls. This might be due to a genetic defect leading to premature ageing of their hearing organ. These data emphasize the importance of providing early information to Turner girls of their predisposition to hearing impairment. Patient awareness of importance of audiological evaluations and the benefit of hearing aids should be stressed.

Life with Turner's syndrome--a psychosocial report from 22 middle-aged women.

Twenty-two middle-aged women (median age 44.5 years) with Turner's syndrome were interviewed about family background, social identity, emotional development, relations, female identity, sexuality and reactions to the diagnosis, to evaluate how the condition has affected their lives and coping style. During the years preceding the diagnosis and hormonal replacement therapy (HRT) they had often isolated themselves as they felt different from their peers. Ovarian failure and infertility, not the body height, were the major problems for most of the women. Infertility had affected the women very deeply and many felt depressed because of this. Adolescent behaviour, a feeling of chronic inferiority or a feeling of grief were different ways of coping with the situation. Median age at sexual debut was 19.5 years. Painful intercourse related to vaginal constriction and sore membranes was commonly reported. Most of the women had stopped HRT because of side-effects. Many of the problems experienced by the women could have been avoided if proper HRT had been administered in due time and on a long-term basis. This emphasizes the importance of regular contact with a gynecologist of special training and interest.

Middle-aged women with Turner's syndrome. Medical status, hormonal treatment and social life.

A study of 49 middle-aged (greater than 35 years old) women with Turner's syndrome was performed to evaluate medical status, hormonal treatment and social life. Most of the women lived a normal social life in stable relationships and all were employed. Some had adopted children and 4 had children of their own. They had all been informed about Turner's syndrome at time of diagnosis, but after the induced puberty they did not know who to turn to with their variety of medical problems. They were healthy except for reduced hearing, which in many cases required hearing aid. Elevated liver enzymes were found in almost all the women. The mechanism behind this finding is unclear, but it does not seem to imply severe liver damage why the indicated estrogen therapy should not be withdrawn from these women. Today amniocentesis and chorionic villus biopsies are commonly used to detect chromosome abnormalities. It is our duty as counsellors to give adequate information on the prognosis of a specific finding in the fetus to help future parents in their decision.