Long-acting narcotic antagonist complexes

We evaluated the ability of close to 100 organic acids to form water-soluble salts with methadone, cyclazocine, naloxone, naltrexone and, more recently, diprenorphine. About half the acids yielded insoluble salts. Polybasic acids affording insoluble salts were evaluated for their ability to form drug:acid:metal complexes with the polyvalent metal ions, Zn++, Al+++, Mg++ and Ca++. Optimum conditions for forming complexes have been developed and the consistency of their composition has been established. Salts were analyzed spectrophotometrically for drug content, and complexes were analyzed for drug and metal content. The in vitro degree of dissociation at equilibrium was measured for the preparations suspended in a simulated physiological buffer, pH 7.3. Preparations of the narcotic antagonist drugs showing relatively low degrees of dissociation in vitro, since it early appeared that a high degree of dissociation contraindicated a prolonged duration of pharmacological action, were evaluated in mice after intramuscular administration at several dose levels by the mouse tail-flick test for the potency and duration of their morphine antagonist activity. Our most promising preparations to date, showing the most prolonged durations of action without evidence of gross toxicity, are naltrexone zinc tannate and naltrexone aluminum tannate. These are undergoing detailed evaluation as potential clinical candidates. Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel.     

Properties of diagnostic data distributions

In applications of statistical methods to medical diagnosis, information on patients' diseases and symptoms is collected and the resulting data-base is used to diagnose new patients. The data-structure is complicated by a number of factors, two of which are examined here: selection bias and unstable population. Under reasonable conditions, no correction for selection bias is required when assessing probabilities for diseases based on symptom information, and it is suggested that these "diagnostic distributions" should form the principal object of study. Transformation of these distributions under changing population structure is considered and shown to take on a simple form in many situations. It is argued that the prevailing paradigm of diagnostic statistics, which concentrates on incidence of symptoms for given disease, is largely inappropriate and should be replaced by an emphasis on diagnostic distributions. The generalized logistic model is seen to fit naturally into the new framework.     

Laryngeal papillomatosis: immunologic and viral basis for therapy

The distressing nature of laryngeal papillomatosis and lack of clinical progress in its treatment are reviewed. Presently accepted and investigative methods of therapy are reviewed with special attention being given to immune therapy. Support for the concept of a viral etiology is discussed and other etiologic agents considered. Known and possibly significant roles of wart virus antibodies are discussed and the importance of complex interplay between maternal and fetal immune systems explored as a possible explanation for some puzzling aspects of laryngeal papillomatosis. Finally, a proposed experimental design is outlined, the purpose of which is to provide a useful animal model to investigate immune changes in laryngeal papillomatosis, as well as effects of surgical or medical therapy.     

College athletics, body size, and cancer mortality

Data are presented on mortality from neoplasms as determined from death certificates in a cohort of 8393 college men, according to athletic status in college. Major athletes (lettermen) died significantly more often from neoplasms than nonathletes. Mean age at death from neoplasms (underlying cause) was significantly lower in major athletes than in both minor athletes and nonathletes. After matching major athletes with nonathletes of comparable body size (height and weight), differences in proportional mortality and mean age at death from neoplasms persisted, although not statistically significant for the smaller samples. Correlation coefficients (Pearson r) and partial r's between weight in college and age at death from neoplasms were negative but of low magnitude. Some possible explanations for the differences between major athletes and nonathletes are discussed.     

Supersensitivity induced by the toxin of Brazilian scorpion venom (Tityus serrulatus Lutz e Mello)

The purified toxin of the Brazilian scorpion venom (TsTX) enhances the pharmacological actions of directly and indirectly acting substances on several preparations. The enhancing action of TsTX is more pronounced for the indirectly acting drugs, which is highly suggestive of a prejunctional site of action. Secondarily, TsTX does also produce an unspecific increase of sensitivity at the level of the pharmacological receptor itself. The mechanism by which these changes are brought about remains to be determined.     

Effect of charcoal-broiled beef on phenacetin metabolism in man

When charcoal-broiled beef was fed to human volunteers, who were then given phenacetin orally, the concentration of phenacetin in the plasma was lowered, but its half-life in the plasma was not changed. The data suggest that feeding charcoal-broiled beef enhances the metabolism of orally administered phenacetin in the intestine or during its first pass through the liver, or both.