The Göteborg protocol for treatment of craniosynostosis.
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Biomedical subjects
Publications and source records attributed to C Lauritzen.
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650 couples with idiopathic subfertility (mean duration: 5.7 year, range 2-21 years) were treated during 2870 cycles by three assisted conception methods (each involving mild ovarian stimulation): I timed intercourse (TI), II intrauterine insemination (IUI). III in vitro fertilization/embryo transfer (IVF/ET). Treatment started with TI in most cases and then changed to IUI after three to six cycles. Couples who failed to conceive were treated after another 3-9 cycles by IVF/ET. An overall cumulative pregnancy rate of 80.2% was reached after 18 treatment months. The pregnancy rates per treatment cycle were: TI 5.3%, IUI 6.9%, IVF/ET 15.8% (per oocyte retrieval).
This prospective pilot study has been carried out to assess the effect of high parenteral doses of estrogens and progestogens on lumbar spine bone density in osteopenic women. Thirteen osteopenic women received 40 mg estradiol valerate and 250 mg hydroxyprogesterone caproate by intramuscular injections once a week for 6 months (so called "pseudopregnancy"). One g oral calcium was added. Six out of the 13 patients (49.5 +/- 4.8 y were peri- and postmenopausal = group A. Seven patients (21.5 +/- 2.2 y) suffered from primary and secondary amenorrhea, in 4 out of them due to gonadal dysgenesis = group B. Estradiol was measured by commercial radioimmunoassay. Bone density was determined by dual-energy X-ray absorptiometry (DEXA) of the upper 4 lumbar vertebrae. Lumbar spine bone density as well as estradiol serum levels were measured before and 3 and 6 months after therapy, respectively. Estradiol increased from 34.8 +/- 7.5 pg/ml to 3226 +/- 393 pg/ml after 3 months and to 2552 +/- 254 pg/ml after 6 months, respectively, in group A. Bone density increased by 15.3 +/- 3.6% within the first 3 months to a total of 18.8 +/- 3.9% after 6 months, respectively. Two patients we have controlled for two years, maintained this increase. In group B estradiol increased from 27.8 +/- 6.5 pg/ml to 3028 +/- 728 after 3 and to 2491 +/- 684 pg/ml after 6 months. Bone density in this group increased by 11.8 +/- 1.9% within 3 and to a total of 18.2 +/- 2.8% after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Estrogens are not carcinogenic. They create however a milieu, which generally stimulates cell division and growth of the target organs, also in cases of existing early neoplastic changes. This growth stimulating effect is dependent on dose and duration of the estrogen effects. Low doses exert no significant influence, medium doses are stimulating, high doses inhibit carcinoma growth, if the tumor is hormone responsive. Cyclic application of a progestogen stops proliferation and induces the specific function of the target tissue. This influence is mediated through a reduction of the number of estrogen receptors, a stimulation of the transformation of estradiol to estrone, a decrease of intracellular metabolism and a reduction of blood perfusion of the target organs. Progestogens therefore act generally preventive against cancer development at the genital organs and probably also on the breast. They should therefore principally be given together with estrogens for at least 10, optimal 12 to 14 days at month. Whether the compromise to give a progestogen only every three or six month will be acting equally carcinoma preventive as the monthly medication, ist not known. In woman bearing risk factors - except proliferative mastopathy - an estrogen-progestogen substitution seems not to increase the inherent risk, rather to reduce it. However nevertheless the manifestation of genital and breast cancer occurs preponderately in women at risk. Familial-genetic immunologic, metabolic factors, weight, race, nutrition, chronic inflammation, regeneration, old age and other risks seem equally or even more important than hormonal factors. Women, who receive a long time estrogen-progestogen substitution, have a lower risk to develop endometrial and ovarian cancer. This is probably also true for mammary and colon cancer. Meta-analyses of all studies could not show so far an increased risk for mammary cancer in estrogen-progestogen substituted postmenopausal women. Women, who receive a postmenopausal long during estrogen-progestogen substitution show statistically a better prognosis of their genital and mammary cancers, if they occur, than unsubstituted controls. Following treated cervical, endometrial and ovarian cancer a strictly indicated estrogen-progestogen substitution is possible without causing drawbacks. The so far valid contraindication against estrogens in post-carcinoma patients does not longer exist. Positive influences on cure rates and survival have been described. In cases of estrogen-progestogen negative receptor mammary cancer cases a substitution is also possible. In all other cases hormones can be given after five years recidive free survival. It is recommended to prescribe not too high doses of estrogens and to combine them with an effective progestogen.(ABSTRACT TRUNCATED AT 400 WORDS)
The adolescent girl needs affection and understanding for all of her problems. She often does not find a satisfying measure of both in her familiar surroundings. Very often sex instruction is faulty, although the AIDS campaigns have led to remarkable improvements (condoms). Instructions for sexual behaviour should take place at home or at school, but not in the street. Nevertheless, the first intercourse occurs mostly unprotected. Teenage pregnancies present not only physical but also psychological problems. Termination of pregnancy means an especially difficult decision for the adolescent girl, often causes crisis and occasionally leads to negative consequences for later fertility. The choice of appropriate contraceptive methods for girls under 16 years of age may also have legal problems. Condoms and barrier methods are possible alternatives to the much safer hormonal contraception with the combination, sequence or minipill. Under certain circumstances, a progestin injection every three months or the 'morning-after pill' as postcoital contraception or, in the case of an abortion or of pregnancy termination, even an intrauterine device can be an alternative for adolescent girls under those exceptional circumstances.
Quantification and qualification of climacteric symptoms had been described by Kupperman et al in 1953. New findings and ideas in the following forty years needed a correction of Kupperman index. Two important groups reduced the essential symptoms only on two ones, vasomotoric hot flushes and genital atrophy. On the contrary, Menopause Rating Scale (MRS) presented here enables registration of so called psychic symptoms, too, essential for quality of life. Complaint from bladder and urethra, hints and muscles and sexual disorders are also registered. For each of the ten symptom groups there is a rating scale from 0.0 (no symptoms) to 1.0 (very strong symptoms), in a graphic, too. In this way an individual profile will be visible. Using MRC it is possible, to quantify a better or worst status during and after treatment and to depict it.
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The chromosome complement of first cleavage stage mouse embryos was analyzed to investigate the effect of slow freezing-fast thawing cryopreservation on chromosome numbers by comparing these numbers with those found fresh after fertilization of control oocytes. Fewer frozen-thawed (34.1%) than control oocytes (75.0%) cleaved to the 2-cell stage after in vitro fertilization. The incidence of hyperploidy was significantly increased by freezing (4.5% vs. 0% in controls). Polyploidy was not significantly affected (17.0% for freeze-thaw embryos vs. 26.2% for controls).
Four N-terminal extended species of the wild-type bovine pancreatic trypsin inhibitor (WT-BPTI), Arg-BPTI (1-BPTI), Met-Glu-Ala-Glu-BPTI (4-BPTI), Ser-Ile-Glu-Gly-Arg-BPTI (5-BPTI) and Gly-Ser-Ile-Glu-Gly-Arg-BPTI (6-BPTI) have been studied by 1H n.m.r. The overall structure of the protein is largely unaffected by the addition of extension peptides. pH titration effects on the C-terminal Ala 58 H beta chemical shift indicate that the structure of 1-BPTI at neutral pH is very similar to that of the WT protein, with a salt bridge between the main chain terminal charges. A salt bridge interaction is prevented by addition of the longer extension peptides. Temperature stabilities are measured by high temperature hydrogen isotope exchange and by microcalorimetry. The stability of 1-BPTI is equal to that of WT-BPTI. A slight decrease in stability is observed for longer extensions, following the order WT-BPTI = 1-BPTI < 5-BPTI = 6-BPTI < 4-BPTI. Small changes in chemical shift are observed for 30 invariant resonances in 4-, 5- and 6-BPTI and for a subset of this group in 1-BPTI. These protons are distributed over about half of the BPTI molecule. The size of the chemical shift changes for many resonances follow the same ranking as the temperature stability. The chemical shift effects are attributed to charge and dielectric effects from extension peptides that probably share a common orientation on the surface of BPTI.
This investigation aimed at evaluating a role for frequencies and amplitudes of repeated HCG stimulations for the optimal maintenance of progesterone (P4) secretion from the bovine corpus luteum in vitro. Slices (100-120 mg) of midluteal bovine corpora lutea were perifused with medium M199 (0.05% BSA, pH 7.2, 38.5 degrees C) and the perifusion effluent collected at 15 minute intervals for 20-29 hours. Unstimulated P4 release (n = 5) was distinctly pulsatile (by Pulsar pulse algorithm), with pulses occurring every 90 +/- 6 minutes (mean +/- SEM) and pulse amplitudes of 14.4 +/- 1.1 ng. Conversely, no pulses were detected in two control perifusions. Unstimulated P4 release increased during the first 5 perifusion hours (from 39.3 +/- 4.6 to 50.3 +/- 5.6 ng/15 min, p less than 0.01), but then appeared to decline (to 29.3 +/- 1.3 ng/15 min, p less than 0.05) towards the end of the perifusion periods. Hourly pulses of HCG (6.7 mM) did not change the P4 pulse amplitudes (16.6 +/- 2.0 ng), the pulse periodicities (105 +/- 15 min) and overall release rates (34.7 +/- 5.7 ng/15 min), nor did they prevent the decline in P4 secretion towards the end of perifusions (n = 5). In contrast, 2-hourly HCG stimulations maintained stable P4 release rates throughout the perifusion periods (34.7 +/- 6.8 ng/15 min), with P4 pulses of similar amplitudes (14.7 +/- 1.7 ng), but of lower periodicities (135 +/- 2 min, p less than 0.05) than during unstimulated conditions (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Partial dissection of the zona pellucida (PZD) is one of several micromanipulatory methods for the treatment of male subfertility. PZD involves the mechanical introduction of a small hole in the zona pellucida of the oocyte prior to insemination. Thus, fusion with the oolemma and fertilization of the oocyte is facilitated for spermatozoa with impaired quality that otherwise would not be able to penetrate the zona. We have established this technique at our clinic and report on the first pregnancy achieved by PZD of the oocyte during our IVF programme.
Constituents of the follicular fluid (FF) have been suspected to influence fertilizability and cytogenetic constitution of human oocytes. Therefore, we analysed the FF concentrations of 17 beta-estradiol (E2), progesterone (P), testosterone (T), and prolactin (PRL) of 114 oocytes recovered for in vitro fertilisation (IVF). 46 of these oocytes were fertilised and transferred to the maternal uterus. Among the unfertilized gametes, 27 were not analysable. 30 were normal haploid, and 11 were classified as abnormal. There was no significant difference between fertilised and unfertilized oocytes for FF concentrations of E2, P, T, and PRL and for the E2/P ratios. Similarly, we detected no significant difference between normal and abnormal oocytes for these parameters.
A significant enhancement of the fertilizing capacity of human spermatozoa by Kallikrein has recently been described in a former study. To assess the therapeutic possibilities it would be of great interest to know more about the biochemical effect of Kallikrein on the fertilizing capacity of human spermatozoa. This fact made the authors investigate 64 semen samples in which the binding score and the fertilizing capacity were determined after application of Kallikrein in a HOP-test (hamsterovum-penetration-test) and compared to the control. Furthermore these results were compared to the varying concentrations of the components of the Kallikrein-Kinin-system. An application of Kallikrein in the swim-up preparation resulted in a higher motility in patients with asthenozoospermia, whereas the patients belonging to the group of oligoasthenozoospermia showed a lower progressive motility compared to the control. The binding score (number of affixed spermatozoa) showed nearly the results in both preparations. On the other hand the fertilizing capacity in the Kallikrein preparation was significantly higher. A possible connection with the concentrations of the components of seminal plasma has not been found, yet, but regarding all results a direct enzymatic effect of Kallikrein on fertilizing potential can be assumed.
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Human oocytes remaining unfertilized or uncleaved during in vitro fertilization (IVF) yield valuable information on the kind and frequency of numerical and structural chromosome aberrations after their fixation. This enables us to assess the maternal contribution to perturbations in the course of fertilization and early embryonic development. Therefore, 566 unfertilized or uncleaved oocytes from our IVF programme were processed for cytogenetic examination. 223 gametes were not analyzable. 260 oocytes were completely karyotyped and chromosome counts could be established for 83 cells. 243 eggs had the normal haploid chromosome complement whereas 100 cells (29.2%) were abnormal. In detail, we found the following aberrations: hypohaploidy = 10.2%, hyperhaploidy = 4.7%, diploidy = 9.0%, tetraploidy = 1.2%, structural anomalies = 2.6%, prematurely condensed sperm chromosomes = 3.2%. Six cells had to be considered in two of these categories. Our results and comparisons with other publications imply that the total rate of anomaies in human oocytes from stimulated cycles amounts to 20 to 30%. This high frequency might be one of the limiting factors for the success rate of IVF.
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