Biomedical subjects

T Joseph

Publications and source records attributed to T Joseph.

At least 37 records · Page 2Linked to original sources

PubMed2000

Species-dependent changes in mechano-energetics of isolated cardiac muscle during hypoxia.

The present study investigates the mechanical and energetic changes induced by hypoxia in isolated cardiac muscles of different species characterized by different myosin isoforms. Classic mechanical parameters of contraction and energetic parameters derived from the tension-velocity relationship were studied in rat and guinea pig left ventricular papillary muscles and in frog ventricular strips before and after 15 min hypoxia (n = 8 in each group). The isomyosin pattern is predominantly V1 with high ATPase activity in rat and V3 with low ATPase activity in guinea pig and frog heart ventricles. At baseline, cardiac mechanical performance was greater in rat than in guinea pig and frog muscle, but the economy of tension generation did not differ significantly between the three species. Hypoxia significantly decreased myocardial mechanical performance in all three groups. Mechanical impairment was more marked in rat than in the other two species and was intermediate in guinea pig. The energetic consequences of hypoxia differed according to species and in a different manner from the mechanical parameters. Hypoxia decreased the economy of tension generation in rat heart, in contrast to no change in guinea pig and frog muscle. These results suggest that in terms of mechano-energetic properties, cardiac muscles with V1 isomyosin were more sensitive to hypoxia than those containing V3 isomyosin.

Adenosine Triphosphatases↗

PubMed2000

Long-term clinical outcome after endoluminal reconstruction of diffusely degenerated saphenous vein grafts with less-shortening wallstents.

OBJECTIVES: This study was designed to evaluate the immediate and long-term clinical results of patients undergoing endoluminal reconstruction in diffusely degenerated saphenous vein grafts (SVGs) with elective implantation of one or more less-shortening Wallstents. BACKGROUND: The optimal treatment strategy for patients with diffusely degenerated SVGs is controversial. Endoluminal reconstruction by stent implantation is one proposed strategy; however, there are few data regarding long-term clinical outcome. METHODS: Between May 1995 and September 1998, 6,534 consecutive patients underwent angioplasty in our institution, including 440 who were treated for SVG lesions. Of these, 126 (115 men, 11 women, median age 69.5 years, range: 33-86 years) with old SVGs (mean age: 13+/-5 years) diffusely degenerated stenosed or occluded (mean lesion length: 27+/-12 mm) were treated electively with implantation of one or multiple (total 197) less-shortening Wallstents. RESULTS: Before discharge, 13 patients (10.3%) sustained at least one major cardiovascular event, including 4 deaths (3.2%), 11 myocardial infarctions (MI) (8.7%), and 3 repeat revascularizations (target vessel = 1, nontarget vessel = 2, 2.4%). Surviving patients were followed for 22+/-11 months: 13 patients (11.1%) died, 11 (9.4%) sustained an MI, 37 underwent angioplasty (31.6%), and 4 (3.4%) underwent bypass surgery. The estimated three-year event-free survival rates (freedom from death, and freedom from death/MI/target vessel revascularization) were (mean +/- SE) 81.1+/-7.8% and 43.2+/-18.5%, respectively. CONCLUSIONS: The long-term clinical outcome of patients undergoing endoluminal reconstruction in diffusely degenerated SVG is relatively poor, mainly because of a high incidence of death or MI and the frequent need for repeat angioplasty. It is unlikely that percutaneous intervention alone will provide a satisfactory or definitive solution for these patients.

Adult↗

PubMed2000

Left ventricular volume analysis for the detection of coronary artery disease during dobutamine stress echocardiography in patients undergoing vascular surgery.

AIMS: The purpose of the study was to prospectively evaluate the effectiveness of left ventricular volume changes analysis as compared to wall motion assessment for detecting coronary artery disease during dobutamine stress echocardiography in patients undergoing elective vascular surgery. METHODS AND RESULTS: Left ventricular volumes, measured by using the ellipsoid biplane method combining the apical four- and two-chamber echocardiographic views, and classical wall motion score were determined at rest and peak stress (dobutamine infusion 5-40 microg/kg/min+/- atropine 0.25-1mg) in 68 consecutive patients. A positive test was defined as a decrease of less than 15% in left ventricular end-diastolic or end-systolic volume at peak stress for volume analysis and as an increase in score between rest and peak stress in one or more segments for wall motion assessment. Stress test was not analysable in five patients. Coronary angiography revealed significant coronary artery disease (coronary stenosis >or=70%) in 28/63 (44%) patients: one-vessel in 15, two- or three-vessel disease in 13. Overall sensitivity and specificity for coronary artery disease detection were 56% and 97% with left ventricular volume analysis, as compared to 64% and 89% with wall motion assessment. For patients with two- or three-vessel disease, sensitivity and specificity of volume analysis reached 92%. CONCLUSION: The present data suggest that left ventricular volume change analysis during dobutamine stress echocardiography could be a reliable method for the detection of extensive coronary artery disease for patients undergoing vascular surgery.

Adrenergic beta-Agonists↗

PubMed2000

Phospholipase D and RalA cooperate with the epidermal growth factor receptor to transform 3Y1 rat fibroblasts.

3Y1 rat fibroblasts overexpressing the epidermal growth factor (EGF) receptor (EGFR cells) become transformed when treated with EGF. A common response to oncogenic and mitogenic stimuli is elevated phospholipase D (PLD) activity. RalA, a small GTPase that functions as a downstream effector molecule of Ras, exists in a complex with PLD1. In the EGFR cells, EGF induced a Ras-dependent activation of RalA. The activation of PLD by EGF in these cells was dependent upon both Ras and RalA. In contrast, EGF-induced activation of Erk1, Erk2, and Jun kinase was dependent on Ras but independent of RalA, indicating divergent pathways activated by EGF and mediated by Ras. The transformed phenotype induced by EGF in the EGFR cells was dependent upon both Ras and RalA. Importantly, overexpression of wild-type RalA or an activated RalA mutant increased PLD activity in the absence of EGF and transformed the EGFR cells. Although overexpression of PLD1 is generally toxic to cells, the EGFR cells not only tolerated PLD1 overexpression but also became transformed in the absence of EGF. These data demonstrate that either RalA or PLD1 can cooperate with EGF receptor to transform cells.

Animals↗

PubMed2000

Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients.

PURPOSE: To evaluate the accuracy of dual-section helical computed tomography (CT) in acute pulmonary embolism (PE) diagnosis. MATERIALS AND METHODS: Of 204 consecutive patients with clinically suspected acute PE (mean age, 58 years +/- 14 [SD]), 158 were enrolled. All patients underwent dual-section helical CT (2.7-mm effective section thickness) and selective pulmonary arteriography within 12 hours of each other. Each image was analyzed independently by two observers, who determined image quality and presence of PE among arterial segments, including at the subsegmental level. The final diagnosis was made with consensus. RESULTS: Selective pulmonary arteriography was considered optimal in 147 (93%), suboptimal in 10 (6%), and inconclusive in one (0.6%) of 158 patients. Dual-section helical CT findings were considered technically optimal in 140 (89%), suboptimal in 11 (7%), and inconclusive in six (4%). Selective pulmonary arteriography demonstrated PE in 62 patients. Four (6%) of 62 patients had isolated subsegmental PE. The sensitivity of dual-section helical CT was 90%, and the specificity was 94%. The positive and negative predictive values were 90% and 94%, respectively. CONCLUSION: Dual-section helical CT is an improvement in helical CT that offers a high sensitivity and specificity for the depiction of PE, including at the subsegmental level. Dual-section helical CT can replace pulmonary arteriography for the direct demonstration of PE in a majority of patients.

Acute Disease↗

PubMed2000

Preliminary evaluation of two new rapid immunoturbidimetric D-dimer assays in patients with clinically suspected venous thromboembolism (VTE).

The practical utility and diagnostic accuracy of two new rapid, automated and quantitative immunoturbidimetric D-dimer methods have been evaluated in a population of 123 randomly selected patients with suspected VTE. The STA Liatest D-dimer and MDA D-dimer methods are based on the photo-optical measurement of the rate of agglutination of antibody-coated latex particles. The VIDAS D-dimer automated Elisa was used as the reference method. Diagnosis was confirmed in 51 patients (29 PE, 19 DVT, 3 DVT+PE). The immunoturbidimetric methods compared favorably with the VIDAS Elisa as judged from the correlation coefficients of linear regression lines (r = 0.82, MDA vs VIDAS; r = 0.75, STA vs VIDAS) and areas under the curve of ROC plots (VIDAS 0.83; STA 0.83; MDA 0.81). At a discriminant value of 500 ng/mL, all three D-dimer assays showed high sensitivity (96-98%), high NPV (93-97%) and moderate specificity (39-42%). Reproducibility of results around the cut-off is an important aspect of the diagnostic utility of D-dimer assays. CV's of duplicate determinations in this critical zone showed average values of 5.4% and 17.0% for MDA and STA, respectively. These data demonstrate that such rapid and automated latex-based methods for the quantitative measurement of D-dimer hold promise as reliable and cost-efficient approaches for the exclusion of VTE. Prospective patient management studies will be required to confirm this.

Adult↗

PubMed2000

Roundtable discussion: Part I--Epidemiologic, demographic, and treatment challenges in hypertension.

Hypertension is one of the most pervasive medical disorders in this country. As the nation's population ages, the number of patients with hypertension can be expected to rise substantially. On December 9, 1999, a panel of managed care medical directors, pharmacy directors, clinicians, and health economists convened in Irvine, Texas to discuss aspects of hypertension management and economic analysis. This roundtable is presented in three parts, including (1) a summary of the challenges of hypertension management from the point of view of the clinician, (2) the introduction of a pharmacoeconomic model of hypertension management, and (3) a discussion of how health plans approach this insidious disorder.

Aged↗

PubMed2000

Roundtable discussion: Part II--Development of a pharmacoeconomic model in hypertension.

Antihypertensive medications are targeted by most health plans as a major cost center. However, the efficacy of these medications, their side effects, and their resulting ability to prevent serious long-term complications must be factored into the value equation. To illustrate the possible economic effects of a single antihypertensive agent's inclusion on a health plan's drug formulary, an innovative pharmacoeconomic model was developed. In this portion of the roundtable, the design, results, and caveats of this model are discussed.

Antihypertensive Agents↗

PubMed2000

Roundtable discussion: Part III--Hypertension management in health plans.

In the final section of the roundtable discussion, participants describe how their individual managed care plans approach hypertension from the standpoints of disease management targeting, strategies to combat noncompliance, and how these plans utilize pharmacoeconomic information in drug formulary decision making.

Antihypertensive Agents↗

PubMed2000

Comparative profiles of sodium valproate and ethosuximide on electro-behavioural correlates in gamma-hydroxybutyrate and pentylenetetrazol induced absence seizures in rats.

Sodium valproate (VPA) and ethosuximide (ESM) were compared on behavioural and EEG changes in gamma-hydroxybutyrate (GHB) and pentylenetetrazole (PTZ) rat models of Absence Seizures (AS). Both GHB, 100 mg/kg i.p. and PTZ, 20 mg/kg i.p., produced repetitive episodes of staring and immobility with concomitant 6 to 9 Hz spike and wave discharges (SWDs) in the EEG. The parameters used for drug evaluation were the number and duration of SWDs/hour. Though the number of SWDs/hour produced by GHB and PTZ were not significantly different, the duration of SWDs was significantly longer in GHB treated rats (P < 0.001) VPA and ESM, at 200 mg/kg i.p., reduced SWD number and duration in GHB pretreated rats, whereas ESM, 50 mg/kg i.p., was four times more effective than VPA, 200 mg/kg i.p., in the PTZ model. Phenytoin (PHY) 20 and Carbamazepine (CBZ) 10 mg/kg i.p., worsened AS, a feature which has also been reported clinically. Both rat models of experimental AS can be used to defect potential anti-absence activity in new chemical entities.

Animals↗

PubMed1999

Ral and Rho-dependent activation of phospholipase D in v-Raf-transformed cells.

Phospholipase D (PLD) activity is commonly elevated in response to mitogenic signals. We reported previously that although the transformed phenotype induced by v-Src was dependent upon Raf-1, the PLD activity induced by v-Src was independent of Raf-1. This observation suggested to us that Raf would not likely be an activator of PLD. However, upon examination of PLD activity in v-Raf-transformed cells, surprisingly, we found that PLD activity is elevated to levels that were even higher than that observed in v-Src-transformed cells. To characterize the mechanism of v-Raf-induced PLD activity, we examined the dependence of v-Raf-induced PLD activity upon protein kinase C (PKC) the small GTPases Ral and Rho, which have all been implicated in the activation of PLD. The v-Raf-induced PLD activity was inhibited by dominant negative mutants for both Ral and Rho. The dependence upon Ral was particularly surprising since Ral is a downstream target of Ras, which is an upstream activator of Raf. Depleting cells of PKC by long term phorbol ester treatment actually increased PLD activity in v-Raf-transformed cells, indicating that v-Raf-induced PLD activity is not dependent on PKC. These data describe a novel mechanism for PLD activation by v-Raf that is independent of PKC, but dependent upon both Ral and Rho GTPases.

3T3 Cells↗

PubMed1999

Coronary stenting in diabetics: immediate and mid-term clinical outcome.

Balloon angioplasty in diabetics is associated with acceptable immediate results but with high rates of restenosis, target vessel revascularization, and late mortality. The impact of coronary stenting on the outcome of these patients remains controversial. We reported the immediate and mid-term clinical outcome of 272 consecutive diabetic patients, representing 12.5% of the population undergoing coronary stenting between May 1995 and April 1997. Diabetes mellitus was insulin-requiring in 58 patients and non-insulin-requiring in 214. Stenting performed on large vessels (mean diameter >/=3 mm) was successful in 99.2% of nondiabetic patients and in all cases in diabetics. During in-hospital stay, the complications rate, including mortality, nonfatal myocardial infarction, emergency coronary bypass surgery, and stent subacute thrombosis, was similar in nondiabetic patients, insulin-requiring, and non-insulin-requiring diabetics (2.55%, 0%, and 2.0%, respectively). No complication occurred in the insulin-requiring group. One patient (0.5%) died from myocardial infarction and another (0.5%) presented a nonfatal myocardial infarction (subacute stent thrombosis) in the non-insulin-requiring group. The clinical follow-up (mean length 13 +/- 8 months) was obtained in 93% and 97% of the insulin-requiring and non-insulin-requiring diabetics, respectively. Overall mortality was significantly higher in insulin-requiring patients (9.3% vs. 2.4%). Nonfatal myocardial infarction and target lesion revascularization rates were similar in the two groups (0% vs. 0.5% and 8.2% vs. 10.5%). These results suggest that coronary stenting in diabetics could be performed with acceptable immediate and mid-term results. Cathet. Cardiovasc. Intervent. 47:279-284, 1999.

Aged↗

PubMed1999

Antagonistic effects of protein kinase C alpha and delta on both transformation and phospholipase D activity mediated by the epidermal growth factor receptor.

Downregulation of protein kinase C delta (PKC delta) by treatment with the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) transforms cells that overexpress the non-receptor class tyrosine kinase c-Src (Z. Lu et al., Mol. Cell. Biol. 17:3418-3428, 1997). We extended these studies to cells overexpressing a receptor class tyrosine kinase, the epidermal growth factor (EGF) receptor (EGFR cells); like c-Src, the EGF receptor is overexpressed in several human tumors. In contrast with expectations, downregulation of PKC isoforms with TPA did not transform the EGFR cells; however, treatment with EGF did transform these cells. Since TPA downregulates all phorbol ester-responsive PKC isoforms, we examined the effects of PKC delta- and PKC alpha-specific inhibitors and the expression of dominant negative mutants for both PKC delta and alpha. Consistent with a tumor-suppressing function for PKC delta, the PKC delta-specific inhibitor rottlerin and a dominant negative PKC delta mutant transformed the EGFR cells in the absence of EGF. In contrast, the PKC alpha-specific inhibitor Go6976 and expression of a dominant negative PKC alpha mutant blocked the transformed phenotype induced by both EGF and PKC delta inhibition. Interestingly, both rottlerin and EGF induced substantial increases in phospholipase D (PLD) activity, which is commonly elevated in response to mitogenic stimuli. The elevation of PLD activity in response to inhibiting PKC delta, like transformation, was dependent upon PKC alpha and restricted to the EGFR cells. These data demonstrate that PKC isoforms alpha and delta have antagonistic effects on both transformation and PLD activity and further support a tumor suppressor role for PKC delta that may be mediated by suppression of tyrosine kinase-dependent increases in PLD activity.

Acetophenones↗

PubMed1999

Intra-fourth-ventricle teratoma.

The computed tomographic (CT) scanning characteristics of a case of intra-fourth-ventricle mature teratoma in a 15-month-old child are described and correlated with intraoperative findings.

Brain Neoplasms↗

PubMed1999

[Reconstruction of saphenous vein grafts using Wallstent endoprostheses. Immediate and mid-term results].

Balloon angioplasty of degenerated saphenous vein grafts is associated with a high incidence of restenosis and of cardiac events in the medium and long term. Implantation of stents has reduced the incidence of these complications in patients with focal lesions. The authors report the short and medium term clinical results of saphenous vein grafts reconstruction in cases of diffuse graft disease with Wallstent endoprostheses in a series of 73 patients. All were pretreated with aspirin, ticlopidine and enoxaparine started 72 hours before the procedure and 15 also received c7E3Fab during angioplasty. One hundred and twenty stents were implanted in 90 saphenous vein grafts. There were 5 deaths (6.9%), 2 of which were cardiac, during the hospital period. One patient (1.4%) underwent secondary coronary bypass surgery. Eight patients (11%) suffered distal embolisation resulting in non-Q wave infarction. Clinical follow-up for an average of 13 months (3-26 months) was obtained in 91% of patients. Five (8.1%) died, three of cardiac causes, and one patient (1.7%) suffered a non-lethal myocardial infarction. A repeat revascularisation procedure of the culprit lesion was performed in 9 patients (15.8%). Angioplasty of other lesions was carried out in 7 patients (12.3%). Reconstruction of venous bypass grafts with diffuse lesions by implantation of Wallstent endoprostheses associated with preventive antiaggregant and anticoagulant therapy is associated with a risk of immediate complications. The medium-term results indicate high morbidity and cardiac mortality rates.

Aged↗

PubMed1999

Effect of sodium valproate and flunarizine administered alone and in combination on pentylenetetrazole model of absence seizures in rat.

Sodium valproate (VPA) and flunarizine (FLU) administered individually and together were examined for their effects on behavioural, and EEG changes in the pentylenetetrazole (PTZ) induced rat model of absence seizures. PTZ, 20 mg/kg, i.p., produced behavioural staring and immobility with concomitant, repetitive 7 to 9 Hz spike/wave discharges (SWDs) in EEG, monitored continuously for 1 hr and thereafter, intermittently for 4 hr, post-vehicle/drug. The number and duration (sec) of SWDs/hr were the parameters used for evaluation of vehicle vs. drug effects in normal as well as rats made epileptogenic by repeated cortical stimulation. VPA, 200 mg/kg, i.p., produced a significant reduction in the number and duration of SWDs at 20 min only in epileptogenic rats, declining to non-significant levels at 60 min, whereas FLU, 10 mg/kg i.p. had no effect on either parameter. The combination of VPA and FLU produced a highly significant reduction of the number and duration of SWDs/h for 60 min in normal and epileptogenic rats. The results provide evidence for a synergistic effect of VPA and FLU in experimental absence seizures and possible potential benefit in pharmaco resistant seizures.

Animals↗

PubMed1998

Acute profound thrombocytopenia after abciximab therapy during coronary angioplasty.

Since the extensive use of abciximab, a potent antiplatelet agent directed against GP IIb/IIIa platelet receptors, to prevent ischemic complications of percutaneous transluminal coronary angioplasty, few cases of thrombocytopenia have been observed. This paper reports a case of acute profound thrombocytopenia (platelet count: 800/mm3) occurring 16 h after abciximab therapy during coronary angioplasty. As thrombocytopenia occurrence is not predictable, platelet count should be evaluated periodically after drug administration. Mechanisms of this adverse effect remain unknown. Platelet transfusion results in a rapid and sustained improvement of platelet count, avoiding the occurrence of major hemorrhagic complications.

Abciximab↗

PubMed1998

Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.

Adult↗