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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 127 records · Page 7Linked to original sources
PubMed1997

Covalent antithrombin-heparin complexes with high anticoagulant activity. Intravenous, subcutaneous, and intratracheal administration.

Although heparin has been used clinically for prophylaxis and treatment of thrombosis, it has suffered from problems such as short duration within compartments in vivo that require long term anticoagulation. A covalent antithrombin-heparin complex has been produced with high anticoagulant activity and a long half-life relative to heparin. The product had high anti-factor Xa and antithrombin activities compared with noncovalent mixtures of antithrombin and heparin (861 and 753 units/mg versus 209 and 198 units/mg, respectively). Reaction with thrombin was rapid with bimolecular and second order rate constants of 1.3 x 10(9) M-1 s-1 and 3.1 x 10(9) M-1 s-1, respectively. The intravenous half-life of the complex in rabbits was 2.6 h as compared with 0.32 h for similar loads of heparin. Subcutaneous injection of antithrombin-heparin resulted in plasma levels (peaking at 24-30 h) that were still detectable 96 h post-injection. Given the increased lifetime in these vascular and intravascular spaces, use of the covalent complex in the lung was investigated. Activity of antithrombin-heparin instilled into rabbit lungs remained for 48 h with no detection of any complex systemically. Thus, this highly active agent has features required for pulmonary sequestration as a possible treatment for thrombotic diseases such as respiratory distress syndrome.

Animals↗
PubMed1997

Comparison of cerebral oximeter and evoked potential monitoring in carotid endarterectomy.

PURPOSE: To assess the cerebral oximeter, which measures regional oxygen saturation (rSO2) continuously and noninvasively, as a cerebral monitor during carotid endarterectomy (CEA). The rSO2 was compared with Somatosensory Evoked Potentials (SSEPs) as an indicator for shunting and as a predictor of postoperative neurological deficits. METHODS: Seventy-two consenting patients undergoing CEA with general anaesthesia were studied. Normocarbia, normothermia and normotension were maintained. Cerebral monitoring consisted of bilateral median nerve SSEPs and the INVOS 3100 cerebral oximeter with the sensor pad placed on the ipsilateral forehead. Decreases in SSEP amplitude of 50% and in rSO2 of 10% were considered clinically significant. Neurological assessment was performed at emergence from anaesthesia, 24 hr postoperatively and at discharge. The rSO2 changes were compared with SSEP changes and with neurological deficits. Statistical analysis was with chi square and analysis of variance P < 0.05 was considered significant. RESULTS: During carotid artery clamping, rSO2 decreased from 72 +/- 8% to 68 +/- 9% and mean arterial blood pressure increased from 92 +/- 14 mmHg to 98 +/- 14 mmHg. In four patients, the carotid artery was shunted because of SSEP changes after cross-clamping. Five patients had > or = 10% decreases in rSO2 following clamp application. Changes in both SSEP and rSO2 occurred in two patients. Three of the four shunted patients had transient postoperative neurological deficits. One patients had a transient deficit without changes in either monitor. There were no persistent postoperative deficits. Compared with SSEPs, rSO2 had a sensitivity of 50% and a specificity of 96%. CONCLUSION: Clinical experience with this evolving technology is ongoing. Its role in neurovascular procedures has yet to be established.

Aged↗
PubMed1997

Analysis of 1;17 translocation breakpoints in neuroblastoma: implications for mapping of neuroblastoma genes.

Deletions and translocations resulting in loss of distal 1p-material are known to occur frequently in advanced neuroblastomas. Fluorescence in situ hybridisation (FISH) showed that 17q was most frequently involved in chromosome 1p translocations. A review of the literature shows that 10 of 27 cell lines carry 1;17 translocations. Similar translocations were also observed in primary tumours. Together with the occurrence of a constitutional 1;17 translocation in a neuroblastoma patient, these observations suggest a particular role for these chromosome re-arrangements in the development of neuroblastoma. Apart from the loss of distal 1p-material, these translocations invariably lead to extra copies of 17q. This also suggested a possible role for genes on 17q in neuroblastoma tumorigenesis. Further support for this hypothesis comes from the observation that in those cell lines without 1;17 translocations, other chromosome 17q translocations were present. These too lead to extra chromosome 17q material. Molecular analysis of 1;17 translocation breakpoints revealed breakpoint heterogeneity both on 1p and 17q, which suggests the involvement of more than 2 single genes on 1p and 17q. The localisation of the different 1p-breakpoints occurring in 1;17 translocations in neuroblastoma are discussed with respect to the recently identified candidate tumor suppressor regions and genes on 1p. In this study, we focused on the molecular analysis of the 17q breakpoints in 1;17 translocations. Detailed physical mapping of the constitutional 17q breakpoint allowed for the construction of a YAC contig covering the breakpoint. Furthermore, a refined position was determined for a number of 17q breakpoints of 1;17 translocations found in neuroblastoma cell lines. The most distal 17q breakpoint was identified in cell line UHG-NP and mapped telomeric to cosmid cCI17-1049 (17q21). This suggests that genes involved in a dosage-dependent manner in the development of neuroblastoma map in the distal segment 17q22-qter. Future studies aim at the molecular cloning of 1;17 translocation breakpoints and at deciphering the mechanisms leading to 1;17 translocations and possibly to the identification of neuroblastoma genes at or in the vicinity of these breakpoints.

Chromosome Mapping↗
PubMed1997

Transcranial Doppler microembolus detection in the identification of patients at high risk of perioperative stroke.

OBJECTIVES: Perioperative ischaemic stroke is the leading cause of morbidity and mortality associated with carotid endarterectomy (CEA). The aim was to test the hypotheses that the detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) during and after the operation may be of value in identifying patients at increased perioperative stroke risk. DESIGN: Open prospective case series. PATIENTS AND METHODS: Eighty-one consecutive patients undergoing CEA with TCD monitoring. Preoperative, intraoperative and interval postoperative TCD monitoring of the middle cerebral artery (MCA) ipsilateral to the operated carotid artery. On-line pre- and intraoperative MES counting and blinded off-line analysis of postoperative MES counts. End-points were any focal neurological deficit and death at 30 days postoperatively. RESULTS: MES were detected in 94% of patients intraoperatively and 71% of cases during the first postoperative hour. MES counts ranged from 0 to 25 per operative phase (range of median counts 0-8) and from 0 to 212 per hour postoperatively (range of median counts 0-4). Eight cases (10%) developed postoperative MES counts greater than 50/h. Five of these eight cases evolved ischaemic neurological deficits in the territory of the insonated MCA, indicating a strong association between frequent postoperative microembolism and the development of early cerebral ischaemia (chi 2 = 34.2, p < 0.0001). Intraoperative MES were not associated with clinical outcome measures. CONCLUSIONS: MES counts of greater than 50/h in the early postoperative phase of carotid endarterectomy are predictive of the development of ipsilateral focal cerebral ischaemia.

Cerebrovascular Disorders↗
PubMed1997

Transcranial Doppler detected cerebral microembolism following carotid endarterectomy. High microembolic signal loads predict postoperative cerebral ischaemia.

Cerebral ischaemia, the most frequent serious complication of carotid endarterectomy (CEA), usually occurs in the early postoperative period and is often the result of thromboembolism. We hypothesized that the early postoperative detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) may be of value in identifying patients at risk of postoperative cerebral ischaemia and that the MES rate may be an important determinant in risk prediction. Sixty-five patients undergoing CEA were studied at intervals up to 24 h postoperatively with TCD insonation of the middle cerebral artery ipsilateral to the operation side. Study design was open and prospective with blinded off-line analysis of MES counts. End-points were any focal ischaemic neurological deficit and/or death up to 30 days postoperatively. MES were detected in 69% of cases during the first hour postoperatively with counts ranging from 0 to 212 MES/h (means 19 MES/h; SEM +2- 4.5; median 4 MES/h). In seven cases (10.8%) counts were > 50 MES/h. Five of these seven cases developed ischaemic neurological deficits in the territory of the insonated middle cerebral artery during the monitoring period. The positive predictive value of counts > 50 MES/h for cerebral ischaemia was 0.71. Frequent signals (> 50 MES/h) occur in approximately 10% of cases in the early postoperative phase of CEA and are predictive for the development of ipsilateral focal cerebral ischaemia.

Brain↗
PubMed1997

Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma.

This is a report of a phase II study of megestrol acetate (160 mg/day, orally) in the treatment of hepatocellular carcinoma (HCC). Forty-six patients with advanced HCC were studied and tumour response, changes in appetite, bodyweight, a feeling of well-being, survival and toxicity were evaluated. Thirty-two patients were able to be evaluated for response; there were no complete responders or partial responders. Twelve patients (38%) had stable disease and seven of these patients had a minor response with a median size reduction in the tumour of 18%. Twenty patients (62%) had progressive disease. Five of 24 (21%) patients had a median reduction in alpha-fetoprotein levels of 59 ng/mL. The overall median survival was 4 months (range 1 week to 27 months). Twenty of 32 (62%) patients had an increased appetite and feeling of well-being. Fourteen of 22 (64%) patients had a median lean bodyweight gain of 5 kg (range 1-14 kg). Toxicities were minimal. Tests for glucocorticoid receptors were performed in 10 patients. Four of five patients who were positive for glucocorticoid receptors in the tumour had a stable disease and all five patients who were negative for glucocorticoid receptors had progressive disease. Megestrol acetate had no significant effect on the tumour in HCC patients. However, megestrol acetate is useful in the palliative management of HCC patients, with improvements in appetite, bodyweight and a feeling of well-being with minimal side effects. Some patients had stable disease, a minor reduction of tumour size and a prolonged survival after megestrol acetate treatment and this response may be related to the presence of glucocorticoid receptors in the HCC tumour.

Aged↗
PubMed1997

Developmental dysplasia of the hip in South Australia in 1991: prevalence and risk factors.

OBJECTIVE: To determine the prevalence of developmental dysplasia of the hip (DDH) in South Australia (SA) in 1991, the proportion of cases detected in the neonatal period and the perinatal risk factors for DDH. METHODOLOGY: Cases of DDH born in SA in 1991 were identified from multiple sources and their clinical data linked to perinatal data provided by midwives; five controls per case were obtained randomly from SA livebirths without congenital abnormalities and adjusted odds ratios (OR) for potential risk factors obtained by logistic regression analysis. South Australia perinatal data were also used to estimate numbers of births with perinatal risk factors for targeted screening. RESULTS: Two hundred and six cases of isolated DDH were identified, giving a prevalence of 10.5 per 1000 births. Of these, 173 (84%) had been detected in the neonatal period. The perinatal risk factors for DDH were identified as breech presentation (OR 9.65), female babies (OR 4.04), first births (OR 1.91) and maternal age of 25 years or more (OR 1.53). Screening breech and firstborn female babies (23% of births) would yield approximately 51% of cases of DDH. CONCLUSIONS: Isolated DDH had a prevalence of 10.5 per 1000 births and 84% of cases had been detected in the neonatal period in SA. Repeated screening during infancy of "at risk' groups of babies is recommended.

Breech Presentation↗
PubMed1997

Trends in perinatal characteristics in South Australia, 1981 to 1994, by place of residence of mother.

We investigated differentials and time trends in perinatal mortality and perinatal risk factors by geographic area of residence in South Australia during 1981-1994, to assess whether sociodemographic inequalities had lessened. The areas analysed were Adelaide and the country region of South Australia, with Adelaide being divided by socioeconomic status into two ares. Subjects were 267,116 singleton births of at least 400 g birthweight (or at least 20 weeks' gestation) notified to the state's perinatal data collection. Year of birth, residential area, and interactions between year of birth and residential area were analysed as predictors of perinatal risk factors and deaths. There was a statistically significant decline in the perinatal death rate in all residential areas (mainly because of a decrease in neonatal deaths), which did not vary significantly by area. The frequency of low birthweight (< 2500 g) increased in the country areas and in the lower socioeconomic areas of Adelaide, but not in the higher socioeconomic areas. Although premature births increased in all areas, the increase was less pronounced for the higher socioeconomic areas of Adelaide. By comparison, although all areas showed an increase in the proportions of mothers aged 35 years or over, the increase was larger for the higher socioeconomic areas. Australia has a national policy of reducing social inequalities in health status. Perinatal mortality rates declined in Adelaide and country residential areas from 1981 to 1994. This trend is favourable, but from the relativities of these rates by residential area, there is not compelling evidence of a reduction in inequalities.

Adolescent↗
PubMed1997

Helicobacter pylori in an institution for disabled children in Hong Kong.

Anti-Helicobacter pylori antibodies were determined in 157 institutionalised Cantonese children, mean age 9.5 +/- 3.9 (SD) years, with profound neurodevelopmental disabilities. Eighty-seven (55.4%) were H. pylori seropositive compared with four of 50 (8%, P > 0.0002) of an age-matched control group, mean age 7.2 +/- 4.3 (SD) years. Eight of 15 seropositive children with a recent history of upper gastrointestinal bleeding underwent endoscopy and in all cases gastric infection with H.pylori was confirmed. Anthropometric data from institutionalised children revealed marked malnutrition but showed no significant difference between seropositive and seronegative children. Disabled children receiving long-term residential care in Hong Kong are confirmed to be at increased risk of H.pylori infection.

Adolescent↗
PubMed1997

Perinatal risk factors for developmental dysplasia of the hip.

AIMS: To identify perinatal risk factors for developmental dysplasia of the hip (DDH) and define the risk for each factor. METHODS: In this case control study, using logistic regression analysis, all 1127 cases of isolated DDH live born in South Australia in 1986-93 and notified to the South Australian Birth Defects Register were included; controls comprised 150130 live births in South Australia during the same period without any notified congenital abnormalities. RESULTS: Breech presentation, oligohydramnios, female sex and primiparity were confirmed as risk factors for DDH. Significant findings were an increased risk for vaginal delivery over caesarean section for breech presentation (as well as an increased risk for emergency section over elective section), high birthweight (> or = 4000 g), postmaturity and older maternal age; multiple births and preterm births had a reduced risk. There was no increased risk for caesarean section in the absence of breech presentation. For breech presentation, the risk of DDH was estimated to be at least 2.7% for girls and 0.8% for boys; a combination of factors increased the risk. CONCLUSIONS: It is suggested that the risk factors identified be used as indications for repeat screening at 6 weeks of age and whenever possible in infancy. Other indications are family history and associated abnormalities.

Adult↗
PubMed1997

The effect of prepubertal diabetes duration on diabetes. Microvascular complications in early and late adolescence.

OBJECTIVE: To define the significance of prepubertal diabetes duration in the development of diabetic microvascular complications in adolescents. RESEARCH DESIGN AND METHODS: Study A compares complications in 38 prepubertal (PreP) and 140 pubertal (Pub) subjects of the same age (10-14 years) and diabetes duration (3-12 years) to determine if the absence of puberty itself confers a lower risk of complications. Study B examines the importance of prepubertal and pubertal diabetes duration in 193 older adolescents (ages 15-22 years) with prepubertal onset of diabetes. Retinopathy status was assessed using stereoscopic fundus photography of seven fields per eye. Albumin excretion rate (AER) was assessed by three consecutive overnight urine collections, using a polyclonal radioimmunoassay. RESULTS: In study A, there were no significant differences between the PreP and Pub groups for retinopathy (27 vs. 29%, P = 0.8) or differences in elevated AER (17 vs. 31%, P = 0.1). In study B, longer prepubertal diabetes duration improved the prediction for retinopathy over postpubertal duration alone (P < 0.0005). No relationship with duration was found for elevated AER (> 7.5, > 15, and > 30 micrograms/min). CONCLUSIONS: Prepubertal subjects with diabetes did not have less retinopathy or elevated albumin excretion compared with pubertal subjects of the same age. Prepubertal diabetes duration is significantly related to the presence of retinopathy in adolescents.

Adolescent↗
PubMed1997

Comparison of the ISAAC video questionnaire (AVQ3.0) with the ISAAC written questionnaire for estimating asthma associated with bronchial hyperreactivity.

BACKGROUND: A standardized protocol is essential for international comparisons of asthma prevalence and severity. The International Study of Asthma and Allergies in Childhood (ISAAC) used a standardized written questionnaire (WQ) and a video questionnaire (AVQ3.0) to survey the prevalence and severity of asthma in 13-14-year-old schoolchildren in different countries. OBJECTIVE: To compare the effectiveness of WQ and AVQ3.0 in predicting bronchial hyperresponsiveness (BHR), defined as having a provocation dose of inhaled methacholine causing a 20% fall in baseline FEV1 of 7.8 mumol. METHODS: One hundred and eighty-nine Chinese schoolchildren completed a written questionnaire followed by a video questionnaire on asthma symptoms. They then underwent bronchial challenge to methacholine. RESULTS: Fair correlations were seen between the first two corresponding questions (moderate wheezing at rest and exercise wheeze) in the two questionnaires with Kapper indices of 0.44 and 0.43, respectively. The ability to predict BHR, as indicated by the Youden's index, was similar between the corresponding questions of the two questionnaires, except for 'severe wheeze' which had a significantly higher Youden's index in AVQ3.0 (0.44) than the corresponding question in WQ (0.11, P < 0.05). CONCLUSION: The ISAAC International video questionnaire is at least as effective as the ISAAC written questionnaire in predicting BHR. It therefore provides a simple and valid tool for international comparisons of asthma prevalence and severity.

Adolescent↗
PubMed1997

Communicating with patients with advanced cancer.

We conducted a prospective study of 130 unselected adults admitted to hospital with advanced malignancy. The study assessed how patients perceived information conveyed to them by physicians and the level of communication between patients and health care staff on questions relating to patients' understanding, pain control, and sense of well-being. Nearly 10% of patients were unaware of a diagnosis of cancer. Of those who knew their diagnosis, one quarter stated that the diagnosis was not disclosed in a clear or caring manner. One third of patients had an incomplete understanding of their prognosis, and patients generally overestimated their understanding when compared to hospital medical officers (HMOs) and nurses. The severity of pain was underestimated by the HMOs in 63% to 89% of patients. Thus HMOs require specific training in communication skills and the management of chronic cancer-related pain in patients with incurable cancer. Professional interpreters should be employed for all patients who are not fluent in English.

Aged↗
PubMed1996

Involvement of calcium in interactions between gingival epithelial cells and Porphyromonas gingivalis.

Porphyromonas gingivalis, a periodontal pathogen can invade primary cultures of gingival epithelial cells. This invasion was significantly inhibited (74-81%) by thapsigargin and 1,2-bis(2-aminophenoxy)ethane-N,N,N1,N1-tetraacetic acid, acetoxymethyl ester (BAPTA/AM), but not by EDTA or amiloride. Release of Ca2+ from an intracellular store and the subsequent increase in cytosolic [Ca2+] may, therefore, be involved in the invasion process, while Ca2+ influx is not. Moreover, cytosolic [Ca2+] was found to increase transiently in about 30% of gingival epithelial cells acutely exposed to P. gingivalis, but not in unexposed cells, or in cells exposed to noninvasive Escherichia coli. These findings indicate that P. gingivalis invasion of epithelial cells is correlated with activation of [Ca2+]-dependent host cell signaling systems.

Actin Cytoskeleton↗
PubMed1996

Lack of class I HLA expression in neuroblastoma is associated with high N-myc expression and hypomethylation due to loss of the MEMO-1 locus.

Class I HLA expression is low in neuroblastoma tumours and cell lines. We have recently mapped a modifier of methylation for HLA-C (MEMO-1) to chromosomal bands 1p35-36.1, a region deleted in many neuroblastomas. Hypomethylation of HLA-C is strongly correlated with allelic loss of the MEMO-1 locus. Here, we show that loss of MEMO-1 is associated with hypomethylation of both the 5' and 3' regions of class I HLA loci. We next investigated the relationship between methylation and expression of class I HLA in 28 cell lines of neuroectodermal tumours. Cell lines with hypermethylated HLA-C and HLA-A loci have relatively high expression, while most cell lines with hypomethylated loci have no or a reduced expression. It was reported earlier that high expression of c- or N-myc can suppress class I HLA expression. Remarkably, also N-myc amplification in neuroblastomas is associated with allelic loss of 1p35-36. Therefore, we have analysed the relationships between allelic loss of the MEMO-1 locus, class I HLA methylation and expression, and N-myc amplification and expression. This study shows a tight inter-relationship between these phenomena. Our data suggest a model in which hypomethylation of class I HLA due to loss of the MEMO-1 locus and high N-myc expression could collaborate in the down-regulation of class I HLA expression.

Cell Fusion↗
PubMed1996

Oral retinoids and pregnancy.

The oral retinoids isotretinoin and etretinate are uniquely effective in the treatment of severe cystic acne and keratinisation disorders. Because of their known teratogenicity, there are strict prescription guidelines, but exposure during pregnancy still occurs. A dedicated effort by women and their clinicians is required, involving patient selection, education and informed consent, detailed contraceptive counselling, and careful monitoring and management, including pregnancy testing before commencement of therapy.

Abnormalities, Drug-Induced↗
PubMed1996

Impairment of the semantic network in schizophrenia.

It is well established that patients with schizophrenia display a variety of language impairments. Despite considerable research, however, the underlying mechanisms of the language deficits in schizophrenia remain unclear. Representations of semantic networks of 56 patients with schizophrenia and 28 normal comparison (NC) subjects of similar ages and educational levels were generated by multidimensional scaling and Pathfinder analyses of their responses on the Animal Fluency Test. On the basis of traditional scoring techniques (i.e., total number of correct animal names generated in 60 s), all patients performed significantly worse than the NC subjects. More detailed analyses of the underlying semantic networks revealed that performance in the patients varied according to age of onset and subtype of schizophrenia. The semantic network of patients with late-onset schizophrenia (i.e., with onset after age 45) was virtually identical to that of the NC group. In contrast, the semantic network of patients with a younger age of onset was disorganized and differed significantly from that of the NC subjects. Findings demonstrated that patients with nonparanoid subtypes displayed greater disorganization in their semantic networks than patients with a paranoid subtype. Although general fluency impairments (e.g., difficulties in initiation, retrieval, and search mechanisms) may be sensitive to schizophrenia, per se, specific deficits in the structure of semantic knowledge may be associated with certain characteristics of individual patients with schizophrenia, such as an earlier age of onset and nonparanoid subtype.

Adult↗