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Biomedical subjects

L Lam

Publications and source records attributed to L Lam.

At least 37 records · Page 2Linked to original sources

Intracoronary brachytherapy: the beginning of the end of restenosis?

Restenosis remains a major problem 20 years after the introduction of coronary angioplasty. Pharmacological therapy has generally been disappointing in reducing the incidence of neointimal hyperplasia. Intracoronary brachytherapy is the latest anti proliferative agent that is showing promise in the fight against restenosis. Radiation therapy has been used for decades in the treatment of benign proliferative disorders. Animal studies have consistently demonstrated the efficacy of radiation therapy in inhibiting neointimal hyperplasia. Clinical trials, using different radioactive isotopes and radiation sources, are now showing dramatic reduction in neointimal hyperplasia and restenosis rates following balloon angioplasty and stenting. Intracoronary brachytherapy is beginning to show promise as one of the truly effective agent against neointimal hyperplasia and restenosis.

Animals↗

Mannose-specific lectins modulate ligand binding to AMPA-type glutamate receptors.

Binding of [3H]AMPA was increased above control levels in rat brain membranes that had been incubated with concanavalin A (Con A) or a lectin from Lens culinaris (LC), both of which bind mannose residues. This did not occur with any of six lectins with other specificities. The magnitude of the increased binding varied from 15% in cortex to 70% in hippocampus and decreased significantly between 3 weeks and 6 months of age. Succinylated Con A was without effect and neither Con A nor LC increased binding to solubilized AMPA receptors. Increases in binding were not obtained in membranes purified from HEK293 cell lines expressing homomeric AMPA receptors. This indicates that mannose specific lectins may enhance binding by cross-linking AMPA receptors to each other or to proteins that are specific to brain. Con A has been reported to reduce glutamate receptor desensitization with higher efficacy at kainate than at AMPA receptors; the increase in binding reported here appears to be unrelated to such effects because (1) it was not affected by drugs that block desensitization and (2) [3H]kainate binding was reduced rather than increased by Con A. These observations suggest that AMPA receptor kinetic properties not involving desensitization are influenced by extracellular interactions between the receptors and other transmembrane proteins.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Can health care assistants replace student nurses?

With the implementation of Project 2000 in the UK the traditional student nurse workforce has largely been replaced by health care assistants (HCAs). This study was carried out in Hong Kong at a time when university-based nurse education is gradually being introduced. Evaluation of a HCA pilot programme in an acute care hospital in Hong Kong provided the opportunity to examine the work of HCAs and hospital-based student nurses during the gradual introduction of university-based nurse education. The data used in this paper were drawn from a larger study evaluating the use of HCAs. The observational data collected at two phases after the introduction of HCAs were analysed using Kruskal-Wallis one way analysis of variance. No significant differences were found in the total amount of all types of activity performed by SNs and HCAs. However in the direct care type of work HCAs performed significantly more basic care and less technical activity than any level of student at phase 1 (P < 0.001) and phase 2 (P < 0.001). These differences in the work undertaken suggest that qualified staff do not perceive SNs and HCAs as equally unqualified. Thus the replacement of SNs with HCAs alone is likely to lead to a notable change in the role of qualified staff in terms of their direct and indirect care activities and in the amount of time spent delegating and supervising unqualified staff.

Health Care Reform↗

Nursing activities following the introduction of health care assistants.

AIM: The purpose of this study was to determine changes in the work nature of nurses after the introduction of Health Care Assistants (HCAs). BACKGROUND: HCAs with a role similar to those adopted in the UK of assisting the nurse were piloted in a teaching hospital in Hong Kong. METHOD: A quasi-experimental design was used to compare the observed activities of HCAs and nurses in four wards of a teaching hospital, before and after the introduction of HCAs. As the amount of staff activity is influenced by the amount of work, patient dependency data were gained from record reviews and nurse interviews. FINDINGS: HCAs in orthopaedic and medical wards provided more basic care than those in surgical and gynaecological wards. Nurses in wards with HCAs performed significantly fewer activities than nurses in control wards. CONCLUSIONS: HCAs presence accounted for a reduction in both direct and indirect care provided by nurses. Overall, HCAs provided more basic than technical and indirect care.

Activities of Daily Living↗

Microsatellite polymorphism of the alpha 1-antichymotrypsin gene locus associated with sporadic Alzheimer's disease.

A variant of the apolipoprotein E gene, APOE*4, is associated with both sporadic Alzheimer's disease (AD) and a subset of familial AD and this association is stronger with early as opposed to late onset AD. Both APOE*4 and alpha 1-antichymotrypsin (ACT) will accelerate the rate of amyloid filament formation and are major constituents of the plaques associated with AD. We now show that a dinucleotide microsatellite allele in the 5'-flanking sequence of the ACT gene, designated A10, in association with APOE*4 significantly increases the risk of developing sporadic AD, which accounts for the majority of AD cases.

Aged↗

The Fontan procedure in adults.

BACKGROUND: A retrospective clinical study was performed to document the course of adult patients undergoing the Fontan procedure. METHODS: Between 1982 and 1994, 21 adults aged 18 to 40 years (mean age, 27 +/- 7 years) underwent a Fontan procedure. Anatomic diagnosis was tricuspid atresia in 9, double-inlet left ventricle in 4, and various single ventricles in 8. Four underwent a right atria-right ventricle connection, 13 had a right atria-pulmonary artery connection, and 4 had a lateral-tunnel Fontan. Three of these 4 had a snare-adjustable atrial septal defect. Preoperative risk factors assessed were left ventricular end-diastolic pressure greater than 10 mm Hg, ejection fraction lower than 0.45, mean pulmonary artery pressure higher than 15 mm Hg, transpulmonary gradient greater than 10 mm Hg, pulmonary artery abnormalities, and atrioventricular valve regurgitation. Mean preoperative risk score was 1.6 /-1.1. Mean New York Heart Association class was 2.6 +/- 0.5. RESULTS: The operative mortality rate was 5% (1/21). Six patients (30%) had a major complication, four being prolonged effusions. One patient was lost to follow-up; the remaining 20 have been followed for a mean of 7.4 +/- 3.8 years. At follow-up, mean New York Heart Association class was 1.7 +/- 0.5. There has been one late death (5%) at 9 2/3 years, which was probably due to ventricular arrhythmia. Three patients (16%) have required and survived reoperation. During follow-up, 7 patients (37%) have had development of atrial arrhythmias requiring medication, and 2 have been treated for ventricular arrhythmias. CONCLUSIONS: These results indicate that properly selected adults can undergo the Fontan procedure with low morbidity and mortality. However, late-developing arrhythmias, need for reoperation, and decreasing ventricular function are serious problems that mandate careful follow-up.

Adult↗

Current views of direct angioplasty in acute myocardial infarct.

OBJECTIVE: The management strategies after acute myocardial infarction (AMI) have been evolving from simple supportive treatment to various protocols of thrombolytic therapies, and then to mechanical revascularization by balloon angioplasty in recent years. However, controversies still exist between which is the best treatment approach. METHODS: An extensive analysis was carried out in over 120 articles reported recently in the literature. RESULTS: Most reported series have shown that direct angioplasty is a feasible and safe option for the management of acute myocardial infarction. Large scale randomised studies comparing direct angioplasty versus thrombolytic therapy in acute myocardial infarction have also reported very favourable acute and long term outcomes by direct angioplasty as compared to thrombolytic therapy. The results are at least equivalent, if not better, by direct angioplasty. Acute results include better reperfusion rate of infarct related artery, less bleeding and stroke complications, shorter hospital stay, and most importantly, lower in-patient mortality (around 2% in direct PTCA group versus 6% in thrombolysis group) and less recurrent ischaemic event (around 10% in direct PTCA group versus 30% in thrombolysis group). Despite some delay in the commencement of treatment by direct angioplasty than thrombolytic therapy, the left ventricular function remains comparable in the two groups and the overall long term outcomes are very favourable with direct angioplasty. Specific indications for direct angioplasty include patients with cardiogenic shock after AMI and patients with contraindications to thrombolysis. No reflow phenomenon is still an issue of concern. It is in general contraindicated to use angioplasty after failure of thrombolysis. The cost implication is not far exceeding that of thrombolysis therapy. CONCLUSIONS: Direct angioplasty for acute myocardial infarction should be established as a treatment option if the circumstances allow. Planning should be carried out at the hospital and community level in order to make direct angioplasty a high priority treatment option for patients with acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

Stent thrombosis with different types of intracoronary stents: is it still a problem?

OBJECTIVE: The reported results of intracoronary stenting with Palmaz-Schatz stents using the low dose anticoagulation protocol have been encouraging and no stent thrombosis was observed. The effectiveness of such method extending to the use of other types of stents was therefore evaluated in this study. METHODS: All patients followed the anticoagulation protocol (heparin and warfarin) using non-heparin-coated stents. From September 1995, 92 patients received intracoronary stenting (69 men, 23 women, mean age 60.9 years). Altogether 117 stents were implanted in 99 target arteries and 106 lesions. RESULTS: A total of 50.4% of the stents were bare stents (stents without protective sheaths). Both coil stents and slotted tubular stents were used. Stenting was performed without the guidance of intravascular ultrasonography and high-pressure poststenting inflation was used in only 24.0% of patients with less than optimal angiographic results. The mean (+/- SD) coronary minimum luminal diameter changed from 0.63 +/- 0.39 mm to 3.12 +/- 0.48 mm immediately after stenting. Both stent thrombosis rate and femoral bleeding complication rate remained at 0%. Four bare stents could not be deployed in the first instance but without sequels. No morbidity nor mortality was recorded. The mean hospital stay remained at a mean of 4.5 days. All patients (100%) were followed up regularly. The mean (+/- SD) clinical follow-up period was 229 +/- 173 days. Clinical symptoms improved in all patients. CONCLUSIONS: These findings further support that the method is safe and stent thrombosis was not observed. Post-stenting recoil was more with coil stents. Dislodgment and potential risk of embolization could not be underestimated with bare stents. The restenosis rate between different types of stents remains to be determined.

Aged↗

School bus related deaths and injuries in New South Wales.

OBJECTIVE: To report the circumstances of paediatric bus related deaths and injuries in New South Wales (NSW) to identify preventable factors. DESIGN: Retrospective survey using two surveillance systems-the NSW Paediatric Death Review Database and the Childsafe Injury Surveillance System. PATIENTS: Children (0-14 years of age) who died or were injured as a result of a school bus related incident. RESULTS: Twenty-two deaths and 58 injuries were recorded. Three of the children who died were passengers (two deaths were due to errant behaviour), two were alighting from the bus (bus door entrapment) and 17 (77%) were pedestrians crossing the road before or as the bus departed. The major causes of death were head injury and blood loss. Seventeen of the injured children were pedestrians and most (82%) of these sustained serious injury requiring admission to hospital. CONCLUSIONS: The greatest risk to schoolchildren from bus related injuries was as pedestrians after alighting from a bus, especially when moving behind the bus. Preventable factors include slowing of traffic (40 kph) near stationary school buses, and parents waiting on the side of the road where the child alights from the bus. Continuing road safety education remains important for schoolchildren and parents as well as for drivers.

Accidents, Traffic↗

No subacute thrombosis and femoral bleeding complications under full anticoagulation in 150 consecutive patients receiving non-heparin-coated intracoronary Palmaz-Schatz stents.

Intracoronary stenting has been shown to have better immediate and long-term clinical outcomes and less restenosis than standard balloon angioplasty. However, the benefit was achieved at the cost of higher rates of coronary thrombosis, bleeding complications, the need for anticoagulation, and longer hospital stay. For the latter reasons there is a tendency to replace the anticoagulants by antiplatelet agents alone after stenting. However, we prospectively monitored 150 consecutive patients (133 men, 17 women, mean age 58.5 years) from two centers since February 1993. They all had coronary artery disease and underwent percutaneous implantation of non-heparin-coated Palmaz-Schatz coronary stents under a full but lower dose of anticoagulation. The femoral approach was used in all patients except one. In the 150 patients, 200 stents were implanted in 165 target arteries with 172 lesions. Stenting was performed without the guidance of intravascular ultrasonography; high-pressure poststenting inflation was used in only 17.3% of patients with less than optimal angiographic results. Coronary angiography was performed at baseline, immediately after the procedure, and after 6 months (mean 207 +/- 53.6 days SD) of stenting. The mean (+/-SD) coronary minimum luminal diameter increased from 0.52 0.31 mm to 3.13 +/- 0.42 mm immediately after stenting was performed and was 2.12 +/- 0.91 mm at 6 months. There was a 0% subacute thrombosis rate and a 0% femoral bleeding complication rate in the whole series. Only three (2%) major events occurred: one Q-wave myocardial infarction from closure of an angioplasty site distal to the stent on a very long lesion, one cerebrovascular accident, and one noncoronary-related death. The only patient who underwent the brachial approach had hematoma; otherwise no other minor event occurred. The mean hospital stay was 4.5 days in one of the two study centers. The long-term clinical follow-up rate was 97.3%. The mean (+/- SD) clinical follow-up period was 589 +/- 363 days. Clinical symptoms improved; the percentage of patients who had angina according to the Canadian Cardiovascular Society functional class II, III, and IV was 31.3%, 44.7%, and 4%, respectively, before stenting was performed and was reduced to 4.7%, 3.7%, and 0%, respectively at 6-month follow-up after stenting was performed. The 6-month angiographic restudy rate was 90.6%, and the restenosis rate was 18.3%. In contrast to other reported series, these results support the idea that with careful puncture technique and meticulous postoperative wound care, intracoronary stenting can be successfully performed with the patient under full anticoagulation without major risks of bleeding and femoral vascular complications. Furthermore with a full but comparatively lower dose of anticoagulation, subacute thrombotic complications can be reduced to 0% even with non-heparin-coated stents without the use of intravascular ultrasound guidance and without the use of adjunctive high-pressure poststenting inflation in most patients. The restenosis rate and long-term clinical outcomes remained very favorable.

Acute Disease↗

L-arginine administration during reperfusion improves pulmonary function.

BACKGROUND: Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of L-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury. METHODS: Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing L-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6). RESULTS: The partial pressure of oxygen in the whole blood group (113.8 +/- 33.1 mm Hg) was significantly less than in controls (417.3 +/- 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 +/- 0.2 mL/cm H2O) than in controls (2.9 +/- 0.4 mL/cm H2O; p < 0.01). The L-arginine and leukocyte-depleted blood groups showed no significant difference from controls. CONCLUSIONS: L-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.

Animals↗

Cardiac gene transfer by intracoronary infusion of adenovirus vector-mediated reporter gene in the transplanted mouse heart.

This study introduces a model for intracoronary gene transfer in murine cardiac isografts using adenovirus vectors. This approach may offer an opportunity to modulate alloreactivity after cardiac transplantation. Donor hearts were infected via the coronary arteries with a volume of 10(9) plaque-forming units per milliliter of a recombinant adenovirus containing the beta-galactosidase-encoding gene (Ad.CMVLacZ). In a control group, 200 microliters of normal saline solution was infused. The grafts were stored in 4 degrees C cold saline solution for 15 minutes, then transplanted heterotopically into syngeneic hosts (B10.BR). The grafts were harvested at 3, 7, 15, or 30 days (n = 5 for each group) after transplantation, and beta-galactosidase activity was assessed by histochemical staining (X-gal). All grafts were functioning when harvested. X-gal staining pattern was nonuniform with positive staining appearing in epicardial, myocardial, and endocardial cells, as well as in the vessel walls. The cells permissive to infection consisted predominantly of myocardial cells. The mean total numbers of beta-gal-positive staining cells per slice were 68.7 +/- 27.3 in the 3-day group, 330.4 +/- 53.8 in the 7-day group, 151.3 +/- 48.0 in the 15-day group, and 39.9 +/- 10.8 in the 30-day group, thus peaking in the 7-day group (p < 0.05). Control isografts (n = 5), retrieved at day 30, revealed no staining activity. In conclusion, our model demonstrates that intracoronary gene transfer to the transplanted murine cardiac grafts is feasible at the time of harvest. Adenovirus-mediated gene transfer produces widespread gene expression which, though perhaps transient, does not adversely affect myocardial structure or function. This technology may allow modification of graft immunogenicity in the future through the production of therapeutic proteins sufficient to modulate local immune responses.

Adenoviridae↗

Chemical modifications of heparin that diminish its anticoagulant but preserve its heparanase-inhibitory, angiostatic, anti-tumor and anti-metastatic properties.

Structural features of heparin potentially important for heparanase-inhibitory activity were examined by measuring the ability of heparin derivatives to affect the degradation of [3H]acetylated heparan sulphate by tumor cell heparanases. IC50 values were determined using an assay which distinguished degraded from undegraded substrate by precipitation of the latter with cetylpyridinium chloride (CPC). Removal of heparin's 2-O-sulphate and 3-O-sulphate groups enhanced heparanase-inhibitory activity (50%). Removal of its carboxyl groups slightly lowered the activity (18%), while combining the treatments abolished the activity. At least one negative charge on the iduronic acid/idose moiety, therefore, is necessary for heparanase-inhibitory activity. Replacing heparin's N-sulphate groups with N-acetyl groups reduced its activity (37%). Comparing this heparin derivative with 2,3-O-desulphated heparin, the placement of sulphate groups appears important for activity since the two structures have similar nominal linear charge density. In addition, unsubstituted uronic acids are nonessential for inhibition since their modification (periodate-oxidation/borohydride-reduction) enhanced rather than reduced heparanase-inhibitory activity. The most effective heparanase inhibitors (2,3-O-desulphated heparin, and [periodate-oxidized, borohydride-reduced] heparin) were tested in the chick chorioallantoic membrane (CAM) bioassay for anti-angiogenic activity and found to be at least as efficacious as heparin. 2,3-O-desulphated heparin also significantly decreased the tumor growth of a subcutaneous human pancreatic (Ca-Pan-2) adenocarcinoma in nude mice and prolonged the survival times of C57BL/6N mice in a B16-F10 melanoma experimental lung metastasis assay.

Animals↗

A rapid and efficient method for DNA extraction from paraffin wax embedded tissue for PCR amplification.

DNA from archival, formaldehyde fixed, paraffin wax embedded human tissue, suitable for amplification by the polymerase chain reaction (PCR), was obtained using a microwave method based on the capture of DNA by magnetic beads. Fragments of the alpha-1-antitrypsin gene (AAT) and the apolipoprotein E gene (APOE) were amplified successfully from human liver and brain tissue, respectively. This procedure provides a more rapid, simple and efficient method for reproducibly obtaining DNA from preserved tissue that has been kept in storage for up to 30 years.

Journal Article↗

Normal hepatic insulin sensitivity in lean, mild noninsulin-dependent diabetic patients.

We studied hepatic and extrahepatic insulin sensitivity and insulin release in seven nonobese patients with mild noninsulin-dependent diabetes mellitus (NIDDM) and 10 control subjects, matched for age, body mass index, and physical fitness. Glucose turnover was studied during sequential hyperinsulinemic euglycemic clamps (insulin infusion, 0.25 and 1.0 mU/kg BW.min), applying the hot-GINF (tracer-enriched glucose infusion) technique and using [6-3H]glucose. Hepatic glucose production was lower in hyperglycemic NIDDM patients during the basal period (P < 0.01), but was equivalent at similar glucose and insulin levels attained during both clamps. In contrast, during the low and high insulin clamps, glucose utilization was lower in NIDDM [14.90 +/- 1.00 vs. 17.24 +/- 0.83 (P < 0.01) and 41.37 +/- 3.05 vs. 50.54 +/- 3.61 mumol/kg BW.min (P < 0.01)]. Accordingly, the glucose infusion rate necessary to maintain euglycemia was lower in NIDDM [7.72 +/- 2.00 vs. 10.68 +/- 1.17 (P < 0.05) and 42.14 +/- 4.50 vs. 51.60 +/- 4.28 mumol/kg BW.min (P < 0.01)]. There was, however, a considerable overlap between patients and controls in the parameters describing insulin sensitivity. The insulin response to orally administered glucose as well as that to a standardized glucose infusion test (GIT) were diminished in NIDDM [average incremental insulin secretion during an oral glucose tolerance test, 88 +/- 28 vs. 251 +/- 50 pmol/L.min (P < 0.05); during first 10 min of GIT, 7 +/- 16 vs. 234 +/- 29 pmol/L.min (P < 0.001)]. There was no overlap in acute phase insulin secretion during the GIT between the groups. In conclusion, nonobese, mild NIDDM patients showed no impairment in hepatic, but a slight reduction in extrahepatic insulin sensitivity, with extensive overlap between diabetic and control subjects. In contrast, impairment of insulin release was very pronounced and without overlap.

Adult↗

Characterization of a HTLV-I-infected cell line derived from a patient with adult T-cell leukemia with stable co-expression of CD4 and CD8.

A long-term T-cell line, termed SP+, was developed from a human T-cell leukemia virus type I (HTLV-I)-infected patient with adult T-cell leukemia that is dependent on exogenous IL-2 for growth. The SP+ expresses a full complimentation of HTLV-I-specific viral proteins, and contains replication competent viral particles. Restriction enzyme digestion followed by Southern blot analysis demonstrated the presence of a single integrated proviral copy and limiting dilution analysis confirmed the clonality of the cell line. Interestingly, phenotypically, the SP+ cell line is CD2+, CD3+ and coexpresses CD4 and CD8, yet lacks TCR alpha beta and TCR tau delta expression. Further ontogenetic characterization of the SP+ cell line demonstrated the lack of thymic T-cell precursor markers, including absence of cell surface expression of CD1, intracellular thymic terminal deoxynucleotidyl transferase (TdT) enzyme, as well as message expression for V(D)J recombinase activating gene-1 (RAG-1). Furthermore, the SP+ cell did express the message for the CD3 delta chain. Taken together, these data suggest that the SP+ cell line resulted from HTLV-I infection of a mature CD4+/CDB+ lymphocyte. This cell line can be potentially useful as a model, both for regulation of cellular functions by HTLV-I and for immunologic functions of mature dual CD4/CD8 positive T-cells.

Antigens, Viral↗

Insulin-stimulated glucose uptake is enhanced in sedentary and endurance-trained low insulin responders.

The mechanisms by which healthy sedentary subjects with low insulin response (LIR; 5-min insulin response to glucose load within lowest quartile of healthy population) maintain a normal glucose tolerance are not clear. We studied glucose uptake and hepatic glucose production in LIR, in healthy subjects with high insulin response (HIR; two highest quartiles of insulin response) matched for weight and physical fitness, and in endurance-trained subjects (ET). For this purpose, we performed hyperinsulinemic euglycemic clamps using the "hot-GINF" method with high-pressure liquid chromatography purified [6-3H]glucose. All groups had a similar basal glucose appearance rate (Ra). During clamps, plasma insulin levels were doubled to 169 +/- 9 pmol/l, whereas Ra decreased similarly in all groups. Glucose utilization rate increased more in LIR and ET than in HIR (to 20.9 +/- 1.5 mumol.kg-1.min-1 in LIR, P < 0.001 vs. HIR; 27.4 +/- 3.6 in ET, P < 0.01 vs. HIR and LIR; and 14.3 +/- 0.6 in HIR). In conclusion, the present study demonstrates increased insulin sensitivity in LIR and ET with respect to glucose uptake but not glucose production.

Adult↗