Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 127 records · Page 7Linked to original sources

PubMed1997

The development of a hybrid expert system for the interpretation of fetal acid-base status.

This article presents the development of an expert system for the interpretation of fetal scalp acid-base status. The system consists of logistic transformations, back-propagation neural networks and decision algorithms connected in series. It checks for out-of-range errors and the physiological coherence between measurements. It then determines whether acidosis should be diagnosed, and if so, whether it is more likely to be metabolic, respiratory or mixed. It will also flag those cases where it is difficult to interpret the data in physiological terms. The system was tested on a database of 2174 scalp blood samples collected at the Queens Medical Centre, Nottingham. Of these 88 samples were rejected as erroneous; 13 because of an out-of-range pH alone (> or = 7.48); 73 because more than one measurement was marginally out of range, and two because the relationship between measurements did not make sense. A total of 527 cases (24.2%) were diagnosed as being acidotic; of these, 139 were respiratory, 114 mixed and 274 metabolic. We were unable to fault the system's interpretation when the cases at the margins between diagnostic categories were reviewed clinically.

Acid-Base Equilibrium↗

PubMed1997

Dopamine requires ascorbic acid to be the prolactin release-inhibiting factor.

A high concentration of dopamine (10(-6) mol/l) inhibited prolactin release for < 60 min during a 2-h perifusion period by use of primary cultured pituitary cells. However, when dopamine (10(-6) mol/l) and control medium were alternately perifused, dopamine inhibited prolactin release for a longer period, indicating that the inability of dopamine to sustain an inhibitory action is likely caused by decreased sensitivity of the lactotrophs to dopamine. When 3 x 10(-7) mol/l dopamine was perifused, prolactin release was inhibited for only 15 min, and the rate of prolactin release was decreased to a nadir by addition of ascorbic acid (10(-4) mol/l) 15 min after the start of dopamine perifusion. Dopamine decreased density of dopamine D2 receptors, and ascorbic acid inhibited the receptor downregulation in GH4ZR7 cells. These results support our hypothesis that dopamine requires a supplementary agent to be the prolactin release-inhibiting factor and that the supplementary agent is ascorbic acid.

Animals↗

PubMed1997

Dorsoventral patterning of the vertebrate neural tube is conserved in a protochordate.

The notochord and dorsal ectoderm induce dorsoventral compartmentalization of the vertebrate neural tube through the differential regulation of genes such as HNF-3beta, Pax3, Pax6 and snail. Here we analyze the expression of HNF-3beta and snail homologues in the ascidian, Ciona intestinalis, a member of the subphylum Urochordata, the earliest branch in the chordate phylum. A combination of in situ hybridization and promoter fusion analyses was used to demonstrate that the Ciona HNF-3beta homologue is expressed in the ventralmost ependymal cells of the neural tube, while the Ciona snail homologue is expressed at the junction between the invaginating neuroepithelium and dorsal ectoderm, similar to the patterns seen in vertebrates. These findings provide evidence that dorsoventral compartmentalization of the chordate neural tube is not an innovation of the vertebrates. We propose that precursors of the floor plate and neural crest were present in a common ancestor of both vertebrates and ascidians.

Amino Acid Sequence↗

PubMed1997

Oral ondansetron 8 mg twice daily is as effective as 8 mg three times daily in the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. S3A-376 Study Group.

The efficacy and safety of ondansetron 8 mg BID compared with 8 mg TID for 3 days in the prevention of nausea and vomiting in 402 patients on cyclophosphamide (> or = 500 mg/m2)-based chemotherapy were evaluated in a multicenter, randomized, double-blind, stratified study. The percentage of patients with no emetic episodes over the 3-day study period was 61% in the ondansetron BID group compared with 58% in the ondansetron TID group. Among patients with at least one emetic episode, the mean time to emesis was 14 hr and 17 min in the ondansetron BID group compared with 12 hr and 48 min in the ondansetron TID group. Patients' daily appetite ratings and nausea scores were not significantly different between groups. Clinical laboratory and adverse event profiles were similar between groups. This study is the first large-scale, double-blind trial to demonstrate that ondansetron 8 mg BID for 3 days, a dosing regimen that may enhance patient convenience and compliance, is as effective as ondansetron 8 mg TID for 3 days in the prevention of nausea and vomiting associated with cyclophosphamide-based chemotherapy.

Administration, Oral↗

PubMed1997

A review of laparoscopy and laparotomy in the management of tubal pregnancy.

A retrospective review was performed of all women who had undergone operation for a tubal pregnancy at the Prince of Wales Hospital, Hong Kong, from November 1992 to March 1994. One hundred and five patients were included---61 were managed by laparoscopy and 44 by laparotomy. There were no differences in age, parity, gestational age, frequency of previous ectopic pregnancy, or laparotomy between the two groups. Sixty per cent of patients in the laparotomy group had a diagnostic laparoscopy prior to the laparotomy. The laparoscopy group had a lower incidence of haemoperitoneum (45.9% vs 75.0%, P<0.05). There was no difference in the mean operating time. The laparoscopic approach was associated with a significant reduction in: intra-operative blood loss (46.7plus minus76.8 mL vs 213.4plus minus149.3 mL. P<0.001), post-operative analgesia requirement (odds ratio 0.08, 95% CI, 0.02-0.32), post-operative morbidity (odds ratio 0.27, 95% CI, 0.12-0.58), length of hospital stay (2.9plus minus2.2 days vs 5.1plus minus1.2days, P<0.001) and recuperation period (11.0plus minus9.3days vs 21.7plus minus8.5 days, P<0.001). Operative laparoscopy has the advantage of combining diagnostic and therapeutic procedures in a single operation, and is a better approach than laparotomy in the management of tubal pregnancy.

Journal Article↗

PubMed1996

Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy.

To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Tissue-engineered skeletal muscle organoids for reversible gene therapy.

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Animals↗

PubMed1996

A novel Ca2+-binding protein, p22, is required for constitutive membrane traffic.

We have identified a novel protein, p22, required for "constitutive" exocytic membrane traffic. p22 belongs to the EF-hand superfamily of Ca2+-binding proteins and shows extensive similarity to the regulatory subunit of protein phosphatase 2B, calcineurin B. p22 is a cytosolic N-myristoylated protein that undergoes conformational changes upon binding of Ca2+. Antibodies against a p22 peptide block the targeting/fusion of transcytotic vesicles with the apical plasma membrane, but recombinant wild-type p22 overcomes that inhibition. Nonmyristoylated p22, or p22 incapable of undergoing Ca2+-induced conformational changes, cannot reverse the antibody-mediated inhibition. The data suggest that p22 may act by transducing cellular Ca2+ signals to downstream effectors. p22 is ubiquitously expressed, and we propose that its function is required for membrane trafficking events common to many cells.

Amino Acid Sequence↗

PubMed1996

Effect of oral estradiol on Lp(a) and other lipoproteins in postmenopausal women. A randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Lp(a) lipoprotein level is an independent risk factor for premature coronary artery disease and cerebrovascular accident. Concentrations of this lipoprotein tend to increase after menopause. OBJECTIVE: To determine whether oral estrogen was effective in lowering concentrations of Lp(a) lipoprotein in postmenopausal women. METHODS: A double-blind, placebo-controlled, cross-over study was conducted during a 12-month period in 100 postmenopausal women who had undergone hysterectomy. They were randomized into two groups: group 1 received oral estradiol, 2 mg/d, for the first 6 months and placebo for the second, and group 2 received these treatments in the reverse order. After completion of the crossover study, the effect of prolonged administration of oral estradiol was examined by placing all patients on active treatment and repeating the lipoprotein measurements approximately 12 months later. RESULTS: No significant differences were noted between the two groups at the commencement of the study (median concentration of Lp[a] lipoprotein, 10.78 mg/dL [range, 2.2 to 108.5 mg/dL] in group 1 and 12.74 mg/dL [range, 0.8 to 98.1 mg/dL] in group 2). Crossover analysis showed a 9.62% reduction in values of Lp(a) lipoprotein with estradiol treatment compared with placebo during 12 months of treatment (P < .001). With prolonged treatment, the median concentration of Lp(a) lipoprotein for those in group 1 decreased from 8.12 mg/dL (range, 1.05 to 57.4 mg/dL) to 5.77 mg/dL (range, 0.84 to 75.39 mg/dL) (P < .001). In group 2, the median concentration decreased from 8.19 mg/dL (range, 2.52 to 99.82 mg/dL) to 7.07 mg/dL (range, 0.70 to 48.79 mg/dL), but this difference was not significant (P = .63). CONCLUSIONS: The results of this study confirm the beneficial effect of oral estradiol on the basic lipoprotein pattern and demonstrate that this treatment is effective in reducing concentrations of Lp(a) lipoprotein in postmenopausal women.

Administration, Oral↗

PubMed1996

Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer.

BACKGROUND: Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear. PURPOSE: A meta-analysis was carried out to provide an objective and quantitative appraisal of the benefits of HAI in terms of tumor response rate and overall patient survival. METHODS: The meta-analysis was based on individual data provided by the principal investigators of six individual trials and on summary data for one trial. Of the seven trials, five compared HAI with floxuridine (5-fluoro-2'-deoxyuridine; FUDR) and intravenous chemotherapy (IVC) with FUDR (three trials) or fluorouracil (5-FU) (two-trials), and two compared HAI with FUDR and an ad libitum control group in which some patients could be left untreated. Response data were analyzed by use of a Mantel-Haenszel test on all randomized patients. Survival data were analyzed by the use of stratified logrank test. Multivariate analyses were performed with use of the logistic regression model for tumor response and the Cox regression model for survival. All P values resulted from two-sided statistical tests. The analyses were performed by an independent secretariat and were reviewed by the collaborators. RESULTS: The tumor response rate was 41% for patients allocated to HAI with FUDR or 5-FU (CR, 2%; PR, 12%). This difference was highly significant, with a response odds ratio of 0.25 (95% confidence interval = 0.16-0.40; P < 10 (-10)). Survival analyses showed a statistically significant advantage for HAI with FUDR compared with control when trials were taken into account (P = .0009) but not when the survival analysis was restricted to trials comparing HAI with FUDR and IVC with FUDR or 5-FU (P = .14). CONCLUSION: These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer. IMPLICATIONS: The therapeutic benefit of use of HAI with FUDR in these patients should be judged together, with an overall evaluation of this therapy in terms of convenience, toxicity, and costs. These end points should be considered in addition to tumor response and survival in further trials involving HAI.

Antimetabolites, Antineoplastic↗

PubMed1996

Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study.

OBJECTIVE: To determine the prevalence and associations of retinal vein occlusion (RVO) in a defined older Australian population. DESIGN: Participants (N = 3654; age, > or = 49 years), representing 88% of the permanent residents from an area west of Sydney, Australia, underwent a detailed eye examination, including stereophotography (Zeiss). The diagnosis of RVO was made clinically and from photographic grading. RESULTS: Signs of RVO were found in 59 participants (1.6%; 95% confidence interval, 1.3-1.9). The prevalence for each age-specific participant was as follows: 0.7%, younger than 60 years; 1.2%, 60 to 69 years; 2.1%, 70 to 79 years; and 4.6%, 80 years or older. There was no significant sex difference in prevalence. Branch RVO was observed in 41 subjects (69.5%); of this number, 10 subjects had branch RVO outside the vascular arcade or in the nasal fundus and 3 subjects developed new vessels. Hemispheric RVO was found in 3 subjects (5.1%), and central RVO was observed in 15 (25%); RVO was bilateral in 3 subjects (5.1%). Visual acuity was affected most in the people with central RVO, with a visual acuity of 20/200 or less in 60% compared with 14% among the people with branch RVO. Retinal vein occlusion was the fifth most frequent cause of unilateral blindness in this population. Significant associations with RVO were found with glaucoma, hypertension, stroke, and angina. CONCLUSIONS: This study emphasizes RVO as an important cause of unilateral visual loss in an older population. The proportion of the 3 vein occlusion sites shows some differences from those of clinic-based reports and suggests a likely selection bias in previous clinic studies.

Aged↗

PubMed1996

RNA expression patterns of a type 2 metallothionein-like gene from rice.

A type 2 metallothionein-like gene from rice, OsMT-2 (Oryza sativa metallothionein-like gene-2), was isolated in its cDNA form and sequenced. By northern analyses OsMT-2 expression was shown to be induced under stress by sucrose starvation, heat shock and, to a lesser extent, abscisic acid, but not excess metals, including copper. Its response to sucrose starvation was transient and different from OsMT-1, a type 1 metallothionein-like gene of rice inducible by copper. These results suggest that while OsMT-2 is also involved in cellular response to stress, its function may be complementary to that of OsMT-1.

Abscisic Acid↗

PubMed1996

Improved intrapartum surveillance with PR interval analysis of the fetal electrocardiogram: a randomized trial showing a reduction in fetal blood sampling.

OBJECTIVE: Our goal was to test the hypothesis that the addition of fetal electrocardiogram time-interval analysis to conventional electronic fetal monitoring would significantly reduce the number of cases requiring fetal scalp blood sampling without an increase in adverse outcome. STUDY DESIGN: A randomized prospective trial was performed in 214 women with high-risk labor. RESULTS: There was a significant reduction in the number of cases that had fetal blood sampling performed in the fetal electrocardiogram plus electronic fetal monitoring group (risk ratio for electronic fetal monitoring alone 3.53; p < 0.01, 95% confidence interval 1.39 to 8.95). The fetal blood samplings performed in the electronic fetal monitoring alone group were less likely to be abnormal (pH < 7.25, base excess < -8.0) than those performed in the fetal electrocardiogram plus electronic fetal monitoring group (risk ratio for electronic fetal monitoring alone 0.62, p = 0.05, 95% confidence interval 0.35 to 1.10). There was a trend of more infants with an arterial umbilical pH < 7.15 and a base excess less than -8.0 mmol/L at birth being unsuspected and more instrumental deliveries for presumed fetal distress being performed in the electronic fetal monitoring alone than in the fetal electrocardiogram plus electronic fetal monitoring group. CONCLUSION: The addition of fetal electrocardiogram analysis to conventional electronic fetal monitoring during labor can reduce significantly the number of parturients undergoing fetal scalp blood sampling and can simultaneously increase its efficiency without an increase in adverse outcome.

Acidosis↗

PubMed1996

Mandibular alveolar ridge augmentation in the dog using distraction osteogenesis.

PURPOSE: This study investigated the use of distraction osteogenesis for alveolar ridge augmentation. MATERIALS AND METHODS: Four dogs each had two superior and two inferior implants placed horizontally into an edentulous mandibular quadrant and, after integration, a distraction device was applied. An osteotomy was made to allow the ridge to be distracted vertically. After 10 mm vertical distraction, the device was stabilized. RESULTS: The vertical augmentation averaged 8.85 +/- 1.05 mm after 10 weeks of healing. Serial sections showed that bone had formed between the distracted segments, creating an augmented ridge. CONCLUSIONS: Distraction osteogenesis has the potential for use in augmentation of the alveolar ridge.

Alveolar Ridge Augmentation↗

PubMed1996

Capsular bag distension with an acrylic intraocular lens.

PURPOSE: To describe the postoperative capsular bag distension that occurs with in-the-bag implantation of the soft acrylic (AcrySof) intraocular lens (IOL). SETTING: Jules Stein Eye Institute, University of California, Los Angeles. METHODS: Nine eyes in nine patients had uncomplicated continuous curvilinear capsulorhexis, phacoemulsification, and in-the-bag implantation of the AcrySof lens. Comprehensive ophthalmic examinations were performed 1 day and 1 and 6 weeks postoperatively. Patients had neodymium:YAG laser posterior capsulotomy; refractions were done before and after the capsulotomy. RESULTS: Comprehensive ophthalmic examination revealed variable degrees of anterior chamber shallowing, anterior displacement of the IOL within the bag, and distension of the posterior capsule away from the IOL. Unexpected postoperative myopic correction was seen in all patients. Postcapsulotomy mean spherical equivalent refractive shift was +3.6 diopters (D) with a shift of at least +4.0 D in four of nine eyes. CONCLUSIONS: Capsular bag distension is a previously described postoperative complication that we observed in association with the AcrySof IOL.

Acrylates↗

PubMed1996

Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle.

The muscle myosins and hexomeric proteins consisting of two heavy chains and two pairs of light chains, the latter called essential (ELC) and regulatory (RLC). The light chains stabilize the long alpha helical neck of the myosin head. Their function in striated muscle, however, is only partially understood. We report here the identification of distinct missense mutations in a skeletal/ventricular ELC and RLC, each of which are associated with a rare variant of cardiac hypertrophy as well as abnormal skeletal muscle. We show that myosin containing the mutant ELC has abnormal function, map the mutant residues on the three-dimensional structure of myosin and suggest that the mutations disrupt the stretch activation response of the cardiac papillary muscles.

Amino Acid Sequence↗

PubMed1996

The fucosyltransferase FucT-VII regulates E-selectin ligand synthesis in human T cells.

Selectin-ligands on T cells contribute to the recruitment of circulating cells into chronic inflammatory lesions in the skin and elsewhere. This report provides the first evidence that a single fucosyltransferase, termed FucT-VII, controls the synthesis of E-selectin ligands in human T-lymphoblasts. The FucT-IV transferase (the ELFT enzyme), in contrast constructs lower avidity E-selectin ligands and requires enzyme levels found only in myeloid cells. Treatment of Jurkat cells with phorbol myristate acetate increased the expression of sialylated Lewis(x)-related sLe(x)related epitopes and induced the synthesis of E-selectin ligands functional at physiologic levels of linear shear-stress. Northern analysis revealed a parallel increase in the steady-state levels FucT-VII mRNA, but there were no increases in the two other leukocyte-associated fucosyltransferases (FucT-IV and VI). The stable transfection of the FucT-VII gene into Jurkat cells induced high levels of the sLe(x)-related epitopes and the synthesis of E-selectin ligands which equal or exceeded the avidity of those on circulating lymphocytes. The growth of T-lymphoblasts under conditions which induced expression of the sLe(x,a) epitopes increased the level of FucT-VII mRNA, the synthesis of sialylated-Lewis(x) structures by cell-free extracts and the synthesis of E-selectin ligands equal in avidity to those on FucT-VII transfectants. In contrast, neither the mRNA levels nor activities of the FucT-IV and VI enzymes increased in association with E-selectin ligand synthesis in T-lymphoblasts. Myeloid cell lines, unlike lymphoblasts, expressed high levels of both the FucT-VII and IV enzymes in conjunction with E-selectin ligands raising the possibility that both enzymes contributed to ligand synthesis. FucT-IV transfected Jurkat cells synthesized low avidity ligands for E-selectin but only in association with CDw65 (VIM-2) carbohydrate epitope. Only blood neutrophils and myeloid cell lines expressed this epitope at the levels associated with E-ligand synthesis in the transfectants. In contrast, native Jurkat cells, blood monocytes, blood lymphocytes, and cultured T-lymphoblasts expressed low levels or none. We conclude that FucT-VII is a principal regulator of E-selectin ligand synthesis in human T-lymphoblasts while both FucT-VII and FucT-IV may direct ligand synthesis in some myeloid cells.

Antigens, CD↗

PubMed1996

The influence of flow cytometric gating strategy on the standardization of CD34+ cell quantitation: an Australian multicenter study. Australasian BMT Scientists Study Group.

The Australian Multi-centre study on CD34+ cell quantitation by flow cytometry documented, first, the extent of variation of CD34+ cell enumeration and, second, the influence of flow cytometric gating on CD34+ cell measurement. A PBSC harvest analyzed by 20 participating centers showed results ranging from 0.64% to 2.80%, with a median of 1.54% CD34+ cells. Of 20 centers, 9 obtained results within +/-10% of the median (the criteria for reproducibility suggested by the ISHAGE Guidelines). The flow cytometric gating strategy was identified as one of the major variables among the methods used. In stage 2, list mode data from two samples were analyzed by 24 Australian and overseas centers, including the authors of three published guidelines. Significantly different CD34+ results were obtained when different gating strategies were used (p < 0.006). When all the centers used the same gating strategy, the measurement of CD34+ cells fell within a narrow range, with 0-7% of results outside +/-10% of the median. However, when different gating strategies were used, the results were more widely scattered, with 17% of centers outside +/-10% of the median. This study demonstrated the potential impact of flow cytometric gating strategy on the reproducibility of CD34+ cell enumeration.

Australia↗