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Biomedical subjects

L Wildt

Publications and source records attributed to L Wildt.

At least 55 records · Page 3Linked to original sources
PubMed1995

Influence of human luteinizing hormone on cell growth and CA 125 secretion of primary epithelial ovarian carcinomas in vitro.

In the present study, the influence of human luteinizing hormone(hLH) on the growth and the CA 125 secretion of primary ovarian carcinoma cell cultures derived from 11 previously untreated patients was investigated. Two different patterns of in vitro growth of unstimulated ovarian carcinoma cells could be detected: 5 cell cultures in which no changes of cell number were observed during an incubation period of 6 days (group A) and 6 cell cultures which grew without any hormonal support (group B). All tumors of group A showed enhanced cell proliferation when hLH was added to the culture medium, reaching a maximum at dosages of 100 mIU/ml on day 2 after incubation, while such an effect was not observed in group B. In most cases, no positive correlation was found between hLH-induced cell growth and CA 125 release. Our findings demonstrated a dose-dependent hLH-induced stimulation of epithelial ovarian tumors in vitro.

Adenocarcinoma↗
PubMed1994

[Calcitriol administration during pregnancy in a partial DiGeorge anomaly].

A 23-year-old pregnant woman was known since birth to have partial DiGeorge syndrome with idiopathic hypoparathyroidism and clinically suspected thymus hypoplasia. The hypocalcaemia had until recently been treated with 1000 IU vitamin D3 daily. During the 9th week of pregnancy the serum calcium level was 1.9 mmol/l, the phosphate one 1.58 mmol/l and parathormone 5.6 pg/ml. To ensure better control, calcitriol was given (1.25-[OH]2-vitamin D3, initially 1 microgram daily and then, from the 22nd week of pregnancy onward, 1.5 micrograms daily), as well as calcium gluconate and lactate (initially 300 mg daily, then 900 mg daily). The serum calcium level at that time was between 2.0 and 2.5 mmol/l. Because of toxaemia of pregnancy the patient was hospitalized and confined to bed during the 37th week, whereupon the serum calcium level rose from 2.2 to 2.7 mmol/l, but a decrease in calcitriol dosage resulted in a decrease to within normal limits within one day. A girl was delivered by section in the 39th week: she had normal serum calcium and phosphate levels and appeared healthy.

Adult↗
PubMed1994

Identification of insulin and insulin-like growth factor I (IGF I) receptors in ovarian cancer tissue.

The objective of this study was to test if specific insulin and insulin-like growth factor I (IGF I) receptors are expressed in ovarian cancer tissue. Thirteen tissue specimens from primary ovarian cancers, 1 specimen from a primary peritoneal carcinoma, 10 specimens from metastatic lesions of ovarian carcinomas, and 4 specimens from recurrent ovarian cancers together with 13 normal ovaries were tested for their content of insulin and IGF-I receptors, by the application of specific insulin and IGF-I receptor radioimmunoassays. The insulin receptor (IR) and IGF-I receptor (IGF R) content in the primary tumors varied between 23.8-321.4 and 16.4-554.2 ng/0.1 mg DNA, respectively. Metastatic lesions contained between 12.3 and 226.7 ng IR/0.1 mg DNA and between 7.5 and 459.4 ng IGF R/0.1 mg DNA. In recurrent tumors the receptor concentrations were in the range of 41.5-79.8 and 48.9-160.9 ng/0.1 mg DNA for insulin and IGF-I receptors, respectively. Normal ovarian tissue contained between 12.2 and 150.1 ng IR and between 21.4 and 420.1 ng IGF R per 0.1 mg DNA, respectively. As both insulin and IGF-I receptors are present in ovarian cancer tissue, the effects of insulin and IGF-I as potential growth factors in ovarian cancer should be further investigated.

Adult↗
PubMed1994

In vitro activity of immunoconjugates between cisplatin and an anti-CA125 monoclonal antibody on ovarian cancer cell lines.

Cis-diammine dichloro platinum (II) (CDDP), is a highly potent antineoplastic agent that is used in the treatment of ovarian cancer. However, the clinical use of CDDP is restricted by its severe side effects. In order to reduce these side effects and to enhance its therapeutic efficacy, we developed specific immunoconjugates consisting of the murine monoclonal antibody OC125 and CDDP, using diethylene triamine pentaacetic acid (DTPA) as a linker. The coupling efficiencies of the different preparations synthesized, varied between 1.10 +/- 0.42 and 2.65 +/- 1.60 mol of CDDP per mol of antibody protein. Despite the chemical modification of the antibody molecule, specific binding activity of the OC125-CDDP conjugates toward the CA125 antigen was maintained as was demonstrated by means of immunohisto-/cytochemical staining of frozen sections of ovarian cancer tissue, amniotic epithelium, and the CA125 positive ovarian cancer cell line NIH:OVCAR 3. The antiproliferative activity of the immunoconjugates was tested against the human ovarian cancer cell lines NIH:OVCAR 3 and SKOV 3, applying a kinetic crystal violet microassay. Despite the promising results obtained with the specific immunostaining of the target cells, no significant antiproliferative activity of our immunoconjugates against the cell lines tested was observed. One possible explanation for the lack of antitumor activity could be the fact that CA125 is released in large amounts by the NIH:OVCAR 3 cells. This may have prevented an efficient immunotargeting of the cancer cells by the formation of soluble immune complexes.

Antibodies, Monoclonal↗
PubMed1993

[Extension of the concept of extracorporeal fertilization by cryopreservation of impregnated oocytes].

Cryopreservation of human embryos within in-vitro fertilization treatment was already proposed in 1977 by Edwards and Steptoe. Today, this procedure is used worldwide by several teams as a standard method to enhance the success rate of IVF. In spite of this, there are many disadvantages of the freezing of embryos, furthermore it is legally prohibited in Germany. We report on a new concept for treatment, which includes the freezing of impregnated oocytes after IVF and their transfer in subsequent cycles. From 109 out of 120 patients who were treated with a long acting GnRH analogue or a contraceptive pill before IVF stimulation, "supernumerary" impregnated oocytes could be frozen. Twenty-three pregnancies resulted after immediate embryo transfer, and thirty patients, who returned for the transfer of cryopreserved oocytes, became pregnant. Neither the IVF pre-treatment, nor the stimulation in the transfer cycles of frozen oocytes with clomiphene citrate, influenced the success rate significantly. Combining the 53 pregnancies, a cumulative pregnancy rate of 49% can be calculated per IVF stimulation treatment. This means a doubling of the success rate, compared with routine IVF treatment. Although there are still problems to be solved, as, for instance, the insufficient implantation rate of 7% after the transfer of frozen/thawed cells, we consider cryopreservation of pronuclear oocytes a useful and promising supplement of IVF treatment. There is no further need for the freezing of embryos.

Chorionic Gonadotropin↗
PubMed1993

Opiate antagonist treatment of ovarian failure.

One-hundred-and-thirty-eight women suffering from hypothalamic or hyperandrogenic ovarian failure were treated with daily doses of 25-150 mg of the opiate antagonist naltrexone for 4-100 weeks. In patients with hypothalamic ovarian failure, treatment with naltrexone alone was followed by an increase of gonadotrophins and by normalization of the menstrual cycle in approximately 70% of patients. Eight of 10 patients who did not respond to naltrexone and had not previously ovulated in response to clomiphene administration exhibited ovulatory cycles when both compounds were administered. Twenty-four pregnancies were achieved in 22 women, corresponding to an overall pregnancy rate of 26%, with a cumulative pregnancy rate closely resembling that of a normal population. In contrast, in hyperandrogenic insulin-resistant patients, the pattern of gonadotrophin secretion did not seem to change dramatically during naltrexone treatment. However, the rise of insulin in plasma following an oral load of glucose (oGTT) was blunted considerably, resulting in normalization of previously elevated circulating insulin levels. Since the time course of plasma glucose after oGTT did not appear to be affected by treatment, this indicates an increase in insulin sensitivity (or a decrease in insulin resistance) during naltrexone therapy. Side-effects of naltrexone treatment were negligible in patients with hypothalamic ovarian failure. Hyperandrogenic patients, however, did experience more intense and prolonged side-effects, such as nausea and dizziness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Pulsatile administration of gonadotrophin releasing hormone and oral administration of naltrexone in hypothalamic amenorrhoea.

Between 1979 and 1990, 73 patients suffering from hypothalamic amenorrhoea were treated by pulsatile administration of gonadotrophin releasing hormone (GnRH) in 359 treatment cycles. Seventy-two pregnancies were achieved. In 64 favourable patients in whom hypothalamic amenorrhoea constituted the only reason for infertility, a pregnancy rate of 29% per cycle could be obtained. Patients who conceived during pulsatile GnRH required an average of only 2.4 cycles per conception. Twelve out of 24 patients with hypothalamic amenorrhoea who exhibited an ovulatory response to pulsatile GnRH, ovulated during oral administration of naltrexone; such responsiveness to opioid antagonism was, however, restricted to the less serious grades. In conclusion, pulsatile administration of GnRH continues to be a highly effective mode of treatment of infertility due to hypothalamic amenorrhoea of various aetiologies. A subgroup of these patients may be successfully treated by the oral administration of naltrexone.

Amenorrhea↗
PubMed1993

Pulsatile administration of gonadotrophin releasing hormone as a diagnostic tool to distinguish hypothalamic from pituitary hypogonadism following neurosurgery.

Nine patients suffering from severe amenorrhoea following neurosurgical or radiotherapy for pituitary tumour or craniopharyngeoma were treated with pulsatile gonadotrophin releasing hormone (GnRH) administration. Seven patients did exhibit ovulatory cycles when GnRH was administered i.v. at a dose of 20 micrograms/pulse, but not at lower doses or when GnRH was administered s.c. Pulsatile GnRH administration may be used to assess the functional integrity of pituitary gonadotrophs and to distinguish pituitary from hypothalamic site of lesion resulting in hypogonadotrophic hypogonadism. It may also be used successfully for treatment of infertility in such patients.

Adolescent↗
PubMed1993

Luteinizing hormone (LH) pulsatility during the oestradiol- and oestradiol/progesterone-induced LH surge in the human female.

Positive feedback reactions were induced in five female volunteers with regular menstrual cycles on the pituitary secretion of luteinizing hormone (LH) during the follicular phase of the cycle by the i.m. administration of oestradiol benzoate ('oestradiol study'), or by oestradiol benzoate followed by progesterone ('oestradiol/progesterone study'). Prior to the administration of the steroids (basal profiles) and during the LH surges following the administration of the steroids (stimulation profiles), blood was drawn at 10-min intervals and the LH pulsatility assessed. The LH pulses occurred at hourly intervals in basal and stimulation profiles, which concurs with data obtained during the normal proliferative phase and the spontaneous mid-cycle surge of the cycle in both the human and the rhesus monkey. Our findings are, however, in sharp contrast with those obtained in the rhesus monkey by the determination of hypothalamic multi-unit activity.

Adult↗
PubMed1993

The effect of flutamide on pulsatile gonadotrophin secretion in hyperandrogenaemic women.

The pulsatile gonadotrophin secretion in hyperandrogenaemic women was examined, following short-term androgen antagonism induced by flutamide, a specific androgen receptor blocker. Flutamide was administered to seven hyperandrogenaemic women and five normal cycling women, at a dose of 250 mg on the evening of day 1, followed by daily doses of 750 mg for 6 days. Blood samples were collected at 10 min intervals for 8 h before (day 1) and during treatment (days 2 and 6). Gonadotrophin and prolactin concentrations were measured in all samples while sex hormone concentrations were analysed in selected samples. Flutamide administration to hyperandrogenaemic women was followed by a decrease in luteinizing hormone (LH) pulse amplitude (P < 0.05), associated with an apparent decline in mean LH concentrations. Follicle stimulating hormone (FSH) showed a significant fall after 6 days of treatment (P < 0.05). Total testosterone, free testosterone, androstenedione and dihydroepiandrosterone sulphate were significantly decreased during flutamide administration, while sex-hormone-binding globulin and oestradiol were not affected. Normal women showed no significant changes in the above mentioned parameters. These results demonstrate that short-term androgen receptor blockade with flutamide reduces gonadotrophin secretion and androgen concentration in hyperandrogenaemic women. Since flutamide is devoid of intrinsic hormonal activity, it is suggested that the observed hormonal changes are secondary to the androgen blockade.

Adolescent↗
PubMed1993

von Willebrand factor: an endothelial marker to monitor in-vitro fertilization patients with ovarian hyperstimulation syndrome.

A retrospective study was conducted to evaluate the possible role of endothelial and extracellular factors in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Plasma changes in von Willebrand-Jürgen factor were correlated with the clinical condition of hyperstimulated patients, since the rise of capillary permeability is the central event in all subsequent morbidity. The corresponding oestradiol levels and ultrasound parameters were assessed. In-vitro fertilization patients designated as 'high responders' and with oestradiol values > 2500 pg/ml and > 8 pre-ovulatory follicles at the time of human chorionic gonadotrophin (HCG) injection were assessed. Among 62 patients, 37 fulfilled these criteria and 18 developed OHSS, indicating the low predictive ability of ultrasound and oestradiol values alone. The remaining 19 patients served as control group. von Willebrand factor-associated antigen in plasma was measured using enzyme-linked immunosorbent assay and ristocetin co-factor activity by an aggregatometric test. Basal values of the two groups of patients did not differ but there were large inter-individual variations. A slight increase occurred in the control group until the day of HCG although individual cycles showed 'no change of pattern' or a 'decreasing tendency' from the start. Some patients allocated to the non-hyperstimulated type showed a steep increase of values followed by a decline. A consistent increase in the OHSS group lasted after embryo transfer even to the late corpus luteum phase. These subtle changes of capillary permeability or damage always preceded the clinical signs, such as ascites, haemoconcentration, hypoproteinaemia and pleural effusion. Mean values differed in the two groups from the day preceding ovum retrieval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Treatment with naltrexone in hypothalamic ovarian failure: induction of ovulation and pregnancy.

Sixty-six women suffering from various grades of hypothalamic ovarian failure were treated with the opiate antagonist naltrexone at doses ranging from 25 to 150 mg per day. This treatment resulted in complete normalization of the menstrual cycle in 49 of 66 patients, as indicated by the pattern of circulating levels of gonadotrophins and ovarian steroids. Five patients failed to respond, three of whom were suffering from primary hypothalamic amenorrhoea. In patients who responded to the administration of naltrexone, there was a dramatic increase in the amplitude and frequency of gonadotrophin pulses, reflecting disinhibition of the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator. Eighteen pregnancies were achieved in 16 women who were also treated for infertility, resulting in a cumulative pregnancy rate closely resembling that of a normal population. There were only minor side-effects that could be attributed to the drug. These data demonstrate that chronic administration of an opiate antagonist will normalize ovarian function in women suffering from different grades of hypothalamic ovarian failure. The data therefore support the view that suppression of the activity of the hypothalamic pulse generator, that directs GnRH release, is mediated by endogenous opioids. Also, that hypothalamic ovarian failure is the consequence of an inappropriate increase in opioid tone impinging on neurons that release GnRH in a pulsatile manner into the pituitary portal circulation.

Adolescent↗
PubMed1993

Purification and characterization of the CA 125 tumor-associated antigen from human ascites.

CA 125 is an antigenic determinant associated with epithelial ovarian carcinomas, which is recognized by a monoclonal antibody, OC 125. The biochemical structure, the immunological characteristics and the physiological function of CA 125 are unknown, principally because the molecule expressing it has not been purified to homogeneity. In the present study, we developed a single, one-step method for purifying CA 125 by column affinity chromatography, using the OC 125 antibody as immobilized ligand. The column proved to be highly specific for the purification of CA 125 from human ascites (HA). The antigen that eluted from the column has a specific activity of 6,240 +/- 120 U of CA 125/mg protein, the specific activity in the initial HA samples being 100 +/- 12 U/mg protein. The purified, immunoreactive CA 125 (IR-CA 125) was shown to be proteinaceous in nature. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration characterization showed that the purified antigen exists as a high molecular weight (MW) complex, of up to 1.5 million daltons, which could be dissociated under strong denaturing conditions, giving rise to moieties with an apparent MW of 205 and 55 kD. IR-CA 125 was also associated with a lower MW protein, with an apparent MW of 10-15 kD. The 205-kD MW protein was immunoreactive CA 125, as measured by immunoradiometric assay after being electroeluted from the polyacrylamide gel. Furthermore, when the affinity-purified antigen was subjected to SDS-PAGE, followed by immunoblotting, the lane which was reactive with the iodinated OC 125 antibody gave rise to a band with a molecular mass of 205 kD. Our results suggest that, on an analytical scale, the affinity column is useful for the purification of CA 125. The purified antigen is being used to investigate the possible role of CA 125 in the growth, development and physiological characteristics of human ovarian carcinomas in in vitro studies.

Antibodies, Monoclonal↗
PubMed1992

The effect of a synthetic GnRH analogue on catamenial epilepsy: a study in ten patients.

Ten female patients suffering from catamenial epilepsy were treated with a synthetic analogue of the gonadotrophin releasing hormone (GnRH) in addition to antiepileptic drugs. Three of the patients became seizure free, in four patients seizure frequency decreased and in one patient seizures were of shorter duration. In only two of the patients was there no therapeutic effect. Adverse effects, including hot flushes, headache and increase in weight, were noticed in eight patients. These results support the hypothesis that treatment with a synthetic GnRH analogue might be helpful in patients with intractable catamenial epilepsies.

Adult↗