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E C Jones

Publications and source records attributed to E C Jones.

At least 37 records · Page 2Linked to original sources
PubMed1999

Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121.

A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.

Adenoviruses, Human↗
PubMed1999

Urinary bladder. Mimics of neoplasia and new pathologic entities.

A wide range of epithelial and mesenchymal pseudoneoplastic disorders of the urinary bladder may clinically and pathologically mimic a malignant neoplasm. These lesions usually require a tissue biopsy for definitive diagnosis. It is important to be aware of these lesions and their spectrum of morphologic appearances to avoid overdiagnosis and inappropriate aggressive therapy.

Adenoma↗
PubMed1999

Renal oncocytoma and chromophobe renal cell carcinoma. A comparison of colloidal iron staining and electron microscopy.

Chromophobe renal cell carcinoma (RCC) is characterized by diffuse cytoplasmic staining with Hale colloidal iron (HCI) and the presence of numerous microvesicles. The eosinophilic variant morphologically may resemble renal oncocytoma. The latter commonly shows focal cytoplasmic HCI reactivity, but microvesicles have not been previously reported. We examined 19 chromophobe RCCs and 28 oncocytomas for their HCI staining patterns. Electron microscopy was performed on 13 chromophobe RCCs and 10 oncocytomas. In all cases of chromophobe RCC, more than 75% of cells showed a diffuse cytoplasmic HCI positivity, whereas a variable proportion of cells in 20 oncocytomas showed focal cytoplasmic staining, in a perimembranous, apical, or perinuclear pattern. Ultrastructurally, chromophobe RCCs contained abundant microvesicles with varying numbers of mitochondria, whereas all oncocytomas contained abundant mitochondria with focal collections of microvesicles. The microvesicles, in perimembranous, apical, or perinuclear clusters or singly scattered throughout the cytoplasm, were morphologically indistinguishable from those in chromophobe RCCs. In most cases, the microvesicle location and HCI staining pattern correlated. Chromophobe RCC and oncocytoma have distinctive morphologic features that usually allow their recognition. In difficult cases, HCI staining and electron microscopy may help, but the presence of HCI positivity or microvesicles in an eosinophilic renal tumor does not rule out oncocytoma.

Adenoma, Oxyphilic↗
PubMed1999

Metanephric adenoma-like tumors of the kidney: report of 3 malignancies with emphasis on discriminating features.

BACKGROUND: Metanephric adenoma is a very rare benign renal tumor; only 80 well-documented cases have been reported to date. We have seen several renal tumors that were originally incorrectly diagnosed as metanephric adenoma. DESIGN: We present 3 unusual renal tumors (2 primary and 1 metastatic), each of which illustrates important pathologic features useful in discriminating metanephric adenoma from malignant mimics. RESULTS: Case 1 involved a 46-year-old man with multiple small, cortical, solid, papillary (chromophil) renal cell carcinomas in his right kidney; the patient developed multiple, histologically identical, solid, papillary (chromophil) carcinomas in the opposite kidney 17 months later. Case 2 involved a 32-year-old woman with a 14-cm right renal tumor who developed soft tissue and bone metastases over a 17-year period. Case 3 involved a 52-year-old woman who presented with a 1.8-cm corticomedullary renal nodule, which eventually proved to represent a metastasis from a poorly differentiated (insular) carcinoma of the thyroid. All 3 tumors superficially resembled metanephric adenoma and consisted of primitive, dark-staining cells arranged in tubules or sheets. Each tumor, however, also had features inconsistent with the diagnosis of metanephric adenoma, including multifocal lesions with a variable nuclear-cytoplasmic ratio and diffuse cytokeratin 7 and epithelial membrane antigen immunopositivity in case 1, a 14-cm-diameter tumor with occasional mitoses in case 2, and a distinct fibrous capsule with capsular and vascular invasion in case 3. In addition, all 3 tumors lacked the cytologic features of bland overlapping nuclei with imperceptible cytoplasm consistently seen in metanephric adenoma. CONCLUSION: Adherence to strict histopathologic criteria will discourage misdiagnosis of a malignant or potentially malignant renal neoplasm as the rare and always benign metanephric adenoma.

Adenoma↗
PubMed1999

A pharmacokinetically guided Phase II study of carboxyamido-triazole in androgen-independent prostate cancer.

We conducted a Phase II clinical trial of the antiproliferative, antimetastatic, and antiangiogenic agent carboxyamido-triazole (CAI), using pharmacokinetic assessment to guide drug dosing. Fifteen patients who had stage D2 androgen-independent prostate cancer with soft tissue metastases were enrolled. Because CAI previously had been shown to decrease prostate-specific antigen secretion in vitro, this marker was not used to assess disease status. The dose of CAI used in this study was calculated so that plasma steady-state maximum concentrations between 2.0 and 5.0 microg/ml would be maintained. Following the initial dosage adjustment, 93% (14 of 15) of patients were within the predicted range. Fourteen of 15 patients were evaluable for response. All of the 14 evaluable patients demonstrated progressive disease at approximately 2 months. Twelve patients progressed by computed tomography and or bone scan at 2 months, whereas two patients demonstrated clinical progression at 1.5 and 2 months. One patient was removed from study at 6 weeks due to grade II peripheral neuropathy lasting >1 month. Although no clinical responses were noted, a 27.7% decrease in serum vascular endothelial growth factor concentration was observed. CAI does not possess clinical activity in patients with androgen-independent prostate cancer and soft tissue metastases. Pharmacokinetically guided dosing, although found to be feasible using a Bayesian approach, was not found to be of practical benefit. Although plasma CAI concentrations were maintained within the designated range, grade III toxicity requiring drug discontinuation was still observed.

Adenocarcinoma↗
PubMed1998

Evaluation of the aortic root by MRI: insights from patients with homozygous familial hypercholesterolemia.

BACKGROUND: In homozygous familial hypercholesterolemia (HFH), the aortic root is prone to develop atherosclerotic plaque at an early age. However, the aortic wall and plaque have not yet been assessed in this condition by MRI. We evaluated the aortic root by use of MRI in 17 HFH patients and 12 normal control subjects in a prospective, blinded, controlled study. METHODS AND RESULTS: Morphological assessment of the aortic root was done with spin-echo and gradient-echo MRI scanning. Comparisons were made with a number of measures of disease severity, including cholesterol-year score, calcium score on electron-beam CT (EBCT), and size of Achilles tendon xanthomas. Atherosclerotic plaque, visible on fat-suppressed images but never on water-suppressed images, was present in 9 HFH patients (53%). Supravalvular aortic stenosis was present in 7 patients with HFH (41%). Maximum supravalvular aortic wall thickness was significantly greater and OD and lumen cross-sectional area (CSA) were smaller in patients than in control subjects (P=0.006, 0.0005, and 0.06, respectively). Maximum wall thickness was associated with a greater calcium score on electron-beam CT (P=0.02). Although the cumulative exposure of the aortic root to cholesterol (the cholesterol-year score) was significantly correlated with the Achilles tendon CSA and vascular calcification, this score did not correlate with the wall thickness or aortic CSA. CONCLUSIONS: This study not only demonstrates the utility of MRI for detecting and characterizing aortic root atherosclerotic plaque and supravalvular aortic stenosis in HFH patients but also suggests that the LDL receptor plays a direct or indirect role in aortic mural development and vascular growth.

Achilles Tendon↗
PubMed1998

Predicting and preventing pressure ulcers in adults with paralysis.

A questionnaire mailed to all 2,295 members of the Eastern Paralyzed Veterans Association measured 45 potential risk factors for pressure ulcers. Logistic-regression analysis and Cox proportional-hazards analyses were used to identify the variables that were independently associated with pressure ulcers. The survey response rate was 42.2%. Among 15 risk factors from a previously published scale by the authors, 7 were independent predictors of pressure ulcer development: level of activity, level of mobility, complete spinal cord injury, urine incontinence or moisture, autonomic dysreflexia, pulmonary disease, and renal disease. In addition, 2 new variables added significant predictive value: being prone to infections that cause breathing problems and paralysis caused by trauma (as opposed to disease). Using these 9 risk factors, a new pressure ulcer risk assessment scale was designed specifically for persons with paralysis who are living in a community setting. It appears to be a more accurate method of predicting pressure ulcers than currently used risk assessment scales.

Adult↗
PubMed1997

Relation of hemodynamic volume load to arterial and cardiac size.

OBJECTIVES: This study sought to assess the relation of Doppler stroke volume (SV) to cardiac and carotid artery size and to determine whether volume load accounts for the parallelism between the two. BACKGROUND: It has been suggested that altered hemodynamic volume load can modify the degree and pattern of left ventricular (LV) hypertrophy from that predicted from blood pressure (BP) alone. METHODS: We related Doppler echocardiographic SV in 342 normotensive or unmedicated asymptomatic hypertensive adults to echocardiographic LV mass, LV internal dimension (LVID), wall thickness, carotid ultrasound arterial lumen diameter, intimal-medial thickness (IMT) and cross-sectional area (CSA). RESULTS: SV was positively related to LV mass (r = 0.42), LVID (r = 0.45), ventricular wall thickness (r = 0.20 to 0.29) and carotid diameter (r = 0.23, all p < 0.0001); CSA (r = 0.17, p < 0.002); and IMT (r = 0.12, p = 0.03). In multivariate analyses controlling for awake ambulatory BP and the circumferential end-systolic stress/end-systolic volume index ratio, SV remained an independent predictor of LV mass and chamber size (both p < 0.0001) but not LV wall thickness. SV also predicted carotid diameter (p < 0.0002), CSA (p = 0.001) and, to a lesser degree, IMT (p = 0.02) after controlling for mean awake BP and age. In additional analyses, LV and carotid dimensions were significantly interrelated independent of SV. CONCLUSIONS: SV measured by invasively validated Doppler echocardiography is associated with LV and carotid artery enlargement and eccentric hypertrophy, independent of arterial pressure, LV contractility, age and body size; however, SV and other variables do not account for the previously documented parallelism between cardiac and arterial structure.

Age Factors↗
PubMed1997

Myxoid and sclerosing sarcomatoid transitional cell carcinoma of the urinary bladder: a clinicopathologic and immunohistochemical study of 25 cases.

We report 25 sarcomatoid carcinomas of the urinary bladder with a prominent myxoid and/or sclerotic appearance. The average age of the patients was 72 years (range, 50-92 yr); 14 were men, and 11 were women. The cystoscopic appearance varied from a large polypoid mass to an intramural mass with bladder wall thickening, often with necrosis and ulceration. The tumors ranged from 3 to 10 cm and were typically rubbery or gelatinous with a brown, pink, or gray color. Microscopy revealed tapering spindle cells with a variable admixture of cohesive non-spindled cells. Twenty-two cases had an invasive overtly epithelial carcinomatous component, and in situ transitional carcinoma was present in 12 cases. All of the cases had areas with myxoid change, ranging from extensive to focal, separating the spindle cells. Fourteen cases had areas of sclerosis. In all the cases, the spindle cells were atypical, at least focally, with hyperchromatic pleomorphic nuclei, prominent nucleoli, and coarse chromatin. Mitotic activity was prominent in the majority of cases, and abnormal mitotic figures were frequent. In eight cases, the myxoid histologic pattern was very reminiscent of an inflammatory pseudotumor, a diagnosis frequently entertained and erroneously made in one case; many of the spindle cells in three of these cases were mildly atypical, with minimal mitotic activity. The spindle cells were immunoreactive for cytokeratin (12 of 19), vimentin (16 of 17), carcinoembryonic antigen (3 of 15) and muscle-specific actin (4 of 16), and nonreactive for epithelial membrane antigen, desmin, S-100, KP1, CD34, and Leu-M1. The epithelioid carcinomatous areas were highlighted by the cytokeratin immunostain. These features and the conventional light microscopic features indicative of a diagnosis of carcinoma distinguish this tumor from reactive of neoplastic mesenchymal lesions.

Aged↗
PubMed1996

Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer.

PURPOSE: A prospective, nonrandomized trial was initiated to determine the duration of neoadjuvant therapy required for prostate specific antigen (PSA) to reach its nadir, evaluate the ability of an ultrasensitive assay to measure decreases in PSA less than 0.2 microgram./l., and characterize the effects of 8 months of neoadjuvant therapy on pathological stage, positive margin rates, proliferation and tumor marker immuno-staining. MATERIALS AND METHODS: We evaluated 50 patients with clinically localized prostate cancer treated by 8 months of reversible androgen ablation before radical prostatectomy. Serum PSA and testosterone levels were measured monthly. RESULTS: Serum PSA decreased by 84% after 1 month and by a further 52% between 3 and 8 months. Using an ultrasensitive assay, serum PSA decreased to undetectable levels (less than 0.1 microgram./l.) or reached its nadir in 22% of the cases after 3 months, 42% after 5 months and 84% after 8 months. Overall, the positive margin rate was 4%. Of the cases 68% were organ-confined and 24% were specimen-confined. The positive margin rate was not increased after reevaluation with cytokeratin, PSA and prostatic acid phosphatase immuno-staining but of 4 cases initially staged as P0 on hematoxylin and eosin evaluation 2 had microscopic foci of cancer with prostatic acid phosphatase staining. Immuno-staining with the proliferation markers proliferation cell nuclear antigen and Ki-67 showed decreased staining in surgical specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develop during prolonged neoadjuvant therapy. CONCLUSIONS: Eight months of neoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, while the ongoing slower decrease reflects decreasing tumor volume.

Androgen Antagonists↗
PubMed1996

Optimal duration of neoadjuvant androgen withdrawal therapy before radical prostatectomy in clinically confined prostate cancer.

Experimental studies have shown that neoadjuvant androgen therapy dramatically reduces the rate of local recurrence after tumor excision. In the clinical setting, a 3-month course of neoadjuvant therapy before radical prostatectomy has been shown to significantly reduce positive margin rates, but follow-up is too short to assess the impact of such therapy on biochemical and clinical recurrence rates. A phase II study using an ultrasensitive assay showed that 8 months of neoadjuvant therapy were required before prostate-specific antigen (PSA) levels to reach their nadir in 84% of study participants. The positive margin rate in this study was substantially lower than those reported in the literature. Importantly, restaging of specimens after prostatic acid phosphatase (PAP) immunostaining did not upstage or increase positive margin rates. In addition, prolonged neoadjuvant therapy did not appear to result in progression of androgen-independent clones. A randomized phase III trial has been initiated to determine whether an 8-month course of neoadjuvant hormonal therapy is superior to a 3-month course in reducing positive margin rates and biochemical recurrences in patients with clinically confined prostate cancer.

Adult↗
PubMed1995

Metanephric adenoma of the kidney. A clinicopathological, immunohistochemical, flow cytometric, cytogenetic, and electron microscopic study of seven cases.

We report seven examples of a distinctive adenomatous tubular cortical neoplasm of the adult kidney. The average age of the patients (six women and one man) was 48.6 years (range, 38-64 years). In six patients the tumor was discovered during investigation of unrelated conditions, and all were treated with total nephrectomy. One tumor was found at autopsy. The tumors were well-circumscribed, nodular, tan-pink masses localized to the kidney, ranging in size from 0.6 to 8 cm. Histological examination demonstrated orderly, closely packed, small round tubules lined by bland, darkly staining oval cells with little cytoplasm, merging with rounded nests of similar cells. Occasional branching, elongated tubules, and papillary infoldings of glomeruloid-like bodies were present but blastema was absent. The tumor cells were immunoreactive for Leu 7 (three of five cases) and vimentin (four of six cases), and a few tumors were immunoreactive for cytokeratin (two of six cases), epithelial membrane antigen (one of six cases), and muscle-specific antigen (one of six cases). Ultrastructural examination of two tumors revealed tubular and solid nests of epithelial cells surrounded by basal lamina, with prominent cell junctions, microvilli, and apical secretory granules. DNA content analysis by flow cytometry yielded diploid histograms (four of four cases). Cytogenetic analysis of one case revealed a normal male karyotype. Clinical follow-up, available for six patients, revealed no evidence of recurrence (mean follow-up, 60.8 months). We believe this is a benign tumor, best classified as a metanephric adenoma because of its embryonic architectural and cytological appearance, that can be recognized by its very characteristic pathological features.

Adenoma↗
PubMed1995

Relationship of effective arterial elastance to demographic and arterial characteristics in normotensive and hypertensive adults.

OBJECTIVE: To evaluate demographic and vascular correlates of the effective arterial elastance noninvasively in normotensive and hypertensive adults. METHODS: In 202 subjects carotid ultrasonography and external arterial tonometry were simultaneously performed; carotid cross-sectional area, absolute and relative wall thicknesses, Peterson's and Young's elastic moduli and beta', a pressure-dependent index of arterial stiffness, were calculated. The impact of reflected waves on central pressure waveforms was evaluated by the 'augmentation index' (the relative increment in systolic pressure caused by the late-systolic peak). Left ventricular mass and relative wall thickness were assessed echocardiographically. The effective arterial elastance was estimated by dividing the pressure at the dicrotic notch by the Doppler-determined stroke index. RESULTS: The effective arterial elastance was higher in women among normotensives but similar between sexes among hypertensive subjects. It was correlated to age, mean blood pressure, body mass index and measures of arterial function, including Peterson's and Young's elastic moduli and beta', and to the augmentation index. It was also related to absolute and relative carotid wall thicknesses, lumen diameter and indexed cross-sectional area. Age, beta' and carotid cross-sectional area independently predicted effective arterial elastance in multiple regression analysis. CONCLUSIONS: Effective arterial elastance is related to demographic and arterial structural and functional characteristics. Increases in effective arterial elastance resulting from altered arterial structure and function may play a role in inducing left ventricular adaptative modifications.

Adult↗
PubMed1995

Benign scrotal inclusion cyst of the male perineum: an unusual post-operative complication.

Common complications after cystourethrectomy include wound infection, pneumonia, pyelonephritis and ureteral obstruction. No perineal cysts have been reported. We describe a perineal cystiic mass excised 14 years after cystourethrectomy. The cyst was lined by keratinizing stratified squamous epithelium with prominent rete ridges and basal pigmentation. A subjacent, concentric layer of smooth muscle was evident. An eccrine sweat gland was present in the cyst wall. Taken together, the features strongly suggest a scrotal inclusion cyst, a hitherto undescribed entity. Although rare, this lesion could masquerade as a local recurrence of carcinoma.

Journal Article↗