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Biomedical subjects

Oskari Heikinheimo

Publications and source records attributed to Oskari Heikinheimo.

At least 19 recordsLinked to original sources

Experience with the levonorgestrel-releasing intrauterine system among HIV-infected women.

BACKGROUND: Safe and effective contraception is needed for women infected with human immunodeficiency virus (HIV). The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective long-term contraceptive that reduces menstrual bleeding and may reduce the risk of pelvic inflammatory disease. Yet, little is known about LNG-IUS use in HIV-infected women. SUBJECTS AND METHODS: Six HIV-infected women had the LNG-IUS inserted between March 1998 and October 2002, and were systemically followed for a mean of 45 months. Indications for LNG-IUS use were contraception in four women and menorrhagia in two women. RESULTS: The LNG-IUS was well tolerated, and menstrual bleeding was reduced in all women. Blood hemoglobin levels increased in each subject, with mean levels being 123 g/L (SD=11.7) before LNG-IUS insertion and 135 g/L (SD=8.7) at 1 year (p=.01). Levels of circulating CD4 lymphocytes and Pap smear findings remained unchanged. CONCLUSIONS: Our limited experience with LNG-IUS use in HIV-infected women is encouraging. The LNG-IUS may be used as an alternative to uterine surgery in HIV-infected women with menorrhagia.

Adult↗

The levonorgestrel-releasing intrauterine system (LNG-IUS) in HIV-infected women--effects on bleeding patterns, ovarian function and genital shedding of HIV.

BACKGROUND: Safe and effective contraceptives are needed for human immunodeficiency virus (HIV)-infected women. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive with additional health benefits. The objective of this study was to evaluate the effects of the LNG-IUS among HIV-infected women. METHODS: Twelve systematically managed HIV-infected women were studied prospectively. Following a 2-month run-in period, the subjects had an LNG-IUS inserted and were followed up for 1 year. Patterns of bleeding, blood haemoglobin and CD4-lymphocyte content, plasma HIV RNA, serum levels of LNG, of estradiol (E(2)) and of ferritin and genital shedding of HIV RNA were monitored. RESULTS: Menstrual bleeding was reduced significantly during the use of the LNG-IUS; this was associated with slight increases in serum haemoglobin and ferritin levels. Serum E(2) concentrations remained in the follicular range in all subjects. Among subjects using antiretroviral medication, the proportion of cervicovaginal lavage specimens with detectable HIV RNA was 10% before and after the insertion of the LNG-IUS. CONCLUSIONS: The effects of the LNG-IUS on bleeding patterns, body iron stores and ovarian function were similar to those seen in healthy women. Genital shedding of HIV RNA was not affected by the LNG-IUS. These data encourage further studies on the effects of the LNG-IUS on reproductive health among HIV-infected women.

Contraceptive Agents, Female↗

Prevalence and risk factors of squamous intraepithelial lesions of the cervix among HIV-infected women - a long-term follow-up study in a low-prevalence population.

HIV-infected women have high risk for precancerous lesions of the uterine cervix. We studied the prevalence and risk factors of squamous intraepithelial lesions (SIL) among systematically followed HIV-infected women enrolled from a population with low HIV prevalence. The study population consisted of 108 HIV-infected women enrolled between 1989 and 2003 with a mean follow-up 4.4 years. Risk factors of SIL were assessed based on samples collected during 2000-02. The overall rates of atypical glandular cells of uncertain significance (AGUS), atypical squamous cells of uncertain significance (ASCUS), low-grade SIL (LSIL) and high-grade SIL (HSIL) were 4, 24, 15 and 5%, respectively. Reduced CD4-lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection (< or > or =5 years), use of antiretroviral medication, or HIV viral load (<50 or > or =50 copies/mL) was not. The cumulative risk of developing SIL after 1 and 5 years was 17% (95% confidence interval [CI] 7-27%) and 48% (95% CI 33-63%), respectively. The cumulative risk of SIL was increased among women younger than 31 years (P = 0.04) as well as in women displaying high initial HIV viral load (P = 0.01). Our results from a low HIV-incidence population re-emphasize the importance of guidelines for cytologic screening of HIV-seropositive women.

Adolescent↗

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Journal Article↗

Comparison of secondary and primary ovarian malignancies reveals differences in their pre- and perioperative characteristics.

OBJECTIVE: Preoperative differentiation of primary and metastatic ovarian tumors is difficult. Young age of the patient, bilateralism and reduced multilocularity are cited characteristics of secondary ovarian malignancies. We sought to identity pre- and perioperative factors which may aid in differentiating metastatic ovarian tumors from primary ovarian malignancies. PATIENTS AND METHODS: We performed a retrospective analysis of demographic parameters, preoperative serum tumor marker levels and ultrasonographic as well as operative findings in 38 patients with secondary ovarian malignancies and 76 control patients with primary epithelial ovarian cancer. All patients were treated at our institute from 1996 to 2003. RESULTS: The proportion of secondary ovarian tumors, of all ovarian malignancies, was 5.2%. The most common sites of origin were the gastrointestinal tract (42%), breast (29%) and peritoneum (16%). Fifty-eight percent of the patients with a secondary ovarian tumor had a history of previous malignancy; 42% of the primary malignancies were detected only following diagnosis of ovarian metastasis. The two patient groups (primary or secondary ovarian malignancy) could not be distinguished by age, parity, menopausal status or history of hysterectomy. Of the serum markers, the preoperative level of serum CA 125 was not different between the two groups. Both serum tumor-associated trypsin inhibitor (TATI) (7.2 +/- 9.6 vs. 4.7 +/- 9.4 mug/l [mean +/- SD]) and carsinoembryonic antigen (CEA) levels (19.7 +/- 30.8 vs. 6.7 +/- 120.0 mug/l) were higher in the group with secondary malignancies (P < 0.02). The metastatic ovarian tumors, as measured preoperatively by ultrasonography (US), were smaller (64 mm, 62-89 mm [median, 95% Cl]) than the primary tumors (105 mm, 104-134 mm) (P < 0.0005). The same was true for tumor sizes measured at surgery (P < 0.05). Furthermore, the secondary tumors were more often solid (50 vs. 10%) (P < 0.005), and more seldom cystic-solid (17 vs. 55%) (P < 0.001). Presence of ascites was more common among patients with primary ovarian malignancies in both preoperative US (P < 0.01) and at operation (P < 0.0001). Bilateralism, presence of adhesions, and carcinosis did not differ between the two groups. CONCLUSIONS: When evaluating a patient with an ovarian tumor, a history of malignancy strongly suggests a metastatic nature. Size less than 9 cm, solid structure, absence of ascites and elevated serum CEA and TATI levels were typical features associated with secondary ovarian malignancies.

CA-125 Antigen↗

Transcription factors GATA-4 and GATA-6, and their potential downstream effectors in ovarian germ cell tumors.

Ovarian germ cell tumors (GCTs) are histologically heterogeneous neoplasms originating from activated germ cells, the oocyte stem cells. These rare tumors often contain many different tissues mixed together, and malignant components are occasionally hidden within benign tissues thus complicating the diagnosis. The reasons for the variable differentiation of germ cells are still largely unknown. As transcription factors GATA-4 and GATA-6 as well as their downstream factors (e.g. HNF-4, BMP-2 and Ihh) are essential for normal yolk sac development, we studied their expression in 19 ovarian GCTs. Endodermal markers were expressed distinctively in different GCT types. The malignant endoderm in yolk sac tumors expressed all factors of endodermal development included in the study. Dysgerminomas, on the contrary, expressed only GATA-4 and, in a minority of cases, Ihh and BMP-2. The results suggest that GATA-4 and GATA-6 detected in the ovarian GCTs have retained their normal function. The fact that GATA-6 and HNF-4 are expressed exclusively in endodermal tissues indicates that these transcription factors play a role in the differentiation of germ cells towards the endodermal phenotype. Analysis of the nuclear transcription factors in tumor tissue could serve as a new informative diagnostic tool for ovarian GCTs.

Adolescent↗

Effect of antiprogesterone mifepristone followed by misoprostol on circulating leptin in early pregnancy.

BACKGROUND: To study the role of progesterone (P4) in the regulation of circulating leptin in early human pregnancy, we measured the levels of leptin before and after administration of the antiprogestin mifepristone, followed by misoprostol in early pregnancy. METHODS: Thirty-four women requesting termination of pregnancy, with < or =63 days of amenorrhea, received 200 mg of mifepristone on day 0, followed by either oral or vaginal administration of 0.8 mg of misoprostol on day 2. Five serial serum samples were assayed for leptin, human chorionic gonadotrophin (hCG), P4, estradiol (E2), cortisol, and mifepristone. RESULTS: Circulating leptin concentrations decreased by 8.7 +/- 29.7% (mean +/- standard deviation) (p < 0.05) following the ingestion of mifepristone. After misoprostol administration on day 2, a decrease of 12.6 +/- 17.0% (p < 0.05) was followed by a rebound on day 3 to 87.6 +/- 25.7% of the pretreatment values. Two weeks after mifepristone, leptin levels had declined by 25.4 +/- 30.4%. In contrast, E2, P4, and hCG concentrations continued to increase following mifepristone, followed by rapid declines from day 2 to day 3. Serum cortisol concentrations increased by 89.7% +/- 82.7% in response to mifepristone, but this increase did not correlate with the decrease in leptin. The decrease in leptin levels on day 2 correlated with the decreases in P4 (r = 0.37, p < 0.05) and in E2 (r = 0.44, p < 0.05) levels. CONCLUSIONS: The fall in leptin levels following mifepristone implies a role for P4 in the regulation of leptin in early pregnancy. Moreover, the significant correlation between the changes in leptin and those of P4 and E2 at the time of luteolysis suggests that corpus luteum may also play a role in the regulation of circulating leptin in early pregnancy.

Abortifacient Agents, Steroidal↗

Pregnancy outcome among HIV-infected women in the Helsinki metropolitan area.

BACKGROUND: Antiretroviral medication and good obstetric practice have greatly reduced the rate of vertical transmission of human immunodeficiency virus (HIV) infection. The incidence of HIV infection has remained low in Finland. Universal antenatal screening has been offered to all pregnant women since 1998. METHODS: We analyzed the outcomes of 52 pregnancies among 45 HIV-infected mothers delivering at our department during 1993-2003. A multidisciplinary team planned the management strategy individually and supported the mother's adherence to treatment. RESULTS: The incidence of HIV infection among women delivering in our hospital district increased from 0.6/10,000 (95% CI 0-1.6) to 4.8/10,000 (95% CI 1.4-8.2) between 1993 and 2002. HIV infection was diagnosed during pregnancy in 40% (18/45) of the mothers. Antiretroviral medication was used prior to pregnancy in 17 (33%) cases; in 34 (66%) cases of the pregnancies, medication was started during the pregnancy. A good virological response (i.e. HIV RNA load <1000/ml during the last trimester) to antiretroviral medication was achieved in 90% (36/40) of the patients; in 60% (24/40) of cases, the HIV RNA load was below the assay detection limit. One mother with advanced HIV infection succumbed to pneumonia shortly after delivery. Of the infants, 92% were born at term, and their mean (+/-SD) birth weight was 3350 +/- 395 g. The Caesarean section (CS) rate was 25% (13/52). All newborns were in good condition, and their mean umbilical pH was 7.23. All newborns received antiretroviral medication. One infant was infected with HIV, the mother was found HIV-positive postpartum. None of the infants born to mothers known to be HIV positive were infected. CONCLUSIONS: A combination of universal antenatal screening and multidisciplinary management allows individualized treatment and prevents vertical transmission of HIV infection.

Adolescent↗

Late follicular phase administration of mifepristone suppresses circulating leptin and FSH - mechanism(s) of action in emergency contraception?

OBJECTIVE: Low dose mifepristone (RU486) is highly effective in emergency post-coital contraception (EC), although the mechanism(s) of action remains unclear. We studied the endocrine actions of 10 mg mifepristone administered orally as a single dose to eight healthy volunteers (aged 20-45 years) during the late follicular phase. METHODS: Serum levels of LH, FSH, oestradiol, progesterone, leptin, mifepristone, cortisol, and gluco-corticoid bioactivity (GBA) were measured before and 1, 2, 4 and 8 h after ingestion of mifepristone on cycle day 10 or 11 (study day 1), and follow-up was continued for 10 days. Ovarian ultrasonography was performed on study days 1 and 7. Similar measurements were carried out during a control cycle. RESULTS: Mifepristone postponed ovulation, as evidenced by a 3.4+/-1.1 day (means+/-s.d.) delay (P < 0.005) in the LH surge and 3.6+/-4.0 day prolongation of the treatment cycle (P = 0.08). During the mifepristone cycle, an LH surge was displayed by five subjects when serum mifepristone levels had declined to 9.5+/-7.1 nmol/l. During the day of mifepristone administration, circulating GBA (P < 0.001) and leptin (P < 0.001) levels declined. On the day after mifepristone administration, mean serum FSH and leptin levels were lower than pretreatment values (3.8+/-1.8 IU/l vs 5.2+/-1.1 IU/l, n = 7, P < 0.05; 28.9+/-6.7 microg/l vs 33.2+/-9.0 microg/l, n = 7, P < 0.05 respectively), and the corresponding difference in the mean serum oestradiol concentration was borderline (452+/-252 pmol/l vs 647+/-406 pmol/l, n = 7, P = 0.056). In contrast to the control cycle, individual leptin levels declined during the follow-up after ingestion of mifepristone (n = 8, P < 0.01). CONCLUSIONS: These data showed that the commonly employed dose of mifepristone for EC delays ovulation and prolongs the menstrual cycle, when given during the late follicular phase. The mechanism of action of mifepristone may include a reduction of FSH secretion via a decrease in circulating leptin.

Adult↗

One- and 2-day mifepristone-misoprostol intervals are both effective in medical termination of second-trimester pregnancy.

Termination of pregnancy because of fetal anomaly requires the utmost clinical sensitivity and individualized patient care. This study compared the efficacy of a 1-day mifepristone and misoprostol interval in medical termination of second-trimester pregnancy performed because of fetal anomaly with that of the standard 2-day interval among the first 100 women in each group. A 200 mg dose of mifepristone was used; 0.4 mg of misoprostol was administered vaginally at 3-h intervals until abortion occurred. When calculated from ingestion of mifepristone, the time to abortion was 28 h 25 min (28:25 h) [23:10-50:40 h; median (range)] and 52:43 h (45:55-83:15 h) (P < 0.0001) in the 1- and 2-day mifepristone-misoprostol groups respectively. However, following initiation of misoprostol administration, the time to abortion [7:25 h (1:00-23:15 h)] was longer (P < 0.05) in the 1-day interval group than in the 2-day interval group [6:20 h (0:45-36:30 h)]; by 12 h, 82 and 87% (n.s.) respectively of the subjects had aborted. The proportions of cases undergoing surgical evacuation of the uterus were 64 and 45% (P < 0.001), in the 1- and 2-day interval groups respectively. Thus both 1- and 2-day mifepristone-misoprostol intervals are valuable in termination of second-trimester pregnancy.

Abortifacient Agents, Nonsteroidal↗

Differential kinetics of serum and cervical insulin-like growth factor-binding protein-1 during mifepristone-misoprostol-induced medical termination of early pregnancy.

The kinetics of cervical and circulating phosphoisoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) in normal and pathological early pregnancy are not well known. We investigated the profiles of IGFBP-1 in serum and in cervical secretion during medical termination of early pregnancy. Sixteen women requesting termination of pregnancy, with <63 days of amenorrhoea, received 200 mg of mifepristone on day 0, followed by either oral or vaginal administration of 0.8 mg of misoprostol on day 2. Serum and cervical swab samples, collected up to 6 weeks following the beginning of the treatment, were analysed for IGFBP-1 using two immunoenzymometric assays recognizing different patterns of IGFBP-1 phosphoisoforms. Serum mifepristone was also assayed. In the cervical samples, IGFBP-1 concentration, measured with both assays, increased substantially 2 days following administration of mifepristone. At 3 h after administration of misoprostol, IGFBP-1 had further increased several-fold in the cervix, but the increase was more pronounced as measured by the assay with preference for the amniotic fluid isoforms of IGFBP-1. A strong negative correlation was found between the time to abortion and the increase in cervical IGFBP-1 after administration of misoprostol, as measured by the assay preferring the phosphorylated isoforms of IGFBP-1. At 6 weeks, IGFBP-1 in the cervix had decreased to lower than pre-treatment levels, as measured by both assays. In serum, both assays showed a significant increase in IGFBP-1 concentrations after administration of mifepristone, and the highest values were measured on day 2, already before misoprostol administration. Thus, the kinetics of circulating and cervical IGFBP-1 differed from each other, indicating different sources and regulation of serum and cervical IGFBP-1.

Abortifacient Agents, Steroidal↗

The learning curve is rapid in medical termination of pregnancy--first-year results from the Helsinki area.

Medical termination of pregnancy by means of mifepristone and prostaglandin became available in Finland in May 2000. We summarize the first year results of medical abortion in a large tertiary care unit in Helsinki. A regimen of 200 mg of mifepristone followed by 0.4 mg vaginally administered misoprostol 2 days later was used. The maximum duration of pregnancy was 56 days. Four hundred and seventeen women, 47% of those with a pregnancy duration of up to 56 days, chose medical instead of surgical abortion. The monthly percentage of medical abortions varied from 27% to 63%. The percentage of complete terminations increased from 92% among the first quarter of the subjects to 97% among the fourth quarter, the overall success rate being 95%. Subject satisfaction, duration and self-estimated amount of bleeding, as well as analgesia needs were similar to those reported elsewhere. Most subjects (61%) chose combined oral contraceptive (COC) pills for future contraception; 75% of the COCs were started around the day of misoprostol administration. The reported amounts and duration of bleeding were not influenced by the immediate start of oral contraceptives. Intrauterine contraception was planned for 28% of the subjects, and 16% of them chose a levonorgestrel-releasing intrauterine device. We conclude that the learning curve in medical termination of pregnancy is rapid, and results comparable to those in centers with extensive experience with the method can be reached within the first year.

Abortifacient Agents, Nonsteroidal↗