Search PubMed⌕ Search

Biomedical subjects

M Ludwig

Publications and source records attributed to M Ludwig.

At least 127 records · Page 7Linked to original sources

Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease.

The beta amyloid peptide derives from its precursor protein via proteolytic cleavage of yet unidentified proteases (beta- and gamma-secretases). Cathepsin D is an intracellular protease with in-vitro beta-secretase-like features. An exonic polymorphism of the cathepsin D gene (alanine to valine transition at position 224, exon 2) has been associated with altered enzyme function. We tested the hypothesis that this polymorphism is associated with an increased risk for Alzheimer's disease in 102 demented patients, 191 healthy subjects, and 160 depressed patients. There was a highly significant overrepresentation of the cathepsin D*T allele in demented patients (14.2%) compared to non-demented controls (6.7%, P = 0.0012). Carriers of the cathepsin D*T allele had a 2.4-fold increased risk for developing AD than non-carriers. Carriers of the apolipoprotein E epsilon 4 allele had a 4.1 -fold increased risk than non-carriers. The odds ratio for subjects with the apolipoprotein E epsilon 4 and the cathepsin D*T allele was 5.9. Our data suggest that the cathepsin D genotype is strongly associated with the risk for Alzheimer's disease.

Aged↗

Ovarian abscess and heterotopic triplet pregnancy: two complications after IVF in one patient.

A patient is reported, who suffered from ovarian abscess after ovarian puncture of a functional ovarian cyst. The cyst has developed after administration of a GnRH agonist depot preparation in the preceeding luteal phase. She was planned to be stimulated for IVF according to the long luteal protocol. The abscess was removed by laparoscopy. and stimulation started two months later after administration of two further GnRH against depot preparations. The patient got pregnant after embryo transfer of three embryos. and a heterotopic triplet pregnancy, with intrauterine twins and a tubal singleton was established. Bilateral salpingectomy was performed, because of bilateral haematosalpinx and previously described bilateral tubal occlusion. The further pregnancy was uncomplicated.

Abdominal Abscess↗

The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment.

The primary objective of the present study was to investigate the cholesterol-lowering effect of fluvastatin on the incidence of cardiac events in hyperlipidaemic patients with symptomatic, clinically-diagnosed (exercise-ECG) coronary heart disease (CHD) during 1 year of treatment. Exercise tolerance, incidence of angina pectoris episodes, use of anti-anginal medication and intimal-medial-thickness (IMT subgroup) of the A. carotis were secondary endpoints. In the double-blind trial a total of 365 male and female patients with stable symptomatic CHD and a low-density lipoprotein cholesterol (LDL-C) above 160 mg/dl on a lipid-lowering diet were randomised to fluvastatin 40 mg (o.a.d. or b.i.d.) or placebo for 1 year. Fluvastatin lowered total cholesterol by 17% and LDL-C by 27%. There was a significantly lower incidence of cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina pectoris) in the fluvastatin group (3 events) as compared to the placebo group (10 events) (P < 0.05). Exercise tolerance improved and the incidence of angina pectoris episodes decreased in both groups, but more pronounced on fluvastatin (n.s.). Exercise-ECG discontinuation due to angina pectoris and ST-segment depression decreased in the fluvastatin group by 55.6 and 70.9%, respectively, and in the placebo group by 39.6 and 46.5% (n.s.). At baseline, a subgroup of 76 patients showed a mean IMT value of 0.73 mm which remained uninfluenced in the fluvastatin and the placebo groups. Fluvastatin was safe and well tolerated. In conclusion, patients with symptomatic CHD get cardiovascular benefit from lipid-lowering therapy with fluvastatin even during the first year of treatment.

Adult↗

Diagnosis and therapeutic management of 18 patients with prostatic abscess.

OBJECTIVES: Our retrospective study aimed to analyze the findings and therapeutic strategies in 18 men who were admitted to our department as outpatient emergency cases with prostatic abscess. METHODS: During the period 1985 to 1997, prostatic abscess was diagnosed in 18 patients (mean age 48 years, range 20 to 68) on the basis of evidence of fluctuation at digital rectal examination and transrectal ultrasound (TRUS) findings. Diagnostic workup included analysis of midstream urine and abscess fluid for leukocytes and pathogens. Therapeutic options were conservative treatment and/or draining procedures. RESULTS: Predisposing diseases were found in 13 men. Fluctuation at digitorectal palpation was present in 15 patients. In 3 patients, diagnosis was based on TRUS. All men demonstrated leukocytes in their midstream urine. Causative pathogens in midstream urine were found in 11 patients. In 3 men, additional microbiologic evaluation of abscess fluid revealed uncommon pathogens. All patients received antibiotic treatment. Nine men with monofocal abscess less than 1 cm in diameter were treated with antibiotic therapy and a suprapubic catheter. Surgical drainage (transperineal or transrectal puncture, partly guided by TRUS, or transurethral unroofing) was performed in 12 patients and included 3 patients in whom conservative treatment failed. CONCLUSIONS: Our data confirm the importance of predisposing factors in the pathogenesis of prostatic abscess. Medical history and analysis of midstream urine indicated a diagnosis that was confirmed by digital palpation. In some cases, TRUS may improve diagnosis and treatment. Although both operative and conservative therapy strategies appear feasible, prostatic abscess chiefly requires individually selected drainage procedures.

Abscess↗

No transfer in a planned ICSI cycle: we cannot overcome some basic rules of human reproduction.

Since intracytoplasmic sperm injection (ICSI) has been introduced in the techniques for the non-causal treatment of severe male factor infertility failure of conventional in-vitro fertilisation and subsequent embryo transfer due to failed oocyte-fertilisation has become rare in these cases. Nonetheless, even in ICSI cycles cases occur where no transfer can be performed for several reasons. The contribution of sperm-, oocyte- and other factors are reviewed in this article. 78 (5.4%) out of 1433 ICSI cycles, performed from 1.1.1995 up to 31.5.1997, in which no transfer could be done, despite a performed follicular puncture, were used as an example. 30 cycles with no fertilisation, 17 with no oocytes, 8 with only degenerated oocytes retrieved, 17 with no injectable sperms, 4 with no normal fertilisation, and 2 with no cleavage after normal fertilisation were identified. In more than two thirds of the cases an oocyte factor, identified by a high FSH, low response to the hormonal stimulation or no fertilization despite the presence of motile sperms, was present. The other cases were attributed to a sperm factor or other causes. After one failed ICSI cycle - i.e. a cycle with no embryo transfer - the chance to conceive is very low in a subsequent cycle. Only 1 out of 24 cycles was successful in terms of an established and ongoing pregnancy.

Adult↗

Heterotopic pregnancy in a spontaneous cycle: do not forget about it!

Heterotopic pregnancies are estimated to be less frequent than 1:30000 if no assisted reproduction technologies (ART) are performed. After ART this entity is more frequent and in the range of 1:100. In the case reported here an ectopic pregnancy was detected in the right fallopian tube at 7+ 1 weeks of gestation. It was misdiagnosed as an ectopic singleton, and treated by laparoscopic salpingectomy, because of a previous ectopic in the same tube. Rising hCG after laparoscopy during the subsequent days followed by ultrasound evaluation revealed a viable intrauterine pregnancy. The pregnancy continued uneventfully and a healthy child was delivered at term. The problems, which lead to the misdiagnosis are discussed. The problem of rare cases in medicine, and the problems of a 'modern' medicine are discussed.

Chorionic Gonadotropin↗

Rational diagnostic steps in acute pyelonephritis with special reference to ultrasonography and computed tomography scan.

Depending on the severity of the clinical syndrome, acute pyelonephritis may require more extensive imaging diagnostics. In the uncomplicated form of the disease, ultrasonography does not appear to be absolutely necessary. In clinically severe cases, however, which fail to respond to antibiotic therapy, ultrasound is the optimal procedure for ruling out urinary tract obstruction. Where there is clinical suspicion of complications proven risk factors, persistent fever and/or continuing pathological inflammation parameters (elevated C-reactive protein levels in serum)-ultrasonography is the primary imaging technique for the exclusion of pyonephrosis, as well as for other complicating factors such as calculi, etc. In cases of insufficient response to antibiotic therapy, we recommend performing a renal computed tomography scan with contrast medium, in order to rule out hypoenhancing zones as hints for severe tissue alterations. This procedure is in accordance with the suggestions of the Society for Uroradiology. In the future, DMSA scintigraphy might constitute an equivalent diagnostic method for the exclusion of these focal inflammatory changes. Above all, DMSA scintigraphy makes it possible to anticipate the development of scars following acute pyelonephritis.

Acute Disease↗

Germ cell migration and early development of the gonads in the trisomy 16 mouse--an animal model for Down's syndrome.

The aneuploid condition of patients with Down's syndrome (trisomy 21) frequently leads to a sub- or infertility of these individuals. Gonads from adults and fetuses with trisomy 21 demonstrated histologically a remarkable reduction in germ cells. Disorders in the germ cell migration, the early development of the gonads as well as meiotic defects are thought to contribute to this pathomorphology. To gain information about premeiotic defects, investigations on the trisomy 16 mouse, an animal model for Down's syndrome, were carried out. By means of morphometric studies a delay in migration and a reduction in primordial germ cells was evaluated in trisomic mice of embryonic day 11 (E11). At day E13 a generalized growth retardation of the developing gonads was obvious in trisomic animals. Additionally performed electron microscopic examinations revealed signs of germ cell demise in trisomy 16 mice. Thus, the mechanisms of a diminished proliferation capacity, impaired migration and premature death of germ cells represent premeiotic disorders that presumably contribute to the pathomorphology observed in the gonads of individuals with Down's syndrome.

Alkaline Phosphatase↗

Prediction of severe ovarian hyperstimulation syndrome by free serum vascular endothelial growth factor concentration on the day of human chorionic gonadotrophin administration.

In this prospective study the concentration of circulating vascular endothelial growth factor (VEGF) was followed in 10 patients with severe ovarian hyperstimulation syndrome (OHSS) after ovarian stimulation and in 15 patients without OHSS. VEGF was assayed by means of two different commercially available kits as either free or total VEGF in serum. The concentration of free VEGF was significantly higher on the days of human chorionic gonadotrophin (HCG) administration (309.4 +/- 165.0 versus 190.3 +/- 127.8 pg/ml, P < 0.05) and embryo transfer (315.0 +/- 125.2 versus 209.3 +/- 137. 2 pg/ml, P < 0.05) in the OHSS compared to the control group. No such difference existed with respect to total circulating VEGF. In addition, there was no significant rise in the free or in the total serum VEGF concentration in the OHSS patients or the controls from the day of HCG administration up to the days of oocyte retrieval or embryo transfer. A cut-off concentration of 200 pg/ml free serum VEGF concentration on the day of HCG treatment resulted in a sensitivity of 90% and a specificity of 80% for the prediction of OHSS development. This is the first report on the parallel measurement of free and total VEGF in serum following ovarian stimulation. The value of the proposed cut-off concentration should be confirmed in a study of a larger group of women.

Adult↗

Genetic sonography as the preferred option of prenatal diagnosis in patients with pregnancies following intracytoplasmic sperm injection.

The option of prenatal diagnosis with nuchal translucency measurement at 10-14 weeks of gestation and second trimester targeted ultrasound including fetal echocardiography (genetic sonography) is reported in patients after intracytoplasmic sperm injection (ICSI). From January 1995 to December 1998, 153 consecutive patients, with a mean age of 32.3 years (+/-4.1) and 29. 6% >/= 35 years, who had become pregnant after ICSI, were studied. They attended our unit for first and second trimester sonography. Of these, 67.8% of primigravid and 80.9% of nulliparous women were included. Multiple pregnancy rate was 19.7%; 189 fetuses were screened in total. Due to the introduction of genetic sonography in 1995, the rate of invasive prenatal diagnosis decreased from 74% in 1995, to 48, 36 and 19% in 1996, 1997, and 1998 respectively. Two inherited numerical and structural chromosomal anomalies in clinically healthy children at birth (1.0%) and four major malformations in all liveborn children and late abortions (2.1%) were recorded. The results demonstrate that especially in women of advanced reproductive age with a long history of infertility, detailed genetic sonography may be a reasonable and highly accepted alternative to avoid even the relatively low risks associated with invasive screening procedures.

Adult↗

Oocyte quality and treatment outcome in intracytoplasmic sperm injection cycles of polycystic ovarian syndrome patients.

Patients with polycystic ovarian syndrome (PCOS) have higher miscarriage rates. It is postulated that this is caused by a lower rate of mature oocytes, and a lower quality of embryos. Retrospectively we analysed 51 intracytoplasmic sperm injection (ICSI) cycles of 31 PCOS patients. These data were compared to age-matched controls (105 cycles) during the same period. All patients of both groups received gonadotrophin-releasing hormone (GnRH) agonists prior to gonadotrophin treatment. The rate of metaphase II oocytes (MII) was not different. However, the mean absolute number of normally fertilized oocytes was significantly higher in PCOS patients (5.00 versus 3.56, P < 0.01), due to a higher number of oocytes retrieved. More embryos were transferred by cycle in the PCOS group (2.69 versus 2.17, P < 0.05), with a higher cumulative embryo score. The overall and multiple pregnancy rate showed no differences and the clinical abortion rate was lower (21 versus 41.67%, P < 0.05) in the controls. Our findings demonstrate that negative factors unconnected to oocyte morphology must be present in PCOS patients. It is possible that only cytoplasmic, not nuclear, maturity is influenced in these patients.

Adult↗

The forgotten child--a case of heterotopic, intra-abdominal and intrauterine pregnancy carried to term.

Heterotopic pregnancies are estimated to be less frequent than one in 30,000 if no assisted reproduction technologies are performed. Here we report a case which occurred in Tanzania. An abdominal pregnancy at term was first misdiagnosed as an ovarian tumour and diagnosed on the first post-partum day of the intrauterine fetus, which was delivered spontaneously. The abdominal pregnancy was then treated by laparotomy and removal of the placenta. The fetus was alive and healthy. The follow-up of the twins was normal.

Adult↗

New aspects of cryopreservation of oocytes and embryos in assisted reproduction and future perspectives.

Cryopreservation of human gametes and tissue has been introduced into assisted reproduction in recent years. The current status as well as new developments of cryopreservation, especially in conjunction with new techniques, are reviewed. Cryopreservation of pronuclear stage oocytes or embryos at the cleavage stage are routine procedures worldwide after conventional in-vitro fertilization (IVF). The data on children born show no increase in malformation rates, or any impaired psychomotor development. The combination of cryopreservation with intracytoplasmic sperm injection (ICSI) has given the same results. Cryopreservation of unfertilized mature and immature oocytes has lead only to a few pregnancies until now. It is still unknown whether ICSI may help to improve these results. Experience using cryopreservation of blastocysts is still limited, with a wide range of pregnancy rates (0-53 %) being reported. Further studies are required before exact numbers for these procedures can be given. The combination of biopsy and cryopreservation appears to have a different impact for subsequent embryo development in animals and humans. Possibly, there is a reduction in embryo developmental potential after these procedures. Currently, the most promising technique is the cryopreservation of ovarian tissue, which has already led to the birth of lambs, mice and rats. The future development of cryopreservation is discussed.

Cryopreservation↗

Possible applications of lasers in assisted reproductive technologies.

Laser systems seem to be the most promising technical tools to be introduced in assisted reproduction treatment in recent years. The 1.48 microm diode laser in particular is on course to supersede conventional mechanical and chemical methods for opening the zona pellucida in assisted hatching, and for biopsy of polar bodies or blastomeres. This is because it works without physically touching the cells, has no traceable toxic effects on living cells and is easy to handle. There will be manifold future possibilities for micromanipulation with lasers, as already demonstrated by the immobilization of spermatozoa prior to intracytoplasmic sperm injection, and the successful dissection of the zona pellucida into two halves with equal diameter for the hemizona assay.

Animals↗

Genetics of male subfertility: consequences for the clinical work-up.

Major principles of genetic failures, chromosomal alterations and the most common syndromes associated with male subfertility should be taken into account before medical therapy and sophisticated techniques of assisted fertilization are applied to help a couple conceive. This review addresses the most common genetic reasons for male subfertility or infertility with special regard to the importance for the clinical work-up in daily routine and the potential risks for the conceptus.

Chromosome Aberrations↗

Intracytoplasmic injection of round and elongated spermatids from azoospermic patients: results and review.

Microinjection is established as the method of choice in the treatment of severe male factor infertility as well as in azoospermic patients. Recent studies have shown that fertilization and cleavage can be achieved by injection of ejaculated as well as testicular elongated spermatids into oocytes. Here we report on the two first pregnancies worldwide resulting from elongated spermatid injection from frozen-thawed testicular tissue. Four patients with complete Sertoli cell-only syndrome (SCOS) and two with spermatogenetic maturation arrest were included in our microinjection programme. Tissues from open testicular biopsies were cryopreserved until the time of follicle puncture. A total of 67 oocytes were harvested. In the two patients with maturation arrest, cryopreserved elongated spermatids were successfully injected, while in two of the other four SCOS patients only cryopreserved round spermatids were available to be injected into the oocytes. Out of 18 injected oocytes, 10 were fertilized in the first group, while nine out of 49 injected oocytes showed fertilization and cleavage in the second group. Two clinical pregnancies were achieved with elongated spermatids from frozen-thawed testicular tissue, while no pregnancy was established in the case of round spermatids. This study confirms that fertilization, cleavage and pregnancy can be successfully achieved in cases with spermatogenetic maturation arrest by injecting cryopreserved elongated spermatids into oocytes. The literature on pregnancies following spermatid injection, as well as the problems using this technique and possible risks, are discussed.

Adult↗