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The functional activity of von Willebrand factor (VWF) is most frequently measured by using the ristocetin cofactor assay (VWF:RCo). However, the method's drawbacks include unsatisfactory precision, sensitivity and availability of automated system applications. We have developed an alternative assay (INNOVANCE VWF Ac) that is based on the binding of VWF to recombinant glycoprotein Ib (GPIb). Two gain-of-function mutations were introduced into a GPIb fragment, allowing an assay format without ristocetin. Fully automated assay applications are available for the BCS/BCS XP systems and the Sysmex CS-2000i, Sysmex CA-7000, Sysmex CA-1500 and Sysmex CA-560 systems.The INNOVANCE VWF Ac assay measuring range extends from 4 to 600% VWF for all systems except the Sysmex CA-560 system. Within-device precision values were found to be between 2 and 7%. The limit of detection was below 2.2% VWF. In a study on the BCS XP system, a total number of 580 sample results yielded a correlation to the VWF:RCo assay of r equal to 0.99 (slope = 0.96). Very similar results were observed when von Willebrand disease samples type 1, 2A, 2B, 2M, 2N and 3 were investigated with the new assay and the VWF:RCo assay. The excellent performance data and comparability to VWF:RCo, together with the ease of use, led us to the conclusion that the ristocetin cofactor assay can be replaced by the new GPIb-binding assay to reliably diagnosing patients with von Willebrand disease.

Background: D-dimer testing is an integral part of the diagnostic algorithm in excluding patients with venous thromboembolism. In this study, we prospectively evaluated the Stratus DDMR D-dimer test in patients suspected of pulmonary embolism (PE) and deep vein thrombosis (DVT)., Methods: Patients suspected of venous thromboembolism were prospectively enrolled at four different clinical sites, with sodium citrate and lithium heparin plasma was tested using the DDMR D-dimer test on the Stratus CS analyzer., Results: 1,012 patients were enrolled for analysis, with 85/603 (14.1%) patients with PE and 80/443 (18.1%) with DVT, and four of the patients (0.4%) with PE and DVT. For the samples collected in 3.2% sodium citrate, the DDMR method had a sensitivity, specificity, and negative predictive value for VTE of 98.0%, 38.1%, and 99.1%, respectively. For the samples collected in lithium heparin, the DDMR method had a sensitivity, specificity, and negative predictive value (NPV) for VTE of 98.9%, 28.8%, and 99.4%, respectively. In PE, DDMR testing on citrate plasma had a sensitivity, specificity, and NPV of 98.8%, 39.5%, and 99.6%, respectively, while heparin samples had a sensitivity, specificity, and NPV for PE of 98.0%, 28.4%, and 99.1%, respectively. In DVT, citrate plasma had a sensitivity, specificity, and NPV for DVT of 97.5%, 32.0%, and 98.3%, respectively, while heparin samples had a sensitivity, specificity, and NPV for DVT of 100%, 27.8%, and 100%, respectively., Conclusion: The Stratus CS DDMR D-dimer can be used in those patients with non-high clinical pre-test probability for the exclusion of PE., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In vitro D-dimer stability in plasma is widely assumed, but has not yet been documented by systematic studies using samples covering a wide range of D-dimer. We investigated the short- and long-term stability of D-dimer in clinical citrated plasma samples with normal and pathological levels. The short-term stability was analysed by measuring D-dimer fresh, after storage of plasma for 4 hours at room temperature (RT) and after an additional 24 h storage at +2 to +8 degrees C (n=40). Long-term stability samples (n=40) were measured fresh and after storage for 19, 25 and 36 months at < or =-60 degrees C. The effect of repeated freezing was analysed by measuring samples (n=50) fresh and after four consecutive freeze-thaw cycles. D-dimer was measured on the BCS System using the INNOVANCE D-Dimer assay (Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany). D-dimer values at baseline ranged from 0.23-22.2 mg/l FEU. The mean percentage change after storage for 4 hours at RT and additional 24 hours at +2 to +8 degrees C was +3.8% and +2.7%, respectively. The mean percentage change after frozen storage for 19, 25 and 36 months at < or =-60 degrees C was -11.7%, -4.8% and -9.3%, respectively. The small decrease of D-dimer values after frozen storage was not time-dependent. Repeated freezing did not significantly alter D-dimer values (mean change < or =5%). The data demonstrate stability of D-dimer in plasma prior to freezing for up to 4 hours at RT and for up to 24 hours at +2 to +8 degrees C as well as in plasma stored for up to three years at < or =-60 degrees C.

The relationships of the microsoroid ferns were studied using a DNA sequence-based phylogenetic approach. Nucleotide sequences for up to four chloroplast genome regions were assembled for 107 samples from 87 species. Microsoroids s.l. include six lineages of which two are species rich. The results indicate that several genera are not monophyletic (e.g. Microsorum), several controversial genera are confirmed to be monophyletic (e.g. Leptochilus), and some genera new to science should be recognized (M. membranaceum clade). Unique insights were gained into the biogeographic history of this highly diverse epiphytic vascular plant lineage that is widespread in continental Asia to Australasia. Evidence was found for splits into lineages diversifying in parallel in continental Asia and Malesia. No evidence was recovered for an African radiation because all African microsoroid species either also are found in Asia or have sister species in continental Asia. In contrast, evidence for independent radiations were discovered for the Australasian region.

Objective: Acute myocardial rejection is a cell-mediated process characterized by increased leukocyte recruitment into the graft myocardial tissue. Transcription factors like STAT-1 and AP-1 are critically involved in this process by regulating vascular adhesion molecule expression. The aim of our study was to investigate the effect of decoy oligodeoxynucleotide (dODN) treatment targeting transcription factors AP-1 and STAT-1 on acute cardiac allograft rejection in a rat transplant model., Methods: Wistar-Furth (WF) cardiac allografts were transplanted into Lewis (LEW) rats after perfusion with STAT-1 or AP-1 dODN solution (5 micromol/l), buffer or the corresponding mutant control ODNs. Grafts were harvested and processed for histologic and immunohistochemical evaluation., Results: As demonstrated by fluorescence dye-labelled dODN, exposure of the grafts to the dODNs during 45 min of warm ischemia resulted in a dominant uptake of naked DNA by the graft endothelium. Treatment with AP-1 and STAT-1 dODNs, but not with vehicle or the control dODNs, significantly prolonged cardiac allograft survival by approximately 40% from 5.6+/-0.5 days to 7.8+/-1.3 days and 7.4+/-0.5 days, respectively (mean+/-S.D., p<0.01, n=5 in each group). Immunohistochemical examination on days 1, 3 and 6 revealed a marked reduction of infiltrating leukocytes (AP-1 dODN: 85%, STAT-1 dODN: 50%), namely T-cells, in the dODN-perfused grafts at day 3 post transplantation. In addition, as demonstrated by immunohistochemical analysis, endothelial expression of ICAM-1 and VCAM-1 was found to be markedly reduced in dODN-treated grafts., Conclusion: Both AP-1 and STAT-1 dODN treatments suppress graft endothelial adhesion molecule expression, reduce graft infiltration and in turn significantly delay acute rejection. The utilization of dODNs in the cardioplegic solution might be a novel strategy to protect transplanted organs from early damage during transplantation, to preserve organ function and bridge the critical phase after transplantation when standard immunosuppression is not yet completely effective.

Statins have been linked to a wide range of vascular benefits, many of them are likely to be due to attenuation of chronic vascular inflammation. Nuclear factor kappaB (NF-kappaB) is one of the key regulators of transcription of a variety of genes involved in immune and inflammatory responses. Therefore, we investigated the effect of statins on TNF-alpha-induced NF-kappaB signaling in human endothelial cells (EC). ECs were pre-incubated for 16 h with cerivastatin (10(-9) to 10(-7) M) or vehicle in the presence or absence of mevalonate, followed by stimulation with 20 ng/ml TNF-alpha. Statin-treatment prevented TNF-alpha-induced NF-kappaB binding activity, nuclear translocation of the NF-kappaB p65 subunit, as well as NF-kappaB controlled tissue factor (TF) gene transcription in cultured EC. IkappaBalpha phosphorylation and IkappaBalpha degradation, however, still occurred in statin-treated cells. TNF-alpha also activated phosphatidylinositol (PI)3-kinase, as reflected by phosphorylation of Akt. Statin treatment of cells abrogated TNF-alpha-induced Akt phosphorylation and p65 nuclear translocation. As observed with statins, inhibition of PI3-kinase activity by Ly294002 also blocked TNF-alpha-induced p65 translocation, but did not prevent IkappaBalpha phosphorylation nor IkappaBalpha degradation. These studies demonstrate that TNF-alpha-induced NF-kappaB activation is abrogated by statin treatment in HUVEC independently of the classical IKK-pathway but via inhibition of PI3-kinase/Akt signaling.

Factor VIIa/tissue factor (FVIIa/TF) interaction has been reported to induce intracellular signalling in cells constitutively expressing TF, independently of downstream activation of the coagulation cascade. It is unknown, however, whether binding of FVII to its cofactor TF alters the gene expression profile in cells which inducible express TF under inflammatory conditions. To address this issue, gene expression patterns in cultured LPS-stimulated monocyte-derived macrophages with or without exposure to FVIIa were compared by cDNA macro-array analysis. Of the 1176 genes examined on the array, a small set of six genes (IL-6, IL-8,TNF-a, GRO-beta alpha-thymosin, cathepsin H) were consistently up-regulated and one gene suppressed (alpha-antitrypsin) in response to FVIIa in activated monocyte-derived macrophages. Among the seven genes identified by array analysis, five genes were finally confirmed by real-time RT-PCR. Interestingly, all of these genes differentially regulated in response to FVIIa (GRO-beta, IL-6, IL-8, TNF-alpha and alpha-antitrypsin) are critical in inflammation. The changes in gene expression were reflected by corresponding changes in the protein concentrations of IL-6 and IL-8 as demonstrated by ELISA. Active site-inhibited FVIIa had no effect on gene expression indicating that FVIIa-induced gene alteration is dependent on the proteolytic activity of FVIIa. The FVIIa-induced alterations in gene expression were found to be TF-dependent but independent of downstream coagulation proteins like thrombin and FXa. In summary, this study demonstrates that binding of FVIIa to its cofactor TF enhances restricted pro-inflammatory genes in activated monocyte-derived macrophages. By up-regulation of chemokines critical for leukocyte recruitment, FVIIa/TF interaction on activated monocyte-derived macrophages could be relevant to prepare monocytes/macrophages for extravasation and may represent a novel amplification loop of leukocyte recruitment.

Objective: Microvascular thrombosis is a common feature of acute inflammatory lung injury, as occurs in sepsis and acute respiratory distress syndrome, but the underlying pathomechanisms are presently not fully understood., Design: Experimental., Setting: University laboratory., Subjects: Lung endothelial cells., Interventions: We characterized the expression of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) as well as plasminogen activator inhibitor (PAI)-1 and PAI-2 in human endothelial cells (EC) from the microvascular pulmonary circulation (HMVEC-L) and compared it with that of EC from pulmonary artery (HPAEC) and umbilical vein (HUVEC) under baseline conditions and upon stimulation with either tumor necrosis factor-alpha or lipopolysaccharide., Measurements and Main Results: Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were employed for quantification of messenger RNA and protein concentrations. Under baseline conditions, comparable PAI-1 expression was noted in all EC. HPAEC were characterized by significantly higher baseline expression of t-PA and PAI-2 compared with HUVEC and HMVEC-L. In contrast, u-PA messenger RNA concentrations were found to be significantly higher in nonstimulated HMVEC-L compared with HUVEC and HPAEC. In all EC, stimulation with tumor necrosis factor-alpha and lipopolysaccharide increased the expression of PAI-1, PAI-2, and u-PA and decreased t-PA expression. The changes in messenger RNA content were reflected by corresponding changes in the protein concentrations., Conclusions: High baseline u-PA expression is a prominent feature of human lung microvascular EC, whereas pulmonary artery EC are characterized by high t-PA concentrations. Microbial and inflammatory challenge provokes up-regulation of PAI-1 and PAI-2 and down-regulation of t-PA in both macro- and microvascular pulmonary EC, which may favor local fibrin deposition.

Objective: The benefits of statin therapy in cardiovascular medicine are ascribed to its lipid-lowering effect as well as its anti-inflammatory properties. Whereas all statins have been shown to reduce cholesterol plasma levels, their effect on inflammatory markers has been inconsistent. Here, we show that statins differ markedly in their effectiveness in preventing activation of NF-kappaB, a transcription factor involved in the activation of immediately early genes during inflammation., Methods: Six statins (atorvastatin (Atv), cerivastatin (Cer), fluvastatin (Flu), lovastatin (Lov), pravastatin (Pra), simvastatin (Sim)) were tested for their ability to influence the induction of NF-kappaB in human monocytes (Mo) during inflammation. Mo isolated from healthy blood donors were incubated with LPS (10 microg/ml) in the presence and absence of statin (0.001-5 microM). NF-kappaB binding activity (EMSA), degradation and phosphorylation of the inhibitor protein IkappaB-alpha (Western blotting), tissue factor (TF) mRNA (rtPCR), and TF activity (clotting assay) were analyzed., Results: All statins inhibited LPS-induced NF-kappaB binding activity in Mo in a dose-dependent manner. The inhibitory effect was due to reduced phosphorylation and degradation of the NF-kappaB inhibitor protein IkappaB, and was primarily dependent on the absence of mevalonate. Whilst this effect appeared with all statins, there were marked differences in the degree of inhibition between the statins. Cer (45 +/- 9% inhibition, p < 0.05) was 9-fold more effective in reducing NF-kappaB activation than Flu (5 +/- 10% inhibition). The differences in the potency of statins (Cer > Atv > Sim > Pra > Lov > Flu) were also reflected at the transcriptional level and the protein level of NF-kappaB controlled tissue factor expression., Conclusions: The finding that statins differ in their potency in interfering with the activation of NF-kappaB signaling in human monocytes further supports the hypothesis that some statins inhibit the inflammatory response more than others.

Background: Stem cells, having the property of self renewal, offer the promise of lifelong repair of damaged tissue. However, somatic tissue-committed primary stem cells are rare and difficult to expand in vitro. Genetically modified stem-like cells with the ability to expand conditionally provide a valuable tool with which to study stem cell biology, especially the cellular events of proliferation and differentiation. In addition, stem cells may be appropriate candidates for therapeutic applications., Methods: Double transgenic mice possesing SV40 T antigen (Tag) under the control of the reverse tetracycline-transactivator (rtTA) were used to establish cell lines. One brain cell line was partially characterized by DNA sequencing, morphology, antigen expression using flow cytometry, confocal microscopy, and electrophysiology using the patch clamp technique. Cell cycle analysis was performed using propidium iodide staining; cell viability and H3-thymidine incorporation assays. The ability of this cell line to differentiate was assessed by confocal microscopy following co-culture with stem cells secreting cytokines., Results: We report here the establishment and partial characterization of a cell line derived from the brain tissue of rtTA-SV40 Tag transgenic mice. Analysis of the morphology and antigen markers has shown that this cell line mimics some aspects of primary glial precursors. The results of electrophysiology are consistent with this and suggest that the cell line is derived from O2A glial precursor cells. Cell cycle progression of this cell line is doxycycline-dependent. In the absence of doxycycline, cells become apoptotic. Differentiation into mature type 2 astrocytes and (precursor) oligodendrocytes can be induced upon withdrawal of doxycycline and addition of epithelial stem cells secreting cytokine, such as hIL3 (human Interleukine 3) or hIL6 to the culture. In contrast, co-culturing with hCNTF (human Ciliary NeuroTrophic Factor)-secreting epithelial stem cells did not induce them to mature into progeny cell types., Conclusion: The differentiation of this O2A glial precursor line does not occur automatically in culture. Additional external help is required from the cell-based delivery of appropriate transgenic cytokines. Withdrawal of doxycycline from the culture medium removes the proliferation signals and induces a fatal outcome.

The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident alveolar macrophages (rAMs). Using the intravenous injected fluorescent dye PKH26, which accumulated in rAMs without labeling blood leukocytes, we developed a technique that permits the identification, isolation, and functional analysis of monocytes recruited into lung alveoli of mice. Alveolar deposition of murine JE, the homologue of human monocyte chemoattractant protein (MCP)-1 (JE/MCP-1), in mice provoked an alveolar influx of monocytes that were recovered by bronchoalveolar lavage and separated from PKH26-stained rAMs by flow cytometry. Alveolar recruited monocytes showed a blood monocytic phenotype as assessed by cell surface expression of F4/80, CD11a, CD11b, CD18, CD49d, and CD62L. In contrast, CD14 was markedly upregulated on alveolar recruited monocytes together with increased tumor necrosis factor-alpha message, discriminating this monocyte population from peripheral blood monocytes and rAMs. Thus monocytes recruited into the alveolar air space of mice in response to JE/MCP-1 keep phenotypic features of blood monocytes but upregulate CD14 and are "primed" for enhanced responsiveness to endotoxin with increased cytokine expression.

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.

Antisense oligodeoxynucleotides (ODN) have become a powerful tool to achieve specific gene inhibition in various cell types, including endothelial cells. The low spontaneous cellular uptake of ODN, however, usually requires the employment of transmembrane carriers, such as the positively charged liposome formulation dioleyloxypropyltrimethyl ammonium chloride/dioleoylphosphatidylethanolamine (DOTMA/DOPE). In the present study, we observed that DOTMA/DOPE per se interferes with the inducible expression of vascular cell adhesion molecule-1 (VCAM-1) in human pulmonary artery endothelial cells (HPAEC). By RT-PCR analysis, a dose-dependent suppression of VCAM-1 but not intracellular adhesion molecule-1 (ICAM-1) mRNA levels in tumor necrosis factor-alpha (TNF-alpha)-challenged HPAEC pretreated with DOTMA/DOPE (5-20 microg/ml) was demonstrated. Correspondingly, a strong reduction of TNF-alpha-induced VCAM-1 but not ICAM-1 cell surface expression on HPAEC was observed. These DOTMA/DOPE-induced changes were not due to alterations in VCAM-1 mRNA stability, nor did DOTMA/DOPE inhibit TNF-alpha-induced NF-kappaB-like binding activity in nuclear extracts of HPAEC, as analyzed by electrophoretic mobility shift assay. In contrast, DOTMA/DOPE effected a dose-dependent increase in AP-1-like binding activity in nuclear extracts of HPAEC, as analyzed by Western blotting and EMSA. We conclude that positively charged liposome preparations may per se inhibit TNF-alpha-induced endothelial VCAM-1 expression, and this may be related to changes in AP-1 but not NF-kappaB-dependent transcriptional control. Notably, when used at concentrations below 5 microg/ml, DOTMA/DOPE may be employed for specific antisense-mediated downregulation of VCAM-1 in the absence of vehicle-related side effects on adhesion molecule transcription.

We report the first use of green fluorescent protein (GFP) for mutation detection. We have constructed a plasmid-based bacterial system whereby mutated cells fluoresce and non-mutated cells do not fluoresce. Fluorescence is monitored using a simple hand-help UV lamp; no additional cofactors or manipulations are necessary. To develop a reversion system, we introduced a +1 DNA frameshift mutation in the coding region of GFP and the resulting protein is not fluorescent in Escherichia coli. Treatment of bacteria containing the +1 frameshift vector with ICR-191 yields fluorescent colonies, indicating that reversion to the wild-type sequence has occurred. Site-directed mutagenesis was used to insert an additional cytosine into a native CCC sequence in the coding region of GFP in plasmid pBAD-GFPuv, expanding the sequence to CCCC. A dose-related increase in fluorescent colonies was observed when the bacteria were treated with ICR-191, an agent that induces primarily frameshift mutations. The highest dose of ICR-191 tested, 16 microg/ml, produced a mutant fraction of 16 x 10(-5) and 8.8 x 10(-5) in duplicate experiments. The reversion system did not respond to MNNG, an agent that produces mainly single-base substitutions. To develop a forward system, we used GFP under the control of the arabinose PBAD promoter; in the absence of arabinose, GFP expression is repressed and no fluorescent colonies are observed. When cells were treated with MNNG or ENNG, a dose-dependent increase in fluorescent colonies was observed, indicating that mutations had occurred in the arabinose control region that de-repressed the promoter. Treating bacteria with 100 microg/ml MNNG induced mutant fractions as high as 82 x 10(-5) and 40 x 10-5 in duplicate experiments. Treating bacteria with 150 microg/ml ENNG induced a mutant fraction of 2.1 x 10(-5) in a single experiment., (Copyright 1998 Elsevier Science B.V.)

After ingestion of 2000 mg tiaprofenic acid (Surgam), a 14-year-old girl was admitted to the clinic. The ingested dose was tolerated without signs of systemic intoxication. Tiaprofenic acid, its metabolites, and products of chemical decomposition were identified by gas chromatography/mass spectrometry in the urine sample of the patient. Additionally, a previously unknown decomposition product of a metabolite was detected. For quantitation of the drug in plasma, a rapid and sensitive high-performance liquid chromatography assay was established.

42 patients aged 75 /+- 12,5 years with orthostatic dysregulation and partly with hypotension were treated with the new combination of 20 mg etilefrine and 2 mg dihydroergotamine (Dihydergot plus) t.i.d. for 2 months in a single blind controlled study. The efficacy of Dihydergot plus was proved by a standardized orthostatic test and evaluation of subjective orthostatic symptoms. The resting blood pressure of the patients with hypotension increased from 106/63 mmHg to 114/67 mmHg. After changing from supine to standing position all patients showed a stabilized haemodynamic reaction. The fall of systolic and increase of diastolic blood pressure as well as the increase of heart rate were reduced and the subjective symptoms improved. There were also an improvement of the patients mood and activities of daily living. Dihydergot plus was well accepted by all patients during the treatment period.

Review of 1400 epidural anaesthesias during labour and delivery. The single shot method resulted in complete analgesia in 83.8% of the cases. There were 2.8% failures. With longer duration of albour 13.4% of the epidural anaesthesias had to be repeated. Epidural anaesthesia was tolerated well by the women in labour. Hypotension occurred in 21.6% of the cases and was corrected by intravenous infusion and positioning of the patient on the side. No adverse effects on the fetus were found. The duration of labour and delivery was not prolonged. The caesarean section rate was not increased by epidural anaesthesia. Because of the more difficult bearing down reflux during the second stage of labour, the incidence of vacuum extractions was increased by 1 to 3%. The incidence of forceps deliveries remained stable. There was no significant increase of abnormal vertex positions. Postpartum headaches because of decompression by loss of cerebrospinal fluid was seen in 2.2% of the cases. The headaches subsided on complete bed rest. One case of total spinal anesthesia with respiratory arrest is reported which necessitated immediate intubation. Another dangerous complication was noted in a Para 2 who suffered a complete uterine rupture below the level of the epidural anesthesia without any clinical signs and symptoms. Therefore continual internal fetal monitoring is considered to be essential in all cases with epidural anaesthesias. Previous caesarean sections or uterine operations are no contra-indications to epidural anaesthesia.

As a presupposition for estimating the mean tissue dose from intravascularly injected Thorotrast results of investigations on tissue distribution and steady state activity ratios of 232Th and daughters in Thorotrast patients were compiled and are presented as "best estimates". Special emphasis has been given to the non-uniformity of Thorotrast distribution on the organ and cellular level on the basis of results from animal experiments. Moreover, the variation widths of the mean tissue doses were calculated from the individual standard errors of the mean Thorotrast tissue distribution and activity ratios. According to the results of Thorotrast tissue distribution analyses about 97% of intravascularly injected colloidal ThO2 are retained by the organs of the reticulo-endothelial-system (RES) of the average Thorotrast patient (liver: 59%; spleen: 29%; bone marrow: 9%). Only 0.7 and 0.1% are distributed within the lungs and the kidneys, respectively. The fractional retention of 232Th in the marrow-free skeleton proved to be 2% on the average. Considering in addition the results on the steady state activity ratios between 232Th and its daughters and self-absorption of alpha-energy in Thorotrast agglomerates the mean annual tissue doses to the liver, spleen, red bone marrow, lungs (respiratory zone), and cells on bone surface, e.g., from 30 ml intravascularly injected Thorotrast are about 30 (10-70), 80 (30-200), 10 (4-27), 4.5 (1.8-11.3), and 15 (6-38) rad. The variation widths of the mean tissue doses given in brackets are based upon an average individual standard error of the mean Thorotrast tissue distribution and activity ratios of 150%. The data on mean tissue doses, however, do not include variations of the dose due to macroscopic inhomogeneities of Thorotrast distribution on the organ level, which in the liver may go up to a factor of 50. Contrary to the mean tissue dose the local annual dose, i.e., the dose to cells adjacent to the surface of 0.1-50 micron Thorotrast aggregates is between 40 and 40,000 rad.

Report on the rare event of a complete ischemia of the right arm immediately postpartum. The infant was delivered by Caesarean Section because of cervical dystocia and fetal distress. The umbilical cord was twice around the neck and the ischemia of the right arm appeared to be due to spasm of the axillary artery. Treatment for shock and infusion of vasodilating drugs (Complamin) relieved the arterial spasm.

The results of our investigations in the Federal Republic of Germany on the indoor and outdoor exposure to natural radiation from gamma rays and radon and thoron daughters are presented. Indoor the median Rn-222 concentration was approximately four times higher than outdoors. A correlation analysis of the data obtained showed that indoors the equilibrium factor F is almost independent of ventilation, Rn-222 concentration and other parameters. The mean equilibrium factor was measured to be F = 0.3 in dwellings and approximately F = 0.4 outdoors. The results of our investigations on diffusion coefficients and exhalation rates showed, that the activity concentration in dwellings and in cellars can generally be explained by the radon exhalation from the building materials. Only in areas of high radon concentrations, the exhalation from the soil was a decisive factor. The mean effective dose equivalent by residence in dwellings amounted to 0.2 - 0.8 mSv/a for Rn-222 daughters and approximately 0.1 mSv/a for Rn-220 daughters. A relationship has been derived which permits the calculation of the expected average radiation exposure in dwellings by gamma radiation and by radon inhalation as function of the radionuclide concentration in building materials.

This paper discusses different possibilities of deriving reference values for the natural radioactivity concentrations in building materials to estimate possible additional radiation exposure for the population. Based on comprehensive experimental and theoretical investigations the consequences of the resulting hypothetical reference activity concentrations in building materials, applying different dose limits, were examined. The calculation of the activity concentration standards was performed for standard conditions obtained by earlier studies on exhalation of Radon-222 and Radon-220 from building materials.

Measurements of the concentrations of 222Rn, its short-lived decay products and of 212Pb - 212Bi were performed in 150 dwellings and in the open air in the Federal Republic of Germany. The concentrations of 222Rn was measured by electrostatic deposition of 218Po. The concentration of the short-lived decay products were measured by air sampling and alpha-spectroscopy. It was found that inside dwellings the average potential alpha-energy concentration of the short-lived daughters is about three times higher than in the open air. The total potential alpha-energy concentration indoors amounts to 2.6 . 10(-3) Working Level (W.L.). Direct measurements of the equilibrium factor inside dwellings gave a mean value of 0.3. A strong dependence of the potential alpha energy concentration on the ventilation rate in dwellings has been observed. These ventilation effects exceed the effects caused by differences in the activity concentrations due to different building materials. The dose calculation results in an average dose to the whole lung due to the inhalation of short-lived radon daughters of about 0.05-0.2 m/Gy/a. An estimate of risk - based on the risk factors for uranium miners - shows an average lifetime risk of about 6 . 10(-4) for the incidence of lung cancer caused by inhalation of radon and thoron daughters in dwellings in the Federal Republic of Germany.

The incidental finding in 1984 of Strongyloides stercoralis larvae in a resident of a chronic care institution who had a vague clinical illness prompted a review of the other residents. Five other cases were identified after exhaustive laboratory investigations. Fecal-oral spread was considered the most likely manner of the spread of infection. The possibility of endemic strongyloidiasis in institutions should be considered, even in temperate climates, when there is unexplained persistent illness or high eosinophil counts. Serologic testing is a useful adjunct to fecal examination in such situations.

The concentration of 226Ra in more than 1000 human bone samples, still born infants, fetuses, blood, mixed diet, drinking water and mineral water has been measured. An age dependence of 226Ra concentration in human bone could be demonstrated. Up to an age of 20 yr two maxima of 226Ra concentration in bone occur, coinciding with the increased velocity of skeleton growth. Normally, the main source for uptake of radium by man is food. In Germany the transfer factor from diet to bone is about 0.098. Compared with data from literature for other countries, mainly the U.S.A., the German value is higher by a factor of about 1.5. This difference may be due to the lower calcium uptake in Germany which leads to higher resorption of radium. Two methods for measuring natural radium concentrations is biological material and water samples are briefly described: a gamma-gamma-coincidence method for indirect measurement of 226Ra via the short lived 214Bi(RaC) and an alpha-spectrometric method for direct measurement of the alpha-emission of 226Ra.

Depressed outpatients (n = 107, age 26-75 years) were treated with either a 50 mg single morning dose of diclofensine (n = 54) or 75-100 mg nomifensine given in two divided doses (n = 53) over a period of three weeks. The baseline mean values of the Depression Status Inventory (DSI index) of Zung corresponded to those of a mildly depressed population, as given by Zung. At the end of the treatment the mean DSI and Anxiety Status Inventory (ASI-index) values of both groups dropped to the levels of a normal population. The side-effect profile of the two treatments was similar. There were no side-effects indicating sedation. Adverse effects of the anticholinergic type were rare. It can be concluded that both diclofensine and nomifensine are beneficial for the treatment of depressed outpatients and that in a dose relation of 2:3 (diclofensine:nomifensine) they lead to a similar improvement in depressive outpatients.

Between 1966 and 1974, 90% of 581 single breech presentations were delivered vaginally. The incidence of Caesarean Section was 9.5%. The overall perinatal mortality was 14%. After elimination of premature deliveries under 1000 grams, stillbirth prior to labour and non-viable anomalies, the perinatal mortality was 5.6%. The perinatal mortality in infants over 2500 grams was 0.69%.

Our first long-term animal experiment made use of 1920 female Wistar rats divided into 20 groups of 96 animals each. These were injected at 12 weeks of age with different volumes and different dosages of Thorotrast which was enriched with 230Th to enhance the alpha-energy emission rate. The purpose of the study was to evaluate the effects due to the colloidal substance and the radiation. In the main experiment, 12 groups of rats were injected intravenously with 60, 120 and 300 microliters Thorotrast. 230Th was added to some Thorotrast preparations so that the total alpha-energy emission rate varied by factors of 1, 2, 5 and 10 relative to normal Thorotrast. Two groups were injected with 12 and 60 microliters of 50-fold enriched Thorotrast. One group was given 600 microliters of normal Thorotrast. In addition, we had 5 control groups, 1 NaCl and 4 Dextrin groups. The latter were injected with 60, 120, 300 or 600 microliters of Dextrin. The first animals died 8 months after injection, and the last 11 animals were killed 41 months after starting the experiment. The number of animals that developed a hepatic or splenic tumor increased by a factor of 10 in the highest dose-rate groups compared to controls. Our results demonstrated a linear correlation between the dose-rate and the number of primary hepatic and splenic tumors. It appeared that the volume of injected Thorotrast, by itself, had little influence on the number of tumors. However, at a constant dose-rate of 10, a 50-fold increase in the volume of Thorotrast (12-600 microliters) decreased the minimal tumor-appearance time by about 250 days.

Reported in this paper is a critical analysis of perinatal mortality which dropped from three to 1.1 per cent, between 1966 and 1978. The number of caesarean sections went up from two to 8.25 per cent, over the same period of time, with all indications having been foetal. No direct relationship was evident with intensive heart rate control of the foetus. The number of low-weight infants, that is less than 2,500 g in birth-weight, did not decrease in the period under review, in spite of tocolysis and cerclage. Perinatal mortality was conspicuous particularly for decline in intra-uterine and postpartum foetal deaths. There was a steady drop in uncorrected perinatal mortality, while the corrected figure remained constant over the past four years, though the rate of caesarean sections had been rising continuously. Therefore, perinatal mortality cannot be further reduced by continued increase in the number of caesarean sections. However, less low-weight births as well as improved monitoring and care of pregnant women will be answered to the problem. --Maternal mortality over the entire period under review amounted to 0.39 per thousand, against a total of 17 871 deliveries.

Report on 10,050 gynaecological operations from 1966 to 1978. The operation rate rose from 691 cases in 1966 to 917 cases in 1978. Whereas the rate of vaginal operations remained approximately the same at about 300 cases per year, the rising operative rate consisted of abdominal operations. Contributing were the increasing rate of Caesarean sections, which rose from 2% in 1966, to 8,25% in 1978, and the introduction of diagnostic and therapeutic laparoscopy especially laparoscopic tubal sterilizations. Liberalization of the indications for operation by Kindermann did not occur in our department. A real escalation in the rate of operation did not occur. We do not consider this required nor clinically justifiable. The same is true for our minor gynaecological procedures which did not show significant increases in their rates despite the relative increase in cerclages, conizations and therapeutic abortions. The total mortality was 0.15% and therefore low despite the relatively high incidence of geriatric surgery (9.3%).

Retrospective investigations on 849 low birth weight infants between 1,001 and 2,500 gm born from 1966 to 1982 were done. The infants were divided into three groups with birth weights from 1,001 to 1,500 gm, from 1,501 to 2,000 gm, and 2,001 to 2,500 gm. The results of spontaneous delivery, delivery with manual assistance and caesarian section were compared. In the weight group 1,001 to 1,500 gm (14%), the perinatal mortality was 32%. In caesarian sections, the perinatal mortality was 19%, in spontaneous deliveries the perinatal mortality was 32% and in delivery with manual assistance the perinatal mortality was 45%. In the second weight group of 1,501 to 2,000 gm the perinatal mortality was 14.8%. Spontaneous delivery had a perinatal mortality of 16%, manual assistance a perinatal mortality of 14% and caesarian section a perinatal mortality of 10%. In both birth weight groups of 1,001 to 1,500 gm and 1,001 to 2,000 gm, the infants born by caesarian section had a significantly improved prognosis. Therefore, we recommend caesarian section in these weight groups for all breech presentations. In vertex presentations, caesarian sections are indicated when additional risk factors especially prolonged labour are apparent. In the third weight group between 2,001 and 2,500 gm the overall perinatal mortality was 4.9%. The spontaneously delivered infants have a mortality of 4.1%. Manual assistance was associated with a perinatal mortality of 5.9%. Caesarian section had a perinatal mortality of 11%.(ABSTRACT TRUNCATED AT 250 WORDS)

In 581 cases of breech presentation during the years 1966--1974 in 90% of cases delivery was possible vaginally. We prefered the method of Lövset und Veit-Smellie. Casarian section was performed in 9,5% of the cases, the mortality of the newborns was 14%. Without the premature newborns (less than 1000 gr), the cases of intrauterine deaths and not viable children with malformations the mortality was 5,6%. The perinatal mortality of the children or more than 2500 gr was merely 0,69%. The general enlargement of the indication for Caesarian section is not recommended.

A case of spontaneous perforation of a tension ulceration in procidentia in an 82 year old woman is reported. A similar case has not been reported in the literature. The extra-ordinary rarity of this observation justifies the publication of this case. The main etiologic factor is considered to be a local perfusion problem of the tissue due to arterial sclerosis of the terminal vessels of the area. The small bowel was replaced. The uterus was replaced. A vaginal packing with clauden and later local treatment of the vaginal ulcers resulted in spontaneous closure of the fistula, histology of the margin of the fistula showed inflammation only and no malignant change. Treatment was completed by a subtotal vaginal colpocleisis according to Labhardt.

At the Swiss Institute for Nuclear Research (SIN) cancer patients are irradiated with negatively charged pi mesons using a 60-beam medical pion generator, the Piotron. A low-pressure tissue-equivalent proportional counter was used to measure absorbed dose and microdosimetric spectra. A method was developed to allow discrimination of events from different beam components, i.e., beam contamination (electrons and muons), pions in flight, and stopping pions. Measurements were performed along the axis and at lateral distances off one of these identical pion beams. The marked changes of total microdosimetric spectra with depth in phantom detected in earlier measurements are mainly due to large variations in the dose contributions of the beam components and much less to changes in the shapes of the individual microdosimetric spectra. The single beam measurements were used to calculate three-dimensional distributions of absorbed dose and of dose mean lineal energy, yD, for dynamic patient irradiations. Within the whole target volume yD remains nearly constant when irradiated with all 60 beams, whereas considerable changes were found for irradiations with 31 beams coming from a semicircle. Both size and shape of target volumes influence yD, the maximum values ranging from 30 to 45 keV/micron.