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Biomedical subjects

S L Chan

Publications and source records attributed to S L Chan.

At least 127 records · Page 7Linked to original sources

Effects of phenoxybenzamine on insulin secretion from isolated rat islets of Langerhans.

In isolated rat islets the alpha 2-adrenergic antagonist phenoxybenzamine was found to be only partially effective at relieving the inhibition of glucose-induced insulin secretion mediated by noradrenaline. Further experiments revealed a direct inhibitory effect of phenoxybenzamine itself on the secretory response to glucose. At concentrations above 1 microM the antagonist inhibited insulin secretion in a dose-dependent manner, with greater than 50% inhibition at 50 microM. The inhibition of secretion developed rapidly in perifused islets, and was not altered when islets were also incubated with idazoxan or benextramine, suggesting that it did not reflect binding of phenoxybenzamine to the alpha 2-receptor. Paradoxically phenoxybenzamine significantly increased the basal secretion rate in the presence of 4 mM glucose. The results demonstrate that phenoxybenzamine can exert direct effects on insulin secretion which are unrelated to its alpha-antagonist properties.

Animals↗

Effects of benextramine on the adrenergic inhibition of insulin secretion in isolated rat pancreatic islets.

Insulin secretion from isolated rat islets of Langerhans in the presence of 4 mM glucose averaged 2.26 +/- 0.20 (S.E.M.) ng/islet per 90 min and was significantly (P less than 0.001; n = 30) increased to 3.28 +/- 0.21 ng/islet per 90 min by the covalent alpha-adrenoceptor antagonist benextramine (10 microM). Glucose (20 mM) also increased the secretion rate (to 6.24 +/- 6.0 ng/islet per 90 min) but, under these conditions, the response was not further enhanced by benextramine. Clonidine and noradrenaline (1 nM-10 microM) each caused dose-dependent inhibition of glucose-induced insulin secretion which was maximal at 1 microM. Benextramine, when added simultaneously with the agonist, relieved, in a dose-dependent manner, the inhibition of secretion induced by either clonidine or noradrenaline with similar sensitivity. Even after a 30-min preincubation with benextramine the antagonist failed to differentiate between noradrenaline, adrenaline and clonidine with respect to inhibition of insulin secretion. In contrast to its effects on adrenergic responses, short-term treatment with benextramine did not significantly affect muscarinic-cholinergic receptor-mediated 45Ca2+ efflux from rat islets of Langerhans perifused in Ca2+-depleted medium. These data suggest that benextramine does not differentiate between clonidine and noradrenaline in rat islets of Langerhans but that it does show preference for alpha-adrenoceptors in this tissue.

Adrenergic alpha-Antagonists↗

Fasting urinary hydroxyproline: creatinine ratios in silicosis.

Fasting urinary hydroxyproline: creatinine (HOP:C) ratios were measured in 74 patients with suspected (borderline) silicosis (10), simple silicosis (46) and complicated silicosis (9 silicotuberculosis, 4 massive fibrosis, and 5 combined silicotuberculosis and massive fibrosis) and in 18 healthy subjects (controls). There was no statistically significant difference in urinary HOP:C ratios between control subjects (mean 13.8, SD 3.6) and suspected silicotics (mean 18.0, SD 7.6); however, urinary HOP:C ratios were significantly higher in both simple silicosis (mean 25.0, SD 9.9, p less than 0.001) and complicated silicosis (silicotuberculosis and progressive massive fibrosis) (mean 28.6, SD 11.3; p less than 0.001). Urinary HOP:C ratios appeared to show a graduated increase to their highest levels in category 2 silicosis and thereafter remained constant or declined slightly in category 3 silicosis and massive fibrosis. The results support the suggestion that urinary hydroxyproline might be useful as an indicator of disease progression in established silicosis. However, further longitudinal studies are needed to confirm its predictive value.

Adult↗

High-performance liquid chromatographic method for isolating organic contaminants from tissue and sediment extracts.

Interest in the assessment of the anthropogenic contamination of the marine environment has accelerated in recent years. Existing methods to analyze environmental samples (e.g., sediments or tissues) for trace amounts of organic contaminants such as aromatic hydrocarbons and chlorinated compounds are tedious and costly. We report a rapid, efficient high-performance liquid chromatography (HPLC) procedure which uses a size-exclusion column to separate the analytes of interest from interfering compounds in the sample matrix. Analytical results from the HPLC method were, in general, comparable to a gravity-column method which had been used for several years. The HPLC method had several other advantages: improved precision; the ability to monitor chromatographic conditions; the potential for automating analyses; and reduced consumption of solvents and other materials.

Animals↗

Total skin electron irradiation for mycosis fungoides: relationship between acute toxicities and measured dose at different anatomic sites.

From June 1978 to June 1986, 50 patients with primary and recurrent mycosis fungoides were treated with total skin electron irradiation (TSEI), using the Stanford technique, to a total dose of 3600 cGy. TSEI was used alone, or in combination with low dose total body photon irradiation, or MOPP. Thermoluminescent dosimeter (TLD) measurements of the prescribed skin dose were obtained on twenty patients. The dorsum of the foot was 24% higher. The axillae, the bottom, and the arch of the foot were significantly underdosed. Frequencies of acute toxicities noted at 2000 cGy were: Skin, Grade I-II (RTOG) 80%. Partial epilation: scalp, 100%; eyebrows and at eyelashes, 20%. Nail dystrophy, 48%. Edema: hands and feet, 44%. Bullae: dorsum of feet, 8%; hands, 4%; and 3600 cGy: Skin, grade III 22%. Total epilation: scalp, 66%; eyebrows and eyelashes, 56%. Nail loss, 38%. Edema: hands and feet, 76%. Bullae: dorsum of feet, 34%; hands, 12%. Conjunctivitis, 4%. Large bullae, were more significant on the dorsum of the feet. Severe moist desquamation occurred in eight patients who had ulcerated lesions on initial presentation. Three patients were hospitalized due to ulceration and skin infection. All patients completed treatment after a short to moderate break. No patient developed skin necrosis, or corneal ulceration. No correlation exists between dose level, degree and onset of toxicity with previous chemotherapy or TBI. We conclude that the overall toxicity of TSEI is well tolerated.

Female↗

The importance of genetics for the optimization of radiation therapy. A hypothesis.

There is growing evidence that a fraction of cancer patients, perhaps as high as 15%, is radiation sensitive because of the action of specific genes. It seems likely that in the near future we shall be able to identify these patients by DNA probes. Therefore, we have calculated the impact on radiation therapy of removing these patients and treating the rest more aggressively. In particular, we assumed that the radiation oncologist will treat with an effective therapeutic dose corresponding to a 5% risk of serious normal tissue injury. Our results, in several instances, show a considerable increase in local control when the 5, 10, or 15% of the most radiosensitive patients are removed from the treated group. This is so, even if we assume that the tumor cells, as well as the normal cells, in radiosensitive patients are more radiosensitive than the tumor cells in patients of normal radiosensitivity.

Female↗

Benefits of dual chamber pacing in sick sinus syndrome.

The effects of DDD (fully automatic) and VVI (ventricular demand) pacing modes on exercise tolerance, symptom diary cards, and Holter monitoring were investigated in a randomised double blind crossover study of 16 patients who had had DDD pacemakers implanted because of frequent syncope. Eight patients presented with sick sinus syndrome and, with one exception, retrograde atrioventricular conduction and eight age and sex matched patients presented with 2:1 or complete atrioventricular block. Maximal symptom limited exercise in those with atrioventricular block was significantly higher after one month of DDD pacing than after VVI pacing. In those with sick sinus syndrome, however, maximal effort tolerance was not significantly different for the two pacing modes. In all but one patient with sick sinus syndrome sinus rhythm developed during exercise in VVI pacing. For both VVI and DDD modes maximal atrial rates were significantly lower in those with sick sinus syndrome. Palpitation and general wellbeing were significantly improved during DDD pacing in the eight patients with sick sinus syndrome. Shortness of breath was improved by DDD pacing in the eight patients with atrioventricular block but not in those with sick sinus syndrome. Holter monitoring showed that sick sinus syndrome patients remained in paced rhythm, either DDD or VVI, for most of the 24 hour period. DDD pacing was better than VVI pacing in sick sinus syndrome with retrograde atrioventricular conduction. Despite their ability to show sinus rhythm and inhibit their pacemakers on exercise patients with sick sinus syndrome are just as likely to have symptomatic benefit from DDD pacing as patients with atrioventricular block.

Adult↗

HLA typing in the Hong Kong Chest Service/British Medical Research Council study of factors associated with the breakdown to active tuberculosis of inactive pulmonary lesions.

As part of a multifactorial study of the causes of breakdown to active tuberculosis of inactive pulmonary lesions, HLA-A, -B, and -DR typing was performed on 256 Hong Kong Chinese patients and 100 healthy control subjects. Patients were classified into those with smear-positive, active pulmonary tuberculosis (n = 103), those with inactive disease (n = 113), and those with breakdown to active disease after 6 months or more of inactivity (n = 40). Separately, 21 multiple-case families comprising 38 available parents and 93 offspring were examined for HLA haplotype segregation in relation to infection. Results of both studies indicate that among Hong Kong Chinese there is no statistically significant association between HLA and susceptibility to pulmonary tuberculosis.

Adolescent↗

Radiological progression and lung function in silicosis: a ten year follow up study.

Chest radiographs and spirometric tests were performed on 81 patients who had silicosis from two granite quarries in 1975, 73 of whom were followed up for two to 10 (mean 7.2) years. Each patient's initial and most recent chest radiographs were assessed independently by three experienced readers, and the yearly declines in forced expiratory volume in one second and forced vital capacity were estimated from two to four (mean 3.45) serial spirometric readings. Estimates of individual dust exposure were based on extensive historical data on hygiene. All but 11 patients were no longer exposed to dust by the start of follow up, but 24 (45%) of 53 patients who had simple silicosis and 11 (55%) of 20 who had the complicated disease showed radiological evidence of disease progression. In patients who had simple silicosis and showed no radiological progression the yearly declines in forced expiratory volume in one second and forced vital capacity were modest (64 ml/year and 59 ml/year, respectively), whereas significantly greater declines in lung function were seen in those who showed radiological evidence of progression (97 ml/year and 95 ml/year, respectively). In addition to radiological progression the previous average dust concentration to which patients had been exposed also influenced declines in both forced expiratory volume in one second and forced vital capacity after allowing for the effects of age, smoking, duration of exposure, history of tuberculosis, initial state of disease, and baseline lung function. The probability of radiological progression was most strongly influenced by the average dust concentration previously exposed to. The progression of simple silicosis is thus accompanied by appreciable declines in lung function and is strongly affected by previous levels of exposure to dust.

Dust↗

A survey of the respiratory health of silica-exposed gemstone workers in Hong Kong.

Respiratory symptoms and radiographic and lung function alterations were studied in a cross-sectional survey of gemstone workers in Hong Kong. The study population included a group of grinders, polishers, and buffers who were heavily exposed to dust (principally free silica) and a less exposed group of cutters and carvers. Among all 218 male workers who answered the respiratory questionnaire, heavily exposed workers reported significantly higher prevalence of respiratory symptoms suggestive of mucus hypersecretion. Radiological pneumoconiosis defined as opacities with profusion of 1/0 and above was found in 27% of 157 workers who accepted radiographic and lung function examination. Radiological opacities were significantly related to increasing years of employment in both groups of workers after taking into account age and smoking habits. Decline in forced vital capacity (FVC) was significantly related to increasing years of employment in both groups after allowing for the effects of age, height, and smoking. A modest decline in forced expiratory volume in one second (FEV1) was related to dust exposure which was of borderline statistical significance in polishers and buffers who smoked. Radiological pneumoconiosis did not have an independent effect on lung function when allowance was made for dust exposure.

Adult↗

Field and laboratory studies of the etiology of liver neoplasms in marine fish from Puget Sound.

A series of field studies was conducted between 1979 and 1985 in Puget Sound, Washington State, to investigate etiological relationships between prevalences of hepatic neoplasms in bottom-dwelling marine fish species, with emphasis on English sole (Parophrys vetulus), and concentrations of toxic chemicals in sediments and affected fish. Statistically significant (p less than or equal to 0.05) correlations have been found between the prevalences of hepatic neoplasms in English sole and the following parameters: sediment concentrations of aromatic hydrocarbons, and concentrations of the metabolites of aromatic compounds in the bile of affected sole. A significant difference (p less than 0.001) was also found between the relative concentrations of aromatic free radicals in the liver microsomes of English sole with liver lesions compared to sole without liver lesions. Laboratory studies designed to evaluate the etiology of the liver neoplasms in English sole have also yielded evidence that is consistent with the view that high molecular weight aromatic hydrocarbons, e.g., benzo[a]pyrene (BaP), are hepatocarcinogens in English sole. The current status of a series of long-term (up to 18 months) exposures of English sole and rainbow trout (Salmo gairdneri) to selected fractions of Puget Sound sediment extracts, enriched with aromatic hydrocarbons and nitrogen-containing aromatic compounds, and to individual carcinogens (e.g., BaP) is discussed.

Animals↗

The bioavailability of isoniazid, rifampin, and pyrazinamide in two commercially available combined formulations designed for use in the short-course treatment of tuberculosis.

The bioavailability of isoniazid, rifampin, and pyrazinamide in 2 combined formulations of the 3 drugs (Rifater) for use primarily in the short-course chemotherapy of tuberculosis has been studied in Chinese patients in Singapore and Hong Kong. One formulation, containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet is suitable for daily use, whereas the other, containing higher proportions of isoniazid and pyrazinamide, is designed for intermittent treatment, each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide. Appropriate dosages for the Chinese patients, whose average weight was approximately 50 kg, were 5 and 6 tablets, respectively. Plasma concentrations of the 3 drugs after giving such dosages of the 2 combined formulations were compared in 16 patients, 8 in Singapore and 8 in Hong Kong, by means of a crossover study, with the concentrations obtained when identical doses of the 3 drugs were given using standard separate drug formulations. The concomitant urinary excretions of the drugs and their major metabolites were also estimated. Very similar results were obtained whether the drugs were given as the combined preparations or in their standard separate formulations, demonstrating the excellent bioavailability of all 3 drugs in each of the 2 combined formulations.

Acetylation↗

Toxic chemicals in sediments and biota from a creosote-polluted harbor: relationships with hepatic neoplasms and other hepatic lesions in English sole (Parophrys vetulus).

High prevalences of idiopathic hepatic lesions, including neoplasms (e.g., hepatocellular carcinomas, cholangiocellular carcinomas) (27%, 20 of 75 fish) and foci of cellular alteration (putative 'preneoplastic' lesions) (44%, 33 of 75 fish), were found in English sole (Parophrys vetulus) exposed to creosote-contaminated sediments in Eagle Harbor, Puget Sound, WA. Sediments from the contaminated region of the harbor contained particularly high concentrations of aromatic hydrocarbons (e.g., benzo[a]pyrene and benz[a]anthracene), and a variety of nitrogen-containing aromatic compounds (e.g., carbazole and acridine). The composition of the aromatic compounds was characteristic of creosote. Dramatically lower concentrations of aromatic compounds were found in sediments from a reference site in which the bottom-dwelling fish examined were free of detectable neoplastic or 'preneoplastic' hepatic lesions. Food organisms in the stomachs of the English sole from Eagle Harbor contained substantially higher concentrations of aromatic hydrocarbons than comparable organisms from the reference site. The concentrations of individual aromatic hydrocarbons in muscle and liver from the Eagle Harbor fish were low; however, high concentrations of metabolites of aromatic compounds were present in the bile. The findings strongly suggest an association between exposure to creosote and the prevalence of hepatic lesions, including neoplasms, in the bottom-dwelling fish, and furthermore support the putative role of aromatic hydrocarbons in liver carcinogenesis in fish.

Animals↗

Toxic chemicals in marine sediment and biota from Mukilteo, Washington: relationships with hepatic neoplasms and other hepatic lesions in English sole (Parophrys vetulus).

High prevalences of idiopathic liver lesions, including 7.5% hepatic neoplasms (e.g., hepatocellular and cholangiocellular carcinomas) and 16.7% foci of cellular alteration (putative preneoplastic hepatic lesions), were found in English sole (Parophrys vetulus) from waters near Mukilteo, a small community on Puget Sound in Washington State. Sediments from the sampling sites contained particularly high concentrations of aromatic hydrocarbons. Substantially lower concentrations of these compounds were found in sediments from another Puget Sound (reference) site in which fish showed no evidence of hepatic neoplasms or foci of cellular alteration. Stomach contents from the fish at Mukilteo contained substantially higher concentrations of the chemicals than did stomach contents of fish from the relatively uncontaminated site. High concentrations of metabolites of aromatic compounds were measured in the bile of fish from Mukilteo. These findings support previously observed relationships between sediment chemicals (e.g., aromatic hydrocarbons) and high prevalences of liver lesions in English sole from Puget Sound. In addition, a dietary route of uptake by English sole of environmental chemicals, including known carcinogens, was documented.

Animals↗