Influence of gestational age and clinical status on bilirubin-binding capacity in newborn infants. Sephadex G-25 gel filtration technique

Total bilirubin-binding capacity was measured by Sephadex G-25 gel filtration in 43 clinically well and 45 clinically ill newborn infants between 26 and 41 weeks' gestation. In the well patients, bilirubin-binding capacity, serum albumin concentration, and the molar-binding ratio of bilirubin to albumin were directly related to gestational age. In the sick patients, serum bilirubin-binding capacity and albumin concentration also correlated with gestational age; however, from 32 to 41 weeks' gestation, the mean values for the sick infants were significantly lower than for the well infants. In the sick infants, the molar binding ratio of bilirubin to albumin was also lower than in the well patients and did not correlate with gestational age. The data are in agreement with previous clinical findings indicating an increased risk for low-bilirubin kernicterus among immature infants and suggest that some critically ill term infants may be at risk for kernicterus at serum bilirubin levels below 20 mg/100 ml.     

Comparison of prefrontal architecture and connections

The advent of new technology has led to a proliferation of studies examining the functional roles of discrete prefrontal cortical areas. This has created a need for more precise information regarding the morphological characteristics of this region. Existing architectonic maps of human and monkey brains are not compatible with regard to areal delineations and topography, creating significant difficulty in interpreting comparative data. Therefore, we have re-examined the comparative morphological organization of the prefrontal cortex in humans and rhesus monkeys. Our analysis indicates that the architectonic areas in both species correspond in terms of morphological features as well as topographical locations. We have developed a common organizational schema for these areas, thereby allowing for a resolution of previous discrepancies. Moreover, in monkeys a connectional analysis has revealed that each of the newly designated areas is characterized by a unique pattern of cortical relationships. The present organizational schema provides a framework for interrelating findings such as those obtained from human brain imaging studies with those from behavioural investigations of non-human primates.     

Experimental comparison of the tuberculostatic activities of INH, INHG and INHG-Na (author''s transl)

A sample of 42 case notes of alcoholic patients were abstracted for 17 items by three different raters. Interrater agreement was generally rather low. Research based on case-note abstraction which does not report on abstraction reliabilities must therefore be viewed with some suspicion. It would be helpful if clinical material could more often be collected in a standardized manner.     

Boosted multivariate trees for longitudinal data

Machine learning methods provide a powerful approach for analyzing longitudinal data in which repeated measurements are observed for a subject over time. We boost multivariate trees to fit a novel flexible semi-nonparametric marginal model for longitudinal data. In this model, features are assumed to be nonparametric, while feature-time interactions are modeled semi-nonparametrically utilizing P-splines with estimated smoothing parameter. In order to avoid overfitting, we describe a relatively simple in sample cross-validation method which can be used to estimate the optimal boosting iteration and which has the surprising added benefit of stabilizing certain parameter estimates. Our new multivariate tree boosting method is shown to be highly flexible, robust to covariance misspecification and unbalanced designs, and resistant to overfitting in high dimensions. Feature selection can be used to identify important features and feature-time interactions. An application to longitudinal data of forced 1-second lung expiratory volume (FEV1) for lung transplant patients identifies an important feature-time interaction and illustrates the ease with which our method can find complex relationships in longitudinal data.     

Infection of human marrow stroma by human immunodeficiency virus-1 (HIV-1) is both required and sufficient for HIV-1-induced hematopoietic suppression in vitro: demonstration by gene modification of primary human stroma

Patients with human immunodeficiency virus-1 (HIV-1) infection often present with bone marrow (BM) failure that may affect all hematopoietic lineages. It is presently unclear whether this failure reflects a direct viral impairment of the CD34+ hematopoietic progenitor cells or whether the virus affects the BM microenvironment. To study the effects of HIV-1 on the BM microenvironment, we examined the stromal cell monolayers in long-term BM culture (LTBMC), which are the in vitro equivalent of the hematopoietic microenvironment. We assessed the hematopoietic support function (HSF) of human stromal layers by determining the cellular proliferation and colony-forming ability of hematopoietic progenitors from BM cells grown on the stromal layers. We show that the HSF is reduced by in vitro infection of the human stromal cell layer by a monocytotropic isolate of HIV-1 (JR-FL). There is no loss of HSF when the stromal cell layer is resistant to HIV-1 replication, either using murine stromal cell layers that are innately resistant to HIV-1 infection or using human stromal cells genetically modified to express a gene that inhibits HIV-1 replication (an RRE decoy). Decreased HSF was seen using either human or murine hematopoietic cells, if the stromal cells were human cells that were susceptible to HIV-1 infection. These in vitro studies implicate HIV-1 replication in the stroma as the essential component causing decreased hematopoietic cell production in HIV-1 infection.