Mynx vascular closure device achieves reliable closure and hemostasis of percutaneous transfemoral venous access in a porcine vascular model.

AIMS: Vascular closure device (VCD)-based venous closure has been anecdotally reported, but systematic evaluation of the reparative response of the vessel wall to venous closure is lacking. The need to control groin complications, and minimize risks associated with postponed sheath removal under conditions of persistent anticoagulation, has generated interest in the role of VCDs for venous access closure. We sought to characterize the vessel wall response to venous closure, both acutely and in delayed fashion at 30 days using angiography, ultrasound, and histology. METHODS: Ten venous 7 Fr sheaths were deployed in the femoral veins of swine. Bilateral venous access sites were subsequently closed utilizing manual compression (MC; control arm: n = 4) or a closure device utilizing an extravascular polyethylene glycol sealant (MynxGrip treatment arm: n = 6). Acute (post closure), 3-day, and 30-day vascular ultrasound, as well as venography (internal jugular approach) were used to assess outcomes. Gross pathology and histology were obtained at the 30-day endpoint for all femoral venous closure sites. RESULTS: Hemostasis was successfully achieved in all cases without access-site complications. Venography and ultrasound confirmed normal ilio-femoral anatomy and flow at all study time points. Gross pathology and histopathology revealed no evidence of deep vein thrombosis, and no abnormalities were seen in the vena cava, heart, or lungs. Histology at 30 days showed complete healing of the vein wall access site, with a small focus of chronic inflammation and fibrosis in the perivascular adventitial tissue of the access tract. There was no microscopic evidence of the sealant. The tissue tract showed mild discrete inflammation (foamy macrophages, lymphocytes, plasma cells) with microgranulomas centered on residual red cells in both treatment and control groups. CONCLUSIONS: This study characterizes the angiographic, ultrasound, and histopathology outcomes of femoral vein closure, and provides insight into the healing mechanisms following venotomy. The bio-resorptive role of MynxGrip extravascular sealant in achieving effective venous closure and preserved long-term vessel patency without venous thromboembolism is demonstrated.

Liquefaction necrosis of mitral annular calcification (LNMAC): review of pathology, prevalence, imaging and management: proposed diagnostic imaging criteria with detailed multi-modality and MRI image characterization.

Liquefactive necrosis within a large spheroid zone of mitral annular calcification (LNMAC) is an atypical but increasingly recognized variant of mitral annular calcification (MAC). Proposed MRI, echo, and CT imaging criteria for diagnosis of this unusual disease entity are discussed along with a review of the prognosis, histopathology, and management implications. A comprehensive ECHO, CT, and MRI imaging approach to diagnostic differentiation from other cardiac masses, allowing characterization of the differing components of this unusual lesion is emphasized. Differentiation from surrounding myocardium, and demonstration of peripheral ring type hyperenhancement, or hyperintense signal in the wall of this lesion, seen with specific inversion recovery MRI sequences is presented as a major diagnostic criterion. The relationship of these MRI image findings to underlying pathology is also discussed. An illustrative case vignette is provided for clinical reference.

Quadricuspid aortic valve with ruptured sinus of valsalva aneurysm to the right atrium.

A 32-year-old man with a sudden onset of chest pain and progressive dyspnea was found to have a ruptured sinus of Valsalva aneurysm to the right atrium with an associated quadricuspid aortic valve. Echocardiographic and angiographic images are presented, with real time transthoracic 3D echo. The patient was successfully operated.

Design of wearable cardiac telemedicine system.

Cardiovascular disease is the world's leading killer disease, accounting for 16.7 million deaths annually. About 22 million people all over the world run the risk of sudden heart failure. However, deaths from cardiovascular diseases have decreased substantially over the past two decades, largely as a result of advances in acute care and cardiac surgery. These developments have resulted in a growing population of patients who have survived myocardial infarction. These patients need to be continuously monitored so that the initiation of treatment can be taken up within the crucial golden hour. The available conventional methods of monitoring restrict the mobility of these patients within a hospital or room. The primary aim of this paper is to design a Wearable Cardiac Telemedicine System that can help the mobility of patients, so as to regain their independence and return to an active social or work schedule, thereby improving their psychological well-being. The whole system has been implemented and tested. The results obtained are encouraging.

Teleophthalmology-based rural eye care in India.

Undoubtedly, blindness is a major trauma, which affects an individual not only physically but also emotionally. There are approximately 46 million visually impaired people throughout the world. It is becoming a global problem. In India alone, 19 million people are totally blind or else have visual defects. Out of this 19 million, 15 million reside in rural areas. India is among the countries which suffers from a shortage of doctors. There are only about 12,000 ophthalmologists in India, with most concentrating their practice in urban localities. Additionally, the inadequate infrastructures of roads, telecommunication, transport and financial status of the patients make it even more difficult to provide health care in rural areas. Teleophthalmology is a new branch of telemedicine that offers solutions to this serious problem. This paper discusses Indian teleophthalmology projects known as Sankara Netralaya Teleophthalmology Project (SNTOP) and Aravind Teleophthalmology Network (ATN). These have proven successful in the state of Tamilnadu, India, both in rural and secondary healthcare centers.

Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study.

BACKGROUND: Some so-called autoimmune diseases in women might be alloimmune and represent a chronic graft-versus-host response attributable to transplacentally acquired fetal cells. Thyroid disease is more common in women than men, and post partum exacerbation of thyroiditis is common. Our aim was to investigate whether there is an association between fetal cell microchimerism and thyroid disease in women. METHODS: Surgical specimens were obtained from 29 women who underwent thyroidectomy for various thyroid disorders. Control specimens were taken from clinically and histologically normal thyroids obtained at necropsy from eight women who died from unrelated conditions. Medical records and pregnancy histories were reviewed. Fluorescence in-situ hybridisation analysis was done with probes specific for X and Y chromosomes. Slides were examined with a fluorescence microscope to detect the presence of male cells-with one X and one Y signal in the nucleus-among maternal cells containing two X signals. FINDINGS: Male cells were seen in thyroid sections from 16 patients but not in those from controls (p=0.01). Male cells (1-165 per slide) were seen individually or in clusters in all thyroid diseases and were not restricted to inflammatory thyroid diseases. In one patient with a progressively enlarging goitre, we noted fully differentiated male thyroid follicles closely attached to and indistinguishable from the rest of the thyroid. INTERPRETATION: Our findings suggest a relation between fetal cell microchimerism and thyroid disease. Furthermore, fetal stem cells might be capable of differentiation into mature thyroid follicles in their mothers with favourable environmental and developmental factors.

Diabetes mellitus and outcome after primary coronary angioplasty for acute myocardial infarction: lessons from the GUSTO-IIb Angioplasty Substudy. Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes.

OBJECTIVES: We sought to compare the efficacy of primary angioplasty in diabetics versus nondiabetics and to evaluate the relative benefits of angioplasty over thrombolytic therapy among diabetics. BACKGROUND: Primary angioplasty for myocardial infarction is at least as effective as thrombolytic therapy in the general population. However, the influence of diabetic status on outcome after primary angioplasty versus thrombolysis remains unknown. METHODS: Patients in the Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) Angioplasty Substudy were randomized to receive either primary angioplasty or accelerated alteplase. The interaction of diabetic status (diabetics n = 177, nondiabetics n = 961) and treatment strategy with the occurrence of the primary end point (death, nonfatal reinfarction or nonfatal, disabling stroke at 30 days) was analyzed (power to detect a 40% relative reduction in the primary end point with alpha = 0.05 and beta = 0.20). Among patients who were randomized to and underwent primary angioplasty, procedural success (defined as residual stenosis <50% and TIMI grade 3 flow) was assessed based on diabetic status. RESULTS: Compared with nondiabetics, diabetics had worse baseline clinical and angiographic profiles. Despite more severe stenosis and poorer flow in the culprit artery, procedural success with angioplasty was similar for diabetics (n = 81; 70.4%) and nondiabetics (n = 391; 72.4%). Outcome at 30 days was better for nondiabetics randomized to angioplasty versus alteplase (adjusted odds ratio, 0.62; 95% confidence interval, 0.41-0.96) with a similar trend for diabetics (0.70, [0.29-1.72]). We noted no interaction between diabetic status and treatment strategy on outcome (p = 0.88). CONCLUSIONS: Primary angioplasty was similarly successful in diabetics and nondiabetics and appeared to be more effective than thrombolytic therapy among diabetics with acute infarction.

Beta3 integrin--a promiscuous integrin involved in vascular pathology.

OBJECTIVE: To determine whether beta3 integrin is present in blood vessels involved by atherosclerosis, Mönckeberg's medial calcinosis, vein graft atherosclerosis, transplant graft vascular disease and arterial restenosis. DESIGN: Retrospective histological and immunohistochemistry examination of tissues obtained from autopsy and surgery. SETTING: Tertiary care hospital. PATIENTS: The patients had surgical excisions of limbs, grafts, veins and arteries for the treatment of ischemic heart disease and peripheral vascular disease. Other tissues were derived from autopsies of the same patient populations. MAIN RESULTS: Beta3 integrin was found in the blood vessels involved in all of the vascular diseases examined. The location of the integrin varied among the diseases. Osteopontin, a bone sialoprotein involved in atherosclerosis and vascular repair, was also commonly detected. CONCLUSIONS: Beta3 integrin expression noted in the present study confirms the presence of this integrin in arteries with restenosis and atherosclerosis, which expands its involvement to the processes of transplant graft vascular disease, peripheral vascular disease and vein graft disease. The integrin may influence cell migration and adhesion by its interaction with noncollagenous matrix proteins, including osteopontin.

Gaucher's disease with valve calcification: possible role of Gaucher cells, bone matrix proteins and integrins.

Gaucher's disease, an autosomal recessive storage disease, leads to deposition of glucocerebrosides in various organs, especially those of the reticuloendothelial system. The heart is not thought to be frequently involved and studies of patients with cardiac involvement have concentrated on myocardial involvement. Despite careful prior investigation Gaucher cells have never been detected in the valves of these patients. Pathological findings of a patient with Gaucher's disease, type IIIc, with prominent cardiac valvular involvement are reported and, for the first time, the presence of Gaucher cells in the valve tissue is documented. There is evidence that the pathogenesis of the valvular injury may be by way of a cell-mediated mechanism involving bone matrix proteins and integrins.

Nematic kink states in a laser field.

We have investigated the nonlinear optical interaction of uniform and kink states of a nematic and a ferrofluid-doped nematic (ferronematic) liquid crystal with an incident laser field. We find that the transition between the permitted uniform oreintational states of these systems is of first order in the case of nematics, and of second order in the case of ferronematics. In the latter case we also find the phenomenon of reentrance. We find new kink states in a magnetic field with topological winding different from pi in the case of nematics, and 2pi in the case of ferronematics. In ferronematics, due to grain segregation the phase diagrams for uniform and kink states are entirely different. In these systems we find a first or second order structural transformation from a single kink into a pair of kinks. Further, we obtain a rich variety of kink states as the intensity of the laser field is varied.

Enhanced angiogenesis and unfavorable remodeling in injured porcine coronary artery lesions: effects of local basic fibroblast growth factor delivery.

There is interest in the role of growth factors in the genesis of arterial remodeling. We studied local administration of basic fibroblast growth factor (bFGF) to coronary lesions to determine whether there is a difference in remodeling and whether neovascularization could be induced in such stenoses and distal myocardium. Pigs were randomized to balloon infusion of either saline or bFGF at each thermally injured arterial site. After the animals were killed, their internal elastic lamina, neointima, and lumen areas were measured. Capillaries were counted in the arteries and myocardium. There was a greater loss of lumen and internal elastic in the bFGF group. The neointima, media, and myocardium in the bFGF treated arteries had statistically more capillaries. This study showed that local intracoronary bFGF, at a dose that results in arterial luminal revascularization in injured segments, adversely affects arterial remodeling. Thus, the angiogenic response to exogenous bFGF may be offset by concomitant shrinkage of injured arterial segments.

Myocardial infarction and cardiac mortality in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial.

BACKGROUND: Cardiac mortality and myocardial infarction (MI) rates are used to evaluate the efficacy of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We compared 5-year cardiac mortality and MI rates in 1829 patients with multivessel disease randomized to CABG or PTCA. METHODS AND RESULTS: The 5-year cardiac mortality rate was 8.0% in patients assigned to PTCA compared with 4.9% in those assigned to CABG (relative risk [RR] of 1.55 with a 95% confidence interval [CI] of 1.07 to 2.23; P=.022). In a subgroup of 1476 nondiabetic patients, there were no significant differences between treatment groups in cardiac mortality either overall (4.6% versus 4.2%; RR= 1.04, 95% CI, 0.65 to 1.66; P=.908) or in subgroups based on symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. The two treatment groups had similar event rates for the combined end point of cardiac death or MI. The RR for cardiac mortality in 264 patients who sustained an MI compared with those who did not was 5.9 (P<.001). MIs were more common after CABG during index hospitalization (P=.004), but in the PTCA group, they were more common after discharge (P<.001). CONCLUSIONS: The Bypass Angioplasty Revascularization Investigation (BARI) trial indicates 5-year cardiac mortality in patients with multivessel disease was significantly greater after initial treatment with PTCA than with CABG. The difference was manifest in diabetic patients on drug therapy. There were no significant differences overall for the composite end point of cardiac mortality or MI between treatment groups or for cardiac mortality in nondiabetic patients regardless of symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery.

The Histopathology of Angiographic Chronic Total Coronary Artery Occlusions Ñ Changes in Neovascular Pattern and Intimal Plaque Composition Associated with Progressive Occlusion Duration.

The current study describes the histopathology of angiographic chronic total occlusions including residual lumen patency, intimal plaque composition, patterns of neovascular channel formation, intimal plaque calcification, and cellular inflammation, analyzed according to occlusion duration and intimal plaque type (fibrocalcific vs. lipid laden vs. mixed). Histologic findings are related to previously described clinical and angiographic predictors of successful chronic total occlusion revascularization.

Histologic correlates of angiographic chronic total coronary artery occlusions: influence of occlusion duration on neovascular channel patterns and intimal plaque composition.

OBJECTIVES: Age-related changes in histologic composition and neovascular channel (NC) pattern of angiographic chronic total coronary artery occlusions (CTOs) were studied to define histologic correlates of age-related revascularization profiles and neovascular channel formation. BACKGROUND: Revascularization of CTOs is frequently characterized by inability to cross or dilate the lesion and a high incidence of reocclusion or restenosis but low periprocedural ischemic complication rates. Little is known about the histopathologic basis of these observations. METHODS: Ninety-six angiographic CTOs from autopsy studies in 61 patients who had undergone coronary angiography within 3 months of death were studied. Abrupt plaque rupture was excluded. Occlusion segments were analyzed for 1) histologic composition as a function of lesion age; and 2) NC pattern as a function of lesion age and intimal plaque (IP) composition. RESULTS: Cholesterol and foam cell-laden IP was more frequent in younger lesions (p = 0.0007), whereas fibrocalcific IP increased with CTO age (p = 0.008). IP NCs arose directly from adventitial vasa vasorum and were anatomically and quantitatively related in terms of number and size (p = 0.0001) to the extent of IP cellular inflammation. IP cellular inflammation exceeded that found in the adventitia (p < 0.001) or media (p = 0.0001) across all CTO ages. In CTOs < 1 year old, the adventitia was associated with a larger number and size of NCs relative to the IP (p = 0.0006 and p = 0.009), media (p = 0.0001 and p = 0.002) and recanalized lumen (p = 0.0001 and p = 0.001). In CTOs >1 year old, the adventitia and IP NC numbers were similar and exceeded NC numbers found in the media (p = 0.0001) and recanalized lumen (p = 0.0001 and p = 0.003). CONCLUSIONS: Angiographic CTO frequently corresponds to less than complete occlusion by histologic criteria. Age-related changes in IP composition from cholesterol laden to fibrocalcific may explain the adverse revascularization profile of older CTOs. IP NC growth derived from the adventitia increases with age and is strongly associated with IP cellular inflammation. IP NC formation may protect against the flow-limiting effects of IP growth.

Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves.

Dystrophic mineralization remains the leading cause of stenotic or regurgitant failure in native human and porcine bioprosthetic heart valves. We hypothesized that cellular expression of noncollagenous matrix proteins (osteopontin, osteocalcin, and osteonectin) that regulate skeletal mineralization may orchestrate valvular calcification. Porcine bioprosthetic heart valves and native human heart valves obtained during replacement surgery were analyzed for cells, matrix proteins that regulate mineralization, and vessels. Cell accumulation and calcification were correlated for both valve types (rho = 0.75, P = 0.01, native; rho = 0.42, P = 0.08, bioprosthetic). Osteopontin expression correlated with cell accumulation (rho = 0.58, P = 0.04) and calcification (rho = 0.52, P = 0.06) for bioprosthetic valves. Osteocalcin expression correlated with calcification (rho = 0.77, P = 0.04) and cell accumulation (rho = 0.69, P = 0.07) in native valves. Comparisons of calcified versus noncalcified native and bioprosthetic valves for averaged total matrix protein mRNA signal score revealed increased noncollagenous proteins mRNA levels in calcified valves (P = 0.07, group I vs. group II; P = 0.02, group III vs. group IV). When stratified according to positive versus negative mRNA signal status, both calcified bioprosthetic valves (P = 0.03) and calcified native valves (P = 0.01) were significantly more positive for noncollagenous proteins mRNA than their noncalcified counterparts. Local cell-associated expression of proteins regulating mineralization suggests a highly coordinated mechanism of bioprosthetic and native valve calcification analogous to physiologic bone mineralization. Modulation of cellular infiltration or cellular expression of matrix proteins that regulate mineralization, may offer an effective therapeutic approach to the prevention of valve failure secondary to calcification.

Arterial remodeling after experimental percutaneous injury is highly dependent on adventitial injury and histopathology.

BACKGROUND: The extent and nature of unfavorable geometric remodeling, especially related to the adventitia, has not been studied previously. The purpose of this study was to examine two methods of experimental arterial injury, characterize the extent of remodeling, and determine if remodeling is injury-specific. METHODS: Two methods for producing coronary stenoses in pigs were used: heat injury using thermal balloon angioplasty (resulting in adventitial fibrosis), and copper stent implantation (resulting in intense inflammation). Histomorphometric parameters included changes in neointimal thickness (delta neointima) from uninjured to injured sections, and differences in area circumscribed by the internal and external elastic laminas (delta internal elastic lamina area and delta external elastic lamina area, respectively). Remodeling was calculated for each lesion as the enlargement of the external elastic lamina area or internal elastic lamina area for incremental neointimal thickening, expressed as the slopes delta external elastic area/delta neointima and delta internal elastic lamina area/delta neointima. RESULTS: Remodeling indices for the heat lesions for the heat lesions were negative (delta internal elastic lamina area/delta neointima = 0.15, delta external elastic lamina area/delta neointima = 0.64) and indicated little remodeling in contrast to copper stent injury (delta internal elastic lamina area/delta neointima = 0.95, delta external elastic lamina area/delta neointima = 1.20). CONCLUSIONS: Remodeling in fibrotic compared to inflammatory lesions differs markedly, and may explain increased restenosis rates observed in thermal balloon angioplasty in patients. This formulation may be useful to study remodeling and restenosis following interventional technologies.

Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin alpha v beta 3 and osteopontin expression during neointima formation.

UNLABELLED: Lumen loss from vascular restenosis remains a leading cause of chronic revascularization failure. OBJECTIVE: We hypothesized that cell-matrix adhesion, migration, and differentiation events that underlie restenosis are mediated by alpha v beta 3 integrin-ligand interactions. METHODS: Using immunohistochemistry and in situ hybridization, we examined the spatial and temporal vessel wall expression of alpha v beta 3 and osteopontin following deep coronary arterial injury. Cell migration and adhesion assays were performed to demonstrate the affinity and specificity of XJ 735 for various vessel wall integrins. The effects of XJ 735 (a selective cyclic Arg-Gly-Asp (RGD) peptidomimetic alpha v beta 3 antagonist) on neointimal hyperplasia and lumen stenosis were tested in a porcine coronary injury model. Normolipemic swine underwent oversized stent injury followed by XJ 735 administration (9 animals, 28 lesions; 1 mg/kg bolus + 7 days 4 mg/kg/d infusion + 21 days 2 mg/kg i.v. bolus 12 hourly) or placebo (10 animals, 30 arterial lesions). RESULTS: Maximal alpha v beta 3 immunoreactivity was observed between 7-14 days following injury in the neointima, media, and adventitia. Maximal osteopontin mRNA signal in the neointima, media, and adventitia was observed at 14, 7 and 28 days respectively. IC50 for XJ 735 alpha v beta 3-mediated inhibition of human and porcine endothelial cell adhesion, and vascular smooth muscle cell migration, ranged from 0.6 to 4.4 microM. In contrast, IC50 for porcine or human alpha IIb/beta 3, alpha 4 beta 1, alpha v beta 5, and alpha 5 beta 1 inhibition exceeded 100 microM. Steady state XJ 735 plasma levels exceeded 5 microM. Despite slightly higher injury scores in XJ 735 treated animals, significant reductions in mean neointima area (43% reduction; p = 0.0009), and mean percent lumen stenosis (approximately 2.9 fold reduction; p = 0.04) were observed in XJ 735 treated animals. XJ 735 treatment did not significantly alter the relative size of the arterial injury and reference sites (geometric remodeling). Comparison of neontima area vs. injury score regression lines revealed significant reductions in slope (p = 0.0001) and intercept (p = 0.0001) for XJ 735. CONCLUSIONS: Selective alpha v beta 3 blockade is an effective anti-restenosis strategy that potently limits neointimal growth and lumen stenosis following deep arterial injury. The co-ordinate spatial and temporal upregulation of alpha v beta 3 expression following vessel wall injury, and the high affinity and specificity of XJ 735 for alpha v beta 3, confirms the importance of this integrin in adhesive and migratory cell-matrix events underlying coronary restenosis.

Brainstem abscess: preoperative MRI appearance and survival following stereotactic aspiration.

Brainstem abscesses are rare and until recently were uniformly fatal. The case of a 49 year old lady with an abscess extending through the midbrain, pons and cerebellar peduncle is presented. She survived following stereotactic aspilation; only the seventh such case. The report is illustrated with very rare preoperative MRI scans.