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Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 343 records · Page 19Linked to original sources
PubMed1998

Trainee specialist: meeting the needs of service provision and career development.

A two-year modular training scheme to enable qualified speech and language therapists (SLTs) to become specialists in the field of acquired neurological disorders in adults was set up to address problems of: difficulty recruiting to senior posts; lack of opportunity for inexperienced therapists to gain experience in this field and the need for structured supervision. The paper describes how time was found to devise and implement the modular Nine Box System, the problems encountered, the advantages and disadvantages of the scheme as a whole and future developments. The scheme has potential to meet the needs of managers in creating a pool of experienced specialists to recruit to senior posts. It meets the needs of junior SLTs in providing a structured means of preparing for specialisation with guaranteed supervision.

Aphasia↗
PubMed1998

Aminopeptidase A expression and enzymatic activity in primary human renal cancers.

The gp160 human kidney differentiation antigen is identical to human aminopeptidase A (APA), a zinc-dependent cell-surface metallopeptidase which hydrolyzes peptides with N-terminal acidic residues. GP160/APA is constitutively expressed by proximal tubule cells, the normal cellular counterpart of most renal cancers (RCs). Immunohistochemical analysis of gp160/APA protein expression in 62 primary renal tumor specimens using monoclonal antibody S4 revealed heterogeneous or homogeneous expression of gp160/APA in 46/51 (90%) of clear cell carcinomas in contrast with 1/8 (13%) papillary renal tumors and 0/3 oncocytomas (p<0.001). Analysis of five primary clear cell carcinomas for gp160 protein expression immunohistochemically and associated APA catalytic activity revealed one tumor which expressed gp160/APA protein which was enzymatically inactive. Direct sequence analysis of DNA derived from this specimen could not detect mutations within the zinc-binding domain which would eliminate gp160/APA catalytic activity. These data indicate that the gp160/APA protein is expressed by primary clear cell but not papillary RCs or oncocytomas, and that alterations in gp160/APA protein including loss of protein expression or enzymatic activity occur in 20% of primary clear cell RCs.

Adenoma, Oxyphilic↗
PubMed1998

Survival and growth of Campylobacter jejuni after artificial inoculation onto chicken skin as a function of temperature and packaging conditions.

Campylobacter jejuni is one of the major causes of food poisoning in humans. C. jejuni is also widespread in food animals, and meat and meat products derived from food animals are the most common vector of bacterial transmission to humans. To determine the role of packing and storage conditions on the replication of C. jejuni on chicken, the virulent strain C. jejuni 81116 was artificially inoculated onto chicken skin pieces (1 cm2) and stored at different temperatures and under various packaging conditions. C. jejuni 81116 remained viable at -20 and -70 degrees C and was able to replicate at 4 degrees C and at ambient room temperature. C. jejuni 81116 was also inoculated onto chicken skin and subjected to repeated freeze thawing and the viability of the inoculum was quantified. C. jejuni 81116 could withstand repeated freeze thawing similar to that which may occur in the domestic home. Under all freezing conditions, C. jejuni 81116 retained a high level of viability and quickly replicated to levels which exceeded Australian food authorities' permitted bacteria level on raw food products after the sample was thawed.

Animals↗
PubMed1998

A descriptive study of the demography, symptomology, management and outcome of the first 300 patients admitted to an independent hospice in Singapore.

The aims of this study were: 1) to describe the demography, symptomology, investigations conducted, non-pharmacological interventions and outcome of patients admitted to an inpatient hospice and 2) to identify the nursing and medical needs of terminally ill patients. Case-notes of the first 300 patients admitted to Dover Park Hospice were studied retrospectively. There were 159 men and 141 women making up 325 admissions. The racial distribution was: Chinese 95.0%, Malays 3.0%, Indians 1.3% and Others 0.6%. Two-thirds of the men (64.2%) had spouses while 44.7% of the women were widowed. The mean age was 64.7 years. The 3 most common cancers were lung (21.7%), colorectal (14.6%) and hepatobiliary (12.5%). A proportion of patients (39.5%) were not known to have any metastases. Most patients were referred from hospitals and the home-care based Hospice Care Association. The commonest reason for admission was for "terminal care" (57.2%). At admission, only 38% of the patients were aware of their diagnoses and prognosis while 30% did not know either. The average length of stay was 25 days with 7.7% of patients having more than one admission. The most common symptoms were pain, anorexia, breathlessness, insomnia, constipation and dry skin. Non-pharmacological interventions ranged from manual evacuation of the rectum to transfers to tertiary hospitals for surgery and other more invasive interventions. Many patients also attended day-care activities (23.1%). Outcome of the 325 admissions were as follows: went home 20%, died in the hospice 73.2%, went home to die 4.9% and others 1.8%.

Adult↗
PubMed1998

What you need to know: detecting alcohol problems in general medical practice.

In the US, about 11% to 20% of patients presenting to general medical clinics are diagnosed as suffering from alcohol abuse or dependence. Alcohol screening in primary care settings, whether in the US or Singapore, can utilise various strategies for the early detection of alcohol problems. This paper briefly reviews several self-reports and screening procedures to assist general practitioners in identifying problem drinkers. The use of CAGE questionnaire, MAST, and its variation, SAAST and the AUDIT, are discussed and evaluated. Likewise, useful biochemical markers of excessive alcohol consumption like the liver enzymes (AST, ALT, GGT), MCV, CDT are described. They can be combined with each other to improve validity or used in conjunction with self-report screening tests for more accurate detection of problem drinkers. In particular, use of the AUDIT for routine screening of alcohol problems in primary care settings is recommended. Selective administration to those with at least two drinks per setting can overcome time constraints. Alternatively, sequential screening utilising the TRAUMA questionnaire with frequency and quantity questions administered to higher frequency drinkers can circumvent concerns about direct questioning. Use of self-reports and when possible, biochemical screening for alcohol problems should be a standard part of primary care practice.

Alcoholism↗
PubMed1998

Antigen-dependent progression of mucosa-associated lymphoid tissue (MALT)-type lymphoma in the stomach. Effects of antimicrobial therapy on gastric MALT lymphoma in mice.

In humans, low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach regress when Helicobacter pylori infection is cured by antimicrobial therapy. Using an animal model of human gastric MALT lymphoma, we observed the effects of Helicobacter felis eradication and the relationship between infection and disease progression. Antimicrobial therapy was given to one-half of the BALB/c mice infected with H. felis for 20 months. Groups of antibiotic-treated and untreated mice were killed 2, 3, and 4 months after antimicrobial therapy (ie, 22, 23, and 24 months after infection). The numbers of mice with MALT decreased after H. felis eradication with no lymphoid follicles seen 4 months after treatment. MALT lymphoma was present in a total of 23% (11/48) of antibiotic-treated infected mice compared with 75% (27/36) in untreated infected mice. These lymphomas were further graded into low-, intermediate-, and high-grade lymphoma. In the untreated mice, lymphoma development was more advanced with 36% low-grade (13/36), 39% intermediate-grade (14/36), and 6% high-grade (large B-cell) lymphoma (2/36) whereas in the treated mice the incidence was 21% (10/48), 6% (3/48), and 0% (0/48), respectively. These observations suggest that antigenic stimulation by H. felis sustained growth and progression of low-grade MALT lymphoma and that primary high-grade gastric lymphomas can evolve from the transformation of these tumors. Eradication of the organism caused low-grade tumors to regress, with inhibition or slowing down of lymphoma development toward high-grade lymphoma. The H. felis mouse model of gastric MALT lymphoma presents an opportunity to address the issues arising from antimicrobial treatment of these tumors in humans.

Animals↗
PubMed1998

On developing self-concepts: a controlled study of children and adolescents with autism.

This study employed the self-understanding interview of Damon and Hart (1988) to assess the self-concepts of two groups of children and adolescents: a group of individuals with autism and a group of nonautistic mentally retarded individuals who were matched for age and for verbal ability. On the basis of an hypothesis concerning the interpersonal origins of social and psychological self-concepts (Hobson, 1990; Neisser, 1988), it was predicted that the participants with autism would show a relative dearth of such concepts in their talk about themselves. In accordance with our predictions, there was a significant group difference in the number and quality of statements that fell into the social category of self-concept; contrary to our predictions, however, there was no group difference in the number of statements that fell into the psychological category. In addition, although there were not significant group differences in the overall production of verbally expressed concepts concerning self-attributes of a physical, active, or psychological kind, even within these categories individuals with autism made fewer references to social interactions or qualities. These results are discussed with regard to theories of self-concept development in typically developing as well as autistic and mentally retarded individuals, and with reference to the limitations of interpersonal understanding ("theory of mind") in people with autism.

Adolescent↗
PubMed1998

Preferred place of death--a local study of cancer patients and their relatives.

BACKGROUND: Knowing the preferred place of terminal care is helpful in the provision of services for the terminally ill. We carried out a survey of cancer in-patients and their relatives to determine the local preference for place of terminal care as well as the factors that affected their choice. METHODS: The study was conducted in the form of an interview survey on patients admitted to a general medical unit and a geriatric medicine unit. Relatives approached were the nearest kin (first degree relatives), or relatives living with the patients. Patients who were not aware of their diagnosis, who were unable to comprehend the questionnaire, or were too ill to participate were not interviewed. RESULTS: Fifty-two percent (23/44) of interviewed patients preferred to die at home if possible (compared to 34%, 15/44, who preferred the hospital). This is particularly so in the elderly and if there is assurance of domiciliary care. Relatives have an almost equal preference for the patient to be at home (45%, 35/77) or in the hospital (42%, 32/77) terminally. Given the support, more (37.5%, 12/32) of those who initially wanted their sick relatives to be in hospital would prefer them to spend their last days at home. CONCLUSION: There is a greater preference in cancer patients for terminal care at home. This is especially so for the elderly and if there is assurance of domiciliary care. This is an impetus for greater support of home care services.

Adult↗
PubMed1997

The KDEL receptor, ERD2, regulates intracellular traffic by recruiting a GTPase-activating protein for ARF1.

The small GTPase ADP-ribosylation factor 1 (ARF1) is a key regulator of intracellular membrane traffic. Regulators of ARF1, its GTPase-activating protein (GAP) and its guanine nucleotide exchange factor have been identified recently. However, it remains uncertain whether these regulators drive the GTPase cycle of ARF1 autonomously or whether their activities can be regulated by other proteins. Here, we demonstrate that the intracellular KDEL receptor, ERD2, self-oligomerizes and interacts with ARF1 GAP, and thereby regulates the recruitment of cytosolic ARF1 GAP to membranes. Because ERD2 overexpression enhances the recruitment of GAP to membranes and results in a phenotype that reflects ARF1 inactivation, our findings suggest that ERD2 regulates ARF1 GAP, and thus regulates ARF1-mediated transport.

ADP-Ribosylation Factor 1↗
PubMed1997

Tobacco smoke is a source of toxic reactive glycation products.

Smokers have a significantly higher risk for developing coronary and cerebrovascular disease than nonsmokers. Advanced glycation end products (AGEs) are reactive, cross-linking moieties that form from the reaction of reducing sugars and the amino groups of proteins, lipids, and nucleic acids. AGEs circulate in high concentrations in the plasma of patients with diabetes or renal insufficiency and have been linked to the accelerated vasculopathy seen in patients with these diseases. Because the curing of tobacco takes place under conditions that could lead to the formation of glycation products, we examined whether tobacco and tobacco smoke could generate these reactive species that would increase AGE formation in vivo. Our findings show that reactive glycation products are present in aqueous extracts of tobacco and in tobacco smoke in a form that can rapidly react with proteins to form AGEs. This reaction can be inhibited by aminoguanidine, a known inhibitor of AGE formation. We have named these glycation products "glycotoxins." Like other known reducing sugars and reactive glycation products, glycotoxins form smoke, react with protein, exhibit a specific fluorescence when cross-linked to proteins, and are mutagenic. Glycotoxins are transferred to the serum proteins of human smokers. AGE-apolipoprotein B and serum AGE levels in cigarette smokers were significantly higher than those in nonsmokers. These results suggest that increased glycotoxin exposure may contribute to the increased incidence of atherosclerosis and high prevalence of cancer in smokers.

Animals↗
PubMed1997

Corticosteroids inhibit lymphocyte binding to endothelium and intercellular adhesion: an additional mechanism for their anti-inflammatory and immunosuppressive effect.

Glucocorticosteroids (GCS) are potent anti-inflammatory and immunosuppressive agents widely used in the treatment of many medical conditions, but their mechanism of action is not yet fully understood. Some of the anti-inflammatory effects of GCS have been attributed to the synthesis of lipocortins, whereas the immunosuppressive effects are thought to be mediated through the inhibition of several immune functions through a down-regulation of cytokine gene expression. Another important mechanism of action of GCS may relate to their ability to interfere with the phenomena of adhesion and migration of inflammatory cells. In this study, the direct effects of GCS on lymphocyte adhesion capacity in vitro were investigated. We demonstrate that GCS inhibit lymphocyte adhesion to endothelium through the down-modulation of lymphocyte adhesion molecules. We also provide evidence that GCS inhibit cell aggregate formation induced by TCR ligation, which directly correlates with the down-modulation of LFA-1 and CD2, but not LFA-3 or ICAM-1. Such down-modulation was paralleled by a decrease in the steady state mRNA level of LFA-1 and CD2 gene products, which suggests a direct GCS control of the expression of these genes. Finally, we show that GCS effects are mediated through the GCS receptor, since they can be completely reversed by the GCS-R antagonist RU-486. This study supports the concept that some of the immunosuppressive and anti-inflammatory effects of GCS are likely to be exerted by the inhibition of adhesion-dependent lymphocyte functions.

Adrenal Cortex Hormones↗
PubMed1997

Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation.

Thirty-six patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) were studied for the presence of the bcr-abl fusion mRNA transcript after an allogeneic matched related (N = 12), partially matched related (N = 4), matched unrelated (N = 14), autologous (N = 5), or syngeneic (N = 1) bone marrow transplant (BMT). Seventeen were transplanted in relapse, and 19 were transplanted in remission. Twenty-three patients had at least one positive bcr-abl polymerase chain reaction (PCR) assay after BMT either before a relapse or without subsequent relapse. Ten of these 23 relapsed after a positive assay at a median time from first positive PCR assay of 94 days (range, 28 to 416 days). By comparison, only 2 relapses occurred in the 13 patients with no prior positive PCR assays; both patients had missed at least one scheduled follow-up assay and were not tested 2 months and 26 months before their relapse. The unadjusted relative risk (RR) of relapse associated with a positive PCR assay compared with a negative assay was 5.7 (95% confidence interval 1.2 to 26.0, P = .025). In addition, the data suggest that the type of bcr-abl chimeric mRNA detected posttransplant was associated with the risk of relapse: 7 of 10 patients expressing the p190 bcr-abl relapsed, compared with 1 of 8 who expressed only the p210 bcr-abl mRNA (P = .02, log-rank test). The RR of p190 bcr-abl positivity compared to PCR-negative patients was 11.2 (confidence interval 2.3-54.8, P = 0.003), whereas a positive test for p210 bcr-abl was apparently not associated with an increased relative risk. In separate multivariable models, PCR positivity remained a statistically significant risk factor for relapse after separately adjusting for donor (unrelated and partially matched v matched, autologous, and syngeneic), remission status at the time of transplant, the presence of acute graft-versus-host disease (GVHD), and type of conditioning regimen (total body irradiation dose of < or = 1,200 cGy v > 1,200 cGy). The PCR assay appears to be a useful test for predicting patients at high risk of relapse after BMT and may identify patients who might benefit from therapeutic interventions. The finding that the expression of p190 bcr-abl may portend an especially high risk of relapse suggests a different clinical and biologic behavior between p190 and p210 bcr-abl.

Acute Disease↗
PubMed1997

From peptide to non-peptide. 3. Atropisomeric GPIIbIIIa antagonists containing the 3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione nucleus.

The benzodiazepinedione class of non-peptidal GPIIbIIIa antagonists has been modified to allow the isolation of noninterconverting rotational isomers, or atropisomers, with the aim of examining their structure-activity relationships as compared to active RGD-containing peptides and other non-peptidal antagonists. Resolution of these antagonists was accomplished by the introduction of a tert-butyl group at N1 and a chlorine at C9 on the 3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione nucleus and enantiospecific substitution on the beta-alanine side chain attached to N4. The relative configuration was determined by single-crystal X-ray analysis. Further, conformational analyses using ab initio calculations were performed to assess the conformational preferences about the beta-alanine side chain. The data support a good topographical correlation between the benzodiazepinedione class of antagonists and the "cupped" presentation of the RGD tripeptide sequence found in the cyclic peptide G4120. The relationship between these compounds with other peptidal and non-peptidal antagonists is discussed.

Benzodiazepinones↗
PubMed1997

Influence of cyclic guanosine monophosphate changes on hemodynamics after reperfusion in liver transplantation.

Orthotopic liver transplantation (OLT) is often associated with hemodynamic instability upon reperfusion, recognized as postreperfusion syndrome. Changes in vascular tone due to humoral factors released upon reperfusion of the graft have been suggested as a possible mechanism. In this study, we looked at the perioperative changes in cyclic guanosine monophosphate (cGMP), a mediator of vascular smooth muscle relaxation, and investigated its relationship with hemodynamic parameters. cGMP was measured in the plasma of 14 patients undergoing OLT by radioimmunoassay serially at the preanhepatic and anhepatic phases, and after reperfusion at 30, 60, and 120 min. Hemodynamic data recorded were systemic and pulmonary arterial pressures, cardiac output, and pulmonary and systemic vascular resistance. cGMP decreased markedly after reperfusion from a baseline level of 5.33+/-0.7 ng/ml to 1.63+/-0.5 ng/ml (P<0.01). Pulmonary arterial pressure increased from 17+/-1.21 mmHg to 23.5+/-1.9 mmHg (P<0.05), and pulmonary vascular resistance increased from 62.8 +/-12.9 dynes/sec/cm5 to 135+/-42.7 dynes/sec/cm5 (P<0.01). Changes in cardiac output and systemic vascular resistance were not significant. The changes in cGMP correlated with pulmonary arterial pressure (r=0.74, P=0.005) and pulmonary vascular resistance (r=0.7, P=0.01). These data confirm the occurrence of hemodynamic changes during OLT, and provide evidence to suggest that the reduction in cGMP after reperfusion may mediate the vascular changes.

Blood Pressure↗
PubMed1997

Increased dopamine activity associated with stuttering.

Position emission tomography using 6-FDOPA as a marker of presynaptic dopaminergic activity was used to investigate the role of the dopamine system in stuttering. Three patients with moderate to severe developmental stuttering were compared with six normal controls. Stuttering subjects showed significantly higher 6-FDOPA uptake than normal controls in medial prefrontal cortex, deep orbital cortex, insular cortex, extended amygdala, auditory cortex and caudate tail. Elevated 6-FDOPA uptake in ventral limbic cortical and subcortical regions is compatible with the hypothesis that stuttering is associated with an overactive presynaptic dopamine system in brain regions that modulate verbalization.

Adult↗
PubMed1997

Coupling of neutrophil apoptosis to recognition by macrophages: coordinated acceleration by protein synthesis inhibitors.

Onset of apoptosis in many cell types, including the neutrophil granulocyte, leads to recognition and ingestion by macrophages, a key regulatory step in clearance of inflammatory cells from inflamed sites. These studies examined the requirement for protein synthesis in neutrophil apoptosis and in the recognition of apoptotic neutrophils by monocyte-derived macrophages. Treatment with cycloheximide or actinomycin D produced a time- and concentration-dependent acceleration of apoptosis in populations of neutrophils purified from human peripheral blood. Both compounds caused significant promotion of apoptosis after 8 h (apoptosis was 7.7 +/- 2.9%, mean +/- SEM, in control populations, 57.5 +/- 4.9% in cycloheximide-treated, and 73.4 +/- 5.5% in actinomycin D-treated populations, n = 4, P < 0.001), which was associated with loss of neutrophil functional ability (assessed by shape change on N-formyl-methionyl-leucyl-phenylalanine stimulation) and increased macrophage recognition and ingestion of neutrophil populations with accelerated apoptosis. These results support the existence of survival proteins, which act as intracellular suppressors of programmed cell death. However, protein synthesis was not required for the recognition process because macrophage recognition was increased pari passu with the morphology of apoptosis.

Apoptosis↗