Shailendra Verma - Academia.edu (original) (raw)

Papers by Shailendra Verma

Research paper thumbnail of International Journal on Recent and Innovation Trends in Computing and Communication

International Journal on Recent and Innovation Trends in Computing and Communication

Research paper thumbnail of Fast magnetic resonance angiography using turbo-FLASH sequences in advanced aortoiliac disease

British Journal of Radiology, 1993

A prospective study using contrast enhanced turbo-FLASH (Fast Low-Angle Shot) magnetic resonance ... more A prospective study using contrast enhanced turbo-FLASH (Fast Low-Angle Shot) magnetic resonance (MR) angiography was performed to assess the arterial anatomy in patients who had advanced atherosclerotic aortoiliac disease. This new imaging sequence was employed in 17 patients and the results were compared with conventional abdominal aortography. MR angiography accurately detected all aortic occlusions (3/3), their sites and their extent. All nine iliac occlusions were correctly identified (sensitivity 100%, specificity of 90%). The sensitivity was 100% for stenosis of 50% or greater in the abdominal aorta, and the iliac and common femoral arteries. The degree of stenosis was overgraded in 20 of 51 lesions (39.2%). Mild stenosis was overgraded as moderate stenosis in 10 and as severe stenosis in three. Moderate stenosis was overgraded as severe stenosis in four. None of the mild or moderate stenoses resulted in areas of signal voids suggestive of occlusions. Three severe stenoses were seen as areas of signal voids (two iliac, one femoral). In the eight patients who had in total 10 aneurysmal dilatations of the aorta or the iliac arteries, MR angiography was superior in demonstrating the true extent of the aneurysms. We conclude that turbo-FLASH MR angiography has the potential to be a useful non-invasive imaging technique for patients with advanced aortoiliac disease.

Research paper thumbnail of Balloon angioplasty of totally and subtotally occluded coronary arteries: results using the hydrophillic terumo radifocus guidewire m (glidewire

Catheterization and Cardiovascular Diagnosis, 1993

Balloon angioplasty was attempted, using hydrophillic Terumo guidewires, in 52 totally and subtot... more Balloon angioplasty was attempted, using hydrophillic Terumo guidewires, in 52 totally and subtotally occluded coronary arteries (50 patients), in which recanalisation by conventional angioplasty guidewires had failed. Hydrophillic guidewires had a crossing success rate of 65.4% (34/52); there was subsequently a technical success rate of 56% (29/52) and clinical success of 39% (20/52). Dissection of the coronary artery was seen in 16/29 technically successful cases. In 12/16 arteries, dissection was small and localised, whereas in 4/16 large and extended distally. There was one myocardial infarction and no peri-procedural deaths. Eleven out of 29 technically successful cases continued to be regarded as successful 12 no postangioplasty. We conclude that the hydrophillic Terumo guidewire can improve the success rate in angioplasty of totally and subtotally occluded coronary arteries when conventional wires have failed. © 1993 Wlley-Liss, Inc

Research paper thumbnail of Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment

Psycho-oncology, 2009

Objective: Studies in breast cancer patients indicate that chemotherapy may cause subtle cognitiv... more Objective: Studies in breast cancer patients indicate that chemotherapy may cause subtle cognitive disturbances in some women, but the course is unclear. The current study evaluated the cognitive effects of adjuvant chemotherapy in post-menopausal breast cancer patients 1 year following completion of treatment.Patients and methods: Breast cancer patients scheduled to receive adjuvant chemotherapy (n=53) completed comprehensive neuropsychological testing before commencing chemotherapy (T1), 1 month after completing chemotherapy (T2), and again 1 year later (T3). A control group of women receiving adjuvant hormonal therapy (n=40) was tested at comparable intervals. A standardized regression-based approach was used to identify cognitive decline, and incidence of decline was compared across treatment groups.Results: Whereas at T2, chemotherapy patients were more likely to show cognitive decline than hormonal patients, by T3, the frequency of reliable cognitive decline was the same in both groups (11 and 10%, respectively). However, those chemotherapy patients receiving hormonal therapy at T3 were inferior to the chemotherapy patients not receiving hormonal treatment on composite measures of processing speed and verbal memory.Conclusion: These data suggest that there is a subtle negative impact of chemotherapy on cognitive function in breast cancer patients shortly following completion of treatment, but that this resolves within 1 year. However, given that our control group comprises breast cancer patients receiving hormonal therapy, and indications that hormonal therapy may also adversely affect cognition, such conclusions must be considered tentative. Copyright © 2008 John Wiley & Sons, Ltd.

Research paper thumbnail of Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study

Psycho-oncology, 2009

Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant ho... more Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients.Participants and Methods: Post-menopausal breast cancer patients scheduled to receive tamoxifen (n=31) or anastrozole (n=14) completed neuropsychological testing around the time of commencement of treatment (T1), and again 5–6 months later (T2). A sample of healthy female volunteers (n=28) was tested at comparable intervals. A standardized regression-based approach was used to assess cognitive change. This method uses test/retest scores of the healthy control group to generate an equation that predicts T2 scores from T1 scores. The difference between the predicted and obtained T2 scores divided by the standard error of the estimate produces a deviation score that reflects the discrepancy from the T1–T2 difference scores that would be expected on the basis of practice and error alone.Results: Analysis of individual deviation scores revealed that both the patients taking tamoxifen and those taking anastrozole were more likely than healthy controls to show reliable cognitive decline from T1 to T2 (39, 64, and 7%, respectively). Processing speed and verbal memory were the cognitive domains most affected.Conclusion: These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area. Copyright © 2008 John Wiley & Sons, Ltd.

Research paper thumbnail of The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study

Psycho-oncology, 2008

Purpose: The primary purpose of this study was to evaluate the cognitive effects of adjuvant chem... more Purpose: The primary purpose of this study was to evaluate the cognitive effects of adjuvant chemotherapy in post-menopausal breast cancer patients.Patients and methods: Breast cancer patients scheduled to receive adjuvant chemotherapy (n = 61) completed comprehensive cognitive testing before and after treatment. A control group of women receiving adjuvant hormonal therapy (n = 51) was tested at comparable intervals.Results: Mean scores for both patient groups were within the normal range relative to published norms on all cognitive tests at both time points, and generally inclined or stayed the same from baseline to retest in both groups. However, in an analysis of individual change scores, the chemotherapy patients were 3.3 times more likely than the hormonal patients to show reliable cognitive decline (31 and 12%, respectively). Chemotherapy subjects showing decline were less educated and had higher baseline depression scores than their counterparts who did not decline. Working memory was the cognitive domain most vulnerable to the effects of chemotherapy.Conclusion: These data support previous findings of a subtle negative influence of chemotherapy on cognitive function in a subgroup of breast cancer patients. The results are discussed in terms of the importance of study design. Copyright © 2007 John Wiley & Sons, Ltd.

Research paper thumbnail of Selection of adjuvant chemotherapy for treatment of node-positive breast cancer

Lancet Oncology, 2005

Over the past two decades, several studies have suggested that regimens that contain anthracyclin... more Over the past two decades, several studies have suggested that regimens that contain anthracyclines are more effective than those that do not. A meta-analysis by the 2005 Early Breast Cancer Trialists' Collaborative Group confirmed that about 6 months of anthracycline-based polychemotherapy in the adjuvant setting reduced the yearly death rate from breast cancer by about 38% for women younger than 50 years and by 20% for women aged 50-69 years. Although this meta-analysis found that survival was better with regimens that contain anthracycline than with regimens based on cyclophosphamide, methotrexate, and fluorouracil, the best use of anthracycline-based regimens remains unclear. Adjuvant regimens in use can be categorised into three groups: standard-dose anthracycline; escalated-dose epirubicin; and anthracyclines and taxanes. The duration of treatment and combination of dose and drugs varies between these three categories. We reviewed the three types of regimen to establish which provide a better outcome in terms of safety, efficacy, cost, and convenience to patients. We found that both escalated-dose epirubicin and anthracycline-taxane regimens were most effective in terms of disease-free survival and overall survival. Of the specific anthracycline-based regimens, the docetaxel, doxorubicin, and cyclophosphamide regimen (TAC); the fluorouracil, 100 mg epirubicin, and cyclophosphamide regimen (FEC100); and the cyclophosphamide, epirubicin, and fluorouracil regimen (CEF) produced the greatest proportional decreases in 5-year death rate.

Research paper thumbnail of Use of Trastuzumab Beyond Disease Progression: Observations from a Retrospective Review of Case Histories

Clinical Breast Cancer, 2004

HER2 overexpression is associated with poor breast cancer prognosis and is the target for the hum... more HER2 overexpression is associated with poor breast cancer prognosis and is the target for the humanized monoclonal antibody trastuzumab. This novel agent, when administered until disease progression in combination with chemotherapy, extends the survival of women with HER2-positive metastatic breast cancer (MBC). However, the optimal duration of trastuzumab therapy remains to be confirmed. We conducted a retrospective case review study of women with HER2-positive MBC who continued to receive trastuzumab beyond disease progression. Objectives were to assess whether treatment beyond disease progression shows any evidence of efficacy and to evaluate the feasibility of this approach. One hundred five patients (median age, 47 years; range, 24-77 years) were identified in 13 centers. Women had received ≤ 6 chemotherapy regimens (median, 1) before trastuzumab therapy. Median survival from first trastuzumab dose was 29 months. The overall response rate to trastuzumab alone or with a taxane as the first regimen was 39%; a further 30% of patients had stable disease as the best response. These rates were 36% and 38% after a second regimen of trastuzumab alone or with paclitaxel or vinorelbine was administered. Some patients responded to both the first and second regimens; others responded to the second regimen after the first had failed. Twenty-two patients experienced cardiac events, of whom 18 received ≥ 1 more trastuzumab regimen. Trastuzumab treatment beyond progression appears to be of value, producing responses and clinical benefit, and is well tolerated without significant cardiac toxicity. The feasibility of this approach warrants examination in prospective trials.

Research paper thumbnail of Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals

European Heart Journal, 2004

The present study was designed to (a) examine the interrelationship between endothelial function ... more The present study was designed to (a) examine the interrelationship between endothelial function and CRP in healthy individuals and (b) evaluate the relationship of each biomarker towards global Framingham risk scores. Brachial artery flow-mediated vasodilatation (FMD), CRP, and traditional cardiovascular risk factors were measured in the Firefighters and Their Endothelium (FATE) study, which recruited 1154 male participants (mean age 47.4+/-9.8 years) with no known history of cardiovascular disease. No relationship was observed between FMD and CRP (p = 0.96). FMD and the Framingham risk score tended to correlate but not significantly (p = 0.07). A lower FMD was related to a higher systolic and diastolic blood pressure (p < 0.001 and p = 0.002, respectively) in the univariate analysis, and higher systolic blood pressure (p = 0.001) in the multivariate analysis. Elevated CRP levels independently correlated most closely with overall Framingham risk score (r = 0.36, p < 0.001) and a weaker although statistically significant relationship was seen with individual traditional cardiovascular risk factors (p < 0.005). The current study provided evidence that brachial artery FMD had no relationship to CRP in a large cohort of healthy subjects. These observations suggest that the predictive value of CRP may be largely independent of abnormalities in endothelial function. The additive prognostic value of endothelial vasodilator testing remains to be established.

Research paper thumbnail of Cyclooxygenase2 Blockade Does Not Impair Endothelial Vasodilator Function in Healthy Volunteers: Randomized Evaluation of Rofecoxib Versus Naproxen on Endothelium-Dependent Vasodilatation

Circulation, 2001

Background-From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has ... more Background-From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has been a topic of increasing concern. This concern stemmed from observations indicating that the COX-2 isoform is the major source of endothelium-derived prostacyclin and, hence, that selective blockade of this enzyme may impair endothelial health. To investigate this matter, we examined the effects of 7 days of treatment with rofecoxib versus naproxen on endothelial function in healthy volunteers. Methods and Results-Thirty-five healthy volunteers were randomized to receive 7-day treatment with either rofecoxib (25 mg/d, nϭ18) or naproxen (750 mg/d, nϭ17). Vascular response measurements were conducted using forearm strain-gauge plethysmography. Changes in forearm blood flow in response to the endothelium-dependent vasodilator acetylcholine (3, 10, and 30 g/min) and the endothelium-independent vasodilator sodium nitroprusside (1 and 10 g/min) were assessed before and after treatment. Acetylcholine evoked a dose-dependent increase in forearm blood flow in all groups. Importantly, treatment resulted in no change in acetylcholine-mediated increases in forearm blood flow in either group (naproxen, Pϭ0.27; rofecoxib, Pϭ0.58). Similarly, there was no change in forearm blood flow in response to sodium nitroprusside (naproxen, Pϭ0.55; rofecoxib, Pϭ0.63).

Research paper thumbnail of Safety and Efficacy of the Multidrug Resistance Inhibitor Incel (Biricodar; VX-710) in Combination with Paclitaxel for Advanced Breast Cancer Refractory to Paclitaxel

Purpose: VX-710 (biricodar, Incel) restores drug sensitivity to P-glycoprotein (MDR1) and multidr... more Purpose: VX-710 (biricodar, Incel) restores drug sensitivity to P-glycoprotein (MDR1) and multidrug resistanceassociated protein (MRP1)-expressing cells. This Phase II study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710 plus paclitaxel in women with locally advanced or metastatic breast cancer who were refractory to prior paclitaxel therapy.

Research paper thumbnail of 1 A Network Simulator for Education and Fast Protocol Development: Nessi

A new and simple Python network simulator Nessi is described in this paper. While other simulator... more A new and simple Python network simulator Nessi is described in this paper. While other simulators focus on minimizing the simulation time, Nessi tries to minimize the development time and the difficulties to implement a new simulation model. As such, it is mainly oriented toward educational use, where it enables students to implement or modify simulation models of protocols with minimal overhead. A second application of Nessi is for verification and performance evaluation of new protocols, where it allows the developer to easily explore different options.

Research paper thumbnail of International Journal on Recent and Innovation Trends in Computing and Communication

International Journal on Recent and Innovation Trends in Computing and Communication

Research paper thumbnail of Fast magnetic resonance angiography using turbo-FLASH sequences in advanced aortoiliac disease

British Journal of Radiology, 1993

A prospective study using contrast enhanced turbo-FLASH (Fast Low-Angle Shot) magnetic resonance ... more A prospective study using contrast enhanced turbo-FLASH (Fast Low-Angle Shot) magnetic resonance (MR) angiography was performed to assess the arterial anatomy in patients who had advanced atherosclerotic aortoiliac disease. This new imaging sequence was employed in 17 patients and the results were compared with conventional abdominal aortography. MR angiography accurately detected all aortic occlusions (3/3), their sites and their extent. All nine iliac occlusions were correctly identified (sensitivity 100%, specificity of 90%). The sensitivity was 100% for stenosis of 50% or greater in the abdominal aorta, and the iliac and common femoral arteries. The degree of stenosis was overgraded in 20 of 51 lesions (39.2%). Mild stenosis was overgraded as moderate stenosis in 10 and as severe stenosis in three. Moderate stenosis was overgraded as severe stenosis in four. None of the mild or moderate stenoses resulted in areas of signal voids suggestive of occlusions. Three severe stenoses were seen as areas of signal voids (two iliac, one femoral). In the eight patients who had in total 10 aneurysmal dilatations of the aorta or the iliac arteries, MR angiography was superior in demonstrating the true extent of the aneurysms. We conclude that turbo-FLASH MR angiography has the potential to be a useful non-invasive imaging technique for patients with advanced aortoiliac disease.

Research paper thumbnail of Balloon angioplasty of totally and subtotally occluded coronary arteries: results using the hydrophillic terumo radifocus guidewire m (glidewire

Catheterization and Cardiovascular Diagnosis, 1993

Balloon angioplasty was attempted, using hydrophillic Terumo guidewires, in 52 totally and subtot... more Balloon angioplasty was attempted, using hydrophillic Terumo guidewires, in 52 totally and subtotally occluded coronary arteries (50 patients), in which recanalisation by conventional angioplasty guidewires had failed. Hydrophillic guidewires had a crossing success rate of 65.4% (34/52); there was subsequently a technical success rate of 56% (29/52) and clinical success of 39% (20/52). Dissection of the coronary artery was seen in 16/29 technically successful cases. In 12/16 arteries, dissection was small and localised, whereas in 4/16 large and extended distally. There was one myocardial infarction and no peri-procedural deaths. Eleven out of 29 technically successful cases continued to be regarded as successful 12 no postangioplasty. We conclude that the hydrophillic Terumo guidewire can improve the success rate in angioplasty of totally and subtotally occluded coronary arteries when conventional wires have failed. © 1993 Wlley-Liss, Inc

Research paper thumbnail of Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment

Psycho-oncology, 2009

Objective: Studies in breast cancer patients indicate that chemotherapy may cause subtle cognitiv... more Objective: Studies in breast cancer patients indicate that chemotherapy may cause subtle cognitive disturbances in some women, but the course is unclear. The current study evaluated the cognitive effects of adjuvant chemotherapy in post-menopausal breast cancer patients 1 year following completion of treatment.Patients and methods: Breast cancer patients scheduled to receive adjuvant chemotherapy (n=53) completed comprehensive neuropsychological testing before commencing chemotherapy (T1), 1 month after completing chemotherapy (T2), and again 1 year later (T3). A control group of women receiving adjuvant hormonal therapy (n=40) was tested at comparable intervals. A standardized regression-based approach was used to identify cognitive decline, and incidence of decline was compared across treatment groups.Results: Whereas at T2, chemotherapy patients were more likely to show cognitive decline than hormonal patients, by T3, the frequency of reliable cognitive decline was the same in both groups (11 and 10%, respectively). However, those chemotherapy patients receiving hormonal therapy at T3 were inferior to the chemotherapy patients not receiving hormonal treatment on composite measures of processing speed and verbal memory.Conclusion: These data suggest that there is a subtle negative impact of chemotherapy on cognitive function in breast cancer patients shortly following completion of treatment, but that this resolves within 1 year. However, given that our control group comprises breast cancer patients receiving hormonal therapy, and indications that hormonal therapy may also adversely affect cognition, such conclusions must be considered tentative. Copyright © 2008 John Wiley & Sons, Ltd.

Research paper thumbnail of Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study

Psycho-oncology, 2009

Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant ho... more Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients.Participants and Methods: Post-menopausal breast cancer patients scheduled to receive tamoxifen (n=31) or anastrozole (n=14) completed neuropsychological testing around the time of commencement of treatment (T1), and again 5–6 months later (T2). A sample of healthy female volunteers (n=28) was tested at comparable intervals. A standardized regression-based approach was used to assess cognitive change. This method uses test/retest scores of the healthy control group to generate an equation that predicts T2 scores from T1 scores. The difference between the predicted and obtained T2 scores divided by the standard error of the estimate produces a deviation score that reflects the discrepancy from the T1–T2 difference scores that would be expected on the basis of practice and error alone.Results: Analysis of individual deviation scores revealed that both the patients taking tamoxifen and those taking anastrozole were more likely than healthy controls to show reliable cognitive decline from T1 to T2 (39, 64, and 7%, respectively). Processing speed and verbal memory were the cognitive domains most affected.Conclusion: These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area. Copyright © 2008 John Wiley & Sons, Ltd.

Research paper thumbnail of The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study

Psycho-oncology, 2008

Purpose: The primary purpose of this study was to evaluate the cognitive effects of adjuvant chem... more Purpose: The primary purpose of this study was to evaluate the cognitive effects of adjuvant chemotherapy in post-menopausal breast cancer patients.Patients and methods: Breast cancer patients scheduled to receive adjuvant chemotherapy (n = 61) completed comprehensive cognitive testing before and after treatment. A control group of women receiving adjuvant hormonal therapy (n = 51) was tested at comparable intervals.Results: Mean scores for both patient groups were within the normal range relative to published norms on all cognitive tests at both time points, and generally inclined or stayed the same from baseline to retest in both groups. However, in an analysis of individual change scores, the chemotherapy patients were 3.3 times more likely than the hormonal patients to show reliable cognitive decline (31 and 12%, respectively). Chemotherapy subjects showing decline were less educated and had higher baseline depression scores than their counterparts who did not decline. Working memory was the cognitive domain most vulnerable to the effects of chemotherapy.Conclusion: These data support previous findings of a subtle negative influence of chemotherapy on cognitive function in a subgroup of breast cancer patients. The results are discussed in terms of the importance of study design. Copyright © 2007 John Wiley & Sons, Ltd.

Research paper thumbnail of Selection of adjuvant chemotherapy for treatment of node-positive breast cancer

Lancet Oncology, 2005

Over the past two decades, several studies have suggested that regimens that contain anthracyclin... more Over the past two decades, several studies have suggested that regimens that contain anthracyclines are more effective than those that do not. A meta-analysis by the 2005 Early Breast Cancer Trialists' Collaborative Group confirmed that about 6 months of anthracycline-based polychemotherapy in the adjuvant setting reduced the yearly death rate from breast cancer by about 38% for women younger than 50 years and by 20% for women aged 50-69 years. Although this meta-analysis found that survival was better with regimens that contain anthracycline than with regimens based on cyclophosphamide, methotrexate, and fluorouracil, the best use of anthracycline-based regimens remains unclear. Adjuvant regimens in use can be categorised into three groups: standard-dose anthracycline; escalated-dose epirubicin; and anthracyclines and taxanes. The duration of treatment and combination of dose and drugs varies between these three categories. We reviewed the three types of regimen to establish which provide a better outcome in terms of safety, efficacy, cost, and convenience to patients. We found that both escalated-dose epirubicin and anthracycline-taxane regimens were most effective in terms of disease-free survival and overall survival. Of the specific anthracycline-based regimens, the docetaxel, doxorubicin, and cyclophosphamide regimen (TAC); the fluorouracil, 100 mg epirubicin, and cyclophosphamide regimen (FEC100); and the cyclophosphamide, epirubicin, and fluorouracil regimen (CEF) produced the greatest proportional decreases in 5-year death rate.

Research paper thumbnail of Use of Trastuzumab Beyond Disease Progression: Observations from a Retrospective Review of Case Histories

Clinical Breast Cancer, 2004

HER2 overexpression is associated with poor breast cancer prognosis and is the target for the hum... more HER2 overexpression is associated with poor breast cancer prognosis and is the target for the humanized monoclonal antibody trastuzumab. This novel agent, when administered until disease progression in combination with chemotherapy, extends the survival of women with HER2-positive metastatic breast cancer (MBC). However, the optimal duration of trastuzumab therapy remains to be confirmed. We conducted a retrospective case review study of women with HER2-positive MBC who continued to receive trastuzumab beyond disease progression. Objectives were to assess whether treatment beyond disease progression shows any evidence of efficacy and to evaluate the feasibility of this approach. One hundred five patients (median age, 47 years; range, 24-77 years) were identified in 13 centers. Women had received ≤ 6 chemotherapy regimens (median, 1) before trastuzumab therapy. Median survival from first trastuzumab dose was 29 months. The overall response rate to trastuzumab alone or with a taxane as the first regimen was 39%; a further 30% of patients had stable disease as the best response. These rates were 36% and 38% after a second regimen of trastuzumab alone or with paclitaxel or vinorelbine was administered. Some patients responded to both the first and second regimens; others responded to the second regimen after the first had failed. Twenty-two patients experienced cardiac events, of whom 18 received ≥ 1 more trastuzumab regimen. Trastuzumab treatment beyond progression appears to be of value, producing responses and clinical benefit, and is well tolerated without significant cardiac toxicity. The feasibility of this approach warrants examination in prospective trials.

Research paper thumbnail of Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals

European Heart Journal, 2004

The present study was designed to (a) examine the interrelationship between endothelial function ... more The present study was designed to (a) examine the interrelationship between endothelial function and CRP in healthy individuals and (b) evaluate the relationship of each biomarker towards global Framingham risk scores. Brachial artery flow-mediated vasodilatation (FMD), CRP, and traditional cardiovascular risk factors were measured in the Firefighters and Their Endothelium (FATE) study, which recruited 1154 male participants (mean age 47.4+/-9.8 years) with no known history of cardiovascular disease. No relationship was observed between FMD and CRP (p = 0.96). FMD and the Framingham risk score tended to correlate but not significantly (p = 0.07). A lower FMD was related to a higher systolic and diastolic blood pressure (p < 0.001 and p = 0.002, respectively) in the univariate analysis, and higher systolic blood pressure (p = 0.001) in the multivariate analysis. Elevated CRP levels independently correlated most closely with overall Framingham risk score (r = 0.36, p < 0.001) and a weaker although statistically significant relationship was seen with individual traditional cardiovascular risk factors (p < 0.005). The current study provided evidence that brachial artery FMD had no relationship to CRP in a large cohort of healthy subjects. These observations suggest that the predictive value of CRP may be largely independent of abnormalities in endothelial function. The additive prognostic value of endothelial vasodilator testing remains to be established.

Research paper thumbnail of Cyclooxygenase2 Blockade Does Not Impair Endothelial Vasodilator Function in Healthy Volunteers: Randomized Evaluation of Rofecoxib Versus Naproxen on Endothelium-Dependent Vasodilatation

Circulation, 2001

Background-From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has ... more Background-From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has been a topic of increasing concern. This concern stemmed from observations indicating that the COX-2 isoform is the major source of endothelium-derived prostacyclin and, hence, that selective blockade of this enzyme may impair endothelial health. To investigate this matter, we examined the effects of 7 days of treatment with rofecoxib versus naproxen on endothelial function in healthy volunteers. Methods and Results-Thirty-five healthy volunteers were randomized to receive 7-day treatment with either rofecoxib (25 mg/d, nϭ18) or naproxen (750 mg/d, nϭ17). Vascular response measurements were conducted using forearm strain-gauge plethysmography. Changes in forearm blood flow in response to the endothelium-dependent vasodilator acetylcholine (3, 10, and 30 g/min) and the endothelium-independent vasodilator sodium nitroprusside (1 and 10 g/min) were assessed before and after treatment. Acetylcholine evoked a dose-dependent increase in forearm blood flow in all groups. Importantly, treatment resulted in no change in acetylcholine-mediated increases in forearm blood flow in either group (naproxen, Pϭ0.27; rofecoxib, Pϭ0.58). Similarly, there was no change in forearm blood flow in response to sodium nitroprusside (naproxen, Pϭ0.55; rofecoxib, Pϭ0.63).

Research paper thumbnail of Safety and Efficacy of the Multidrug Resistance Inhibitor Incel (Biricodar; VX-710) in Combination with Paclitaxel for Advanced Breast Cancer Refractory to Paclitaxel

Purpose: VX-710 (biricodar, Incel) restores drug sensitivity to P-glycoprotein (MDR1) and multidr... more Purpose: VX-710 (biricodar, Incel) restores drug sensitivity to P-glycoprotein (MDR1) and multidrug resistanceassociated protein (MRP1)-expressing cells. This Phase II study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710 plus paclitaxel in women with locally advanced or metastatic breast cancer who were refractory to prior paclitaxel therapy.

Research paper thumbnail of 1 A Network Simulator for Education and Fast Protocol Development: Nessi

A new and simple Python network simulator Nessi is described in this paper. While other simulator... more A new and simple Python network simulator Nessi is described in this paper. While other simulators focus on minimizing the simulation time, Nessi tries to minimize the development time and the difficulties to implement a new simulation model. As such, it is mainly oriented toward educational use, where it enables students to implement or modify simulation models of protocols with minimal overhead. A second application of Nessi is for verification and performance evaluation of new protocols, where it allows the developer to easily explore different options.