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Biomedical subjects

S C Chan

Publications and source records attributed to S C Chan.

At least 109 records · Page 6Linked to original sources

Detection of toluenediamines in the urine of a patient with polyurethane-covered breast implants.

Breast prostheses are implanted for augmentation or during reconstructive surgery. One of the more commonly used prostheses is the polyurethane-sponge-covered silicone gel implant. Some clinicians are concerned about the safety of this product because the polyurethane foam disintegrates in vivo, and its subsequent fate is not known. Polyurethane is a polymer formed by reacting diisocyanates and polyols. This study indicates that the polymer sponge breaks down into its reactive monomers, 2,4- and 2,6-toluenediisocyanate, which are converted into their corresponding diamines. We present evidence of the excretion of the diamine metabolites in the urine of a patient implanted with polyurethane-covered prostheses.

Adult↗

Pitfalls of percutaneous-endoscopic biliary stent placement.

Percutaneously inserted transhepatic guide wire improves the success rate of endoscopic biliary stenting. However, we have encountered several pitfalls with this approach. In one patient, as a result of the stability provided by the transhepatic guide wire, the stent was pushed excessively into the liver parenchyma. In another patient, the proximal end of the stent was embedded in liver parenchyma in the lateral view during fluoroscopy, despite apparently good positioning in the anteroposterior view. Avoidance of central puncture during establishment of percutaneous transhepatic biliary drainage and checking two planes with fluoroscopy may help to reduce this risk. Close attention to these potential technical pitfalls would further improve the success rate of endoscopic biliary stenting.

Biliary Tract↗

Pattern of anti-asthmatic drug utilization in Hong Kong compared to other parts of the world.

Inhaled drugs are now considered first line agents for the treatment of asthma, whereas oral beta-agonists, theophylline and its derivatives have been relegated to a secondary role. To determine whether current prescribing in Hong Kong conforms to these recommendations, we have evaluated anti-asthmatic drug utilization in the territory as reflected by 1984-86 drug sales (courtesy Medical and Health Department, Hong Kong). Sales/prescription statistics were also obtained from corresponding agencies of other governments and from published literature. If appropriate, data for comparison was expressed as defined daily doses (DDDs) per 1000 inhabitants per day. In contrast to the pattern of utilization in several developed nations, in Hong Kong (a) oral anti-asthmatic agents (particularly beta agonists) were more commonly utilized than inhaled drugs, and (b) inhaled therapy mainly consisted of non-selective beta-agonists, steroids being very rare. Further education is required to improve anti-asthmatic drug utilization patterns in the community.

Asthma↗

Cephalosporin and aminoglycoside utilization in different parts of the world.

Cephalosporin and aminoglycoside utilization in Hong Kong during 1984, 1985 and 1986, were evaluated from wholesale data and compared with corresponding Swedish statistics and with UK data from a survey of non-hospital prescriptions. Details regarding each drug and category were collated, adjusted for population and if appropriate expressed as defined daily doses (DDDs)/1000 inhabitants/day. With respect to cephalosporins: (a) overall sales (especially those of the newer and more expensive parenteral drugs) were increasing; (b) parenteral sales were much larger in Hong Kong hospitals than in the community (up to about 106 versus 16 kg/million inhabitants/year respectively), but in Sweden they were comparable (up to about 38 and 41 kg/million inhabitants/year respectively); (c) non-hospital oral utilization appeared greater in the UK than in Sweden and Hong Kong (up to about 0.7, 0.4 and 0.4 DDDs/1000 inhabitants/day respectively); (d) oral sales to hospitals were greater in Hong Kong than Sweden (up to 0.3 compared to 0.1 DDDs/1000 inhabitants/day respectively) and (e) oral paediatric formulations (liquids) were most popular in Hong Kong, a higher proportion of children in Hong Kong being one possible reason. Non-hospital sales of gentamicin and kanamycin in Hong Kong were much greater than in Sweden (up to about 0.20 and 0.06 vs. 0.01 and 0.00 DDDs/1000 inhabitants/day respectively), whereas UK utilization appeared almost non-existent. Topical neomycin sales in Hong Kong were much more popular than in Sweden (up to about 60 vs. 9 g/million inhabitants/day). These regional differences in antibiotic utilization may be related to respective health care systems (and thus the affordability and availability of drugs) and prescribing preferences (cultural and/or promoted by drug companies), quite apart from possible differences in drug efficacy, drug tolerance and the prevalence and severity of various infections.

Aminoglycosides↗

The modes of binding of ligands to cardiac muscarinic receptors.

Ionizable groups on the cardiac M2 muscarinic receptor which regulate the binding of ligands have been examined by studying the pH dependence of the ligand affinity constants. The presence of three titratable residues (approximate pK values, 5.4, 6.8 and 7.5) whose protonation modulates antagonist binding has been demonstrated. Cardioselective antagonists are selectively affected by the protonation state of the pK 6.8 residue, whereas the binding of antagonists having differing selectivities is more strongly affected by protonation of the pK 5.4 residue on cardiac receptors. Methoctramine is capable of binding to both the pK 5.4 and 6.8 residues simultaneously. Protonation of the residue of highest pK produces a conformational change at the receptor which can affect both agonist and antagonist binding. It is now possible to demonstrate differences both in the way ligands bind to a given receptor subtype and in the way a given ligand binds to different subtypes.

Animals↗

Portal thrombosis complicating appendicitis: ultrasound detection and hepatic computed tomography lobar attenuation alteration.

Lobar attenuation difference of liver on computed tomography was seen in a case of portal pyemia complicating perforated appendicitis. Left portal vein thrombus was detected first by ultrasound and subsequently confirmed by computed tomography. The left lobe of the liver showed greater contrast enhancement during the dynamic computed tomography study. The possible cause of this lobar attenuation difference is discussed.

Adult↗

Altered leukocyte protein kinase activity in atopic dermatitis.

Previous studies have demonstrated elevated cyclic-AMP-specific phosphodiesterase (PDE) activity in mononuclear leukocytes (MNL) from patients with atopic dermatitis (AD). We questioned whether increased kinase activation could account for this observation. In these studies, we measured abnormally lower basal calcium/phospholipid-dependent protein kinase (PK-C) phosphorylation in MNL from patients with AD. Basal cAMP-dependent protein kinase (PK-A) phosphorylation was concomitantly higher in MNL from patients with AD. These results are in agreement with earlier reports that PK-A activity may have a negative influence on PK-C activity in certain cell systems. Stimulation with the H1-histamine agonist, thiazolylethylamine (TEA), of MNL from normal donors but not patients with AD, resulted in statistically significant increases in PK-C phosphorylation. This implies receptor down regulation or functional desensitization in AD cells. Altered basal protein kinase phosphorylation and abnormal response to selective histamine agonists seen in MNL from patients with AD could explain elevated PDE activity.

Dermatitis, Atopic↗

[Two cases of persistent trigeminal artery variant].

Two cases of persistent trigeminal artery variant were found in 2000 cases who had examination of cerebral angiography in our hospital from 1975 to 1986. The first case was a 44-year-old female who admitted in our hospital for the examination of vertigo. Cerebral angiography demonstrated a superior cerebellar artery originating from the precavernous portion of the right internal carotid artery. The second case was a 67-year-old female who admitted in our hospital for the treatment of subarachnoid hemorrhage. Cerebral angiography demonstrated an anterior inferior cerebellar artery originating from the precavernous portion of the right internal carotid artery. In this case, a fusiform aneurysm was found in the origin of the persistent trigeminal artery variant. The ruptured aneurysm was thought to be a basilar artery aneurysm.

Adult↗

Frequency of "blue bodies" in pulmonary cytology specimens.

To determine the frequency of occurrence of "blue bodies" (BBs), 2,010 pulmonary cytology specimens (1,403 sputum and 607 bronchial specimens) from 1985 were reviewed. The smears were examined microscopically by transmitted and polarized light. BBs were extracellular structures, occurring most commonly in clusters but sometimes conglomerated. With Papanicolaou stain, they had a characteristic birefringent laminated brown core and a nonbirefringent blue rim. Chemical microanalysis and energy-dispersive x-ray analysis revealed that their chemical composition was calcium carbonate. A total of 233 specimens contained BBs, with a frequency of 10.5% in bronchial specimens and 12% in sputum. Only 8.6% of the BBs had co-existent pulmonary malignancy. We concluded that BBs were common structures in pulmonary cytology and were not associated with pulmonary malignancy or pulmonary fibrosis in our series. They must be distinguished from contaminants, staining artifacts, and parasitic ova.

Adolescent↗

Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes.

We have previously reported histamine desensitization of human blood mononuclear leukocytes resulting in reduced cAMP responses to beta-adrenergic agonists, histamine and prostaglandin E1. This heterologous desensitization occurred at low, micromolar histamine concentrations and was accompanied by elevation of cAMP-phosphodiesterase (PDE) activity in these cells. We have now investigated the activity of PDE in the lymphocyte and monocyte fractions of mononuclear leukocytes to determine the site of histamine effect. PDE activity per cell was higher in monocytes (0.075 +/- 0.070 units) than lymphocytes (0.026 +/- 0.08) units). Monocytes responded to 10(-6) M histamine stimulation with a much greater increase in PDE activity (0.354 +/- 0.1 units) than did lymphocytes (0.047 +/- 0.015 units). Histamine receptor studies, using thiazolylethylamine and chlorpheniramine as H1-agonist and antagonist respectively and dimaprit and cimetidine as H2-agonists and antagonists respectively, indicated that the histamine stimulation of PDE activity is mediated predominantly through H1 histamine receptor in the monocytes and the H1 receptor in the lymphocytes. Previously histamine had been thought to increase cyclic AMP by acting on H2 receptors to activate adenylate cyclase. Our studies show that stimulation of H1 or H2 receptors by low histamine concentration can cause the opposite effect i.e. increased catabolism and a net reduction in cAMP levels. The localization of this effect predominantly to monocytes indicates a potentially important mechanism for histamine action on immune regulation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Elevated mononuclear leukocyte phosphodiesterase in allergic dogs with and without airway hyperresponsiveness.

To investigate if mononuclear leukocyte beta-adrenergic hyporesponsiveness of Basenji greyhound (BG) dogs is associated with atopy or nonspecific airway hyperresponsiveness, we examined the relationship between mononuclear leukocyte cAMP phosphodiesterase levels, airway responsiveness to methacholine, and intradermal allergen responses in 17 BG dogs, five unrelated purebred Basenjis, and five greyhounds. BG dogs were hyperresponsive to aerosols of methacholine compared to Basenjis and greyhounds. Both BG dogs and Basenjis were allergic and had increased leukocyte cAMP phosphodiesterase activity compared to greyhounds. We concluded that the leukocyte abnormality is not associated with airway hyperresponsiveness. The leukocyte abnormality is either associated with the allergic state, with some hereditary trait that BG dogs acquired from the Basenji ancestry, or the leukocyte abnormality is necessary but not sufficient for the development of airway hyperresponsiveness.

3',5'-Cyclic-AMP Phosphodiesterases↗

Non-Hodgkin's lymphoma as a cause of hypoadrenalism.

Non-Hodgkin's lymphoma which presents as adrenocortical insufficiency is rare, however, it should be a well-recognised entity because, in addition to specific chemotherapy or radiotherapy, it needs hormonal replacement. We report a patient with diffuse histiocytic lymphoma, who had remission for seven years and relapsed with Addisonian crisis.

Adrenal Gland Neoplasms↗

Cyclic nucleotide function in trachealis muscle of dogs with and without airway hyperresponsiveness.

We examined basal adenosine 3',5'-cyclic monophosphate (cAMP) levels, isoproterenol (ISO)-stimulated cAMP responses, basal cAMP, and guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase (PDE) activities and protein-kinase (PK) activities in trachealis muscle from five Basenji-greyhound (BG) and four greyhound dogs to determine whether the inverse relationship between in vivo and in vitro airway responsiveness could be due to altered cyclic nucleotide metabolism. Basal cAMP levels were not significantly different (PNS) in muscle from BG (11.6 +/- 0.53 pmol/mg protein) and greyhound dogs (10.30 +/- 1.60 pmol/mg protein). The cAMP responses to stimulation with ISO were enhanced in BG compared with greyhound dogs. The low Michaelis constant (1) for Km-cAMP PDE activity (Km = 0.63 microM) was significantly less (P less than 0.005) in BG dogs (1.54 +/- 0.28 pmol.min-1.mg protein-1) than greyhounds (11.76 +/- 2.48). Endogenously active PK activity was significantly greater (P less than 0.005) in BG (54.74 +/- 5.39 pmol.min-1.mg protein-1) than in greyhound dogs (15.50 +/0 2.20). Increases in PK activity with 5 microM cAMP added were not significantly different between BG (14.79 +/- 6.00) and greyhound dogs (7.04 +/- 2.14). Approximately 90% of both endogenous PK activity and cAMP-activated PK activity in BG and greyhound dogs was inhibited by a cAMP-dependent PK inhibitor (PKI'). These data suggest that decreased cyclic nucleotide degradation due to decreased cyclic nucleotide PDE activity with increased PK could account for the in vitro hyporesponsiveness of airway smooth muscle in BG dogs as a protective adaptive mechanism.

3',5'-Cyclic-AMP Phosphodiesterases↗

Monocyte localization of elevated cAMP phosphodiesterase activity in atopic dermatitis.

Patients with atopic dermatitis (AD) manifest a number of immune abnormalities which correlate with in vitro defects including lymphocyte transformation, chemotaxis, and cytotoxicity. Past studies have shown reduced leukocyte cyclic 3',5'-adenosine monophosphate (cAMP) levels after exposure to adenylate cyclase-active agonists, and we have demonstrated that this results from increased catabolism due to elevated cAMP-phosphodiesterase activity. These results were obtained in preparations containing mixtures of lymphocytes and monocytes. In order to determine more precisely the cellular site of the defect we have separated the leukocytes into lymphocyte- and monocyte-enriched preparations using either Percoll-gradient centrifugation or adherence isolation. Both techniques yielded over 93% pure lymphocytes, whereas the former yielded 64% monocytes compared with the latter method which generated 94% pure monocytes. Atopic monocytes, obtained by either technique, consistently showed elevated phosphodiesterase activity compared with those of the nonatopic monocytes. Such differences were not evident in lymphocyte preparations from normal and atopic subjects. In spite of the increased rate of cAMP degradation in atopic leukocytes, the resting cAMP levels do not differ from those of normal subjects. We questioned whether this is caused by increased cAMP synthesis and evaluated cellular adenylate cyclase activity. We found no evidence in AD cells for an increased rate of adenylate cyclase catalysis, either basal activity or after stimulation by forskolin. Therefore, the resting cAMP levels must have been compensated by other mechanisms. Impaired cyclic nucleotide metabolism in atopic monocytes may affect a number of immunologic and inflammatory reactions and could account for many of the clinical abnormalities in atopic diseases.

3',5'-Cyclic-AMP Phosphodiesterases↗

Distribution of morphine in body fluids and tissues in fatal overdose.

Two cases of fatal overdose with morphine are presented. Large amounts of the drug were involved in both cases, one by oral ingestion, the other by intravenous injection. Morphine concentrations in various body fluids and tissues are compared to those in the literature.

Administration, Oral↗

Elevated leukocyte phosphodiesterase as a basis for depressed cyclic adenosine monophosphate responses in the Basenji greyhound dog model of asthma.

The BG dog manifests various characteristics of human asthma, including airway hyperreactivity to low concentrations of methacholine. Studies have suggested that airway hyperreactivity in asthma is related to inadequate intracellular cAMP responses. We studied cAMP characteristics in MNL from 19 BG and 14 mongrel dogs. beta-Adrenergic receptors were assessed by 125I CYP in the presence and absence of propranolol. The responses of cAMP to ISO were measured by radioimmunoassay. Adenylate cyclase activity was determined in homogenized MNL preparations by cAMP generation. PDE activity was quantitated by radioenzyme assay. Mongrel dog leukocyte ISO-stimulated cAMP levels doubled, whereas there were negligible increases in MNL from BG dogs. Basal PDE levels were higher in BG dogs than in mongrel dogs. The PDE inhibitor Ro 20-1724 restored ISO-stimulated cAMP responses in MNL of BG dogs. Adenylate cyclase activity was not lower in MNL homogenates from BG dogs than in mongrel dogs. Cells from both BG and mongrel dogs demonstrated similar receptor numbers and affinities of saturable, specific beta-adrenergic binding over a 10 pM to 400 pM range. Our results suggest that depressed cAMP responses in BG dogs are due to high PDE activity rather than to a defect in the beta-adrenergic receptor adenylate cyclase system.

Adenylyl Cyclases↗

Phosphodiesterase inhibition by Ro 20-1724 reduces hyper-IgE synthesis by atopic dermatitis cells in vitro.

Peripheral blood mononuclear leukocytes (MNL) from patients with atopic dermatitis spontaneously produce large amounts of IgE in vitro. These cells also show markedly elevated levels of cAMP phosphodiesterase (PDE) which may be responsible for the observed abnormal cAMP responsiveness. Treatment of atopic dermatitis MNL with varying concentrations of the cAMP PDE inhibitor Ro 20-1724 resulted in progressively decreasing amounts of IgE synthesis, statistically significant at the 10(-4) M and 10(-5) M concentrations. There was a close correlation between PDE inhibition and inhibition of IgE synthesis, r = 0.93, p less than 0.05. To define the cellular target of the drug, we used monoclonal antibodies directed toward MNL subsets (Lyt 3, OKT8, OKT4, monocyte-myeloid) in a modified "panning" method to perform experiments with purified subsets. With untreated subsets, removal of OKT4-positive cells significantly reduced IgE synthesis; readdition of OKT4-positive cells enhanced IgE synthesis. OKT8 cells and monocytes did not affect IgE synthesis. Pretreatment of T cell-depleted MNL with Ro 20-1724 resulted in significantly more inhibition of IgE synthesis than did pretreatment of T enriched cells prior to recombination with the reciprocal untreated subset and subsequent culture. Similarly, pretreatment of monocyte-depleted cells resulted in significantly more inhibition of IgE synthesis than pretreatment of monocyte-enriched cells prior to recombination and culture. The majority of the effect appeared to be mediated by a direct effect on the B cells. However, some inhibition of IgE synthesis was also achieved through pretreatment of T enriched cells. Since pretreatment of isolated suppressor/cytotoxic or helper/inducer T-cell subsets did not give the same degree of inhibition as with unfractionated T cells, a T-T interaction may be involved in this aspect. The imidazolidinone derivative, Ro 20-1724, significantly and consistently inhibited both the elevated cAMP phosphodiesterase activity and the elevated spontaneous IgE synthesis of MNL from patients with atopic dermatitis. These findings demonstrate a previously undescribed link between cAMP PDE levels and in vitro IgE synthesis.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗