Johan Wassélius

Chronic iliac vein occlusion: midterm results of endovascular recanalization.

Purpose: To evaluate patency and clinical outcome in patients treated with endovascular recanalization and stent placement for chronic iliac vein occlusions. Methods: During a 14-year period (1994–2008), 59 (38 women; median age 39 years) of 62 patients with chronic occlusion of the iliac vein segment in 66 limbs were successfully treated with endovascular recanalization and stent placement. A prospectively maintained database was analyzed retrospectively to obtain information on clinical details, endovascular techniques, and outcome. Results: Three (5%) procedures failed for technical reasons. Three (5%) complications occurred, 2 (3%) of which were perforations requiring transfusion and procedure termination. Initial clinical success after 6 months was achieved in 49 (83%) of the 59 patients successfully treated initially. Primary patency after a median imaging follow-up of 25 months was 67% (44/66), assisted primary patency was 75% (49/66), and secondary patency was 79% (52/66). Fifteen (23%) of 66 limbs were asymptomatic after a median clinical follow-up of 32 months, 34 (52%) limbs were improved, 13 (20%) were unchanged, and 4 (6%) were worse compared to before intervention. Actuarial primary, assisted primary, and secondary patency rates using Kaplan-Meier survival analysis were 70%, 73%, and 80%, respectively, at 5 years. Conclusion: Endovascular recanalization and stent placement is a safe and effective treatment for occluded iliac veins and adjacent segments. Clinical midterm results are encouraging. Recanalized and stented segments remain patent in the majority of patients after 2 years. Endovascular treatment can ease symptoms and prevent further deterioration of patients with post-thrombotic syndrome.

High 18F-FDG Uptake in Synthetic Aortic Vascular Grafts on PET/CT in Symptomatic and Asymptomatic Patients

Graft infection is a serious complication to vascular surgery. The aim of this study was to assess 18F-FDG uptake in vascular grafts in patients with or without symptoms of graft infection. Methods: In all 2,045 patients examined by PET/CT at our clinic, 16 patients with synthetic aortic grafts were identified and reevaluated for 18F-FDG accumulation. Clinical and biochemical data were obtained from patient records. Results: High 18F-FDG uptake was found in 10 of 12 grafts in the patients who underwent open surgery and in 1 of 4 grafts in patients who underwent endovascular aneurysm repair. On the basis of biochemical and clinical data, it was concluded that 1 of the 16 patients had a graft infection at the time of investigation. Conclusion: 18F-FDG uptake in vascular grafts was found in the vast majority of patients without graft infection. The risk of a false-positive diagnosis of graft infection by 18F-FDG PET/CT is evident.

Cystatins - Extra- and Intracellular Cysteine Protease Inhibitors: High-level Secretion and Uptake of Cystatin C in Human Neuroblastoma Cells.

Cystatins are present in mammals, birds, fish, insects, plants, fungi and protozoa and constitute a large protein family, with most members sharing a cysteine protease inhibitory function. In humans 12 functional cystatins exist, forming three groups based on molecular organisation and distribution in the organism. The type 1 cystatins (A and B) are known as intracellular, type 2 cystatins (C, D, E/M, F, G, S, SN and SA) extracellular and type 3 cystatins (L- and H-kininogen) intravascular proteins. The present paper is focused on the human cystatins and especially those of type 2, which are directed (with signal peptides) for cellular export following translation. Results indicating existence of systems for significant internalisation of type 2 cystatins from the extracellular to intracellular compartments are reviewed. Data showing that human neuroblastoma cell lines generally secrete high levels, but also contain high amounts of cystatin C are presented. Culturing of these cells in medium containing cystatin C at concentrations found in body fluids resulted in increased intracellular cystatin C, as a result of an uptake process. At immunofluorescence cytochemistry a pronounced vesicular cystatin C staining was observed. The simplistic denotation of the type 2 cystatins as extracellular inhibitors is thus challenged, and possible biological functions of the internalised cystatins are discussed. To illustrate the special case of high cellular cystatin content seen in cells of patients with hereditary cystatin C amyloid angiopathy, expression vectors for wild-type and L68Q mutated cystatin C were used to transfect SK-N-BE(2) cells. Clones overexpressing the two variants showed increased secreted levels of cystatin C. Within the cells the L68Q variant appeared to mainly localise to the endoplasmic reticulum rather than to acidic vesicular organelles, indicating limitations in the transport out from the cell rather than increased uptake as explanation for the elevated cellular cystatin levels seen in hereditary cystatin C amyloid angiopathy.

Correlations between cholinergic neurons and muscarinic m2 receptors in the rat retina

ACETYLCHOLINE is well established as the neurotransmitter of starburst amacrine cells in the vertebrate retina but their function is poorly understood. We compared the distribution of muscarinic m2 receptors in the rat retina with the localization of the starburst cell processes. mAChR2 immunoreactivity appeared in a central band in the inner plexiform layer, which did not co-localize with the processes of the cholinergic amacrine cells. We found co-labelling of VAChT and ChAT making it highly unlikely that there are undetected cholinergic neurons in rat retina. Most mAChR2 receptors were located far from the cholinergic neurons, suggesting that most of them are unlikely to be associated with conventional cholinergic synapses.

FDG-Accumulating Atherosclerotic Plaques Identified with 18F-FDG-PET/CT in 141 Patients

PurposeThe aim of this study was to describe the prevalence of atherosclerotic plaques based on [18F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in a large population characterized by high risk of cardiovascular disease.ProceduresOne hundred forty-one patients referred to our department for FDG-PET/CT for suspected lung cancer were re-evaluated for atherosclerotic lesions. Cardiovascular risk factors were analyzed based on patient records.ResultsForty-two percent of the patients had three cardiovascular risk factors or more. Nine percent of all plaques were assessed as active FDG-accumulating plaques, 88% were inactive calcified plaques, and 2% were mixed. The abdominal aorta was the vessel with the highest plaque count. Patients with one risk factor had significantly less active and inactive plaques.ConclusionsThe observed association between the numbers of cardiovascular risk factors and the numbers of FDG-accumulating plaques as well as calcified plaques further supports the validity and value of FDG-PET/CT in the non-invasive identification and characterization of atherosclerotic disease.

Time-to-time correlation of high-risk atherosclerotic lesions identified with [(18)F]-FDG-PET/CT

ObjectiveIt has been shown that [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can identify macrophage-rich high-risk atherosclerotic plaques in animal models as well as in patients with atherosclerotic plaques in the carotid arteries. The development of inflamed macrophage-rich plaques over time is not well known. This study was performed to determine the variability of such FDG-accumulating plaques between consecutive PET/CT examinations.MethodsTwenty-eight patients who underwent two whole-body FDG-PET/CT examinations within 7 months for malignant diseases were re-evaluated for atherosclerotic lesions in major arterial segments. The plaques were identified as active, inactive, or mixed depending on their appearance on PET and CT. Every identified plaque was compared with that of the other examination to evaluate the time-to-time correlation.ResultsThe time-to-time correlation was close to 100% for calcified inactive plaques and about 50% for FDG-accumulating active plaques, with a high consistency between all examined arterial segments in this material.ConclusionsA large proportion of FDG-accumulating plaques can be identified on consecutive FDG-PET/CT examinations within 7 months.

Cathepsin B in the rat eye.

BackgroundCathepsin B is a mammalian cysteine protease. The enzyme has been suggested to participate in the patophysiological processes of keratoconus as well as in the corneal response to infectious agents. This study describes the localization of cathepsin B in the rat eye.MethodsCathepsin B was identified in rat ocular tissues by Western blotting and immunohistochemistry. Cathepsin B mRNA levels were analyzed in the tissues by quantitative real-time cDNA amplification (QRT-PCR).ResultsCathepsin B is present in the epithelium, in stromal cells and in the endothelium of the cornea. It is also present in the epithelium lining the ciliary processes, in occasional stromal cells in the iris, in the anterior subcapsular lens epithelium and in various cell types in the retina. At all locations cathepsin B is present in cytoplasmic granules, presumably lysosomes. QRT-PCR analysis detected cathepsin B mRNA in all these tissues in amounts correlating to the immunodetection results, suggesting that the enzyme detected is locally produced.ConclusionsCathepsin B is present in several tissues and cell types throughout the rat eye. It is localized to cytoplasmic granules, presumably lysosomes. Our results suggest that it is probably also produced in the same cell types.

Cystatin C uptake in the eye

BackgroundAs a secreted protein, cystatin C is assumed to play its role in the extracellular compartment, where it can inhibit virtually all cysteine proteases of families C1 (cathepsin B, L, S) and C13 (mammalian legumain-related proteases). Since many of its potential target enzymes in the eye reside in intracellular compartments, we sought evidence for a cellular uptake of the inhibitor in ocular tissues.MethodsFluorescence-labeled human cystatin C was injected intravitreally into normal rat eyes. Ocular tissues were subsequently examined using ELISA, fluorescence microscopy, and immunohistochemistry. Cystatin C uptake was additionally studied in an in vitro retina model.ResultsCystatin C administered intravitreally in vivo is taken up into cells of the corneal endothelium and epithelium, the epithelial cells lining the ciliary processes, and into cells in the neuroretina (mostly ganglion cells) and the retinal pigment epithelium. The uptake is demonstrable also in vitro and was, in the neuroretina, found to be a high-affinity system, inhibited by cooling the specimens or by adding the microfilament polymerization inhibitor, cytochalasin D, to the medium.ConclusionsThere is an active, temperature-dependent uptake system for cystatin C into several cell types in the cornea, ciliary body, and retina. The cell types that take up cystatin C are generally the same that contain endogenous cystatin C, suggesting that much or all cystatin C seen intracellularly in the normal eye may have been taken up from the surrounding extracellular space. The uptake indicates that the inhibitor may exert biological functions in intracellular compartments. It is also possible that this uptake system may regulate the extracellular levels of cystatin C in the eye.

Preoperative CT angiography versus Doppler ultrasound mapping of abdominal perforator in DIEP breast reconstructions: A randomized prospective study.

Is there a difference in surgery time and complication rate when Doppler ultrasound (US) is used for the preoperative mapping of perforators in comparison with computer tomography angiography (CTA)? Women who were candidates for breast reconstruction using the deep inferior epigastric perforator (DIEP) free flap were enrolled in a prospective randomized study. The operating time was 249 ± 62 min (mean ± SD) in the CTA group (n = 32) and 255 min ± 75 in the US group (n = 31)--hence a difference of 6 min on average. No flaps were lost. Sixteen complications occurred in 15 patients: seven in the CTA group and nine in the US group. Complications were remedied without delay and all patients came through with a favorable reconstruction. Preoperative mapping of perforators with US is satisfactory enough provided the microsurgery team has proper experience in breast reconstruction with the DIEP flap.

Developmental expression of DCC in the rat retina

The protein product of the deleted in colorectal cancer (DCC) gene possesses netrin-binding activity and may be involved in axonal guidance during retinal development. The temporal and spatial expression of DCC was analyzed in developing rat retina by means of immunoblotting and immunohistochemistry as well as by reverse transcription-polymerase chain reaction. Transient DCC protein expression is evident on ganglion cell axons in embryonic and neonatal retina. Double labeling experiments demonstrate DCC immunolabeling on processes that stratify in the inner plexiform layer and are derived from cholinergic amacrine cells. This pattern is maintained during the early postnatal period. DCC immunolabeling in the inner plexiform layer declines with age and is not observed in adult retina. The down-regulation of the DCC protein is confirmed by Western blot analysis. mRNA for DCC is expressed in embryonic, postnatal and adult retina and shows no correlation with the protein down-regulation. We suggest that DCC expression may be correlated with the functional segregation of the inner plexiform layer.