Gonadotrophin-releasing hormone agonist dose-dependency of pituitary desensitization during controlled ovarian hyperstimulation in IVF

The aim of this study was to find the minimal effective daily s.c. dose of the gonadotrophin-releasing hormone (GnRH) agonist, triptorelin acetate, that suppresses the GnRH-induced release of luteinizing hormone (LH) at time of human chorionic gonadotrophin (HCG) injection and thereby prevents spontaneous LH surges during in-vitro fertilization (IVF) stimulation cycles. Therefore, a double-blind, prospective and randomized titration study was performed. A total of 48 IVF patients were divided into four groups of 12 patients. Each group received a different dose of triptorelin acetate, namely 5, 15, 50 or 100 microg s.c. daily. Standard ovarian stimulation was carried out using urinary follicle stimulating hormone (FSH) preparations. A 500 microg GnRH test was performed 90 min before the HCG injection in order to measure the degree of pituitary desensitization. Spontaneous LH surges were not detected in any of the groups, although three patients in the 5 microg group had ovulated at the time of ovum retrieval. The pituitary LH response to the GnRH test at time of HCG, expressed as area under the curve (AUC), appeared to be dose-dependent. Thus, a daily s.c. dose of 100 microg triptorelin acetate appears to be too high, since adequate desensitization of the pituitary (i.e. no spontaneous LH surge) can be achieved with doses as low as 15 and 50 microg.      

B lymphocytes secreting IgG linked to latent transforming growth factor- beta prevent primary cytolytic T lymphocyte responses

B lymphocytes secreting IgG linked to latent transforming growth factor (TGF)-beta (IgG-TGF-beta) prevent cytolytic T lymphocyte (CTL) responses to unrelated antigens in mixed lymphocyte cultures (MLC) so long as resting resident macrophages and functional Fc receptors are present. This was shown using IgG-secreting plaque-forming cells (PFC) to sheep erythrocytes (SRBC) obtained from popliteal lymph nodes of mice injected repeatedly in foot pads with SRBC. Remarkably, as few as approximately 300 PFC prevented CTL responses of 5 x 10(5) normal syngeneic spleen cells in MLC. Supranatants of short-term cultures of PFC also prevented CTL responses, and suppression was prevented by eliminating or dissociating IgG and TGF-beta present in supranatants or by antibody against active TGF-beta. Furthermore, the latency- associated peptide of latent TGF-beta was detected in approximately 10% of foci of IgG captured from single PFC, indicating that at least some B lymphocytes secrete IgG-TGF-beta as a complex. Resting resident macrophages (which do not produce latent TGF-beta) and functional Fc receptors were required for suppression, consistent with idea that IgG- TGF-beta is taken up through Fc receptors for IgG and that active TGF- beta, cleaved from latent TGF-beta of the complex, is delivered directly to potentially responding CTL. If CTL responses in man are similarly regulated by B lymphocytes, then an ongoing B cell response in patients with chronic viral infections or bearing immunogenic cancers may prevent effective therapeutic vaccination.      

Colorectal adenocarcinoma with micropapillary pattern and its association with lymph node metastasis.

Micropapillary carcinoma has been reported as an aggressive variant of carcinoma in several organs, where it is associated with frequent lymphovascular invasion and poor clinical outcome. This study explored the clinicopathological features of colorectal adenocarcinoma with a micropapillary carcinoma component and compared them with those of conventional colorectal adenocarcinoma. One hundred seventy-eight consecutive cases of surgically resected colorectal carcinomas were studied for tumor size, type, depth of invasion, nodal and distant metastases, tumor stage, and percentage and extent of micropapillary component. Among 178 cases of colorectal carcinoma, 34 (19.1%) cases had a micropapillary component, which ranged from 5 to 60% of the entire tumor. Lymph node metastasis was identified in 25 of 34 (73.5%) carcinomas with micropapillary component, whereas they were detected in 61 of 144 (42.4%) cases without micropapillary component (P=0.001). Lymphovascular invasion was identified more frequently in carcinoma with micropapillary component (41.2%) than carcinoma without micropapillary component (20.1%; P<0.05). Distant metastases occurred in 4 of 34 cases (11.7%) with micropapillary component and in 10 of 144 cases (6.9%) without micropapillary component (P=0.311). Multivariate regression analysis demonstrated that the presence of micropapillary component, as well as tumor stage and lymphovascular invasion are independent predictors of regional nodal metastasis.     

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.      

Respiratory effects in two-dimensional Fourier transform MR imaging

Respiratory and other regular motions during two-dimensional Fourier transform magnetic resonance imaging produce image artifacts consisting of local blurring and more or less regularly spaced "ghost" images propagating along the direction of the phase-encoding magnetic field gradient. The patterns of these ghost artifacts can be understood in terms of the technique of image production and basic properties of the discrete Fourier transform. This understanding permits, without respiratory gating, production of images of improved quality in body regions in which there is significant respiratory motion. In particular, the ghosts can be maximally separated from the primary image by choosing intervals between phase-encoding gradient pulse increments that are equal to one-half the respiratory period; they can be minimally separated by choosing an interval equal to the respiratory period. Increasing the number of signal averages between each phase-encoding increment decreases the intensity of the ghosts.     

Preventive effect of magnesium supplement on noise-induced hearing loss in the guinea pig

The effect of magnesium (Mg) on noise-induced hearing loss was investigated in two groups of adult pigmented guinea pigs maintained either on optimal or suboptimal (physiologically high or low) Mg produced by different diets. The total Mg concentrations of the perilymph (PL), cerebrospinal fluid, blood plasma and red blood cells were measured by atomic absorption spectrometry and were found to differ significantly between the two groups (P < 0.01). One ear of each animal was exposed to either a single shooting impulse at a peak pressure level of 187 dB or two impulse noise series at a rate of 1/s and peak pressure levels of 150 dB (1,000 impulses) and 167 dB (2,280 impulses), respectively. Temporary (TTS) and permanent (PTS) hearing threshold shifts in anesthetized animals were measured 2 h and 1 week after the noise exposure, using auditory brain stem response (ABR) audiometry at a frequency range from 3.75 to 30 kHz. Exposure to the single noise impulse resulted in a mean TTS that was significantly lower in the high Mg group than that in the low Mg group (P < 0.05), although no substantial PTS was observed in either group. In the animals exposed to 150 dB noise, the TTS showed a tendency towards an Mg-related reduction at the higher frequencies. A small difference in PTS was found between the low Mg and high Mg groups, but was not significant. Exposure to the 167-dB noise series caused a considerable TTS, which was significantly lower in the high Mg group at 7.5 and 15 kHz than in the low Mg group (P < 0.05). The mean PTS showed a significant difference between the two Mg groups over the whole frequency range (P < 0.05) and was found to correlate negatively with the total Mg concentrations of both PL and plasma (P < 0.05). Moreover, the high Mg group showed a faster recovery from the hearing threshold shift than the low Mg group. The present findings show that preventive oral Mg supplements can significantly reduce the rate of acoustic trauma caused by high-level impulse noise exposure in the guinea pig. Received: 23 March 1999 / Accepted: 15 April 1999     

Brain Death and Organ Donation in Germany: Analysis of Procurement in a Neurosurgical Unit and Review of Press Reports

Summary  Objective. A prospective study was undertaken to determine the number of potential organ donors in a neurosurgical intensive care unit and to record the actual number of organ donations. The reasons for refusal of organ donations were analysed with respect to the controversial public discussion of the brain death concept and the transplantation law in Germany.  Methods. From 1994 to 1997, the number of cases of brain death, and the number of cases in which relatives consented or refused to organ donation as well as the number of actual organ explantations was recorded. Over the same period, press reports of 5 German language newspapers were analysed with regard to the authors' position on brain death and transplantation law, their qualification, intention, and mode of presentation.  Results. Annually, about 70 deaths occurred on the department's intensive care unit of which almost 30% of the patients were determined to have suffered brain death without any obvious contraindications against organ donation. The refusal rate of relatives rose from 56% up to 78%, and the rate of organ donors thus decreased from 5% in 1994 to 4% presently in the department. About 100 reports were published each year in the analysed newspapers, of which about 90% voiced approval of organ transplantation. During the review period, the depiction became more objective (57% in 1994 to 82% in 1997) and the suspicious attitude toward the technique of brain death diagnosis declined. Whereas 50% of the articles rejected the brain death concept in 1994, this figure decreased to 39% in 1997 and conversely the concept of consent rose from 33% in 1994 to 56% in 1997.  Conclusion. In Germany, the relatives refusal rate in organ donation is continuously high, presumable due to a depressing 39% of press reports rejecting the brain death concept, and resulting in a very low number of organ donations. There is hope that the transplantation law which has finally passed German parliament in 1997, confirming the brain death concept as well as the legal principle of prior consent by the donor or consent by the relatives will eventually result in an increase of organ donation especially when supported by an educational campaign which is embodied in the transplantation law.     

Patientenverfügungen und Bevollmächtigungen in gesundheitlichen Angelegenheiten älterer psychisch kranker Menschen

In clinical practice and in research projects the presence of an advance directive or an appointment of a health-care proxy may substantially contribute to decisions of diagnostic and therapeutic interventions, if a person has lost his ability to consent. A special questionnaire was given to a non representative sample of 206 elderly inpatients suffering from different psychiatric disorders. The majority of these patients (57%) supported the necessity of such instruments. In a further 5.4% of the interviewees written documents, either advance directive or determination of a health-care proxy, were already present. However, 25% of the interviewed patients did not approve of the usefulness of these instruments and 12.5% answered that they were not able to give any decision. Among the interviewed patients, age, gender and the psychiatric disorder present were not associated with approval or refusal. However, higher education was related to the approval of advance directives. This study demonstrates that in a relatively large sample of elderly patients with psychiatric disorders approval of an advance directive and a determination of a health-care proxy is present in a substantial majority. The results suggest that there is urgent need for more intensive information of elderly people about these documents. This could contribute to a decision process about medical interventions in incapacitated persons which is in accordance with their former will.     

Deliveries in short-stay hospitals: United States, 1980

During 1980 3.8 million women with deliveries were discharged from short-stay non-Federal hospitals in the United States. These women made up a sizable portion--9.9 percent--of all the discharges (excluding newborn infants) during that year. Women with deliveries remained hospitalized an average of 3.8 days and used 14.2 million days of inpatient hospital care. This was only 5.2 percent of the total days spent in hospitals by all patients discharged during the year. Most of the women who had a delivery were in their twenties, were white, and were married. The largest percent of deliveries occurred in the South Region, followed by the North Central, Northeast, and West Regions. The percent of women with deliveries was lowest in the smallest hospitals and highest in the largest hospitals. Most of the women with deliveries were discharged from nonprofit hospitals. About half of the women had a normal delivery and about half had some sort of complication. Women more likely to have a complicated delivery were older, were races other than white, had an unknown marital status, and had delivered in the South Region. These women also stayed in the hospital longer, on the average, than did women with normal delivery. The most frequently occurring complications were forceps or vacuum extraction without mention of indication and obstetrical trauma. Episiotomy was the most common procedure. Other frequently performed procedures were low forceps or vacuum extraction with or without episiotomy, cesarean section, repair of obstetric laceration, and bilateral destruction or occlusion of fallopian tubes.