[Cardiac magnetic resonance imaging : Trends and developments]. / Kardiale Magnetresonanztomographie : Trends und Entwicklungen.

BACKGROUND: In its almost 25 years of clinical use, cardiac magnetic resonance imaging (CMR) has been developed for a wide range of indications due to the development of robust techniques and their comprehensive validation. CMR-based assessment of cardiac volumes and systolic ventricular function as well as the characterization of focal myocardial scars belongs today to standard cardiac imaging. More recently, the introduction of accelerated acquisition techniques, quantitative myocardial T1- and T2-mapping methods and 4­dimensional (4D) flow measurements as well as new postprocessing techniques such as myocardial feature tracking have attracted attention. METHODS: This review is based on a comprehensive literature search in the PubMed database on new CMR techniques and their clinical application. RESULTS AND CONCLUSION: This article provides an overview of the latest technical developments in the field of CMR and their possible applications based on the most important clinical MR issues.

[Options for soft tissue reconstruction in pseudarthrosis]. / Möglichkeiten der Weichteilrekonstruktion bei Pseudarthrosen.

BACKGROUND: Pseudarthrosis can develop as a complication after conservative or operative fracture treatment and after elective orthopedic surgery. The treatment is challenging and is made more difficult when accompanied by large soft tissue defects or impairments in wound healing. In this case close and early coordination between trauma and plastic surgeons is crucial in order to develop a coherent and interdisciplinary treatment plan. METHODS: Due to the positive effects on bone consolidation and osteomyelitis, timely soft tissue reconstruction via a pedicled vascularized flap or free flap coverage should be preferred. If blood circulation in the affected extremity appears to be compromised, this should first be optimized by vascular intervention or bypass surgery. In atrophic, aseptic pseudarthrosis, bone and soft tissue reconstruction can be performed consecutively in one single procedure, whereas septic pseudarthrosis always require complete resection of all infected debris prior to wound closure. Examples of two commonly used free flaps are the latissimus dorsi muscle flap and the fasciocutaneous anterolateral thigh (ALT) flap. As multiple variations have been described for both procedures, the reconstructive portfolio lists many additional options available for soft tissue reconstruction. Fasciocutaneous flaps should be preferred whenever bone consolidation requires additional surgical interventions in the future.

Multiple Structural Transitions in Langmuir Monolayers of Charged Soft-Shell Nanoparticles.

We have investigated the morphologies of Langmuir layers of charged, polymeric hard-core/interlayer/soft-shell nanoparticles spread at the air-water interface. Depending on various mutual interactions, which are correlated to the areal densities of the deposited nanoparticles, we observed ordered patterns of nondense and closed-packed arrangements of core/interlayer/shell (CIS) nanoparticle ordering. At low areal densities, we found an almost regular distribution of the charged CIS nanoparticles on the water surface, which resulted from long-range repulsive electrostatic interactions between them. At higher areal densities, domains of more closely packed and ordered nanoparticles were formed, coexisting with regions of randomly and sparsely distributed nanoparticles. We relate these domains to the interplay of electrostatic repulsion and capillary attraction caused by the dipolar character of like-charged particles at the interface, allowing for a characteristic separation distance between nanoparticles of about 3-4 times the nanoparticle diameter. At relatively high areal densities, attractive van der Waals forces were finally capable of making nanoparticles to come in contact with each other, leading to densely packed patches of hexagonally ordered nanoparticles coexisting with regions of rather well-ordered nanoparticles separated by about 1 µm and regions of randomly and sparsely distributed nanoparticles. Intriguingly, upon re-expansion of the area available per nanoparticle, these densely packed patches disappeared, indicating that steric repulsion due to the presence of soft shells as well as long-range electrostatic repulsive forces were strong enough to assure reversibility of the morphological behavior.

Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences.

OBJECTIVES: To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. METHODS: One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixon reconstruction and dual-ratio signal discrimination algorithm ("screening" sequence); fat-saturated, multi-gradient-echo sequence with 12 echoes; gradient-echo T1 FLASH opposed- and in-phase. Bland-Altman plots were generated and correlation coefficients were calculated to compare the sequences. RESULTS: The screening sequence diagnosed fat in 33, iron in 35 and a combination of both in 4 patients. Correlation between R2* values of the screening sequence and the standard relaxometry was excellent (r = 0.988). A slightly lower correlation (r = 0.978) was found between the fat fraction of the screening sequence and the standard sequence. Bland-Altman revealed systematically lower R2* values obtained from the screening sequence and higher fat fraction values obtained with the standard sequence with a rather high variability in agreement. CONCLUSIONS: The screening sequence is a promising method with fast diagnosis of the predominant liver disease. It is capable of estimating the amount of hepatic fat and iron comparable to standard methods. KEY POINTS: • MRI plays a major role in the clarification of diffuse liver disease. • The screening sequence was introduced for the assessment of diffuse liver disease. • It is a fast and automated algorithm for the evaluation of hepatic iron and fat. • It is capable of estimating the amount of hepatic fat and iron.

Anomalous ground state of the electrons in nanoconfined water.

Water confined on the scale of 20 Å, is known to have different transport and thermodynamic properties from that of bulk water, and the proton momentum distribution has recently been shown to have qualitatively different properties from that exhibited in bulk water. The electronic ground state of nanoconfined water must be responsible for these anomalies but has so far not been investigated. We show here for the first time, using x-ray Compton scattering and a computational model, that the ground state configuration of the valence electrons in a particular nanoconfined water system, Nafion, is so different from that of bulk water that the weakly electrostatically interacting molecule model of water is clearly inapplicable. We argue that this is a generic property of nanoconfinement. The present results demonstrate that the electrons, and hence the protons as well, of nanoconfined water are in a distinctly different quantum state from that of bulk water. Biological cell function must make use of the properties of this state and cannot be expected to be described correctly by empirical models based on the weakly interacting molecules model.

Morphological changes during annealing of polyethylene nanocrystals.

Polymer crystals are metastable and exhibit morphological changes when being annealed. To observe morphological changes on molecular scales we started from small nanometer-sized crystals of highly folded long-chain polymers. Micron-sized stripes consisting of monolayers or stacks of several layers of flat-on oriented polyethylene nanocrystals were generated via evaporative dewetting from an aqueous dispersion. We followed the morphological changes in time and at progressively higher annealing temperatures by determining the topography and viscoelastic properties of such assemblies of nanocrystals using atomic force microscopy. Due to smallness and high surface-to-volume ratio of the nanocrystals, already at 75 °C, i.e. about 60 degrees below the nominal melting point, the lateral size of the crystal coarsened. Intriguingly, this occurred without a noticeable reduction in the number of folds per polymer chain. Starting at around 110 °C, chain folds were progressively removed leading to crystal thickening. At higher temperatures, but still below the melting point, prolonged annealing allowed for surface diffusion of molten polymers on the initially bare substrate, leading eventually to the disappearance of crystals. We compared these results to the behavior of the same nanocrystals annealed in an aqueous dispersion and to bulk samples.

[The new S2k AWMF guideline for the treatment of Bell's palsy in commented short form]. / Die neue S2k AWMF Leitlinie zur idiopathischen Fazialisparese in kommentierter Kurzform.

A new S2k AWMF guideline for the treatment of idiopathic facial palsy has been published. An accurate differential diagnosis is indispensable as 25-40% of all facial palsy cases are of non-idiopathic origin. It is explicitly recommended to treat patients with idiopathic facial palsy with steroids. Steroids favour a complete recovery, decrease the risk of synkinesis, autonomic sequelae and contractures. Adjuvant antiviral therapy cannot be recommended. On current data there is not sufficient evidence that the combination of steroids with antiviral drugs has a benefit for the patients. Even when not supported by randomized trials, adjuvant symptomatic therapy to protect the cornea and to avoid complications is recommended. There is no scientific evidence that physical therapy has any benefit but it should be taken into account because of psychological reasons. A benefit of acupuncture has not been proven. If eye closure remains incomplete as result of defective healing, one therapeutic option is lid loading of the upper eye lid. Moreover, in case of severe persistent palsy, several well-established microsurgical nerve and muscle plasty procedures are available.

[Augmentation in surgical sepsis : Chances and limitations in the treatment of osteitis with calcium hydroxyapatite containing antibiotics]. / Augmentation in der septischen Chirurgie : Chancen und Limitationen in der Behandlung der Osteitis mit antibiotikahaltigem Kalziumhydroxylapatit.

BACKGROUND: The surgical treatment of osteitis or fracture-related infections (FRI) is often associated with large bone defects. The treatment of these defects remains a major challenge in trauma surgery. Within the concept of tissue engineering, the development of various hybrid bone graft substitutes, such as calcium hydroxyapatite with added antibiotics, is continuously progressing. OBJECTIVE: Chances and limitations in the treatment of osteitis with calcium hydroxyapatite containing antibiotics. MATERIAL AND METHODS: Overview of the results of a 2-stage (infection) pseudarthrosis model on rat femurs treated with Cerament® G (Bonesupport, Lund, Schweden). Evaluation of the clinical experiences based on three case examples of osteitis treated with calcium hydroxyapatite containing antibiotics (Cerament® G or Cerament® V). RESULTS: After establishment of a 2­stage pseudarthrosis model on the rat femur, the osteoconductive and osteoinductive potential of calcium hydroxyapatite containing antibiotics could be confirmed. In the clinical application, the use of Cerament® G seems to lead to a more favorable outcome in small cavitary defects. The recurrence rates are higher than previously described, especially for larger segmental defects. CONCLUSION: Taking the clinical and experimental results into consideration, a stricter evaluation of the indications for the use of Cerament® G is necessary to achieve the best possible outcome for patients.

[Artificial intelligence in the management of anti-VEGF treatment: the Vienna fluid monitor in clinical practice]. / Künstliche Intelligenz im Management der Anti-VEGF-Therapie: der "Vienna Fluid Monitor" in der klinischen Praxis.

The Vienna fluid monitor is an artificial intelligence (AI) algorithm for the precise localization and quantification of retinal fluid. The algorithm is designed to help clinicians to make objective and accurate decisions in the anti-vascular endothelial growth factor (anti-VEGF) therapy of patients with neovascular age-related macular degeneration. The goal of the implementation is to optimize patient safety, preserve visual function and simultaneously to reduce the treatment burden on the healthcare system and patients.

Insulin resistance is not associated with myocardial steatosis in women.

AIMS/HYPOTHESIS: Insulin resistance, an independent risk-factor for cardiovascular disease, precedes type 2 diabetes and is associated with ectopic lipid accumulation in skeletal muscle and liver. Recent evidence indicates that cardiac steatosis plays a central role in the development of diabetic cardiomyopathy. However, it is not known whether insulin resistance as such in the absence of type 2 diabetes is associated with heart steatosis and/or impaired function. We therefore assessed myocardial steatosis and myocardial function in a sample of women with normal insulin sensitivity, insulin resistance, impaired glucose tolerance (IGT) and type 2 diabetes. METHODS: Magnetic resonance imaging and localised spectroscopy were used to measure left ventricular dynamic variables and myocardial lipid accumulation in interventricular septum of non-diabetic, age- and BMI-matched insulin-sensitive (n = 11, 47 ± 6 years, BMI 25 ± 2 kg/m(2); clamp-like index [CLIX] = 9.7 ± 0.7) and insulin-resistant (n = 10, 48 ± 5 years, 27 ± 4 kg/m(2); CLIX = 4.5 ± 0.4) women with normal glucose tolerance as well as of women with IGT (n = 6, 45 ± 5 years, 28 ± 6 kg/m(2); CLIX = 3.6 ± 1.1) and type 2 diabetes (n = 7, 52 ± 10 years, 27 ± 3 kg/m(2)). RESULTS: Myocardial lipid content was increased in type 2 diabetic women only (insulin-sensitive 0.4 ± 0.2% [means ± SD]; insulin-resistant 0.4 ± 0.1%; IGT 0.5 ± 0.2%; type 2 diabetes 0.7 ± 0.3%; p < 0.05). In insulin-resistant and type 2 diabetic women, stroke volume was lower (-15% and -27%, respectively, vs insulin-sensitive) and heart rate was higher (11% and 14%, respectively, vs insulin-sensitive, p < 0.05). No other differences in systolic and diastolic function were observed between study groups. CONCLUSIONS/INTERPRETATION: In contrast to liver and skeletal muscle, insulin resistance as such is not associated with increased myocardial lipid accumulation.

Core and surface temperatures in a red-blood-cell unit during storage and transport.

BACKGROUND AND OBJECTIVES: Temperature tracing of stored red-blood-cell concentrates (RBCs) is inevitable with respect to RBC quality control. RBC temperature, which should not exceed 10°C, is usually assessed by devices attached to the surface of the RBC pouch, assuming that surface temperature adequately represents the thermal state of RBC. We investigated under which conditions this assumption is true. MATERIALS AND METHODS: Eighteen thermocouples (TC) equidistantly mounted on a two-layer plastic grid were installed in a pouch to determine temperature distribution in the unit. Two TCs were attached to each side of the bag to evaluate surface temperatures. One was further installed in each investigation room to assess ambient room temperatures. Temperature distributions and time-temperature courses were measured under constant temperatures and various warming and cooling conditions. RESULTS: At homogeneous storage temperatures, only small gradients were measured between core and surface temperatures. Removed from cooling chamber to room temperature or back from room to storage temperature, core and surface time-temperature curves drifted apart. Surface and core temperature diverged the more, the faster ambient temperatures altered. The situation could be stabilized by thermal isolation: handled in a transport box, or even better in an air cushion envelope, surface and core courses approached and ultimately closely followed each other, respectively. CONCLUSION: RBC temperature monitoring devices attached to the surface of the RBC pouch very well describe the core temperature under constant temperature conditions. During transport, thermal isolation of the RBC unit is necessary to control RBC temperature precisely by surface temperature measurements.

Surface-induced breakout crystallization in cylinder-forming P(I-b-EO) diblock copolymer thin films.

We have found very slow crystallization in thin films of cylinder-forming poly(isoprene-b-ethyleneoxide) (P(I-b -EO)) diblock copolymers with PEO being the minority block. The film was crystallized at room temperature after melting at 62 °C. Imaging methods were combined with X-ray reflectometry and grazing-incidence small-angle X-ray scattering and diffraction. Initially, hexagonally packed, amorphous PEO cylinders lie in the film plane. After 148 days, crystallized, finger-like terraces were observed over the entire film surface. The terrace height is 20% higher than the repeat distance in the as-prepared film. Thus, at the film surface, the cylinders have been destroyed by crystalline lamellae lying in the film plane. The PEO chain stems are perpendicular to the substrate surface and are once-folded and fully interdigitated. The substrate-near layers still consist of the hexagonally packed, amorphous PEO cylinders within the PI matrix.

The proton momentum distribution in strongly H-bonded phases of water: a critical test of electrostatic models.

Water is often viewed as a collection of monomers interacting electrostatically with each other. We compare the water proton momentum distributions from recent neutron scattering data with those calculated from two electronic structure-based models. We find that below 500 K these electrostatic models, one based on a multipole expansion, which includes the polarizability of the monomers, are not able to even qualitatively account for the sizable vibrational zero-point contribution to the enthalpy of vaporization. This discrepancy is evidence that the change in the proton well upon solvation cannot be entirely explained by electrostatic effects alone, but requires correlations of the electronic states on the molecules involved in the hydrogen bonds to produce the observed softening of the well.

Heat dissipation in Sm3+ and Zn2+ co-substituted magnetite (Zn0.1SmxFe2.9-xO4) nanoparticles coated with citric acid and pluronic F127 for hyperthermia application.

In this work, Sm3+ and Zn2+ co-substituted magnetite Zn0.1SmxFe2.9-xO4 (x = 0.0, 0.01, 0.02, 0.03, 0.04 and 0.05) nanoparticles, have been prepared via co-precipitation method and were electrostatically and sterically stabilized by citric acid and pluronic F127 coatings. The coated nanoparticles were well dispersed in an aqueous solution (pH 5.5). Magnetic and structural properties of the nanoparticles and their ferrofluids were studied by different methods. XRD studies illustrated that all as-prepared nanoparticles have a single phase spinel structure, with lattice constants affected by samarium cations substitution. The temperature dependence of the magnetization showed that Curie temperatures of the uncoated samples monotonically increased from 430 to 480 °C as Sm3+ content increased, due to increase in A-B super-exchange interactions. Room temperature magnetic measurements exhibited a decrease in saturation magnetization of the uncoated samples from 98.8 to 71.9 emu/g as the Sm3+ content increased, which is attributed to substitution of Sm3+ (1.5 µB) ions for Fe3+ (5 µB) ones in B sublattices. FTIR spectra confirmed that Sm3+ substituted Zn0.1SmxFe2.9-xO4 nanoparticles were coated with both citric acid and pluronic F127 properly. The mean particle size of the coated nanoparticles was 40 nm. Calorimetric measurements showed that the maximum SLP and ILP values obtained for Sm3+ substituted nanoparticles were 259 W/g and 3.49 nHm2/kg (1.08 mg/ml, measured at f = 290 kHz and H = 16kA/m), respectively, that are related to the sample with x = 0.01. Magnetic measurements revealed coercivity, which indicated that hysteresis loss may represent a substantial portion in heat generation. Our results show that these ferrofluids are potential candidates for magnetic hyperthermia applications.

Correlation of Retinal Thickness and Swept-Source Optical Coherence Tomography Angiography Derived Vascular Changes in Patients with Neovascular Age-Related Macular Degeneration.

Purpose: The aim of this study was to investigate whether structural OCT changes, in specific retinal thickness, is associated with the vascular response within the nAMD CNV lesion. In other words, whether SSOCTA derived parameters may prove suitable to assess CNV activity in future.Methods: During the first 3 months patients were prospectively followed with visits at days 7, and 14 after each anti-VEGF treatment up to day 90. At baseline, day 30 and 60 Aflibercept was administered. OCT-derrived retinal thickness (RT) and OCTA-derived CNV lesion parameters (vessel area [VA]), total vessel length [TVL], total number of junctions [TNJ], junction density [JD]) were determined. Parameters were exported from SSOCT/A (PlexElite, Zeiss) images using the semi-automated AngioTool software. Additionally, the superficial and deep vascular plexus fractal dimension of the para- and perifoveal region were identified. Consequently, all OCTA derived parameters were correlated with RT.Results: 16 consecutive patients presenting with treatment-naïve, SSOCTA-positive CNV lesions were included. A weak to moderate statistically significant correlation was found between the mean RT of the inner as well as the outer ETDRS ring with the SSOCTA-derived vascular markers vessel area (VA; r2 = -0.38, p < .001; r2 = -0.47, p < .001, respectively), total vessel length, (TVL; r2 = -0.38, p < .001; r2 = -0.48, p < .001, respectively) and total number of junctions (TNJ; r2 = -0.35, p < .001; r2 = -0.44, p < .001, respectively). Junctions density (JD), and all variables based on fractal dimension (FD) did not show statistically significant correlations with retinal thickness measurements.Conclusions: In summary, we could confirm a moderate, however, statistically significant correlation between mean para- and perifoveal retinal thickness and the SSOCTA derived vascular parameters VA, TVL, and TNJ. This leads us to the conclusion that an SSOCTA-based activity analysis of the CNV complex is not yet a substitute for retinal thickness or in-depth fluid analysis in patients with nAMD.

Changes in the zero-point energy of the protons as the source of the binding energy of water to A-phase DNA.

The measured changes in the zero-point kinetic energy of the protons are entirely responsible for the binding energy of water molecules to A phase DNA at the concentration of 6 water molecules/base pair. The changes in kinetic energy can be expected to be a significant contribution to the energy balance in intracellular biological processes and the properties of nano-confined water. The shape of the momentum distribution in the dehydrated A phase is consistent with coherent delocalization of some of the protons in a double well potential, with a separation of the wells of 0.2 Å.

Smoking in pregnancy: a risk factor for adverse neurodevelopmental outcome in preterm infants?

AIM: To assess whether smoking in pregnancy influences neurodevelopmental outcome at 2-years of age in preterm infants with a gestational age <32 weeks. METHODS: Between January 2003 and December 2005 we prospectively enrolled 181 infants born alive between 23 and 32 weeks of gestation; 142 infants (78.5%) completed the follow-up visit. The association between candidate risk factors and delayed motor or mental development (Bayley Scales of Infant Development II; psychomotor or mental developmental index <85) was analysed by means of logistic regression analysis. RESULTS: Low maternal age, smoking in pregnancy, low gestational age, low birth weight, small for gestational age, chronic lung disease, intracerebral haemorrhage, periventricular leucomalacia, and retinopathy of prematurity (stages 3 and 4) all were associated with an increased risk for delayed development (p < 0.05, each). Smoking in pregnancy, small for gestational age and chronic lung disease maintained significance in a multivariable analysis. CONCLUSION: Smoking in pregnancy emerged as a risk predictor for adverse neurodevelopmental outcome in our study. Strategies to reduce smoking in pregnancy should be further endorsed.

[Demographic population forecasts: theoretical framework, assumptions, and prediction uncertainty]. / Demografische Bevölkerungsprognosen: Theoretische Grundlagen, Annahmen und Vorhersagesicherheit.

Population forecasts are not only highly demanded by scientists, politicians, and economists, but also by the general public. Thereby the wish of the users for only one forecast runs contrary to the uncertainty of the future developments of the population. In the past, but also today, population forecasts were and are predominantly accomplished by applying a deterministic approach: the Cohort Component Method. To counteract the uncertainty of future trends in the demographic processes in fertility, mortality, and migration, different scenarios are applied. Many studies have analyzed ex post the accuracy of past population projections. They show that, in addition to other factors, the time horizon and the level of regional aggregation influence the accuracy of the forecast outcomes. In particular, errors in the assumptions about future trends in fertility, mortality, and migration determine the accuracy of the forecasts. In many cases, these assumptions under- or overestimated the real trends. Progress in the question on uncertainty was made in recent years using a new approach: probabilistic forecasts which include probabilities of future trends in demographic processes.

Non-Union After Multiple Lumbar Fusion Surgeries in a Patient With Facioscapulohumeral Muscular Dystrophy: A Case Report and Review of the Literature.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a rare condition affecting 1/20,000 persons and the third most common muscular dystrophy condition, with an autosomal dominant pattern of inheritance characterized by progressive muscular weakness primarily involving the face, shoulder girdle, and upper arm. The condition is associated with atrophic musculature of the trunk and core leading to difficulties with gait, posture, and function. FSHD leaves as many as 20% of patients wheelchair-bound and most commonly presents with low back, neck, and shoulder pain. CASE DESCRIPTION: We present the case of a patient with FSHD who underwent multiple spinal fusion surgeries without relief in her back pain. Imaging studies serve to highlight the extent of paraspinal muscle atrophy and provides the basis for a discussion on the preoperative factors that may predict patients most likely to benefit from surgery. We then provide a brief review of the literature on the role of paraspinal muscle atrophy in back pain. CONCLUSIONS: This case adds to our understanding of the surgical management of patients with FSHD and patients with atrophic core musculature as a whole.

Dilated Epidural Venous Plexus Causing Radiculopathy: A Report of 2 Cases and Review of the Literature.

BACKGROUND: A dilated epidural venous plexus (DEVP) is a rare cause of radiculopathy, back pain, cauda equina syndrome, and other neurological symptoms. This vascular mass can be secondary to inferior vena cava obstruction, portal hypertension, vascular agenesis, and hypercoagulable states. Although rare, DEVP should be considered in the differential diagnosis for patients who present with lumbar radiculopathy. CASE DESCRIPTION: We present 2 cases involving patients with lumbar DEVP as well as a literature review of the role of hypercoagulability, vascular anatomy, and inferior vena cava thrombosis in the development of DEVP. The first patient had a history of recurrent deep vein thrombosis, systemic lupus erythematosus, and antiphospholipid syndrome. The diagnosis of DEVP was determined after intraoperative biopsy. The patient reported symptom resolution at her 6-month postoperative appointment. The second patient developed DEVP associated with Klippel-Trenaunay syndrome. She presented with back pain and leg weakness, and DEVP was diagnosed via magnetic resonance imaging. A neurosurgeon is currently following the patient. We believe this is the first case of Klippel-Trenaunay syndrome associated with DEVP. CONCLUSIONS: If a patient presents with an enhancing epidural lesion on magnetic resonance imaging and neurological symptoms, DEVP should be considered in the differential diagnosis. Additionally, a search for inferior vena cava thrombosis should be performed as well as risk factors for venous hypertension and hypercoagulable states.