Distribution of forced expiratory volume in one second and forced vital capacity in healthy, white, adult never-smokers in six U.S. cities

As part of a longitudinal study of the respiratory health effects of air pollution, we measured the lung function of 2,454 white adults 25 to 74 yr of age who had never smoked and who reported no respiratory symptoms. These measurements were analyzed to develop a simple model for the cross-sectional dependence of pulmonary function on height, sex, and age. Both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) can be effectively standardized for body size by dividing each pulmonary function measurement by the square of the standing height (HT2). The age-specific distribution of these standardized measurements is approximately Gaussian, with variance that is independent of age. Plots of FEV1/HT2 and FVC/HT2 against age showed a nonlinear relationship consistent with an increase in the rate of pulmonary function loss with age. On the basis of these graphic analyses, both pulmonary function measurements were fitted to a four-parameter normative model including sex and linear and quadratic terms in age as dependent variables. This model gave predictions that were very close to those from more complicated models currently in use. Predicted percentile levels were calculated for each sex and age, and shown to describe the observations well. The estimated annual change in height-standardized lung function based on the cross-sectional model was compared with the observed change between the first and second examinations of these adults 3 yr later. The observed changes were close to predicted values, except for subjects younger than 35 yr of age at their first examination. The observed change was larger for men than for women. Such simple longitudinal comparisons are subject to selection bias. In this study, subjects in the lowest quartile of FEV1/HT2 for their age and sex at the first examination had a lower probability of providing a lung function measurement 3 yr later.     

Effect of indomethacin in autotransplanted colonic tumors

Seventy-five male Sprague-Dawley rats received weekly injections of dimethylhydrazine (DMH) for six months. Indomethacin was given orally to 40 of the rats. At the end of the allotted period, colonic tumors were autotransplanted into the subcapsular space of the left kidney. The autopsy demonstrated colonic tumors in 32 of 34 rats treated with DMH (94.1 percent), but only in 15 of 40 rats (37.5 percent) treated with DMH-indomethacin. Successful kidney autotransplantation was accomplished in 20 of 32 DMH-treated rats (63 percent) and in 5 of 15 DMH-indomethacin-treated rats (33.3 percent) Thus, the induction of colonic tumors by DMH and successful kidney autotransplants can be substantially abrogated by synchronous treatment with indomethacin. Supported by grants from the Cancer Society of Stockholm and the karolinska Institute.     

Effect of food deprivation on survival after hemorrhage in the rat

The changes in plasma glucose concentration and hematocrit during, and 7-day survival after, 60-min hemorrhagic hypotension (55 mmHg MAP) were investigated in postprandial and 6- or 24-h food-deprived rats. During hemorrhage, postprandial rats developed hyperglycemia, 30% greater than 6-h and 150% higher than 24-h food-deprived rats. Blood loss and plasma refill were greater in postprandial rats compared to 24-h food-deprived rats. Food deprivation for 24 h resulted in significantly increased mortality (6/13) posthemorrhage. All postprandial rats survived (13/13). A further three groups of animals deprived of food for 24 h were submitted to hemorrhage volume similar to that of postprandial rats. When no infusion was given during hemorrhage all rats died after hemorrhage (10/10). Saline infusion did not increase survival. Infusion of a similar volume of hypertonic glucose resulted in improved survival (not significant vs postprandial). Short-term food deprivation alters responses to stress and influences the outcome after standardized hemorrhage. Induction of hyperglycemia during hemorrhage was associated with survival.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

Observer variability in the pulmonary examination

Observer variability in the pulmonary examination was assessed by having four blindfolded observers (two medical students and two pulmonary physicians) twice examine 31 patients with abnormal pulmonary findings. Examiners were consistent in the repetitive detection of pulmonary abnormalities in 74–89% of the examinations; conversely, 11–26% of the time they disagreed with themselves. Although pulmonary specialists recorded fewer (55% of observations) abnormal findings than did medical students (74%), they were significantly (p=0.008) less self-consistent than were the students. There was no clear trend in agreement between examiners (kappa=0.20−0.49). Each examiner’s findings were compared with those of physicians specially trained in pulmonary examination. Dichotomous variables (wheezes, crackles, rubs) were more reliably detected (kappa=0.30−0.70) than graded variables (tympany, dullness, breath sound intensity), where kappa=0.16−0.43. The authors suggest that dichotomous variables deserve greatest clinical reliance; that time in training, alone, does not improve clinical performance; and that there is a disconcertingly large amount of inter- and intraobserver disagreement in this fundamental clinical task. Received from the Division of General Internal Medicine, Department of Medicine; the Division of Biometry, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina; and the Ambulatory Care Service and Health Services Research Field Program, Durham V.A. Medical Center, Durham, North Carolina.