Detection of human papillomavirus DNA by in situ hybridization and polymerase chain reaction in human papillomavirus equivocal and dysplastic cervical biopsies.

One hundred twenty-one paraffin-embedded cervical biopsy specimens were tested for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction. By in situ hybridization using probes for HPV types 6/11, 16/18, 31/33/35, 42/43/44, 51/52, and 45/56, HPV DNA was found in none of 20 normal/squamous metaplasia biopsy specimens, in one of 76 HPV equivocal biopsy specimens, in seven of 12 condyloma/mild dysplasia biopsy specimens, and in 12 of 13 moderate/severe dysplasia biopsy specimens. Polymerase chain reaction using HPV L1 consensus sequence primers followed by filter hybridization of the amplification products was positive for HPV DNA in two of 20 normal/squamous metaplasia biopsy specimens, in 23 of 76 HPV equivocal biopsy specimens, in eight of 12 condyloma/mild dysplasia biopsy specimens, and in 12 of 13 moderate/severe dysplasia biopsy specimens. Among biopsies that tested positive by polymerase chain reaction but that were negative by in situ hybridization, the most commonly identified HPV was type 16. We conclude that although HPV equivocal biopsy specimens contain HPV DNA more frequently than histologically normal tissue, the majority of biopsy specimens in this category test negative for HPV DNA. The clinical significance of a positive test for HPV, in the absence of unequivocal histologic changes, remains to be determined.

Short-term effects of estrogen and progestin on blood pressure of normotensive postmenopausal women.

Blood pressure rises in women with increasing age, possibly related to the decrease in production of female hormones that accompanies menopause. Although estrogen or progestin administration alone consistently does not lower blood pressure in postmenopausal women, possible interactions of these two hormones in affecting blood pressure are not well understood. We studied 12 surgically postmenopausal, normotensive women, aged 51 +/- 2 years (SEM). Treatment for each subject consisted of 1 week each of placebo, estrogen (conjugated equine estrogens, 2.5 mg/day), progestin (medroxyprogesterone acetate, 60 mg/day), and combined estrogen and progestin, given in varied order. At the end of each week, auscultatory blood pressures were measured while patients were seated. Neither estrogen nor progestin alone either increased or decreased blood pressure significantly, whereas combined estrogen and progestin lowered systolic, diastolic, and mean blood pressures 6 to 7 mm Hg (P less than .05). Treatment order was unrelated to the change in blood pressure values. The authors suggest that administering progestin with estrogen may be more effective in lowering blood pressure than either hormone alone in postmenopausal women.

Cytologic diagnosis of human papillomavirus infection: spindled nuclei.

The classic cytologic criteria, koilocytotic atypia and dyskeratocytosis, fail to identify most cases with colposcopic and histologic evidence of cervical condylomata. The purpose of this study was to identify a novel cytologic diagnostic criterion, spindled nuclei, to predict the presence of human papillomavirus (HPV) infection of the cervical epithelium. Review of the hospital records of 100 consecutive cases with spindled nuclei on Papanicolaou smear identified 36 patients in whom a colposcopic examination and/or cervical biopsy had been performed between January 1, 1988, and March 31, 1989. Ninety-seven percent of these 36 cases were positive by colposcopy and 89% of the cases were positive by cervical biopsy for changes of condyloma or intraepithelial neoplasia. HPV DNA hybridization in situ was positive in 16 of 36 patients, and the probe for types 31/33/35 most often stained histologic sections showing condylomatous change without concurrent dysplasia. Electron microscopy of spindled nuclei showed evidence of HPV-type viral particles in the five cases examined.

Progestin and estrogen reduce sleep-disordered breathing in postmenopausal women.

Women exhibit sleep-disordered breathing syndromes less commonly than men before but not after the age of menopause, suggesting that female hormones may exert a protective effect. We sought to determine whether combined progestin and estrogen treatment decreased sleep-disordered breathing in healthy postmenopausal women. Nine ovarihysterectomized women [50 +/- 2 (SE) yr of age] were studied after 1 wk of treatment with placebo (lactose) or combined progestin and estrogen (medroxyprogesterone acetate, 20 mg tid, and Premarin, 1.25 mg bid). Subjects showed few respiratory disturbances during placebo treatment. Despite this, combined progestin and estrogen administration reduced the number of sleep-disordered breathing episodes in every subject, decreasing the average number of episodes per subject from 15 +/- 4 to 3 +/- 1. The duration of hypopneas also decreased with hormone treatment. Thus the presence of progestin and estrogen may be involved in protecting premenopausal women against sleep-disordered breathing.

Combined effects of female hormones and metabolic rate on ventilatory drives in women.

Increased resting ventilation (VE) and hypoxic and hypercapnic ventilatory responses occur during pregnancy in association with elevations in female hormones and metabolic rate. To determine whether increases in progestin, estrogen, and metabolic rate produced a rise in VE and hypoxic ventilatory response (HVR) similar in magnitude to that observed at full-term pregnancy, we studied 12 postmenopausal women after 1 wk of treatment with placebo, progestin (20 mg tid medroxyprogesterone acetate), estrogen (1.25 mg bid conjugated equine estrogens), and combined progestin and estrogen. Progestin alone or with estrogen raised VE at rest and decreased end-tidal PCO2 (PETCO2) by 3.9 +/- 0.8 and 3.3 +/- 0.6 Torr, respectively (both P less than 0.05), accounting for approximately one-fourth of the rise in VE and three-fourths of the PETCO2 reduction seen at full-term pregnancy. The addition of mild exercise sufficient to raise metabolic rate by 33-36% produced the remaining three-fourths of the rise in VE but no further decline in PETCO2. Combined progestin and estrogen raised HVR and hypercapnic ventilatory response more consistently than progestin alone and could account for one-half of the increase in HVR seen at full-term pregnancy. Mild exercise alone did not raise HVR, but when exercise was combined with progestin and estrogen administration, HVR rose by amounts equal to that seen at full-term pregnancy. We concluded that female hormones together with mild elevation in metabolic rate were likely responsible for the pregnancy-associated increases in VE and HVR.