Umbilical vein constriction at the umbilical ring: a longitudinal study.

OBJECTIVE: It has been suggested that constriction of the umbilical vein (UV) at the umbilical ring has hemodynamic effects. We aimed to determine the occurrence and extent of such constriction in serial observations. METHODS: This was a prospective longitudinal study of UV velocities at the umbilicus measured at approximately 4-week intervals between 19 and 42 weeks' gestation in 129 low-risk singleton pregnancies. Each participant was examined three to five times. Multilevel modeling was used to construct the reference ranges and to test associations between variables. RESULTS: Gestational age-specific reference percentiles of UV velocities at the umbilicus were established based on 469 observations. Fetuses were able to alter the UV velocities considerably during the second half of pregnancy, signifying a varying degree of UV constriction. Of a total of 129 fetuses, 56 (43.4%) never had high UV blood velocity (i.e. > 46 cm/s, the highest quartile), 42 (32.6%) fetuses had high UV blood velocity on one occasion and 31 (24.0%) fetuses on two or more occasions. In 36 (27.9%) fetuses the UV velocity at the umbilical ring was > 300% of the mean gestational age-specific reference value at the intra-abdominal section on at least one occasion. Constriction of the UV at the umbilical ring did not affect the pulsatility of the umbilical artery, and was not associated with adverse perinatal outcome in this study. CONCLUSIONS: Low-risk fetuses may well constrict the UV at the abdominal wall with velocities extending over wide ranges on one or more occasions during the second half of pregnancy. Rather than being a risk for complications, the constriction seems to be part of physiological development and possibly a regulatory mechanism.

Reference ranges for serial measurements of blood velocity and pulsatility index at the intra-abdominal portion, and fetal and placental ends of the umbilical artery.

OBJECTIVE: To construct reference ranges for serial measurements of umbilical artery (UA) blood flow velocity and pulsatility index (PI) at standardized insonation sites during the second half of pregnancy. METHODS: This was a prospective longitudinal study of the umbilical circulation. UA blood flow velocities were measured at the intra-abdominal portion, fetal end and placental end at 4-weekly intervals at 19-42 weeks of gestation in 130 low-risk singleton pregnancies. A total of 513 observations were used to construct the reference ranges using regression statistics and multilevel modeling. RESULTS: UA blood velocities and PI were higher at the intra-abdominal portion and fetal end than at the placental end. The gestational age-related increase of end-diastolic velocity was greater than the corresponding increase of the peak systolic velocity at all locations. The mean differences (delta values) of UA blood velocities between the fetal and placental ends increased and that of PI decreased with advancing gestational age. CONCLUSION: UA Doppler parameters vary significantly at different locations. We have established new reference ranges for the UA velocities and PI at standardized locations based on longitudinal observations, which should be useful for the surveillance of fetuses with repeated observations.

Doppler-derived umbilical artery absolute velocities and their relationship to fetoplacental volume blood flow: a longitudinal study.

OBJECTIVES: To construct reference ranges for serial measurements of the umbilical artery (UA) absolute blood flow velocities in the second half of pregnancy and to test the hypothesis that significant associations exist between UA velocities and placental volume blood flow assessed from umbilical vein blood flow velocities and diameter. METHODS: This was a prospective longitudinal study of the umbilical circulation. UA absolute velocities and umbilical vein blood flow were measured at 4-weekly intervals between 19 and 42 weeks' gestation in 130 low-risk singleton pregnancies. A total of 511 observations were used to construct the reference ranges and assess the association between UA absolute velocities and placental volume flow using multilevel modeling. RESULTS: Both UA absolute velocities and placental volume blood flow showed a steady increase throughout the second half of pregnancy. However, the gestational age-related increase in the UA end-diastolic velocity (EDV) was greater than the corresponding increase in the peak systolic velocity (PSV). The time-averaged intensity-weighted mean velocity (TAWMV)/time-averaged maximum velocity (TAMXV) was 0.6 indicating probably not a completely parabolic velocity profile. There was a significant positive association (P < 0.00001) between UA absolute velocities and placental volume blood flow, but this association was modified by the gestational age. The intraobserver coefficients of variation for the UA PSV, EDV, TAMXV and TAWMV and placental volume blood flow were 10.17%, 16.29%, 11.46%, 18.18% and 8.61%, respectively. CONCLUSION: We have established new reference ranges for the UA absolute velocities based on longitudinal data. They show a significant association with fetoplacental volume blood flow and may have a clinical value in the assessment of the umbilical circulation.

Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone.

OBJECTIVE: To show that local application of the levonorgestrel intrauterine device was a better therapy for endometrial hyperplasia (EH) compared to per-oral gestagen treatment based on subjective (WHO criteria) and objective (prognostic data-based morphometric and stereological method/D score, predicting the risk of cancer development for each single patient) evaluation. METHODS: Women between 30 and 70 years with EH and D score > 0 were treated with levonorgestrel intrauterine device (n = 26) and the results compared to a historic group of women treated with per-oral gestagen (n = 31). In both treatment groups only patients with low risk (D score > 1) and uncertain risk (D score = 0-1) of cancer development were included. Endometrial specimens were investigated prior to treatment and after 3 months of therapy. The endometrial samples from the two groups were examined by light microscopy and objective data-based morphometry to assess tissue characteristics and to evaluate nuclear size variation. RESULTS: After 3 months all patients treated with levonorgestrel intrauterine device showed regression of hyperplasia, whereas 14 of 31 patients in the per-oral group still had persisting disease. The objective morphometric analysis showed reduction in nuclear size for both treatment groups, including the D score > 1 as well as the D score 0-1 patients. However, the reduction was most obvious for the levonorgestrel intrauterine device-treated patients with initial D score of 0-1. CONCLUSION: The present study indicates that levonorgestrel intrauterine device is a superior alternative to per oral treatment of endometrial hyperplasia. By using objective morphometric treatment monitoring we have shown that the hyperplasia patients with the highest malignant potential (D score = 0-1) were those taking most benefit from local high-dose levonorgestrel therapy.

Computerised morphometric study of the paraurethral tissue in young and elderly women.

AIM: Changes in structural support of the urethra and bladder neck have been proposed to be among the most important factors in the pathogenesis of stress urinary incontinence. In this context, we histologically investigated the paraurethral area in continent women to quantify the relative distribution of connective tissue, smooth muscle, vessels, nerves, and striated muscle. Previously published literature gives only descriptive evaluations of the relative distribution of these tissue components. METHODS: We used a computerised morphometric method, which allowed us to estimate the paraurethral tissue distribution in a more objective way. The material was obtained by dissection during autopsy in five premenopausal and five postmenopausal women. RESULTS: Paraurethral tissue consisted of 56% connective tissue (SD, 5%), 30% smooth muscle (SD, 5%), 11% blood vessel (SD, 6%), 2% striated muscle (SD, 3%), and 1% nerves (SD, 1%). We also found that the distribution of different tissue components along the length of the urethra did not differ at a statistically significant level. Furthermore, there was a statistically significant difference in the amount of connective tissue and blood vessels in the postmenopausal women compared with the premenopausal women. CONCLUSIONS: The present study shows that the paraurethral area is built of heterogeneous tissue with small changes in its composition along the course of urethra. Increase in connective tissue was found to be the dominating change in the process of ageing.

Laparoscopic methotrexate treatment of ectopic pregnancy: feasibility, efficacy, safety and intrauterine pregnancy rates.

We set out to investigate efficacy, methotrexate (MTX) plasma concentrations, and toxicity following a single injection of MTX into the gestational site in the treatment of ectopic pregnancy. This was a non-randomised, non-blinded prospective clinical trial. Eighteen women with unruptured tubal pregnancies and in stable haemodynamic condition were studied. MTX 1 mg/kg was injected into the ectopic pregnancy guided by laparoscopy. Serum betahCG levels were estimated before MTX treatment and on days 1, 4 and 13. In 14 patients plasma MTX was determined 1 h and 6 h after the injection. We found an adequate decline in betahCG was achieved in 17 (94%) patients, and tubal surgery avoided in 15 (83%). At 6 hours following drug administration, mean plasma MTX concentration (0.36+/-0.21 microM) was only 12% of mean peak level (3.1+/-1.0 microM). Six (39%) demonstrated slightly elevated, but completely reversible liver enzymes. None reported any subjective adverse effects. At the 4-7 year follow-up nine of 12 (75%) women had delivered healthy babies. It is concluded that intratubal injection of 1 mg/kg MTX appears to be an effective and safe treatment of ectopic pregnancy.

[A new minimally invasive surgical method for stress incontinence in women]. / Ny og minimalt invasiv operasjonsmetode ved stressinkontinens hos kvinner.

Present surgical methods in the treatment of female urinary incontinence require relatively extensive surgery and several days in hospital. 84 consecutive patients (age 34-78 years) with proven stress incontinence were operated with the new tension-free vaginal tape procedure (TVT) and studied prospectively from November 1996 to August 1998. The operation was carried out under local anaesthesia, a procedure which allows the surgeon to check during the operation that continence is achieved. 52 patients (62%) were discharged from the hospital the same day. After four months, 79 out of 82 patients (96%) were cured or had improved considerably. No serious complications occurred. Four patients experienced various degrees of retention. The tension-free vaginal tape method seems to be an effective minimal invasive surgical procedure for the treatment of female stress incontinence. However, randomized controlled studies and long term follow-up are needed for a more complete evaluation of its merits versus the Burch colposuspension which is considered the "gold standard".

[Occurrence of bacterial vaginosis among abortion seekers]. / Forekomst av bakteriell vaginose blant abortsøkere.

Bacterial vaginosis is the most common vaginal infection during the fertile period. The clinical diagnosis is based on three of Amsel's four criteria: thin, grey-white discharge, vaginal fluid pH above 4.5, a fishy odour on addition of 10% potassium hydroxide solution to the vaginal fluid, and the presence of clue cells on a saline wet mount. A probably more sensitive indicator of the diagnosis is based on Gram-stain, where the normal lactobacillus-dominated vaginal flora is changed to the lactobacillus deficient flora of bacterial vaginosis. The condition is probably associated with higher risk of complications in connection with pregnancy and gynaecological surgery. A prospective study of bacterial vaginosis based on microscopy of Gram-stained smears was conducted among 168 women applying for first trimester abortion. The prevalence of bacterial vaginosis was 24% and of Chlamydia trachomatis 8.4%. Four patients (10.3%) in the vaginosis group were treated with antibiotics for certain or suspected postabortal endometritis, as against six patients (5.4%) in the group without bacterial vaginosis.

Laser doppler-recorded reactive hyperaemia in the forearm skin during the menstrual cycle.

OBJECTIVE: By means of laser Doppler flowmetry to describe the changes in resting microvascular perfusion and post-occlusive reactive hyperaemia in skin of the forearm and finger pulp throughout the menstrual cycle. DESIGN: Prospective descriptive study. SETTING: University Hospital of Tromso, Norway. SAMPLE: Fifteen nonsmoking healthy women were studied in the follicular (days 2 to 7) and the luteal (days 19 to 24) phase of the menstrual cycle. RESULTS: Resting perfusion in forearm and finger pulp as well as post-occlusive reactive hyperaemia in finger pulp were unchanged from the follicular to the luteal phase. The peak perfusion value of the reactive hyperaemic response after 1 min of arterial occlusion was significantly reduced from the follicular to the luteal phase (P<0.01) in forearm skin. The repayment for the blood flow debt, which is the hyperaemic response in percentage of the ischaemic build-up, was also reduced (P<0.01). After 3 min of arterial occlusion, significant reductions in peak post-occlusive flow (P<0.01), recovery time, which is the total duration of the hyperaemic response (P<0.01), and the repayment (P<0.01) were observed. A significant correlation was found between the ratio serum oestradiol/progesterone and repayment after 3 min of arterial occlusion in forearm skin (r=0.71,P<0.001). CONCLUSIONS: Vascular reactivity is altered during the menstrual cycle. In the luteal phase, significant reductions in peak perfusion, repayment and recovery time were seen. The mechanisms behind these findings are unclear, but probably involve changes in both serum oestradiol and progesterone levels.

Effect of probenecid, verapamil and progesterone on the concentration-dependent and temperature-sensitive human erythrocyte uptake and export of guanosine 3',5' cyclic monophosphate (cGMP).

Elevated extracellular cGMP levels have been observed in various clinical conditions, and the analyte has been proposed as a diagnostic marker of cardiovascular as well as malignant diseases. However, the use of extracellular cGMP as a pathophysiological marker requires detailed knowledge about the cellular biokinetics of cGMP (synthesis, metabolic conversion and export). In the present study the transport of cGMP in human erythrocytes has been further characterized. The uptake of cGMP was dependent on a concentration gradient and was temperature-sensitive, compatible with passive diffusion. The cGMP export was temperature-sensitive, saturable (Km = 3.4 +/- 1.0 mu mol l-1), inhibited by probenecid and verapamil and stimulated by progesterone. The results show that human erythrocytes possess a cGMP transport system similar to that found in other cells and that extracellular levels of cGMP are dependent on intracellular levels, membrane transport and influenced by physiological factors and pharmacological agents.

[Pregnancy, births and infants after in-vitro-fertilization in Norway, 1988-1991]. / Svangerskap, fødsel og barn etter in vitro-fertilisering i Norge, 1988-91.

We studied 1,165 pregnancies after in vitro fertilization in six public hospitals in Norway in the years 1988-91. The annual number of pregnancies increased from 158 in 1988 to 365 in 1991. The mean number of replaced embryos was reduced from 3.7 to 2.7. The rate of multiple births was not significantly altered in the same period, 24.3% were twin births and 5.7% triplet births. 19.3% of the pregnancies ended in abortion and 8.4% were ectopic. 782 births were registered in the Medical Birth Registry of Norway and compared with all other births during the period. Gestational hypertension, bleeding and preterm birth were observed more often in pregnancies after in vitro fertilization. The proportion of infants with very low birth weight (> 1,500 g) after in vitro fertilization was 9.7%, and nearly 50% of these were triplets. The relative risk of stillbirth and death during the first year of life, adjusted for maternal age and birth order, was 3.1 (95% CI 2.4-4.0) and 2.3 (95% CI 1.5-3.5) for singletons alone. The proportion of multiple births should be reduced.

[Transcervical resection of the endometrium. An alternative to hysterectomy in dysfunctional uterine hemorrhage]. / Transcervikal endometriereseksjon. Et alternativ til uterusekstirpasjon ved dysfunksjonell uterinblødning.

Transcervical electroresection of the endometrium was performed in 104 patients with dysfunctional uterine bleeding which did not respond to conservative treatment. Transcervical resection was offered as an alternative to abdominal hysterectomy. Re-resection was performed in 17 women (16%) because the initial section did not have the desired effect. Altogether 122 resections were performed. 79% of the women were satisfied after the initial resection and 93% when the procedure was repeated. During a follow-up period of six to 28 months after treatment, a hysterectomy was performed in 18 (17%) patients, but unacceptable uterine bleeding was the indication in only five of these cases. One major complication occurred, a small bowel perforation which required intestinal resection. Three uterine perforations occurred without any damage to neighbouring organs. Except for transient headache in a few patients, no clinical symptoms of glycine toxicity were seen. It is concluded that transcervical endometrial resection seems to represent an additional option for surgical treatment of dysfunctional uterine bleeding, but the procedure is not without risk. The long-term results of this procedure must be compared with those achieved by traditional abdominal hysterectomy.