The Role of Interventional Radiology in the Management of Deep Venous Thrombosis: Advanced Therapy

Deep vein thrombosis (DVT) is often managed with a health care pathway that funnels patients to anticoagulation therapy alone. This “usual treatment” is designed to stop propagation and embolisation of venous thrombus but not remove it. Surgical thrombectomy was once the only option in severe cases in which limbs were threatened, but thrombus removal is no longer restricted to emergency cases. Interventional radiologists are now using advanced endovascular techniques to achieve thrombus removal in a minimally invasive manner in a very short treatment time, thereby quickly restoring patency, relieving acute symptoms, and potentially limiting the subsequent development of postthrombotic syndrome when followed with anticoagulation and compression regimens. This article provides an overview of the interventions available for treating DVT. One of the newer “single-session” techniques is isolated pharmacomechanical thrombolysis, which is described here in detail with supporting cases.     

Evaluation of micro-CT for emphysema assessment in mice: comparison with non-radiological techniques

Objectives

To define the potential, limitations and synergies of micro-CT and other non-radiological techniques for the quantification of emphysema and related processes in mice, by performing a complete characterization of the elastase-induced emphysema model.

Materials and methods

Ninety A/J mice (45 treated and 45 controls) were studied at different time points using breath-hold gated micro-CT, functional test parameters, RT-PCR for RNA cytokine expression, Luminex technology for cytokine plasma concentration and histomorphometry.

Results

Both histomorphometry and micro-CT imaging reflect rapid initial emphysema progression followed by steady-state development at decreasing rates. Cytokine measurements reveal an acute inflammatory response within the first 24?h that disappears after the first week. Limited systemic effect was observed based on plasma cytokine concentration. Lung compliance decreases during the acute inflammation phase and increases afterwards.

Conclusion

Histomorphometry is the most sensitive technique since it detects airspace enlargement before the other methods (1?h after treatment). Micro-CT correlates well with histology (r2?=?0.63) proving appropriate for longitudinal studies. Functional test parameters do not necessarily correlate with the extent of emphysema, as they can be influenced by acute inflammation. Finally, cytokine measurements correlate with the presence of inflammation in histology but not with emphysema.     

Improved measurement of drug exposure in the brain using drug-specific correction for residual blood

A major challenge associated with the determination of the unbound brain-to-plasma concentration ratio of a drug (K_p,uu,brain), is the error associated with correction for the drug in various vascular spaces of the brain, i.e., in residual blood. The apparent brain vascular spaces of plasma water (V_water, 10.3 μL/g brain), plasma proteins (V_protein, 7.99 μL/g brain), and the volume of erythrocytes (V_er, 2.13 μL/g brain) were determined and incorporated into a novel, drug-specific correction model that took the drug-unbound fraction in the plasma (f_u,p) into account. The correction model was successfully applied for the determination of K_p,uu,brain for indomethacin, loperamide, and moxalactam, which had potential problems associated with correction. The influence on correction of the drug associated with erythrocytes was shown to be minimal. Therefore, it is proposed that correction for residual blood can be performed using an effective plasma space in the brain (V_eff), which is calculated from the measured f_u,p of the particular drug as well as from the estimates of V_water and V_protein, which are provided in this study. Furthermore, the results highlight the value of determining K_p,uu,brain with statistical precision to enable appropriate interpretation of brain exposure for drugs that appear to be restricted to the brain vascular spaces.     

Pharmacological uncoupling of activation induced increases in CBF and CMRO2

Neurovascular coupling provides the basis for many functional neuroimaging techniques. Nitric oxide (NO), adenosine, cyclooxygenase, CYP450 epoxygenase, and potassium are involved in dilating arterioles during neuronal activation. We combined inhibition of NO synthase, cyclooxygenase, adenosine receptors, CYP450 epoxygenase, and inward rectifier potassium (Kir) channels to test whether these pathways could explain the blood flow response to neuronal activation. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO₂) of the somatosensory cortex were measured during forepaw stimulation in 24 rats using a laser Doppler/spectroscopy probe through a cranial window. Combined inhibition reduced CBF responses by two-thirds, somatosensory evoked potentials and activation-induced CMRO₂ increases remained unchanged, and deoxy-hemoglobin (deoxy-Hb) response was abrogated. This shows that in the rat somatosensory cortex, one-third of the physiological blood flow increase is sufficient to prevent microcirculatory increase of deoxy-Hb concentration during neuronal activity. The large physiological CBF response is not necessary to support small changes in CMRO₂. We speculate that the CBF response safeguards substrate delivery during functional activation with a considerable ‘safety factor''. Reduction of the CBF response in pathological states may abolish the BOLD–fMRI signal, without affecting underlying neuronal activity.     

In vivo quantification of monoamine oxidase A in baboon brain: a PET study using [11C]befloxatone and the multi-injection approach

[¹¹C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of the monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study in baboons the interactions between the MAO-A binding sites and [¹¹C]befloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocol—three injections of labeled and/or unlabeled befloxatone—allowed the evaluation of all the model parameters from a single PET experiment. In particular, the brain regional concentrations of the MAO-A binding sites (B′_max) and the apparent in vivo befloxatone affinity (K_d) were estimated in vivo for the first time. A high binding site density was found in almost all the brain structures (170±39 and 194±26 pmol/mL in the frontal cortex and striata, respectively, n=5). The cerebellum presented the lowest binding site density (66±13 pmol/mL). Apparent affinity was found to be similar in all structures (K_dV_R=6.4±1.5 nmol/L). This study is the first PET-based estimation of the B_max of an enzyme.     

Autoinflammatorische Syndrome/Fiebersyndrome

Hereditary periodic (fever) syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or joint symptoms. Some of these disorders present with organ involvement and serological signs of inflammation without fever. There is a strong serological inflammatory response with an elevation of serum amyloid A (SAA), resulting in an increased risk of secondary amyloidosis. There are monogenic disorders (familial mediterranean fever (FMF), hyper-IgD-syndrome (HIDS), cryopyrin-associated periodic syndromes (CAPS), ??pyogenic arthritis, acne, pyoderma gangrenosum?? (PAPA), and ??pediatric granulomatous arthritis (PGA) where mutations in genes have been described, which in part by influencing the function of the inflammasome, in part by other means, lead to the induction of the production of IL-1??. In ??early-onset of enterocolitis (IBD)??, a functional IL-10 receptor is lacking. Therapeutically, above all, the IL-1 receptor antagonist anakinra is used. In case of TRAPS and PGA, TNF-antagonists (etanercept) may also be used; in FMF colchicine is first choice. As additional possible autoinflammatory syndromes, PFAPA syndrome (periodic fever with aphthous stomatitis, pharyngitis and adenitis), Schnitzler syndrome, Still??s disease of adult and pediatric onset, Beh?et disease, gout, chronic recurrent multifocal osteomyelitis (CRMO) and Crohn??s disease also are mentioned.     

FTO mRNA Expression in Extremely Obese and Type 2 Diabetic Human Omental and Subcutaneous Adipose Tissues

Background

Fat mass and obesity-associated protein (FTO) gene expression is known to correlate with obesity. Our aim was to investigate the FTO gene expression in paired omental and subcutaneous human adipose tissues from morbid and obese patients. To understand the role of CD68-positive macrophages in adipose tissues, the correlation with adiposity parameters such as adipocyte diameter and adipocyte radius was also measured. Drug and adiposity correlations were also analyzed.

Methods

Paired omental and subcutaneous adipose tissue were excised during elective surgery from morbidly obese (n?=?9) and obese (n?=?5) patients. FTO expressions were determined by quantitative PCR. Tissue sections were analyzed for their CD68 protein expressions by immunuhistochemistry.

Results

Omental and subcutaneous adipose tissue FTO gene expression levels were not found to differ significantly among morbidly obese and obese study groups. Serum aspartate aminotransferase e and alanine transaminase levels were found to be in negative correlation with subcutaneous fat tissue FTO expression rate. Antidiabetic drug use was found to be in correlation with adiposity. Both subcutaneous and omental fat cell diameters were found to have correlation with antidiabetic drug use. Omental fat cell diameter was found to enlarge together with omental CD68 protein expression. Subcutaneous macrophage number decreased while omental fat cell radius increased. Omental macrophage number was found in correlation with subcutaneous macrophage number.

Conclusions

Antidiabetic therapy was found to increase adiposity in omental and subcutaneous fat. Further research is needed with larger samples to explore the exact role of FTO in obesity.     

Strategische ��berlegungen bei mit spinaler Isch?mie assoziertem intramuralem H?matom

Intramural hematoma (IMH) forms ?C along with classic aortic dissection and penetrating aortic ulcer ?C the entity of acute aortic syndrome. Whereas thoracic pain is a common symptom in these patients, an association of IMH with spinal cord ischemia has been rarely described. We present a case of lower limb paraparesis in a patient with IMH type B. General considerations regarding IMH evaluation and treatment are discussed in the face of spinal cord protection strategies.     

Versatile use of rectus abdominis muscle and musculocutaneous flaps for soft-tissue reconstruction: our clinical experiences in 25 cases

The rectus abdominis muscle and musculocutaneous flaps have contributed to the efficient reconstruction of tissue defects that require a large amount of cutaneous and muscular tissue. In this article, outcomes of soft-tissue defects after reconstruction with the rectus abdominis muscle and musculocutaneous flaps were retrospectively analyzed. From August 2003 to June 2009, 25 flaps were transferred to reconstruct a wide variety of soft-tissue defects in the breast, chest wall, groin, perineal, and head and neck regions, as well as the upper and lower extremities. The rectus abdominis muscle and musculocutaneous flaps were used as part of 11 different approaches in 25 cases. There were 13 male and 12 female patients; the mean patient age was 44.2 years. The mean follow-up period was 8 months (range, 4–15 months). The overall success rate was 100%, and all flaps healed uneventfully. All reconstructive procedures were completed without any major complications. Rectus sheets were repaired primarily, and no mesh application was used. Minor complications related to transferred flaps were wound infection and dehiscence in one case, wound dehiscence in two cases, and flap lymphedema in one case. Minor complications related to the donor site were seroma in one case and wound infection and dehiscence in another case. This study presents our experience with the rectus abdominis muscle and musculocutaneous flaps in a series of 25 cases. The indications for the use of this particular flap with other flaps are discussed.     

The use of fibre-based demineralised bone matrix in major acetabular reconstruction: surgical technique and preliminary results

Acetabular osteolysis associated with socket loosening is one of the main long-term complications of total hip arthroplasty. In case of major bone loss, where <50% host bone coverage can be obtained with a porous-coated cementless cup, it is generally agreed that a metal ring or cage in association with a cemented component and allograft bone should be used. In order to promote allograft bone consolidation and incorporation, we have associated demineralised bone matrix (DBM, Grafton® A Flex) to the construct ion. Here we describe the technical details of major acetabular reconstruction using the Kerboull acetabular reinforcement device with allograft bone and DBM. This device has a hook that must be placed under the teardrop of the acetabulum and a plate for iliac fixation. The main advantages of this device are help in restoring the normal centre of hip rotation, guiding the reconstruction and partially unloading the graft. The Kerboull acetabular reinforcement device has provided a 92% survival rate free of loosening at 13-year follow-up in a consecutive series of 60 type III and IV deficiencies. Our preliminary results using DBM indicate faster allograft consolidation and remodelling.