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Biomedical subjects

E B Weiss

Publications and source records attributed to E B Weiss.

At least 19 recordsLinked to original sources

An extremely compensatible cigarette by design: documentary evidence on industry awareness and reactions to the Barclay filter design cheating the tar testing system.

BACKGROUND: The Barclay cigarette (Brown & Williamson) was introduced in 1980 in the USA in the most expensive launch in history. In the USA and around the world, Barclay was later determined to have a grooved filter design that was compromised by human smokers in the normal act of smoking, but that was measured as ultra-low tar using the standard tar testing protocol. OBJECTIVES: To evaluate whether Brown & Williamson knew of the compensatability of Barclay during the design process and before it was released; to evaluate initial responses of competing tobacco companies to Barclay, before complaints were made to the Federal Trade Commission in 1981. METHODS: Internet databases of industry documents (Tobacco Documents Online, Legacy Tobacco Documents Library, Brown & Williamson Litigation discovery website, Guildford and major company websites) were searched using key words, key dates, and targeted searches. Documents related specifically to the development, evaluation and release of the Barclay cigarette and related to the responses by competing tobacco companies were examined. RESULTS: Documents indicate the manufacturer was aware of Barclay design problems and was planning, before release, to respond to criticism. Competing companies quickly detected the filter groove stratagem and considered developing their own similar filter, but eventually backed off. CONCLUSION: The design problems with Barclay were readily understood by cigarette manufacturers, including the maker of Barclay, before official governmental evaluations occurred. Testing involving measured exposures to human smokers may in the end be crucial to identifying problems with novel cigarette designs.

Attitude to Health↗

A perspective on controversies over neonatal circumcision.

Controversy continues to surround the issue of male circumcision, especially in the United States. The following report reviews the history of this practice, along with the medical and sociopolitical positions currently espoused. It is our conclusion that, as the safest and most commonly performed surgical procedure in this country, the benefits of posthetomy, which include a reduction in some kinds of cancer and sexually transmitted diseases, well outweigh the risks cited by those who oppose it.

Circumcision, Male↗

Isolation and characterization of guinea-pig tracheal smooth muscle cells that retain differentiated function in long-term subculture.

A simple 30-min enzyme digestion procedure has been used to release guinea-pig tracheal smooth muscle cells that retain differentiated function in long-term subculture. Primary cell cultures initially consist of numerous epithelial colonies and 70-1000 morphologically differentiated smooth muscle cells per 600 mg (wet weight) tracheal tissue depending on the age of the animal. Both cell types proliferate to form a confluent monolayer within 5-17 days. Pure subcultures of tracheal smooth muscle cells are obtained by limited trypsin digestion of the primary culture. Eighty percent of these subcultured smooth muscle cells retain the ability to contract in response to histamine (10(-6) M) and to form reaggregates even after 20 or more passages. Examination of these cells by electron microscopy reveals both biosynthetic and contractile components of smooth muscle. Analysis of this dual phenotype may provide valuable information about the regulation of tracheal smooth muscle cell growth and differentiation.

Animals↗

Superoxide anion generation during airway anaphylaxis.

Extracellular release of superoxide anion (O-2) during in vitro anaphylaxis in guinea pig trachealis was found to exhibit both a time- and a concentration-dependent generation of O-2. Trachealis O-2 release was unaffected by treatment with diphenhydramine HCl (10(-5) M, 10(-6) M). While indomethacin (10(-5) M) augmented anaphylaxis tension it did not enhance O-2 release. However, the semiselective SRS-A antagonist FPL 55712 (10(-5) M) resulted in essentially complete inhibition of O-2 generation. These data indicate that O-2 generation occurring during acute airway anaphylaxis is associated with the activation of SRS-A products.

Anaphylaxis↗

Leukotriene-associated toxic oxygen metabolites induce airway hyperreactivity.

The effect of toxic oxygen metabolite scavengers was examined in a guinea pig trachealis model of leukotriene (LTD4)-induced synergism upon histamine contractures. Under both physiologic (2.5 mM) and low (OmM) extracellular calcium conditions, LTD4 (10(-7) to 10(-9) M) potentiated histamine isometric tension responses. This LTD4-induced histamine hyperresponse was inhibited by pretreatment with superoxide dismutase. Inhibition of LTD4 receptor binding by FPL 55712 (10(-5) M) also aborted this interaction. Actual trachealis superoxide anion (O2-) generation by LTD4 was observed with a maximal release of 15 nM O2-/CPK unit X 10(-2) over 60 min. Phorbol myristate acetate (PMA) also generated O2- in this preparation. Trachealis muscle hyperreactivity to histamine induced by 10(-8) M LTD4 assayed in OmM (Ca++)E was not induced by PMA. It is concluded that exogenous LTD4 activates toxic oxygen metabolites which interact to induce an acquired hyperreactivity to agonist histamine in trachealis smooth muscle.

Animals↗

Toxic oxygen products alter calcium homeostasis in an asthma model.

After anaphylactic or synthetic leukotriene C4 contractions in guinea pig trachealis muscle, an accelerated initial rate and greater total myorelaxation are induced in these muscle preparations when they are immersed in calcium-free medium, O(Ca++)E. Inhibition of the late phase of anaphylaxis (ANA) by FPL 55712 (10(-5) mol/L) eliminated the post-ANA O(Ca++)E-augmented myorelaxation, suggesting a causal role for SRS-A products. Hypoxia or superoxide dismutase/catalase pretreatment also abolished the post-ANA or leukotriene C4 O(Ca++)E-augmented myorelaxation. The data support the hypothesis that toxic oxygen products generated with SRS-A and/or LTC4 induce an alteration in Ca++ homeostasis in airway smooth muscle. In this model of allergic asthma, airway smooth muscle alteration after ANA may contribute to the pathogenesis of asthma and/or airway hypersensitivity associated with allergic asthma.

Anaphylaxis↗

Leukotriene effect in airways smooth muscle: calcium dependency and verapamil inhibition.

The extracellular calcium (Ca++) E dependency of the synthetic leukotrienes (LT) C4, D4 and E4 and inhibition of LTC4 by verapamil was demonstrated on guinea pig trachealis in vitro. LTC4 exhibited an intrinsic potency 170 X greater than histamine. Tension development by LTC4, D4 and E4 was equipotent at 2.5 mM (Ca++)E. Tension studies in 0.5 mM (Ca++)E indicate these three leukotrienes to be (Ca++)E dependent with a potency ranking of LTC4 greater than LTD4 and LTE4 (P less than 0.05 and P less than 0.001 respectively). Inhibition of LTC4 by verapamil yielded an IC50 of approximately 1.1 X 10(-4)M with complete inhibition at 2.2 X 10(-4)M; this antagonism was non-competitive. The specific dependency of verapamil inhibition of LTC4 to (Ca++)E was demonstrated by reversal of verapamil antagonism with 5.0 mM (Ca++)E. Synthetic leukotrienes C4, D4 and E4 are dependent upon (Ca++)E for their myotropic activity, an action non-competitively inhibited by the calcium channel blocker verapamil.

Acetylcholine↗

Effect of calcium antagonists in experimental asthma.

Verapamil was found to be an effective inhibitor of isometric tension in in vitro, experimental anaphylaxis in guinea pig trachealis smooth muscle. The mean IC50 for protection studies was 2 X 10(-4) M; the drug was also effective as a bronchoreversal agent. The inhibitory effect of verapamil upon the initial rate of isometric muscle tension suggests an action beyond simple calcium channel inhibition. No inhibition of tracheal mast cell histamine release was observed. Verapamil was slightly more potent than theophylline in this in vitro anaphylactic model.

Anaphylaxis↗

Calcium hypersensitivity in airways smooth muscle. Isometric tension responses following anaphylaxis.

The isometric tension of anaphylactic guinea pig trachealis muscle preparation was examined at subphysiologic extracellular calcium concentrations, in vitro. Paired observations of control to passively sensitized (egg albumin antiserum) and antigen-challenged muscles (anaphylaxis) were made to exposure to trace Ca++ followed by cumulative Ca++ replacement. Following anaphylaxis, a leftward shift of the Ca++ concentration-tension responses was found at 0.25--0.5 mM Ca++ (p less than 0.001); EC50 was 1.5 x greater than control. A greater maximal tension was also noted at 2.52 mM Ca++. Passively sensitized muscles did not exhibit this heightened response. Subthreshold tissue chemical mediators are tentatively excluded as causative. An increased sensitivity to extracellular Ca++ exists in resting smooth muscle following anaphylaxis.

Anaphylaxis↗

T3 thyrotoxicosis in a child.

We report the case of a 5-year-old hyperthyroid boy with normal serum T4 levels are elevated serum T3 levels. The findings are diagnostic of T3 thyrotoxicosis, a condition that has been very infrequently reported in childhood. We postulate that low dietary iodine intake may be an etiologic factor in some cases of T3 thyrotoxicosis.

Child, Preschool↗

The inhibitory action of lidocaine in anaphylaxis.

The action of lidocaine, a local anesthetic, was investigated during anaphylaxis in guinea pigs after passive sensitization in vitro of lung tissue and trachealis muscle. Pretreatment of the trachealis muscle with 8.54 mM lidocaine resulted in the total inhibition of anaphylactic isometric tension. Full reversal of anaphylactic-induced contractures was rapidly achieved with concentrations of 4.27 mM lidocaine. Release of histamine from both lung tissue and trachealis muscle was inhibited by 73 to 82 per cent, respectively, over concentration ranges of 2.13 to 8.54 mM lidocaine. A bimodal effect on sensitized tissues was noted, with lidocaine causing a slight release of histamine in the trachealis muscle of 1.6 per cent at a concentration of 8.54 mM. Lidocaine did not impair the initial passive sensitization process, nor did it appear to elute antibody once it was cell bound. The dual inhibitory effect on mast-cell release of mediators and on muscle contraction by lidocaine may be related in part to common processes involving the binding or flux of calcium.

Amines↗