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Biomedical subjects

E Holland

Publications and source records attributed to E Holland.

27 records · Page 2Linked to original sources

Effect of diuretics on allergen-induced contractions of passively sensitized human bronchi in vitro.

Inhaled furosemide has been shown to protect subjects with asthma from bronchoconstriction induced by a wide variety of stimuli, including allergen, but the mechanism of action is controversial. We have used an in vitro model of allergen-induced bronchoconstriction to examine the effects of furosemide and other ion transport inhibitors. Human bronchial rings were passively sensitized by incubation with serum from an atopic donor and were challenged with Dermatophagoides pteronyssinus. Allergen-challenged bronchial rings developed bronchoconstriction which was effectively inhibited by the cysteinyl-leukotriene antagonist ICI 198,615 (10(-7) M) and to a lesser extent by terfenadine (10(-5) M). Assessed over 60 min furosemide 10(-6), 10(-5), and 10(-4) M inhibited contractions by a mean (95% confidence interval [CI]) 7.9% (-23.5, 39.3%, p > 0.05), 44.2% (12.9, 75.2%, p < 0.01), and 86.9% (55.5, 118.3%, p < 0.001) respectively (n = 5). The same concentrations of bumetanide inhibited contractions by 21.5% (-8.4, 51.4%, p > 0.05), 13.6% (-16.3, 43.4%, p > 0.05) and 51.6% (21.7, 81.4%, p < 0.01) respectively (n = 5). The sodium transport inhibitor amiloride and the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) were without effect (both 10(-4) M; n = 4). Furosemide increased PGE2 production by the bronchial rings by 134% (95% CI 53, 259%). Indomethacin (3 x 10(-6) M) blocked the furosemide-induced increase in PGE2 production and reduced the protection afforded by 10(-4) M furosemide against allergen-induced contractions from 67.9% to 34.7% (mean difference 33.2%; 95% CI 9.7, 56.6%; p < 0.01; n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Production of PGE2 by bovine cultured airway smooth muscle cells and its inhibition by cyclo-oxygenase inhibitors.

1. Prostaglandin E2 (PGE2) is thought to be an important inhibitory modulator of inflammatory processes in the airway. It inhibits inflammatory cell function and cholinergic neurotransmission in vitro and roles have been postulated in vivo in refractoriness and in the mechanism of action of the diuretic agent, frusemide. 2. The production of PGE2 by bovine cultured airway smooth muscle cells has been studied under a range of conditions. The effects of cyclo-oxygenase inhibitors (flurbiprofen, indomethacin, acetyl salicylic acid) on serum-induced production of PGE2 were assessed over a range of concentrations (10(-7)-10(-4) M). 3. Serum-stimulated production of PGE2 in control wells ranged from 350 to 800 ng PGE2 ml-1 in cells from different animals. All three cyclo-oxygenase inhibitors inhibited PGE2 production with an order of potency, flurbiprofen > indomethacin > acetyl salicylic acid. Log IC50 values were -6.24 for flurbiprofen, -5.23 for indomethacin and -3.50 for acetyl salicylic acid. 4. PGE2 production was stimulated by arachidonic acid (10(-5) M) or addition of the proinflammatory mediator, bradykinin (10(-8)-10(-5) M). 5. Incubation of cells for 24 h with 5 bromo deoxyuridine (BRDU) (10(-4) M) to prevent DNA synthesis did not alter PGE2 production in response to serum, suggesting that it was not a function of proliferation per se. 6. Our study suggests that airway smooth muscle may be an important source of PGE2. Production of PGE2 may be a novel feedback mechanism whereby airway smooth muscle cells can negatively modulate airways inflammation. The differing potencies of the cyclo-oxygenase inhibitors may explain the contrasting effect of these drugs in recent studies in asthma.

Animals↗

Peripheral anterior synechiae formation with anterior chamber intraocular lenses.

In a cross-sectional study, 88 eyes with anterior chamber intraocular lenses (AC-IOLs) were evaluated by goniophotography by one masked observer for the presence of peripheral anterior synechiae (PAS) and by another masked observer for the length of the AC-IOL. Sixty-eight of the 88 lenses had PAS which were strongly correlated with the lens being oversized (P less than .001). However, differences in haptic style or lens rigidity were not associated with the presence of PAS.

Anterior Chamber↗

Malnutrition and hyperglycemia associated with TPN do not alter polymorphonuclear leukocyte adherence to nylon.

Polymorphonuclear leukocyte (PMN) adherence to nylon was assayed in blood obtained from 10 malnourished patients before and during therapy with total parenteral nutrition (TPN). All patients demonstrated minimal to moderate loss of visceral and somatic protein. Adherence of PMN was unaltered by malnutrition or during the 4 wk of TPN in spite of hyperglycemia, which required insulin therapy in 4 patients. There was no correlation of blood sugar levels and PMN adherence.

Blood Glucose↗

Growth and maturation of children with insulin-dependent diabetes mellitus.

The purpose of this paper is to define criteria used for classifying patients into varying degrees of diabetic control and to verify that children with diabetes maintained in higher degrees of metabolic control do not have delayed growth and maturation. Growth records of 252 children with insulin-dependent diabetes who have been under continuous observation in our clinic at three- to five-month intervals for at least three years and up to 16 years have been individually reviewed and analyzed. All children received two daily injections of a mixture of two parts of an intermediate to one part of regular insulin and were instructed to eat structured meals of high-quality selected foods. An over-all rating for diabetic control based primarily on the frequency and degree of glycosuria was made for the time period between clinic visits. The over-all diabetic control rating and the size of the subgroups were "good"--20 per cent, "fair to good"--64 per cent, and "fair"--16 per cent. All children maintained in "good" and "fair to good" control (84 per cent), grew and matured at a normal rate regardless of the age at onset or duration of diabetes. All children in lower degrees of control coming under care for greater than 24 months after diagnosis had accelerated growth during the early months after attaining a higher degree of control.

Adolescent↗