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Biomedical subjects

T L Cheng

Publications and source records attributed to T L Cheng.

At least 19 recordsLinked to original sources

The spectrum of intoxication and poisonings among adolescents: surveillance in an urban population.

AIM: Among adolescents, poisoning is a leading cause of injury mortality in the United States. This study describes the epidemiology of poisonings, intoxication, and maladaptive effects of drugs among adolescents age 10-19 years in a large city. METHODS: An injury surveillance system used records at seven hospitals, medical examiner records, and vital records over a two year period. RESULTS: Of 633 cases (618 injuries/100 000/year), 6% were unintentional, 36% self-inflicted, 41% alcohol intoxication, and 15% maladaptive effects of drugs. Alcohol was involved in 45% of cases, 23% illegal drugs, 23% non-prescription drugs, 19% prescription drugs; 19% involved more than one substance. Hospitalization was required in 20%; 8% transferred to another hospital; one died from intoxication. The authors found high rates of self-inflicted poisoning, intoxication, and maladaptive effects of drugs among this urban population. CONCLUSION: The study highlights the need to broadly define poisonings among adolescents and the challenge of assessing intent in some cases.

Adolescent↗

Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance.

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.

Adult↗

Urban youths' perspectives on violence and the necessity of fighting.

OBJECTIVES: To assess youth perceptions of the causes and consequences of violence generally, the causes and consequences of fighting specifically, and to determine how best to approach fighting in the context of violence prevention activities. METHODS: Thirteen structured focus group interviews with youths from three high violence urban settings: a large, urban high school, a training center for disadvantaged youths, and a school for adjudicated youths. Participants were 120 urban, predominately African-American youths and young adults ages 14-22 years (mean: 17.2 years). Seven focus groups were conducted with females, and six with males. RESULTS: Adolescents identified the causes of violence on multiple levels including: individual, family, interpersonal, and community level factors. Most youths (89%) had been in a physical fight. Participants felt that fighting was not "right", but identified situations in which it was necessary. Specifically, fighting was used as a problem solving tool, and could prevent escalation of violence. Youths felt that the adults in their lives, including physicians, were generally ill equipped to give advice about violence, as adults' experiences were so removed from their own. Participants looked to experienced role models to offer problem solving and harm reduction strategies. Youths were open to receiving anticipatory guidance about violence and fighting from primary care physicians they felt comfortable with, and who showed respect for their experiences. CONCLUSIONS: Interventions that include blanket admonitions against fighting should be reassessed in light of youth perceptions that fighting plays a complex role in both inciting and preventing more serious violence.

Adolescent↗

Potentiation of antitumor immunity by antibody-directed enzyme prodrug therapy.

Antibody-directed enzyme prodrug therapy (ADEPT) has displayed antitumor activity in animal models and clinical trials. We examined whether antitumor immunity is generated during ADEPT by employing an immunoenzyme composed of the monoclonal antibody (MAb) RH1 conjugated to beta-glucuronidase to target rat AS-30D hepatocellular carcinoma tumors. A glucuronide prodrug of p-hydroxyaniline mustard was used to treat malignant ascites after immunoenzyme localization at the cancer cells. ADEPT cured more than 96% of Sprague-Dawley rats bearing advanced malignant ascites, and all cured rats were protected from a lethal challenge of AS-30D cells. Immunization with radiation-killed AS-30D cells or AS-30D cells coated with immunoenzyme did not provide tumor protection. Likewise, ex vivo treatment of tumor cells by ADEPT before injection into rats did not protect against a tumor challenge. AS-30D and N1-S1 hepatocellular carcinoma cells but not unrelated syngeneic tumor cells were lysed by peritoneal exudate cells isolated from ADEPT-cured rats. Depletion of CD8(+) but not CD4(+) T cells or natural killer (NK) cells reduced the cytolytic activity of peritoneal lymphocytes. ADEPT did not cure tumor-bearing rats depleted of CD4(+) and CD8(+) T cells even though it was curative when given 7 days after tumor transplantation in rats with an intact immune system, indicating that ADEPT can synergize with host immunity to increase therapeutic efficacy. These results have important implications for the clinical application of ADEPT.

Aniline Mustard↗

Violent injuries among adolescents: declining morbidity and mortality in an urban population.

STUDY OBJECTIVE: Adolescent homicide rates are decreasing nationally for unclear reasons. We explore changes in intentional injury morbidity and mortality within the context of other injuries and specific causes. METHODS: We performed surveillance of hospital, medical examiner, and vital records for nonfatal injury among adolescents age 10 to 19 years living in the District of Columbia from June 15, 1996, to June 15, 1998, and fatal injury from 1989 to 1998. RESULTS: Over the 2-year study period, 15,190 adolescents were seen for injury, resulting in an event-based rate of 148 injuries per 1,000 adolescents per year; 7% required hospitalization, and 0.8% died. Interpersonal intentional injuries accounted for 25% of all injuries, 45% of hospitalizations, and 85% of injury deaths. Assault morbidity decreased with no change noted for unintentional and self-inflicted injury. Firearm injuries, stabs, and assaults with other objects showed the largest decrease, with no decrease in unarmed assaults. Injury mortality peaked in 1993 and has declined since. Firearms caused 72% to 90% of all injury deaths from 1989 to 1998, most the result of homicide. CONCLUSION: There has been a decline in intentional injury rates over the study periods related to decreased weapon injury; data suggest a change in the lethality of fighting methods but no change in unarmed fighting behavior.

Adolescent↗

Assessing an educational intervention to improve physician violence screening skills.

OBJECTIVES: Health professionals play an integral role in assessing the risk of violence in their patients. However, there have been few evaluations of violence prevention education programs for health care personnel. The objective of this study was to evaluate the effects of a violence-screening education program on pediatric residents' and medical students' comfort level and skills in the identification and management of violence risks. SETTING: Adolescent clinic of a tertiary care pediatric hospital. PARTICIPANTS: Fifty-six second-year residents and third-year medical students assigned to a 4-week adolescent clinic rotation. DESIGN: Randomized, controlled comparison study conducted over a 1-year period. INTERVENTION: On alternate months, medical students and residents in the intervention group participated in a 3-hour workshop on violence prevention. The workshop included a didactic session with an overview of firearm, media, and sexual violence; a discussion of risk factors for adolescent violence; and training on the approach to the adolescent interview. Participants also discussed violence risks in the community with a panel of teen health educators, engaged in one-on-one role play with the youth educators, and received feedback on their violence screening skills. The control group received the standard ambulatory clinic manual with articles on violence prevention. EVALUATION METHODS: All participants completed prerotation and postrotation questionnaires assessing their self-reported screening practices, as well as perceived importance and confidence in violence screening. Participants also interviewed and examined an adolescent standardized patient (SP) in the clinic. SPs completed evaluations on the content of the residents' and students' screening, their interpersonal skills, and their skill in the identification and management of the violence-related problem. RESULTS: Over 12 months, 30 control and 26 intervention participants were recruited. There were no differences in prerotation questionnaire scores for intervention and control groups in screening practices, perceived importance and confidence in violence screening. Postrotation intervention participants reported more screening compared with controls on violence in school/neighborhood and fighting history. There was also greater perceived importance in asking about access/use of weapons and violence in school/neighborhood. Intervention participants also had improved performance compared with controls on SP evaluations of screening for violence, identification and management of the violence-related scenario, and interpersonal skills. CONCLUSION: A violence prevention education program with teen health educators improved participants' self-reported violence questioning, as well as increased perceived comfort and importance in violence screening. Participants in the program also improved their identification and management of a standardized violence-related scenario presented in an adolescent clinic setting. adolescent violence, physician education, violence risk screening.

Adolescent↗

Sensitive measurement of polyethylene glycol-modified proteins.

An IgM monoclonal antibody (AGP3) against polyethylene glycol (PEG) was used to assay PEG-modified proteins by ELISA. PEG-modified beta-glucuronidase could be measured at concentrations as low as 15 ng/mL, corresponding to 750 pg (1.8 fmol) of conjugate. This ELISA should be generally applicable to all PEG-modified proteins because AGP3 binds the backbone of the PEG chain independent of the linker used for PEG attachment.

Animals↗

A review of teen-tot programs: comprehensive clinical care for young parents and their children.

Comprehensive clinical programs for teenage mothers and their children, also known as teen-tot programs, have been a promising intervention to improve outcomes of teenage childbearing and parenting. However, much remains unknown regarding the efficacy of such programs. We reviewed four published evaluations of programs that provided medical care, counseling, contraception, guidance for parenting, and assistance with staying in school. The evaluations reported moderate success in preventing repeat pregnancies, helping teen mothers continue their education, and improving teen and infant health over 6 to 18 months. However, the evaluations had limitations that may have reduced or accentuated observed effectiveness. Teen-tot programs will continue to face the challenges of sustaining adequate long-term interventions and evaluations, and reducing the high attrition rate among program participants. It is concluded that increased support and funding for teen-tot programs and more complete evaluations are warranted.

Adolescent↗

Teaching prevention in pediatrics.

Pediatrics has attempted to inculcate the "culture of prevention" into practice, both through anticipatory guidance in well-child care and through behavioral interventions in sick care. The effectivenesses of many components of well-child care have not been conclusively demonstrated, particularly in health education, counseling, and anticipatory guidance, nor has teaching prevention in pediatrics been thoroughly evaluated. This article reviews methods of teaching prevention in pediatrics and highlights innovative programs. Teaching programs use the wide range of approaches now common in medical education, in a variety of inpatient and outpatient sites. Programs across the country are trying new approaches to teaching traditional topics or are introducing new topics into their curricula. Examples of specific programs are given, organized by the themes of the programs. The field needs to develop in three major directions. First, there is a need to develop competencies and curricula in prevention issues of contemporary importance, including the new morbidities, cross-cultural issues, cost-effectiveness, quality of care, and practice in managed care and other community settings. Second, further work is needed to evaluate programs and measure educational outcomes. This feedback must in turn be used to redefine competencies, curricula, and programs, Third, there needs to be an accessible clearinghouse, and educational tools need to be disseminated. To be effective, a curriculum for prevention in pediatrics cannot stand alone, but must be part of a vertically and horizontally integrated curriculum. Further, creating horizontally and vertically integrated curricula in prevention teaching across disciplines should be the standard.

Child↗

Sports injuries: An important cause of morbidity in urban youth. District of Columbia Child/Adolescent Injury Research Network.

INTRODUCTION: Sports injuries account for substantial morbidity and medical cost. To direct intervention, a population-based study of the causes and types of sports injuries was undertaken. METHOD: An injury surveillance system was established at all trauma center hospitals that treat residents 10 to 19 years old in the District of Columbia and the Chief Medical Examiner's Office. Medical record abstractions were completed for those seen in an emergency department, admitted to the hospital, or who died from injury June 1996 through June 1998. FINDINGS: Seventeen percent (n = 2563) of all injuries occurred while participating in 1 of 6 sports (baseball/softball, basketball, biking, football, skating, and soccer) resulting in an event-based injury rate of 25.0 per 1000 adolescents or 25.0/1000 population year. Rates were higher in males for all sports. The most common mechanisms were falls (E880-888) and being struck by or against objects (E916-918). Hospitalization was required in 2% of visits and there were no deaths. Of those requiring hospitalization, 51% involved other persons, 12% were equipment-related, and 8% involved poor field/surface conditions. Of all baseball injuries, 55% involved ball or bat impact often of the head. Basketball injuries included several injuries from striking against the basketball pole or rim or being struck by a falling pole or backboard. Biking injuries requiring admission included 2 straddle injuries onto the bike center bar and collision with motor vehicles. Of all football injuries, 48 (7%) involved being struck by an opponent's helmet and 63 (9%) involved inappropriate field conditions including falls on or against concrete, glass, or fixed objects. In soccer there were 4 goal post injuries and a large proportion of intracranial injuries. There were 51 probable or clear assaults during sports and an additional 30 to 41 injuries from baseball bat assaults. CONCLUSIONS: Many sports including noncontact sports involved injuries of the head suggesting the need for improved head protection. Injuries involving collisions with others and assaults point to the need for supervision and enforcement of safety rules. The 16% of sports injury visits and 20% of hospitalizations related to equipment and environmental factors suggest that at least this proportion of injury may be amenable to preventive strategies. Design change may be warranted for prevention of equipment-related injuries. The many injuries involving inappropriate sports settings suggest the need for and use of available and safe locations for sports.

Adolescent↗

Pediatric residency education.

OBJECTIVE: On February 1, 1997, new pediatric Residency Review Committee guidelines became effective. Eighteen months later, pediatric residency program directors were queried regarding the implementation of these guidelines. Because both the challenge to implement these guidelines and the opportunities to shape pediatric graduate medical education rest with the program directors, obtaining the feedback and suggestions from this group is seen as the keystone of future planning endeavors. METHODS: A 20-question multiple-choice/opened-ended questionnaire was sent to the 201 members of the Association of Pediatric Program Directors in 2 mailings in August and September 1998. RESULTS: A final response rate of 70% was achieved. Very few program directors reported difficulties in instituting the new residency review committee requirements. The exceptions to this pattern were those requirements pertaining to limitations on time spent in intensive care experience and in the neonatal intensive care unit, wherein 34% of the respondents identified barriers. Although the majority of respondents regarded these requirements as very good or sufficient, some program directors expressed concern regarding insufficient amounts of time available for preparation in intensive care (18%), neonatal intensive care unit (22%), behavioral/developmental pediatrics (16%), and in adolescent medicine (13%). In general, programs have been more successful in defining new competencies than in developing curricula to teach them. The majority of respondents also indicated that their residents' exposure was excellent or satisfactory in all 6 of the following practice settings: private office-based practice for continuity clinic, private office-based practice for outpatient rotation, predominately managed care practice, community clinics for continuity clinic, community clinics for outpatient rotation, and hospital-based practice for continuity clinic. They also indicated that they had no serious concerns about the types of career development assistance offered to residents and the types of follow-up tracking of residents. CONCLUSION: The findings from this survey have reaffirmed the merit of the current system of pediatric residency education. They have also revealed the commitment of program directors to address the complex issues generated by the evolution of health care delivery, and thereby contribute to the optimal provision of pediatric health care now and in the future.

Adolescent↗

Final report of the FOPE II Education of the Pediatrician Workgroup.

This report from the FOPE II Education of the Pediatrician Workgroup assesses the current status and future trends of pediatric education. The attributes of each level of the education process (undergraduate, residency, fellowship, continuing medical education [CME]) are considered within the framework of lifelong learning. The pediatric education of nonpediatrician providers is carefully considered. The Workgroup proposes and describes a new model for pediatric education that encompasses educational needs assessment, curriculum development and outcomes evaluation. Particular attention is paid to CME, with a review of the strengths and problems of the current system. The proposal for improving CME in the 21st century highlights the need for each pediatrician to have a "CME home," and several models and scenarios are explored. Appendices summarize the results of several surveys conducted on behalf of the Workgroup, and list societal trends and advances in pediatric health care that will influence pediatric education in the future. Pediatrics 2000;106(suppl):1175-1198; pediatric education, educational needs assessment, curriculum development, outcomes evaluation.

Curriculum↗

Characterization of an antineoplastic glucuronide prodrug.

The specificity of tumor therapy may be improved by preferentially activating antineoplastic prodrugs at tumor cells pretargeted with antibody-enzyme conjugates. In this study, the conditions required for the efficient activation of p-hydroxyaniline mustard glucuronide (BHAMG) to p-hydroxyaniline mustard (pHAM) were investigated. pHAM induced cross-links in linearized double-stranded DNA at about 180-fold lower concentrations than BHAMG, indicating that the nucleophilicity of pHAM was decreased by the presence of a glucuronide group. The partition coefficient of BHAMG was about 1890 times lower than pHAM in an octanol-water two-phase system, suggesting that the reduced toxicity of BHAMG was due to both hindered diffusion across the lipid bilayer of cells and decreased reaction with nuclear DNA. BHAMG was significantly less toxic to BHK cells that expressed cytosolic Escherichia coli-derived beta-glucuronidase (betaG) compared with cells that were engineered to secrete betaG, demonstrating that extracellular localization of betaG was required for optimal activation of BHAMG. The extended retention of mAb RH1 on the surface of AS-30D cells was also consistent with extracellular activation of BHAMG. Taken together, our results indicate that the low toxicity of BHAMG was due to hindered cellular uptake and low alkylating activity. BHAMG must be enzymatically activated outside of tumor cells for maximum cytotoxicity, and non-internalizing antibodies are preferred for human tumor therapy by targeted antibody-enzyme activation of BHAMG.

Aniline Mustard↗

Determinants of counseling in primary care pediatric practice: physician attitudes about time, money, and health issues.

OBJECTIVES: To assess pediatrician goals and practice in preventive counseling, and to use social learning theory to examine physician attitudes about preventive health issues, time, and reimbursement to explain physician counseling behavior. DESIGN: Random sample survey of American Academy of Pediatrics fellows. PARTICIPANTS: A total of 1620 pediatricians were surveyed with a return rate of 72%. The 556 pediatricians who had finished training and who currently performed child health supervision were included. METHODS: Pediatricians were asked about their goals in 6 areas of health supervision: biomedical issues, development, behavior, family functioning, safety education, and supportive interpersonal interaction. They were also asked about the prevalence of counseling, importance of specific topics, their self-efficacy, outcome expectation in these areas, and their concerns about time and reimbursement for preventive counseling. RESULTS: Assurance of physical health and normal development were the most important goals of child health supervision among the pediatricians surveyed. Goals involving behavioral, family, and safety issues were less important and less likely to be addressed in practice. Most did not regularly discuss family stress, substance abuse, gun safety, and television. In these areas, physicians had less confidence they could provide guidance and lower expectation that they could prevent problems. Only 17% felt that they receive adequate reimbursement for preventive counseling. Most have adequate time (53%) and receive adequate respect (57%) for their preventive efforts. Physicians who were more concerned about time for preventive counseling reported less overall counseling (r = -0.28, P<.001). Concern about reimbursement was not associated with reported counseling. Multiple regression analysis found that the primary predictors of physician counseling were an issue's importance, a physician's perceived self-efficacy, and perceived effectiveness of counseling, while concerns about time and reimbursement were secondary. CONCLUSIONS: Physician goals in child health supervision were primarily biomedical, with psychosocial and safety issues of lesser importance. Concern about time for preventive counseling was associated with less reported counseling. Physician attitudes regarding the importance of a health issue and their confidence and effectiveness in counseling were more predictive of physician practice than their attitudes about time and reimbursement for preventive care.

Adult↗

Bystander killing of tumour cells by antibody-targeted enzymatic activation of a glucuronide prodrug.

RHI-betaG-PEG, formed by linking poly(ethylene glycol)-modified beta-glucuronidase to Mab RH1, was employed to examine bystander killing of antigen-negative N1S1 rat hepatoma cells by activation of a glucuronide prodrug (BHAMG) of p-hydroxyaniline mustard (pHAM) at antigen-positive AS-30D rat hepatoma cells. Sequential treatment of cells with 10 microg ml(-1) RH1-betaG-PEG and 20 microM BHAMG was not toxic to N1S1 cells but killed 99% of AS-30D cells. Over 98% of N1S1 cells, however, were killed in mixed populations containing as few as 2% AS-30D cells after identical treatment, demonstrating an in vitro bystander effect. Subcutaneous injection of AS-30D and N1S1 cells in BALB/c nu/nu mice produced solid tumours containing both cells. Uptake of radiolabelled RH1-betaG-PEG in solid AS-30D and mixed AS-30D/N1S1 tumours was 11.6 and 9.3 times greater than a control antibody conjugate 120 h after i.v. injection. Intravenous treatment with RH1-betaG-PEG and BHAMG cured seven of seven nude mice bearing solid s.c. AS-30D tumours and significantly delayed, compared with control conjugate and prodrug treatment, the growth of mixed N1S1/AS-30D tumours with one cure, showing that targeted activation of BHAMG kills bystander tumour cells in vivo.

Aniline Mustard↗

A new paradigm of injury intentionality.

OBJECTIVE: To improve understanding of processes leading to injury and assess more specifically the degree of intentionality. METHODS: A new paradigm was developed that characterizes the act of inflicting injury (self, other, not inflicted) and the motive. Motives are determined for the act of injury and for the outcome. To test this, 986 cases of adolescent injuries in seven hospitals were reviewed. Three investigators independently classified all cases using the new paradigm and three used standard definitions of intent. Inter-rater reliability was measured. RESULTS: Of injuries inflicted by others, 61% were intentional using the standard classification. In the new paradigm 67% were intended acts and 59% involved intentional motive for outcome. Altogether 87% of sports injuries were coded as unintentional acts compared with 96% using standard methods. Using standard classification there was 93% agreement between paired raters, with an average kappa of 0.86. In the new paradigm questions on intentionality of act, outcome, and infliction of act, the agreement was 89%, 91%, 88%, with a kappa of 0.79, 0.80, 0.76, respectively. CONCLUSIONS: This paradigm defines a spectrum of injury intent, enhances understanding of the causal sequence of injury, and has important implications for research and prevention.

Adolescent↗

A STD/HIV prevention trial among adolescents in managed care.

OBJECTIVE: To determine if sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, risk assessment, and education tools provided as part of office-based primary care reduce adolescent risky sexual behaviors. DESIGN: A randomized intervention trial with 3- and 9-month follow-up. SETTING: Five staff-model managed care sites in Washington, DC (n = 19 pediatricians). PATIENTS: Consecutive 12- to 15-year-olds receiving a general health examination; 81% minority. Participation rate = 215/432 (50%). Nine-month follow-up rate = 197/215 (92%). INTERVENTION: Audiotaped STD risk assessment and education about staying safe (safer = condoms, safest = abstinence). MAIN OUTCOME MEASURES: Adolescent-reported sexual intercourse and condom use. RESULTS: More intervention adolescents reported pediatrician discussion on 11/13 sexual topics. Although more vaginal intercourse (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.04-5.84) was reported in the intervention group at 3 months, this was not true of overall sexual intercourse (OR = 1.55, 95% CI =.73-3.32). More sexually active adolescents reported condom use in the intervention group at 3 months (OR = 18.05, 95% CI = 1.27-256.03). At 9 months, there were no group differences in sexual behaviors; however, more signs of STD were reported by the control (7/103) than the intervention group (0/94). CONCLUSIONS: STD risk assessment and education tools administered in a single office visit facilitated STD/HIV prevention education. Any impact on sexual activity and condom use was short-lived. Further research is needed to develop brief, office-based sexual risk reduction for young adolescents.

Adolescent↗