Prediction of equivalent environments by energy exchange and assessments of physiological strain and discomfort

The described equivalence postulate was confirmed experimentally by examining physiological responses as well as discomfort sensation in a series of predicted equivalent conditions during exercise (congruent to 3 met). ET or the equivalent Ta at 50% RH is a single independent variable that is uniquely related to the mean skin temperature (Tsk), skin wettedness (w), body core temperature (Tcore) and sense of discomfort.     

Acute acid-base disorders. 2. Specific disturbances

Evaluation of the acid-base status of the body requires measurement of bicarbonate (total carbon dioxide) concentration, pH, and partial pressure of CO2 in arterial blood. Calculation of standard bicarbonate and base excess or deficit is not necessary. The normal concentration of free hydrogen ions (H+) is approximately 40 millimoles/liter, which is equivalent to a pH of 7.4. The normal load of fixed acids is 50 to 80 millimoles in 24 hours. A steady state is maintained by excretion of an equal amount of H+ by the kidneys, which at the same time regenerate bicarbonate to replenish buffer stores. Renal excretion of H+ is in the form of titratable acid and ammonium. Synthesis of ammonia can increase severalfold under the stimulus of acidosis. This is the chief mechanism of long-term compensation. Metabolic acidosis can be due to an excessive acid load (endogenous or exogenous), impaired renal excretion of H+, or bicarbonate loss. Determination of the "anion gap" (unmeasured anions) helps to establish the mechanism of acidosis. Acidosis with a normal anion gap is due to either bicarbonate loss or ingestion of certain chloride salts. A gap larger than normal indicates the presence in the body of acids other than acidfying chloride salts. Management of metabolic acidosis requires accurate diagnosis, clear understanding of the mechansim, and individualized treatment. Metabloic alkalosis is due to loss of H+ (usually from stomach or kidneys) or ingestion of alkali. Measurement of urinary chloride helps establish the mechanism of alkalosis. In saline-responsive alkalosis, the urinary chloride level is very low. This is usually due to gastric loss of H+, and the condition responds to administration of saline solution. When the urinary chloride level is only moderately low, the alkalosis is probably not due to gastric loss of H+. This form of alkalosis (saline-resistant) does not respond well to administration of saline solution and requires use of potassium in treatment. Apprpriate compensatory responses to acidosis or alkalosis are critical to survival. Compensation for metabloic acidosis consists of hyperventilation and enhanced renal excretion of H+, chiefly as ammonium. In metabolic alkalosis, compensation is mainly renal excretion of bicarbonate. Respiratory acidosis is due to alveolar hypoventilation. In chronic situations, a compensatory rise in serum bicarbonate concentration is expected. Management consists of treatment of the cause of hypoventilation. Respiratory alkalosis is due to hyperventilation. Treatment requires identification and correction of the cause of hyperventilation.     

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.