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Biomedical subjects

L Wildt

Publications and source records attributed to L Wildt.

At least 19 recordsLinked to original sources

Treatment of hereditary angioneurotic oedema (HANE) with tibolone.

OBJECTIVE: Eight women, aged 25-58 years, with hereditary angioneurotic oedema (HANE) were treated with tibolone, a synthetic steroid exhibiting oestrogenic, androgenic and progestational activity. DESIGN: Pilot study. RESULTS: Tibolone at a dose of 2.5-7.5 mg/day significantly reduced the number and severity of attacks and the number of ampoules of C1-esterase inhibitor (C1-INH) needed for symptomatic therapy. The efficacy of tibolone was comparable to that of danazol, while the androgenic side-effects were considerably reduced. CONCLUSIONS: Tibolone may represent an alternative to danazol administration for the prophylaxis of HANE in women.

Adult↗

Predictive value of impaired uterine transport function assessed by negative hysterosalpingoscintigraphy (HSSG).

BACKGROUND: Hysterosalpingoscintigraphy (HSSG) has given insight into the dynamics of rapid sperm transport inside the female genital tract. RESULTS: While there is an increase of an ipsilateral transport on the side bearing the dominant follicle in 70% of the subjects in the periovulatory phase, 15% of the patients do not demonstrate transport to the fallopian tubes (negative HSSG). In these patients the pregnancy rate achieved spontaneously or by intrauterine insemination is significantly reduced compared to the patients who showed an intact transport mechanism confirmed by positive HSSG. On the other hand, by means of assisted reproductive techniques (ART), pregnancy rates were higher in the group of patients showing negative HSSG (P < 0.0005). CONCLUSIONS: Our data clearly indicate that HSSG is a helpful method to evaluate the integrity of the utero-tubal transport mechanism. As pregnancy rates remain low in patients with negative HSSG, this result should be considered as an indication for IVF-treatment even in patients with patent fallopian tubes and normozoospermia of the partner.

Fallopian Tube Patency Tests↗

Tissue perfusion essential for spermatogenesis and outcome of testicular sperm extraction (TESE) for assisted reproduction.

PURPOSE: In order to determine if there are areas of major and minor perfusion in a single testicle and if the quality of sperm is correlated with quantity of perfusion we collected testicle tissue for TESE in accordance to the local testicle tissue perfusion. METHODS: A patient undergoing TESE underwent testicular perfusion mapping using contrast enhanced ultrasound. The exposed tissue was scanned with a Laser Doppler scanner and perfusion rates were determined measuring tissue perfusion units (TPUs). Tissue was biopsied and sperm were selected and prepared for assisted reproduction. RESULTS: The total amount of isolated sperm correlated highly with the intensity of tissue perfusion showing high number of sperm in areas with high TPUs. CONCLUSIONS: This is the first demonstration that sperm quality and quantity is depending on tissue perfusion within the testicle. To further improve infertility treatment we propose that random biopsies could be replaced by perfusion-dependent collection of testicular tissue.

Biopsy↗

Lipid peroxidation at various estradiol concentrations in human circulation during ovarian stimulation with exogenous gonadotropins.

The aim of our study was to investigate the correlation between serum malondialdehyde levels and serum estradiol concentrations in healthy human female subjects. Nine hundred and fifty-five blood samples, from infertile women undergoing controlled ovarian hyperstimulation treatment with recombinant follicle-stimulating hormone, were collected for estradiol and malondialdehyde measurements. Five groups were formed according to serum estradiol levels: Group I (< 50 pg/ml), group II (50 - 299 pg/ml), group III (300-999 pg/ml), group IV (1000-1999 pg/ml) and group V (> or = 2000 pg/ml). One-way analysis of variance was used for comparisons. Mean malondialdehyde concentrations were 1.74 +/- 0.24 mmol/ml (group I), 1.53 +/- 0.20 mmol/ml (group II), 1.69 +/- 0.24 mmol/ml (group III), 1.77 +/- 0.21 mmol/ml (group IV) and 1.86 +/- 0.20 mmol/ml (group V), respectively. Mean serum malondialdehyde level at physiological estradiol concentrations (50-199 pg/ml, group II) was significantly (p < 0.01) lower than the mean malondialdehyde levels in other groups. Mean malondialdehyde concentrations among the remaining groups did not significantly differ. Our findings suggest that in vivo lipid peroxidation might be increased when circulating estradiol concentrations are below (< 50 pg/ml) or above (> 300 pg/ml) the physiological limits. High blood estradiol levels in human female subjects during ovarian stimulation with exogenous gonadotropins could be associated with increased serum malondialdehyde concentrations.

Adult↗

Acute hormonal responses of a high impact physical exercise session in early postmenopausal women.

The effect of a single bout of exercise on hormones affecting bone metabolism was studied in 25 early postmenopausal women with osteopenia. The complex training session was performed between 8:00 a.m. and 9:05 a.m. Serum concentrations of dehydroepiandrosterone-sulfate (DHEA-S), total testosterone, free testosterone, 17beta-estradiol, cortisol, human growth hormone (hGH), insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-3 (IGFBP-3) were determined. Blood samples were obtained immediately before (baseline) and after exercise, as well as 2 h and 22 h post-exercise. DHEA-S increased by 10% immediately after exercise and remained increased 2 h later. Testosterone showed no increase immediately after exercise but fell by 21% 2 h post-exercise. Free testosterone was increased by almost 20% immediately after exercise and returned to baseline levels after 2 h. Two hours post-exercise a 20% increase in the estradiol level was measured. Cortisol decreased by 36% during exercise and a further 14% during the next 2 h, a loss higher than the normal diurnal decrease. hGH increased by 80% during exercise and fell 30% under baseline values after 2 h. Even though the assessment period was prolonged to 22 h no significant change could be demonstrated for IGF-I. Serum IGFBP-3 showed a biphasic increase. During the exercise session IGFBP-3 increased by 35%, returned to baseline values 2 h post-exercise and increased again by 40% 22 h post-exercise. In summary, this study showed that a single bout of exercise typically used in osteoporosis prevention programs could have an influence on hormones affecting bone metabolism.

Adaptation, Physiological↗

Determination of velocity of tubar transport with dynamic hysterosalpingoscintigraphy.

Transport of 99mTc labelled albumin macroaggregates (MAA) can be used as a substitute for assessing transport of spermatozoa within the female genital tract. As yet, the velocity of tubar MAA transport has not been systematically studied in a large group. Dynamic hysterosalpingoscintigraphy (HSS) was performed after intrauterine instillation of 10-20 MBq 99mTc-MAA in 88 pre-ovulatory women suffering from infertility. They had to have anatomical patency of both tubes and at least one enlarged follicle. The direction and the latency of transport were evaluated. Forty-four per cent of patients exhibited MAA transport only to the dominant follicle, 31% to both ovaries and 16% to the contralateral ovary. In 9% no transport was visible. Fifty per cent of all patients studied exhibited MAA transport to the dominant follicle within 30 s, 75% within 20 min. Transport velocity in women having bilateral or ipsilateral transport did not differ significantly. There was no significant correlation between the size of the follicle and transport velocity. We conclude that in the majority of cases MAA transport occurs within 30 s after instillation. The variation in transport time between 30 s and 20 min suggests that dynamic scintigraphy is, in principle, better suited to a refined analysis of tubar function than static HSS.

Adult↗

VEGF plasma pattern in ovulation induction: evidence for an episodic secretion and lack of immediate effect of hCG.

Vascular endothelial growth factor (VEGF) is a potent stimulator of vascular proliferation and permeability. Ovarian granulosa cells have been identified as a major source of the cytokine and r-hCG was able to stimulate VEGF mRNA expression in vitro. In this study we have investigated the immediate effect of ovulation induction with hCG on peripheral VEGF levels in 6 women with primary infertility enrolled in the IVF/ET program. The patients underwent a 24-hour continuous blood withdrawal with sampling intervals of 15 minutes starting from 5 hours before ovulation induction with 10.000 IU hCG. Ovulation induction with hCG had no significant immediate effect on mean peripheral VEGF levels. However, VEGF plasma levels did exhibit significant episodic fluctuations with rapid increases every 90-120 minutes without any relation to circulating hCG levels. Taken together, the results of this study suggest that VEGF is released episodically and that systemic VEGF levels are not acutely altered by ovulation induction with hCG.

17-alpha-Hydroxyprogesterone↗

[Fetal phonocardiography with a novel approach].

The long-term recording of the fetal heart rate (FHR) variability is one of the most frequently used tools of routine fetal diagnostics which is usually carried out by the means of ultrasound cardiography. Frequent measurement of FHR is recommendable, however the cost of high quality ultrasound devices is unfortunately so high that this technology is not viable for low-cost devices used in the home-care sector. An alternative approach of FHR recording can be based on the fully non-invasive, passive acoustic recording, called phonocardiography. The evaluation of fetal phonocardiograms is complicated by various internal and external noise factors. The development of accurate and robust fetal phonocardiographs has been studied by biomedical researchers since long. This paper presents a novel two-channel phonocardiographic device and an advanced signal processing method, which provides a performance comparable to that of ultrasound cardiography. The proposed system offers an optimal trade-off between complexity and feasibility and it is viable in low-cost, stand-alone, battery-powered FHR monitoring devices. The developed system provided 83% accuracy compared to the simultaneously recorded reference ultrasound records.

Artifacts↗

Genotyping of thrombotic risk factors by MALDI-TOF mass spectrometry.

OBJECTIVES: Individual risk of thrombotic disease is highly associated with allelic sequence variations in the blood clotting factor V (F5) and factor II (F2) genes. The polymorphism (G1691A) in F5 causing the amino acid substitution R506Q and a genetic variation in the 3' untranslated region of F2 (G20210A) are highly prevalent in the Caucasian population. These findings raise the need for an efficient, cost-effective screening technique. DESIGN AND METHODS: Thrombotic risk alleles were determined by allele specific elongation and termination of extension primers. Primer extension products were analyzed by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). RESULTS: Using MALDI-TOF-MS, the polymorphisms F5 (G1691A) and F2 (G20210A) were unequivocally and reliably detectable either alone or in combination (multiplex). Results were confirmed by conventional sequence analysis and, in each case, fully matched data obtained by gel-based genotyping. CONCLUSIONS: Due to its accuracy and sensitivity, this procedure can serve as an alternative method for clinical genotyping. It also possesses the potential for high throughput screening.

Alleles↗

The detrimental role of colloidal volume substitutes in severe ovarian hyperstimulation syndrome: a case report.

Although, the mechanisms for the development of ovarian hyperstimulation syndrome (OHSS) are still not clear, the symptoms usually correlate with the levels of serum estradiol and ovarian enlargement. We report a case, where the clinical course was unusually prolonged. When menstrual bleeding had already occurred, serum estradiol was less than 10 pg/ml and the ovaries were almost normal in size, the patient developed pleural effusion and a significant alteration in blood-coagulation. This was most likely caused by an over-infusion of hydroxyethyl starch (HES) over 10 days. The pleural effusion contained high levels of HES, reaching 74% of the plasma concentration as measured by a novel method after acidic hydrolysis of HES. Carbohydrates as dextran and HES are well known to interact with the blood-coagulation system. Increase capillary permeability, typical of OHSS, leads to loss of colloidal substances into the third space, where HES is slowly degraded and osmotic pressure is high. This might prolong and aggravate the urine of OHSS.

Adult↗

On the role of human chorionic gonadotropin (hCG) in the embryo-endometrial microenvironment: implications for differentiation and implantation.

Recent evidence suggests that human chorionic gonadotropin (hCG), in addition to its well-known endocrine effects on the corpus luteum, may act as a growth and differentiation factor during pregnancy. According to experimental results, its mode of action may be divided into three sequential phases. During the first phase, which begins at the blastocyst stage and lasts until the occurrence in the serum, hCG acts preferentially in a juxtacrine manner. We have used an intrauterine microdialysis system developed in our laboratory to administer low concentrations of hCG to the endometrium of women in the luteal phase of the menstrual cycle. HCG administration provoked profound effects on paracrine parameters of differentiation (IGFBP-1, prolactin) and implantation (LIF, M-CSF). VEGF, a cytokine important for neoangiogenesis, was significantly stimulated by hCG (P < .01), suggesting a role for hCG in the control of endometrial vascularization and placentation. The investigation of endometrial parameters of tissue remodeling revealed a significant increase of MMP-9 (P < .05) but not of TIMP-1 following hCG infusion. The second, endocrine, phase of hCG action is marked by the appearance of hCG in the maternal serum. Rising systemic hCG levels cause a very rapid elevation of serum progesterone reflecting the rescue of the corpus luteum. Other endocrine functions of hCG include its intrinsic thyrotropic activity as well as modulation of fetal testicular, ovarian, and adrenal function. The third phase may be characterized by the expression of full-length hCG/LH receptors on the trophoblasts themselves. Before the ninth week of gestation, human villous trophoblasts express a truncated hCG/LH receptor isoform (50 kDa) and are probably not responsive to hCG. Later, the expression pattern is switched to the full-length receptor (80 kDa), allowing hCG also to modulate the differentiation of the trophoblasts themselves. A special feature is the self-regulation of hCG biosynthesis that may in part explain the unique secretion profile of the hormone with peak levels during the first trimester followed by a rapid decline after the tenth week of gestation. In summary, hCG seems to have a variety of local and systemic functions in and outside the embryo-endometrial microenvironment.

Cell Differentiation↗

Peripheral levels of vascular endothelial growth factor (VEGF) are higher in gonadotropin stimulated as compared to natural ovarian cycles.

The purpose of the present study was to investigate the stability of vascular endothelial growth factor (VEGF) in plasma samples and the influence of ovarian hyperstimulation on systemic levels of VEGF. Stability assays for VEGF in plasma samples revealed significant increases following even short incubations of samples at room temperature (< or = 2 h, p < 0.001). To investigate a possible impact of controlled ovarian hyperstimulation (COH) on peripheral VEGF levels, serial blood collection over one menstrual cycle was performed in unstimulated as well as in gonadotropin-stimulated cycles for in vitro fertilisation/embryo transfer (IVF/ET) (10 women each). Peripheral levels for VEGF were significantly higher in gonadotropin stimulated cycles as compared to non-stimulated cycles (p < 0.001). There was no significant difference between follicular phase and luteal phase levels in either group. VEGF levels tended to correlate with the number of follicles detected by vaginal sonography prior to oocyte aspiration (p = 0.051). In conclusion, VEGF levels are elevated in gonadotropin-stimulated IVF/ET cycles as compared to natural cycles.

Chorionic Gonadotropin↗

Secretory pattern of leptin and LH during lactational amenorrhoea in breastfeeding normal and polycystic ovarian syndrome women.

Several studies have suggested that leptin modulates hypothalamic-pituitary-gonadal axis function. A synchronicity of LH and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome (PCOS), suggesting that leptin may modulate the episodic secretion of LH. The aim of the present investigation was to assess the episodic fluctuations of circulating LH and leptin during lactational amenorrhoea in fully breastfeeding normal and PCOS women at 4 and 8 weeks postpartum, in order to establish LH-leptin interactions in the reactivation of the gonadal axis during this period. Six lactating PCOS patients and six normal lactating women of similar age and body mass index were studied. During a 12 h period on the 4th and 8th weeks postpartum, blood samples were collected at 10 min intervals for 12 h (22:00-10:00). Serum LH and leptin concentrations were measured in all samples. For pulse analysis, the cluster algorithm was used. To detect an interaction between LH and leptin pulses, an analysis of co-pulsatility was employed. LH concentrations tended to increase in both groups between the 4th and 8th weeks postpartum; however, serum leptin concentrations were not modified. Leptin pulse frequencies were similar at the 4th and 8th weeks postpartum, and did not differ between groups. Moreover, leptin pulse frequency was higher than LH pulse frequency in both groups, and in the two study periods. There was no synchronicity between LH and leptin pulses, and there were no increments in leptin concentration during the night. The fact that leptin concentrations were not modified and no synchronicity between LH and leptin pulses was observed suggests that, during lactational amenorrhoea, circulating leptin is probably not involved as a primary signal in promoting the reactivation of pulsatile LH secretion.

Adult↗

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: metabolic aspects.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine-metabolic disorder in women, a high percentage of whom exhibit peripheral insulin resistance. After delivery, in normal women, lactation imposes a metabolic adaptation, the impact of which on the insulin resistance of PCOS patients is not known. The aim of this study was to evaluate the effect of lactation on insulin resistance, glucose and insulin metabolism, and sex hormone-binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP)-1 concentrations in fully breast-feeding normal and PCOS women during the postpartum period (lactational amenorrhoea) and also after weaning. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age and body mass index (BMI) were selected for the study. At the 4th and the 8th week postpartum (pp), and 8 weeks after weaning, a 2 h, 75 g oral glucose tolerance test (oGGT) was performed, followed by an insulin tolerance test 2 days later. For the oGGT, glucose and insulin were measured in each sample and SHBG and IGFBP-1 were determined in the fasting sample. RESULTS: During lactation, fasting insulin levels were similar in both groups. In LPCOS women 2 h insulin concentrations were significantly higher, and SHBG and IGFBP-1 concentrations were significantly lower, than those observed in NL women. In both groups, insulin sensitivity evaluated by the insulin tolerance test was not modified. After weaning, in LPCOS women, SHBG and IGFBP-1 concentrations remained lower and insulin concentrations remained higher than those observed in NL women ( P < 0.05 ). CONCLUSIONS: In PCOS women, insulin resistance is not modified during lactation. Lactation has a transitory beneficial effect on insulin levels and biological markers of insulin resistance.

Adult↗

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: endocrine aspects.

BACKGROUND: The aim of this study was to evaluate the changes in gonadotrophin concentrations and the dynamics of the episodic fluctuations of circulating LH during night-time, in fully breastfeeding normal women and in those with polycystic ovarian syndrome (PCOS) during lactational amenorrhoea and after weaning, in order to provide insights into the onset of this syndrome. Additionally, ovarian activity was evaluated by ultrasound examination and steroid concentrations. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age were selected. On the 4th and 8th week postpartum (PP) and eight weeks after weaning, blood samples were collected every 10 min (10.00--20.00h). Gonadotrophin concentrations were determined in all samples. Steroid hormones were measured in one fasting sample and ovarian morphology was assessed by ultrasound. RESULTS: On the 8th week PP, LH pulse frequency was higher and FSH concentrations were lower in LPCOS women compared with NL women, and steroid hormone concentrations remained low, except for androstenedione which was higher in LPCOS patients. After weaning, similar differences were observed between both groups. PCOS patients also showed enlarged ovaries with a PCOS pattern in the three study periods. CONCLUSIONS: The enlarged ovaries associated with higher androstenedione concentrations suggest that PCOS is a primary ovarian defect, making it difficult to establish if the abnormal LH pattern observed in these women is primary or secondary to the ovarian dysfunction.

Adult↗

Molecular aspects of direct LH/hCG effects on human endometrium--lessons from intrauterine microdialysis in the human female in vivo.

The regulation of human implantation is still unknown. Evidence derived from experiments in vitro and from animal systems suggest a direct impact of the embryo on endometrial differentiation and the implantation process itself. Being one of the earliest embryonic products, hCG may be a key mediator of this embryo-maternal communication. Using a multiplex nested rT-PCR approach we have been able to demonstrate the presence of full-length and truncated hCG/LH-receptor mRNA in human endometrium and in decidua. The expression of functional receptors appears to be cycle-dependent and regulated by changes in the alternative splicing pattern. To investigate possible direct effects of hCG on endometrial paracrinology in the human female in vivo, we have developed an intrauterine microdialysis system that allows the continuous sampling from the uterine cavity over several hours as well as the application of exogenous hCG and the monitoring of the tissue response to this stimulus. HCG administration during the secretory phase significantly modulated several endometrial paracrine parameters that correlate to endometrial differentiation (IGFBP-1), angiogenesis (VEGF), implantation (LIF, M-CSF) and tissue remodelling (MMP-9). In summary, intrauterine microdialysis is a novel tool for the clinical assessment of endometrial paracrinology in vivo. HCG appears to directly modulate endometrial differentiation and function in humans.

Alternative Splicing↗

Freezing of human ovarian tissue--not the oocytes but the granulosa is the problem.

The freezing of human ovarian tissue may be the key for restoring fertility after systemic therapy of cancer. In contrast to others we investigated the survival rate of whole follicles, and had a special look at the granulosa cells. Ovarian tissue was collected laparoscopically (n = 10) and divided into equal parts for freezing (n = 1570) or as control (n = 1660). The cryopreservation was done slowly, or as a ultrarapid freezing. After thawing the number of follicles, oocytes and granulosa cells surviving was counted and corrected for equal volumina of the samples. While 84.5% of the oocytes survived freezing, only 40.4% of the follicles were intact after thawing. The data show that the procedure damaged follicles, which mainly affected the granulosa cells. As the intactness of follicles may play a critical role for the maturation of the oocytes after thawing the protocols should be optimised to meet the needs of oocytes and granulosa cells.

Adult↗

Oestrogen and age estimations of perimenopausal women.

We estimated the age of perimenopausal women at a first visit and measured the concentrations of oestradiol in serum. The accuracy of estimation of age strongly correlated with oestradiol concentrations: age was overestimated when oestradiol was low and underestimated when oestradiol was high.

Adult↗