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Biomedical subjects

S Chang

Publications and source records attributed to S Chang.

At least 163 records · Page 9Linked to original sources

Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo.

OBJECTIVE: T cells treated with DNA methylation inhibitors overexpress lymphocyte function-associated antigen 1 (LFA-1), which results in autoreactivity, and the autoreactive cells cause a lupus-like disease in vivo, suggesting a mechanism by which some agents may cause drug-induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA-1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity. METHODS: Cloned murine T helper 2 cells were treated with Pca, N-acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA-1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo. RESULTS: Pca and Hyd were more potent than their analogs or HU in all 3 assays. CONCLUSION: The results support a relationship between LFA-1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug-induced lupus.

Animals↗

Giant retinal tear as a complication of attempted removal of intravitreal lens fragments during cataract surgery.

PURPOSE: To report giant retinal tear and retinal detachment as a complication of attempted removal of intravitreal lens fragments at the time of cataract surgery and to evaluate the anatomic and visual acuity outcomes of pars plana vitrectomy and retinal reattachment surgery. METHODS: Retrospectively, 10 patients with giant retinal tear, retinal detachment, and intravitreal lens fragments in 10 eyes were reviewed. RESULTS: In 10 eyes, retrieval of intravitreal lens fragments using the limbal approach by deep vitrectomy, copious vitreous cavity irrigation, or deep vitreous cavity phacoemulsification had been attempted by the anterior segment surgeon at the time of cataract surgery in each patient. The average interval from cataract surgery to the initial vitreoretinal consultation was 8 days. Each of the 10 eyes had a giant retinal tear involving the inferior retina: in four eyes, of between 90 degrees and 180 degrees; in four, equal to 180 degrees; and in two, of greater than 180 degrees. After pars plana vitrectomy and retinal detachment repair, nine (90%) of 10 eyes had retinal reattachment, but seven patients required more than one operation. One eye had persistent retinal detachment, and one eye had corneal graft failure. Seven (70%) of the 10 eyes had best-corrected final visual acuity of 20/200 or better; three eyes had light-perception, hand-motion, and counting-fingers vision. CONCLUSIONS: Aggressive attempts at intravitreal lens fragment retrieval from a limbal-based approach should be avoided because these procedures may result in serious retinal complications, such as formation of a giant retinal tear.

Aged↗

Modification of amino acids at shock pressures of 3.5 to 32 GPa.

Amino acids were subjected to shock impact over a pressure range of 3.5 to 32 GPa both within and without meteoritic mineral matrices. The extent of amino acid destruction, racemization, and conversion to secondary amino acids was examined. Abundances of parent compounds decreased by a factor of 10(3) over this pressure range. Racemization also occurred, but some residual optical activity remained in the amino acids surviving shocks up to 32 GPa. Secondary amino acids formed in the high peak pressure range; those identified were beta-alanine, glycine, alanine, gamma-aminobutyric acid, and beta-aminoisobutyric acid. At 30 GPa, the abundances of these daughter compounds exceeded those of the remaining initial amino acids. As the concomitant effects of high mechanical stress and temperature accompanying shocks cannot be separated in this work, their relative contribution to the observed transformations cannot be estimated. The survival of amino acids in shock experiments suggests that, after formation or emplacement of amino acids in carbonaceous chondrite parent bodies, these objects never experienced impact velocities greater than 5 km/s, which suffices to generate 30 GPa for typical silicate/silicate impacts. These results also provide guidelines for choosing appropriate capture media for interplanetary dust particles on Earth-orbiting platforms.

Aluminum↗

A prescription survey in a hospital hypertension outpatient clinic.

AIMS: The objective of this study was to investigate drug utilization in the management of hypertension in Hong Kong. METHODS: We conducted a prescription survey to examine the use of antihypertensive drugs in a hypertension clinic in a regional hospital and the resulting expenditure incurred. The use of concurrent medications such as antidiabetic drugs and lipid-lowering agents was also examined. RESULTS: During a 7-week study period, 530 prescriptions were collected. All except 14 patients received antihypertensive drugs with 262 (50.8%) on monotherapy and 254 (49.2%) on combination therapy. Calcium channel blocking agents and beta-adrenoceptor blocking agents were the two most popular antihypertensive drugs used in both monotherapy (38% and 31%, respectively) and combination therapy (27% and 33%, respectively). Forty-nine patients (19%) received three antihypertensive drugs or more. The number of antihypertensive drugs showed a significant positive correlation with the duration of attendance at the clinic (r=0.88, P < 0.001). Of the total 530 prescriptions, 5.6% and 10% contained antidiabetic drugs and lipid-lowering agents, respectively. Calcium channel blocking agents, angiotensin converting enzyme (ACE) inhibitors and lipid lowering agents, accounted for 82% (HK$211,654; pounds sterling 1 approximately HK$12) of the total drug expenditure (HK$258,115). Seventy-nine percent of the lipid lowering agents prescribed were hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors. Amlodipine accounted for 26% of usage but contributed to 41% of the overall costs of calcium channel blocking agents. Alpha1-adrenoceptor blocking agents were only used infrequently and were the most expensive class of drugs, due to the preferred use of doxazosin rather than prazosin which is far cheaper than the former. CONCLUSIONS: In view of the use of these often costly drugs for long-term therapy, monitoring of their use and its correlation with clinical outcomes and quality of life is essential to ensure the optimal use of health care resources.

Antihypertensive Agents↗

Case-control assessment of diet and lung cancer risk in African Americans and Mexican Americans.

In this case-control study we determined whether dietary differences underlie some of the ethnic and sex differences in US lung cancer rates. We examined the relationship between diet and lung cancer development in 137 lung cancer cases (93 African Americans and 44 Mexican Americans) and 187 controls (78 African Americans and 109 Mexican Americans). Cases reported a higher daily mean total fat intake (p < 0.001), whereas controls had a higher daily mean intake of dietary fiber (p < 0.001) and fruits (p = 0.02). Ethnic differences in diet were also observed: Mexican Americans consumed less total fat (p < 0.02) and more fiber (p < 0.001) and vegetables (p = 0.08) than African Americans. Additionally, men consumed more total fat (p = 0.08) and less fiber (p = 0.001), fruits (p < 0.001), and vegetables (p = 0.002) than women. Multivariable analysis, after adjustment for the effects of pack-years of smoking, age, total energy intake, sex, and ethnicity, demonstrated a positive association between high total fat consumption and lung cancer risk (p < 0.01) and an inverse association between high fruit consumption and lung cancer risk (p = 0.05). In conclusion, our findings support the hypothesis that diet, particularly high fat consumption and low fruit and vegetable consumption, contributes (independent of cigarette smoking) to the excess lung cancer risk in African-American men, who have the highest lung cancer rates in the United States.

Black or African American↗

Development of pattern visual evoked potentials: longitudinal measurements in human infants.

PURPOSE: This experiment used longitudinal testing to trace the emergence of the major components of pattern visual evoked potentials (VEPs) in infants, using two paradigms: large-checkerboard pattern reversal and low spatial frequency pattern onset. METHODS: Testing with both pattern-reversal and pattern-onset stimuli was performed on the same infants. Testing was conducted at weekly intervals during the first three postnatal months, and at intervals of 2 weeks to 1 month thereafter. RESULTS: The pattern-reversal and early pattern-onset responses recorded within individual subjects showed remarkably systematic developmental sequences. The broad, positive component seen at 200 to 250 ms in infants could be traced readily through the developmental sequence, to become the more sharply tuned positive component seen at about 100 ms in adults. Responses to low spatial frequency pattern onsets in infants were larger and more reliable than those in adults. The late components of the pattern-onset response, generally attributed to pattern offset, emerged later and with more complex changes. In all cases, response amplitude was much more variable than response latency, both within and between subjects. CONCLUSIONS: Frequent VEP recording in a longitudinal design can reveal systematic and detailed transitions of wave-form during development.

Adolescent↗

The point prevalence of wounds in a teaching hospital.

BACKGROUND: Wounds are a common problem, particularly in the elderly population. The scale of wound problems in hospital is largely unknown because wounds are widely dispersed. The present study examined the point prevalence of hospital wounds and undertook a pressure ulcer risk assessment of all patients on one day. METHODS: All 360 inpatients were surveyed and thoroughly examined. A risk scale for pressure sore development, the Norton score, was applied. When wounds were found, information was collected to determine their aetiology. RESULTS: Forty leg ulcers, 40 pressure sores, 85 surgical wounds and seven other types of wounds were found. Most leg ulcer and pressure sore cases were admitted for other reasons. The Norton score did not predict all cases of pressure ulceration. A total of 52% of wounds did not qualify for additional funding under current funding criteria. CONCLUSION: The prevalence of non-surgical wounds in Heidelberg Repatriation Hospital was easily underestimated. Wound care management can be optimized by staff education and protocol design, early identification of troublesome wounds and of at-risk patients, and a cross-sectional approach that incorporates wound-management teams.

Aged↗

Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells.

Prostaglandin synthesis requires cyclooxygenase-1 (COX1) or -2 (COX2), which mediate the conversion of arachidonate to prostaglandin H2. COX1 is the predominant constitutive isoform, whereas COX2 expression is typically low. In the present studies we cloned rabbit COX2 and determined its distribution in unstimulated tissues. Screening rabbit eye and uterine libraries yielded two cDNAs containing identical inserts with a 1,812-nucleotide open-reading frame. This encoded a 604-amino acid polypeptide, 90% identical to human, rat, and mouse COX2. Expression of the rabbit COX2 in HEK-293 cells enhanced prostanoid synthesis. Constitutive COX2 mRNA expression was highest in kidney and urinary bladder. COX2 expression was primarily in renal outer medullary interstitial cells with cortical expression in macula densa. In cultured medullary interstitial cells, COX2 mRNA predominated, with little COX1 expression. Interstitial cell COX2 mRNA but not COX1 was induced by phorbol ester and epidermal growth factor but suppressed by dexamethasone. Phorbol ester also upregulated immunoreactive COX2. Constitutive COX2 in these tissues has important implications for side effects of COX2-selective inhibitors.

Amino Acid Sequence↗

Overview of the hospital formulary systems in Hong Kong. Princess Margaret Hospital as a baseline.

OBJECTIVE: To investigate the popularity of formulary systems in all Hong Kong hospitals and to compare these with the newly introduced formulary system in a major government hospital, the Princess Margaret Hospital (PMH), as the baseline. DESIGN: Questionnaire and selected interviews by pharmacy students. SETTING: All hospital pharmacies in Hong Kong. PARTICIPANTS: Department managers (directors of pharmacy services) of hospital pharmacies. MAIN OUTCOME MEASURE: The popularity of the hospitals' formulary systems and their formulary decision-making strategies. Calculations of cost savings of the new formulary system in PMH and a comparison of the PMH system with the US standards were also made. RESULTS: Among 38 responding hospitals, 35 (92%) had a formulary handbook and 21 (55.3%) claimed to have a formulary system. The evaluation processes and formulary decision-making procedures were found to be inadequate because basic components in drug evaluation (e.g., standardized criteria for drug evaluation) were not used regularly. However, the formulary system in PMH was found to be comparable with the US standards. Substantial cost savings were made through rejection of less cost-effective drugs by the Formulary Subcommittee in PMH. CONCLUSIONS: In general, comprehensive formulary systems are still not popular in Hong Kong. This may be due to insufficient staffing and lack of administrative and physicians' support. The new formulary system in PMH can be used as a model to develop a successful formulary system in which hospital pharmacists can prove their expertise for the benefit of both hospitals and patients in Hong Kong.

Attitude of Health Personnel↗

Commitment to the underserved: evaluating the effect of an extracurricular medical student program on career choice.

BACKGROUND: This study was conducted to compare the practice locations and characteristics of physicians who participated as medical students in an extracurricular program to foster interest in careers of service to medically underserved populations with those of their classmates who did not participate in the program. METHODS: Using a mailed questionnaire, we conducted a cross-sectional study of graduates from the classes of 1983-1987 at one southwestern, public medical school. All Commitment to Underserved People (CUP) participants (n = 94) and a random sample of nonparticipating classmates (n = 188) were surveyed. CUP is an extracurricular project with components in each of 4 years of medical school that provides peer and faculty support, curriculum enrichment, and direct service to medically underserved populations. Outcome measures included the size of community of practice, practice type, and practice patient characteristics. RESULTS: Sixty seven (71%) of CUP participants and 126 (67%) of nonparticipants responded. CUP participants were more likely to be women, to specialize in family practice, to practice in the Indian Health Service (IHS) or overseas, to be located in a community of 25,000 or less, and to have participated in the state, service-payback loan program. In multiple regression, the specialty of family practice was associated with practice in a small community, the IHS, and a community health center; CUP participation was correlated with practice in small communities, the IHS, and a foreign country. CONCLUSIONS: Participation in the CUP program was associated with the specialty choice of family practice and with practice in settings associated with medically underserved populations. The CUP program has been successful in sustaining entering medical students' interests in underserved practice.

Journal Article↗

Serial proton magnetic resonance spectroscopy imaging of glioblastoma multiforme after brachytherapy.

The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormnal metabolite levels in nonenhancing regions of solid tumor.

Aspartic Acid↗

[Physiological effects of cabin temperature decrease on human].

To study effects of cabin temperature on human body, changes in rectal temperature, local skin temperature, local skin heat fluxes and skin infrared thermogram were observed in 5 male subjects dressed in different thermal insulation clothings under 20 degrees C, 15 degrees C and 10 degrees C cabin temperatures. The results showed that, average skin temperature and tip temperature obviously dropped, and skin heat fluxes increased with falling of cabin temperature, and changes of local skin infrared thermogram were significant. Subjective feeling were comfortable and cool at cabin temperature of 20 degrees C and 15 degrees C respectively. While subjective feeling was cold and there was a thermal debt of body 144 kJ/m2 at 10 degrees C which indicated that it was slightly cold but tolerable. The results may be valuable in determining the lowest tolerable limit of cabin temperature.

Acclimatization↗

[Thermoregulation under simulated weightlessness].

The effect of simulated weightlessness on thermoregulation was studied in 5 subjects. The experiment consisted of 3d baseline measurements, 7d head-down bed rest and 2d recovery. Circadian rhythm was assessed by continuous measurements of rectal temperature and skin temperature with 2h intervals. Heat Stress Protein 70 (HSP70) was measured by Western-blot Dot method and the facial surface temperature distribution was measured by HR-2 infrared thermography. The results showed that rectal temperature keeps the wake-sleep variation, but the circadian rhythm changed during bed rest, and the change of rectum temperature rhythm appeared mainly in the early-days of bed rest; HSP70 and facial surface temperature increased during bed rest.

Bed Rest↗

Breast cancer survival and the timing of tumor removal during the menstrual cycle.

In a retrospective cohort study of 262 premenopausal breast cancer patients treated at the Mayo Clinic between 1965 and 1985, we investigated whether survival was associated with the timing of tumor removal during the menstrual cycle. Participants were women < or = 50 years old who had not used exogenous hormones, been pregnant, been lactating, or given birth within 6 months of diagnosis. The menstrual cycle day at surgery was used to assign women to group 1 (cycle days 0-7), group 2 (cycle days 8-15), or group 3 (after cycle day 15). Cox proportional hazards analysis adjusting for age at diagnosis, stage, tumor size, grade, and node involvement showed a nonsignificantly worse survival for group 2 than for group 3 [hazard ratio (HR), 1.41; 95% confidence interval (CI), 0.89-2.23]. Stratification revealed that the association between survival and timing of tumor removal during the menstrual cycle was slightly stronger among patients with stage II disease (adjusted HR, 1.56; 95% CI, 0.92-2.63). The association was the same among patients with stage II disease and node involvement (adjusted HR, 1.57; 95% CI, 0.82-3.03). Prospective studies using hormone measurements to define menstrual cycle status more accurately than the reported day of the menstrual cycle could provide further insight about the postulated association.

Adult↗

Identification of regulatory sequences of juvenile hormone-sensitive and -insensitive serum protein-encoding genes.

The promoters of three juvenile hormone (JH)-sensitive, and one JH-insensitive hexamerin-encoding genes (Hex) were isolated from Trichoplusia ni, and sequences necessary for, or affecting, transcriptional activity were identified by biochemical and functional methods. The transcription start points (tsp) for each of the four Hex were determined biochemically, by both primer extension and the sequencing of multiple, independent full-length cDNA clones. The function of each inferred tsp, as an actual tsp, was confirmed by in vitro transcription assay. The transcription initiator sequence, GNACAGT, was identical for three of the Hex, while the fourth used a divergent motif. Using the in vitro transcription system, a minimal core promoter of 60 bp (bp -34 to +24) of the BJHSP1 (basic JH suppressible protein 1) gene, containing a single TATA box motif approximately 30 bp upstream of the tsp, was functionally sufficient to support alpha-amanitin-sensitive transcription. The same construct was also transcriptionally functional in a homologous cell line transfection assay. The corresponding region of the other Hex also contains a similarly positioned TATA box motif, and promoter constructs for each, that included that included the tsp, initiator and inferred basal transcription apparatus binding site, were all transcriptionally functional in a cell line transfection assay. The action of sequences 5' to the minimal promoter region in modulating the rate of transcription was shown by a cell line transfection assay of a nested deletion series of the promoter for the BJHSP1 gene, in which the results identified a strongly suppressive element between positions -160 and -109. This system of Hex genes, including those sensitive to JH and one not sensitive, should be useful in a comparative approach toward identifying those regulatory motifs that are functionally necessary to transduce the regulatory action of JH.

Animals↗