Complex floral traits shape pollinator attraction to ornamental plants.

BACKGROUND AND AIMS: Ornamental flowering plant species are often used in managed greenspaces to attract and support pollinator populations. In natural systems, selection by pollinators is hypothesized to result in convergent multimodal floral phenotypes that are more attractive to specific pollinator taxa. In contrast, ornamental cultivars are bred via artificial selection by humans, and exhibit diverse and distinct phenotypes. Despite their prevalence in managed habitats, the influence of cultivar phenotypic variation on plant attractiveness to pollinator taxa is not well resolved. METHODS: We used a combination of field and behavioural assays to evaluate how variation in floral visual, chemical and nutritional traits impacted overall attractiveness and visitation by pollinator taxonomic groups and bee species to 25 cultivars of five herbaceous perennial ornamental plant genera. KEY RESULTS: Despite significant phenotypic variation, cultivars tended to attract a broad range of pollinator species. Nonetheless, at the level of insect order (bee, fly, butterfly, beetle), attraction was generally modulated by traits consistent with the pollination syndrome hypothesis. At the level of bee species, the relative influence of traits on visitation varied across plant genera, with some floral phenotypes leading to a broadening of the visitor community, and others leading to exclusion of visitation by certain bee species. CONCLUSIONS: Our results demonstrate how pollinator choice is mediated by complex multimodal floral signals. Importantly, the traits that had the greatest and most consistent effect on regulating pollinator attraction were those that are commonly selected for in cultivar development. Though variation among cultivars in floral traits may limit the pollinator community by excluding certain species, it may also encourage interactions with generalist taxa to support pollinator diversity in managed landscapes.

Bacteria Affect Plant-Mite Interactions Via Altered Scent Emissions.

Epiphytic bacteria have been shown to affect the composition of volatiles released by plants and as a consequence the behavior of other organisms towards the plant, such as herbivores and/or pathogens. In this study, we explored the effects of inoculation with three bacterial strains, namely Pseudomonas syringae, Pantoea ananatis, and Pseudomonas putida, on the composition of leaf volatile organic compounds (VOCs) emitted by bean plants (Phaseolus vulgaris L.). In addition, we examined responses of the two-spotted spider mite (Tetranychus urticae) to VOCs by measuring leaf damage and oviposition of female adults after bacterial inoculation. Colonized bean plants emitted different VOCs depending on the bacterial inoculum. The quantities of volatiles 1-undecanol and (Z)-3-hexen-1-ol significantly increased after P. syringae inoculation, while methyl salicylate and anisole increased in response to P. ananatis. T. urticae females preferred control plants over plants inoculated with P. syringae or P. putida in olfactometer assays, while no particular preference was recorded in the presence of P. ananatis. Furthermore, leaf damage caused by spider mites was 3-fold lower in plants inoculated with P. syringae than in control plants and plants inoculated with P. ananatis. Subsequently, the number of eggs laid on leaves inoculated with P. syringae was significantly lower than on those inoculated with P. ananatis or on the control ones. Moreover, a significantly higher number of spider mites selected methyl salicylate odor source over 1-undecanol, in a two-choice bioassay. The results demonstrate the bacterial involvement in plant-arthropod interactions and suggest further investigation on the potential use of bacteria as biocontrol agents in agriculture.

A systematic review on the long-term success of calcium phosphate plasma-spray-coated dental implants.

The objectives of the current review were (1) to systematically appraise, and (2) to evaluate long-term success data of calcium phosphate (CaP) plasma-spray-coated dental implants in clinical trials with at least 5 years of follow-up. To describe the long-term efficacy of functional implants, the outcome variables were (a) percentage annual complication rate (ACR) and (b) cumulative success rate (CSR), as presented in the selected articles. The electronic search yielded 645 titles. On the basis of the inclusion criteria, 8 studies were finally included. The percentage of implants in function after the first year was estimated to be 98.4 % in the maxilla and 99.2 % in the mandible. The estimates of the weighted mean ACR-percentage increased over the years up to 2.6 (SE 0.7) during the fifth year of function for the maxilla and to 9.4 (SE 8.4) for the mandible in the tenth year of function. After 10 years, the mean percentage of successful implants was estimated to be 71.1 % in the maxilla and 72.2 % in the mandible. The estimates seem to confirm the proposed, long-term progressive bone loss pattern of CaP-ceramic-coated dental implants. Within the limits of this meta-analytic approach to the literature, we conclude that: (1) published long-term success data for calcium phosphate plasma-spray-coated dental implants are limited, (2) comparison of the data is difficult due to differences in success criteria among the studies, and (3) long-term CSRs demonstrate very weak evidence for progressive complications around calcium phosphate plasma-spray-coated dental implants.

Bone reaction adjacent to microplasma-sprayed calcium phosphate-coated oral implants subjected to an occlusal load, an experimental study in the dog.

BACKGROUND: A new microplasma spraying equipment (MSE) to deposit calcium phosphate (CaP) ceramic coatings onto titanium substrates has been developed. With this system, it is possible to spray fine particles and to apply textured hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat power of the microplasma jet, overheating of the powder particles as well as excessive local overheating of the substrate are diminished. Furthermore, because of the small laminar plasma jet, it is possible to achieve high spray efficiency in the case of spraying for dental implants. Also, the low level of noise (25-50 dB) and hardly any dust makes it possible to operate MSE under conditions of normal workrooms. OBJECTIVE: The aim was to investigate, in a mandibular dog model, the effect of functional load on soft-tissue adaptation as well as crestal bone-level changes around titanium implants provided with newly developed microplasma-sprayed CaP coatings. MATERIAL AND METHODS: For histomorphometrical evaluation, 56 screw-type titanium implants were inserted into the mandibles of seven adult Beagle dogs. The implants were either acid etched without an additional coating, coated with a conventionally plasma-sprayed CaP ceramic (PS), coated with a microplasma-sprayed CaP ceramic (MPS) or with a microplasma-sprayed coating at only the apical part (aMPS). To assess the effect of occlusal loading, a split-mouth design was used. Six weeks after implantation, the implants in one half of the mandible of each dog were functionally loaded whereas the contra lateral implants served as control. One year after loading, the animals were sacrificed. Soft-tissue dimension as well as marginal bone level were histologically assessed. RESULTS: Histometric analysis of undecalcified histologic sections included the evaluation of the sulcus depth, the dimension of the junctional epithelium and the connective tissue as well as the first bone-to-implant contact. For MPS-surfaced implants, functional loading was associated with--compared with the non-loaded state--unchanged soft-tissue dimension. Furthermore, the soft-tissue dimension did not differ from the dimensions around non-coated, PS and aMPS implants. Moreover, the first bone-to-implant contact was not significantly altered by functional loading and comparable non-coated, PS and aMPS implants. CONCLUSION: Within the limits of the experiment, we conclude that, in comparison, functional loading does not affect the marginal soft-tissue response to MPS CaP-coated implants. However, in comparison, functional loading might affect marginal bone response to MPS CaP-coated implants.

Drought-induced reduction in flower size and abundance correlates with reduced flower visits by bumble bees.

Reduced water availability can cause physiological stress in plants that affects floral development leading to changes in floral morphology and traits that mediate interactions with pollinators. As pollinators can detect small changes in trait expressions, drought-induced changes in floral traits could affect pollinator visitations. However, the linkage between changes in floral traits and pollinator visitations under drought conditions is not well explored. We, therefore, tested whether drought-induced changes in floral morphology and abundance of flowers are linked to changes in pollinator visitations. We conducted flight cage experiments with a radio frequency identification system for automated visitation recordings with bumble bees (Bombus terrestris) and common charlock (Sinapis arvensis) as the model system. In total, we recorded interactions for 31 foraging bumble bees and 6569 flower visitations. We found that decreasing soil moisture content correlated with decreasing size of all measured morphological traits except stamen length and nectar tube width. The reductions in floral size, petal width and length, nectar tube depth and number of flowers resulted in decreasing visitation rates by bumble bees. These decreasing visitations under lower soil moisture availability might be explained by lower numbers of flowers and thus a reduced attractiveness and/or by increased difficulties experienced by bumble bees in handling smaller flowers. Whether these effects act additively or synergistically on pollinator behaviour and whether this leads to changes in pollen transfer and to different selectionp ressures require further investigation.

Bone-supportive behavior of microplasma-sprayed CaP-coated implants: mechanical and histological outcome in the goat.

BACKGROUND: New microplasma spray (MPS) equipment to deposit calcium phosphate (CaP) ceramic coatings onto titanium substrates has been developed. With this apparatus, it is possible to spray fine particles, as well as to apply textured hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat power of the microplasma jet, overheating of the powder particles as well as excessive local overheating of the substrate is reduced. Furthermore, because of the small laminar plasma jet, it is possible to achieve high spray efficiency in the case of spraying of dental implants. Additionally, the low level of noise (25-50 dB) and hardly any dust makes it possible to operate the MSE under normal workroom conditions. OBJECTIVE: The aim of this study was to examine the biological properties of different MPS - CaP coatings on titanium implants when inserted into the femoral condyle of goats. MATERIAL AND METHODS: For histomorphometrical evaluation as well as mechanical testing, 48 screw-type titanium implants were inserted into the femoral condyles of 12 goats each. The implants were either coated with a conventionally plasma-sprayed CaP ceramic, MPS CaP ceramic, or acid-etched without an additional CaP coating. Six and 12 weeks after implantation, the animals were sacrificed and bone-to-implant contact, amount of bone, as well as mechanical bone fixation were evaluated. RESULTS: For bone-to-implant contact no statistically significant difference was found between the different CaP coatings. However, statistically significant differences were found between non-coated, acid-etched titanium implants and CaP-coated implants after 6 and 12 weeks of healing. The bone values were not statistically significantly different between the different CaP coatings at 6 and 12 weeks. Furthermore, CaP ceramic-coated implants showed statistically significantly higher torque values compared with the non-coated implants after 6 and at 12 weeks of healing. No significant differences existed between the various types of CaP coatings. CONCLUSION: On the basis of our observations, we conclude that conventionally plasma-sprayed CaP ceramic-coated implants, as well as MPS-coated implants have a comparable effect on adjacent bone response.

Bone reaction adjacent to microplasma-sprayed CaP-coated oral implants subjected to occlusal load, an experimental study in the dog. Part I: short-term results.

BACKGROUND: A new microplasma spraying equipment (MSE) to deposit calcium phosphate ceramic (CaP) coatings onto titanium substrates has been developed. With this system, it is possible to spray fine particles and to apply textured hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat power of the microplasma jet, overheating of the powder particles as well as excessive local overheating of the substrate is diminished. Furthermore, because of the small laminar plasma jet, it is possible to achieve high spray efficiency in the case of spraying for dental implants. Also, the low level of noise (25-50 dB) and hardly any dust makes it possible to operate MSE under conditions of normal workrooms. OBJECTIVE: The aim was to investigate, in a mandibular dog model, bone biological properties and the occlusal loading effects of titanium implants provided with newly developed microplasma-sprayed CaP coatings. MATERIAL AND METHODS: For histomorphometrical evaluation, 48 screw-type titanium implants were inserted into the mandibles of six adult beagle dogs. The implants were either acid etched without additional coating, coated with a conventionally plasma-sprayed CaP ceramic, coated with a microplasma-sprayed CaP ceramic or with a microplasma-sprayed coating at the apical part only. To assess the effect of occlusal loading, a split-mouth design was used. Six weeks after implantation, the implants in one half of the mandible of each dog were functionally loaded, while the contra lateral implants served as control. Six weeks after loading, the animals were sacrificed and bone-to-implant contact as well as the amount of bone around the implants were assessed. RESULTS: Irrespective of surface and functional load, no statistically significant differences (P>0.05) were found either for bone-to-implant contact or for the amount of bone between the various implant surfaces. On the other hand, functional loading of the non-coated implants was associated with a tendency towards crestal bone loss. CONCLUSION: Within the limits of the experiment, we conclude that functional loading of MPS CaP coatings induces a favorable bone response, and furthermore, that the bone response, irrespective of the loading condition, does not differ from conventional plasma-sprayed CaP coatings.

[POCT in coagulation. Quality assurance]. / Qualitätssicherung bei POCT-Methoden in der Hämostaseologie.

In the last years several point of care testing (POCT) systems used for coagulation parameters have been developed and became daily routine. As for other POCT applications (e. g. blood gas analysis) there is a need for user education and continuous improvement of quality assurance. For some POCT coagulation systems a comprehensive quality management has not been established yet. According to the feasibility and availability of control material and system self control each POCT coagulation method described in this article has a varying concept of quality management. Besides a high quality standard in manufacturing systems, devices and reagents the education of the user and the automatic self control of the instrument as well as the application of electronic and/ or liquid control samples contribute to the total quality assurance. Even if a "like versus like" control material is not available a comprehensive quality management should be implemented in daily routine concerning pre-analytic as well as technical and post-analytic criteria. Anyway to do nothing as the available control material seems to be not suitable is a bad decision.

Isolation of prostate-derived single cells and cell clusters from human peripheral blood.

The detection of blood-borne prostate cancer (PCA) cells may help with clinical staging and the further understanding of PCA metastases. We discovered prostate-specific antigen (PSA)-positive stained but not PSA mRNA-expressing blood cells by means of cell sorting and PSA reverse transcription-PCR in patients. Therefore, we developed a cytokeratin immunomagnetic method to isolate PSA-positive epithelial cells from the circulating blood of PCA patients. We obtained blood-borne single cells from 6 of 10 PCA patients and clustered cells from 8 of 10 PCA patients. Patients with benign prostate hyperplasia tested negative for cell clusters. The reported isolation method yielded prostate-derived cells or clusters of them from PCA-diagnosed patients.

Bees, birds and yellow flowers: pollinator-dependent convergent evolution of UV patterns.

Colour is one of the most obvious advertisements of flowers, and occurs in a huge diversity among the angiosperms. Flower colour is responsible for attraction from a distance, whereas contrasting colour patterns within flowers aid orientation of flower visitors after approaching the flowers. Due to the striking differences in colour vision systems and neural processing across animal taxa, flower colours evoke specific behavioural responses by different flower visitors. We tested whether and how yellow flowers differ in their spectral reflectance depending on the main pollinator. We focused on bees and birds and examined whether the presence or absence of the widespread UV reflectance pattern of yellow flowers predicts the main pollinator. Most bee-pollinated flowers displayed a pattern with UV-absorbing centres and UV-reflecting peripheries, whereas the majority of bird-pollinated flowers are entirely UV- absorbing. In choice experiments we found that bees did not show consistent preferences for any colour or pattern types. However, all tested bee species made their first antennal contact preferably at the UV-absorbing area of the artificial flower, irrespective of its spatial position within the flower. The appearance of UV patterns within flowers is the main difference in spectral reflectance between yellow bee- and bird-pollinated flowers, and affects the foraging behaviour of flower visitors. The results support the hypothesis that flower colours and the visual capabilities of their efficient pollinators are adapted to each other.

Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood.

BACKGROUND: Serum levels of lipoprotein(a) [Lp(a)] are determined largely by genetic variation in the gene encoding for apolipoprotein(a) [apo(a)], the specific protein component of Lp(a) that is very homologous to plasminogen. High plasma levels of Lp(a) increase the risk for premature atherosclerotic vessel diseases. We investigated the little-characterized role of Lp(a) as a risk factor for venous thromboembolic diseases, alone and in conjunction with established thrombophilic risk factors of proteins regulating blood coagulation and fibrinolysis. METHODS AND RESULTS: Serum levels of Lp(a) and lipids, protein C, protein S, and antithrombin, as well as the size of apo(a) isoforms and the presence of the factor V:Q(506) mutation, were determined in 186 consecutively admitted children from neonates to 18 years old with a history of venous thrombosis and in 186 age- and disease-matched control subjects. Children with a history of venous thrombosis had a significantly higher median Lp(a) level (19 versus 4.4 mg/dL) than control subjects. The risk for thromboembolic events in children with Lp(a) levels in the upper quartile, ie, >30 mg/dL, was 7.2 (95% CI, 3.7 to 14.5). The size of apo(a) isoforms was inversely related to Lp(a) levels and to the risk for thromboembolic events. Compared with the highest quartile of the apo(a) size distribution, the lowest quartile was associated with a risk of 8.2. In addition, multivariate statistical analysis gives evidence that the factor V:Q(506) mutation (OR/CI, 2.8/1.6 to 4.9), protein C (OR/CI, 6.5/2.1 to 19), and antithrombin deficiency (OR/CI, 10.4/1.2 to 90) were independent risk factors of childhood venous thrombosis. Coincidence of elevated Lp(a) with factor V:Q(506) mutation or deficiencies of protein C or antithrombin further increased the risk for thromboembolic events to 8.4. CONCLUSIONS: Lp(a) >30 mg/dL is a risk factor for venous thromboembolism in childhood. Lp(a) measurements should be included in the screening of causal factors in children with venous thromboembolic events.

Protease inhibitors in spontaneous cervical artery dissections.

BACKGROUND AND PURPOSE: Observations in patients with arterial aneurysms, fibromuscular dysplasia, and spontaneous cervical artery dissection (sCAD) indicate that protease inhibitor deficiency might boost the enzymatic destruction of arterial tissue and increase the risk of these arterial wall diseases. Here we present the first large investigation of the protease inhibitor hypothesis in patients with sCAD. METHODS: Eighty patients with sCAD were compared with 80 age- and sex-matched healthy individuals. Alpha1-antitrypsin (alpha1-AT) and alpha2-macroglobulin (alpha2-MG) levels, and alpha1-AT genotypes were assessed and compared between groups. RESULTS: alpha1-AT and alpha2-MG levels as well as alpha1-AT genotypes did not differ significantly between patients and controls. The frequency of Z alleles in the patient group was higher than in the control group and than in other cohorts from Europe; however, the difference remained nonsignificant. All patients with Z alleles had internal carotid artery dissections. CONCLUSIONS: Overall, this data does not support the hypothesis that protease inhibitor levels or alpha1-AT genotypes play an important role in the etiology of sCAD. The present data does not exclude that the Pi-Z allele might have an influence on subgroups of sCAD, such as internal carotid artery dissections.

D609-phosphatidylcholine-specific phospholipase C inhibitor attenuates thapsigargin-induced sodium influx in human lymphocytes.

Previously, we reported that the phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor tricyclodecan-9-yl xanthogenate (D609) potentiates thapsigargin-induced Ca(2+) influx in human lymphocytes. In the present study we examined the effect of D609 on the thapsigargin-induced Na(+) entry. We found that the early phase of the thapsigargin-induced increase in the intracellular Na(+) concentration (approx. 1-2 min after stimulation) was attenuated after preincubation of lymphocytes with D609. By contrast, thapsigargin-induced Na(+) influx was not affected in the presence butan-1-ol, which inhibits phosphatidylcholine-specific phospholipase D (PC-PLD). The thapsigargin-induced Na(+) influx could be mimicked by PC-PLC exogenously added to the lymphocyte suspension, whereas addition of PC-PLD had no effect. In addition, thapsigargin stimulated formation of the physiological PC-PLC products, diacylglycerol. Cell-permeable diacylglycerol analogue, dioctanoyl-glycerol (DOG), produced time- and concentration-dependent increase in the intracellular Na(+) concentration. Both thapsigargin- and DOG-induced Na(+) increases were not affected in the presence of Na(+)/H(+) antiport inhibitor, HOE609, or Na(+)/Ca(2+) antiport inhibitor, dimethylthiourea, as well as in the presence of Co(2+) and Ni(2+), which block store-operated Ca(2+) entry. By contrast, markedly reduced thapsigargin- and DOG-induced Na(+) influx were noted in the presence of flufenamic acid, which blocks the non-selective cation current (I(CRANC)). In conclusion, our results suggest that diacylglycerol released due to the PC-PLC activation contributes to the thapsigargin-induced Na(+) entry.

Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for congenital heart disease.

OBJECTIVE: Recently, an association between the homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infants with congenital neural tube defects or congenital oral clefts has been shown. However, no data are available so far with respect to the MTHFR 677TT genotype in children with underlying structural congenital heart disease (CHD). METHODS: We investigated the MTHFR genotype in 114 Caucasian CHD patients aged newborn to 16 years (median 0.6 years; 53% male) and in 228 age- and sex-matched healthy controls. RESULTS: In childhood patients with CHD the homozygous MTHFR 677TT genotype was found in 21 out of 114 subjects (18.4%) compared with 21 out of 228 controls (9.2%; odds ratio (OR) 2.2, 95%-confidence interval (CI) 1.2-4.3; P=0.027). In patients with pulmonary valve stenosis, hypoplastic left heart syndrome, coarctation of the aorta, aortic valve stenosis or subaortic stenosis the frequency of the TT genotype varied between 38 and 67% with corresponding ORs from 6.1 (CI, 1.4-27.5; P=0.034) to 20.4 (CI, 1.8-235.0; P=0.025), whereas in other structural CHD the frequency of this genotype was not significantly different from the controls. CONCLUSIONS: With the present study we can show for the first time that the embryonal MTHFR 677TT genotype is significantly associated with the development of structural congenital heart malformations during early pregnancy. It remains to be clarified, whether this genotype is at least a risk marker or a risk factor for structural congenital heart malformations.

Symptomatic ischemic stroke in full-term neonates : role of acquired and genetic prothrombotic risk factors.

BACKGROUND AND PURPOSE: The present multicenter case-control study was prospectively designed to assess the extent to which single and combined clotting factor abnormalities influence the onset of symptomatic ischemic stroke in full-term neonates. METHODS: Lipoprotein (Lp)(a); the factor V (FV) G1691A mutation; the prothrombin (PT) G20210A variant; the methylenetetrahydrofolate reductase (MTHFR) T677T genotype; antithrombin; protein C; protein S; and anticardiolipin antibodies (ACAs) were investigated in 91 consecutively recruited neonatal stroke patients and 182 age- and sex-matched healthy controls. RESULTS: Sixty-two of 91 stroke patients (68.1%) had at least 1 prothrombotic risk factor compared with 44 control subjects (24.2%) (odds ratio [OR]/95% confidence interval [CI], 6.70/3.84 to 11.67). An increased Lp(a) level (>30 mg/dL) was found in 20 patients and 10 controls (OR/95% CI, 4.84/2. 16 to 10.86); FV G1691A was present in 17 patients and 10 controls (OR/95% CI, 3.95/1.72 to 9.0); the PT G20210A variant was detected in 4 patients and 4 controls (OR/95% CI, 2.04/0.49 to 8.3); the MTHFR TT677 genotype was found in 15 patients and 20 controls (OR/95% CI, 1.59/0.77 to 3.29); and protein C type I deficiency was found in 6 neonates. Neither antithrombin deficiency nor protein S deficiency was found in the neonatal patients studied. Acquired IgG ACAs were found in 3 cases. Additional triggering factors, ie, asphyxia, septicemia, maternal diabetes, and perinatally acquired renal venous thrombosis, were reported in 54.0% of patients. CONCLUSIONS: Besides acquired triggering factors, the data presented here suggest that genetic prothrombotic risk factors play a role in symptomatic neonatal stroke.

Hemostasis in normotensive and hypertensive men: results of the PROCAM study. The prospective cardiovascular Münster study.

BACKGROUND: The greater than normal cardiovascular risk of hypertensive patients could be partly due to an impairment of hemostatic balance found in such individuals. OBJECTIVE: To examine the relationship between hemostatic variables and blood pressures in 1950 apparently healthy male participants in the prospective cardiovascular Münster study aged 40-65 years. METHODS: Blood pressure and other variables were determined, including fibrinogen level, coagulation factor VII clotting activity, protein C level, antithrombin III level, plasminogen activator inhibitor-1 level, euglobulin fibrinolytic activity, and von Willebrand factor level. RESULTS: Age-adjusted mean values of coagulation factor VII clotting activity, plasminogen activator inhibitor-1 level, antithrombin III level, and protein C level in hypertensives and borderline hypertensives were significantly higher than those in normotensive men (e.g. for hypertensive versus normotensive men, coagulation factor VII clotting factor activity 111.5 versus 106.1%, plasminogen activator inhibitor-1 level 5.05 versus 3.22 arbitrary units/ml, and protein C level 111.1 versus 107.0%, P < 0.05-0.01). For most of the hemostatic variables we found positive bivariate correlations to blood pressure (P < or = 0.05). Exceptions were von Willebrand factor level (no correlation to blood pressure), and euglobulin fibrinolytic activity (a negative correlation to systolic blood pressure and no correlation to diastolic blood pressure). Significance persisted in the multiple logistic regression analysis with the exception of the relationships between systolic and diastolic blood pressures and fibrinogen level as well as euglobin fibrinolytic activity after adjustment for age. After adjustment for age and body mass index significance for relationships between systolic blood pressure and coagulation factor VII clotting activity as well as protein C level was also lost. CONCLUSIONS: We conclude that the greater than normal cardiovascular risk of hypertensive patients is partly due to an imbalance in hemostasis.

Prothrombotic risk factors in children with acute lymphoblastic leukemia treated with delayed E. coli asparaginase (COALL-92 and 97 protocols).

Hereditary prothrombotic risk factors have been shown to increase the risk of venous thrombosis in children treated with the combination of E. coli asparaginase and steroids. In the present study the role of prothrombotic risk factors in children with ALL treated according to the COALL study protocol was investigated in 108 consecutively recruited childhood patients. The prevalence rates of prothrombotic risk factors [factor V G1691A mutation, the prothrombin G20210A variant, the TT677 methylenetetrahydrofolate reductase genotype, deficiencies of protein C, protein S, antithrombin, elevated lipoprotein (a)] in this cohort were within the range reported for healthy Caucasians, and comparable to previously reported data for other leukemic patients. Venous thromboembolism occurred in 3 of the 108 children (induction n = 1; reinduction n = 2: 2.8%), and none of these children carried a prothrombotic risk factor. The results of the present study, suggest that the role of hereditary and acquired disturbances of coagulation in the development of thromboses might depend on the treatment regimen.

High prevalence of the I278T mutation of the human cystathionine beta-synthase detected by a novel screening application.

Classical homocystinuria due to cystathionine beta-synthase deficiency is one of the disorders revealing a high risk of thromboembolic events and vascular disease. This autosomal-recessively inherited metabolic disorder is considered to be rare with an estimated prevalence of 1:130,000 in the German population. In this study, we developed a novel multiplex PCR generating allele specific fragment lengths to analyse individual genotypes of the two most frequent cystathionine beta-synthase alterations, the I278T mutation, which is worldwide found on up to the half of homocystinuric alleles, and the adjacent polymorphism 844ins68. Screening of 200 unrelated German control subjects revealed a frequency of heterozygosity of 1.5% for 1278T corresponding to a calculated frequency of homozygosity of 1:17.800. Our data indicate that homocystinuria due to cystathionine beta-synthase deficiency is a frequently unrecognized disorder resulting in a high risk of thromboembolic events.

Foetal growth restriction in children with prothrombotic risk factors.

Placental infarction is frequently observed in low birth weight children. To evaluate whether low birth weight in healthy term neonates is associated with foetal inherited prothrombotic risk factors this retrospective study was conducted. Outcome measures were "birth weight in the lowest quartile" and "birth weight in the lowest decile" in singletons with a gestational age of > or =37 weeks. The analyses were based on 375 Caucasian children screened at the Monster childhood thrombophilia centre with complete data for all prothrombotic risk factors (factor V G1691A, prothrombin G20210A, elevated lipoprotein (a), protein C-, protein S-, antithrombin-deficiency). The proportion of children in the lowest birth weight quartile increased from 23.7% to 30.5% to 48.0% for children with no, only single heterozygous and multiple or homozygous defects respectively. The respective adjusted odds ratios (95% confidence intervals) of thrombophilia for birth weight in the lowest quartile (lowest decile) were 1.53 (0.76-3.08) in carriers of one prothrombotic risk factor and 4.01 (1.48-10.84) in subjects carrying multiple or homozygous defects. We identified foetal thrombophilia as an additional cause of low birth weight.

Thrombolysis in newborns and infants.

This review analyses literature reports from 1970 to 1998 assessing the use of streptokinase (SK), urokinase (UK) or recombinant tissue-type plasminogen activator (rt-PA) for thrombolytic therapy in neonates and infants. From 1970 to 1998 182 infants were reported to have received SK (n = 54; 29.5%), UK (n = 41; 22.5%) or rt-PA (n = 87; 48%). During thrombolytic therapy no concomitant heparin administration or low dose heparin therapy (5 U/kg/h) were recorded. To perform reocclusion prophylactics heparin was reinitiated at the end of thrombolytic therapy usually in the recommended dosage of 20 U/ kg/h. The overall thrombolytic patency rate in neonates varied from 39% to 86%. Besides bleeding from local puncture sites or recent catheterisation sites (10.4%), pulmonary embolism was reported in 1.1% of the 182 infants. Major bleeding complications, i.e. pulmonary bleeding (0.6%), gastrointestinal bleeding (0.6%) or intraventricular haemorrhage (IVH 2.7%) are rarely reported side effects and only 2 thrombolysis related deaths due to haemorrhage were mentioned. Bleedings reported in the central nervous system (n = 4) mainly occurred in preterm infants (n = 3). In conclusion, data of this preliminary analysis suggest that there is no big difference (p = 0.09; chi2-test) in the efficacy rate between the 3 thrombolytic agents used in the first year of life. In each case an assessment must be made with respect to the relative benefit conferred by thrombolytic therapy in preventing organ or limb damage versus the potential side effects, costs and inconvenience for the childhood patient. Controlled prospective multicentre studies on thrombolytic therapy in neonates and infants are recommended to evaluate patency rates and adverse effects for the different thrombolytic agents used.