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Biomedical subjects

R Chan

Publications and source records attributed to R Chan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Percutaneous treatment of a pancreatic fistula after pancreaticoduodenectomy.

Breakdown of the pancreaticojejunal anastomosis after a Whipple procedure is reported to occur in as many as 15% of cases. Intraoperative placement of a drain adjacent to the anastomosis is performed to allow the creation of a controlled pancreaticocutaneous fistula in the event of an anastomotic disruption. The authors present a case of successful percutaneous treatment of a disrupted pancreaticojejunal anastomosis. This was achieved with use of the resulting pancreaticocutaneous fistula for access to restore internal drainage, followed by fistula occlusion with use of gelatin pledgets.

Anastomosis, Surgical↗
PubMed2001

Retinal pigment epithelium translocation and central visual function in age related macular degeneration: preliminary results.

PURPOSE: To test the feasibility of a new surgical technique, and to assess visual function over the translocated retinal pigment epithelium (RPE) cells in patients operated upon for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). MATERIALS AND METHODS: Six patients presenting previously untreated exudative AMD underwent surgical excision of the subfoveal CNV with RPE translocation and were followed from 1 to 10.5 months. The surgery consisted of a standard three port pars plana vitrectomy (TPPPV), excision of the CNV and RPE translocation. Pre and post-operative ocular examination included best-corrected visual acuity measurement, fundus color stereo photography and fundus fluorescein angiography. Optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (cLSO) were performed post-operatively. A cross fixation target and a single-point flashing light were projected on different areas of the posterior pole using a cLSO. Photopic 10-2 perimetry, photopic fine matrix mapping, cLSO microperimetry were also performed pre and post-operatively in four patients. OCT cross-sectional scans and cLSO RPE autofluorescence were recorded to detect the presence of viable translocated RPE. Visual acuity, fixation, photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry were tested for the presence of central visual function. RESULTS: RPE could be effectively translocated at the time of CNV removal from the edge of the RPE defect to a subfoveal location. OCT showed the translocated RPE as an area of increased optical reflectivity with optical shadowing external to it. cLSO showed autofluorescence of the translocated RPE. The cross fixation target was seen when projected on the translocated RPE. During eccentric fixation, the patients could see a flashing point-target projected on the translocated RPE. Photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry showed presence of central visual function. CONCLUSIONS: The authors propose that translocation of RPE at the time of CNV removal, from the edge of the RPE defect to a subfoveal location, may have a role in the surgical management of AMD.

Aged↗
PubMed2001

Incidence of deep vein thrombosis after colorectal surgery in a Chinese population.

INTRODUCTION: Contemporary studies indicate that the incidence of deep vein thrombosis (DVT) is increasing in the Asian population. The present study aims to evaluate the incidence of postoperative DVT in Chinese patients undergoing surgery for colorectal malignancies. METHODS: Fifty-one consecutive patients with carcinoma of the rectum or sigmoid colon scheduled for resection were included in the study. None of the study subjects were given any form of DVT prophylaxis. Serial duplex ultrasound of both lower limbs were examined in the preoperative and postoperative periods. RESULTS: Three patients were excluded from the study because of the presence of DVT noted preoperatively. A total of 20/48 (41.7%) patients developed asymptomatic calf vein thrombosis. One out of 20 patients required anticoagulation because of thrombus propagation. None of the subjects showed signs or symptoms of DVT or pulmonary embolism. A total of 7/20 thrombi resolved completely at 4 weeks after operation. Only old age and smoking were identified as being associated with a higher incidence of DVT. Disseminated disease, type of operation, duration of operation and postoperative complications did not appear to be risk factors for DVT. CONCLUSION: A high incidence of asymptomatic calf vein thrombosis occurred after colorectal surgery for malignancies in Chinese. The majority did not progress even without anticoagulation.

Age Factors↗
PubMed2001

Bi-modality (chemo-radiation) versus tri-modality (chemo-radiation followed by surgery) treatment for carcinoma of the esophagus.

The purpose of the study was to investigate the difference in overall survival in patients with localized carcinoma of esophagus treated using chemo-radiation (bi-modality, BM) or chemo-radiation followed by surgery (tri-modality, TM). From 1981 to 1999, 65 patients were identified who had localized carcinoma of the esophagus treated with either concurrent chemo-radiation (BM, n=22) or concurrent chemo-radiation followed by surgery (TM, n=43) at the University of Texas Medical Branch at Galveston. All 65 patients received concurrent chemotherapy and external beam radiation. Radiation was delivered by linear accelerators (greater-than-or-equal 6 MV), except in one patient who had part of his treatment given by a Co-60 machine. Chemotherapy consisted of 5-fluorouracil and cisplatin plus minus vinblastine under different regimens. Median follow-up time was 10 months (range=1-195 months) for all patients. Of the 14 patients still alive, the median follow-up time was 32 months (range=2-192 months). No difference in overall survival was detected between the two treatment groups, BM vs. TM (P=0.394) despite a selection bias favoring the TM group. Five-year survival rates of the BM and TM groups were 17% and 18%, respectively; 10-year survival rates were 17% and 12%, respectively. The presence of significant past medical history (P=0.017) and a complete pathologic response in the TM group (P < 0.001) were significant independent predictors of survival. We did not find any difference in survival between chemo-radiation or chemo-radiation followed by surgery in patients with localized carcinoma of the esophagus. Use of biologic markers and functional imaging should be explored in order to segregate patients with different tumor biology for treatment using different treatment strategies.

Aged↗
PubMed2001

The repeatability and accuracy of axial length and anterior chamber depth measurements from the IOLMaster .

BACKGROUND: Axial length and anterior chamber depth have been measured clinically using conventional ultrasound biometry. Recently, a non-contact device has become available to measure these parameters. This study evaluated the repeatability and accuracy of this device. METHODS: The axial length and anterior chamber depth were measured by two practitioners on a group of young subjects using the IOLMaster followed by a conventional ultrasound biometer operated by a third practitioner. The accommodation was controlled in ultrasound biometry through a full correction on the non-measured eye and a distant fixation target. RESULTS: There was good repeatability and accuracy of axial length assessment. The mean difference between the IOLMaster and ultrasound biometry was -0.099 mm, with 95% limits of agreement between 0.66 and -0.85 mm. The axial length was slightly shorter from the IOLMaster and the difference was not significant. The anterior chamber depth was repeatable but was shown to be deeper than the ultrasound results. The mean difference in anterior chamber depth between the IOLMaster and ultrasound biometry was 0.15 mm, with 95% limits of agreement between 0.34 and -0.03 mm. It is suggested that the former device is not measuring the axial anterior chamber depth. CONCLUSIONS: The IOLMaster is a non-contact 'optical' A-scan which is simple to use and good for axial length assessment. The anterior chamber depth assessment should be further evaluated.

Adult↗
PubMed2001

Evolution of myrmecophytism in western Malesian Macaranga (Euphorbiaceae).

Plants inhabited by ants (myrmecophytes) have evolved in a diversity of tropical plant lineages. Macaranga includes approximately 300 paleotropical tree species; in western Malesia there are 26 myrmecophytic species that vary in morphological specializations for ant association. The origin and diversification of myrmecophytism in Macaranga was investigated using phylogenetic analyses of morphological and nuclear ITS DNA characters and studies of character evolution. Despite low ITS variation, the combined analysis resulted in a well-supported hypothesis of relationships. Mapping myrmecophytism on all most parsimonious trees resulting from the combined analysis indicated that the trait evolved independently between two and four times and was lost between one and three times (five changes). This hypothesis was robust when tested against trees constrained to have three or fewer evolutionary transformations, although increased taxon sampling for the ITS analysis is required to confirm this. Mapping morphological traits on the phylogeny indicated that myrmecophytism was not homologous among lineages; each independent origin involved a suite of different specializations for ant-plant association. There was no evidence that myrmecophytic traits underwent sequential change through evolution; self-hollowing domatia evolved independently from ant-excavated domatia, and different food-body production types evolved in different lineages. The multiple origins of myrmecophytism in Macaranga were restricted to one small, exclusively western Malesian lineage of an otherwise large and nonmyrmecophytic genus. Although the evolution of aggregated food-body production and the formation of domatia coincided with the evolution of myrmecophytism in all cases, several morphological, ecological, and biogeographic factors appear to have facilitated and constrained this radiation of ant-plants.

Animals↗
PubMed2001

Prescribers prefer people: The sources of information used by doctors for prescribing suggest that the medium is more important than the message.

AIMS: The sources of prescribing information are legion but there is little knowledge about which are actually used in practice by doctors when prescribing. The aims of this study were to determine the sources of prescribing information considered important by doctors, establish which were used in practice, and investigate if hospital and primary care physicians differed in their use of the sources. METHODS: Two hundred general practitioners (GPs) and 230 hospital doctors were asked to rate information sources in terms of their importance for prescribing 'old' and 'new' drugs, and then to name the source from which information about the last new drug prescribed was actually derived. RESULTS: Among 108 GPs, the Drugs and Therapeutics Bulletin and medical journal articles were most frequently rated as important for information on both old and new drugs while pharmaceutical representatives and hospital/consultant recommendations were more important for information on new drugs, as opposed to old. In practice, information on the last new drug prescribed was derived from pharmaceutical representatives in 42% of cases and hospital/consultant recommendations in 36%, with other sources used infrequently. Among 118 hospital doctors, the British National Formulary (BNF) and senior colleagues were of greatest theoretical importance. In practice, information on the last new drug prescribed was derived from a broad range of sources: colleagues, 29%; pharmaceutical representatives, 18%; hospital clinical meetings, 15%; journal articles, 13%; lectures, 10%. GPs and hospital doctors differed significantly in their use of pharmaceutical representatives (42% vs 18%) and colleagues (7% vs 29%) as sources of prescribing information (P < 0.0001 for both). CONCLUSIONS: The sources most frequently rated important in theory were not those most used in practice, especially among GPs. Both groups under-estimated the importance of pharmaceutical representatives. Most importantly, the sources of greatest practical importance were those involving the transfer of information through the medium of personal contact.

Communications Media↗
PubMed2001

A comparative study of cervical cytology, colposcopy and PCR for HPV in female sex workers in Singapore.

This study examined the prevalence of human papillomavirus (HPV) infection in a cohort of female sex workers in Singapore. HPV infection was diagnosed by clinical examination, Papanicolaou (Pap) smears, histology and polymerase chain reaction (PCR). One hundred and eighty-seven female sex workers who came for their routine medical screening were enrolled into the study. PCR was positive for HPV in 27 (14.4%), 20 of these had a single HPV type detected, while 7 had multiple types of HPV detected. The most common HPV types identified were types 16, 58 and 18. In conclusion, HPV infection is moderately prevalent among sex workers as tested by PCR, but routine screening with Pap smears does not appear to be a sensitive method of diagnosis for HPV infection.

Adult↗
PubMed2001

Computed tomographic-pathologic correlation of gross tumor volume and clinical target volume in non-small cell lung cancer: a pilot experience.

CONTEXT: Computed tomographic (CT) scan data are used regularly in radiation treatment planning for patients with lung cancer. To our knowledge, the relationship of the CT images of tumors and their corresponding microscopic extent has not yet been studied in detail. OBJECTIVE: To correlate tumor sizes on CT with tumor sizes measured microscopically (ie, the gross tumor volume [GTV]-clinical target volume margin) in non-small cell lung cancers. DESIGN: Prospective pilot study. SETTING: Single institution. PATIENTS: Patients with operable non-small cell lung cancer were identified preoperatively. INTERVENTIONS: Once the surgical specimen was available, it was oriented with the surgeon and the pathologist. Seven whole-mount, cross-sectional histologic glass slides were made from 5 tumors using formalin fixation and hematoxylin-eosin staining. The pathologist then outlined the cancer-containing area under the microscope (Micro-GTV) and the area of surrounding inflammatory response (Micro-GTV + inflammation). Preoperative CT scans were used for outlining tumor on the corresponding slice (CT-GTV). MAIN OUTCOME MEASURES: Correlation of the areas of Micro-GTV, Micro-GTV + inflammation, and CT-GTV was performed. RESULTS: There was an obvious trend that the CT-GTV was bigger than the Micro-GTV, except in specimen 1, in which the 2 areas were about equal. However, on comparing the values for the CT-GTV and the Micro-GTV + inflammation, the difference between the 2 areas became smaller. CONCLUSIONS: Modern CT scans might overestimate the GTV in non-small cell lung cancer. The GTV-clinical target volume margin could actually be zero or even a negative value. The findings in this small study are interesting and provoking. Further study with a larger number of patients and more rigid quality control is warranted to confirm our findings.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Molecular and morphological reassessment of relationships within the Vittadinia group of Astereae (Asteraceae).

Morphological and ITS (internal transcribed spacer) sequence data for 40 species of the Austral-Pacific genera Camptacra, Kippistia, Minuria, Peripleura, Tetramolopium, and Vittadinia as well as one semiherbaceous species of Olearia were subjected to cladistic analysis, separately and together. Minuria, Peripleura, and Tetramolopium are paraphyletic as currently defined. Tetramolopium vagans from Australia appears to represent an undescribed genus. Both Kippistia suadefolia and Peripleura diffusa show close affinity to Minuria species, and Minuria macrorhiza appears to contain two distinct but closely related species. Vittadinia and the remaining species of Tetramolopium and Peripleura form a strong affinity group. The distribution of indels and the combined analysis each provide evidence that the Hawaiian and Cook Island species of Tetramolopium are descended from New Guinea species. The combined analysis also suggests that the Cook Island species T. mitiaroense is sister to the Hawaiian clade. Olearia arguta groups strongly with Camptacra and shows no close affinity with either of the arborescent species of Olearia used to root these analyses. Marked homoplasy among morphological characters indicates why generic delimitation in the group has been problematic.

Journal Article↗
PubMed2000

S-nitrosoglutathione reduces nonocclusive thrombosis rate following balloon overstretch injury and intracoronary irradiation of porcine coronary arteries.

PURPOSE: Intracoronary radiation (IR) suppresses neointima formation following balloon injury in animal models. High doses of radiation exacerbate thrombosis and delay re-endothelialization. The free radical nitric oxide (NO) has been reported to inhibit platelet aggregation, reduce neointimal hyperplasia, and stimulate re-endothelialization. This study examined the effects of a chemical NO donor on neointima formation, thrombosis, and healing of irradiated porcine coronary arteries. METHODS AND MATERIALS: Vascular lesions were created in the coronary arteries of 59 domestic swine by overstretch balloon injury. Arteries were then left untreated or were treated with intracoronary gamma-radiation using Iridium-192 in each artery to deliver 5 or 15 Gy at 2 mm from the center of the source. The chemical NO donor S-nitrosoglutathione (GSNO) was infused i.v. at a rate of 250 microg/min for 10 min before injury, followed by a continuous infusion for 60 min. Animals were euthanized at 14 days and their arteries were analyzed for histomorphometric indices of proliferation and thrombosis. RESULTS: A dose of 15 Gy reduced the ratio of intimal area to medial fracture length (IA/FL) versus control (0.06 +/- 0.05 0.54 +/- 0.10 [p < 0. 001]) but increased the nonocclusive thrombosis rate compared to controls (85% vs. 30%; p < 0.05). A low dose of 5 Gy did not affect neointima formation. Treatment with GSNO reduced thrombosis in all treated groups: control, 15%; 5 Gy, 18%; and 15 Gy, 35% (p < 0.05) without affecting neointima formation. CONCLUSION: Systemic administration of GSNO during balloon injury and IR was tolerated well by the swine and resulted in reduction of the thrombosis rate, especially at high doses, without apparent effect on neointima formation.

Animals↗
PubMed2000

Dose-finding, safety, and tolerability study of an oral platelet glycoprotein IIb/IIIa inhibitor, lotrafiban, in patients with coronary or cerebral atherosclerotic disease.

BACKGROUND: Antiplatelet therapy is the mainstay of the treatment and secondary prevention of cardiovascular and cerebrovascular ischemic events. We assessed the safety, tolerability, and pharmacodynamics of lotrafiban, an oral platelet glycoprotein IIb/IIIa inhibitor, as a secondary prevention strategy in patients with cerebrovascular or cardiovascular disease. METHODS AND RESULTS: Overall, 451 patients with a recent cardiovascular or cerebrovascular acute ischemic event were randomized in a double-blind fashion to 1 of 5 dosing regimens for 12 weeks: placebo or 5, 20, 50, or 100 mg lotrafiban, both twice daily with 300 to 325 mg/d aspirin. The primary end point was the incidence and tolerability of major and minor bleeding during treatment. Secondary end points included inhibition of platelet aggregation and clinical events. The placebo and lotrafiban 5-mg groups had similarly low rates of minor and major bleeding, but the 100-mg arm was terminated early because of excess major bleeding. Protocol-defined thrombocytopenia (<100 000 platelets/microL) occurred in 5 lotrafiban-treated patients (1.4%, 95% CI 0.2% to 2.7%) and 1 placebo patient (1.1%, 95% CI 0% to 3.1%). Three lotrafiban-treated patients had a nadir platelet count <20 000/microL (0.9%, 95% CI 0% to 1.8%). Lotrafiban produced dose-dependent inhibition of platelet aggregation; 5 mg lotrafiban did not differ significantly from placebo, whereas 100 mg inhibited aggregation by nearly 100%. CONCLUSIONS: -Lotrafiban provides dose-dependent platelet inhibition when administered to a range of patients with atherosclerosis. The level of platelet inhibition appears to correlate with bleeding risk and drug tolerability.

Administration, Oral↗
PubMed2000

A novel platinum-iridium, potentially gamma radioactive stent: evaluation in a porcine model.

In-stent restenosis (ISR) is a major problem within stented arteries. Surface treatment of stents with platinum and gold were found to have the maximum charge with least neointima formation (NF). This study was designed to evaluate platinum (maximum electrical charge) as a material to make stents to reduce NF. Iridium was added to make an alloy suitable for stent manufacture, with the potential to make the stent radioactive. We implanted the novel platinum-iridium (PI) stent in 10 porcine coronaries and compared to the Palmaz-Schatz (PS) stent implanted in 8 coronary arteries. Six weeks after implantation, angiography of the stented vessel was performed before sacrifice. The coronaries were perfusion-fixed and stained, and vessel parameters were analyzed by computer-aided histomorphometry. The thrombus formation and the inflammatory response was less in the PI stent (0.04 +/- 0.1 vs. 0.24 +/- 0.2, P = 0.005; and 1.1 +/- 0.5 vs. 2.4 +/- 0.3, P < 0.001). The NF from PI-stented arteries was smaller in size than the PS controls (1.9 +/- 0.6 mm(2) vs. 2.4 +/- 0.4 mm(2), P = 0.06). However, PI stents presented with higher recoil than the PS stent (16% vs. 5%, P < 0.001). Platinum-iridium is a highly biocompatible material with high performance, low inflammatory response with small NF. This stent does not lead to thrombus formation and has the potential (due to the presence of iridium) to be irradiated to form a gamma radioactive stent. Cathet. Cardiovasc. Intervent. 51:364-368, 2000.

Animals↗
PubMed2000

The PRESTO (Prevention of restenosis with tranilast and its outcomes) protocol: a double-blind, placebo-controlled trial.

BACKGROUND: Tranilast is a unique drug in clinical development for the prevention of restenosis after percutaneous transluminal coronary revascularization (PTCR). Tranilast interferes with proliferation and migration of vascular medial smooth muscle cells induced by platelet-derived growth factor and transforming growth factor beta1. Collagen synthesis in vascular medial smooth muscle cells is inhibited by tranilast, which also inhibits the release or production of cyclooxygenase-2 and restores cytokine-induced nitric oxide production. These mechanisms may contribute to the reduction of angiographic restenosis after coronary intervention previously reported in clinical studies. METHODS: The primary objective of this multicenter study of 11,500 patients is to compare the composite clinical event rate of death, myocardial infarction, or the need for ischemia-driven target vessel revascularization of tranilast (300 and 450 mg twice daily) for 1 or 3 months with that of placebo in patients undergoing PTCR with or without stenting for single or multiple vessels over a 9-month period. The lesions can be de novo or restenotic. All revascularization procedures and the use of glycoprotein IIb/IIIa agents are permitted. The inclusion criteria are meant to allow an "all comer" approach for generalization of results to the broadest possible PTCR population. A subset population (n = 2000) will undergo 9-month follow-up angiography, 1000 of which will also undergo intravascular ultrasound (n = 1000). This study is the first tranilast trial to be conducted in a Western population to confirm the improved angiographic findings reported in Japanese patients and to determine if the clinical sequelae of restenosis are also reduced. CONCLUSION: This multicenter study is the largest restenosis trial planned to date. It will test whether tranilast, a drug with multiple actions aimed at affecting proliferation and migration of vascular smooth muscle cells, can reduce clinical, angiographic, and intravascular ultrasound assessments of restenosis.

Adolescent↗
PubMed2000

Vascular repair after balloon overstretch injury in porcine model effects of intracoronary radiation.

OBJECTIVES: The purpose of this study was to evaluate the effect of IR on thrombus formation and dissection repair following overstretch balloon injury in porcine coronary arteries. BACKGROUND: Exposure of blood to the injured arterial wall after percutaneous transluminal coronary angioplasty (PTCA) induces thrombus formation and inflammation in the dissection plane. Neointima formation is related to smooth muscle cell (SMC) proliferation and migration into the preformed thrombus. Intracoronary radiation (IR) with doses of 10 to 25 Gy using either beta or gamma emitters can prevent neointima accumulation by reducing SMC proliferation. However, there are some indications that IR may delay the process of dissection repair after PTCA. The purpose of this study was to evaluate the effect of IR on thrombus formation and dissection repair after overstretch balloon injury in porcine coronary arteries. METHODS: Forty porcine coronaries were injured by balloon overstretch followed by either 0 or 18 Gy of 90Y prescribed to 1.2 mm from the balloon center. The animals were euthanized 14 days after treatment, and intimal area (IA) and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis. Dissections were quantified by tracing the length, thickness and area behind the dissection flap. The rate of dissections was calculated for each group. Thrombi were identified and designated as intraluminal thrombus or thrombus within dissection planes (mural thrombus), and area measurements were obtained. RESULTS: The irradiated group showed a significant reduction of IA/FL (0.55 +/- 0.29 vs. 0.05 +/- 0.09; p < 0.001). No difference was observed in the rate of dissection between control and irradiated arteries (77% vs. 88%, respectively). The control group showed a smaller dissection area (0.19 +/- 0.28 mm2 vs. 0.32 +/- 0.29 mm2; p < 0.05) with smaller mural thrombi (0.03 +/-0.01 mm2 vs. 0.29 +/- 0.30 mm2; p < 0.001). A strong correlation between dissection area and neointima area was observed only in the control group (R2 = 0.474; p < 0.003; alpha0.05 = 0.862). A positive correlation between mural thrombus and dissection area was observed only in the irradiated group (R2 = 0.889; p < 0.001; alpha0.05 = 1.00). CONCLUSIONS: These results suggest that the dissection area may be a useful parameter by which to quantify the extent of injury and repair after IR and may indicate an incomplete healing process after IR at this time point.

Angioplasty, Balloon, Coronary↗
PubMed2000

Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress.

Corticotropin-releasing hormone (Crh) is a critical coordinator of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released from the paraventricular nucleus (PVN) of the hypothalamus activates Crh receptors on anterior pituitary corticotropes, resulting in release of adrenocorticotropic hormone (Acth) into the bloodstream. Acth in turn activates Acth receptors in the adrenal cortex to increase synthesis and release of glucocorticoids. The receptors for Crh, Crhr1 and Crhr2, are found throughout the central nervous system and periphery. Crh has a higher affinity for Crhr1 than for Crhr2, and urocortin (Ucn), a Crh-related peptide, is thought to be the endogenous ligand for Crhr2 because it binds with almost 40-fold higher affinity than does Crh. Crhr1 and Crhr2 share approximately 71% amino acid sequence similarity and are distinct in their localization within the brain and peripheral tissues. We generated mice deficient for Crhr2 to determine the physiological role of this receptor. Crhr2-mutant mice are hypersensitive to stress and display increased anxiety-like behaviour. Mutant mice have normal basal feeding and weight gain, but decreased food intake following food deprivation. Intravenous Ucn produces no effect on mean arterial pressure in the mutant mice.

Animals↗
PubMed2000

Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial.

BACKGROUND: Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events. METHODS: Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. RESULTS: The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.

Administration, Oral↗