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Biomedical subjects

Anthony Yim

Publications and source records attributed to Anthony Yim.

10 recordsLinked to original sources

Bronchiolitis obliterans following lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is the main and late chronic complication after lung transplantation. It remains a major impediment to long-term outcome. Unfortunately, the survival rate of lung transplant recipients lags behind that of other organ transplant recipients, and BOS accounts for more than 30% of all mortality after the third year following lung transplantation. Most recent studies suggest that immune injury is the main pathogenic event in small airway obliteration and the development of BOS. Early detection of BOS is possible as well as essential because prompt initiation of treatment may halt the progress of the disease and the development of chronic graft failure. Current treatment of BOS is disappointing despite advances in surgical techniques and improvements in immunosuppressive therapies. Therefore, a clear understanding of the pathogenesis of BOS plays a major role in the search for new and effective therapeutic strategies for better long-term survival and quality of life after lung transplantation.

Bronchiolitis Obliterans↗

Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis.

STUDY OBJECTIVES: Minimal-access thymectomy has become increasingly popular as surgical treatment for patients with nonthymomatous myasthenia gravis (NTMG) because of its comparable efficacy, safety, and lesser degree of tissue trauma compared with conventional open surgery. We reviewed and analyzed our data on video-assisted thoracic surgery (VATS) thymectomy and present the clinical outcomes according to the Myasthenia Gravis Foundation of America classification. DESIGN: A retrospective review of VATS thymectomy for NTMG in a university hospital over a 12-year period. Data were collected from the medical records and supplemented with telephone surveys. The impact of surgery and other variables potentially affecting complete stable remission (CSR) were calculated using Kaplan-Meier survival curves; comparisons between survival curves was performed using the log-rank test. RESULTS: A total of 38 consecutive patients underwent VATS thymectomy for NTMG. Median postoperative stay was 3 days. Pathologic examination revealed thymic hyperplasia in 61.1% of cases, normal thymus in 22.2%, and thymic atrophy in 16.6%. There was no perioperative mortality; complications occurred in four patients. After a median follow-up of 69 months, 91.6% of patients experienced improvement, with crude CSR achieved in 22.2%. Kaplan-Meier survival curve demonstrated a 75% CSR rate at 10-year follow-up. On univariate analysis, only disease duration < or = 12 months (p = 0.03) was associated with a statistically significant improvement in CSR. CONCLUSIONS: VATS thymectomy for NTMG results in symptomatic improvement in the vast majority of patients, with a high rate of CSR. The procedure is associated with low morbidity and no perioperative mortality. Future studies on thymectomy for myasthenia gravis should be reported in a standardized manner to allow accurate comparisons between results in the absence of randomized prospective trials.

Adult↗

The pathobiology of endothelin-1 in vein graft disease: are ETA receptor antagonists the solution to prevent vein graft failure?

Despite the exploration of a large number of disparate drugs in animal models and clinical trials, no pharmacological intervention, with the exception of aggressive lipid lowering therapy has reduced late vein graft failure in man. The importance of devising more effective strategies is exemplified by the considerable economic consequences of vein graft failure. Worldwide, there are currently more than 1,000,000 coronary artery bypass graft surgery (CABG) operations a year, the same number of patients undergoing infrainguinal bypass (IIBS) for vascular diseases of the lower limb. The pathophysiology of vein graft failure is complex, involving disparate factors that include adhesion of platelets and leukocytes, rheological forces, metalloproteinase expression, proliferation and migration of vascular smooth muscle cells, neointima formation, oxidative stress, hypoxia and neural re-organisation. Although this diverse aetiology may seem to preclude any single drug type as being effective in preventing vein graft failure, one factor that is involved in every facet of vein graft pathobiology is endothelin-1 (ET-1). Thus, in this review, we will consider the diverse aetiology of vein graft disease in relation to ET-1 and will then present an argument (with evidence) that ET-1(A) (ET(A)) receptor antagonists constitute a potentially effective means of preventing vein graft failure.

Animals↗

Spectral karyotyping indicates complex rearrangements in lung adenocarcinoma of nonsmokers.

Adenocarcinoma (AdC) of the lung represents a common histologic subtype of non-small cell lung cancer. While there is a rising incidence of AdC in nonsmoking women, information on the cytogenetic changes involved has been minimal to date. In the present study, spectral karyotyping analysis uncovered the genome-wide chromosomal aberrations in two AdC tumors derived from women who were lifelong nonsmokers. Simple and complex structural rearrangements were indicated. A ploidy status of hypertetraploidy was suggested in both cases, with recurring derivative translocations involving chromosome arms 3q, 8q, 12q, 15q, 22q, and Xq.

Adenocarcinoma↗

A Phase I-II study of sequential administration of topotecan and oral etoposide (toposiomerase I and II inhibitors) in the treatment of patients with small cell lung carcinoma.

BACKGROUND: Topotecan (9-dimethylaminomethyl-10-hydroxycampthothecin) is a new topoisomerase I inhibitor with promising efficacy in the treatment of patients with small cell lung carcinoma (SCLC). Combination with a topoisomerase II inhibitor may potentate the therapeutic effect of topotecan, although there has been conflicting preclinical information on the combination. The objectives of this study were to establish the maximum tolerated dose and to determine the efficacy of the sequential combination of intravenous topotecan and oral etoposide in the treatment of patients with SCLC. METHODS: Patients with histologically confirmed, limited or extensive stage SCLC were eligible. The dose escalation scheme of three cohorts (six patients per cohort) started at intravenous topotecan 0.5 mg/m(2) per day for 5 days and oral etoposide 50 mg twice daily for 7 days (21-day cycles). Subsequent dose levels involved escalation of topotecan to 0.75 mg/m(2) per day and 1.0 mg/m(2) per day for 5 days. A Phase II study was conducted at one dose level below the maximum tolerated dose. The authors alternated the drug sequence with each consecutive cycle and compared the hematologic toxicity between the two sequences. RESULTS: Thirty-six patients (21 patients with limited disease and 15 patients with extensive disease) received a total of 173 courses of sequential combination chemotherapy (topotecan --> etoposide, 88 courses; etoposide --> topotecan, 85 courses). The authors identified dose levels for the Phase II study as follows: topotecan, 0.75 mg/m(2) per day for 5 days; and etoposide, 50 mg twice daily for 7 days. The dose-limiting toxicity was neutropenia. At this dose level, the incidence of Grade 3-4 neutropenia and the incidence of Grade 3-4 thrombocytopenia were 25% and 10.9%, respectively. Two patients died from neutropenic sepsis. There was no significant difference in hematologic toxicities between the two sequences. Complete and partial response rates were 5.6% and 55.6%, respectively (limited disease, 9.5% and 66.75%; extensive disease, 0% and 40%, respectively). The median progression free survival was 31.9 weeks (limited disease, 36.1 weeks; extensive disease, 28.9 weeks; 95% confidence interval, 25.6-36.0 weeks), and the median overall survival was 52.4 weeks (limited disease, 54.9 weeks; extensive disease, 30.1 weeks; 95% confidence interval, 39.6-57.7 weeks). CONCLUSIONS: Combination therapy with topoisomerase I and II inhibitors is a safe and effective regimen for patients with SCLC. Future research on this combination should focus on an oral regimen for patients with extensive disease and poor tolerance to cisplatin. The authors recommend an oral dosage of topotecan at 1.2 mg/m(2) per day (equivalent to intravenous topotecan at 0.75 mg/m(2) per day) for 5 days followed by etoposide 50 mg twice daily for 7 days.

Administration, Oral↗

The geometry of unstented and stented pig common carotid artery bypass grafts.

The long-term success of arterial bypass grafting with autologous saphenous veins is limited by neointimal hyperplasia (NIH), which seemingly develops preferentially at sites where hydrodynamic wall shear is low. Placement of a loose-fitting, porous stent around end-to-end, or end-to-side, autologous saphenous vein grafts on the porcine common carotid artery has been found significantly to reduce NIH, but the mechanism is unclear. In a preliminary study, we implanted autologous saphenous vein grafts bilaterally on the common carotid arteries of pigs, placing a stent around one graft and leaving the contralateral graft unstented. At sacrifice 1 month post implantation, the grafts were pressure fixed in situ and resin casts were made. Unstented graft geometry was highly irregular, with non-uniform dilatation, substantial axial lengthening, curvature, kinking, and possible long-pitch helical distortion. In contrast, stented grafts showed no major dilatation, lengthening or curvature, but there was commonly fine corrugation, occasional slight kinking or narrowing of segments, and possible long-pitch helical distortion. Axial growth of grafts against effectively tethered anastomoses could account for these changes. CFD studies are planned, using 3D MR reconstructions, on the effects of graft geometry on the flow. Abnormality of the flow could favour the development of vascular pathology, including NIH.

Animals↗

Pulsatile extracorporeal circulation--let it be?

Cardiopulmonary bypass (CPB) is known to induce a whole body inflammatory response. Since the 1970's, a number of trials have explored the effects of pulsatile CPB on systemic organ function and inflammatory response. Clinical benefits of neuroprotection, improved myocardial and splanchnic perfusion, as well as attenuated systemic inflammatory response have been reported. However, skepticism for pulsatile CPB remains because of inconsistencies of clinical benefits and 'non-standardized' trials. Tarcan and colleagues compared clinical, haemodynamic, biochemical and haematological parameters in patients with chronic obstructive pulmonary disease undergoing CPB with pulsatile flow versus those without. They found higher circulating white cell count and lower neutrophil count at 1 hour post-operatively in the pulsatile group compared with non-pulsatile group, which was attributed to higher pulmonary neutrophil sequestration. In addition, the pulsatile CPB group had lower pulmonary vascular resistance at 1 hour post-operatively and shorter ventilation time. In the current study, confirmation for pulmonary neutrophil sequestration in the form of bronchoalveolar lavage (BAL) or histology would have been welcomed, and additional markers such as neutrophil elastase or matrix metello-proteinases in BAL, and other measurements of lung function may help clarify the association between neutrophil sequestration, lung injury and clinical endpoints. The role of pulsatile CPB in certain high-risk patients remain uncertain, and until more definite evidence of benefit is available, we should be cautious of its universal application.

Cardiopulmonary Bypass↗