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Biomedical subjects

A Fung

Publications and source records attributed to A Fung.

At least 19 recordsLinked to original sources

Transport of living cells with magnetically assembled nanowires.

We present a technique of transporting and positioning living cells internalized by nickel (Ni) nanowires guided by magnetic field. Nanoscale magnetic nanowires are internalized by the Rat Neuroblastoma (ATCC number CRL-2754) and the cells are transported and positioned by magnetic fields from the magnetic material-coated electrodes. This technique may enable the interfacing between neurons and electronic devices to empower investigations pertaining to non-invasive neuron probing as well as nanofabricated neural pharmacological technologies.

Animals↗

Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation.

A 52-year-old man developed essential thrombocythemia (ET) with JAK2 V617F mutation after orthotopic liver transplantation (OLT). Retrospective analysis showed that, despite a low platelet count, the JAK2 mutation was already found at presentation 14 months before OLT. The high platelet count that would have been typical of ET might be masked by the cirrhosis-related hypersplenism. Thrombocythemia became obvious after OLT. The patient subsequently developed blastic transformation 12 months afterward, a process probably accelerated by the immunosuppression required for the OLT.

Amino Acid Substitution↗

Tumor necrosis factor alpha promoter polymorphism and the risk of chronic lymphocytic leukemia and myeloma in the Chinese population.

The -308 GA promoter polymorphism of tumor necrosis factor alpha (TNFalpha) has been reported to be associated with an increased risk of lymphoid malignancies in Caucasians. We studied the incidence and prognostic significance of this polymorphism in Chinese patients with plasma cell myeloma (PCM), chronic lymphocytic leukemia (CLL) and lymphomas. Despite a far lower incidence of PCM and CLL in the Chinese population compared with Caucasians, the rates of TNFalpha-308A were similar to those in Caucasians, both in the study and control populations. Similarly, there was no increased rate of TNFalpha-308A in all the lymphomas studied, irrespective of lineage. However, TNFalpha-308A is significantly associated with female CLL cases and confers a strong negative prognostic impact for Chinese CLL. These argue for a possible biological role for increased TNFalpha production in CLL progression in low-risk individuals.

Adult↗

Molecular epidemiology of follicular lymphoma in Chinese: relationship with bcl-2/IgH translocation and bcl-6 397G/C polymorphism.

The relative incidence of follicular lymphoma (FL) compared with diffuse large B-cell lymphoma (DLCL) is low in Chinese. This may be due to a lower incidence of t(14;18)-mediated disease, a rapid transformation of FL to DLCL, or a lower incidence of FL-prone genetic polymorphisms (e.g., bcl-6 G397C). Using a conventional and long-distance polymerase chain reaction technique, we showed that 93% (43/46) of Chinese FL cases are t(14;18) related and are molecularly indistinguishable from Caucasian cases. The translocation was uncommonly found in Chinese DLCL cases (8/58, 14%). Furthermore, the incidence of bcl-6 hypermutation in FL and DLCL cases appeared to be comparable. These data do not suggest a high incidence of transformation from FL to DLCL in Chinese. Sequencing study also did not show an increased incidence of G397C polymorphism (heterozygote+homozygotes) in FL compared to a population with Chinese background or DLCL cases (25+5% vs 30+4% vs 22+3%). The reasons for the lower incidence of FL in Chinese remain unanswered.

Adult↗

Aberrant p15 gene promoter methylation in therapy-related myelodysplastic syndrome and acute myeloid leukaemia: clinicopathological and karyotypic associations.

Seventeen patients with therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-MDS/AML) were examined for aberrant p15 gene methylation by methylation-specific polymerase chain reaction. Ten patients (58%) showed p15 methylation, which was significantly related to monosomy/deletion of chromosome 7q, but not to antecedent chemotherapy, blast count, leukaemic evolution or survival. In three of six patients with marrow samples obtained prior to the diagnosis of t-MDS/AML, p15 methylation predated disease development by up to 2 years. Bone marrow transplantation led to the disappearance of p15 methylation in one patient. These results showed that p15 methylation was an early event in the evolution of some t-MDS/AML patients.

Acute Disease↗

Analysis of Clonality in Kimura's Disease.

Kimura's disease is a chronic inflammatory disorder of unknown etiology. A 62-year-old man presented with asymptomatic cervical lymphadenopathy associated with eosinophilia and increased serum immunoglobulin E. Excision biopsy showed Kimura's disease. Three years later another groin lymph node appeared and showed similar pathologic features. Polymerase chain reaction for Ig heavy chain and T-cell receptor (TCR) genes on DNA extracted from the cervical lymph node showed smear patterns. However, polymerase chain reaction for TCRdelta gene showed a clonal rearrangement. Sequencing showed a complete VDJ rearrangement (Vdelta1-N-Ddelta2-N-Jdelta), confirming the presence of a clonal T cell population. The same clonal TCRdelta rearrangement was amplified by polymerase chain reaction from the groin lymph node biopsied 3 years later. These results showed that the primary and recurrent lesions were biologically related. Furthermore, the presence of identical T cell clones in different sites and at different times suggested that a clonal T cell population might have contributed to the pathogenesis in this case of Kimura's disease.

Angiolymphoid Hyperplasia with Eosinophilia↗

FORUM: Reinventing Environmental Regulation from the Grassroots Up: Explaining and Expanding the Success of the Toxics Release Inventory.

/ The success of the Toxics Release Inventory (TRI) stands in stark contrast to most other environmental regulations in the United States. Between its inception in 1988 and 1995, releases of chemicals listed on the TRI have declined by 45%. We argue the TRI has achieved this regulatory success by creating a mechanism of "populist maxi-min regulation." This style of regulation differs from traditional command-and-control in several ways. First, the majorrole of public agencies is not to set and enforce standards, but to establish an information-rich context for private citizens, interest groups, and firms to solve environmental problems. Second, environmental "standards" are not determined by expert analysis of acceptable risk, but are effectively set at the levels informed citizens will accept. Third, firms adopt pollution prevention and abatement measures in response to a dynamic range of public pressures rather than to formalized agency standards or governmental sanction. Finally, public pressure ruthlessly focuses on the worst polluters-maximum attention to minimum performers-to induce them to adopt more effective environmental practices. TRI has inadvertently set in motion this alternative style of regulation that has, in turn, dramatically reduced toxics emissions in the United States. By properly understanding the mechanisms that drive TRI's accomplishments, more intentional public policy designs can expand the system of populist maxi-min regulation and achieve even more rapid toxics reduction.

Journal Article↗

Factors associated with failure of medical therapy in patients with unstable angina and non-Q wave myocardial infarction. A TIMI-IIIB database study.

CONTEXT: Current management of patients with unstable angina and non-Q wave myocardial infarction generally consists of intensive medical therapy, with angiography and revascularization sometimes limited to those who fail such therapy. AIM: To determine if certain baseline characteristics are predictive of patients who fail medical therapy, since such patients could then be expeditiously directed to a more invasive strategy in a cost-effective manner. METHODS: The study cohort consisted of the 733 patients in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB study who were randomized to conservative strategy. Patients were to be treated with bedrest, anti-ischaemic medications, aspirin, and heparin, and were to undergo risk-stratifying tests, consisting of an exercise test with ECG and thallium scintigraphy, scheduled to be performed within 3 days prior to, or 5 days after, hospital discharge and 24 h Holter monitoring scheduled to begin 2-5 days after randomization. Baseline clinical and ECG characteristics were compared between patients who 'failed' medical therapy and those who did not 'fail'. Failure was defined using clinical end-points (death, myocardial infarction, or spontaneous ischaemia by 6 weeks after randomization) or a strongly positive risk-stratifying test. For each test an ordered failure profile of results was calculated and consisted of death, myocardial infarction, or rest ischaemia occurring prior to performance of the test, a markedly abnormal test result, and no abnormality. RESULTS: Clinical end-points occurred in 241 (33%) patients and were more likely to occur in patients who at presentation were older, had ST-segment depression on the qualifying ECG, or were being treated with heparin or aspirin. Characteristics independently predictive of developing a clinical event or an abnormal exercise treadmill test included: ST-segment depression on the qualifying ECG, history of prior angina, family history of premature coronary disease (i.e. onset <55 years of age), prior use of heparin or aspirin, and increasing age. By combining these baseline risk characteristics for each outcome the incidence of developing a clinical event ranged from 8% if none was present to 63% if all six were present, and of developing a markedly abnormal risk stratifying test from 8-21% if none were present to approximately 90% if all six were present. CONCLUSIONS: Baseline characteristics associated with developing a clinical event or a markedly abnormal risk stratifying test were similar: rest anginal episode accompanied by ST-segment depression and occurring despite treatment with aspirin and heparin, a history of angina, older age, and family history of coronary disease. Patients with these characteristics are appropriate candidates for expeditious cardiac catheterization and consideration for revascularization, while patients without them may be suitable for medical management alone.

Aged↗

Outpatient self-management of warfarin therapy: a pilot study.

Self-testing and adjusting of warfarin dosages by patients is an evolving strategy for management of oral anticoagulation. We performed this open, prospective, 3-month pilot study to assess the feasibility of conducting a large, randomized trial comparing self-managed with physician-managed anticoagulation. Ten competent patients with planned anticoagulation for at least 3 months were provided education on warfarin therapy and trained to use an individualized warfarin nomogram. International normalized ratios (INRs) were determined weekly for 12 weeks and reported with warfarin dosages to the investigator for the first 8 weeks only. Eight patients elected to use a home monitor (ProTime) to measure INRs. Patients maintained 76.5% (range 50-91.7%) of INRs within the target range. In 119 dosage adjustment decisions, there were only 3 errors (2.5%). No bleeding or thrombotic complications occurred. To confirm concordance, initial and final INRs were measured concurrently by the ProTime monitor and laboratory. The mean absolute difference for 16 paired INR determinations was 0.33 (range 0.02-0.9). All patients expressed satisfaction and a desire to continue with self-management. This pilot study provides support for conducting a prospective, large-scale, randomized trial.

Administration, Oral↗

Macroangiopathy--does it play a role in young people?

Using a novel ultrasound method, brachial artery endothelial and smooth muscle physiology were studied in 20 adolescents with IDDM and in 20 nondiabetic subjects matched for age (13-22 years), gender and vessel size. Endothelium-dependent dilatation (EDD) was assessed in response to flow (EDD) and endothelium-independent vasodilatation after sublingual glyceryl trinitrate (GTN). Both EDD and GTN were reduced in those with IDDM compared with controls: 5 vs. 9%, (p = 0.0002) and 14 vs. 21% (p = 0.002). Abnormal EDD was found in 12 IDDM adolescents (diabetes duration 3.3-14.9 years). The mean urinary albumin excretion rate of the diabetic group with abnormal EDD was 5.76 +/- 2.82 vs. 8.05 +/- 4.88 microg/min in those with normal EDD (p = 0.25). In the diabetic adolescents there was no significant correlation observed between the test for early large vessel disease, HbAlc and tests for diabetic microangiopathy.

Adolescent↗

Adult-to-adult living donor liver transplantation using extended right lobe grafts.

OBJECTIVE: The authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. SUMMARY BACKGROUND DATA: The efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. METHODS: From May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-to-recipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. RESULTS: Median blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 months). CONCLUSIONS: When performed by a team with experience in hepatectomy and transplantation, LDLT, using an extended right lobe graft, can achieve superior results. The technique extends the success of LDLT from pediatric recipients to adult recipients and opens a new donor pool for adults to receive a timely graft of adequate function.

Acute Kidney Injury↗

Role of gender and vascular endothelium in rat aorta response to 17 beta-estradiol.

Estrogen supplementation in postmenopausal women offers significant cardiovascular protection. The mechanism for this benefit is unclear but may be due to an interaction of estrogen with the blood vessel wall (vascular smooth muscle and endothelium). We examined the response of weight-matched female and male endothelium-intact and -denuded aortae to 17 beta-estradiol, its interaction with noradrenaline, and the effect of N-nitro-L-arginine. Estradiol produced relaxation responses that were significantly greater in female endothelium-intact preparations. This response was sensitive to N-nitro-L-arginine, while the response to 17 beta-estradiol in male endothelum-intact and both female and male endothelum-denuded preparations was resistant. Estradiol also inhibited contractions to noradrenaline, which was more pronounced in the female endothelium-intact aortic rings. These data imply that estradiol interacts preferentially with the female vascular endothelium, but there exists an endothelium-independent process that can also be activated in the male aorta. Further studies are warranted to elucidate these differential mechanisms.

Animals↗

Evolution of early TIMI 2 flow after thrombolysis for acute myocardial infarction. GUSTO-1 Angiographic Investigators.

BACKGROUND: Patients with early Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolysis appear to have outcomes similar to thrombolytic failures. To evaluate the origin and evolution of early TIMI 2 flow, we examined early and late angiographic and ventriculographic data from the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-1) angiographic study. METHODS AND RESULTS: Of the 914 patients with both 90-minute and 5- to 7-day catheterizations, 278 patients had TIMI grade 2 flow at 90 minutes. At follow-up, 188 (67%) had improved to TIMI grade 3 flow. At 90 minutes, patients with TIMI grade 2 flow had greater infarct vessel narrowing and a significantly greater incidence of thrombus than patients with TIMI grade 3 flow. At the 5- to 7-day follow-up, patients whose flow had improved from TIMI grade 2 at 90 minutes to grade 3 flow at follow-up had larger-caliber vessels (minimum luminal diameter, 0.99 +/- 0.47 versus 0.84 +/- 0.48 mm; P = .03) and a lower incidence of visible thrombus (26% versus 38%, P = .04) than those with persistent TIMI grade 2 flow. These patients also had a higher mean ejection fraction (57.5 +/- 14.1% versus 52.8 +/- 12.9%, P = .02) and better infarct zone wall motion (-2.1 +/- 1.5 versus -2.6 +/- 1.3 SD per chord, P = .01) at the 5- to 7-day follow-up. Patients in whom flow improved from TIMI grade 2 at 90 minutes to TIMI grade 3 by 5 to 7 days had significantly better left ventricular function than patients with persistent TIMI grade 0, 1, or 2 flow and constituted a group whose left ventricular function was intermediate between those who had no reperfusion (TIMI grades 0 and 1) and those whose reperfusion was complete (TIMI grade 3). CONCLUSIONS: These data suggest that incomplete clot lysis plays a significant role in the pathogenesis of TIMI grade 2 flow. Furthermore, early TIMI grade 2 flow may be sufficient to provide prolonged myocyte viability, which will further recover if flow normalizes.

Aged↗

Synthesis and structure-activity relationships of 2-pyridones: a novel series of potent DNA gyrase inhibitors as antibacterial agents.

Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-alpha]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10-17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis.

Animals↗