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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 199 records · Page 11Linked to original sources
PubMed1993

Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas.

Biliary glycoprotein (BGP) is the human homologue of a cell adhesion molecule (CAM) of the rat designated Cell-CAM. The BGP gene is a member of the carcinoembryonic antigen gene family, which belongs to the immunoglobulin superfamily. BGP is expressed in cells of epithelial and myeloid origin. In granulocytes, BGP is a main antigen of the CD66 cluster of differentiation antigens that mediate the binding to endothelial E-selectin. Since BGP is a major human CAM, the expression of BGP was studied in 21 colorectal carcinoma tissue specimens and in the respective adjacent normal mucosae. As an internal control for epithelial mRNA, the expression of cytokeratin 18 was evaluated in parallel. In addition, the expression of carcinoembryonic antigen and nonspecific crossreacting antigen, which are highly homologous to BGP, was investigated. Two BGP mRNAs of 3.9 and 1.5 kilobases were detected in the normal colonic mucosa samples. The median of the tumor-to-normal ratios of mRNA expression was 0.2 for both BGP mRNAs. In contrast, the median was 1.2 for cytokeratin, 1.0 for carcinoembryonic antigen, and 1.4 for nonspecific crossreacting antigen. Relative to cytokeratin 18 expression, the expression of BGP was reduced to < or = 0.1 in half of the tumors and to < or = 0.4 in > 80% of the tumors. These findings indicate that the loss or reduced expression of the adhesion molecule BGP is a major event in colorectal carcinogenesis.

Antigens, CD↗
PubMed1993

Prevalence of neural tube defects in South Australia, 1966-91: effectiveness and impact of prenatal diagnosis.

OBJECTIVE: To determine trends in total prevalence of neural tube defects in South Australia during 1966-91, the impact of prenatal diagnosis on birth prevalence, and the effectiveness of prenatal screening for neural tube defects in 1986-91. DESIGN: All births and terminations of pregnancy affected by neural tube defects and information on prenatal screening were ascertained from multiple sources including the South Australian perinatal and abortion statistics collections, birth defects register, and state maternal serum alpha fetoprotein screening programme. SETTING: Southern Australia. SUBJECTS: All 1058 births and terminations of pregnancy affected by neural tube defects in 1966-91. MAIN OUTCOME MEASURES: Total prevalence and birth prevalence of individual and all neural tube defects. The proportion of screened cases detected prenatally. RESULTS: Total prevalence of neural tube defects during 1966-91 was 2.01/1000 births with no upward or downward trend. However, birth prevalence fell significantly (by 5.1% a year), with an 84% reduction from 2.29/1000 births in 1966 to 0.35/1000 in 1991 (relative risk = 0.16, 95% confidence interval 0.07 to 0.34). The fall was 96% for anencephaly and 82% for spina bifida. 85% of defects, both open and closed, were detected before 28 weeks' gestation in women screened by serum alpha fetoprotein or mid-trimester ultrasonography, or both, in 1986-91 (99.0% for anencephaly and 75.7% for spina bifida). CONCLUSIONS: While the total prevalence of neural tube defects in South Australia remained stable, prenatal diagnosis and termination of pregnancy resulted in an 84% fall in birth prevalence during 1966-91. Screening detected over four fifths of cases in 1986-91.

Confidence Intervals↗
PubMed1993

Birthweight-specific trends in perinatal mortality by hospital category in South Australia, 1985-1990.

OBJECTIVE: To investigate differences by birthweight in risk of perinatal death between level 3 hospitals (which provide care for high risk pregnancies and neonatal intensive care) and other hospitals in South Australia, using perinatal data for the 1985-1990 period. DESIGN: Analysis of birthweight-specific trends in risk of perinatal death by hospital category for singleton births, adjusting for risk factors. SUBJECTS: 114 725 singleton births of at least 400 g birthweight (or at least 20 weeks' gestation) born in hospitals in the 1985-1990 period and notified to the perinatal data collection. MAIN OUTCOME MEASURE: The relative odds of a perinatal death, as opposed to a live birth which survived the neonatal period. RESULTS: Births at level 3 hospitals had a higher crude risk of perinatal death than those at other hospitals, but this was due to the higher frequency of low birthweights at level 3 hospitals. For birthweights under 2000 g, and especially for the very low birth-weights, there was a higher risk at non-level-3 than level 3 hospitals. There was also the unexpected finding that births at level 3 hospitals in the 2500-2999 g range had a comparatively high risk of perinatal death. There was little difference in risk for births of higher birthweight. CONCLUSIONS: The greatly reduced risk of perinatal death in level 3 hospitals for babies with birthweights under 2000 g seems likely to be due to the specialist services in these hospitals. Further investigation is required to determine why babies in the 2500-2999 g range of birthweights had a comparatively high risk of perinatal death at these hospitals. This appears to be due, at least in part, to an excess contribution of deaths from congenital abnormalities. Also, it seems that the higher prevalence of complications in pregnancy in level 3 hospitals, and the transfers for induction of labour after intrauterine fetal death, would have made a contribution. These same factors may also have affected the risk in level 3 hospitals for higher birthweight births.

Birth Weight↗
PubMed1993

Preoperative concurrent 5-fluorouracil infusion, mitomycin C and pelvic radiation therapy in tethered and fixed rectal carcinoma.

PURPOSE: This is a Phase I/II study of preoperative concurrent radiation and chemotherapy in tethered and fixed rectal carcinoma. This study examined the curative resectability, the acute toxicities during chemo-radiation and the surgical complications. METHODS AND MATERIALS: Between 1986 and 1990, 46 patients were treated with preoperative pelvic radiation (4000 cGy in 20 fractions in 4 weeks), 5-Fluorouracil infusion (20 mg/m2, days 1-4 and 15-18) and Mitomycin C (8 mg/m2, day 1). This was followed by surgery 6 to 8 weeks later. 30 patients had tethered tumors and 16 patients had fixed tumors. RESULTS: After preoperative chemo-radiation, 41 patients (89%) underwent curative resection. Two patients (4%) had no residual tumor found (T0N0M0). Seven patients (15%) had nodal metastases. Two patients developed grade 3 neutropenia (WBC = 1-2 x 10(9)/L) during chemo-radiation. Five patients had delay in perineal wound healing. One patient had an anastomotic leak. Four patients developed stomal stenosis which required surgical revision. The 2-year actuarial survival was 73%. The 2-year local relapse rate was 16%. Patients with fixed carcinoma had a higher incidence of local failure (38% vs. 10%) and the difference was statistically significant (p = 0.0036). The 2-year distant failure rate was 41%, and the rates were similar for both tethered and fixed carcinomas. CONCLUSION: Preoperative pelvic radiation, chemotherapy and surgery could achieve a curative resection rate of 89% in tethered and fixed rectal carcinomas. However, distant metastases remained the major cause of failure.

Adenocarcinoma↗
PubMed1993

Survival benefit of tamoxifen therapy in adenocarcinoma of pancreas. A case-control study.

BACKGROUND: Clinical data suggest tamoxifen may improve the survival of patients with unresectable ductal adenocarcinoma of pancreas. METHODS: Eighty patients (50 women and 30 men) with biopsy-documented unresectable or incompletely resected ductal adenocarcinoma of the pancreas were treated with 20 mg of tamoxifen twice daily. The survival of the tamoxifen-treated group was compared with that of a case-control group of another 80 patients with pancreatic cancer, matched for age, sex, TNM stage, and bypass procedure versus biopsy. RESULTS: The median survival times for the tamoxifen-treated group versus controls were 7 and 3 months, respectively (P < 0.0001). For women older than 60 years of age and treated with tamoxifen, the median survival time was 12 months. Multivariate analysis of the 160 patients showed that tamoxifen therapy, female sex, absence of metastases at diagnosis, and bypass procedure are all of independent prognostic significance for prolonged survival. CONCLUSIONS: Patients with unresectable or incompletely resected ductal adenocarcinoma of pancreas may have a prolonged survival benefit while receiving tamoxifen treatment. This potential benefit is most prominent in older women.

Adenocarcinoma↗
PubMed1993

Quantification of polymerase chain reaction products in agarose gels with a fluorescent europium chelate as label and time-resolved fluorescence spectroscopy.

We have 5'-end-labeled one polymerase chain reaction (PCR) primer with the europium chelator 4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA). After performing PCR in the presence of another unlabeled primer, we separated the 362 bp PCR product with 2% low melting point agarose gel electrophoresis. The gel was then immersed into a Eu3+ solution. During soaking, Eu3+ diffuses into the gel and associates with BCPDA to form a fluorescent complex of long fluorescence lifetime. This complex can be quantified by scanning the gel with a time-resolved fluorometric reader. Because BCPDA and Eu3+ are not fluorescent by themselves, background signals are very low. The detection limit was about 5 ng of DNA. We have also shown that the BCPDA-labeled product could be blotted and detected on the membrane by using an anti-BCPDA antibody. These two technologies may find applications other than in PCR, e.g. in fluorescence-based DNA sequencing and in solution hybridization.

Blotting, Southern↗
PubMed1993

Conventional versus laparoscopic surgery for acute appendicitis.

A total of 155 consecutive patients with suspected acute appendicitis were studied to compare laparoscopic and conventional operations. Patients were not randomized: laparoscopy was performed when a suitably trained surgeon and laparoscopic instruments were available. Laparoscopic appendicectomy was attempted in 51 patients and was successful in 46 (90 per cent); all conversions to open operation were because of marked inflammatory adhesions around the appendix. There were no intraoperative complications. Reintroduction of normal diet and discharge from hospital occurred earlier after laparoscopic than open surgery (P < 0.05). The requirement for analgesia after successful laparoscopic surgery was less than that after conventional appendicectomy, but the difference was not significant. The incidence of wound infection was reduced after the laparoscopic procedure (P = 0.06). It is concluded that laparoscopic appendicectomy is practical and may have advantages over conventional operation, although a randomized study is necessary.

Acute Disease↗
PubMed1993

Multivariate Cox regression analysis of covariates for patency rates after femorodistal vein bypass grafting.

Multivariate Cox regression analysis of patency rates for 750 consecutive femorodistal autogenous vein graftings for chronic lower limb ischemia showed that significant independent prognostic covariates were the type of graft (long saphenous or arm vein), presence of diabetes, and absence of a past history of myocardial ischemia. Analysis assumes that patients withdrawn with patent grafts due to death or loss to follow-up would have followed the same course as those who remain, and the degree to which this could distort results was studied. Patients who died with patent grafts were more likely to have had past myocardial ischemia and critical lower limb ischemia. Cox regression analysis for 600 operations after excluding patients who died with patent grafts then showed that significant independent covariates were the type of graft (long saphenous or arm vein) and indication (claudication or critical ischemia); then age, sex, hypertension, diabetes, myocardial ischemia, date of operation, surgeon, site of distal anastomosis, or first compared to repeat operations had no significant influence. Cox regression analysis helps determine which covariates influence graft patency rates, but results are affected by censored data, particularly from patients who die with patent grafts.

Adult↗
PubMed1993

Amniotic band syndrome: a population-based study in two Australian states.

A search for cases of amniotic band syndrome was made in two population-based Australian birth defects registries, using defined selection criteria. Over a period of 4 years in Western Australia and 5 years in South Australia, 25 cases of amniotic band syndrome had been identified as such by the two registries, and an additional 15 new cases were identified by the study selection process, giving an annual prevalence of amniotic band syndrome over the study period of 2.03 per 10,000 births. Similar proportions of male and female infants were affected, although the syndrome was more common in mothers younger than 25 years of age, and in first births. Limb defects only (upper and/or lower) were found in 24 cases, limb-body-wall defects in four cases, and complex craniofacial and other malformations in 12 cases. A heightened awareness of the syndrome should enhance the identification of amniotic band syndrome, which has implications for genetic counselling, and our understanding of the aetiology and pathogenesis of this condition.

Amniotic Band Syndrome↗
PubMed1993

Influence of age and hemodynamics on myocardial blood flow and flow reserve.

BACKGROUND: Aging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity. METHODS AND RESULTS: Myocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31 +/- 9 versus 64 +/- 9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895 +/- 1070 versus 8634 +/- 1890; P < 0.01). Myocardial blood flow at rest averaged 0.76 +/- 0.17 mL.min-1.g-1 in the younger volunteers and 0.92 +/- 0.25 mL.min-1.g-1 in the older volunteers (P < 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0 +/- 0.8 versus 2.7 +/- 0.6 mL.min-1.g-1; P = NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1 +/- 0.9 versus 3.0 +/- 0.70; P < 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows. CONCLUSIONS: Aging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.

Adult↗
PubMed1993

Serum ultrafiltrable copper, total copper and caeruloplasmin concentrations in gynaecological carcinomas.

Serum copper and caeruloplasmin concentrations are elevated in various carcinomas, but it is not known whether the rise in serum copper is due to elevation of caeruloplasmin alone or whether it is also due to the elevation of 'free' copper. We therefore determined ultrafiltrable copper to answer this question. Serum ultrafiltrate was prepared using the Amicon micropartition system and ultrafiltrable (free) copper was determined by flameless atomic absorption spectrophotometry. Serum total copper was determined by flame atomic absorption spectrometry and caeruloplasmin by rate nephelometry. There was no significant difference in the ultrafiltrable copper concentration between patients with gynaecological tumours and control subjects. However, total copper and caeruloplasmin concentrations were significantly elevated in cancer patients compared with control subjects. In contrast to total copper and caeruloplasmin concentrations, ultrafiltrable copper concentrations showed no significant increase with increase in the stage of the cancer.

Adult↗
PubMed1993

Serum lipid profile and its association with some cardiovascular risk factors in an urban Chinese population.

The lipid profile of a Chinese population, which has a lower prevalence of coronary heart disease compared with Caucasians, is studied to determine whether lipid-modifying disease prevention programs are necessary. The study population consisted of 910 men (mean age 36.7 +/- 9.2 yrs) and 603 women (mean age 38.6 +/- 9.1 yrs), who were employees of a public utility company and non-medical staff of a district hospital. Indices of obesity, fasting cholesterol (TC), and its various subfraction, triglycerides (TG), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B) concentrations were measured. Glucose tolerance was also estimated by measuring fasting and 2 h glucose after a 75 g oral glucose load. The lipid profile was similar to that of the North American population, with an overall prevalence of low density lipoprotein cholesterol (LDL-C) > or = 4.1 mmol/L of 21% and 11% in men and women respectively. Similar variations with age, sex, smoking and glucose tolerance compared with Caucasian populations were observed. The high prevalence of subjects with "undesirable" lipid values in this Chinese population, which at present has a coronary artery disease prevalence of one-eighth to one-quarter compared with that in Caucasians, suggests that the incidence of the disease may well rise in the future to pose a similar problem to that in Caucasian populations. Cut off values of lipids conferring increased cardiovascular risks need to be determined in this population, so that public health strategies may be formulated.

Adult↗
PubMed1993

Delayed implantation of demineralized bone powder after local irradiation in rats.

Previous studies have shown that osteoinduction is inhibited when demineralized bone powder (DBP) is implanted within 48 hours of local irradiation (i.e., when the acute effects of radiation injury are present). This study sought to determine whether normal osteoinduction can proceed if the implantation of DBP is delayed until 21 days postirradiation. At 21 days, the acute effects of radiation injury are likely to have subsided, but the long-term effects have not yet appeared. Twenty-eight-day-old rats were administered a radiation dose of either 7 or 20 Gy over a localized area of one thigh. The contralateral, nonirradiated thigh served as a control. Demineralized bone powder was subcutaneously implanted 21 days later. Subcutaneous pellets were retrieved at various intervals thereafter (up to Day 45) and were histologically graded for evidence of osteoinduction. No difference in osteoinduction was detected at any time interval in pellets from the 7-Gy-treated sites, compared with controls. Pellets from the 20-Gy-treated sites, however, demonstrated significantly a lower osteoinductive response at each interval. These latter pellets showed small scattered areas of osteoinduction and reduced formation of marrow elements. Thus, although osteoinduction proceeds normally when the implantation of DBP is delayed for 21 days after irradiation with 7 Gy, this is not the case when 20 Gy are administered. Given the absence of gross impairment of tissue vascularity in irradiated sites, it is possible that inhibition of osteoinduction after higher doses of radiation results from permanent damage to mesenchymal precursor cells.

Animals↗
PubMed1993

Isoforms of human HGF and their biological activities.

Hepatocyte growth factor (HGF) is a plasminogen-like protein thought to be a humoral mediator of liver regeneration. It is produced by stromal fibroblasts and acts as a mitogen for a variety of target cells. Scatter factor, a stimulant of epithelial and vascular endothelial cell motility, is the same as HGF. HGF mediates its effects by activation of a membrane-spanning tyrosine kinase, recently identified as the met proto-oncogene product. We purified a naturally occurring hepatocyte growth factor variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule. This smaller molecule, derived from an alternative HGF transcript, lacked mitogenic activity but specifically inhibited HGF-induced mitogenesis. Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the c-met proto-oncogene product. Thus, the same gene encodes both a growth factor and its direct antagonist.

Amino Acid Sequence↗
PubMed1992

Expression cloning of a human dual-specificity phosphatase.

Using an expression cloning strategy, we isolated a cDNA encoding a human protein-tyrosine-phosphatase. Bacteria expressing the kinase domain of the keratinocyte growth factor receptor (bek/fibroblast growth factor receptor 2) were infected with a fibroblast cDNA library in a phagemid prokaryotic expression vector and screened with a monoclonal anti-phosphotyrosine antibody. Among several clones showing decreased anti-phosphotyrosine recognition, one displayed phosphatase activity toward the kinase in vitro. The 4.1-kilobase cDNA encoded a deduced protein of 185 amino acids with limited sequence similarity to the vaccinia virus phosphatase VH1. The purified recombinant protein dephosphorylated several activated growth factor receptors, as well as serine-phosphorylated casein, in vitro. Both serine and tyrosine phosphatase activities were completely abolished by mutagenesis of a single cysteine residue conserved in VH1 and the VH1-related (VHR) human protein. These properties suggest that VHR is capable of regulating intracellular events mediated by both tyrosine and serine phosphorylation.

Amino Acid Sequence↗
PubMed1992

A perinatal perspective on South Australia in the 1980s.

OBJECTIVE: To assess changes in sociodemographic characteristics of mothers, their obstetric management and perinatal outcomes in the 1980s. DESIGN: A survey of data recorded in the South Australian perinatal data collection. For singleton births, we compared risks of stillbirth, neonatal death and perinatal death by year of birth, after adjusting for risk factors. SUBJECTS: There were 176,637 births of at least 400 g birthweight (or at least 20 weeks' gestation) notified to the perinatal data collection between 1981 and 1989. MAIN OUTCOME MEASURES: Frequency of risk factors and relative risks of stillbirth, neonatal death and perinatal death by year of birth. RESULTS: There have been changes in the sociodemographic characteristics of mothers, their obstetric management and perinatal outcomes during the 1980s. Crude perinatal mortality rates have not increased, despite increases in the frequency of low birthweight, preterm births, mothers aged 35 years and over, and some other risk factors. After adjusting for risk factors, the risks of stillbirth, neonatal death and perinatal death were lower among singletons in 1987-1989 than in the 1981-1982 reference period. CONCLUSION: Advances in clinical management may be preventing increases in stillbirths, neonatal deaths and perinatal deaths in response to increased numbers of births with low birthweight, preterm delivery and some other risk factors in South Australia.

Adult↗