POPULATION ASSESSMENTS OF INFECTION WITH SCHISTOSOMA MANSONI: EFFECTS OF BIAS CAUSED BY THE RELATIVE SENSITIVITY OF DIAGNOSTIC TECHNIQUES (PUERTO RICO)

This study establishes the extent and relevance of bias of population estimates of prevalence, incidence, and intensity of infection with Schistosoma mansoni caused by the relative sensitivity of stool examination techniques. The population studied was Parcelas de Boqueron in Las Piedras, Puerto Rico, where the Centers for Disease Control, had undertaken a prospective community-based study of infection with S. mansoni in 1972. During each January of the succeeding years stool specimens from this population were processed according to the modified Ritchie concentration (MRC) technique. During January 1979 additional stool specimens were collected from 30 individuals selected on the basis of their mean S. mansoni egg output during previous years. Each specimen was divided into ten 1-gm aliquots and three 42-mg aliquots. The relationship of egg counts obtained with the Kato-Katz (KK) thick smear technique as a function of the mean of ten counts obtained with the MRC technique was established by means of regression analysis. Additionally, the effect of fecal sample size and egg excretion level on technique sensitivity was evaluated during a blind assessment of single stool specimen samples, using both examination methods, from 125 residents with documented S. mansoni infections. The regression equation was: Ln KK = 2.3324 + 0.6319 Ln MRC, and the coefficient of determination (r('2)) was 0.73. The regression equation was then utilized to correct the term "m" for sample size in the expression P ((GREATERTHEQ) 1 egg) = 1 - e('-ms), which estimates the probability P of finding at least one egg as a function of the mean S. mansoni egg output "m" of the population and the effective stool sample size "s" utilized by the coprological technique. This algorithm closely approximated the observed sensitivity of the KK and MRC tests when these were utilized to blindly screen a population of known parasitologic status for infection with S. mansoni. In addition, the algorithm was utilized to adjust the apparent prevalence of infection for the degree of functional sensitivity exhibited by the diagnostic test. This permitted the estimation of true prevalence of infection and, hence, a means for correcting estimates of incidence of infection. ^

Molecular structure of antibodies against small ligands

Antibodies which bind bioactive ligands can serve as a template for the generation of a second antibody which may react with the physiological receptor. This phenomenon of molecular mimicry by antibodies has been described in a variety of systems. In order to understand the chemical and molecular mechanisms involved in these interactions, monoclonal antibodies directed against two pharmacologically active alkaloids, morphine and nicotine, were carefully studied using experimental and theoretical molecular modeling techniques. The molecular characterization of these antibodies involved binding studies with ligand analogs and determination of the variable region amino acid sequence. A three-dimensional model of the anti-morphine binding site was constructed using computational and graphics display techniques. The antibody response in BALB/c mice to morphine appears relatively restricted, in that all of the antibodies examined in this study contained a $\lambda$ light chain, which is normally found in only 5% of mouse immunoglobulins. This study represents the first use of theoretical and experimental modeling techniques to describe the antigen binding site of a mouse Fv region containing a $\lambda$ light chain. The binding site model indicates that a charged glutamic acid residue and aromatic side chains are key features in ionic and hydrophobic interactions with the ligand morphine. A glutamic acid residue is found in the identical position in the anti-nicotine antibody and may play a role in binding nicotine. ^

Devices in heart failure: potential methods for device-based monitoring of congestive heart failure.

Congestive heart failure has long been one of the most serious medical conditions in the United States; in fact, in the United States alone, heart failure accounts for 6.5 million days of hospitalization each year. One important goal of heart-failure therapy is to inhibit the progression of congestive heart failure through pharmacologic and device-based therapies. Therefore, there have been efforts to develop device-based therapies aimed at improving cardiac reserve and optimizing pump function to meet metabolic requirements. The course of congestive heart failure is often worsened by other conditions, including new-onset arrhythmias, ischemia and infarction, valvulopathy, decompensation, end-organ damage, and therapeutic refractoriness, that have an impact on outcomes. The onset of such conditions is sometimes heralded by subtle pathophysiologic changes, and the timely identification of these changes may promote the use of preventive measures. Consequently, device-based methods could in the future have an important role in the timely identification of the subtle pathophysiologic changes associated with congestive heart failure.