Medizin - Open Access LMU - Teil 13/22 Archiv

Purpose: Multifetal pregnancy reduction is a widespread `therapy' to diminish the risk of prematurity and adverse outcome for the survivors in higher order multiple gestation. The aim of our study was to determine the maternal and neonatal outcome of multifetal pregnancies under a conservative pregnancy management. Study Design: A retrospective review of 112 multifetal pregnancies is presented. All higher order multiple pregnancies delivered after 25 weeks of gestation and managed at a single institution between 1982 and 1999 are included. Results: Triplets, quadruplets and quintuplets were delivered at a mean gestational age of 31 + 5, 29 + 5 and 28 + 4 weeks, respectively. The perinatal mortality was 14 for triplets and 36 for quadruplets. No quintuplet died in the perinatal period. Respiratory distress syndrome occurred in 23% of triplets, 65% of quadruplets and 75% of quintuplets, intracranial hemorrhage was diagnosed in 14% of triplets, 15% of quadruplets and 10% of quintuplets and retinopathy of prematurity was found in 10% of triplets, 9% of quadruplets and 25% of quintuplets. Discussion: Despite a low neonatal mortality, morbidity of higher order multiple gestations remains significant. Mortality and morbidity are related to preterm delivery but do not exceed the rates of singletons or twins of an identical gestational age. Favorable prognostic landmarks are a gestational age >30 weeks and a number of fetuses per pregnancy less than or equal to4. Conclusion: The risks of multifetal pregnancies are significant. Therefore, evidence-based counseling of couples seeking treatment for infertility and prevention of higher order multiple pregnancies through the prudent use of reproductive techniques attains paramount importance. Copyright (C) 2002 S. Karger AG, Basel.

Incremental lines in dental cementum of museum specimens of 11 free-ranging great apes were compared to the respective structures in 5 captive specimens of known age-at-death, and with many known life-history parameters. While the dental cementum of the free-ranging apes was regularly structured into alternating dark and light bands, 4 out of 5 captive animals showed marked irregularities in terms of hypomineralized bands which could all be dated to the year 1963. Cementum preservation was insufficient in the fifth specimen and did not permit such a differentiation. All 4 captive apes had been kept in a zoo located in the northern hemisphere, where 1963 was characterized by an extremely cold winter. Since cold stress is a calcium-consuming process, the lack of available calcium in newly forming cementum could be responsible for the observed hypomineralization. The appositional growth characteristics of dental cementum serve as a record for such life-history events. Copyright (C) 2002 S. Karger AG, Basel.

Growing evidence supports the substantial pathophysiological impact of platelets on the development of acute lung injury. Methods for studying these cellular mechanisms in vivo are not present yet. The aim of this study was to develop a model enabling the quantitative analysis of platelet kinetics and platelet-endothelium interaction within consecutive segments of the pulmonary microcirculation in vivo. New Zealand White rabbits were anesthetized and ventilated. Autologous platelets were separated from blood and labeled ex vivo with rhodamine 6G. After implantation of a thoracic window, microhemodynamics and kinetics of platelets were investigated by intravital microscopy. Velocities of red blood cells (RBCs) and platelets were measured in arterioles, capillaries and venules, and the number of platelets adhering to the microvascular endothelium was counted. Kinetics of unstimulated platelets was compared with kinetics of thrombin-activated platelets. Velocity of unstimulated platelets was comparable to RBC velocity in all vessel segments. Unstimulated platelets passed the pulmonary microcirculation without substantial platelet-endothelial interaction. In contrast, velocity of activated platelets was decreased in all vascular segments indicating platelet margination and temporal platelet-endothelium interaction. Thrombin-activated platelets adhered to arteriolar endothelium; in capillaries and venules adherence of platelets was increased 8-fold and 13-fold, respectively. In conclusion, using intravital microscopy platelet kinetics were directly analyzed in the pulmonary microcirculation in vivo for the first time. In contrast to leukocytes, no substantial platelet-endothelium interaction occurs in the pulmonary microcirculation without any further stimulus. In response to platelet activation, molecular mechanisms enable adhesion of platelets in arterioles and venules as well as retention of platelets within capillaries. Copyright (C) 2002 S. Karger AG, Basel.

Background/Aim: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported. Methods: Eluates were derived from antibody-based immunoadsorption of a patient suffering from primary FSGS, a patient with systemic lupus erythematosus, and a healthy volunteer. The cytosolic free Ca2+ concentration ({[}Ca2+](i)) of differentiated podocytes was measured by single-cell fura-2 microfluorescence measurements. Free and total immunoreactive kinin levels were measured by radioimmunoassay. Results: FSGS eluates increased the {[}Ca2+](i) levels concentration dependently (EC50 0.14 mg/ml; n = 3-19). 1 mg/ml eluate increased the {[}Ca2+](i) values reversibly from 82 +/- 12 to 1,462 +/- 370 nmol/l, and then they returned back to 100 16 nmol/l (n = 19). The eluate-induced increase of {[}Ca2+](i) consisted of an initial Ca2+ peak followed by a Ca2+ plateau which depended on the extracellular Ca2+ concentration. The eluate-induced increase of {[}Ca2+](i) was inhibited by the specific B-2 kinin receptor antagonist Hoe 140 in a concentration-dependent manner (IC50 2.47 nmol/l). In addition, prior repetitive application of bradykinin desensitized the effect of eluate on {[}Ca2+](i). A colonic epithelial cell line not reacting to bradykinin did not respond to eluate either (n = 6). Similar to FSGS eluates, the eluate preparations of both the systemic lupus patient and the healthy volunteer led to a biphasic, concentration-dependent {[}Ca2+](i) increase in poclocytes which again was inhibited by Hoe 140. Free kinins were detected in all eluate preparations. Conclusion: The procedure of antibody-based immunoadsorption leads to kinin in the eluate which elevates the {[}Ca2+](i) level of podocytes via B-2 kinin receptors. Copyright (C) 2002 S. Karger AG, Basel.

The architecture and compartmentalization of the kidney has stimulated the development of an array of microtechniques to study the functional differences between the distinct nephron segments. With the vast amounts of genomic sequence data now available, the groundwork has been laid for a comprehensive characterization of the molecular pathways defining the differences in nephron function. With the development of sensitive gene expression techniques the tools for a comprehensive molecular analysis of specific renal microenvironments have been provided: Quantitative RT-PCR technologies now allow the analysis of specific mRNAs from as little as single microdissected renal cells. A more global view of gene expression regulation is a logical development from the application of large scale profiling techniques. In this review, we will discuss the power and pitfalls of these approaches, including their potential for the functional characterization of nephron heterogeneity and diagnostic application in renal disease. Copyright (C) 2002 S. Karger AG, Basel.

There is increasing evidence suggesting that the neurotransmitter gamma-aminobutyric acid (GABA) is a local factor involved in the regulation of endocrine organs. Examples of such functions are documented in the pancreas, but recent results suggest that GABA may act in a similar way in the pituitary, in which GABA receptors are expressed and pituitary growth hormone (GH) cells provide a source of GABA. We hypothesised that GABA secreted in somatotropes may act as an autoregulatory signaling molecule. To test this hypothesis we first examined the nature of GABA receptors expressed by GH cells. RT-PCR analysis demonstrated that GABA-B receptor subunits R1 and R2 are present in the whole rat pituitary. Laser microdissection of immunostained GH cells, followed by RT-PCR as well as immunoelectron microscopy, showed that GABA-B receptors are expressed on somatotropes. To investigate GABA-B receptor function in somatotropes, we used rat GH3 adenoma cells, which, like pituitary GH cells, express GABA-B R1 and R2 (as assessed by RT-PCR and immunoelectron microscopy) and produce GABA (checked by high performance liquid chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by bactofen, a GABA-B receptor agonist. By contrast, blocking GABA-B receptors by an antagonist, phaclofen, decreased GH levels. We conclude that in GH-producing cells, GABA acts as an autocrine factor via GABA-B receptors to control GH levels. Copyright (C) 2002 S. KargerAG, Basel.

We performed a service-based epidemiological study of dystonia in Munich, Germany. Due to favourable referral and treatment patterns in the Munich area, we could provide confident data from dystonia patients seeking botulinum toxin treatment. A total of 230 patients were ascertained, of whom 188 had primary dystonia. Point prevalence ratios were estimated to be 10.1 (95% confidence interval 8.4-11.9) per 100,000 for focal and 0.3 (0.0-0.6) for generalised primary dystonia. The most common focal primary dystonias were cervical dystonia with 5.4 (4.2-6.7) and essential blepharospasm with 3.1 (2.1-4.1) per 100,000 followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4-1.5) per 100,000. Copyright (C) 2002 S. Karger AG, Base.

Atypical neuroleptics are increasingly used in the treatment of bipolar and schizoaffective disorders. Currently, numerous controlled short-term studies are available for clozapine, olanzapine, risperidone or quetiapine, but long-term data are still missing. Three patients (2 with bipolar disorder, 1 with schizoaffective disorder) are described who showed a marked reduction of affective symptomatology after clozapine had been added to mood stabilizer pretreatment. The patients were seen once a month before and after the introduction of clozapine for at least 6 months. Treatment response was evaluated using different rating scales (IDS, YMRS; GAF; CGIBP) and the NIMH Life Chart Methodology. All patients showed a marked improvement after the add-on treatment with clozapine had been initiated. Clozapine was tolerated well with only transient and moderate weight gain and fatigue as only side effects. This case series underlines the safety and efficacy of clozapine as add-on medication in the treatment of bipolar and schizoaffective disorders. Copyright (C) 2002 S. Karger AG, Basel.

Objective: To test whether an ultramolecular dilution of homeopathic Thyroidinum has an effect over placebo on weight reduction of fasting patients in so-called ‘fasting crisis’. Design: Randomised, placebo-controlled, double-blind, parallel group, monocentre study. Setting/location: Hospital for internal and complementary medicine in Munich, Germany. Subjects: Two hundred and eight fasting patients encountering a stagnation or increase of weight after a weight reduction of at least 100 g/day in the preceding 3 days. Intervention: One oral dose ofThyroidinum 30cH (preparation of thyroid gland) or placebo. Outcome Measures: Main outcome measure was reduction of body weight 2 days after treatment. Secondary outcome measures were weight reduction on days 1 and 3, 15 complaints on days 1–3, and 34 laboratory findings on days 1–2 after treatment. Results: Weight reduction on the second day after medication in the Thyroidinum group was less than in the placebo group (mean difference 92 g, 95% confidence interval 7–176 g, P=0.034). Adjustment for baseline differences in body weight and rate of weight reduction before medication, however, weakened the result to a non-significant level (P=0.094). There were no differences between groups in the secondary outcome measures. Conclusions: Patients receiving Thyroidinum had less weight reduction on day 2 after treatment than those receiving placebo. Yet, since no significant differences were found in other outcomes and since adjustment for baseline differences rendered the difference for the main outcome measure non-significant, this result must be interpreted with caution. Post hoc evaluation of the data, however, suggests that by predefining the primary outcome measure in a different way, an augmented reduction of weight on day 1 after treatment with Thyroidinum may be demonstrated. Both results would be compatible with homeopathic doctrine (primary and secondary effect) as well as with findings from animal research.

Changes in ATP-induced increase in {[}Ca2+], during collecting duct ontogeny were studied in primary monolayer cultures of mouse ureteric bud (UB) and cortical collecting duct (CCD) cells by Fura-PE3 fluorescence ratio imaging. In UB (embryonic day E14 and postnatal day P1) the ATIP-stimulated increase (EC50 approximate to 1 muM) in fluorescence ratio (DeltaR(ATP)) was independent of extracellular Ca2+ and insensitive to the P2 purinoceptor-antagonist suramin (1 mM). From day P7 onward when CCD morphogenesis had been completed DeltaR(ATP) increased and became dependent on extracellular Ca2+. This ATP-stimulated Ca2+ entry into CCD cells was non-capacitative and suramin (11 mM)insensitive, but sensitive to nifedipine (30 muM) and enhanced by Bay K8644 (15 muM), a blocker and an agonist of L-type Ca2+ channels, respectively. Quantitative RT-PCR demonstrated similar mRNA expression of L-type Ca2+ channel alpha1-subunit, P2Y(1), P2Y(2), and P2X(4b) purinoceptors in UB and CCD monolayers while the abundance of P2X(4) mRNA increased with CCD morphogenesis. In conclusion, both embryonic and postnatal cells express probably P2Y(2)-stimulated Ca2+ release from intracellular stores. With development, the CCD epithelium acquires ATP-stimulated Ca2+ entry via L-type Ca2+ channels. This pathway might by mediated by the increasing expression of P2X(4)-receptors resulting in an increasing ATP-dependent membrane depolarization and activation of L-type Ca2+ channels. Copyright (C) 2002 S. Karger AG, Basel.