Cow's Milk Exposure and Asthma in a Newborn Cohort: Repeated Ascertainment Indicates Reverse Causation

The effect of cow's milk consumption on childhood asthma has been debated for several years. This study attempts to provide further insight into this association through the use of a longitudinal study design. Newborns from parents with atopic history were recruited from Germany, Austria, and England (n = 696). For five repeated ascertainments, information was collected on cow's milk exposure, incidence of doctor-diagnosed asthma, and confounders. Generalized estimation equations, incorporating different models (concurrent, delayed, combined, and reverse causation), were used to determine this association. No association between cow's milk consumption and childhood asthma was found for the concurrent effects model (OR = 0.81, 95% confidence interval [CI]: 0.55, 1.20). In the delayed effects model, the direction of the association varied with time of follow-up. Thus, we stratified by period, which resulted in a significant protective delayed effect at 36 months (OR = 0.18, 95% CI = 0.06, 0.49). However, reverse causation negated this finding since the presence of asthma in prior months led to a reduction in further exposure to cow's milk (OR = 0.40, 95% CI = 0.16, 0.99). Hence, cow's milk consumption does not protect against childhood asthma. The apparent protection of cow's milk against asthma may result from parents of asthmatic children avoiding cow's milk, rather than actual prophylaxis.     

Effects of a specific benzodiazepine antagonist (RO 15-1788) on cerebral blood flow

RO 15-1788, a specific benzodiazepine antagonist, although it effectively antagonizes the clinical effects of benzodiazepines (i.e., sedation and amnesia), can also induce subjective agonist effects such as sedation or inverse agonist effects such as anxiety. The purpose of this study was to investigate in seven healthy volunteers the effect of RO 15-1788 on cerebral blood flow when intravenously injected alone or with midazolam and to compare its effects with midazolam administered alone. Cerebral blood flow was measured with the 133xenon inhalation technique and the drugs were administered simultaneously in a double-blind, randomized fashion during the four following sessions: placebo-placebo; midazolam-placebo; RO 15-1788-placebo; midazolam-RO 15-1788. No difference in cerebral blood flow was noted between the placebo-placebo, the RO 15-1788-placebo, and the RO 15-1788-midazolam sessions--although midazolam injected alone decreased cerebral blood flow by 30%. The sedation, amnesia, and the electroencephalograph (EEG) and muscle tone changes observed with midazolam-placebo were not present during the RO 15-1788-placebo and RO 15-1788-midazolam sessions. This study demonstrates the absence of effects of RO 15-1788 on cerebral blood flow when injected alone and the efficacy of this new drug in antagonizing the depressant effects of midazolam on cerebral hemodynamics.     

Comparative echocardiographic study of junior and senior basketball players

The echocardiographic data on 14 junior and 15 senior players in a first-division basketball club were compared. No difference was found between the senior and junior players as regards the thickness of the interventricular septum (11.47 vs 11.21 mm) or the thickness of the posterior wall of the left ventricle (9.8 vs 9.86 mm). The adults displayed a larger left ventricular end-diastolic diameter (56.8 vs 53.6 mm, P less than 0.05), end-diastolic volume (194 vs 164 ml, P less than 0.05), stroke volume (142 vs 116 ml, P less than 0.05), right ventricular diameter (27.9 vs 23.2, P less than 0.01), aortic root diameter (35.0 vs 32.0, P less than 0.05), and left atrial diameter (42.7 vs 37.2, P less than 0.01). However, among these, only the stroke volume and right ventricular diameter remained significantly different after normalization to body surface area. A significant difference could not be demonstrated in the linear ejection fraction, the ejection fraction, or the fractionated interventricular septum and posterior wall thicknesses. The examinations indicated that left ventricular hypertrophy had fully developed by the age of 18 years in the basketball players and that there was no further enhancement in adults. However, the left ventricular, right ventricular, and left atrial volume were larger in the adults than in the junior players.     

Application of magnetic resonance imaging to evaluation of femoral neck structure in growing girls.

Conventional density measures by dual-energy X-ray absorptiometry (DXA) are confounded by increases in bone size and do not assess bone geometry. We assessed precision of magnetic resonance imaging (MRI) and used MRI, DXA, and hip structure analysis (HSA) to assess 7-mo changes in bone structure at the femoral neck in 18 prepubertal girls. At baseline, girls were 10.4 (0.5) yr, 144.0 (8.2) cm, and 35.2 (7.0) kg, on average. Total bone and cortical cross-sectional area (ToA and CoA) were calculated from high-resolution T1-weighted MRI oblique axial images of the femoral neck. We used proximal femur DXA scans (Hologic QDR-4500) and the HSA program to estimate bone cross-sectional area (CSA), and calculate section modulus. MRI precision was determined by scanning 10 volunteers (13-46 yr old) three times with and without repositioning. Precision (CVrms) was 2% for ToA and 7% for CoA. Significant correlations were observed between FN area and MRI-derived ToA (r = 0.57, p = 0.013) and CoA (r = 0.47, p = 0.050). There were significant positive changes over 7 mo by both methods. In conclusion, MRI provides useful information on femoral neck bone area in children. The reproducibility of cortical dimensions at the femoral neck needs improvement through technical modifications and appropriate analysis software.     

Predicting life span for applicants to inpatient hospice

The advent of hospice programs and their funding under Medicare has recently made eligibility for substantial insured services turn on whether a patient has less than three or six months to live. The implicit assumption is that physicians can provide this prediction accurately. To test this assumption and to improve predictions, the life spans of 108 consecutive applications for inpatient hospice care were estimated independently by two oncologists, an internist, an oncology nurse, and a hospice social worker, based on data in a ten-page multidisciplinary application packet. The applicants were followed up until death. Actual life span was correlated with predictions. The median (+/- SD) life span was 3.5 +/- 12.4 weeks. The predictions as a group were overly optimistic about survival by an average of 3.4 weeks. The best prognosticator's prediction was only moderately correlated with actual life span, and no two prognosticator's predictions correlated closely with one another. Predicting actual interval until death was more accurate than predicting a 90% confidence interval around the time of death, though the latter procedure was better at avoiding the error of unpredicted long-term survivors. This imprecision in "expert" estimation of life span poses substantial problems for hospice programs and policymakers.     

Epstein-Barr virus-transformed human precursor B cell lines: altered growth phenotype of lines with germ-line or rearranged but nonexpressed heavy chain genes

A series of lymphoblastoid cell lines (LCLs) have been established by in vitro infection of fetal bone marrow and fetal liver cells with Epstein-Barr virus (EBV). While most lines showed the usual mature B cell phenotype, a small proportion were cytoplasmic and surface immunoglobulin (Ig) heavy and light chain negative. Analysis of gene rearrangements indicated that the Ig- lines were either germ-line or nonproductively rearranged when probed for JH and were in germ-line configuration for C chi; no mu or chi mRNA could be detected in such cells. Precursor B cell lines were indistinguishable from their normal Ig+ counterparts in their expression of a wide variety of cell surface markers including "activation" antigens usually associated with the lymphoblastoid state; even the single LCL showing germ-line heavy and light chain genes expressed B lineage-specific cell surface antigens. However, the Ig- lines were distinct from their Ig+ counterparts in three important respects: (a) they grew much more slowly and achieved lower saturation densities, (b) they showed unusually high proportions (8-16%) of cells in EBV-productive cycle, and (c) they contained unusually high proportions (up to 40%) of cells expressing free joining (J) chain. These results suggest that precursor B cells differ in their response to the growth-transforming effects of EBV such that the virus-cell interaction in precursor B cell lines is inherently less stable than in conventional LCL. In particular there may be a greater movement of cells out of cycle and along the B cell maturation pathway. It is possible that such movement leads in individual cells either to virus replication or to a "sterile" plasmacytoid differentiation with J chain expression in the absence of Ig synthesis.