Neonicotinoid insecticides inhibit cholinergic neurotransmission in a molluscan (Lymnaea stagnalis) nervous system.

Neonicotinoids are highly potent and selective systemic insecticides, but their widespread use also has a growing impact on non-target animals and contaminates the environment, including surface waters. We tested the neonicotinoid insecticides commercially available in Hungary (acetamiprid, Mospilan; imidacloprid, Kohinor; thiamethoxam, Actara; clothianidin, Apacs; thiacloprid, Calypso) on cholinergic synapses that exist between the VD4 and RPeD1 neurons in the central nervous system of the pond snail Lymnaea stagnalis. In the concentration range used (0.01-1 mg/ml), neither chemical acted as an acetylcholine (ACh) agonist; instead, both displayed antagonist activity, inhibiting the cholinergic excitatory components of the VD4-RPeD1 connection. Thiacloprid (0.01 mg/ml) blocked almost 90% of excitatory postsynaptic potentials (EPSPs), while the less effective thiamethoxam (0.1 mg/ml) reduced the synaptic responses by about 15%. The ACh-evoked membrane responses of the RPeD1 neuron were similarly inhibited by the neonicotinoids, confirming that the same ACh receptor (AChR) target was involved. We conclude that neonicotinoids act on nicotinergic acetylcholine receptors (nAChRs) in the snail CNS. This has been established previously in the insect CNS; however, our data indicate differences in the background mechanism or the nAChR binding site in the snail. Here, we provide the first results concerning neonicotinoid-related toxic effects on the neuronal connections in the molluscan nervous system. Aquatic animals, including molluscs, are at direct risk while facing contaminated surface waters, and snails may provide a suitable model for further studies of the behavioral/neuronal consequences of intoxication by neonicotinoids.

[Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany - Austria - Switzerland)]. / Management der postpartalen Blutung (PPH): Algorithmus der Interdisziplinären D-A-CH-Konsensusgruppe PPH (Deutschland - Österreich - Schweiz).

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

SAPHO syndrome with ankylosis of the temporomandibular joint.

SAPHO syndrome is a rare combination of different symptoms with unknown aetiology. A complete ankylosis of the temporomandibular joint (TMJ) in a patient with SAPHO syndrome has not been described previously. The goal of this case report is to present the disease, give an overview about the frequency of mandibular involvement and describe different therapeutic strategies. The complication of an ankylosis of the TMJ is noted and the literature is reviewed. The authors report a 42-year-old patient with SAPHO syndrome and recurrent swelling of the right mandible and the soft tissue. The persisting involvement of the mandible resulted in a complete osseous ankylosis of the right TMJ and required resection with alloplastic replacement of the right condyle. SAPHO syndrome should be suspected in some cases of 'therapy resistant osteomyelitis' of the mandible. Smaller joints, such as the TMJ may also be affected. Treatment of SAPHO syndrome should include antibiotics and NSAIDs; corticosteroids may be helpful. Surgery is the ultimate treatment.

Delivery of a live newborn in a triplet pregnancy complicated by preeclampsia after intrauterine demise of two and expulsion of one triplet: a case report.

Delayed interval delivery in twin pregnancies is an unusual occurrence, even more so in triplet pregnancies. We report on a delayed interval delivery in a dichorionic triamniotic triplet pregnancy after in vitro fertilization (IVF). Because of severe twin to twin transfusion syndrome (TTTS), two fetuses demised at 22 weeks of gestation. One of the two fetuses spontaneously aborted at 25 weeks of gestation. The remaining live fetus and the second demised fetus were delivered by cesarean section 9 weeks later because of the occurrence of preeclampsia. This case indicates that delayed interval delivery in triplets is possible and that preeclampsia can occur after intrauterine demise of two fetuses.

The value of Allen's test in harvesting a radial forearm flap: correlation of ex-vivo angiography and histopathological findings.

The radial forearm flap is one of the most commonly raised free flaps. In most cases an Allen's test is sufficient for preoperative assessment of the palmar arch, but an intact palmar arch does not imply that the radial artery is suitable for microvascular anastomosis. For a patient operated for oral squamous cell carcinoma, reconstruction was planned with a radial forearm flap. The flap had to be discarded because of advanced atherosclerosis in the presence of a negative Allen's test. The correlation of an ex-vivo angiography and the histopathologic findings was assessed. In cases of expected vascular disease, further examinations like color flow Doppler ultrasound are recommended to ensure sufficient perfusion of the radial artery.

Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction.

OBJECTIVES: To correlate levels of angiogenic growth factors with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). METHODS: In 16 women with pre-eclampsia and 15 women with isolated IUGR, pulsatility indices (PI) in the umbilical and uterine arteries were measured by Doppler ultrasonography. At delivery, maternal and fetal blood (umbilical vein and artery separately) was sampled and angiogenic growth factors measured by means of enzyme linked immunosorbent assay (ELISA). RESULTS: Umbilical artery PI was significantly higher in women with IUGR than in those with pre-eclampsia, whereas uterine artery PI was not statistically significantly different. Maternal soluble fms-like tyrosine kinase-1 (sFlt-1) levels were higher in women with pre-eclampsia than in those with IUGR (P < 0.0001). Umbilical vein basic fibroblast growth factor (bFGF) levels were lower in women with pre-eclampsia than in those with IUGR (P < 0.05). Placental growth factor (PlGF) levels in the umbilical vein were below the detection limit in nearly all samples of IUGR fetuses and lower than in those with pre-eclampsia (P < 0.001). Maternal PlGF levels were inversely correlated with PI values of both vessels. In the umbilical vein sFlt-1 was positively and soluble kinase insert domain receptor (sKDR) negatively correlated with umbilical artery PI. No correlation could be found in the serum of the umbilical artery for all growth factors and for vascular endothelial growth factor (VEGF) in all compartments. CONCLUSIONS: The correlations between maternal and fetal angiogenic growth factor serum levels and Doppler ultrasound indices of uterine and umbilical arteries in pre-eclampsia and IUGR reflect the severity of the disorders especially for the fetus. A combination of both measurements may be useful in future screening for early prediction of pregnancy complications. Published by John Wiley & Sons, Ltd.

Ruptured false abdominal aortic aneurysm during pregnancy: Caesarean delivery followed by aortic reconstruction.

We describe a case of a successfully treated ruptured abdominal aortic aneurysm during pregnancy. The importance of close clinical follow-up after any aortic reconstructions is highlighted.

New insights in hypertensive disorders of pregnancy.

Research reported during the past year has enhanced our understanding of conditions that lead to the complex changes that are observed in hypertensive disorders of pregnancy. An association between placental pathology and a multisystem disorder that is characterized by endothelial dysfunction which involves genetic and immunological investigations has been identified. On the basis of these findings, promising screening tools for early detection of pre-eclampsia were identified. No marked changes in anaesthetic approach to hypertensive disorders of pregnancy occurred during the period of review, apart from a reappraisal of spinal anaesthesia as a safe technique in caesarean section, even in patients with severe pre-eclampsia. A multidisciplinary approach to management and therapy is needed and the right balance must be sought between the needs of the mother and baby, both of which are jeopardized by the hypertensive disorders of pregnancy.

[The significance of lymph node status in papillary and follicular thyroid gland carcinoma for the nuclear medicine physician]. / Die Bedeutung des Lymphknotenstatus beim papillären und follikulären Schilddrüsenkarzinom für den Nuklearmediziner.

The impact of lymph node metastases on prognosis of differentiated thyroid cancer is discussed controversially. Therefore the data of 596 patients with papillary or follicular thyroid cancer are analysed retrospectively, which have been treated between 1980 and 1995 at the Clinic and Policlinic for Nuclear Medicine of the University of Würzburg. The influence of lymph node metastases on prognosis with respect to survival is analysed with the univariate Kaplan-Meier-method and with the multivariate discriminant analysis. In addition, the influence of the prognostic factor "lymph node involvement" on distant metastases is analysed by a stratified comparison and an univariate test. In papillary thyroid cancer, the 15 year-survival-rate for stage pN1 is significantly lower (p < 0.001) with 88.7% as compared to stage pN0 (99.4%). In patients with follicular thyroid cancer this difference is even more pronounced (64.7% versus 97.2%, p < 0.001). However, the multivariate discriminant analysis shows that the only prognostic factors are tumour stage and distant metastases, and--in papillary thyroid cancer--patient's age. So lymph node metastases are not an independent prognostic factor concerning survival. However, lymph node metastases have a prognostic unfavourable influence with respect to distant metastases especially in papillary thyroid cancer stage pT4 (distant metastases in patients with negative lymph nodes 0% and in patients with positive lymph nodes 35.3% [p < 0.001]).

[Incidence of familial non-medullary thyroid carcinoma in the patient register of the Clinic and Polyclinic of Nuclear Medicine, University of Würzburg]. / Häufigkeit des familiären nicht-medullären Schilddrüsenkarzinoms im Krankengut der Klinik und Poliklinik für Nuklearmedizin der Universität Würzburg.

AIM: In this study the incidence rate of familial non-medullary thyroid carcinoma was investigated in the first and second grade relatives of patients registered at the Clinic and Polyclinic for Nuclear Medicine, University of Würzburg. PATIENTS AND METHODS: In this study 596 patients with differentiated thyroid carcinoma were enclosed, who were treated between 01.01.81 and 31.12.95. The data concerning a familial occurrence were studied by a retrospective survey-based analysis. These data were compared to a literature analysis for familial non-medullary thyroid carcinoma. RESULTS: 14 patients of the 596 patients treated showed a familial occurrence (2.3%). All these patients suffered from papillary thyroid carcinoma. According to the prognostic factors (tumor state, lymph node involvement, metastatic disease) no differences could be evaluated in the different groups (sporadic versus familial non-medullary thyroid disease). CONCLUSION: A familial occurrence of differentiated thyroid carcinomas is not frequently observed, but should be considered due to further genetic diseases.

Successful treatment of severe myocardial failure after postpartum haemorrhage with the use of an intra-aortic balloon pump.

We report a 29-year-old primigravid who developed cardiac failure following postpartum haemorrhage unresponsive to volume resuscitation and therapy with catecholamines and phosphodiesterase-inhibitors. Transoesophageal echocardiography (TEE) demonstrated left atrial and ventricular dilatation and global left ventricular hypokinesis. No elevation of serum MB-isoenzyme fraction was detected and other organ functions remained stable. Although emergency cardiac transplantation was considered in the presented patient, the institution of intra-aortic counterpulsation was decided on as a first treatment option. Intra-aortic balloon counter-pulsation rapidly improved cardiac function and led to weaning from pharmacological cardiac support within a few days. Mechanical circulatory assist devices can be life-saving in postpartum-haemorrhage-associated cardiac failure.

Pre-eclampsia: a disorder of placental mitochondria?

Pre-eclampsia is a common, pregnancy-induced, multisystem disease leading to severe complications in the mother and foetus. The aetiology of pre-eclampsia remains a mystery, but a growing body of evidence suggests that a mitochondrial defect might cause the impairement of differentiation and invasion of the trophoblast that leads to this disorder. This hypothesis is the topic of ongoing studies that, if confirmed, would be highly relevant to preventative strategies for this disease.

[Prediction of preeclampsia:new hypotheses, new approaches]. / [Prädiktion der Präeklampsie: neue Hypothesen, neue Ansätze]

Preeclampsia is a multisystem disorder affecting 5.8% of primigravidas. It is a progressive disease with a very variable mode of presentation and rate of progression. Of all the features of the syndrome, hypertension and pregnancy-induced proteinuria are the classic clinical manifestations. This disease causes severe complications of the mother and the fetus. Neither are factors available for prediction, nor are there strategies for prevention and therapy of this disease. The accumulated evidence strongly suggests that failure or incomplete trophoblastic invasion (end of first, beginning of second trimester) of the spiral arteries, resulting in narrowed spiral arteries and subsequent endothelial damage, is responsible for the occurrence of this disease (third trimester). The reason for trophoblastic failure is not known. After clinical symptoms have occurred, only symptomatic therapeutic options are available. In this paper, we discuss potential ways to find specific and sensitive predictive parameters according to the current knowledge of the pathophysiology of this pregnancy-induced severe disorder.

Activity of retinoic acid receptor-gamma selectively binding retinoids alone and in combination with interferon-gamma in breast cancer cell lines.

Retinoids modulate several cell functions and especially inhibit the growth of a wide variety of cells including breast cancer. Retinoic acid receptor-gamma (RAR-gamma) has been shown to mediate the antiproliferative activity of retinoids. To further test this hypothesis we examined the effects of different RAR-gamma selectively binding retinoids (CD2325, CD2247, CD666 and CD437) on breast cancer cell lines. With exception of CD2247, all retinoids inhibited proliferation of MCF-7, SKBR-3, T47D and ZR-75-1 breast cancer cell lines, similar to the natural compound all-trans retinoic acid (ATRA). In addition, all 4 compounds were able to act synergistically with interferon-gamma (IFN-gamma) in all breast cancer cell lines including the retinoid-resistant BT-20 and 734-B lines. In functional transactivation assays we demonstrated that only in the MCF-7 cell line, TPA-mediated AP-1 activity was suppressed only by ATRA and CD2325, whereas in SKBR-3, another RA-sensitive breast cancer cell line, it was not. The synergistic antiproliferative activity involving retinoids and IFN-gamma could not be explained by an enhanced anti-AP-1 activity. No correlation was found between expression of RARs and cellular retinoic acid binding proteins (CRABPs) and antiproliferative effects of the retinoids. RAR-gamma selectively binding retinoids are potent inhibitors of breast cancer cell proliferation, alone and in combination with IFN-gamma. For this reason and because of a possible low toxicity, as compared with retinoic acid, we speculate that these RAR-gamma selective binding retinoids might be of clinical importance.

Mallory-Weiss syndrome in a patient with hemophilia A and chronic liver disease.

Eighty percent of hemophiliacs exposed to plasma products are seropositive to hepatitis B and an even higher percentage are seropositive to hepatitis C. Post-transfusion hepatitis is followed by cirrhosis in up to 25% of the cases. In the wake of portal hypertension, the development of oesophageal varices entails the risk of life-threatening hemorrhage. We report on a patient with moderate hemophilia A (factor VIII:C 4-11%) who suffered from massive hematemesis, melaena and evolving shock after excessive alcohol ingestion. The diagnosis of Mallory-Weiss syndrome and the differential diagnosis of bleeding oesophageal varices as well as prognostic consequences are discussed.

Partial purification and characterization of rabbit-kidney brush-border (Ca2+ or Mg2+)-dependent adenosine triphosphatase.

The ATPase activity of rabbit-kidney brush border can be activated almost equally well by Ca2+ and Mg2+ and, therefore, should be called (Ca2+ or Mg2+)-ATPase. This enzyme was solubilized and enriched 14-fold by the following steps: pretreatment with papain removed 69% of alkaline phosphatase without attacking a significant portion of the ATPase activity. Addition of 1% cholate removed 65% of the protein but no ATPase activity. The combination of cholate (0.5%) and deoxycholate (0.4%) solubilized most of the ATPase activity and most of the remaining protein. A column chromatography of the extract on Sepharose CL-2B resulted in an 6.5-fold increase of specific ATPase activity. A precipitation by ammonium sulfate (40% saturation) produced an additional 1.9-fold increase. The yield of this partial purification was 16%. Towards the nucleotides UTP and GTP the enzyme showed an activity slightly higher, and towards ITP and CTP an activity slightly lower than that with ATP. ADP was split about half as fast as ATP. AMP was not accepted by the enzyme. Replacing MgCl2 by CaCl2 resulted in an ATPase activity of 92% of that with MgCl2. Using calcium- and magnesium-ATP as substrates, apparent Km values of 0.22 and 0.33 mM, respectively, were obtained. The gel electrophoresis revealed the enrichment of a protein with an apparent Mr of 95000 and also that of microvillus actin.