Effect of various factors on in vitro fertilization (IVF) and embryo transfer in the human in clomiphene/hMG/hCG stimulated cycles

In the present study we tried to analyse data obtained on the occasion of an in vitro fertilization programme at the department of obstetrics and gynecology of the University of Kiel, to extract some of the important factors, because their positive or negative influence on the success of extracorporal insemination, embryo transfer and implantation has not been clearely defined till now and to value their concern. Between July 1982 and February 1983 105 sterile patients with ovulatory menstrual cycles have been treated by the technique of in vitro fertilization and embryo transfer, successively. Follicular growth was stimulated by 150 mg clomiphen daily from 3rd to 7th day and application of 225 IU hMG on 6th, 8th and 10th day. Finally ovulation was timed 36 hours before follicular puncture by 5000 IU hCG. In 24 per cent endogenous LH peak could be observed. In 86 per cent of the 80 patients exactly timed one oocyte was to be found minimally. In 68 per cent of these patients after all an embryo transfer was done (24 times one embryo, 13 times two, 9 times three and once four embryos). 89% of the embryos have been transfered as 4-or 8-cell stage, only 11 per cent as two cell stage. Transfer took place 48 to 50 hours following insemination. There was no correlation between the maturity classified morphologically of the oocytes and the diameter of their follicles. The speed of development of the embryos was not correlated with the size of their follicles. too. In 60-70 per cent of all cases, in which an embryo transfer was possible, husbands had normal spermiogram. The percentage of unfertilised oocytes following insemination using non-optimal sperma was increased in all types of cycles, additionally there was a reduction of the developing speed of resulting embryos. Doubtless two the four pregnancies resulted after insemination using sperma of less quality. The conjugation rate is said to be not correlated directly with the exactness of timing of the application of hCG with reference to follicular maturity, but in all pregnancies hCG was injected simultaneously with the peak of estradiol.     

Antibodies to estrogen receptor: Immunochemical similarity of estrophilin from various mammalian species

Immunoglobulin obtained from the serum of rabbits immunized with a highly purified preparation of estradiol-receptor complex from calf uterine nuclei has been shown to contain specific antibodies to the receptor protein (estrophilin) by four criteria: (a) precipitation of the radioactive steroid upon addition of goat antibody against rabbit gamma globulin to a mixture of the tritiated estradiol-receptor complex and the immunoglobulin, (b) adsorption of the estradiol-receptor complex by the immunoglobulin linked to Sepharose, (c) adsorption of the estradiol-receptor complex in the presence of the immunoglobulin by Staphylococcus aureus protein-A linked to Sepharose, and (d) the ability of the immunoglobulin to increase the sedimentation rate of the estradiol-receptor complex. Antibodies to calf nuclear estrophilin were shown to crossreact with the nuclear receptor of rat uterus, as well as with the extranuclear receptor of calf, rat, mouse, and guinea pig uterus and of human breast cancer. The antibodies do not react with either the nuclear or extranuclear dihydrotestosterone-receptor complexes of rat prostate or with the extranuclear progesterone-receptor complex of chick oviduct. These findings indicate an immunochemical similarity among estrophilins from several mammalian species, as well as between extranuclear and nuclear forms of the receptor, but not among receptor proteins for different steroid hormones.     

Adrenoceptor subtypes in the control of burn-induced plasma extravasation

Burn trauma is known to induce a significant rise in circulating catecholamine levels and despite catecholamines being potent endogenous vasoactive agents with known actions on microvascular permeability, their effect on burn edema has been poorly investigated. The present study in rats investigated the role and importance of adrenergic receptor subtypes in the regulation of basal capillary permeability in normal skin and hyperpermeability in partial- and full-thickness skin burns. Edema was quantified by spectrophotometric analysis of extravasated Evans blue-albumin. Evaluation was based on intravenous administration of the following adrenergic agonists and antagonists: l-phenylephrine (alpha(1)-receptor agonist), prazosin (alpha(1)-receptor antagonist), clonidine (alpha(2)-receptor agonist), yohimbine (alpha(2)-receptor antagonist), prenalterol (beta(1)-receptor agonist), terbutaline (beta(2)-receptor agonist), or propranolol (beta(1)- and beta(2)-receptor antagonist). Results showed increased capillary permeability in normal skin following administration of terbutaline (p<0.01) and yohimbine (p<0.01). In partial-thickness burns, clonidine significantly (p<0.05) reduced edema formation, whereas in full-thickness burns edema was significantly reduced by clonidine (p<0.05) and l-phenylephrine (p<0.01). In conclusion, the inhibition of postburn edema induced by stimulation of alpha(1)-receptors (l-phylephrine) and alpha(2)-receptors (clonidine) could be secondary to increased vascular resistance and reduced tissue perfusion pressure and/or suppressed inflammatory reaction in the burn injury. In the treatment of burn patients, clonidine is particularly interesting since the agent has previously been proven to induce potent analgesia in thermally injured.     

How should we assess the clinical relevance of guidelines in primary health care?

Background

Experiences from disseminating guidelines for pharmacotherapy in “quality circles”.

Objective

To assess the “clinical relevance” of the guidelines, 142 GPs participating in 8 quality circles supplied by the Kassenärztliche Vereinigung Hesse (Association of Statutory Health Insurance Physicians) were continually interviewed by questionnaires administered in the circles. The findings of the survey of the participants had to be reviewed by the authors of the guidelines.

Methods

A total of 142 physicians (GPs) participating in a structured advanced training for pharmacotherapy were continuously interviewed from 2001–2003 by a questionnaire. They were asked which of the 135 recommendations selected from the 8 guidelines they had used in practice. The results of the survey were later presented to the 15 authors of the guidelines who had also been acting as moderators of the quality circles. As “peers” they were asked by questionnaire to review the findings and to judge which of the recommendations they themselves estimated as “essential”, “important” or “non-essential” to the success of the therapy.

Results

As “acceptance” of a recommendation by the participants we defined: “used in practice ?”=”yes”. The rate of “acceptance” varied widely and four groups of almost equal rate of acceptance could be identified: recommendations that had been applied in 90–100% were classified as “very high”, 75–89% as “high”, 50–75% as “problematic” and less than 50% as “very low” acceptance. The reviewers evaluated almost all of the recommendations that had been applied by the participants in a high or very high rate as “essential” or “important”. On the other hand the reviewers estimated almost half of the recommendations with a “very low” rate of acceptance as “non-essential” (40%) or made no answer (7%). With respect to the 31 recommendations with problematic application on the side of the participants, among the reviewers a consent evaluating them as “essential” or “important” or “non-essential” for therapy existed only for 8 (26%).

Conclusions

The implementation of guidelines in quality circles does not assure a high rate of compliance with recommendations on the side of the target group. Authors of guidelines should recognize their latent reservations with respect to the relevance of their own recommendations. Evaluation of the compliance with guidelines should consider that not every recommendation claims the same grade of relevance. Estimating the relevance of a given recommendation seems to be an indispensable but neglected task of implementation.     

Subjective versus interviewer assessment of global quality of life among persons with schizophrenia living in the community: A Nordic multicentre study

Background: Few studies have investigated differences between subjective and externally assessed quality of life in individuals with a severe mental illness. In a sample of 387 patients with schizophrenia living in the community the present study investigated the association between subjective and interviewer-rated quality of life, clinical and sociodemographic factors related to the two assessments, and if discrepancies in the assessments were related to any clinical or social features of the patients. Method: The study was a Nordic multicentre study with a cross-sectional design. Instruments used were the Lancashire Quality of Life Profile, the Brief Psychiatric Rating Scale, the Interview Schedule for Social Interaction, Camberwell Assessment of Needs and General Assessment of Functioning. Results: The correlation between subjective and interviewer-rated quality of life was moderate (ICC=0.33). More severe affective symptoms, fewer emotional relations and a lower monthly income were related to poorer subjectively rated quality of life but in a stepwise multiple regression analysis accounted for only 14.1 of the variance. Poorer interviewer-rated quality of life was mainly related to a more severe psychopathology but also to a lower monthly income, fewer emotional relations and not being employed. Together these factors accounted for 45.5 of the variance. A greater discrepancy between the subjective and the interviewer rating was found in patients with less affective symptoms, unemployment, and a better social network. Conclusion: Only a moderate correlation between subjective and interviewer-assessed global quality of life was found, implying that the sources of assessment differed, as was also shown in subsequent regression models. It is concluded that both perspectives on the patient’s quality of life may be valuable for treatment planning, especially in cases where differences in quality of life assessment related to the patient’s psychopathology may be expected.     

Folate deficiency-induced hyperhomocysteinemia attenuates, and folic acid supplementation restores, the functional activities of rat coagulation factors XII, X, and II

Hyperhomocysteinemia (HH) constitutes a risk marker for thrombosis, but the pathophysiological mechanisms in thrombus formation are still unresolved. We investigated the influence of HH on single coagulation factor functions and evaluated the platelet GpIIb/IIIa receptor function in HH-induced changes in whole-blood coagulation profiles (WBCP). Three groups of 12 rats were investigated: control rats, folate deficient-HH (FD-HH) rats, and treated rats. Plasma total homocysteine was 7.1 micromol/L in controls, 31.3 micromol/L in FD-HH rats, and 7.6 micromol/L in treated rats. Factor (F) II:C, FX:C, and FXII:C were reduced in FD-HH rats compared with controls and normalized in treated rats (P < 0.05). FVII:C activity did not differ among the groups. Factor VIII:C activity was greater in FD-HH rats than in controls (P < 0.05). Blockage of the platelet GpIIb/IIIa receptor by Integrilin (Schering-Plough A/S) did not abolish the FD-HH-induced increase in whole-blood coagulation velocity, irrespective of the dosage of Integrilin. In conclusion, FD-HH reduced the functional activities of FXII:C, FX:C and FII:C, whereas FVII:C was unchanged and FVIII:C increased. These findings may partially explain the prolonged initiation phase of WBCP in FD-HH rats. The changes in single coagulation factor functions and WBCPs in FD-HH rats were reversed by treatment with folic acid.     

Rosette inhibition test: A multicentre investigation of early pregnancy factor in humans

The rosette inhibition test for the detection of early pregnancy factor is described in detail. The extended methodology presented here represents the cumulative experience of three independent laboratories. Special reference is made to the effect on the assay of varying the conditions of rosette formation between lymphocytes and sheep red blood cells. Antilymphocyte sera prepared for use in the rosette inhibition test fell into three catagories: (i) with no rosette inhibiting activity, (ii) with rosette inhibiting activity which is not affected by the presence of EPF, and (iii) rosette inhibiting activity which is significantly increased in the presence of EPF. To date, this third reaction has been found to be a specific indication of the presence in serum of early pregnancy factor.