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Biomedical subjects

M Ludwig

Publications and source records attributed to M Ludwig.

At least 37 records · Page 2Linked to original sources

Temporal dissociation of the feedback effects of dendritically co-released peptides on rhythmogenesis in vasopressin cells.

Vasopressin neurones fire action potentials in a rhythmic 'phasic' pattern, characterised by alternating periods of activity and silence. Vasopressin and dynorphin are co-packaged in neurosecretory vesicles that are exocytosed from vasopressin cell dendrites and terminals and both have been implicated in the generation of phasic activity patterning through autoregulatory mechanisms. Here, identified supraoptic nucleus vasopressin cells exhibiting spontaneous phasic activity were recorded from urethane-anaesthetised rats administered the V1 vasopressin receptor antagonist, OPC 21268, or the kappa-opioid receptor antagonist, nor-binaltorphimine. OPC 21268 elevated firing rate throughout each burst whereas nor-binaltorphimine excitation emerged over the course of each burst, indicating a progressive activation of kappa-opioid receptor mechanisms during bursts. To determine whether changes in post-spike excitability could account for these effects, we plotted the probability of action potential firing with time after the preceding action potential (hazard function) and found that, similarly to firing rate, this too was elevated by OPC 21268 throughout each burst whilst the excitatory effects of nor-binaltorphimine progressively increased over the course of each burst. Thus, the temporal organisation of the feedback effects of these co-released peptides is different, with vasopressin effectively causing an immediate reduction in overall excitability whilst dynorphin causes a progressive decrease in post-spike excitability over the course of each burst.

Action Potentials↗

Different preferences for prenatal diagnosis in pregnancies following assisted reproduction versus spontaneous conception.

The uptake of prenatal diagnosis in 436 singleton and 146 twin pregnancies following assisted reproduction was compared with a matched group of spontaneous conceptions. The first and second trimester ultrasound examination included target fetal anatomic evaluation and screening by specific markers described for fetal aneuploidy. Women with assisted conception attended significantly more often for first trimester prenatal diagnosis (57.9 versus 34.9%, P < 0.01), but had fewer examinations in the early second trimester at 15-18 weeks (37.8 versus 48.8%, P < 0.01) than those with spontaneous conception. Screen positive results of 6.5 and 6.9% for first trimester examination and 6.0 and 7.3% for second trimester examination were found in assisted conceptions and controls respectively. A significantly higher rate of invasive prenatal diagnosis was observed in the second trimester for spontaneous conceptions, 20.0 versus 11.8% (P < 0.01) compared with assisted conceptions. This was attributed to the higher rate of invasive procedures in advanced maternal age >/=35 years of 40.7 versus 28.6% (P = 0.01) in spontaneous and assisted conceptions respectively. With the purpose of avoiding invasive testing, women with assisted conception were more likely to use the results of the ultrasound examination to guide their final decision about invasive testing, rather than undergo genetic amniocentesis as a first option.

Amniocentesis↗

Cumulative pregnancy rates and drop-out rates in a German IVF programme: 4102 cycles in 2130 patients.

Cumulative pregnancy rates are useful in counselling couples on their chance of conceiving during infertility treatment. Patients also have to be counselled about the physical and psychological stress of infertility treatment. Beside the pregnancy rates, drop-out rates are a direct, and may be the most important, marker of physician quality in an IVF programme. Data from 4102 IVF cycles in 2130 patients in Germany were analysed retrospectively. Data were analysed using descriptive statistics as well as the Kaplan-Meier procedure. A real cumulative pregnancy rate of 31.2% was achieved after four cycles with an expected cumulative pregnancy rate (ECPR) of 53.3%. Age was a significant factor regarding pregnancy rates (ECPR after four cycles: 57.1% <35 years, 44.8% > or =35 years, 35.4% > or =40 years). The drop-out rate of non-pregnant patients increased from 39.9% after the first cycle to 62.2% after the fourth cycle, indicating the enormous stress and frustration that increased during the course of treatment. The drop-out rate should be used as an important marker of quality control. The presented data give, for the first time, a good basis for this counselling procedure in Germany.

Adult↗

Low-level gonosomal mosaicism in women undergoing ICSI cycles.

PURPOSE: Females with low-level gonosomal mosaicism (LLGM) scheduled for ICSI were retrospectively analyzed and compared to control groups. The prevalence of this mosaicism as well as its impact for an ICSI treatment were evaluated. METHODS: Routine cytogenetic analysis was done in 891 females scheduled for ICSI treatment. For comparison 294 females with recurrent abortions and 104 women with clinical or cytogenetical affected children, who also had routine chromosome analysis, were acquired. RESULTS: In the ICSI group the incidence of LLGM was significantly lower compared to the group of females with recurrent abortions (3.9% vs. 8.5%, p < 0.01). The incidence was similar between the groups of ICSI females and females with cytogenetical or clinically affected children (5.8%, p = 0.43). Neither anamnestic factors nor outcome parameters were different between females with and without LLGM undergoing ICSI. CONCLUSION: There is no higher incidence of LLGM in females undergoing ICSI. In those who show LLGM, fertility capacity is not reduced.

Abortion, Habitual↗

[Attitudes toward oocyte donation and surrogate motherhood are strongly influenced by own experiences].

The aim of the study was to find out the attitudes of different groups towards technologies which are prohibited by the German Embryo Protection Law. We evaluated by using a questionnaire, in how far oocyte donation and surrogate motherhood were accepted in Germany in different groups of the population. 34 infertile patients, 74 patients who asked for preimplantation genetic diagnosis (PID), 29 women, who had finished family planning, and 59 medical students were asked for their opinion in a standardized and closed questionnaire. Overall the different groups, especially medical students, were very critical towards oocyte donation and surrogate motherhood. However, to help another couple to conceive a child 68.6 % of PID patients, 62.1 % of infertile patients, 43.2 % of women with finished family planning, and 47.6 % of students were prepared to donate oocytes. On the other hand, only 40.9 %, 40.0 %, 25.9 %, and 13.2 % of PID patients, infertile patients, women with finished family planning and medical students, respectively, would accept oocyte donation for themselves. Regarding surrogate motherhood, the PID group and students were strictly against the idea to be a surrogate mother by themselves. Members of the infertile group as well as those women with finished family planning were more indifferent regarding this question. Students and women with finished family planning, however, would prefer adoption, whilst PID- and infertility groups are more indifferent. Men are more positive towards both techniques as compared to women. As compared to known data from other countries, the acceptance of oocyte donation in all groups and surrogate motherhood is comparable to other European countries, when only PID patients and infertile patients are respected. The other two groups are more critical against surrogate motherhood. To conclude, it becomes apparent how opinions regarding these techniques are influenced by the own situation and experiences.

Adoption↗

Genetic and molecular aspects of hypospadias.

Hypospadias, a midline fusion defect of the male ventral urethra, is a relatively common genital anomaly occurring in 0.3 - 7 of 1000 live male births. The anatomical location of the misplaced urethral meatus determines the severity of this anomaly with the severity increasing from distal to proximal. Glandular and penile hypospadias, the most common forms, often appear as an isolated anomaly and account for the majority of hypospadias, whereas about 20 % are classified as scrotal and perineal types. These latter forms frequently occur in association with other genital anomalies such as microphallus, bifid scrotum, penoscrotal transposition, and cryptorchidism, and may represent an intersex phenotype. Besides a higher incidence in consanguineous families and a suggested recessive inheritance, in other families a dominant transmission is likely. The recurrence risk in the next generation seems to be correlated with the severity of hypospadias. Only 30 % of severe hypospadias can be attributed to defects in the synthesis of testosterone or adrenal steroid hormones, receptor defects, syndrome-associated hypospadias, chromosomal anomalies, defects in other genetic factors, or exogenous forms. To identify the underlying causes of the remaining 70 % "idiopathic" hypospadias, familial and twin studies were performed. Familial studies can help identify gene loci and, subsequently, candidate genes by mutational analysis. Either linkage analysis in large families with many affected individuals suspicious for a monogenic trait or association studies in cases of a complex inheritance in many families with a few affected individuals can be performed. Microarrays and proteomics can help detect gene expression or protein differences. Furthermore, genetically modified animal models can be used to detect phylogenetically homologous genes in man. In addition to an optimal documentation and acquisition of blood and tissue samples this requires a close cooperation between clinicians in the operative and non-operative specialties as well as geneticists.

Abnormalities, Multiple↗

[Optimisation of possible success in an IVF program].

The success of an IVF (in vitro fertilisation) programme is mainly dependent an the quality of the IVF laboratory. Beside this the quality of ovarian stimulation play another, but not as important role. In the 4 (th) quarter of 2003 we have changed the culture media for oocytes and embryos in the IVF laboratory of ENDOKRINOLOGIKUM Hamburg from simple to complex media (G-1 version 3). As protein source we used HSA-solution. Before embryo transfer equilibration for 1 hour in EmbryoGlue was performed, which contains hyaluran. Hyaluran is said to improve implantation rates by different ways. The media were bought from Vitrolife Schweden AB (Kungsbacka, Schweden) via a German distributor. These data were compared to those of two previous 3-month-periods (3rd quarter 2003 und 4th quarter 2002). The study design was prospective, with two historical control groups. In the three study periods 255, 343 and 503 patients were treated by either conventional IVF or ICSI (intracytoplasmic sperm injection). The cohorts were comparable regarding their anamnestic data. The number of patients treated which the GnRH antagonist cetrorelix (Cetrotide) significantly increased from 24.9 % to 49.5 % and 60.9 %. Under this protocol significantly less oocytes were retrieved (10.23 vs. 8.73 vs. 8.88), leading to slightly less embryos (1.94 vs. 1.91 vs. 1.85, not significant, n. s.). The cumulative embryo score significantly decreased from 28.58 to 24.10. It was significantly higher in the study cohort as compared to the two control cohorts (32.44). The clinical pregnancy rate significantly increased to 25.29 % in the study cohort as compared to the two historical control cohorts (15.02 % and 18.75 %). We could achieve a significant improvement in the success rates of our IVF program by switch from simple to more complex culture media in the IVF laboratory. The use of the GnRH antagonist protocol with cetrorelix (Cetrotide) lead to more comfort to the patients but did not influence the results.

Adult↗

Magnocellular dendrites: prototypic receiver/transmitters.

The hypothalamic magnocellular neurones of the supraoptic and paraventricular nuclei of mammals are among the best understood of all peptidergic neurones, and therefore serve as a model for understanding the functions of other peptidergic neurones. The release of vasopressin- and oxytocin-containing neurosecretory vesicles from their dendrites was first established 15 years ago. This local release is now known to have many functions, including controlling the interactions between oxytocin neurones and their surrounding glia, and facilitating and inhibiting the electrical activation of the neurones. Technical advances now permit dynamic analysis of dendritic release. Here, we review recent studies that focus on the conditional priming of dendritic peptide release by peptide-induced liberation of intracellular calcium, and the role of dendritic protein synthesis in the dendritic peptide release and the control of receptive properties of the neurones.

Animals↗

Periurethral abscess formation due to Neisseria gonorrhoeae.

Abscess formation secondary to chronic urethritis of the posterior male urethra caused by Neisseria gonorrhoeae has become an atypical and rare urological complication. Periurethral abscess formation has been reported to be associated with gonococcal infections, but in such rare cases a delay in the diagnosis of gonococcal infection seems to have been the cause for this periurethral complication. A case with a primary diagnosis of periurethral abscess with N. gonorrhoeae infection is reported--successful treatment included transurethral incision and antibiotic therapy.

Abdominal Abscess↗

[Chronic pain syndrome in uorology].

Chronic pain of the genital region remains a therapeutic challenge. Among men, symptoms are mainly related to the prostate, bladder and scrotal organs, and among women to the bladder and vagina. Only some of the cases demonstrate pathologic changes of the symptomatic organs requiring specific treatment. Among pain medications, peripheral analgesics are the most suitable. In the case of chronic pain, which can be classified according to Gerbershagen, a psychosomatic origin also has to be considered and needs to be evaluated. Analgesics are of minor importance in the treatment of psychosomatic syndromes but tricyclic antidepressants or anticonvulsants may be helpful. Relaxation techniques also need to be considered.

Chronic Disease↗

[European Association of Urology guidelines on urinary and male genital tract infections].

Today, the classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis, chancroid and inguinal granuloma, only account for a small proportion of all known sexually transmitted diseases (STDs). Other bacteria and viruses as well as yeasts, protozoa and epizoa must also be regarded as causative organisms of STD. Taken together, all sexually transmitted infections comprise more than 30 relevant STD pathogens. However, not all pathogens that can be sexually transmitted manifest diseases in the genitals and not all infections of the genitals are exclusively sexually transmitted. Concise information and tables summarising the diagnostic and therapeutic management of STDs in the field of urology allow a synoptic overview, and are in agreement with the recent international guidelines of other specialist areas. Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and recommended regimens are presented.

Disease Notification↗

No influence of body weight on pregnancy rate in patients treated with cetrorelix according to the single- and multiple-dose protocols.

The question of whether adjustment to body weight is necessary in in-vitro fertilization (IVF) cycles using GnRH antagonists is currently under discussion. Therefore, a data analysis of five prospective studies using either the single- or the multiple-dose antagonist protocol with cetrorelix (Cetrotide) was performed. The influence of stimulation procedure, gonadotrophins and body weight on pregnancy rate was evaluated in a linear logit model. The effect of the stimulation procedure and body weight on the cumulus-oocyte complex (COC) and follicle number was explored in an ANOVA model. Cetrorelix plasma concentrations were tested for any correlation with body weight. Baseline and outcome parameters in different body weight groups (<50 kg, 50-59 kg, 60-69 kg, 70-79 kg, > or =80 kg) were assessed for human menopausal gonadotrophin and recombinant human FSH stimulation separately. Cetrorelix plasma concentrations were correlated with body weight, but no influence of the type of stimulation or body weight on pregnancy rate was found. Body weight did not influence cetrorelix plasma concentrations. In contrast, body weight significantly influenced the number of retrieved COC as well as the number of follicles on the day of human chorionic gonadotrophin administration. Body weight does not influence the outcome of treatment in cetrorelix cycles.

Body Weight↗

Developments in drugs for ovarian stimulation.

Drugs for ovarian stimulation have been improved during the last decades. Initially gonadotrophins were extracted from human pituitary glands and urine; nowadays they are produced from transformed cell-lines. All three gonadotrophins--follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotrophin (hCG)--are now marketed as recombinant (r-) products. The near-100% pure FSH preparations might, in some situations, cause abnormally low LH levels and it is likely that the addition of LH may be beneficial in these situations. It is possible that r-LH will become available in sufficient dosages to replace hCG for ovulation induction and this may reduce the incidence of ovarian hyperstimulation syndrome due to its shorter half-life. In parallel to the development of gonadotrophin preparations, protocols for ovarian stimulation are now more comfortable for the patients, especially with the introduction of gonadotrophin receptor hormone (GnRH)-agonists in the early 1980s and, more recently, the introduction of GnRH-antagonists.

Chorionic Gonadotropin↗

Influence of autogenous leucocytes and Escherichia coli on sperm motility parameters in vitro.

Urogenital infections are considered important factors in male infertility. In this in vitro study we have evaluated the impact of leucocytes in association with an artificial infection with Escherichia coli on the motility of human spermatozoa. Ejaculates and blood samples were obtained from healthy donors with normal semen parameters. Ejaculates were prepared by swim-up technique and five fractions were isolated for incubation. Leucocyte subtypes were separated from blood samples by gradient centrifugation. Purified sperm suspensions were adjusted to a concentration of 20 x 106 ml-1 and incubated with lymphocytes/ monocytes, polymorphonuclear granulocytes (PMN), and E. coli. Samples were incubated for up to 6 h at 37 degrees C. Motility analysis was performed using a computer-assisted sperm analyzer (CASA). Spermatozoa incubated with 3 x 106 PMN ml-1 revealed a significant (P=0.003) decrease in progressive motility after 2 h. This decrease remained weakly significant (P=0.024) after 4 and 6 h. Lymphocytes and monocytes had no effect on sperm motility. Spermatozoa incubated with granulocytes and E. coli demonstrated highly significant alterations in motility after 4 and 6 h of incubation (P < 0.001). The PMN indicate an effect on motility of spermatozoa under experimental conditions. However, the results suggest that bacteria are the primary agents that interfere with sperm motility.

Ejaculation↗

Significance of inflammation on standard semen analysis in chronic prostatitis/chronic pelvic pain syndrome.

The impact of defined urogenital inflammations on standard ejaculate parameters is still a matter of controversial debate. Basic spermiogram parameters has been analysed in patients with inflammatory and noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-NIH IIIA/IIIB) with regard to indicators of inflammation in prostatic secretions and/or the ejaculate. A total of 112 consecutive patients symptomatic for chronic pelvic pain were included in the study. All of them underwent a 'four glass-test' including leukocyte determination in expressed prostatic secretions followed by ejaculate analysis according to WHO. The analysis included pH, volume, total sperm count, sperm density, motility, morphology (Shorr stain), vitality (eosin stain), and counting of peroxidase positive leukocytes (PPL). Patients were first subgrouped according to elevated leukocyte counts in prostatic secretions, and then according to the number of PPL in semen. Leukocytes neither in the prostatic secretions nor in the ejaculate were associated with reduced standard semen parameters. Our data supports previous results that elevated leukocyte counts in prostatic secretions and in ejaculate, as indicators of inflammation have no negative impact on total sperm count, sperm density, motility, morphology, and sperm vitality in patients with CP/CPPS.

Chronic Disease↗

[Intima media thickness of the carotid arteries: early pointer to arteriosclerosis and therapeutic endpoint].

An early sign of atherosclerosis is hypertrophy of the arterial wall. Increased intima-media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. There are important differences in B-mode measurements of carotid IMT between laboratories. These might concern on IMT image acquisition (in relation to the segment and/or the wall of measure) as well as determination of the echo boundary defining the IMT interfaces and the difference in relationship between anatomic and sonographic structures of the near and far arterial wall. Measurements derived from the near wall reflect thickness of a part of media and intima influenced by sonographic artefacts, rather than that of the total intima-media complex. Two main approaches are used for measuring IMT: 1) manual measurement at multiple extracranial carotid sites in near and far walls, and 2) automated computerized measurement, restricted to the far wall of the distal common carotid artery. Intra- and inter-observer variabilities have been found to vary in manual measurements between 0.09 to 0.13 mm and 0.12 to 0.18 mm (absolute differences). The best reproducibility of manual IMT-measurements is found at the far wall of the common carotid artery 1 cm from the bulb in the site of two parallel wall contours without local thickening. For automated measurements lower intra- and inter-observer variabilities have been reported. IMT of the common carotid artery is strongly influenced by age. For younger age groups (20 to 30 years) mean IMT values of 0.5 mm have been reported, while IMT values of 0.9 mm have been found for older subjects (60 to 70 years). Carotid IMT correlates with other risk factors such as systolic blood pressure, serum lipids and smoking, as well as being positively linked to the presence and extend of coronary artery disease in both women and men. The demonstration of a correlation between IMT and cardiovascular events such as stroke and myocardial infarction in clinical studies of atherosclerosis progression and cardiovascular outcomes have led to FDA accepting 2D ultrasound as a valid technique in clinical studies of atherosclerosis. Regression or slowing of progression of increased carotid IMT by various antihypertensive and lipid-lowering drugs agents have been reported. In addition to carotid IMT measurement as a predictive value of future vascular events the presence of plaques or stenosis in the carotid artery tree increases drastically the risk for cardiovascular events. Therefore the authors of this article propose the use of high resolution Duplex-Sonography for the assessment IMT of the common carotid artery as well as the detection of plaques and stenosis in clinical practice. In conclusion, high-resolution Duplex-sonography seems promising for the detection, quantification and serial investigations of structural alterations of the arterial wall. The method is sensitive enough to be applied in clinical studies of the progression and regression of early preintrusive atherosclerotic lesions in extracranial carotid arteries. Moreover IMT of the common carotid artery can be used as a therapeutic endpoint.

Arteriosclerosis↗

The 2001 Giessen Cohort Study on patients with prostatitis syndrome--an evaluation of inflammatory status and search for microorganisms 10 years after a first analysis.

During the last years tremendous changes have occurred in the epidemiologic knowledge and the diagnostic process of the prostatitis syndrome. A new worldwide-accepted classification system has become the gold standard in contemporary literature. The aim of this study was to compare the inflammatory and infectious status of men with prostatitis syndrome with results from our study cohort from 1992. A total of 168 symptomatic men (mean age 43.2 years; range 18-79) attending the Giessen prostatitis outpatient department were included. All men underwent a standard four-glass-test including leucocyte analysis in all specimens. A routine search for Ureaplasma urealyticum and Chlamydia trachomatis was performed. Ejaculate analysis following World Health Organization (WHO) criteria has been performed including the evaluation of increased number of peroxidase-positive leucocytes (PPL). Men were classified according to the National Institutes of Health (NIH) prostatitis classification. The distribution of patients according to NIH criteria is as follows: NIH II (4.2%), NIH IIIA (31.5%), NIH IIIB (50.0%) and urethroprostatitis (14.3%). Chlamydial infection was present in one man (0.6%). Only two men with increased leucocytes in prostatic secretions demonstrated > or =106 million ml-1 PPL in semen. As compared with our cohort study 10 years ago, the proportion of the different subtypes of the prostatitis syndrome have remained stable. The aetiological spectrum of chronic bacterial prostatitis has not changed whereas, in contrast, the prevalence of C. trachomatis now is found to be strikingly reduced. Using the WHO cutpoints for leucocytospermia the inclusion of seminal leucocytes to the diagnostic process has not influenced the distribution between inflammatory (type NIH IIIA) and noninflammatory (type NIH IIIB) chronic pelvic pain syndrome.

Adult↗