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.

Allopurinol-induced arteritis in partial HGPRTase deficiency. Atypical seizure manifestation.

A 17-year-old boy with partial hypoxanthine-guanine phosphoribosyl transferase deficiency developed a hypersensitivity reaction to allopurinol. The reaction was manifested by the development of bizarre, atypical seizures. The patient had been neurologically normal prior to the reaction. Seizures disappeared following discontinuation of allopurinol therapy. Allopurinol apparently can cause a diffuse vasculitis involving cerebral vessels after many year of therapy, resulting in atypical seizures.

Folic acid nonresponsive homocystinuria due to methylenetetrahydrofolate reductase deficiency.

Four siblings from a family with 11 children of Irish ancestry were observed to suffer from an essentially identical clinical illness, consisting of delayed psychomotor development in infancy and childhood, severe mental retardation, and upper motor neuron dysfunction. Death occurred at an early age in three siblings. In cases in which detailed physical examinations were performed, ectopia lentis, marfanoid features, and severe bony deformities were absent. Homocystinuria, homocystinemia, relatively normal concentrations of methionine and cystine in tissue fluids, and absence of methylmalonic aciduria were found. A deficiency of methylenetetrahydrofolate reductase was demonstrated in cultured skin fibroblasts from two siblings. Postmortem examination of two of the three patients who died showed extensive vascular thrombosis. No biochemical improvement was observed in the surviving child following treatment with large doses of folic acid.

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.

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.

Hormonal therapy and cholelithiasis.

This report is to alert the abdominal surgeon to a new factor responsible for a rising incidence of cholelithiasis in the younger woman. The cause of cholelithiasis has been explained on the basis of biochemical changes with mechanical obstruction. The role of estrogen-progesterone elevation in pregnancy with associated hypercholesteremia is well-known. Little known are reports (more common in non-American literature) that female hormones effect a sluggishness of gallbladder function. Thus, a chemical change with a functional type of obstruction in the biliary tree predisposes toward cholelithiasis. A survey of 1346 cholecystic operations from 1969 through 1973 showed the expected greater incidence in women. Women under 40 years of age who received hormonal medication were younger when operated upon than a comparable group not receiving hormonal therapy. The incidence of gallbladder disease in young women using hormonal therapy should be expected to increase in the coming years. Cholelithiasis should be suspected in the young female taking birth control medication. X-ray study is indicated and early surgery is desirable to prevent morbidity, mortality and the complications of cholecystic disease.

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.