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Biomedical subjects

G Chang

Publications and source records attributed to G Chang.

At least 55 records · Page 3Linked to original sources

A polymorphism of the 5 alpha-reductase gene and its association with prostate cancer: a case-control analysis.

Prostate cancer (CaP) is the most commonly diagnosed, nondermatological cancer in the United States. The development and progression of CaP is influenced by androgens. 5 alpha-Reductase, type II, converts testosterone to dihydrotestosterone and is critical to the development of the prostate. A TA dinucleotide repeat polymorphism exists in the 3' untranslated region of the 5 alpha-reductase type II gene. 5 alpha-Reductase alleles with longer TA repeats are more common in African-Americans, the group with the highest incidence of CaP. It has been hypothesized that the longer TA repeat alleles might be associated with increased risk of CaP. We studied this potential association within the Physician's Health Study, a predominantly Caucasian cohort study. Using PCR we identified the TA genotype in 590 men with CaP and 802 age-matched controls. The frequency of each allele in the controls was TA(0), 0.87, TA(9), 0.13, and TA(18), 0.01. Homozygotes for the longer TA alleles, TA(9) and TA(18), were underrepresented among cases with an odds ratio of 0.47 (confidence interval, 0.20-1.12), but this was not statistically significant (P = 0.08, two tailed). Our analysis does not support the prior hypothesis that longer TA alleles confer an increased risk of CaP in a predominantly Caucasian population; in fact, longer TA alleles are more prevalent in men without CaP.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Women and alcohol abuse in primary care. Identification and intervention.

Female problem drinkers are less likely than men to be identified in the primary care setting. The authors studied 24 adult women attending a general, internal medicine clinic to assess the efficiency of self-reports of alcohol consumption when compared with physician identification and other measures and the impact of a brief intervention on alcohol consumption. Despite the high rate of lifetime (79%) and current (67%) alcohol diagnoses, no patient was in alcohol treatment. Physician identification of alcohol problems was least sensitive but most specific, when compared with other measures. Brief intervention, as offered in this study, did not appear to modify alcohol consumption.

Adult↗

Crystal structure of the lactose operon repressor and its complexes with DNA and inducer.

The lac operon of Escherichia coli is the paradigm for gene regulation. Its key component is the lac repressor, a product of the lacI gene. The three-dimensional structures of the intact lac repressor, the lac repressor bound to the gratuitous inducer isopropyl-beta-D-1-thiogalactoside (IPTG) and the lac repressor complexed with a 21-base pair symmetric operator DNA have been determined. These three structures show the conformation of the molecule in both the induced and repressed states and provide a framework for understanding a wealth of biochemical and genetic information. The DNA sequence of the lac operon has three lac repressor recognition sites in a stretch of 500 base pairs. The crystallographic structure of the complex with DNA suggests that the tetrameric repressor functions synergistically with catabolite gene activator protein (CAP) and participates in the quaternary formation of repression loops in which one tetrameric repressor interacts simultaneously with two sites on the genomic DNA.

Allosteric Regulation↗

Six-month follow-up of naltrexone and psychotherapy for alcohol dependence.

BACKGROUND: The goal of this study was to examine the persistence of naltrexone's effects on drinking outcomes among alcoholics following discontinuation of treatment and to determine whether coping skills therapy improves long-term outcomes compared with supportive therapy. METHODS: Eighty of 97 alcohol-dependent subjects randomized to receive naltrexone or placebo and either coping skills therapy or supportive therapy for 12 weeks were assessed at a 6-month off-treatment follow-up. RESULTS: Subjects who received naltrexone were less likely to drink heavily or to meet criteria for alcohol abuse or dependence than subjects who received placebo. The effect of naltrexone therapy on abstinence rates persisted only through the first month of follow-up. Coping skills therapy was associated with decreased levels of drinking among subjects who received placebo. Psychotherapy condition, however, did not predict alcohol diagnosis at follow-up. CONCLUSIONS: Some but not all of the benefits resulting from short-term naltrexone treatment persist after discontinuation of treatment. The findings suggest that continued treatment with naltrexone may be beneficial for some patients.

Adaptation, Psychological↗

Does volume of clinical experience affect performance of clinical clerks on surgery exit examinations?

BACKGROUND: Controversy persists over the educational value of student clerkship clinical activities. METHODS: Students (109) from the class of 1995 recorded their clinical experiences in a logbook during their surgical clerkship at one of four affiliated teaching hospitals. The influence of clinical experience on examination scores and on correlations between prerotation and postrotation examination performance was determined. RESULTS: Between sites, marked variation in clinical experience was observed but postrotation scores were similar. High-volume experience in emergency admissions and feedback was associated with better objective structured clinical examination (OSCE) performance, but high-volume outpatient clinic experience was associated with less satisfactory OSCE performance. Correlations between prerotation examination performance and the OSCE was increased by feedback on emergency and elective admissions, in a positive and negative direction, respectively. CONCLUSIONS: These data show that surgical clerks' clinical skills were enhanced by an increased volume of some but not all clinical experiences and that feedback does not necessarily enhance performance. These data suggest that both the volume of clinical experience and the quality of feedback should be carefully monitored by surgical clerkship directors.

Alberta↗

Naltrexone, relapse prevention, and supportive therapy with alcoholics: an analysis of patient treatment matching.

Alcohol-dependent patients (N = 97) were randomly assigned to receive either naltrexone or placebo and either relapse prevention therapy or supportive therapy. The present report explored the hypothesis that patients could be matched to the above treatments on the basis of specific pretreatment characteristics. Treatment matching variables explored included craving, alcohol dependence severity, and cognitive measures of learning and memory. Results of linear regression analyses tentatively suggest that patients experiencing higher levels of craving and poorer cognitive functioning may derive the greatest benefit from naltrexone versus placebo. For psychotherapy, lower levels of verbal learning were associated with poorer drinking outcomes for relapse prevention therapy but not for supportive therapy. Conversely, higher levels of verbal learning were associated with better outcomes for relapse prevention therapy but not for supportive therapy.

Adolescent↗

Cardiac papillary fibroelastoma.

Papillary fibroelastomas are rare cardiac tumors, but they are the most common primary tumor of the heart valves. These lesions occur on any of the valves or endothelial surfaces of the heart and may be detected by echocardiography, cardiac catheterization, during open heart operation for other conditions, or at autopsy. Because of their potential for cerebral and coronary embolization, even small papillary fibroelastomas should be excised.

Aged↗

Functional characterization of human immunodeficiency virus type 1 nef genes in patients with divergent rates of disease progression.

We have studied the sequence and function of the human immunodeficiency virus type 1 (HIV-1) nef genes from nine patients with highly divergent rates of disease progression enrolled in a longitudinal study of HIV disease. Over an average of 7.8 years of follow-up, three patients had net positive changes in CD4+ T-cell counts, three patients had net negative changes in CD4+ T cells but did not develop AIDS, and three patients progressed to AIDS. The nef gene from each of these patients was amplified and cloned, and the sequence of 8 to 10 clones was determined. Only 2 of 88 (2.3%) nef genes recovered from these nine patients were grossly defective. Moreover, there was no relationship between the phylogeny of nef sequences and the corresponding rates of disease progression from these patients. Representative nef genes from all nine patients were tested for their abilities to downregulate cell surface CD4 in a transient-transfection assay. There was no correlation found between the functions of the nef genes from these patients and their corresponding rates of disease progression. We conclude that the nef gene is not a common mediator of the rate of HIV disease progression in natural infection.

Acquired Immunodeficiency Syndrome↗

Defective accessory genes in a human immunodeficiency virus type 1-infected long-term survivor lacking recoverable virus.

We have been studying a patient who acquired human immunodeficiency virus (HIV) infection via a blood transfusion 13 years ago. She has remained asymptomatic since that time. The blood donor and two other recipients have all died of AIDS. Although this patient has shown persistently strong seroreactivity to HIV type 1 (HIV-1) antigens by Western blot (immunoblot), she has been continually HIV culture negative in results from multiple laboratories over the last 6 years and has a very low viral burden. Her CD4+ T-cell count has fluctuated around a mean of 399 cells per microliters, with little change in lymphocyte subset percentages. Strong cellular immune responses to HIV-1 epitopes by this patient have been demonstrated. We now report the results of an intensive molecular genetic analysis of the HIV-1 proviral quasispecies from this patient sampled over 5 years. Long terminal repeat region sequences supported the argument for normal basal and Tat-mediated promoter activities. Sequential sequencing of the nef gene revealed a low frequency (8.3%) of defective genes and a striking lack of sequence evolution. Functional analysis of predominant nef genes by both a cell surface CD4 downregulation and a viral infectivity complementation assay showed wild-type function. In contrast, sequential analysis of an amplicon containing the vif, vpr, vpu, tat1, and rev1 genes revealed the presence of inactivating mutations in 64% of the clones. These data suggest that this patient, initially infected with a virulent swarm of HIV-1, is presently infected with a more-attenuated viral quasispecies as a result of effective host immunity.

Acquired Immunodeficiency Syndrome↗

Problem-based learning: its role in undergraduate surgical education.

OBJECTIVE: To familiarize the surgeon with problem-based learning (PBL) and to discuss the current and future role of PBL in undergraduate surgical education. DATA SOURCES: Two meta-analyses comparing the outcome of a PBL curriculum with a traditional curriculum and other studies in the English-language literature. STUDY SELECTION: Data on the effectiveness of PBL can best be assessed by a meta-analysis in which the conclusions of many studies are reviewed and combined to provide a more comprehensive picture. The studies chosen represent those from the only two recent meta-analyses of the problem that have appeared in reputable journals. DATA EXTRACTION: Results reported are those obtained using appropriate techniques and published in reputable journals. Information relevant to the major issues in undergraduate surgical training was selected for inclusion. DATA SYNTHESIS: PBL depends on self-directed learning, triggered by a clinical problem. The students meet in small groups led by a facilitator and discuss carefully designed clinical cases. At the conclusion, the students will have encountered all the information necessary to solve the case and, in so doing, will have gained knowledge that in a conventional curriculum would usually have been disseminated by lecture. There were only small differences between graduates from the two types of curricula. Those from a PBL curriculum had comparable examination results to those from a traditional curriculum on both basic science and clinically based examinations but were happier with their educational experiences. CONCLUSIONS: Centres that have adopted a PBL approach have found improved student motivation and enjoyment, but there has been no convincing evidence of improved learning. An intelligent combination of both traditional and PBL approaches will likely provide the most effective training for undergraduate surgical clerks.

Canada↗

[Systemic and local administration of interferon-gamma impairs wound healing].

Interferon-gamma (IFN-gamma), which is a member of cytokine family, has many physiological functions. In this study, we evaluated the effects of IFN-gamma on wound healing in a model of incised wound of rat skin. Twenty Wistar rats were divided into three groups, consisting of IFN-gamma local administration (n = 8), IFN-gamma systemic administration (n = 8) and normal saline control (n = 4). IFN-gamma was administered in doses of 2,000 u/rat, and then daily. Wound areas were measured everyday. At day 10, tissue from wounds was obtained, and it was evaluated for protein amount in granulation tissue and also subjected to morphometric analysis with hemotoxylin and eosin and collagen fibril stain. We found that IFN-gamma impaired wound healing after either systemic or local administration as compared with control, as evidenced by reduction of new collagen fibril deposition and delay of reepidermidalization. On days 7 and 10 after wounding, wound area in normal saline treated rats was much smaller than those in rats treated with IFN-gamma. These results indicated that the impairing effects of IFN-gamma on wound healing must be considered when it is used in clinic.

Animals↗

Using genetic algorithms for solving heavy-atom sites.

A novel procedure has been developed for locating heavy-atom positions in crystals of macromolecules. This method used genetic algorithms (GA's) to search for heavy-atom sites that are consistent with an observed difference Patterson function. The procedure is straightforward to apply, space-group independent, and particularly powerful for cases involving non-crystallographic symmetry of multiple heavy atoms in the asymmetric unit. In this paper, we introduce how GA's are used for determining the heavy-atom positions and show how this method is more efficient than a sequential search.

Journal Article↗

Serologic response to standard inactivated influenza vaccine in human immunodeficiency virus-infected children.

We compared the serologic response of 46 human immunodeficiency virus (HIV)-infected children and adolescents and 61 age-matched controls to standard trivalent inactivated influenza vaccine (A/Taiwan (H1N1), A/Shanghai (H3N2), B/Yamagata). Children were immunized according to the package insert recommendations before the 1990 to 1991 influenza season. Serum antibody titers to influenza A were determined before and 1 month after each vaccination and compared for study and control subjects. Serologic responses of HIV-infected participants were correlated with absolute CD4 counts and stage of HIV disease. Regardless of age or HIV status, all groups responded with significant increases in antibody to the influenza A strains (range, 2.1-fold to 11.8-fold), with the exception that antibody to H3N2 rose only 1.5-fold (P = 0.058) among HIV-positive subjects > or = 9 years old. Pre- and postimmunization antibody titers were significantly higher for controls than for HIV-positive subjects. There was no correlation between serologic responses and CD4 counts among HIV-infected subjects, but those with Centers for Disease Control and Prevention-defined acquired immunodeficiency syndrome responded significantly less well to vaccine. We conclude that HIV-infected children and adolescents produce significant antibody rises after inactivated influenza A vaccination but that their absolute antibody concentrations are lower than those seen in age-matched controls.

Acquired Immunodeficiency Syndrome↗

Screening and monitoring coeliac disease: multicentre trial of a new serum antibody test kit.

A multicentre trial was conducted to evaluate a new test for anti-gliadin antibodies (AGA) in serum (Coeliac Screening Kit, CSK, Medical Innovations Limited, Artarmon, NSW, Australia). The test showed excellent reproducibility for both anti-gliadin IgA and IgG detection. The average intraassay coefficient of variation (CV) was 3.0% for IgA and 2.4% for IgG (n = 6), while the average interassay CV was 6.4% for IgA and 4.3% for IgG (n = 3). By defining a positive test as both IgA and IgG elevated, a sensitivity of 93% in untreated coeliacs (n = 75) was observed. The corresponding specificities in healthy adults (n = 130) and healthy children (n = 77) were > 99% and 100% respectively, while in patients with other gastrointestinal disorders (disease controls) the specificity was 94% (n = 129). The test was also useful in monitoring patients, with anti-gliadin IgA and IgG falling for up to a year after commencing a gluten-free diet (GFD) (12 adults). In some patients however, antibody levels did not reach the normal cutpoint after many months on a GFD, which may reflect the patients' poor adherence to their gluten free diet. The test was superior to the Pharmacia anti-gliadin ELISA, and should be useful as an aid to the diagnosis of coeliac disease, as well as in the follow-up of treated patients.

Adult↗

Prevalence of medical illness in patients with anxiety disorders.

OBJECTIVE: This investigation examines the prevalence and characteristics of medical illness in 711 patients enrolled in the Harvard/Brown Anxiety Disorders Research Program (HARP), a multi-center, longitudinal study of anxiety disorders. METHOD: Eligible subjects were those with present or past index anxiety disorders: panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia without panic disorder, social phobia, or generalized anxiety disorder. They were assessed by trained raters using structured diagnostic interviews and the Medical History Form II. RESULTS: Patients with panic disorder and co-morbid major depressive disorder had significantly higher rates of reported medical illness than anxiety disorder patients without depression. When the rates of medical illness for all subjects were compared with those from the Rand Health Insurance Experiment, we found the prevalence of several medical problems to be disproportionately increased. CONCLUSIONS: Although our results are preliminary, it appears that patients with panic disorder have more reported medical problems than the public at large, in particular, more ulcer disease, angina, and thyroid disease. Somatic complaints in patients with panic disorder, therefore, need to be carefully considered.

Adult↗

[Clarithromycin in pediatric age. Personal experience].

The authors report their experience on the use of oral suspension of Clarithromycin in respiratory infections in the pediatric age. Thirty-three patients affected by various infectious pathologies of the respiratory tract, treated with oral Clarithromycin at the dosage of 15 mg/kg/day, were studied. The therapeutic outcome was very encouraging, the drug well tolerated and without side effects.

Administration, Oral↗