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Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 145 records · Page 8Linked to original sources
PubMed1996

Group A streptococcal bacteremia: the role of tumor necrosis factor in shock and organ failure.

Severe group A streptococcal infections associated with early onset shock and multiorgan failure define the streptococcal toxic shock syndrome. In the United States, group A streptococcal strains most commonly isolated are M types 1 and 3, which produce pyrogenic exotoxin type A. The role of tumor necrosis factor (TNF)-alpha and the dynamics of cardiovascular and laboratory abnormalities were investigated in a baboon model of group A Streptococcal bacteremia that mimics human Streptococcal toxic shock syndrome. Profound hypotension, leukopenia, metabolic acidosis, renal impairment, thrombocytopenia, and disseminated coagulopathy developed within 3 h after intravenous infusion of M type 3, pyrogenic exotoxin A-producing group A streptococci. Serum TNF-alpha peaked at 3 h and returned to baseline by 10 h. Mortality was 100%. Anti-TNF-alpha monoclonal antibody treatment markedly improved mean arterial blood pressure, tissue perfusion, and survival, suggesting that TNF-alpha plays an important role in the induction of shock and organ failure in group A streptococcal bacteremia.

Animals↗
PubMed1996

Hypericin: a new laser phototargeting agent for human cancer cells.

Laser activation of anthracycline-related drugs combines chemotherapy with photoablation for improved treatment. Hypericin, a structurally related anthraquinone, was tested for laser activation and cytotoxicity in human cancer cells. Viability of P3 squamous cell carcinoma cells incubated with 1 to 20 microgram/mL hypericin was reduced by more than 95% after 1 minute exposure at 4 degrees C to an argon laser (514 nm, 5 W), a KTP-532 laser (532 nm, 5 W), or a 20-A xenon lamp. Viability was reduced over 90% in six human carcinoma, sarcoma, and melanoma cell lines by this combined treatment, but only trace toxicity was seen after separate exposure to hypericin or light alone. These results show that hypericin is a sensitive agent for phototherapy of human cancer cells in vitro and indicate that this drug may be useful for tumor targeting via minimally invasive imaging-guided laser fiber optics.

Anthracenes↗
PubMed1996

Gonadoblastoma in patient with Turner's syndrome.

A 15-year-old phenotypic female referred for the investigation of primary ammenorrhea, was found to have a 45,XO karyotype and an ovarian cyst. She demonstrated some of the features of Turner's syndrome, as well as virilization. On laparotomy, she was found to have bilateral gonadoblastomas. She was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Subsequently, repeated chromosomal analysis detected the presence of Y chromosomes, which was confirmed by the use of polymerase chain reaction (PCR). The difficulties encountered in searching for the Y chromosome in patients with gonadoblastoma are discussed. Prophylactic gonadectomy is suggested in those cases associated with atypical features.

Adolescent↗
PubMed1996

Cervical ripening before induction of labour in patients with an unfavourable cervix: a comparative randomized study of the Atad Ripener Device, prostaglandin E2 vaginal pessary, and prostaglandin E2 intracervical gel.

One hundred and nineteen women with singleton pregnancy and cephalic presentation requiring induction of labour in the presence of an unfavourable cervix (Bishop score < or = 4) were studied. Five patients were excluded because of failure to comply with the protocol. Cervical ripening was carried out using 3 different methods; 36 used the Atad Ripener Device, 39 received 0.5 mg PGE2 intracervical gel and 39 received at least one 3 mg PGE2 intravaginal pessary. There were no differences in the demographic characteristics and the indications for induction. Five patients developed complications during the ripening period necessitating intervention; 3 required emergency Caesarean section and 2 delivered vaginally. Although statistically there were no differences among the 3 methods of cervical ripening, the power of the study is probably not large enough to show the differences. The PGE2 pessary appears to be more effective with 68% of patients either going into labour during cervical ripening or succeeding in the cervical ripening compared to around 50% in the Atad and PGE2 gel groups. The vaginal delivery rate was 87.2% in the pessary group compared to 72.2% in the Atad group and 84.6% in the gel group. The duration of labour was also shorter in the pessary group with 73.5% delivered within 24 hours compared to 57.7% in the Atad group and 57.6% in the gel group. Although the results of the Atad device seem to be inferior, the risk of uterine hyperstimulation from the use of the device is probably lower than that of the PGE2 and may therefore be preferable in women with fetuses at high risk of fetal hypoxia.

Adult↗
PubMed1996

Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: flutamide versus diethylstilbestrol.

PURPOSE: Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone. Therapy with diethylstilbestrol (DES), leuprolide, or bilateral orchiectomy has been reported to be equivalent. DES is the cheapest preparation, but has the potential for serious cardiovascular or thromboembolic complications. Flutamide is a novel antiandrogen with fewer side effects. PATIENTS AND METHODS: The Eastern Cooperative Oncology Group (ECOG) conducted a double-blind, randomized study to compare the efficacy of flutamide (250 mg three times daily) to DES (1 mg three times daily) as the primary hormonal therapy for patients with stage D2 prostate cancer. Patients were stratified by performance status, disease sites, and history of cardiovascular disease at randomization. RESULTS: Forty-eight patients received DES and 44 flutamide. Patient characteristics were evenly distributed between the two treatments. The overall response rate was similar (DES, 62%; flutamide, 50%). Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3% of patients on DES and in 17.6% on flutamide (P = .051). Other toxicities were similar between the two treatment arms. However, DES produced significantly longer time to treatment failure (26.4 v 9.7 months, P = .016) and longer survival than flutamide (43.2 v 28.5 months, P = .040). CONCLUSION: As the primary hormonal therapy for stage D2 prostate cancer, DES caused more serious cardiovascular or thromboembolic complications than flutamide. Despite this, flutamide was not as active an initial agent as DES. However, the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined, and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies.

Administration, Oral↗
PubMed1996

Human vitreous hyaluronidase: isolation and characterization.

PURPOSE: Hyaluronic acid (HA) is the predominant glycosaminoglycan (GAG) of the human vitreous. Interaction of this HA with vitreous collagen is important for maintaining gel structure. The mechanism of HA homeostasis in the vitreous is incompletely understood. The aim of this study was to determine whether hyaluronidase, an endoglycosidase that degrades HA, was present in human vitreous. METHODS: Vitreous samples were collected from post-mortem eye bank specimens and from non-hemorrhagic, non-inflamed biopsy specimens. Vitreous hyaluronidase was purified by a series of column chromatographic steps, and its activity was measured by an ELISA-like assay and by substrate gel electrophoresis through and HA-impregnated gel. The purified hyaluronidase was also analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and by Western blotting. RESULTS: Hyaluronidase activity was detected in vitreous samples from both post-mortem and biopsy specimens. The enzyme was most active at acid pH, but demonstrated significant activity at neutral pH. The partially purified enzyme migrated as a 59 kDa protein on SDS-PAGE, and a single band on Western blots. CONCLUSIONS: Hyaluronidase is present in the human vitreous. Thus, hyaluronidase may be involved in HA catabolism in the vitreous and may play a role in determining its gel structure.

Blotting, Western↗
PubMed1996

Cellular and metabolic basis of Clara cell tolerance to multiple doses of cytochrome P450-activated cytotoxicants. I: Bronchiolar epithelial reorganization and expression of cytochrome P450 monooxygenases in mice exposed to multiple doses of naphthalene.

The objectives of this study were to quantitatively define alterations in the epithelial populations and expression of cytochrome P450 monooxygenases in distal airways which are associated with the tolerance resulting from repeated exposure of mice to the acute Clara cell toxicant, naphthalene. Bronchiolar epithelium of mice treated daily for 7 days with an acutely cytotoxic dose of naphthalene (200 mg/kg/day) quantitatively resembles the bronchiolar epithelium of control animals in terms of proportions of ciliated and nonciliated cells and nuclear and cytoplasmic volumes. Subsequent treatment of tolerant animals with higher doses (300 mg/kg) does not produce the same Clara cell injury observed in previously untreated mice after a single treatment with 300 mg/kg. After repeated exposures to naphthalene, cellular expression of immunoreactive cytochrome P450 monooxygenases 2B and 2F, P450 reductase and Clara cell secretory protein significantly decreased in bronchiolar epithelium. Although metabolism of naphthalene to the 1R,2S-naphthalene oxide is depressed in microsomes derived from whole-lung homogenates of tolerant animals, metabolism of naphthalene in distal airways isolated by microdissection is unchanged from the controls at saturating substrate concentrations. When substrate concentrations are less than the apparent K(m) for naphthalene (< 0.05 mM), the rate of naphthalene metabolite production is markedly lower in distal airways of tolerant mice compared with controls. Covalent binding of reactive naphthalene metabolites in lungs of tolerant mice is also unchanged from control. In conclusion, after repeated exposure to short-term cytotoxic doses of naphthalene distal bronchioles of tolerant mice 1) are lined by epithelium which resembles that of controls; 2) express lower levels of P450 proteins; 3) have reduced levels of naphthalene monooxygenase activity, but only at less than saturating concentrations and 4) have no decrease in covalent binding of reactive metabolites to proteins.

Animals↗
PubMed1995

In situ hybridization to chromosomes stabilized in gel microdrops.

Conventional chromosome in situ hybridization procedures rely on fixation to glass slides followed by microscopic evaluation. This report describes the development of a microdrop in situ hybridization to chromosomes in suspension. Chromosomes encapsulated in gel microdrops (GMDs) composed of an agarose matrix withstood stringent hybridization and denaturation conditions. Because of the increased stability, hybridization to encapsulated chromosomes was detected by flow cytometry as well as conventional microscopy. Thus, the MISH method offers a means for chromosome hybridization without slides and may enable identification and isolation of chromosome using hybridization rather than nucleic acid binding dyes.

3T3 Cells↗
PubMed1995

Purification and characterization of a heat-stable wheat substrate for wheat embryo calcium-dependent protein kinase.

A heat-stable wheat protein (WP) that is a good substrate for wheat embryo Ca(2+)-dependent protein kinase (CDPK) was purified from wheat embryo by a procedure involving batchwise anion exchange chromatography on DEAE-cellulose (DE52), passage through Phenyl-Sepharose CL-4B, heat and acid treatment and anion exchange HPLC on a DEAE-5PW column. WP is phosphorylated by CDPK to a stoichiometry of about 0.8 mol phosphoryl per mol WP. The Km for WP is 3.5 microM. WP is phosphorylated by CDPK on Ser residues. [32P]phosphoWP exactly copurifies on SDS-PAGE with WP (59 kDa). Phosphorylation of WP by CDPK is largely Ca(2+)-dependent. The N-terminal amino acid sequence of WP has homology with bacterial azurins. Evidence for two serine phosphorylation sites was obtained from sequencing of phosphopeptides derived from tryptic and chymotryptic digests of phosphoWP. One major site of phosphorylation is inferred to be on a serine within the sequence KKMASMK. WP is one of the best endogenous protein substrates yet found for wheat embryo CDPK. A 59kDa protein is phosphorylated in vivo in sprouting wheat.

Amino Acid Sequence↗
PubMed1995

Peripheral blood progenitor cells mobilized by recombinant human granulocyte colony-stimulating factor plus recombinant rat stem cell factor contain long-term engrafting cells capable of cellular proliferation for more than two years as shown by serial transplantation in mice.

Mobilized peripheral blood progenitor cells (PBPC) have been shown to provide rapid engraftment in patients given high-dose chemotherapy. PBPC contain cells with long-term engraftment potential as shown in animal models. In this study we have further analyzed mobilized PBPC for their ability to support serial transplantation of irradiated mice. Transplantation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) plus recombinant rat stem cell factor (rrSCF) mobilized PBPC resulted in 98% donor engraftment of primary recipients at 12 to 14 months post-transplantation. Bone marrow (BM) cells from these primary recipients were harvested and transplanted into secondary recipients. At 6 months posttransplantation, all surviving secondary recipients had donor engraftment. Polymerase chain reaction (PCR) analysis showed greater than 90% male cells in spleens, thymuses, and lymph nodes. Myeloid colonies from BM cells of secondary recipients demonstrated granulocyte/macrophage colony-forming cells (GM-CFC) of male origin in all animals. In comparison, transplantation of rhG-CSF mobilized PBPC resulted in decreased male engraftment in secondary recipients. BM cells from secondary recipients, who originally received PBPC mobilized by the combination of rrSCF and rhG-CSF, were further passaged to tertiary female recipients. At 6 months posttransplantation, 90% of animals had male-derived hematopoiesis by whole-blood PCR analysis. These data showed that PBPC mobilized with rhG-CSF plus rrSCF contained cells that are transplantable and able to maintain hematopoiesis for more than 26 months, suggesting that the mobilized long-term reconstituting stem cells (LTRC) have extensive proliferative potential and resemble those that reside in the BM. In addition, the data demonstrated increased mobilization of LTRC with rhG-CSF plus rrSCF compared to rhG-CSF alone.

Animals↗
PubMed1995

Extensor digitorum brevis reflex in normals and patients with radiculopathies.

This prospective study evaluated the extensor digitorum brevis deep tendon reflex (EDBR) in a normal population and in patients with L-5 and S-1 radiculopathies. There were 88 subjects: 53 normals, 17 L-5, and 18 S-1 radiculopathy subjects. The clinical EDBR revealed a 91% specificity, with 18% sensitivity for L-5, and 11% for S-1. The electrodiagnostic EDBR yielded increased sensitivities of 35% for L-5 (P = 0.07) and 39% for S-1 (P = 0.04), with 87% specificity. H-reflexes showed 50% sensitivity for the S-1 group (P = 0.0006) and 91% specificity. EDBR latencies were significantly related to age and leg length (r2 = 0.46, P < 0.0001). Age alone explained 26% (P < 0.0001) of the EDBR variability and leg length 20% (P < 0.0001). EDBR clinical and electrodiagnostic reflexes have low sensitivities, high specificities, and do not discriminate L-5 from S-1 root involvement.

Adult↗
PubMed1995

Computerised fetal heart rate analysis in labour--effect of sampling rate.

OBJECTIVE: To study the effect of sampling rate on the accuracy of fetal heart rate recording in labour. DESIGN: Prospective observational study. METHODS AND SUBJECTS: The fetal heart rate was obtained from 153 fetuses in labour. The heart rate data was sampled at a rate of 0.5 Hz (every 2 s) and the means and standard deviations of 5-min segments compared against the mean and standard deviation for all beats in the same time interval. RESULTS: There was a highly significant correlation between the means (r = 0.994, p < 0.001) and standard deviations (r = 0.957, p < 0.001) of FHR sampled on successive beats compared with 2 s sampling. CONCLUSION: Two second sampling of the fetal heart rate in labour will allow a highly complex analytical algorithm to process the signal in near real time for objective analysis.

Algorithms↗
PubMed1995

Current therapy for cutaneous melanoma.

We review the current therapy for melanoma. The diagnosis, prognostic variables, staging, treatment, and follow-up guidelines for cutaneous melanoma are reviewed from the earliest to the most advanced stages. New guidelines for margins are discussed. A new, evolving, innovative radiographic technique, positron emission tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose, may be useful to identify subclinical nodal and visceral disease. Recent advances with respect to tumor vaccines, gene therapy, immunotherapy, and interleukin 2 as well as current concepts regarding lymph node dissection are discussed.

Humans↗
PubMed1995

Anterior maxillary advancement using tooth-supported distraction osteogenesis.

PURPOSE: This study used the principle of distraction osteogenesis to advance the anterior maxilla of the dog using a totally tooth-supported distraction device. MATERIALS AND METHODS: After an anterior maxillary osteotomy, the distraction device was activated 0.5 mm every 12 hours to advance the anterior segment 10 mm in 10 days. RESULTS: Serial tooth and radiographic measurements indicated that on the 10th day the average tooth advancement was 8.4 mm +/- 1.5 mm and the average skeletal advancement was 4.0 mm +/- 1.5 mm. After 6 weeks the average tooth advancement was 7.2 +/- 1.6 mm and the average skeletal advancement was 3 +/- 1.3 mm. At 3 months the tooth advancement was 6.2 +/- 1.5 mm and at 6 months the tooth advancement was 5.0 +/- 1.1 mm. Bone healing was present in all animals. CONCLUSION: This results of this study indicate that a tooth-borne maxillary distraction device will result in significantly greater dental movement than skeletal movement and that skeletal fixation may be needed for appliances used to advance the maxilla.

Animals↗
PubMed1995

The effect of povidone-iodine solution applied at the conclusion of ophthalmic surgery.

PURPOSE: Povidone-iodine 5% solution decreases the incidence of postoperative endophthalmitis when used on the eye for preoperative preparation. We sought to determine whether it also minimized conjunctival bacterial flora immediately after surgery by preventing bacteria present on the surface of the eye from entering surgical wounds. METHODS: In 42 eyes of 40 patients, at the conclusion of surgery, on an alternating basis, each patient received either a drop of a broad-spectrum antibiotic solution (polymyxin B sulfate-neomycin sulfate-gramicidin) or a 5% povidone-iodine solution in the operated-on eye. Bacterial cultures were taken before and after surgery and 24 hours later. The 38 unoperated-on eyes in the unilateral cases served as control eyes. RESULTS: Relative to the control group, povidone-iodine was effective in preventing an increase in the number of colony-forming units (P = .035), while the antibiotic was not. At 24 hours after surgery, the species count was lower in the eyes receiving povidone-iodine than in the antibiotic-treated eyes (P = .034) and was increased in the antibiotic group since the completion of surgery (P = .013), but was lower in the povidone-iodine and antibiotic groups than in the control eyes for both groups (P < .01). CONCLUSIONS: Povidone-iodine 5% solution applied to the eye at the conclusion of surgery was more effective at minimizing the number of colony-forming units and species for the first postoperative day than was a broad-spectrum antibiotic. While not true for the antibiotic, the antimicrobial effect of povidone-iodine lasted for at least 24 hours after the completion of surgery.

Bacteria↗
PubMed1995

An adjustable fetal weight standard.

The monitoring of fetal weight is an important aspect of antenatal care. To construct an individually adjustable standard, we developed a model to link the predicted birth weight to a fetal weight curve which outlines how this weight is to be reached in an uncomplicated pregnancy. A formula was derived which describes the median fetal weight at each gestation as a proportion of the optimal term weight, and also defines the 90th and 10th centile curves as normal limits. We analyzed a birth weight database of 38,114 singleton, routine ultrasound-dated pregnancies resulting in term deliveries. By stepwise multiple regression analysis, we derived coefficients for the factors that act as variables on term birth weight in our population. Apart from gestational age and sex, the maternal height, weight at first visit, ethnic group, parity and smoking all have significant and independent effects on birth weight. The variation due to ethnic group appears to be physiological in this population. Smoking is associated with a reduction in birth weight, which is independent of maternal physique and related to the number of cigarettes per day as reported at the first visit. We have developed a software program which calculates, on the basis of pregnancy variables entered at the first visit, an adjusted normal range for fetal size. This can be printed out as a chart and used for antenatal surveillance of growth.

Birth Weight↗