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Biomedical subjects

C Y Lo

Publications and source records attributed to C Y Lo.

11 recordsLinked to original sources

Choice of palliation for malignant hilar biliary obstruction.

Clinical data from 50 consecutive patients with unresectable hilar tumors situated at or proximal to the common hepatic duct were retrospectively analyzed to aid in the selection of appropriate palliative measures. Thirty-four patients had cholangioenteric bypass (CEB) to either left (28 patients), right (3 patients), or both (3 patients) intrahepatic ductal systems. Sixteen patients had nonoperative drainage (NOD) established either endoscopically (4 patients), percutaneously (9 patients), or using a combined endoscopic-percutaneous approach (3 patients). When compared with patients with CEB, patients with NOD had more frequent medical problems (p less than 0.03) and lower serum albumin levels on admission (p less than 0.03). While comparable postprocedural complications (13 CEB patients versus 4 NOD patients) were observed, patients with NOD had a significantly higher hospital mortality (9 CEB patients versus 9 NOD patients, p less than 0.05). Excluding the 12 patients (6 CEB patients versus 6 NOD patients) who died within 30 days after drainage, the quality of survival of the remaining 38 patients was analyzed with reference to 6 objective parameters. Although patients with NOD had significantly more frequent admissions relating to their catheters (p less than 0.02), there was no qualitative difference in the survival rate between the two groups of patients. For selected high-risk patients with limited life expectancy, NOD should be offered. However, additional prospective studies are required to decide the best choice of palliation for patients who are not at such high risk.

Aged

Surgery for malignant obstructive jaundice: analysis of mortality.

Surgery on patients with malignant obstructive jaundice carries formidable morbidity and mortality rates. Clinical records of 120 consecutive patients who had a serum total bilirubin levels of 100 mumol/L or greater before exploration were analyzed retrospectively to provide guidelines for better management. Although most patients underwent bilienteric bypass to either the extrahepatic (n = 45) or intrahepatic ductal system (n = 28), resection was possible in 32 (26.7%). Complications developed in 42 patients (35%), among whome 12 (10%) required reexploration and 32 (26.7%) died within the same hospitalization. Identification of risk factors associated with hospital deaths after surgery was conducted on 84 of the 120 (group A) patients randomly selected from the entire study period. Based on multivariate analysis, age greater than 65 years, a raised serum aspartate transaminase value greater than 90 IU, and serum urea level greater than 7 mmol/L before surgery were the risk factors selected from 39 different clinical (n = 6), laboratory (n = 26), and operative (n = 7) parameters studied. The predictive value was validated in the remaining 36 patients (group B), and a high-risk patient population had been isolated. Because both serum urea and aspartate transaminase values correlated significantly with the necessity of urgent exploration, aggressive nonoperative treatment should be used to control the emergency. Alternative therapeutic options or perioperative management should be considered for the selected high-risk patients before definitive surgical biliary decompression.

Adult

A new enzyme immunoassay specific for blastomycosis.

A highly specific enzyme immunoassay (EIA) was developed for the serodiagnosis of blastomycosis. Among the earliest sera available from eight active cases of blastomycosis, seven were reactive by EIA, three by immunodiffusion, and three by complement fixation. The one seronegative case was associated with acquired immunodeficiency syndrome (AIDS). No cross-reaction was observed with sera from 12 patients with active histoplasmosis or from five patients with active coccidioidomycosis or from 23 healthy persons. In contrast, all patients' sera cross-reacted in conventional EIAs based on commercial immunodiffusion antigens. The blastomycosis-specific EIA seems to offer sensitivity without compromising specificity. Rheumatoid factors, which could cause false-positive reactions, were controlled for.

Antigens, Fungal

Hyperproliferation of conjunctival fibroblasts from patients with cicatricial pemphigoid.

The characteristic conjunctival scarring in cicatricial pemphigoid is a consequence of subepithelial fibrosis. The fibroblast is the cellular element responsible for fibrosis. To increase the understanding of the pathogenesis of abnormal fibrosis in cicatricial pemphigoid, the growth characteristics of conjunctival fibroblasts, from untreated patients with cicatricial pemphigoid (n = 9) and normal controls (n = 6), were studied in tissue culture. The latent period until fibroblast outgrowth began from the conjunctival explant was determined, as were the plating efficiency and doubling time of cells from first-passage cultures. Outgrowths of fibroblasts from patients with cicatricial pemphigoid appeared significantly sooner than from controls, 8.1 +/- 3.8 vs 19.3 +/- 6.4 (mean +/- SD) days. While there was no significant difference in the plating efficiency between fibroblasts from cicatricial pemphigoid (mean +/- SD, 116.4% +/- 44.6%) and those from controls (71.0% +/- 39.4%), the doubling time was significantly faster for cicatricial pemphigoid than for controls, 26.5 +/- 8.5 vs 50.7 +/- 7.8 hours. Thus, conjunctival fibroblasts from patients with cicatricial pemphigoid are hyperproliferative in tissue culture when compared with normal controls. Therefore, scarring, which characterizes cicatricial pemphigoid, may be due, in part, to excessive fibroblast proliferation.

Aged

Predictive values.

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Bayes Theorem

An assessment of urease-based enzyme-linked immunosorbent assay.

The use of urease in enzyme-linked immunosorbent assays (ELISAs) offers the advantages of convenience and safety. However, urease-based ELISA, performed in standard microtitre format, could result in false positive reactions upon prolonged incubation. False positive reactions appeared when wells containing substrate solution absorbed ammonia liberated from a reactive well nearby. Thus, the intensity of the false reaction was proportional to that of the urease reaction. The transfer of ammonia was demonstrated by pyrolysis-mass spectrometry. When urease conjugates were compared with peroxidase conjugates in the detection of IgG and IgM, there was no evidence that one enzyme was superior to the other in terms of increasing the sensitivity or the speed of ELISA.

Ammonia

Separation and identification of triglycerides, cholesteryl esters, cholesterol, 7-dehydrocholesterol, dolichol, ubiquinone, alpha-tocopherol, and retinol by high performance liquid chromatography with a diode array detector.

A simple isocratic high performance liquid chromatography (HPLC) system is described that allows separation and identification of cholesteryl esters, triglycerides, ubiquinone, alpha-tocopherol, dolichol, cholesterol, 7-dehydrocholesterol, and retinol. This consisted of a normal phase cyanopropyl column with 0.1% isopropanol in heptane as the solvent. The effluent was monitored with an LKB model 2140 diode array detector which enabled the lipids to be identified by their characteristic absorption spectra. This system was applied to a sample of dog liver in which cholesteryl esters, retinyl esters, triglycerides, ubiquinone, dolichol, cholesterol, and retinol were identified. Retinyl esters and vitamin D esters were identified by their similarity in absorption spectra to retinol and vitamin D. A system to transfer and store the chromatograms on the VAX PDP-11 or an optical disc is also described.

Cholesterol

Brain and optic system pathology in hypocholesterolemic dogs treated with a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The cholesterol lowering compound lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34 HMG CoA reductase), was given in nine separate experiments to normocholesterolemic dogs at rates up to 180 times the maximum therapeutic dose in man (1 mg/kg/day). Mean serum total cholesterol concentrations were reduced as much as 88% below normal. Clinical evidence of neurotoxicity occurred in up to 37% of animals given 180 mg/kg/day lovastatin for 11 or more days, especially in one laboratory where the dosing regime resulted in higher concentrations of plasma drug levels. Dogs receiving 60 mg/kg/day or less never exhibited neurologic signs. The central nervous system (CNS) of affected dogs exhibited endothelial degeneration and hemorrhagic encephalopathy. Focal extravasation of horseradish peroxidase occurred frequently (6/8) in the retrolaminar optic nerve of asymptomatic or clinically affected dogs given 180 mg/kg/day lovastatin, with endothelial degeneration and discrete optic nerve degenerative lesions interpreted as ischemic. The association between the degree of hypocholesterolemia and occurrence of clinical signs was not exact. Total brain cholesterol was similar in treated and control dogs. Hypocholesterolemic dogs had proportionally lowered serum concentrations of alpha-tocopherol, but oral supplementation of this vitamin did not prevent the neurologic syndrome. Endothelial degeneration in the CNS and optic nerve may have reflected in vitro morphologic effects of HMG CoA reductase inhibitors due to extreme inhibition of nonsterol isoprene synthesis. Retinogeniculate axonal (Wallerian-like) degeneration occurred in greater than or equal to 12% of dogs given 60 mg/kg/day or more lovastatin, with central chromatolysis of occasional retinal ganglion cells. These neuroaxonal changes may have been secondary to vascular effects, but superimposed direct neurotoxic action at the high dosage levels of lovastatin could not be excluded. There was no evidence of drug induced adverse effects in the CNS of dogs given up to 30 mg/kg/day lovastatin for 2 years.

Animals

Inhibition of hydroxymethylglutaryl-coenzyme A synthase by L-659,699.

A beta-lactone isolated from Fusarium sp. has been shown to be a potent specific inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase [(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating), EC, 4.1.3.5] from rat liver. The structure of this beta-lactone, termed L-659,699, is (E,E)-11-[3-(hydroxy-methyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4 - undecadienenoic acid. A partially purified preparation of cytoplasmic HMG-CoA synthase from rat liver was inhibited by L-659,699 with an IC50 of 0.12 microM. The enzyme HMG-CoA reductase, beta-ketoacyl-CoA thiolase, acetoacetyl-CoA synthetase, and fatty acid synthase were not inhibited to any extent by this compound. In cultured Hep G2 cells, the compound inhibited the incorporation of [14C]acetate into sterols with an IC50 of 6 microM, while incorporation of [3H]mevalonate into sterols in these cells was not affected. The activity of HMG-CoA reductase in the cultured Hep G2 cells was induced in a dose-dependent manner by incubation with L-659,699. A 37-fold increase in reductase was observed after a 24-hr incubation with 62 microM L-659,699. The effect of a number of analogs of L-659,699 on HMG-CoA synthase is also discussed.

Animals

Immunologic evidence that staphylococcal alpha toxin is oriented on membranes.

Antibodies to staphylococcal alpha toxin were separated into two distinct populations. One population prevented binding of alpha toxin onto erythrocyte membranes. The other population neutralized after the toxin was bound onto erythrocytes and thereby brought about an indirect hemagglutination reaction. The data suggest that alpha toxin has a membrane-binding region.

Animals