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Biomedical subjects

A Y Chen

Publications and source records attributed to A Y Chen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Challenges and relevance of problem-based learning in dental education.

The rôle of PBL as an innovative approach in medical education has been well documented. There has been an emerging trend of incorporating PBL into the dental curriculum. The potential advantages of PBL as a mode of learning encompass the enhancement of an integrated approach in solving dental-treatment-related problems, the development of critical thinking and problem solving skills and the encouragement of independent life-long learning. PBL was introduced into the dental curriculum as a pilot project in the Faculty of Dentistry, National University of Singapore in summer 1996. An example of a case-based study was illustrated and the learning objectives of the study were highlighted. Initial feedback from students indicated a positive attitude to this mode of learning in terms of cognitive, affective and psychomotor skills. Strategies to enhance learning in the PBL environment include time allocation for self-study, availability of resource materials and use of appropriate assessment methods. Problems that remain to be resolved include the choice of appropriate outcome assessment measures to evaluate the effectiveness of PBL as a mode of learning in undergraduate dental education.

Attitude↗
PubMed1999

Methods for creating and animating a computer model depicting the structure and function of the sarcoplasmic reticulum calcium ATPase enzyme.

This paper describes the developmental process used to visualize the calcium ATPase enzyme of the sarcoplasmic reticulum. The steps involved were evaluating scientific information, consulting with scientists, model making, storyboarding, and creating and editing in a computer medium. The product was a computer-generated animation depicting the relationship between the structure and function of the sarcoplasmic reticulum calcium ATPase enzyme.

Calcium-Transporting ATPases↗
PubMed1999

DNA topoisomerase I-targeting drugs as radiation sensitizers.

Combination chemoradiation, alone or as an adjuvant to surgery, has been shown to improve treatment outcomes in a number of human malignancies, but may be limited by normal tissue toxicities. A primary challenge in radiation oncology is the development of drugs that can selectively enhance the cytotoxicity of ionizing radiation against tumor cells. Mammalian DNA topoisomerase I is the major cytotoxic target of a number of newly developed anticancer drugs that have shown efficacy against solid tumors, including colon cancer, ovarian cancer, lung cancer, cancer of the head and neck, and pediatric cancers. Topoisomerase I-targeting drugs exert their cytotoxic effect by producing enzyme-mediated DNA damage, rather than by directly inhibiting enzyme catalytic activity. DNA topoisomerase I recently has been established as a biochemical mediator of radiosensitization in cultured mammalian cells by camptothecin derivatives. Interestingly, this sensitization appears to be schedule-dependent, cell cycle phase-specific, cell line-dependent, and not strictly dependent on drug cytotoxicity. Clinical chemoradiation trials using camptothecin derivatives are currently ongoing. Future studies aimed at better understanding the underlying mechanisms of molecular radiosensitization with topoisomerase I-targeting drugs are pivotal to the clinical application of these agents, as well as in guiding the development of more effective radiosensitizers.

Animals↗
PubMed1999

Drug-radiation interactions in tumor blood vessels.

Obliteration of the tumor vasculature is an effective means of achieving tumor regression. Antiangiogenic agents have begun to enter cancer clinical trials. Ionizing radiation activates the inflammatory cascade and increases the procoagulative state within blood vessels of both tumors and normal tissues. These responses are mediated through oxidative injury to the endothelium, leading to induction of cell-adhesion molecules and exocytosis of stored proteins from the endothelial cytoplasm. Agents that activate homeostatic responses in the endothelium can enhance thrombosis and vasculitis of irradiated tumor blood vessels. Proinflammatory and prothrombotic biological response modifiers given concurrently with ionizing radiation are known to induce vascular obliteration and necrosis of tumors. Other mechanisms of interaction between antiangiogenic agents and ionizing radiation include the direct cytotoxic effects of these agents. Interactions between drugs and radiation therapy might therefore occur at the level of the vascular endothelium. The importance of this paradigm is that the endothelium might not develop resistance to drugs or radiation because of lessened potential for mutagenesis and clonogenesis. The future design of clinical trials must consider the effects of radiation therapy on the vascular endothelium.

Angiogenesis Inhibitors↗
PubMed1998

Outcomes analysis of voice and quality of life in patients with laryngeal cancer.

OBJECTIVE: To assess relationships between voice satisfaction and global quality of life in patients who have been treated for laryngeal cancer. DESIGN: Cross-sectional survey study. SETTING: Veterans Affairs Medical Center. PATIENTS: Eighty patients who had completed treatment for laryngeal cancer with either total laryngectomy (n=17), radiotherapy (n=24), or both (n=39). MAIN OUTCOME MEASURES: Subscale scores on a general health status instrument (the Medical Outcomes Study 36-item short-form health survey), and a validated voice-specific functional status instrument (the Voice Handicap Index). RESULTS: Self-rated global health did not correlate significantly with emotional, functional, or physical voice handicap, although some subscales on the 36-item short-form health survey correlated with voice handicap scores. Global health status scores did not differ between patients who had undergone laryngectomy with a tracheoesophageal puncture and patients treated with radiotherapy only. Physical voice handicap scores did not differ significantly between those who underwent tracheoesophageal puncture and those who had radiotherapy, but emotional (P=.07) and functional (P=.01) handicap scores were lower in patients treated with radiotherapy. However, there was considerable overlap in voice handicap scores, with many patients who had had tracheoesophageal puncture showing less voice handicap than patients treated with radiotherapy. CONCLUSIONS: These data demonstrate that health status is affected by other factors than voice handicap in patients with laryngeal cancer. In addition, there is a large amount of individual variation in voice handicap after treatment. These findings illustrate the need for prospective studies assessing voice handicap and quality of life after treatment for laryngeal cancer.

Activities of Daily Living↗
PubMed1998

Growing use of laparoscopic cholecystectomy in the national Veterans Affairs Surgical Risk Study: effects on volume, patient selection, and selected outcomes.

OBJECTIVE: To study the introduction of laparoscopic cholecystectomy to the 43 tertiary-care university-affiliated Veterans Administration medical centers (VAMCs) participating in the National Veterans Affairs Surgical Risk Study from October 1991 through December 1993. SUMMARY BACKGROUND DATA: Previous studies in the private sector have documented growth in the number of cholecystectomies and falling clinical thresholds for cholecystectomy with the introduction of laparoscopic cholecystectomy. METHODS: The following were analyzed for changes over time: measures of patient preoperative risk, complexity of surgery, severity of biliary disease, numbers of procedures, postoperative length of stay, and 30-day postoperative mortality and general complication rates. RESULTS: The number of cholecystectomies performed laparoscopically increased, but the total number of cholecystectomies performed remained stable over time. The proportion of patients with acute cholecystitis, emergent cholecystectomies, and technically complex cholecystectomies did not change or increased slightly over time. Adjusted odds for postoperative general complications were lower for laparoscopic than for open cholecystectomy, but 30-day postoperative mortality and general complication rates for all cholecystectomies remained constant over time. Postoperative length of stay for all cholecystectomies fell significantly. Implementation rates of laparoscopic cholecystectomy varied widely between hospitals. Laparoscopic cholecystectomy was adopted more slowly and used in a lower percentage of cholecystectomies than in non-VA settings. CONCLUSIONS: In contrast to non-VA studies showing increases in overall cholecystectomy volume since the introduction of laparoscopic cholecystectomy, these VAMCs implemented laparoscopic cholecystectomy without growth in cholecystectomies or a change in the clinical threshold for cholecystectomy. Laparoscopic cholecystectomy was associated with better outcomes, but its introduction in the setting of stable cholecystectomy volume and biliary disease case mix did not change postoperative mortality and complication rates. The stable cholecystectomy volume and biliary disease case mix, slower adoption, and lower use of laparoscopic cholecystectomy contrast with previous reports and may result from differences in patients and organization and financing of VA versus non-VA settings.

Aged↗
PubMed1998

In search of the transfusion trigger.

Red blood cell transfusions are used commonly in orthopaedic surgery and cost billions of dollars annually. The goals of transfusion are to reduce mortality and morbidity and improve functional status that result from anemia and inadequate O2 delivery. Risks of infections from transfusion are low and continue to decline, but evidence is growing that red cell transfusions are immunosuppressive and predispose patients to postoperative infections. However, there actually are very little data on when transfusion is indicated. Observational data suggest that transfusion does not reduce mortality in patients with preoperative or postoperative hemoglobin levels 8 g/dL or greater, although no conclusions could be drawn about the effect of transfusion in patients with hemoglobin 8 g/dL or less. Large, well performed randomized clinical trials are needed to establish the efficacy of transfusion. Until better data are available, orthopaedic surgeons will have to rely on clinical judgement in decisions regarding transfusions. Using a higher transfusion threshold in patients with cardiovascular disease is recommended.

Anemia↗
PubMed1997

Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells.

Dendritic cells (DCs) are professional antigen-presenting cells that process and present antigenic peptides and are capable of generating potent T-cell immunity. A murine tumor model was developed to evaluate methods of genetic immunization to the human MART-1/Melan-A (MART-1) melanoma antigen. A poorly immunogenic murine fibrosarcoma line (NFSA) was stably transfected with the MART-1 gene. This transfected tumor [NFSA(MART1)] grows progressively in C3Hf/Kam/Sed (H-2k) mice. Partial protection against a challenge with NFSA(MART1) could be achieved with i.m. injections of a MART-1 expression plasmid or with systemic administration of an adenovirus vector expressing MART-1. However, superior protection was achieved when granulocyte macrophage colony-stimulating factor/interleukin-4-differentiated murine DCs transduced with an adenovirus vector expressing MART-1 were used for immunization. Both partial and complete protection could be achieved with i.v. administration of MART-1-engineered DCs. Splenocytes from immunized mice contained MHC class 1-restricted CTLs specific for MART-1. This preclinical model of genetic immunization supports a therapeutic strategy for human melanoma.

Adenoviridae↗
PubMed1997

Mammalian DNA topoisomerase I mediates the enhancement of radiation cytotoxicity by camptothecin derivatives.

The role of DNA topoisomerase I as a biochemical mediator of radiosensitization in cultured mammalian cells by camptothecin derivatives was studied. We found that, in Chinese hamster DC3F cells, camptothecin enhanced the cytotoxicity of radiation in a schedule-dependent manner. At 4 microM, a sensitizer enhancement ratio of 1.45 was observed when radiation was used concurrently with or immediately after drug treatment. By comparison, no enhancement was obtained if radiation preceded camptothecin treatment. Consistently, in human breast cancer MCF-7 cells, sensitizer enhancement ratios of 1.43, 1.38, and 1.05 were observed when radiation was used concurrently with, immediately after, or prior to treatment with 20(S)-10,11-methylenedioxycamptothecin (MDCamp). Three studies indicated that an intact stereospecific interaction between camptothecin derivatives and DNA topoisomerase I is essential in the induction of radiosensitization: (a) higher concentrations of camptothecin were required to radiosensitize the camptothecin-resistant DC3F/C-10 cells; (b) a newly identified topoisomerase 1-targeting Hoechst 33342 also radiosensitized DC3F cells; and (c) 20(S)-methylenedioxycamptothecin, but not its noncytotoxic 20(R)-stereoisomer, radiosensitized MCF-7 cells by obliterating the "shoulder" of the radiation survival curve. The mechanism of radiosensitization was investigated in DC3F cells. We found that camptothecin only minimally enhanced the cytoxic effect of radiation in G1-phase cells obtained by a mitotic shake-off technique as well as in plateau-phase cells arrested by growing to confluency. Our data suggest a potential development of topoisomerase I drugs as radiosensitizers in treating human malignancies.

Animals↗
PubMed1997

Factors predictive of poor compliance with follow-up care after facial trauma: a prospective study.

We performed a prospective study of 59 consecutive patients with facial trauma who were treated at an urban public hospital. We obtained demographic and clinical data before treatment, then recorded compliance with clinic follow-up care. As expected, young, minority male patients, victims of assault, and blunt mechanisms of injury predominated in our series, and midface fractures and soft tissue injuries were most commonly seen. Thirty-one (52%) patients were admitted, and 28 (48%) were treated as outpatients. Although 66% of patients kept their initial follow-up appointment, only 46% of patients were seen to completion of the follow-up period. We used univariate and multivariate analyses to identify factors predictive of poor compliance with follow-up care. Factors predictive of poor compliance with the initial follow-up appointment identified in the multivariate analysis were orbital injury site (p < 0.001), Caucasian race (p = 0.007), and not having a telephone at home (p = 0.043). Factors predictive of poor compliance with completion of follow-up were failure to keep initial appointment (p < 0.001), and treatment with observation, suture only, or open reduction internal fixation only (p = 0.018). Age, marital status, employment status, education level, and hospital admission of the patient were not predictive of compliance with follow-up care. Because compliance with follow-up care may be poor, patients with facial trauma should be managed aggressively initially. In particular, patients with orbital fractures, and those treated with watchful waiting only may have poorer long-term compliance with follow-up care.

Adolescent↗
PubMed1996

Otolaryngologic disease progression in children with human immunodeficiency virus infection.

OBJECTIVES: To evaluate the prevalence of otolaryngologic disease in children born to mothers infected with human immunodeficiency virus (HIV) and to assess the correlation between HIV disease severity and the incidence density of recurrent otitis media (OM) and sinusitis based on the revised 1994 Centers for Disease Control and Prevention (CDC) clinical-severity index. DESIGN: Case series. SETTING: Academic, tertiary care children's hospital. PATIENTS: One hundred forty-five children (73 boys, 72 girls) with vertically acquired HIV infection and 153 (77 boys, 76 girls) children who had maternal exposure to HIV but later were found not to be infected ("seroreverters"), followed up on a regular basis since birth. MAIN OUTCOME MEASURES: Prevalence of recurrent OM (3 episodes in 6 months or 4 episodes in 12 months), sinusitis, parotitis, and lymphadenopathy; incidence density of recurrent OM and sinusitis based on the 1994 CDC clinical-severity index. RESULTS: Sixty-four HIV-infected children (44%) and 13 seroreverters (8.5%) had recurrent OM (P < .001); 29 HIV-infected children (20%) and 1 seroreverter (0.6%) had sinusitis (P < .001). Eight HIV-infected patients developed tympanic membrane perforations and 25 HIV-infected children required otologic surgery. Three HIV-infected patients had parotitis. The incidence density of recurrent OM increased as HIV clinical (P = .001) and immunologic (P = .03) status worsened. In contrast, the incidence density of sinusitis did not significantly correlate with increased HIV disease severity. CONCLUSION: The prevalence of recurrent OM and sinusitis is significantly greater in HIV-infected children than in seroreverters. The incidence density of recurrent OM also significantly correlates with disease progression in HIV-infected children as measured by the 1994 CDC clinical-severity index.

Disease Progression↗
PubMed1996

Duplex ultrasonography to diagnose failing arterial prosthetic grafts.

BACKGROUND: Although several reports have documented the usefulness of a surveillance program with duplex ultrasonography (DU) to diagnose failing autologous vein bypasses, the effectiveness of DU to detect failing arterial prosthetic grafts has not been confirmed. We attempted to determine whether our program, which included DU and other noninvasive techniques (NonDU), was useful for this purpose. METHODS: Between July 1, 1991, and September 30, 1994, 85 prosthetic bypasses in 59 patients performed for lower extremity ischemia were entered into a graft surveillance protocol. There were 35 femoropopliteal, 16 femorotibial, 15 iliofemoral, 13 axillofemoral, and 6 femorofemoral bypasses. Both DU and NonDU were performed 1 week and every 3 months after the initial bypass or after graft revision. NonDU criteria of a failing graft included changes in symptoms or pulses, decreased ankle/brachial index greater than 0.15, or diminution of ankle pulse volume recordings greater than 50%. Normal grafts were bypasses that had less than 50% stenosis documented by arteriography or remained patent. Problem grafts were those that required revision or thrombosed before intervention. Follow-up of patient grafts ranged between 3 and 36 months (mean, 11 months). RESULTS: DU predicted 17 (81%) of 21 problem grafts versus only 5 (24%) diagnosed by NonDU (p = 0.001). Lesions associated with these 21 grafts were perianastomotic in 10 cases, in adjacent inflow or outflow arteries in 8 cases, and intrinsic to the graft in 3 cases. The likelihood of a graft thrombosing in the presence of a normal test was 7% (4 of 58) for DU compared with 21% (16 of 76) for NonDU (p = 0.04). CONCLUSIONS: DU is more sensitive than NonDU in predicting failure of prosthetic grafts. This study suggests that DU should routinely be performed as part of a surveillance program for peripheral arterial prosthetic bypasses.

Aged↗
PubMed1996

Penetrating injuries of the face.

We reviewed 78 consecutive cases of penetrating facial injuries treated at Ben Taub General Hospital in Houston, Texas, between 1992 and 1994, and we analyzed injury patterns on the basis of (1) the mechanism of injury, and (2) the entry zone of the wounds. We found that gunshot wounds were more likely to require emergent airway establishment than shotgun wounds or stab wounds (p = 0.03). We noted a higher prevalence of globe injury among shotgun wounds than among gunshot wounds (p = 0.02). Nine (12%) patients had intracranial penetration of a bullet or shotgun pellet. Patients with gunshot wounds required open reduction and internal fixation of facial bone fractures more frequently than patients with shotgun wounds (p = 0.01). Thirty patients underwent arteriograms, and 10 demonstrated positive findings. Although there were only 3 deaths in our series, 29 (37%) patients overall had some complication caused by their penetrating facial trauma, including blindness in 12 patients. There was no significant difference in the prevalence of complications between gunshot, shotgun, and stab wounds (p = 0.18). With these injury patterns in mind, we describe an algorithm for evaluation and management of penetrating injuries of the face.

Adolescent↗
PubMed1995

The guanylyl cyclase-A receptor transduces an atrial natriuretic peptide/ATP activation signal in the absence of other proteins.

Attempts to activate partially purified preparations of the guanylyl cyclase-A (GC-A) receptor with atrial natriuretic peptide (ANP) have previously failed, leading to speculation that essential cofactors are lost during purification procedures. The receptor was modified to contain the FLAG epitope (DYKDDDDK), expressed in Sf9 cells, and purified to apparent homogeneity (4.3 mumol cyclic GMP formed/min/mg protein; 5.8 mmol 125I-ANP binding site/mg protein) by a combination of immunoaffinity, Q-Sepharose FF, and wheat germ agglutinin batch chromatography. High initial protein/detergent ratios, the presence of glycerol (40%), and the inclusion of protein phosphatase inhibitors in all buffers resulted in the purification of a receptor that continued to transduce the ANP/ATP activation signal. Both native and purified GC-A contained a single class of high affinity ANP binding sites (Kd = 60 pM) and an equivalent EC50 for ATP (0.3 mM). Positive cooperativity as a function of MnGTP was retained during purification. Thus, GC-A is capable of transducing a ligand binding signal in the absence of other proteins.

Adenosine Triphosphate↗
PubMed1995

Sequential addition of temperature-sensitive missense mutations into the PB2 gene of influenza A transfectant viruses can effect an increase in temperature sensitivity and attenuation and permits the rational design of a genetically engineered live influenza A virus vaccine.

We have previously described a strategy for the recovery of a synthetic influenza A virus wild-type (wt) PB2 gene (derived from influenza A/Ann Arbor/6/60 [AA] virus) into an infectious virus. It was possible to introduce an attenuating temperature-sensitive (ts) mutation at amino acid residue 265 of the AA wt PB2 gene and to rescue this mutant gene into infectious virus. Application of this new technology to influenza A virus vaccine development requires that multiple attenuating mutations be introduced to achieve a satisfactorily attenuated virus that retains the attenuation (att) phenotype following replication in vivo. In this report, we demonstrate that putative ts mutations at amino acids 112, 556, and 658 each indeed specify the ts and att phenotypes. Each of these mutations was introduced into a cDNA copy of the AA mutant mt265 PB2 gene to produce three double-mutant PB2 genes, each of which was rescued into an infectious virus. In general, the double-mutant PB2 transfectant viruses were more ts and attenuated in the lower respiratory tracts of hamsters than the single-mutant transfectant viruses, and the ts phenotype of two of three double-mutant PB2 transfectant viruses was stable even after prolonged replication in the upper respiratory tracts of immunocompromised mice. Two triple-mutant PB2 transfectant viruses with three predicted amino acid substitutions resulting from five nucleotide substitutions in the cDNA were then generated. The triple-mutant PB2 transfectant viruses were more ts and more attenuated than the double-mutant PB2 transfectant viruses. These results indicate that sequential introduction of additional ts mutations into the PB2 gene can yield mutants that exhibit a stepwise increase in temperature sensitivity and attenuation compared with the preceding mutant(s) in the series. Furthermore, the level of temperature sensitivity of the transfectant viruses correlated significantly with the level of attenuation of these viruses in hamsters. Although the triple-mutant PB2 transfectant viruses were attenuated in hamsters, intranasal administration of these viruses elicited a vigorous serum hemagglutination-inhibiting antibody response, and this was associated with resistance of the lower respiratory tract to subsequent wt virus challenge. These observations suggest the feasibility of using PB2 reverse genetics to generate a live influenza A virus vaccine donor strain that contains three attenuating mutations in one gene. It is predicted that reassortant viruses derived from such a donor virus would have the properties of attenuation, genetic stability, immunogenicity, and protective efficacy against challenge with wt virus.

Animals↗