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Biomedical subjects

K C Kent

Publications and source records attributed to K C Kent.

At least 73 records · Page 4Linked to original sources

Lower extremity spiral CT angiography versus catheter angiography.

Both catheter and spiral computed tomography (CT) angiography of the lower extremity vasculature were performed in six patients with clinically symptomatic peripheral vascular disease. Forty-eight arteries were studied and were independently evaluated for arterial stenoses and occlusions. Compared with catheter arteriography, CT angiography correctly depicted segmental occlusions and significant stenoses (> 50%) in 26 of 28 arteries, yielding a sensitivity of 92.9%, a specificity of 96.2%, and an overall accuracy of 95.5%.

Aged↗

Dynamic contrast-enhanced subtraction MR angiography of the lower extremities: initial evaluation with a multisection two-dimensional time-of-flight sequence.

PURPOSE: To determine the clinical feasibility of a contrast material--enhanced two-dimensional (2D) magnetic resonance (MR) angiographic sequence in lower extremity arteries. MATERIALS AND METHODS: Four healthy volunteers and 12 patients underwent dynamic contrast-enhanced MR angiography; all patients also underwent conventional angiography. A 2D multisection gradient-echo sequence with image subtraction was used for all MR imaging examinations. RESULTS: Oblique-coronal contrast-enhanced MR angiography was completed in less than 4 minutes, with a 256 x 512 matrix. The arterial contrast enhancement ratio was 2.0 +/- 0.8 (standard deviation), and the pre- and post-contrast contrast-to-noise ratios were 2.1 +/- 13.8 and 46.2 +/- 18.7, respectively. The sensitivity for MR angiography was 100% and specificity was 69% for distinction of vessels with greater than 50% stenoses from normal or mildly stenotic vessels. CONCLUSION: Dynamic contrast-enhanced 2D MR angiography is capable of increasing intraarterial signal intensity and depicting small vessel anatomy of the lower extremities over a large field of view in a short imaging time.

Adult↗

Balloon catheterization induced arterial expression of embryonic fibronectins.

Fibronectins (FNs) comprise a family of adhesive extracellular matrix proteins that arise by alternative splicing in three regions: V (IIICS), EIIIA (ED-A), and EIIIB (ED-B). FNs bearing the EIIIA and EIIIB segments are prevalent during embryogenesis, expressed to lesser degrees in normal adult tissues, and may be locally reexpressed at adult tissue injury. RNase mapping shows that normal rat arteries express low levels of FNs that are predominantly EIIIA- and EIIIB-. Following balloon injury, arterial walls produce increased total levels of FN transcripts that preferentially include both the EIIIA and EIIIB segments. However, despite inducing increased total FN mRNA, balloon injury does not alter the relative composition of V120+, V95+, AND V0 spliced forms. In situ hybridization reveals that as early as 4 days after injury medial cells express increased total FN mRNA, and by 7 days substantial neointimal and focal medial synthesis of EIIIA+, EIIIB+, and V120+ FNs occurs; macrophages do not significantly contribute to this observed vascular FN synthesis. Consistent with the mRNA data, immunofluorescence microscopic analysis reveals increased deposition of EIIIB+ and V+ FN protein forms in injured arterial walls, particularly within the neointima. Our results suggest that local synthesis of specific FN isoforms is important to the neointimal formation that ensues after balloon injury.

Alternative Splicing↗

Requirement for protein kinase C activation in basic fibroblast growth factor-induced human endothelial cell proliferation.

The intracellular signaling mechanisms that mediate basic fibroblast growth factor (bFGF)-induced angiogenesis have not been fully identified. In particular, whether activation of the intracellular enzyme protein kinase C (PKC) is necessary or sufficient for bFGF-induced mitogenesis of human endothelial cells is not clear. Accordingly, the effect of bFGF stimulation on the Ca2+ increase and PKC activity of normal human endothelial cells (HEC) was studied, as was the effect of inhibition of PKC and the distribution of PKC isoenzymes in these cells. The addition of bFGF to cultured HEC increased overall PKC activity in the absence of an increase in intracellular Ca2+ and markedly stimulated their proliferation, as did the addition of PKC-activating phorbol esters. bFGF-induced proliferation was prevented by the PKC inhibitors chelerythrine and H-7 and by downregulation of PKC after prolonged incubation with phorbol esters. In contrast, these inhibitors did not prevent HEC proliferation induced by epidermal growth factor. Because of the failure of bFGF to increase Ca2+, we determined whether bFGF-induced proliferation could be mediated by novel or atypical PKC isoenzymes (which are not regulated by Ca2+). Investigation of the isoenzyme distribution of confluent and subconfluent HEC by immunoblotting, Northern transfer analysis, and polymerase chain reaction of reverse-transcribed RNA revealed the presence of several novel and atypical isoenzymes (PKC-delta, -eta, -theta, and -zeta) as well as small amounts of the conventional (Ca(2+)-regulated) isoenzymes PKC-alpha and -beta. Activation of PKC by bFGF, in the absence of an increase in intracellular Ca2+, suggests that one or more of these Ca(2+)-independent PKC isoenzymes are both necessary and sufficient for HEC proliferation after bFGF.

Alkaloids↗

Preoperative assessment of the carotid bifurcation. Can magnetic resonance angiography and duplex ultrasonography replace contrast arteriography?

BACKGROUND AND PURPOSE: Noninvasive studies are used with increasing frequency to assess the carotid bifurcation before endarterectomy. Therefore, assessment of their diagnostic accuracies is essential for appropriate patient management. We prospectively evaluate two noninvasive tests, magnetic resonance angiography (MRA) and duplex ultrasonography (DU), as potential replacements for contrast arteriography (CA). METHODS: A blinded comparison of three-dimensional time-of-flight (TOF) MRA, two-dimensional TOF MRA, and DU in 176 arteries was performed. CA was used as the standard of comparison. RESULTS: Three-dimensional TOF MRA had a sensitivity of 94%, a specificity of 85%, and an accuracy of 88% for the identification of 70% to 99% stenosis; two-dimensional TOF MRA had a sensitivity and specificity that were approximately 10% lower than those of three-dimensional TOF MRA. DU resulted in a sensitivity of 94%, a specificity of 83%, and an accuracy of 86%. Combining data from three-dimensional TOF MRA and DU, allowing for CA only for disparate results, yielded a sensitivity of 100%, a specificity of 91%, and an accuracy of 94% among concordant noninvasive tests, with CA required in 16% of arteries. MRA accurately differentiated 17 carotid occlusions from 16 high-grade (90% to 99%) stenoses, whereas with DU two patent arteries were identified as occluded and one occluded artery was identified as patent. CONCLUSIONS: Three-dimensional TOF MRA is the most accurate noninvasive test. Combined use of MRA and DU results in a marked increase in accuracy to a level that obviates the need for CA in a majority of patients.

Aged↗

Peripheral vascular complications of directional coronary atherectomy and stenting: predictors, management, and outcome.

The hospital course of 688 patients consecutively treated with directional coronary atherectomy (375 procedures) or Palmaz-Schatz stenting (376 procedures) was evaluated to identify incidence, predictors, and outcome of major vascular complications. Major vascular complications (defined as surgical repair, major hematoma, or bleeding with a > 10-point hematocrit decrease requiring transfusion alone, or nonsurgically managed arteriovenous fistula, pseudoaneurysm, retroperitoneal hematoma or femoral neuropathy) occurred in 11.7% of procedures, and were more common after stenting than after directional coronary atherectomy (16.8% vs 6.7%, p < 0.001). In particular, surgical repair was required after 10.1% of stenting procedures, versus 5.1% of directional coronary atherectomies (p < 0.02). Multivariable analysis identified age > 70 years, coronary stenting, female gender, multiple procedures during the index hospitalization, and a low nadir platelet count as independent predictors of major vascular complications (all p < 0.03). In the stent subgroup, excessive anticoagulation, nadir platelet count, hypertension, and sheath removal protocol (other than a same-day, activated clotting time-guided protocol) were all independent predictors of vascular complications. Thus, the overall risk of vascular complications with new device procedures (stenting, directional atherectomy) is greater than that traditionally seen with balloon angioplasty alone, and is determined by patient-related factors, procedure type, and management parameters.

Aged↗

Alternative splicing produces a divergent cytoplasmic tail in the human endothelial thromboxane A2 receptor.

Thromboxane A2 (TxA2) causes contraction of vascular smooth muscle and aggregation of platelets; paradoxically, it also induces formation of the vasodilator and antiaggregant prostacyclin by human endothelium. To determine if the molecular structure of the endothelial TxA2 receptor differs from that of the previously characterized receptor from placenta, we isolated a putative TxA2 receptor cDNA from a human endothelial library. The predicted amino acid sequence revealed a structure of 369 amino acids, in which a novel cytoplasmic tail replaced the carboxyl-terminal portion of the previously characterized TxA2 receptor; this divergence in cytoplasmic domains resulted from the nonsplicing of a potential intron in the placenta TxA2 receptor. Northern hybridization reveals that the expression of the TxA2 receptor in endothelial RNA decreases 6-fold following stimulation with an endoperoxide analog. Polymerase chain reaction using oligonucleotide primers specific to each cytoplasmic domain revealed that only the novel receptor was expressed in endothelium, while both receptors were expressed in placenta. Overexpression of the endothelial TxA2 receptor cDNA in Chinese hamster ovary cells conferred the ability to bind a known receptor antagonist and mobilize Ca2+ in response to TxA2 mimetics. This finding of a new TxA2 receptor in endothelium suggests that a family of these receptors may result from alternative splicing of the cytoplasmic (carboxyl) tail.

Alternative Splicing↗

Do neck incisions influence nerve deficits after carotid endarterectomy?

OBJECTIVES: To determine whether transverse neck incisions for carotid endarterectomy were associated with a similar or greater incidence of cranial nerve complications when compared with vertical skin incisions, and to assess the patient's perception of the appearance of the incision. DESIGN: Prospective, but not randomized. SETTING: A university-affiliated tertiary care hospital. PATIENTS/INTERVENTIONS: Eighty-five consecutive carotid endarterectomy procedures were evaluated prospectively in 80 patients. Although patients were not randomly assigned, consideration was given to having approximately the same number of patients who had carotid endarterectomy performed through transverse neck incision as through vertical neck incision. Forty-four carotid endarterectomies were performed with a vertical incision and 41 procedures were performed with a transverse incision. MAIN OUTCOME MEASURE: To determine the incidence of cranial nerve dysfunction (primarily nerves VII and XII) after operation. RESULTS: The incidence of palsies of cranial nerves VII and XII in the two groups was similar; there was no statistical significance (the seventh nerve palsy, 32% transverse vs 25% vertical; the 12th nerve palsy, 15% transverse vs 20% vertical). Seventy-two percent of the deficits had disappeared by the 3- to 6-month follow-up. Patients expressed a clear preference for the transverse incision (P = .04). CONCLUSIONS: Although surgical exposure was simpler with the vertical incision, adequate exposure with the transverse incision was always possible. The incidence of mostly temporary deficits of cranial nerves VII and XII was similar. Patients favored the transverse incision.

Aged↗

Effect of angiotensin II on human vascular smooth muscle cell growth.

Inhibitors of the production of endogenous angiotensin II (A-II) can diminish the hyperplastic response produced by arterial injury in animals; however, a similar effect in humans has not been observed. To explain this discrepancy, we compared the effect of A-II on rat aortic smooth muscle cells (R-SMC) and smooth muscle cells derived from human saphenous veins (H-SMC). A-II (10-1000 nM) significantly increased the proliferative rate of R-SMC incubated in 10% serum, but a similar effect was not observed with H-SMC. Incubation of R-SMC for 24 hr with A-II (1 microM) produced a significant increase in cell size (7%) and protein production (18%), whereas no hypertrophic response was noted in H-SMC exposed to A-II. In neither R-SMC nor H-SMC did A-II, in any concentration, induce cell migration. Stimulation of R-SMC with A-II resulted in tyrosine phosphorylation of five proteins (approximately 120, approximately 108, approximately 68, 45, 42 kDa). The 42- and 45-kDa proteins, which we have previously identified as mitogen-activated protein kinases (MAP-K), remained phosphorylated for 1 hr. In H-SMC, only MAP kinases were tyrosine phosphorylated, but with less intensity than in R-SMC, and only for 20 min. In protein kinase C-depleted SMC, tyrosine phosphorylation of MAP kinase was inhibited in both cell types. A-II produced hypertrophy and hyperplasia of R-SMC, but not H-SMC. Differences in intracellular signaling might account for these disparate effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Retroperitoneal hematoma after cardiac catheterization: prevalence, risk factors, and optimal management.

PURPOSE: Retroperitoneal hematoma is an unusual, but potentially serious, complication after cardiac catheterization. The predisposing factors, typical presentation, and clinical course of this iatrogenic complication are identified, and the role of surgery in its treatment is defined. METHODS: A retrospective review of 9585 femoral artery catheterizations over a 5-year period allowed identification and evaluation of all patients with retroperitoneal hemorrhage. RESULTS: Retroperitoneal hematoma developed in 45 patients (overall prevalence 0.5%), with the highest frequency after coronary artery stenting (3%). In the group of patients who underwent coronary artery stenting, statistically significant predictors of this complication included protocol for sheath removal, female sex, nadir platelet count, and excessive anticoagulation. Signs and symptoms included suprainguinal tenderness and fullness in 100%, severe back and lower quadrant pain in 64%, and femoral neuropathy in 36%. Most patients were treated successfully with transfusion alone. Seven patients (16%) required operation; in four, hypotension unresponsive to volume resuscitation developed early after catheterization; and, in three, a progressive fall in hematocrit level led to surgery 24 to 72 hours after catheterization. CONCLUSIONS: Retroperitoneal hematoma after cardiac catheterization can usually be treated by transfusion alone. A small subset of patients who have development of hypotension unresponsive to volume resuscitation require urgent operation.

Aged↗

Neuropathy after cardiac catheterization: incidence, clinical patterns, and long-term outcome.

PURPOSE: Neuropathy is a rare, but potentially morbid, complication of cardiac catheterization. In this study, we report the incidence of this complication and describe its clinical presentation, cause, and natural history. METHODS: Between 1988 and 1993, 9585 cardiac catheterizations were performed at this institution. Patients in whom femoral neuropathy developed were identified through a cardiology registry. Hospital and outpatient records and personal interviews were used to determine the presentation and clinical course of each of these patients. RESULTS: Peripheral neuropathy developed in 20 patients (incidence = 0.21%). Two clinical patterns emerged. In 16 patients, large retroperitoneal hematomas were documented by either computed tomography scanning or by physical examination. These patients were admitted with a lumbar plexopathy involving the femoral, obturator, or lateral femoral cutaneous nerves. Long-term follow-up revealed persistent mild sensory neuropathy in five patients and a mild motor deficit in one. In four patients a groin hematoma or false aneurysm developed which resulted, in paresthesias involving the medial and intermediate cutaneous branches of the femoral nerve. Symptoms completely resolved in all four patients, although false aneurysms were surgically repaired in two. CONCLUSIONS: Neuropathy after cardiac catheterization can be initially disabling, but it is usually completely reversible. Operation is recommended only for coexisting complications.

Boston↗

MR angiography of the carotid bifurcation: artifacts and limitations.

Although conventional angiography has traditionally been the preoperative study of choice before carotid endarterectomy, alternative noninvasive methods, particularly MR angiography, are being used increasingly for evaluation of the carotid bifurcation [1, 2]. In this essay, we illustrate the limitations of and artifacts associated with two-dimensional (2D) and three-dimensional (3D) time-of-flight (TOF) MR angiography vs conventional angiography when assessing disease of the carotid bifurcation.

Artifacts↗

A prospective study of the clinical outcome of femoral pseudoaneurysms and arteriovenous fistulas induced by arterial puncture.

PURPOSE: Although spontaneous thrombosis of femoral false aneurysms (FAs) and arteriovenous fistulas (AVFs) has been reported, the frequency of this occurrence is unknown. This prospective study was designed to establish the natural history of FA and AVF and to evaluate factors that might predict eventual thrombosis of these lesions. METHODS: Twenty-two patients with either femoral FAs (n = 16) or AVFs (n = 6) induced by percutaneous arterial punctures were evaluated prospectively. After an initial duplex scan, all patients were monitored with serial scans, either in hospital or weekly as outpatients, depending on the stability of the process. Operative repair was performed for the following indications: (1) a greater than 100% increase in size of a FA by duplex scan, (2) the development of symptoms, or (3) continued patency of the lesion after 2 months of observation. RESULTS: Nine of 16 FAs and four of six AVFs closed spontaneously; FAs greater than 6 cm3 (1.8 cm in diameter) required repair more often (p = 0.065). However, size was not an absolute predictor of the need for repair because two small aneurysms (1.6 and 0.7 cm3) remained patent, although both patients were discharged safely from the hospital, and two large aneurysms (13.2 and 10.7 cm3) thrombosed spontaneously. Three of seven patients whose aneurysms required repair received anticoagulation continuously from the time of catheterization until repair became necessary. None of the patients whose FAs closed spontaneously were receiving anticoagulants at the time of thrombosis (p = 0.02). Neither length of the FA neck, velocity in the FA cavity, size of original arterial puncture, nor velocity in the AVF correlated with thrombosis. CONCLUSIONS: We conclude that (1) all FAs do not thrombose spontaneously and at least one third require surgical repair, (2) patients receiving continuous anticoagulation should undergo aneurysm repair, (3) discharge of patients with FAs less than 6 cm3 is safe (the majority of these FAs will eventually thrombose spontaneously), and (4) many AVFs close spontaneously and repair is not required unless symptoms or signs of progressive enlargement develop.

Aneurysm, False↗

Identification of functional PGH2/TxA2 receptors on human endothelial cells.

Although functional receptors for thromboxane A2 and prostaglandin H2 (TxA2/PGH2) have been identified in platelets and vascular smooth muscle cells, receptor-mediated events in human endothelial cells stimulated by these endoperoxides have not been shown. Using cultured endothelial cells harvested from human umbilical or saphenous veins, we measured the effect of the TxA2 mimetic U46619 on mobilization of cytoplasmic calcium ([Ca2+]i), as well as release of prostacyclin and expression of the proto-oncogene c-fos, intracellular events that have been linked to [Ca2+]i rise in stimulated endothelial cells. Addition of U46619 to confluent fura 2-loaded endothelial cells caused a concentration-dependent rise in intracellular [Ca2+]i, with agonist concentrations of 300 nM producing a maximal [Ca2+]i rise. This [Ca2+]i rise was a uniform response observed in all individual endothelial cells throughout the monolayer, as shown by microspectrofluorimetric visualization. Similar effects were seen with a structurally dissimilar endoperoxide analogue, I-BOP, and with the naturally occurring endoperoxide PGH2. The initial [Ca2+]i rise was not reduced when extracellular [Ca2+]i was chelated with EGTA, but a later "plateau" phase was eliminated. An antagonist of the receptor for TxA2/PGH2 (SQ29548) strongly inhibited [Ca2+]i mobilization. Stimulation of endothelial cells with U46619 also transiently increased expression of the proto-oncogene c-fos, as determined by RNA hybridization, and induced a fivefold increase in prostacyclin release. Thus, endoperoxides can stimulate human venous endothelial cells by means of TxA2/PGH2 receptors, whose occupancy can activate intracellular events associated with functional changes.

Bridged Bicyclo Compounds, Heterocyclic↗

Accuracy of clinical examination in the evaluation of femoral false aneurysm and arteriovenous fistula.

A prospective study was undertaken to define the comparative value of physical examination versus duplex scanning in the detection of femoral false aneurysm and arteriovenous fistula after percutaneous femoral artery puncture. Fifty-three patients were referred to the vascular surgery service after femoral artery catheterization for evaluation of a groin hematoma or a new femoral bruit. All patients were evaluated initially by a vascular surgeon and then by duplex scan. The results of these evaluations were compared with the findings at operation. Physical examination was 100% sensitive and 100% specific in the diagnosis of arteriovenous fistula, whereas duplex scan achieved a sensitivity of only 58% and a specificity of 100%. Physical examination was 92% sensitive and 93% specific in the detection of femoral false aneurysm compared with a sensitivity of 83% and a specificity of 100% for duplex scanning. Physical examination is the best method for detecting and following patients with arteriovenous fistula. False aneurysms can be detected reliably by physical examination, although evaluation with a duplex scan is necessary to identify the precise size and anatomy of these lesions.

Aged↗

Transforming growth factor-beta inhibits human vascular smooth muscle cell growth and migration.

BACKGROUND: Transforming growth factor-beta (TGF-beta) is released after vascular injury and may influence the healing response of the vessel wall. We investigated the effect of this growth factor on proliferation and migration of human venous smooth muscle cells (SMC) and the signal transduction mechanisms through which TGF-beta exerts this effect. METHODS: SMC derived from human saphenous vein were used in a 72-hour proliferation assay and a 6-day migration assay. Cells were exposed to TGF-beta alone and in the presence of platelet-derived growth factor (PDGF), basic fibroblast growth factor (b-FGF), epidermal growth factor, and serum. The ability of TGF-beta to activate tyrosine kinases, phosphatases, or protein kinase C was evaluated by use of Western blotting with an antiphosphotyrosine antibody. RESULTS: In a concentration-dependent manner, TGF-beta inhibited proliferation induced by PDGF, b-FGF, epidermal growth factor, and serum. This inhibitory effect was independent of SMC density. TGF-beta also inhibited migration induced by PDGF and b-FGF. Exposure of cells to TGF-beta did not lead to tyrosine phosphorylation of cellular substrates or activation of protein kinase C. CONCLUSIONS: TGF-beta inhibits both migration and proliferation of human SMC. This inhibitory effect is not mediated through protein kinase C, mitogen-activated protein kinase, or tyrosine kinases.

Calcium-Calmodulin-Dependent Protein Kinases↗

Identification and functional characterization of protein kinase C isozymes in platelets and HEL cells.

To determine if selective activation of individual isozymes of protein kinase C (PKC) might explain the apparently divergent effects of PKC stimulation on platelets, we purified and characterized the isozymes from both platelets and human erythroleukemia (HEL) cells, a cell line that has many features of megakaryocytes. Two peaks of platelet PKC activity were resolved by hydroxylapatite chromatography; immunoblot analysis revealed that these two peaks represented the alpha and beta isozymes of PKC. In contrast, HEL cells produced only a single peak that contained the beta isozyme. None of the other PKC isozymes were detected in these fractions. The cytosol of platelets and HEL cells, however, were both found to contain the PKC-delta isozyme. Northern hybridization analyses and mRNA amplification by the polymerase chain reaction demonstrated the presence of mRNA encoding the alpha, beta, and delta PKC isozymes in platelets, but only the beta and delta isozymes in HEL cells. Phorbol myristate acetate (PMA), thrombin, or an endoperoxide analog induced the phosphorylation of the 47-kDa substrate of PKC (pleckstrin) found in platelets and HEL cells; preincubation of either HEL cells or platelets with PMA reduced the intracellular Ca2+ rise induced by thrombin. Thus, although both HEL cells and platelets contain PKC-beta and the recently described PKC-delta isozymes, the widely distributed alpha isozyme of PKC is absent in HEL cells; however, isozymes other than PKC-alpha are sufficient for some PMA-mediated functions that are similar to those seen in stimulated platelets.

Base Sequence↗