Development of a sample equilibration system for the TEOM continuous PM monitor.

In recent years, scientific discussion has included the influence of thermodynamic conditions (e.g., temperature, relative humidity, and filter face velocity) on PM retention efficiency of filter-based samplers and monitors. Method-associated thermodynamic conditions can, in some instances, dramatically influence the presence of particle-bound water and other light-molecular-weight chemical components such as particulate nitrates and certain organic compounds. The measurement of fine particle mass presents a new challenge for all PM measurement methods, since a relatively greater fraction of the mass is semi-volatile. The tapered element oscillating microbalance (TEOM) continuous PM monitor is a U.S. Environmental Protection Agency (EPA) PM10 equivalent method (EQPM-1090079). Several hundred of these monitors are deployed throughout the United States. The TEOM monitor has the unique characteristic of providing direct PM mass measurement without the calibration uncertainty inherent in mass surrogate methods. In addition, it provides high-precision, near-real-time continuous data automatically. Much attention has been given to semi-volatile species retention of the TEOM method.

Visual testing for readiness to drive after stroke: a multicenter study.

OBJECTIVE: The purpose of this study was to determine the ability of a visual-perception assessment tool, the Motor-Free Visual Perception Test, to predict on-road driving outcome in subjects with stroke. DESIGN: This was a retrospective study of 269 individuals with stroke who completed visual-perception testing and an on-road driving evaluation. Driving evaluators from six evaluation sites in Canada and the United States participated. Visual-perception was assessed using the Motor-Free Visual Perception Test. Scores range from 0 to 36, with a higher score indicating better visual perception. A structured on-road driving evaluation was performed to determine fitness to drive. Based on driving behaviors, a pass or fail outcome was determined by the examiner. RESULTS: The results indicated that, using a score on the Motor-Free Visual Perception Test of < or =30 to indicate poor visual-perception and >30 to indicate good visual perception, the positive predictive value of the Motor-Free Visual Perception Test in identifying those who would fail the on-road test was 60.9% (n = 67/110). The corresponding negative predictive value was 64.2% (n = 102/159). Univariate logistic regression analyses revealed that older age, low Motor-Free Visual Perception Test scores and a right hemisphere lesion contributed significantly to identifying those who failed the on-road test. CONCLUSIONS: The predictive validity of the Motor-Free Visual Perception Test is not sufficiently high to warrant its use as the sole screening tool in identifying those who are unfit to undergo an on-road evaluation.

Localization of NCAM on NCAM-B-expressing cells with inhibited migration in collagen.

The extracellular matrix is a key element in neuronal development and tumour invasion, providing a substratum which sustains the adhesion and migration of cells. In order to study interactions between the neural cell adhesion molecule (NCAM) and collagen, we transfected mouse L cells with cDNA encoding the human transmembrane NCAM isoform of 140 kDa (NCAM-B). An L-cell/collagen type I system was used to study the influence of NCAM expression on in vitro invasion. We here report that migration of NCAM-expressing cells in collagen was inhibited compared to that of NCAM-negative cells transfected with the empty vector. Immunofluorescence confocal laser scanning microscopy (CLSM) and immunogold electron microscopy using anti-human NCAM antibodies demonstrated a heterogeneous distribution of NCAM on the plasma membrane of transfected L cells grown on collagen. NCAM was preferentially located at the surface of broad cytoplasmic protrusions and slender extensions, some of which were facing the collagen. This was in contrast to the homogeneous surface distribution of NCAM on cells grown on plastic. These data suggest that NCAM and collagen type I interact, and that this might lead to the migration inhibition of NCAM-expressing cells.

Birth weight-specific rates as a bias in the effects of smoking and other perinatal hazards.

Perinatal mortality was examined in the Ontario Perinatal Mortality Study (1960 to 1961) subset of 31,788 births and perinatal deaths among English-speaking Canadian-born women. Overall perinatal mortality rose from 22.0 to 28.2 per 1000 if the mother smoked, a 27% increase. When perinatal mortality was computed in birth weight-specific groups (less than 2500 g and 2500 g or more), the rates for smokers were lower than those for nonsmokers in both subgroups. These results occurred because maternal smoking had an even stronger effect on birth weight than on perinatal mortality, increasing the proportion of births of infants weighing less than 2500 g by 106%. These data confirm the hazard of maternal smoking for the unborn, and pinpoint how some studies that have seemingly inconsistent results have erred in analysis.

Long-term effects of prenatal x-ray of human females. I. Reproductive experience.

A cohort of singleton black human females exposed to diagnostic x-ray in utero and controls matched by parity, hospital of birth and birthdate have have been followed to ages 25-30 years in Baltimore, Maryland. The search for possible effects of prenatal irradiation has focused on health, growth, development and reproductive experience of exposed and control women. This paper reports findings related to reproductive experience. From an original data set of 1458 matched exposed-control pairs of women, questionnaire responses were received from 1109 exposed and 1124 control women including 852 each from pairs in which both the exposed and control woman responded. After careful search for alternative explanations of the findings, the authors concluded that females exposed in utero to low doses of x-ray (probably 1-5 rads) had significant increases in their rates of early onset of menses, births at age 15 years or less, numbers of living children, stillbirths, and sterilizing operations by their mid-twenties. These findings are compatible with animal studies in which prenatal irradiation kills many oocytes, but accelerates the development of remaining cells to stages more closely correlated with fertility. Although these animals subsequently became sterile, this cannot be tested in the current study because significantly more of the irradiated women have had surgical sterilizations.

Long-term effects of prenatal x-ray of human females. II. Growth and development.

Experimental studies and studies of survivors of in-utero exposure to atomic bomb blasts have shown significant stunting of growth and mental retardation following these exposures. Central nervous system damage following very low doses of x-ray at around the time of birth has also been observed in experimental animals. This long term follow-up studies of 1458 human females exposed in utero to diagnostic x-rays and of 1458 matched unexposed controls studied in Baltimore, Maryland, included measurements of height, weight and school achievement. Women who had been exposed to x-rays in utero were significantly shorter in their mid-twenties than were their matched, unexposed controls, even after adjustment for other social and economic factors. However, additional follow-up revealed that mothers of exposed women were also shorter than the control mothers. Short stature appeared to be a selective factor for x-ray during pregnancy (mostly pelvimetry, 1947-1952). Mothers' and daughters' heights were similarly correctly among exposed and control mother-daughter pairs, suggesting that the height differences between exposed daughters and their controls were due to these selective factor rather than to any direct effect of radiation on growth. Exposed women reported poorer school achievement than control women. However, except for a higher proportion of exposed women leaving school because of pregnancy, these measurements were no longer significantly different when rates were simultaneously adjusted for socioeconomic differences between exposed and control women.

Long-term effects of prenatal x-ray of human females. III. Mortality and morbidity.

Experimental studies and long-term studies of humans exposed to ionizing radiation in utero and after birth show that these exposures increase the risk of cancer in childhood and in later life. A possible life-shortening effect has also been reported. This study followed to their mid-twenties 1458 women exposed in utero to diagnostic x-rays and 1458 matched, unexposed controls in Baltimore, Maryland, and obtained responses from over 1100 women in each group. Information about general health and specific diseases was obtained from questionnaires. Deaths were ascertained through family members and death certificates. Mortality rates were slightly higher among exposed than control women, and did not differ by gestational age at the time of exposure. Exposed women reported poor general health significantly more often than controls. Specific diseases occurred similarly in the two groups, although exposed women reported more epilepsy or fits, more ovarian tumors, and more high blood pressure. The strong correlation between weight and high blood pressure and the heavier weights of exposed women seemed to account for this difference. In summary, these matched exposed and control women, followed to their mid-twenties, experienced similar rates of morbidity and mortality. Radiation-induced cancers and life-shortening effects, if any, might not become evident until older ages.

Respiratory effects on household exposures to tobacco smoke and gas cooking.

The records of 1,724 residents of Washington County, Maryland, who had participated in 2 studies of respiratory symptoms and ventilatory function were analyzed to evaluate the effects of exposures at home to tobacco smoke generated by other members of their households and to fumes from the use of gas as a cooking fuel. Currently smoking subjects showed the highest frequency of respiratory symptoms and impaired ventilatory function; former smokers showed a lower frequency of these findings; and persons who had never smoked had the lowest prevalence of abnormal respiratory findings. The presence of a smoker in the household other than the subject was not associated with the frequency of respiratory symptoms, and only suggestively associated with evidence of impaired ventilatory function. The use of gas for cooking was related to an increased frequency of respiratory symptoms and impaired ventilatory function among men, being most marked among men who had never smoked. There was not evidence that cooking with gas was harmful to women.

Hypothesis: the role of the lung in stomach carcinogenesis.

It is proposed that pulmonary defense mechanisms play an important role in stomach carcinogenesis. Inhaled carcinogens reach the stomach by normal pulmonary clearance and account for the association of stomach cancer with dusty occupations. We postulate that although familial and other factors determine the susceptibility to endothelial cancer (both stomach and lung), those persons whose pulmonary clearance mechanisms are more susceptible to impairment by cigarette smoke retain carcinogens and other particulate matter in the lungs and are at increased risk for lung cancer. Those whose clearance mechanisms are not impaired continue to clear these particles from their lungs, unconsciously swallow the cleared particles, receive more of these substances in the stomach, and are at increased risk for stomach cancer. This accounts for: first, the very striking dose-response relationship between the amount of smoking and lung cancer mortality and the relatively weak relationship between smoking and stomach cancer, and second, for observed reciprocal relationships in time trends of mortality between stomach cancer and lung cancer.

Is ABH nonsecretor status a risk factor for obstructive lung disease?

In a multidisciplinary study of risk factors for chronic obstructive pulmonary disease (COPD), a significantly more impairment of forced expiration was observed in ABH nonsecretors than in ABH secretors among 1017 white adults. (ABH refers to the "A" and "B" antigens of the ABO blood group system and "H", the heterogenetic substance which is found in persons of all ABO types including type "O".) Nonsecretors had significantly lower mean values of forced expiratory volume in one second as a percentage of forced vital capacity (FEV1/FVC%) and a significantly larger proportion of them had aberrant values, defined as FEV1/FVC% less than 68. These differences remained when mean values or rates of aberrancy were adjusted for other factors reported to alter risk of airway obstruction. In view of the known COPD-peptic ulcer and nonsecretor-duodenal ulcer associations, these findings suggest that the ability to secrete ABH antigens into secretions of the respiratory and gastrointestinal tract may have a protective effect on epithelialized organs in general, or on the lung and portions of the gut specifically.

Alcohol consumption and airway obstruction.

To clarify the basis of the reported association between alcohol and pulmonary disease, the relationship between intake of alcohol and pulmonary function was examined in 2,539 community-dwelling adult participants in an ongoing longitudinal study of risk factors for airway obstruction. Forced expiratory volume in 1 s, expressed as a percentage of forced vital capacity, was used as the indicator of airway obstruction, and forced vital capacity expressed as a percentage of the predicted value was used as an index of restriction. Although crude (unadjusted) mean values of the ratio of forced expiratory volume in 1 s to forced vital capacity were significantly lower for heavy than for light drinkers, the difference disappeared when adjustment was made for numerous confounding factors (including such recognized risk factors for pulmonary disease as cigarette smoking, low socioeconomic status, male sex, and age). There was also no evidence of an association between consumption of alcohol and airway restriction. Although these findings do not rule out a possible effect of alcohol on pulmonary disease, its impact, if any, is probably the result of interaction with other factors associated with alcoholism, if not derived primarily from those other factors.

Tocainide conjugation in humans: novel biotransformation pathway for a primary amine.

The metabolism of tocainide, an experimental antiarrhythmic drug, was studied in humans. Urinary excretion of unchanged drug was 28-55% in 24 hr after oral dosing. Urine hydrolysis with hydrochloric acid or beta-glucuronidase increased tocainide recovery to 55-79%. Saccharo-1,4-lactone inhibited the beta-glucuronidase-mediated tocainide recovery increase. Adjustment of urine to pH 13 produced a compound identified as 3-(2,6-xylyl)-5-methylhydantoin. Evidence suggests that it was derived from the same metabolite that formed the additional tocainide after acid or beta-glucuronidase treatment. Tocainide carbamoyl O-beta-D-glucuronide is the structure proposed for the metabolite. The suggested pathway for its formation involves the addition of carbon dioxide to the amino nitrogen of tocainide followed by uridine diphosphate-glucuronic acid conjugation.

Assay of tocainide in blood by high-pressure liquid chromatography.

A sensitive, specific, high-pressure liquid chromatographic assay for the determination of tocainide in whole blood is described. The residue from a methylene chloride extract of alkalinized blood was resolvated in a mobile phase of methanol--water (47:53) containing 1% acetic acid and 6.16 mM 1-octanesulfonic acid, adjusted to pH 4.0. Chromatography was performed on a reversed-phase column with detection at 254 or 225 nm. The limits of accurate measurement were 2 microgram/ml for a 1-ml blood sample monitored at 254 nm and 0.2 microgram/ml for a 2-ml sample monitored at 225 nm. The assay was tested on samples from emergency protocol patients and was also found suitable for single-dose pharmacokinetic studies.

How does maternal smoking affect birth weight and maternal weight gain? Evidence from the Ontario Perinatal Mortality Study.

A large data set was used to examine the possibility that maternal smoking during pregnancy causes low birth weights by reducing maternal appetite, eating, and weight gain. As always, birth weight distributions shifted downward as maternal smoking level increased. Maternal weight gain distributions, on the other hand, were the same for smokers and nonsmokers. Within each level of maternal weight gain, from less than five pounds to over 40 pounds, the more the mothers smoked the greater was the percentage of neonates weighing less than 2,500 grams. This evidence supports a direct effect of maternal smoking on birth weight, possibly due to the hypoxic effects of carbon monoxide, rather than one mediated through eating. Efforts to prevent or reduce smoking should have greater benefits for mother and child than would efforts to increase food intake among pregnant women who smoke.

The effects of maternal smoking in pregnancy.

PIP: A review of the extensive literature on the effects of smoking in pregnancy reveals that smoking causes significant reductions in birthweight, increases in premature births, increases in fetal and neonatal loss, and possible long-term disabilities in height, reading ability, and social adjustment. The association for the physical effects is dose-related. The effect of maternal smoking on perinatal mortality is positive and proportional to the level of smoking but varies according to other characteristics of the pregnancy. Studies indicate that this increased perinatal mortality is not due to aspects of the fetus but to smoking-related pregnancy complications. The immediate cause of most smoking-related fetal deaths is probably anoxia; the cause of neonatal mortality results from the increased risk of early delivery to smokers. It is recommended that the risks associated with smoking in pregnancy be widely publicized. Patients, especially those with high risk factors, should be advised against continued smoking during pregnancy.^ieng

Absorption kinetics of procainamide in humans.

Plasma procainamide concentrations following the administration of 500 mg of procainamide hydrochloride via intravenous infusion, conventional capsules, and sustained-release tablets were compared in 11 healthy male volunteers. Two-compartment open modeling of the plasma levels from the intravenous infusion experiments yielded mean Kel, k12, and k21 values of 0.0162, 0.0542, and 0.0233 min-1, respectively. The bioavailability of the oral preparations (versus intravenous) averaged 83% for the capsule and 79% for the sustained-release tablet. Calculations using a previously reported method suggested that absorption was a first-order process with mean ka's of 0.0336 and 0.0039 min-1 for the capsule and sustained-release tablet, respectively. The sustained-release formulation exhibited delayed release and adequate bioavailability.

Maternal smoking, pregnancy complications, and perinatal mortality.

Analysis of data from the Ontario Perinatal Mortality Study has shown that perinatal mortality increases directly with the level of maternal smoking during pregnancy. Increases in smoking level are associated with increases in the frequency of early fetal deaths and of neonatal deaths due to premature delivery. These deaths in turn are associated with smoking-related increases in the incidence of bleeding during pregnancy, abruptio placentae, placenta previa, and premature and prolonged rupture of the membranes.