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Biomedical subjects

L Wong

Publications and source records attributed to L Wong.

At least 253 records · Page 14Linked to original sources

Pharmacologic prophylaxis of allergic rhinitis: relative efficacy of hydroxyzine and chlorpheniramine.

The efficacy of hydroxyzine and chlorpheniramine in preventing exacerbations of ragweed allergic rhinitis was compared in a double-blind, randomized manner. Ninety-five subjects with positive skin tests, a history of two previous symptomatic seasons, and discontinuation of immunotherapy for at least 1 yr received either hydroxyzine 150 mg/day, chlorpheniramine 24 mg/day, or placebo during the 1978 ragweed season. Subjects in the placebo group experienced annoying or disabling sneezing 50% of days during the period of highest pollen counts whereas those in the chlorpheniramine and hydroxyzine groups experienced this symptom with equal severity only 22% and 12% of days, respectively. Suppression of rhinorrhea and itchy nose was similar although less dramatic. Both antihistamines were more effective than placebo in altering conjunctivitis, but neither decreased the frequency or severity of nasal stuffiness. Skin tests to ragweed decreased in diameter during the season by 38%, 13%, and 3% among patients receiving hydroxyzine, chlorpheniramine, and placebo, respectively. Frequent drowsiness occurred initially in subjects taking both antihistamines but did not persist. Thus, prophylactic antihistamine therapy effectively prevents most symptoms of seasonal allergic rhinitis without persistent drowsiness. These data further suggest a therapeutic advantage for hydroxyzine over chlorpheniramine in the doses used.

Adolescent↗

Relationship of formulation and dosing interval to fluctuation of serum theophylline concentration in children with chronic asthma.

Completeness of absorption and fluctuations in serum, theophylline concentration were examined in 14 children, 8 to 17 years of age (mean 12.4), with chronic asthma treated in variable sequence with a slow-release formulation at eight- and 12-hour intervals, and plain tablets every six hours. The total fraction absorbed for the slow-release formulation was 0.98 +/- 0.07 (mean +/- SEM) during the eight-hour and 0.99 +/- 0.04 during the 12-hour regimens. Observed fluctuations in serum concentration were closely approximated by predictions determined from absorption of single doses in adult volunteers. Available single-dose absorption data then were used to compare predicted fluctuations in serum concentration among nine formulations (18 brand names) for eight- and 12-hour dosing in an average child and adult (elimination half-lives of 3.7 and 8.2 hours, respectively). Although predicted peak concentrations were less than twice the trough for all products when given at 12-hour intervals to an average nonsmoking adult, only two of the nine formulation (both from the same manufacturer) were likely to maintain predicted fluctuations within the 10 to 20 micrograms/ml therapeutic range during 12-hour dosing intervals in an average child. Most children and those adults with rapid elimination generally will require eight-hour dosing with the other products.

Adolescent↗

The bronchial leak squeak: a new sign for the physical diagnosis of bronchopleurocutaneous fistula.

We describe a unique physical diagnostic sign that we have observed in seven patients with bronchopleurocutaneous fistulas. Such patients have a highpitched squeak over the affected chest area during sustained Valsalva maneuver. We postulate that turbulence across the bronchial fistula due to high transbronchial pressure gradient during the Valsalva maneuver produces the squeaking sound. The pitch of the leak squeak sign is higher in smaller fistulas than in larger fistulas; decreases in intensity and increases in pitch occurred in two patients in whom the bronchial fistula slowly closed. The absence of the leak squeak sound in patients with spontaneous pneumothorax suggests that this sign can be used to differentiate central airways from alveolar air leaks.

Adult↗

Prevention of graft rejection following bone marrow transplantation.

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.

Actuarial Analysis↗

Clinical findings in workers exposed to pentachlorophenol.

Comparative findings are presented on the health and exposure status of groups of individuals in Hawaii with and without occupational exposure to pentachlorophenol (PCP). Occupational exposure to PCP occurred through employment at firms engaged in the treatment of wood with either PCP alone or PCP plus other compounds as preservative chemicals. Mean serum levels were 0.32 ppm for 32 control individuals, 1.72 ppm for 24 workers exposed to PCP and other wood preservative chemicals, and 3.78 ppm for 22 workers exposed to PCP as the sole preservative chemical. Age-standardized prevalence rates were significantly higher among the PCP-exposed than among the controls for low-grade infections or inflammations of the skin and subcutaneous tissue, protective membrane of the eyes and the mucosa membrane of the upper respiratory tract. Strong to moderate statistical associations were observed between PCP exposure and increased occurrence of bands (immature leucocytes) and basophils, increased plasma cholinesterase, alkaline phosphatase, gamma globulin and uric acid, and decreased serum calcium. Despite these statistical associations, laboratory values considered to be clinically abnormal were few and not significantly greater in occurrence among the PCP-exposed individuals.

Adult↗

Medical management of noninfectious rhinitis.

Noninfectious rhinitis and the clinical pharmacology of drugs used in its treatment, including specific treatment recommendations, are reviewed. Characterized by hyperreactivity of the nasal mucosa to a variety of stimuli, noninfectious rhinitis can be classified either as seasonal or perennial allergic rhinitis (when antigens can be identified) or as vasomotor or nonallergic rhinitis (when antigens are not identifiable). However, noninfectious rhinitis is probably better viewed as a continuum between these extremes rather than as definitive categories. Treatment measures include removal of offending agents when possible, and injection of allergenic extracts to decrease sensitivity to inhalant allergens. Among the pharmacologic alternatives, the classical H1 antihistamines competitively inhibit the action of mast-cell histamine at its receptor sites and thus decrease sneezing, nasal pruritus, rhinorrhea, and conjunctivitis. Orally bioavailable alpha-adrenergic agents such as pseudoephedrine and phenylpropanolamine decrease nasal congestion that responds poorly to antihistamines. Topical vasoconstrictors are contraindicated in chronic rhinitis because of the complications of rebound congestion. Systemic corticosteroids are effective but rarely appropriate for chronic rhinitis. Potent topical corticosteroids such as intranasal beclomethasone dipropionate are useful for severe nasal congestion. Cromolyn sodium, an inhibitor of histamine release from mast cells, appears to have some efficacy in suppressing symptoms of allergic rhinitis and conjunctivitis when used topically. Anticholinergics have occasionally been recommended to reduce rhinorrhea, but little data on their efficacy are available.

Adolescent↗

Opiate receptor binding and analgesic effects of the tetrahydroisoquinolines salsolinol and tetrahydropapaveroline.

Salosolinol and tetrahydropapaveroline bind to opiate receptors in rat brain with affinities of 6.2 and 1.95 x 10(-5)M respectively. Their ability to displace 3H-naloxone is decreased about 4-fold by 100 mM sodium ion. Both of these agents have antinociceptive effects when given to rats intraventricularly. Their potency is comparable to the enkephalins, and their effect is blocked by naloxone.

Analgesics↗

Plasma concentrations of propranolol and 4-hydroxypropranolol during chronic oral propranolol therapy.

1 The plasma levels of propranolol and 4-hydroxypropranolol have been measured in 17 hypertensive patients receiving chronic oral therapy with propranolol. 2 The range of plasma propranolol concentrations was from 5.3 to 300 ng/ml, and that of 4-hydroxypropranolol was from 2.1 to 36.0 ng/ml. 3 The mean (+/- s.d.) plasma concentration ratio of 4-hydroxypropranolol to propranolol was 0.130 (+/- 0.005); however, a very wide range was observed with individual values ranging from 0.057 to 0.241. 4 A statistically significant correlation was observed between the plasma concentration of 4-hydroxypropranolol and that of propranolol. 5 Propranolol and 4-hydroxypropranolol plasma concentrations were each significantly, but poorly, correlated with daily propranolol dose. 6 The clinical significance of the results has been discussed.

Adult↗

Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats.

Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VLDL) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL, secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [(3)H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apoVLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are separated by polyacrylamide gel electrophoresis. Similar patterns are noted when non-recirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.

Animals↗

Turnover of apoE in normal and hypercholesterolemic rats.

The turnover of apoE in the total lipoprotein fraction (p less than 1.21 g/ml) of normolipemic and hypercholesterolemic rats was compared. The specific activity of 125I-labelled apoE in the lipoproteins was determined after isolation of the apoprotein by immunoaffinity chromatography. The serum apoE decay curves showed rapid first and slower second phases. The first phase of the curve of hypercholesterolemic animals suggests some sequestration of the apoprotein. The half-lives of apoE in the second phase were approximately 7 and 23 h in the normal and hypercholesterolemic sera, respectively. Elevated apoE levels and moderate hypercholesterolemia persisted one week after restoration of the normal diet, indicating that the increased apoprotein level seen in hypercholesterolemic rats was not solely to VLDL or chylomicron remnants. However, due to the elevated apoE levels in the hypercholesterolemic rats, the total replacement rates of the apoprotein appeared to be greater than that in normolipemic animals, consistent with the concept that in the steady state there is an increase in apoE secretion in hypercholesterolemic animals rather than a decrease in catabolism.

Animals↗

Responsiveness of the lamb ductus arteriosus to prostaglandins and their metabolites.

The relative potencies of the prostaglandins A1, A2, E1, E2, F2alpha and their 15-keto-, 15-keto-13,14-dihydro-, and 13,14-dihydro-metabolites were investigated on isolated lamb ductus arteriosus preparations contracted by exposure to elevated PO2. All the prostaglandins (except PGF2alpha and its 15-keto-metabolites) relaxed the tissue. However, only PGE1, E2, and their 13,14-dihydro-metabolites, were effective at concentrations below 10(-8) M. Therefore, events that alter metabolism of circulating PGs in the perinatal period may have significant effects on the relative patency or closure of the ductus arteriosus.

Animals↗

The levels of apolipoprotein-E in hypercholesterolemic rat serum.

The levels of apolipoprotein-C (apo-E) in serum and isolated liproproteins from diet-induced hypercholesterolemic, and to some extent hypertriglycerdemic rats were measured by electroimmunoassay. The hypocholesterolemia was accompanied by a mild hypertriglyceridemia. The apo-E was increased by 60% in the hypercholesterolemic serum with a 5- and 50-fold increase in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) respectively. However, the proportion of apo-E in nascent VLDL isolated from the hepatic Golgi apparatus of hypercholesterolemic rats was significantly decreased. In control serum, 40--50% of the apo-E is found in the density greater than 1.21 g/ml fraction, although this is at least partially due to ultracentrifugation. The aproprotein is absent from the density greater than 1.21 g/ml fraction from hypercholesterolemic serum, suggesting that it is bound more firmly to the lipoprotein complex. It is concluded that the large increases in apo-E in the VLDL and LDL density ranges of serum from hypercholesterolemic rats may in part be accounted for by the utilization of apo-E normally found at higher densities.

Amino Acids↗

A comparison of some immunological characteristics of very low density lipoproteins of normal and hypercholesterolemic rat sera.

The immunological characteristics of a very low density lipoproteins (VLDL) from normal and hypercholesterolemic rat sera were compared using polyspecific antisera to VLDL and high density lipoproteins (HDL) and monospecific antisera to apo-B, apo-C, apo-A-I, and apo-E. Ultracentrifugally isolated VLDL from normal serum were studied by immunodiffusion and found to contain both discrete and associated (with apo-B) apo-C and apo-E, probably in the form of lipid-containing lipoproteins. However, immunoelectrophoresis of whole serum revealed only an associated form of the liporpotein having pre-beta mobility (i.e., VLDL), suggesting that the presence of discrete lipoproteins in isolated VLDL, each containing a single apoprotein family, may represent ultracentrifugal artifacts. Ultracentrifugally isolated VLDL from diet-induced hypercholesterolemic rat serum contained only trace amounts of apo-C and large quantities of apo-E, both of which were totally associated with apo-B. VLDL isolated by ultracentrifugation from perfusate of normal and hypercholesterolemic livers contained only associated lipoprotein complexes made up of apo-B, apo-C, and apo-E in the former but only apo-B and apo-E in the latter. These data suggest that normal VLDL are secreted as lipoprotein complexes containing apo-B, apo-C, and apo-E, which may become destabilized in the circulation. However, VLDL from hypercholesterolemic serum shows a marked diminution in the quantity of apo-C as indicated by the relative incorporation of [3H]leucine in vivo and by polyacrylamide gel electrophoresis of apo-VLDL.

Animals↗