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Biomedical subjects

K S Chan

Publications and source records attributed to K S Chan.

At least 55 records · Page 3Linked to original sources

Termination of second trimester pregnancy with gemeprost and misoprostol: a randomized double-blind placebo-controlled trial.

A prospective randomized double-blind placebo-controlled trial was conducted in 70 subjects to determine whether pre-treatment with misoprostol could facilitate termination of second trimester pregnancy by gemeprost. The women received either 400 micrograms oral misoprostol or placebo tablets 12 hours before the administration of vaginal pessary of gemeprost 1 mg every 3 hours. There were no significant differences in induction-abortion interval and the amount of gemeprost required between the misoprostol and the placebo group. There was no significant difference in the incidence of side effects or analgesic requirement between the two groups. We conclude that oral misoprostol is not useful in facilitating termination of second trimester pregnancy by gemeprost.

Abortion, Induced↗

Single-tube nested PCR in the diagnosis of tuberculosis.

AIMS: To evaluate the usefulness of a single-tube nested polymerase chain reaction (PCR) assay in the diagnosis of tuberculosis in 1497 pulmonary and 536 extrapulmonary specimens. METHODS: A single-tube nested PCR, utilising two sets of primers with different melting temperatures (88 degrees C for external primers; 70 degrees C for internal primers) to augment sensitivity and specificity without increasing the risk of amplicon contamination, was evaluated. Specimens were initially tested for the repetitive IS6110 sequences and if negative, retested for the universal 38 kilodalton sequence and for inhibitors. dUTP/Uracil-N-glycosylase and Instagene treatment were used to minimise contamination and the effect of inhibitors, respectively. RESULTS: Using culture as the gold standard, the overall sensitivity of the assay was 89% for pulmonary and 42% for extrapulmonary specimens. Sensitivity varied greatly with respect to sample type (92% for follow up specimens from a chest hospital and 70% for non-follow up specimens from a general hospital). The smear positivity rates were 15% for extrapulmonary specimens, and 69% and 45%, respectively, for follow up and non-follow up specimens from pulmonary sites. Specificity was 99.7%. Inhibitors were present more frequently in extrapulmonary than in pulmonary specimens (13.4% v 2.7%). CONCLUSION: Despite the high sensitivity of the PCR assay for the diagnosis of tuberculosis in pulmonary specimens, it was less effective in the extrapulmonary samples. This is probably because of the lower bacterial load in extrapulmonary specimens, the presence of more inhibitors adversely affecting the PCR assay and the higher volume of specimens used for culture.

Base Sequence↗

Growth hormone secretagogues: characterization, efficacy, and minimal bioactive conformation.

Another class of growth hormone (GH) secretagogues has been discovered by altering the backbone structure of a flexible linear GH-releasing peptide (GHRP). In vitro and in vivo characterization confirms these GH secretagogues as the most potent and smallest (M(r) < 500) reported. Anabolic efficacy is demonstrated in rodents with intermittent delivery. A convergent model of the bioactive conformation of GHRPs is developed and is supported by the NMR structure of a highly potent cyclic analog of GHRP-2. The model and functional data provide a logical framework for the further design of low-molecular weight secretagogues and illustrate the utility of an interdisciplinary approach to elucidating potential bound-state conformations of flexible peptide ligands.

Amino Acid Sequence↗

IS6110 based amplityping assay and RFLP fingerprinting of clinical isolates of Mycobacterium tuberculosis.

AIMS: To evaluate the usefulness of two IS6110 based typing methods, an amplityping assay and restriction fragment length polymorphism (RFLP) analysis, for fingerprinting respiratory isolates of Mycobacterium tuberculosis. METHODS: For amplityping, a pair of primers which amplify the intervening sequence between the repetitive insertion sequence IS6110 was used to generate a banding pattern which was confirmed by hybridisation. This assay was compared with conventional chromosomal DNA RFLP typing in the evaluation of 110 epidemiologically diverse isolates. RESULTS: Polymerase chain reaction (PCR) amplityping generated a single pattern in Hong Kong Chinese strains, but two and four diverse patterns in Filipino and Vietnamese strains, respectively, and could be completed within four days. When compared with chromosomal DNA RFLP typing, which took three weeks to complete, four different RFLP patterns could be seen among the Chinese strains, while seven patterns were found in the Filipino and Vietnamese strains. No change in amplityping or RFLP patterns was found in 36 sequential isolates from the same patients after anti-tuberculosis treatment for up to 12 months, despite the emergence of resistance in three of these strains. No specific amplityping or RFLP pattern could be related to different patterns of drug susceptibility. CONCLUSION: PCR amplityping could be used initially as a rapid typing method to distinguish strains originating from different localities. This could be important for investigation of outbreaks of tuberculosis--for example, in refugee camps.

Bacterial Typing Techniques↗

Semi-automatic quantitation of nucleolar organizer regions in non-Hodgkin's lymphomas.

Nucleolar organizer regions may be useful in the diagnosis and classification of non-Hodgkin's lymphomas. In this study of 46 cases we applied morphometric analysis with quantitation of physical descriptors of the nuclear profile (area, perimeter) and both number and area of stained nucleolar organizers therein enclosed to a series of lymphomas and benign lymphoid infiltrates. While nuclear outlines were manually traced small organizer regions within the nuclear profiles were semi-automatically outlined by a thresholding procedure subjected to manual override. This results in determination of number, area and perimeter of organizer regions. Data were corrected for section thickness effects and a stereologic (three-dimensional) analysis was additionally performed. We found an increase in mean number and area of nucleolar organizers per nucleus in high grade lymphomas compared to benign infiltrates and lower grade lymphomas. Volume and thickness corrected data showed a decrease in organizer number with concomitant increase in organizer volume in the higher grade lymphomas. Multivariate analysis of the cases, previously classified histologically, showed that clear resolution could be obtained, on the basis of physical descriptors, both between as well as within groups of the three tumor grades.

Humans↗

Endobronchial tuberculosis: diagnostic features and therapeutic outcome.

BACKGROUND: Endobronchial tuberculosis (EBTB) is not seen often in the adult population. In most cases it is associated with pulmonary tuberculosis. During its course significant tracheobronchial stenosis may develop. In this study we report our experience with patients with EBTB. METHODS: The records of 38 patients in whom EBTB had been proved by fibre optic bronchoscopy, microbiology and histology studies were evaluated. RESULTS: Symptoms were non-specific and represented mainly the co-existing pulmonary tuberculosis. Signs characteristic of airway obstruction were rare (localized wheezing in 6%). Indications for bronchoscopy were radiographic features (87%), microscopy smear negatives (8%), wheezing (3%), and blood stained sputum (3%). The lesions were more likely to be seen in the main and upper bronchi. In 5% of patients the lower trachea was involved. Most lesions looked inflamed (51%), followed by caseous (19%), granulomatous (17%), ulcerative (12%), and fibrotic appearance (1%). The degree of stenosis was nil (22%), minor (45%), significant (13%), subtotal (13%), or total (7%). The patients were treated with a combination of antituberculosis drugs. Four patients underwent surgical procedures. Dilatation techniques were used in two patients for a right and left main bronchus stenosis respectively, with significant improvement in one. Dilatation in combination with laser therapy of a right intermediate bronchus stenosis did not result in re-expansion of the dependent part of the lung due to pleural adhesions. Left pneumonectomy was performed in one patient for destroyed lung. Twenty-two patients agreed to follow up bronchoscopy. The macroscopic appearance of the mucosa had improved in most cases but the degree of stenoses was unchanged in a considerable proportion (58%). Bronchial stenosis in one patient subsided during therapy but developed again at a later stage. CONCLUSIONS: Patients with pulmonary tuberculosis and radiographic evidence of volume loss are recommended to undergo bronchoscopy to rule out EBTB. Specific symptoms for EBTB are rare. Biopsy of inflamed areas of bronchial mucosa seems to be indicated. Despite adequate antituberculosis therapy tracheobronchial stenosis may develop. Long term follow up including bronchoscopy seems therefore advocated. Dilatational intervention may be indicated in selected cases.

Adolescent↗

Benzodiazepine peptidomimetic inhibitors of farnesyltransferase.

A structural survey of protein Zn2+ binding geometries was instigated based upon the functional requirement of Ras farnesyltransferase for Zn2+. The Cys-X-X-Cys motif found in Zn(2+)-binding proteins such as aspartate transcarbamylase was used as a template to devise a bidentate-coordination model for Cys-A1-A2-X peptide inhibitors. Accordingly, replacement of the central dipeptide with the hydrophobic scaffold 3-amino-1-carboxymethyl-2,3-dihydro-5- phenyl-1H-1,4-benzodiazepin-2-one (BZA) yielded a peptidomimetic inhibitor, Cys(BZA)Met, of moderate potency (IC50 = 400 nM). N-Methylation of the cysteine amide improved potency almost 100-fold (IC50 = 0.3-1 nM). The increased affinity presumably correlates with a preferred conformation of the inhibitor which maximizes a hydrophobic interaction between the scaffold and the enzyme, and the proper presentation of cysteine and methionine to allow bidentate coordination at Zn2+. These non-peptide inhibitors have been shown to block farnesylation of the Ras protein in intact cells and provide lead compounds for the development of new cancer therapeutic agents.

Alkyl and Aryl Transferases↗

Use of PCR in routine diagnosis of treated and untreated pulmonary tuberculosis.

AIMS: To assess the routine use of a polymerase chain reaction (PCR) assay for the direct detection of Mycobacterium tuberculosis in expectorated sputum specimens. METHODS: A pair of primers (20-mer) were designed to amplify the 38 kilodalton protein of M tuberculosis. The specificity of the assay was evaluated in 31 M tuberculosis strains, 15 atypical mycobacterium species, and several commensal bacteria of the upper respiratory tract. The assay was subsequently applied to 519 sputum specimens from 85 inpatients of a chest hospital in Hong Kong. RESULTS: An amplified product of 239 base pairs was found in all M tuberculosis strains, standard strains of M bovis, and M africanum but not in the other bacterial strains tested. For the 51 patients with pulmonary radiographic lesions, the diagnosis of pulmonary tuberculosis was subsequently confirmed by both culture and PCR in 41 of them. Five patients who were treated before admission were positive by PCR alone. All but one patient in the control group (patients with acute exacerbation of chronic obstructive airway diseases) or those with atypical mycobacterial diseases were PCR negative. The PCR remained positive after four weeks of anti-tuberculosis treatment in 29 patients, 16 of whom had become culture negative. CONCLUSION: This PCR assay is a useful technique for the diagnosis of untreated and recently treated cases of pulmonary tuberculosis.

Base Sequence↗

Disseminated histoplasmosis mimicking miliary tuberculosis: a case report.

A 35-year-old Chinese man who was known to have insulin-dependent diabetes mellitus was admitted for fever and weight loss. During his hospital stay, he fell to his death from his ward at the twelfth floor. The clinical features, radiological findings and gross organ changes at autopsy closely simulated miliary tuberculosis. Histology, however, revealed extensive necrosis of the adrenal glands, lungs, spleen, kidneys and thyroid associated with the presence of Histoplasma capsulatum organisms. This case highlights the similarity both clinically and pathologically between histoplasmosis and tuberculosis and emphasizes the need to be aware of this infection in a nonendemic area among patients with a compromised immune system.

Adult↗

Quantitative perimeter and area measurements of digital images.

Quantitative estimations of perimeter and area from digitized video images, and the application of these features in morphometry, are discussed. Estimations from manual tracings via interactive peripherals and from chain codes are addressed. Topics discussed are calibration, determination of vertical and horizontal pixel resolution, effects of tracing jitter, and for chain codes, the spatial quantization scheme representation of the digital contour. Finally, new perimeter estimators for 4-connected and 8-connected chain codes for non-unity pixel aspect ratio are presented with simulation results.

Animals↗

Cyclic RGD peptide analogues as antiplatelet antithrombotics.

Stimulation of platelets activates GPIIbIIIa, the heterodimeric integrin receptor, to bind fibrinogen (Fg), which results in platelet aggregation. GPIIbIIIa/Fg binding inhibitors are potentially suitable for acute use during and after thrombolytic therapy as antithrombotic agents. Incorporation of the tripeptide sequence Arg-Gly-Asp (RGD), a common structural element of many integrin ligands, into cyclic peptides produced a series of peptides of the general structure BrAc-(AA1)-RGD-Cys-OH, which were prepared by solid-phase peptide synthesis. Cyclization was accomplished by reaction of the N-terminal bromoacetyl group with the cysteine sulfhydryl at pH 8 at high dilution, resulting in thioether-bridged cyclic peptides [cyclo-S-Ac-(AA1)-RGD-Cys-OH]. Use of alpha-substituted bromoacetyl groups gave rise to an analogous series of acetyl-substituted thioether-bridged cyclic peptides. Oxidation of the thioethers produced separable diastereomeric sulfoxide-bridged cyclic peptides. After thorough evaluation in a GPIIbIIIa ELISA assay and a platelet aggregation assay, G-4120 (70A; AA1 = D-Tyr; sulfoxide bridge) was selected for further investigation as an antithrombotic agent. G-4120 was equipotent in the platelet aggregation assay to kistrin, a highly potent inhibitor of fibrinogen-mediated platelet aggregation isolated from snake venom (IC50 = 0.15 microM).

Amino Acid Sequence↗

[Involvement of the central nervous system in disseminated tuberculosis].

Four weeks after starting tuberculostatic treatment (with isoniazid, rifampicin, streptomycin and pyrazinamide) a 21-year-old man with pulmonary tuberculosis developed symptoms of a radiculomyelopathy as well as mild renal failure. After isoniazid and streptomycin had been discontinued and ethambutol and high doses of vitamin B6 had been added all signs and symptoms improved. However, 4 weeks later tuberculous meningitis occurred which at first seemed to respond to administration of 5 antituberculosis drugs and dexamethasone. But 3 weeks later the patient sustained a partial hemiparesis. Its cause was proven to be a tuberculoma in the region of the brainstem. During further administration of tuberculostatic drugs and glucocorticoids the symptoms gradually receded over 8 months. A 54-year-old man with pulmonary tuberculosis developed cranial nerve pareses and symptoms of cerebellar involvement (trunk ataxia, intention tremor, dysdiadochokinesia) 3 weeks after starting tuberculostatic treatment. Computed tomography revealed multiple intracerebral tuberculomas which gradually shrank with continuation of the tuberculostatic treatment plus glucocorticoids. These two case reports illustrate that in tuberculosis involvement of the CNS can express itself clinically through complex symptoms, sometimes even after the start of tuberculostatic treatment.

Adrenal Cortex Hormones↗

The selection of patients for accelerated radiotherapy on the basis of tumor growth kinetics and intrinsic radiosensitivity.

Mathematical modeling was used to reach qualitative conclusions concerning the relative rate of local tumor control that might be achieved by using accelerated fractionation to treat only the patients with the most rapidly growing tumors, compared with the control rates that could be expected from either conventional or accelerated radiotherapy alone. The results suggest that concomitant boost therapy is equally or more effective than conventional dose fractionation for all tumors, regardless of their growth kinetics. For tumors with very short clonogen doubling times, CHART (continuous hyperfractionated accelerated radiotherapy) may be even more effective than concomitant boost treatment, but CHART is less effective than conventional or concomitant boost therapy for tumors with longer clonogen doubling times. Thus, there is a rationale for using a predictive assay of tumor clonogen doubling times to identify the patients who should be treated with CHART. However, improvements in local tumor control resulting from concomitant boost treatment or the selective use of CHART are not likely to be apparent in the population as a whole, because the overall control rates are largely determined by refractory tumors having little chance of control with any of the treatments and by highly responsive tumors that are likely to be controlled regardless of the treatment choice. Differences in control rates with different treatment strategies are most apparent in the stochastic fraction of the population, which excludes those patients for whom there is either very little chance (e.g. less than 1%) or a very high chance (e.g. greater than 99%) of achieving local control with both treatments. The stochastic fraction can be approximated by excluding those patients with the most radioresistant and the most radiosensitive tumors, since intrinsic tumor radiosensitivity appears to be the single most important factor determining treatment outcome.

Dose-Response Relationship, Radiation↗

A dBASE III system for managing 35 mm slides in pathology.

We describe the design and management of a 35 mm slide database using a menu-driven dBASE III PLUS programme and a microcomputer in a large department of pathology that also caters for the individual pathologist. Existing systems described in the literature are geared towards slides of general medicine and do not address the needs of the individual pathologist. A total of 11,481 slides in the Department of Pathology, Faculty of Medicine, University of Malaya, were filed into a single database with each record representing one slide. Nine fields which comprised the slide accession number, reference number, slide category, SNOMED codes, and a description of the slide in natural language, seemed adequate for slide definition. The menu-driven programme had functions which included the abilities to add, delete, edit and back-up records, and to search for desired slides. Although slides may be searched for in various fields, we found that searches using natural language alone were both comprehensive and efficient, provided a standard format of description was adhered to and data entries scrutinized carefully for errors. We believe therefore, that for the pathologist working alone, coded language fields are not absolutely necessary, as manual coding and additional data entry can be time consuming. As expected, for databases larger than 10,000 slides, a 80286 microprocessor-based microcomputer was more efficient. We are of the opinion that a system such as ours is very useful for a large department of pathology or the individual pathologist to file and retrieve 35 mm slides.

Databases, Factual↗

Megaloblastic anaemia--a review from University Hospital, Kuala Lumpur.

During a 5 year period, 28 adult patients with megaloblastic anaemia (MA) were treated in University Hospital. 71% of the patients were Indians. Symptoms of anaemia was the main presenting complaint in 18 (64%) of patients while in 2 patients peripheral neuropathy was the main problem. Pancytopenia was a common finding (present in 18 (64%) patients) while 6 (21%) patients had severe thrombocytopenia (less than 20 x 10(9)/L). The peripheral blood morphology provided important diagnostic clues i.e. macrocytes and/or hypersegmented neutrophils seen in most patients. Concurrent iron deficiency 'dampened' the megaloblastic picture. Though most patients suffered from MA of nutritional origin, 3 patients were diagnosed to have pernicious anaemia and 2 patients had myelodysplastic syndrome. Important practice points were detection of concurrent infection and hypokalemia which necessitated appropriate treatment. The controversy of blood transfusion in treatment of MA and the importance of reassessing patients after treatment were highlighted.

Anemia, Macrocytic↗

Referential communication skill levels of moderately mentally retarded adolescents.

Referential communication skills of moderately mentally retarded adolescents (20 speaker-listener dyads) were investigated. In Study 1, subject performance on referential communication activities divided into three skill levels requiring sampling, comparison, and critical-features analysis was examined. Degree of idiosyncratic messages communicated by retarded speakers was investigated in Study 2. Listening competence of retarded and adult listeners was compared in Study 3. Retarded subjects did consistently better on referential communication tasks requiring only sampling than on tasks requiring comparison or critical analysis. Referential communication messages provided by retarded speakers did not have greater meaning to themselves than to others. Finally, retarded listeners and adult listeners did not differ significantly in their ability to utilize the information given by retarded speakers. Implications of the findings for the study of the social communications of retarded children were discussed.

Adolescent↗

Taking the role of retarded children: effects of familiarity and similarity.

As a first step in improving social relations between nonhandicapped and retarded children, this study was designed to investigate children's ability to take a retarded child's role and the effects of two variables on this ability: (a) familiarity with the characteristics of retarded children and (b) similarity of experiences to those of retarded youngsters. Findings were interpreted as indicating that children's ability to take the perspective of retarded children may be a productive area for further research.

Child↗