A prospective study of women with ASCUS or LSIL pap smears at baseline and HPV E6/E7 mRNA positive: a 3-year follow-up.

Human papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.

[Indications and controindications of hormone replacement therapy in menopause]. / Indicazioni e controindicazioni della terapia ormonale sostitutiva in menopausa

Menopause is a physiological event of women's life that is the end of menstrual cycles and the end of the fertile period. Normally the age at which women reach menopause is between 50 and 52 years, as the world average. Menopause occurs when the functional ovarian reserve is exhausted or can be induced by surgical removal of the ovaries. What follows, however, is the establishment of a state of hypoestrogenism, which potentially affects various organs and systems (genito-urinary system, cardiovascular system, skeleton, skin, brain) and quality of life of women (varying degrees of vasomotor symptoms, vaginal atrophy, osteoporosis). Hormone replacement therapy (HRT), it is based on estrogen or estrogen and progesterone, can be used to compensate for estrogen deficiency and to prevent or limit the damages that may result. During the years, there have been several observational studies designed to identify the risks and benefits arising from the use of postmenopausal hormone replacement therapy, in spontaneous and surgical menopause. In fact, although several studies have shown that women treated with estrogen enjoyed a better overall level of health, over the last decade have raised doubts about the safety of hormone replacement therapy long term. In our study we try to discuss, based on a review of the literature and evidence available to date, what are the present indications and controindications to the use of hormone replacement therapy.

Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: a case series.

BACKGROUND: Treatment of patients with secondary pulmonary hypertension has been unsatisfactory. OBJECTIVE: To describe exercise capacity, functional class, and hemodynamic variables after long-term intravenous infusion of prostacyclin in patients with secondary pulmonary hypertension. DESIGN: Case series. SETTING: Academic referral center. PATIENTS: 33 patients with secondary, precapillary pulmonary hypertension (New York Heart Association class III or IV). INTERVENTION: Continuous intravenous prostacyclin administered by portable infusion pump on a compassionate-use basis. MEASUREMENTS: Functional class, treadmill time, and hemodynamic variables. RESULTS: Patients were followed for an average of 12.7 +/- 5.6 months. Exercise tolerance and New York Heart Association class improved in each patient. The duration of treadmill exercise increased from 186 seconds to 491 seconds, an increase of 305 seconds (95% CI, 194 to 417 seconds; P < 0.001). Mean pulmonary artery pressure decreased from 60 mm Hg to 46 mm Hg, a decrease of 14 mm Hg (CI, 9 to 19 mm Hg; P < 0.001). Cardiac output increased from 3.90 L/min to 6.30 L/min, an increase of 2.40 L/min (CI, 1.56 to 3.25 L/min; P < 0.001). The pulmonary vascular resistance decreased from 1143 dynes x s/cm5 to 575 dynes x s/cm5, a decrease of 567 dynes x s/cm5 (CI, 407 to 727 dynes x s/cm5; P < 0.001). Patients with collagen vascular disease, congenital heart disease, and portopulmonary hypertension were analyzed with other patients and separately. All groups had a statistically significant reduction in mean pulmonary artery pressure and a statistically significant increase in cardiac output. CONCLUSION: Intravenous prostacyclin may be effective in the treatment of patients with certain types of secondary pulmonary hypertension.

Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension.

BACKGROUND: Primary (idiopathic) pulmonary hypertension is a progressive, fatal disease. Conventional therapy with anticoagulant and vasodilator drugs may improve symptoms and survival among selected patients, but there is no evidence that the disease can be reversed. METHODS: We evaluated the effects of long-term therapy (i.e., for more than one year) with intravenous epoprostenol (prostacyclin) in patients with advanced primary pulmonary hypertension. The base-line evaluation included an assessment of pulmonary vascular dilation in response to intravenous adenosine. The epoprostenol dose was increased monthly to the maximum tolerated. Long-term therapy was evaluated by measuring improvement in symptoms, exercise capacity, and hemodynamic measures. RESULTS: We evaluated 27 patients with primary pulmonary hypertension over a mean (+/-SD) period of 16.7+/-5.2 months. Intravenous adenosine had a variable effect on pulmonary vascular resistance (mean reduction, 27 percent; range, 0 to 56; P<0.001). Epoprostenol therapy was initiated and the rate of infusion was increased by an average of 2.4 ng per kilogram of body weight per minute each month. Twenty-six of the 27 patients had improvement in symptoms and hemodynamic measures, and overall, pulmonary vascular resistance declined by 53 percent to 7.9+/-3.8 resistance units (P<0.001) at the time of restudy. The long-term effects of epoprostenol exceeded the short-term pulmonary vasodilator response to adenosine in all but one patient. Seven of the eight patients who had minimal pulmonary vasodilation in response to adenosine (mean reduction in resistance units, <20 percent) still had a significant reduction in pulmonary vascular resistance when treated with epoprostenol (mean, 39+/-14 percent; P=0.002). CONCLUSIONS: In primary pulmonary hypertension, long-term therapy with epoprostenol lowers pulmonary vascular resistance beyond the level achieved in the short term with intravenous adenosine. Epoprostenol appears to have sustained efficacy in this disorder.