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Biomedical subjects

M Ludwig

Publications and source records attributed to M Ludwig.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo.

We investigated the influence of endogenous kappa-opioids on the activity of supraoptic neurons in vivo. Administration of the kappa-antagonist nor-binaltorphimine (200 micrograms/kg, i.v.), increased the activity of phasic (vasopressin), but not continuously active (oxytocin), supraoptic neurons by increasing burst duration (by 69 +/- 24%) and decreasing the interburst interval (by 19 +/- 11%). Similarly, retrodialysis of nor-binaltorphimine onto the supraoptic nucleus increased the burst duration (119 +/- 57% increase) of vasopressin cells but did not alter the firing rate of oxytocin cells (4 +/- 8% decrease). Thus, an endogenous kappa-agonist modulates vasopressin cell activity by an action within the supraoptic nucleus. To eliminate kappa-agonist actions within the supraoptic nucleus, we infused the kappa-agonist U50,488H (2.5 micrograms/hr at 0.5 micrograms/hr) into one supraoptic nucleus over 5 d to locally downregulate kappa-receptor function. Such infusions reduced the spontaneous activity of vasopressin but not oxytocin cells and reduced the proportion of cells displaying spontaneous phasic activity from 26% in vehicle-infused nuclei to 3% in U50, 488H-infused nuclei; this treatment also prevented acute inhibition of both vasopressin and oxytocin cells by U50,488H (1000 micrograms/kg, i.v.), confirming functional kappa-receptor downregulation. In U50, 488H-infused supraoptic nuclei, vasopressin cell firing rate was increased by nor-binaltorphimine (100 and 200 micrograms/kg, i.v.) but not to beyond that found in vehicle-treated nuclei, indicating that these cells were not U50,488H-dependent. Thus, normally functioning kappa-opioid mechanisms on vasopressin cells are essential for the expression of phasic firing.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy.

We have investigated a mouse F9 embryonic carcinoma cell line, in which both vinculin genes were inactivated by homologous recombination, that exhibits defective adhesion and spreading [Coll et al. (1995) Proc. Natl. Acad. Sci. USA 92, 9161-9165]. Using a magnetometer and RGD-coated magnetic microbeads, we measured the local effect of loss and replacement of vinculin on mechanical force transfer across integrins. Vinculin-deficient F9Vin(-/-) cells showed a 21% difference in relative stiffness compared to wild-type cells. This was restored to near wild-type levels after transfection and constitutive expression of increasing amounts of vinculin into F9Vin(-/-) cells. In contrast, the transfection of vinculin constructs deficient in amino acids 1-288 (containing the talin- and alpha-actinin-binding site) or substituting tyrosine for phenylalanine (phosphorylation site, amino acid 822) in F9Vin(-/-) cells resulted in partial restoration of stiffness. Using atomic force microscopy to map the relative elasticity of entire F9 cells by 128 x 128 (n = 16,384) force scans, we observed a correlation with magnetometer measurements. These findings suggest that vinculin may promote cell adhesions and spreading by stabilizing focal adhesions and transferring mechanical stresses that drive cytoskeletal remodeling, thereby affecting the elastic properties of the cell.

Animals↗
PubMed1998

Interruption of central noradrenergic pathways and morphine withdrawal excitation of oxytocin neurones in the rat.

1. We have tested the hypothesis that morphine withdrawal excitation of oxytocin neurones that follows from administration of naloxone to morphine-dependent rats is a consequence of excitation of noradrenergic neurones. 2. Female rats were made morphine dependent by intracerebroventricular (i.c.v.) infusion of the opioid at increasing doses over 5 days. On the sixth day, the rats were anaesthetized with urethane or pentobarbitone and prepared for blood sampling to determine plasma oxytocin by radioimmunoassay or for in vivo extracellular recording of the firing rate of identified oxytocin neurones from the supraoptic nucleus. Morphine withdrawal was induced by intravenous (i.v.) injection of the opioid antagonist naloxone (5 mg kg-1). 3. In one group of rats the noradrenergic projections to the hypothalamus were lesioned by i.c.v. injection of 6-hydroxydopamine immediately prior to the induction of morphine dependence. In these rats the oxytocin secretion induced by i.v. cholecystokinin was reduced to 9 % of that seen in sham-lesioned rats but in contrast, no attenuation of morphine withdrawal-induced oxytocin secretion was observed. 4. i.c.v. infusion of the alpha1-adrenoreceptor antagonist benoxathian, at up to 5.3 microg min-1, dose- dependently inhibited the withdrawal excitation of oxytocin neurones in morphine-dependent rats under urethane anaesthesia, and benoxathian reduced withdrawal-induced oxytocin secretion to 37 % of that of vehicle-infused rats. i.c.v. benoxathian also inhibited the activity of oxytocin neurones in morphine-naïve rats. Similarly, microdialysis administration of 2 mM benoxathian directly onto the surface of the supraoptic nucleus reduced the activity of oxytocin neurones by 53 %. 5. Thus noradrenergic systems are not essential for the expression of morphine withdrawal excitation, since chronic neurotoxic destruction of the noradrenergic inputs to the hypothalamus did not affect the magnitude of withdrawal-induced oxytocin secretion. However, tonically active noradrenergic inputs influence the excitability of oxytocin neurones, and acute antagonism of this noradrenergic tone can powerfully impair the ability of oxytocin neurones to exhibit morphine withdrawal excitation.

Adrenergic alpha-Antagonists↗
PubMed1998

Differences in F9 and 5.51 cell elasticity determined by cell poking and atomic force microscopy.

We studied the elasticity of both a wild type (F9) mouse embryonic carcinoma and a vinculin-deficient (5.51) cell line, which was produced by chemical mutagenesis. Using cell poking, we measured the effects of loss of vinculin on the elastic properties of these cells. F9 cells were about 20% more resistant to indentation by the cell poker (a glass stylus) than were 5.51 cells. Using the atomic force microscope to map the elasticity of wild type and vinculin-deficient cells by 128 X 128 force scans, we observed a correlation of elasticity with cell poking elastometric measurements. These findings, as well as previous atomic force, rheologic, and magnetometric measurements [Goldmann and Ezzell, Exp. Cell Res. 226 (1996) 234-237; Ezzell et al., Exp. Cell Res. 231 (1997) 14-26], indicate that vinculin is an integral part of the cytoskeletal network.

Animals↗
PubMed1998

Haemophilia B: database of point mutations and short additions and deletions--eighth edition.

The eighth edition of the haemophilia B database (http://www.umds.ac. uk/molgen/haemBdatabase.htm ) lists in an easily accessible form all known factor IX mutations due to small changes (base substitutions and short additions and/or deletions of <30 bp) identified in haemophilia B patients. The 1713 patient entries are ordered by the nucleotide number of their mutation. Where known, details are given on: factor IX activity, factor IX antigen in circulation, presence of inhibitor and origin of mutation. References to published mutations are given and the laboratories generating the data are indicated.

Computer Communication Networks↗
PubMed1998

Ankylosing spondylitis and infections of the female urogenital tract.

Thirty-two female patients with confirmed ankylosing spondylitis (AS) and 33 women of similar age with pure ileitis terminalis Crohn were examined for genitourinary infection. Urethral syndrome was found in 15 out of 32 patients with AS: 11 of them had urethritis and 4 urethritis associated with vaginitis. Five women of the control group suffered from urethritis. In all cases with genitourinary infection, Chlamydia trachomatis was isolated. By comparing the AS-patients (urogenital infection group and the non-infected group) with regard to other present clinical parameters, it was found, as expected, that the erythrocyte sedimentation rate in the 1st hour was significantly higher in the infected group. In addition, the infected patients had a significantly higher incidence of enthesopathy, involvement of the spinal column, and higher C-reactive protein values (CRP > or = 5 mg/l). A family history of AS was equally present. Other clinical parameters, such as inflammatory involvement of the joints and HLA-B27 correlation, did not differ significantly between infected and non-infected patients.

Adult↗
PubMed1998

Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12-18 weeks and in a trisomy 16 mouse.

An increase in the nuchal translucency that can be detected at 10-14 weeks of gestation by ultrasound forms the basis for a screening test for chromosomal abnormality. Several mechanisms leading to this increase in skin thickness have been proposed, including changes of the extracellular matrix, cardiac defects and abnormalities of the large vessels. This study examines the composition of the extracellular matrix of the skin in gestational age-matched fetuses with trisomy 21, 18 and 13 from 12-18 weeks. Immunohistochemistry was applied with monoclonal and polyclonal antibodies against collagen type I, III, IV, V and VI and against laminin and fibronectin. Collagen type VI gene expression was further studied by in situ hybridization to detect differences in expression patterns of COL6A1, COL6A3 and COL1A1 between normal fetuses and those with trisomy 21. The ultrastructure of tissue samples was studied by transmission electron microscopy (TEM) and additionally by immunogold TEM. Further, we examined the morphology of the skin in an animal model for Down's syndrome, the murine trisomy 16, by light and TEM. The dermis of trisomy 21 fetuses was richer in collagen type VI than that of normal fetuses and other trisomies, and COL6A1, located on chromosome 21, was expressed in a wider area than COL6A3, which is located on chromosome 2. Collagen type I was less abundant in the skin of trisomy 18 fetuses, while the skin of all three trisomies contained a dense network of collagen type III and V in comparison with normal fetuses. Collagen type IV, of which two genes are located on chromosome 13, was expressed in the basement membranes of the skin in all fetuses and additionally in the dermal fibroblasts only of trisomy 13 fetuses. Likewise, laminin was present in all basement membranes of normal and trisomic fetuses as well as in dermal fibroblasts of fetuses with trisomy 18. LAMA1 and LAMA3 genes are located on chromosome 18. Dermal cysts were found in the skin of trisomy 18 and 13, but not in trisomy 21 and normal fetuses. Ultrastructural findings showed that an extracellular precipitate containing glycosaminoglycans was regularly present in the skin of trisomy 21 fetuses and murine trisomy 16 embryos. In conclusion, this study suggests that the skin edema in fetal trisomies is characterized by specific alterations of the extracellular matrix that may be attributed to gene dosage effects as a result of a genetic imbalance due to the condition of fetal trisomy.

Animals↗
PubMed1998

Structural organisation of the gene encoding the alpha-subunit of the human amiloride-sensitive epithelial sodium channel.

The human amiloride-sensitive epithelial sodium channel (ENaC) is a member of the degenerin/ENaC family of ion channels and regulates fluid and electrolyte absorption across a number of epithelia, including kidney, colon and lung. Native ENaC has been shown to be a multimer made up of at least three homologous subunits (alpha, beta, gamma) and mutations affecting the channel complex have been identified in various human diseases. "Gain of function" mutations in one of the three ENaC subunits have been found to cause pseudoaldosteronism (Liddle's syndrome) and ENaC "reduction of function" mutations are found in patients affected with the recessive form of pseudohypoaldosteronism (PHA) type 1. In this report, we describe the genomic organisation of the human alphaENaC gene. Human alphaENaC consists of 13 exons spanning 17 kb on chromosome 12p13 and contains at least eight Alu sequences. In addition to the intron/exon boundaries, we have deciphered almost all the intron sequences and 475 bp of the CCAAT-less and TATA-less 5' flanking region.

Base Sequence↗
PubMed1998

Naloxone-induced supersensitivity of oxytocin neurones to opioid antagonists.

Here we report that a single administration of naloxone to conscious rats produces no significant increase in oxytocin release, but when repeated 3-4 days later results in a large release of oxytocin. Plasma oxytocin concentrations were measured in conscious and urethane-anaesthetized rats pretreated with naloxone or isotonic saline on Day 1. On Days 2, 3 or 4, a second dose of naloxone was given, producing an increase in oxytocin secretion in naloxone-pretreated groups (P < 0.05 vs. controls) on Day 3 and 4, but not on Day 2. The specificity of the opioid antagonist supersensitivity was determined by injection of the kappa-antagonist nor-binaltorphimine (nor-BNI). Pretreated rats (naloxone, saline or nor-BNI, Day 1) received an additional acute nor-BNI injection (Day 4) which increased plasma oxytocin concentration in the three groups. However, this increase was higher in naloxone-pretreated rats with no differences between the nor-BNI- and saline-pretreated animals. Measurements of electrical activity of single supraoptic nucleus oxytocin neurons and of plasma oxytocin concentration (Day 4) showed that naloxone modestly enhanced the responsiveness of oxytocin neurons to cholecystokinin (CCK) in naloxone-pretreated rats (by comparison with saline-pretreated rats), but had only a small effect on basal firing rate that did not differ between naloxone-pretreated rats and saline-pretreated rats. To investigate whether naloxone-pretreatment modified the effect of morphine on CCK-induced oxytocin release, on Day 4 CCK was injected i.v. with or without morphine. Morphine at a dose of 0.1 mg/kg did not affect CCK-induced oxytocin release, whereas 1 mg/kg of morphine blocked this release in both saline- and naloxone-pretreated rats. The results suggest that naloxone induces opioid antagonist supersensitivity on oxytocin secretion, mainly by up-regulating kappa-opioid mechanisms on oxytocin nerve terminals in the posterior pituitary.

Animals↗
PubMed1998

Dendritic release of vasopressin and oxytocin.

In addition to the release of neurotransmitters from their axon terminals, several neuronal populations are able to release their products from their dendrites. The cell bodies and dendrites of vasopressin- and oxytocin-producing neurones are mainly located within the hypothalamic supraoptic and paraventricular nuclei and neuropeptide release within the magnocellular nuclei has been shown in vitro and in vivo. Local release is induced by a range of physiological and pharmacological stimuli, and is regulated by a number of brain areas; locally released peptides are mainly involved in pre- and postsynaptic modulation of the electrical activity of magnocellular neurones. Spatial and temporal differences between peptide release within the nuclei and that from the distant axonal varicosities indicate that the release mechanisms are at least partially independent, supporting the hypothesis of locally regulated dendritic release of vasopressin and oxytocin. In this respect, magnocellular neurones show similarities to other neuronal populations and thus autoregulation of neuronal activity by dendritic neuromodulator release may be a general phenomenon within the brain.

Animals↗
PubMed1998

Serum concentration of vascular endothelial growth factor cannot predict the course of severe ovarian hyperstimulation syndrome.

Vascular endothelial growth factor (VEGF) is stated to be a possible promoter of the development and the severity of ovarian hyperstimulation syndrome (OHSS). The secretion of VEGF in granulosa cells seems to be human chorionic gonadotrophin (HCG) dependent. In this prospective study, the data of 10 patients suffering from severe OHSS with ascites and pleural effusions (haematocrit, fluid balance, serum HCG, serum oestradiol) were analysed. The serum VEGF concentration declined during the period of clinical improvement but provided no additional diagnostic information for the further course of OHSS. VEGF was neither an early marker of improvement, nor of worsening of the clinical picture of the OHSS. Serum oestradiol concentrations and serum VEGF concentrations showed a statistical correlation (r = 0.33, P < 0.001). There was no correlation between haematocrit and VEGF, nor between serum HCG and VEGF. To conclude, although VEGF may be involved in the pathogenesis of OHSS, it is not an important clinical marker for the course of an OHSS.

Ascites↗
PubMed1998

The effect of multiple cryopreservation procedures and blastomere biopsy on the in-vitro development of mouse embryos.

Preimplantation genetic diagnosis is currently used in clinical practice. In experienced hands the biopsy procedure alone does not affect the further in-vitro and in-vivo developmental potential of animal and human embryos. No data exist on the combination of cryopreservation of embryos at the pronuclear and/or 8-cell stage and/or biopsy at the 8-cell stage. Pronuclear stages of mouse F1 hybrids (C57Bl/jxCBA) were harvested and divided into several experimental groups. The developmental rates of zygotes, which were neither biopsied nor cryopreserved were used as data control. Others were only cryopreserved at the pronuclear stage (C-PN), or at the cleavage stage (C-CS), or both. Each of these groups was also combined with or without a biopsy. Only the hatched blastocyst rate (HBR), but not the 'simple' blastocyst rate, showed significant differences between groups. Neither C-PN (HBR = 60.42%), nor C-CS (63.16%), nor a combination of both (59.46%) had an impact on the hatched blastocyst rate when compared with that of the control group (67.46%). The biopsy procedure (55.93%) also proved not to be harmful for the embryos. The embryos, which were C-PN and C-CS, and subsequently biopsied, showed a significantly lower hatched blastocyst rate (39.62%) than that of the control, C-PN, C-CS, and C-PN/C-CS groups (P < 0.05). The combination of C-PN and cleavage-stage biopsy also lead to a lower hatched blastocyst rate (42.22%), compared with that of the control group (P < 0.05). It was concluded that couples must be advised that an effect on embryos which have undergone a combined cryopreservation and micromanipulation procedure cannot be ruled out. However, cryopreservation at the pronuclear or at the 8-cell stage alone, or in combination with a biopsy procedure, does not influence the further development of the embryo.

Animals↗
PubMed1998

Interactions between trophoblast and uterine epithelium: monitoring of adhesive forces.

At embryo implantation, it is postulated that the initial contact between blastocyst and maternal tissues is by adhesion of the trophoblast to the uterine epithelium. This cell-to-cell interaction is thought to be critical for implantation, although the actual adhesive forces have never been determined. In the present study, the atomic force microscope (AFM) was used to study the adhesion between human uterine epithelial cell lines (HEC-1-A; RL95-2) and human trophoblast-type cells (JAR). Specific interaction forces of these epithelia via their apical cell poles were determined on the basis of approach-and-separation cycles. For this purpose, the AFM tip was functionalized with JAR cells, then brought to the surface of uterine epithelial monolayers and was kept in contact for different periods of time (ms, 1, 10, 20, 40 min). The approach force curves displayed repulsive interactions for both HEC-1-A and RL95-2 cells. However, RL95-2 cells (with a smooth surface structure and a thin glycocalyx) showed lower values of the repulsive regime than HEC-1-A cells (with a rough surface structure and a thick glycocalyx). After having overcome repulsive interactions, the initial contact was followed by adhesive interactions. For contact times of 20 and 40 min, RL95-2 cells, but not HEC-1-A cells, showed specific JAR binding, i.e. the separation force curves displayed repeated rupture events in the range of 1-3 nN with a distance between 7-15 microm and, thereafter, a final rupture event at a distance of up to 45 microm. These features point to the formation of strong cell-to-cell bonds. Collectively, these studies provide the first definition of interaction forces between the trophoblast and the uterine epithelium, and are consistent with the hypothesis that an RL95-2-like architecture of uterine epithelial cells, i.e. an non-polarized phenotype, is essential for apical adhesiveness for the human trophoblast.

Cell Adhesion↗
PubMed1998

Treatment of uterine fibroids with a slow-release formulation of the gonadotrophin releasing hormone antagonist Cetrorelix.

A depot preparation of the third-generation gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix (SB-75) was used for preoperative treatment in twenty premenopausal patients with symptomatic uterine fibroids who were to undergo surgery. In a prospective, open, randomized setting 60 mg of Cetrorelix pamoate salt was administered i.m. on cycle day 2. Patients were randomized for a second dose of 30 or 60 mg of Cetrorelix depot, which was administered according to the degree of oestradiol suppression (<50 pg/ml) on treatment day 21 or 28. Surgery was done after 6 or 8 weeks of treatment, depending on second dosage administration. Weekly transvaginal sonography (TVS) and magnetic resonance imaging (MRI) before and after treatment was performed, for fibroid volume assessment. Sixteen patients showed satisfactory suppression of gonadotrophins and sex steroid secretion, avoiding any initial flare-up effect. In these patients a mean shrinkage rate of largest fibroid volume of 33.5% at the end of treatment could be observed according to TVS, while the mean shrinkage rate obtained after 14 days of treatment was 31.3%. In good responders (shrinkage >20%) largest fibroid volume at day 14 was approximately 56.7% of basic assessment. Although MRI showed minor mean shrinkage rates of only 25.4% of the initial volume, these differences in comparison to TVS assessment were not statistically significant. The avoidance of any initial flare-up in gonadotrophin secretion may explain this extremely fast reduction in fibroid size. The advantages of GnRH antagonist treatment in this indication consist in the short treatment time with a fast restoration of the ovarian function. The rate of poor responders may be reduced by using an improved slow release preparation.

Adult↗
PubMed1998

Ovarian hyperstimulation syndrome (OHSS) in a spontaneous pregnancy with fetal and placental triploidy: information about the general pathophysiology of OHSS.

An ovarian hyperstimulation syndrome (OHSS) in spontaneous pregnancies is a very rare event. Hence, clinicians might make wrong decisions, such as laparotomy, because of suspicion of an ovarian carcinoma, or severe complications such as renal insufficiency may develop because the diagnosis and treatment of OHSS are delayed. Here we report a case of a woman in the 15th week of gestation, presenting with a partial hydatidiform mole and a triploidy of fetus and placenta, with an ongoing and severe OHSS even after legal induced abortion. A low vascular endothelium growth factor (VEGF) concentration (50 ng/ml) was measured when human chorionic gonadotrophin (HCG) exceeded 1000 IU/l and was followed by VEGF concentrations >900 ng/ml, when the OHSS developed. The literature on spontaneous pregnancies associated with OHSS is reviewed, and possible reasons for the clinical course presented in this study and the reviewed reports are discussed. The findings in this case contribute to our theory that VEGF is a causative factor of OHSS, but has no impact on the course of this disease.

Abortion, Induced↗