Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care.

To ascertain how effective the Beck Depression Inventory for Primary Care (BDI-PC) was for differentiating medical inpatients who were and were not diagnosed with DSM-IV major depression disorders (MDD), this 7-item self-report instrument composed of cognitive and affective symptoms was administered to 50 medical inpatients along with the Depression subscale (HDS) from the Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983, Acta Psychiatrica Scandinavica, 67, 361-370). The Mood Module from the Primary Care Evaluation of Mental Disorders (Spitzer et al., 1995, Prime-MD instruction manual updated for DSM-IV) was used to diagnose MDD. The internal consistency of the BDI-PC was high (alpha = 0.86), and it was moderately correlated with the HDS (r = 0.62, P < 0.001). The BDI-PC was not significantly correlated with sex, age, ethnicity, or type of medical diagnosis. A BDI-PC cut-off score of 4 and above yielded the maximum clinical efficiency with both 82% sensitivity and specificity rates. The clinical utility of the BDI-PC for identifying medical inpatients who should be evaluated for MDD is discussed.

Categorical regression analysis of acute exposure to tetrachloroethylene.

Exposure-response analysis of acute noncancer risks should consider both concentration (C) and duration (T) of exposure, as well as severity of response. Stratified categorical regression is a form of meta-analysis that addresses these needs by combining studies and analyzing response data expressed as ordinal severity categories. A generalized linear model for ordinal data was used to estimate the probability of response associated with exposure and severity category. Stratification of the regression model addresses systematic differences among studies by allowing one or more model parameters to vary across strata defined, for example, by species and sex. The ability to treat partial information addresses the difficulties in assigning consistent severity scores. Studies containing information on acute effects of tetrachloroethylene in rats, mice, and humans were analyzed. The mouse data were highly uncertain due to lack of data on effects of low concentrations and were excluded from the analysis. A model with species-specific concentration intercept terms for rat and human central nervous system data improved fit to the data compared with the base model (combined species). More complex models with strata defined by sex and species did not improve the fit. The stratified regression model allows human effect levels to be identified more confidently by basing the intercept on human data and the slope parameters on the combined data (on a C x T plot). This analysis provides an exposure-response function for acute exposures to tetrachloroethylene using categorical regression analysis.

A database designed to support dose-response analysis and risk assessment.

Risk assessment for various human exposures depends on evaluation of existing toxicological literature from a variety of sources. Risk assessors may have limited resources for obtaining raw data, performing additional analyses and initiating new laboratory or epidemiological studies. These constraints must be balanced against a need to improve scientific credibility by developing improved statistical and analytical methods that optimize the use of the available information. A database is described that was designed specifically to support emerging analytical approaches for dose-response assessment, while accommodating the diverse nature of published literature. The database allows entry of exposure and response information in a relational multi-table design, with closely controlled standard fields for recording values and free-text fields for describing unique aspects of a study. To include data needed for current as well as proposed methods, multiple fields were created for different data types and for exposure characterization. The database structure allows rapid access to, and versatile use of, toxicological data for dose-response analyses.

Sacrococcygeal teratoma in Sweden: a 10-year national retrospective study.

Thirty-two children with sacrococcygeal teratoma have been treated during the last 10 years (1980 to 1989) in Sweden. A retrospective study was performed in four departments of pediatric surgery that treat sacrococcygeal teratomas in children from the whole of Sweden. Prenatal and perinatal histories were reviewed together with interval to diagnosis, Altman classification, histology, and serum alpha-fetoprotein. Details of surgical management +/- adjuvant chemotherapy and outcome of patients were also documented. In 8 patients the teratoma was diagnosed prenatally by ultrasonography and there was one postoperative death in this group. Multiagent chemotherapy was used in all but one of 11 patients with malignant teratomas (in 8 of them a cisplatin, bleomycin, vinblastine combination). Only one patient with a malignant tumor treated by single-agent chemotherapy died, 8 others were still alive and tumor-free after 1 to 9 years (mean time, 5.4 years). Two patients developed late relapses and were treated by surgical resection. Metastases occurred in five of the 11 malignant tumors, one at presentation and in four patients 10 to 29 months following surgery. All relapses had distant metastases as well as local disease. Serum alpha-fetoprotein was used in monitoring some of these patients.

Sacrococcygeal teratoma in Sweden between 1978 and 1989: long-term functional results.

Thirty-four patients operated with sacrococcygeal teratoma in Sweden between 1978 and 1989 were reviewed. Twenty-five children were available for functional follow-up. The patients and their parents were interviewed for bowel and micturition habits. Fourteen patients from this number were subjected to anorectal manometry (56%). Fifteen children reported normal bowel habits (60%). In 10 patients (40%) soiling was observed. However, four of them were under 3 years of age and wearing diapers, which made the functional evaluation difficult. The manometries showed normal and resting tone and squeezing pressures in 10 patients and subnormal values in four patients who also had soiling problems. All investigated children showed normal rectoanal inhibition reflex. Twenty-one patients reported normal micturition, in four (16%) urinary incontinence was recorded. Two of the latter children required intermittent clean catheterization, one was on medication and the last one lives without any treatment. No difference in functional outcome was noted between patients with intrapelvic or extrapelvic tumor location. Retrospectively, it is not possible to know whether the observed functional outcome is due to tumor growth or the result of surgery. Preoperative clinical investigation and in some cases anorectal manometry and cystometry could theoretically resolve this problem.

Electric properties of rat liver cell cultures on gas-permeable membranes.

In rat hepatocytes grown on gas-permeable membranes (Petzinger et al. In Vitro Cell. Dev. Biol. 24: 491-499, 1988), cellular and canalicular potentials as well as input resistances were measured using two-channel microelectrodes. In HCO3(-)-containing solutions, we found -30.9 +/- 0.4 (SE) (n = 141) and -13.9 +/- 1.4 mV (n = 22) for cell and canalicular membrane potentials, respectively. There was no dependence of these parameters on the age of the primary culture. Canalicular input resistance, however, increased from 13.3 +/- 2.0 M omega (n = 4) at day 1 after seeding to 36.1 +/- 5.0 M omega (n = 9) at day 2 and stabilized thereafter, while cell input resistance continuously decreased from 37.0 +/- 3.3 M omega at 1 h (n = 6) to 5.2 +/- 2.1 M omega (n = 27) at 3 days after preparation. In ion substitution experiments there were no changes in the transference numbers for K+, Na+, or Cl- that could account for this effect. Cable analysis, however, revealed that the decrease in input resistance reflects a time-dependent increase in electrical coupling between cells. We conclude that rat liver cells on gas-permeable membranes are highly suited for the quantitative analysis of cell-to-cell interaction. In addition, cells and canaliculi are readily accessible with two-channel microelectrodes, making this preparation a promising tool for electrophysiological analysis of hepatocellular transport mechanisms.

Absorption of dissociated and undissociated short-chain fatty acids across the colonic epithelium of guinea-pig.

Diffusion potentials for Na+, Cl-, acetate (Ac-), propionate (Pr-) and butyrate (Bu-) across the isolated epithelium of the proximal and the distal colon of guinea-pig were measured with flowing electrodes in Ussing chambers. Permeabilities of the anions are expressed in relation to the permeability of sodium. Unidirectional fluxes of Na+ and short-chain fatty acids (SCFAs) were estimated. Fluxes of SCFA anions and of undissociated SCFAs were calculated from relative permeabilities and flux values. In the proximal colon of guinea-pig 50% of SCFAs were transported in the dissociated and 50% in the undissociated form; transport rates of the three SCFAs were similar. In the distal colon SCFA transport was based primarily on diffusion of the free acids; the ratios of fluxes were: HAc/Ac- = 2.4; HPr/Pr- = 6.9; HBu/Bu- = 9.3, and transport rates increased with chain length of the SCFA.

Is gastro-intestinal mucus an ion-selective barrier?

The mucus layer at the epithelial surface seems to be responsible for the formation of a microclimate in which the concentrations of H+, K+, Na+, and Cl- are rather constant. It is possible that this is not due simply to an unstirred layer effect, but also to a higher diffusion resistance of mucus. Flux measurements revealed that sodium and potassium permeabilities in mucus are 50% lower than those in saline. Dilution and biionic diffusion potentials indicated a higher relative permeability of mucus for sodium and potassium than for chloride. Thus mucus represents a diffusion barrier, slightly more permeable for cations than for anions.

Mentally retarded and nonretarded adults' sensitivity to spatial structure.

The sensitivity of mentally retarded and nonretarded adults to changes in the structure of their perspectives when those changes are occluded from view during a walk was examined in two studies. Sensitivity was tested by starting participants at a target object located in one room of an unfamiliar office building, walking them via a circuitous path into a new room from which the target was occluded from view, and then asking them to aim a pointer straight at it. Direction judgments were collected across variations in the number of turns in the walk, spatial arrangements of rooms, amount of the subjects' attention available during the walk, and the availability of visual-environmental cues. Results indicate that retarded and nonretarded persons show similar levels of sensitivity to changes in perspective when they walk without visual-environmental cues (i.e., with eyes closed). In the presence of visual-environmental cues, however, the accuracy of nonretarded subjects increased dramatically whereas the retarded subjects did not improve at all. The similarities and differences in performance are related to differences in the perceptual learning thought to mediate use of proprioceptive cues and the inferential processes thought to mediate use of visual-environmental cues.

Effects of adrenal steroids on Na transport in the lower intestine (coprodeum) of the hen.

The influence of adrenal steroids on sodium transport in hen coprodeum was investigated by electrophysiological methods. Laying hens were maintained on low-NaCl diet (LS), or on high-NaCl diet (HS). HS hens were pretreated with aldosterone (128 micrograms/kg) or dexamethasone (1 mg/kg) before experiment. A group of LS hens received spironolactone (70 or 160 mg/kg, for three days). The effects of these dietary and hormonal manipulations on the amiloride-sensitive part of the short-circuit current were examined. This part is in excellent agreement with the net Na flux, and therefore a direct electrical measurement for Na transport. After depolarizing the basolateral membrane potential with a high K concentration, the apical Na permeability and the intracellular Na activity were investigated by current-voltage relations for the different experimental conditions. Plasma aldosterone concentrations (PA) were low in HS hens, dexamethasone-treated HS hens and spironolactone-treated LS hens (less than 70 pM). In contrast LS hens and aldosterone-treated HS hens had a PA concentration of 596 +/- 70 and 583 +/- 172 pM, respectively. LS diet (chronic stimulation) had the largest stimulatory effect on Na transport and apical Na permeability. Hormone-treated animals had three- to fourfold lower values. Spironolactone supply in LS hens decreased Na transport and apical Na permeability about 50%. The results provide evidence that both mineralo- and gluco-corticoids stimulate Na transport in this tissue by increasing the apical Na permeability. Quantitative differences between acute and chronic stimulation reveal a secondary slower adaptation in apical membrane properties.

Comparative sensitivity of measurements of lung damage made by bronchoalveolar lavage after short-term exposure of rats to ozone.

Consequences of exposure of rats for 2 days or less to O3 at various concentrations between 0.12 and 0.96 ppm were measured using several assays performed on bronchoalveolar lavage fluid. Changes in apparent lung permeability were assessed by measurement of recovery of labelled bovine serum albumin in lung lavage fluid after intravenous injection ("permeability index"). The relative sensitivity of this assay was compared with the sensitivity of measurements of changes in protein and of enzyme content in lavage fluid. Permeability index increased in an exposure concentration-dependent manner after 6 or 24 h of exposure to O3 at or above levels of 0.4 ppm. Permeability index was also increased after 2 days of exposure to 0.2 ppm of O3. The activities of lactate dehydrogenase, acid phosphatase, and N-acetyl-beta-D-glucosaminidase in lung lavage fluid were less sensitive indicators of O3 damage than was altered permeability index. Increased lactate dehydrogenase activity could only be detected after continuous exposure of rats for at least 1 day to 0.64 (or higher) ppm of O3, while acid phosphatase and N-acetyl-beta-D-glucosaminidase activities were increased after exposure of rats to O3 at 0.4 ppm or above for 1 day. Activities of these enzymes were not increased after 6 h of exposure to 0.64 ppm of O3 or after 2 days of exposure to 0.2 ppm. Increased lavage protein content was the most sensitive measurement of the consequences of O3 exposure to rats in these protocols. The lavagable protein content increased after exposure of rats to O3 for 6 h at 0.4 ppm and for 1 or 2 days of exposure to 0.12 ppm, the current peak hourly National Ambient Air Quality standard for O3. While the biological significance of these observations remains to be determined, measurement of lavage protein content is a simple, sensitive indicator of acute changes in the lung caused by exposure to environmentally relevant concentrations of O3.

Synergistic interaction of ozone and respirable aerosols on rat lungs. II. Synergy between ammonium sulfate aerosol and various concentrations of ozone.

Pulmonary responses after continuous exposure of rats to concentrations of ozone (O3) ranging from 0.12 to 0.64 ppm were quantified by measuring tissue collagen synthesis rate, tissue protein and DNA content, and various constituents of bronchoalveolar lavage fluid. After 7 days of exposure to 0.64 ppm of O3, lung collagen synthesis rate and tissue content of protein and DNA were elevated. After shorter durations of exposure to 0.64 ppm of O3, significant elevations were observed in the protein content and the activities of lactate dehydrogenase, acid phosphatase, and N-acetyl-beta-D-glucosaminidase from lavage fluid. After exposure of rats to 0.20 ppm of O3 for 7 days, changes could be detected in both lung collagen synthesis rate and tissue protein content. Total lavagable protein content, a sensitive indicator for O3-induced effects upon the lung, was significantly elevated in lungs of rats exposed to 0.12 or 0.20 ppm of O3. To examine whether a synergistic interaction occurred between 0.20 or 0.64 ppm of O3 and acid aerosols, rats were continuously exposed to O3 with and without concurrent exposure to 5 mg/m3 of ammonium sulfate. A synergistic interaction between 0.20 ppm of O3 and ammonium sulfate aerosol was observed by measurement of total lavagable protein and of lung collagen synthesis rate. These results demonstrate that ammonium sulfate aerosol interacts synergistically with O3 at concentrations of O3 that approach ambient levels.

Synergistic interaction of ozone and respirable aerosols on rat lungs. I. Importance of aerosol acidity.

A synergistic interaction, as defined by biochemical and morphological criteria, between ozone (or NO2) and respirable aerosols of ammonium sulfate or sulfuric acid has been described previously. Experiments in the present paper show that it is the acidity, not the sulfate content, of the aerosol that is responsible for such synergy; neutral aerosols of Na2SO4 or NaCl do not elicit synergistic effects when combined with ozone. Aerosol size (and, therefore, site of deposition in the lung) is also an important determinant of synergy with ozone; 0.5 micron mass median aerodynamic diameter (MMAD) aerosols are effective whereas 0.02 micron MMAD aerosols are not. The synergistic interaction between ozone and acidic aerosols could be demonstrated by biochemical and toxicological criteria in addition to those we have previously reported, for example increases in whole lung protein content and free (acid-soluble) proline content of lungs. A synergistic interaction has been demonstrated at concentrations of 0.64 ppm (1.3 mg/m3) of ozone and 1 mg/m3 of acid aerosol in this study. We conclude that acidity of an aerosol determines whether or not it interacts synergistically with ozone, and that an aerosol size that impacts maximally upon the alveolar duct region of the lung is most active with ozone.

The effect of lung alpha-tocopherol content on the acute toxicity of nitrogen dioxide.

The effect of lung vitamin E content on early direct damage to lung by NO2 was studied by exposing three groups of rats differing in lung vitamin E content to 0, 10, 20, 30, and 40 ppm NO2 for 4 hr. Lung vitamin E contents of 3.24, 17.4, and 87.7 micrograms/lung were obtained by maintaining animals on semipurified diets containing 0, 10, or 1000 mg/kg of d-alpha-tocopherol acetate. Animals were sacrificed immediately after the 4-hr exposure and lung damage was assessed by assaying the lung lavage content of protein, sialic acid, lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (GDH), acid phosphatase (AP), and aryl sulfatase (AS), all of which increase in lavage fluid in a concentration-dependent manner over the range of NO2 concentrations used. Increases in lavagable protein, sialic acid, AP, and AS were not affected by the different vitamin E contents, while the increases in LDH, MDH, and GDH were significantly attenuated in the 1000-mg/kg diet group relative to the 0- and 10-mg/kg diet groups. Lipid peroxidation was not detectable in NO2-exposed lungs by either conjugated diene measurement or thiobarbituric-acid-reactive materials, with the exception of a slight increase in thiobarbituric-acid-reactive material in free cells. These results suggest two mechanisms of NO2 damage to lung. The attenuation of the appearance of some lavage parameters by high vitamin E is consistent with lipid peroxidation as a necessary event in the damage responsible for their appearance, although the lack of change in indicators of lipid peroxidation in the whole lung suggests that peroxidation occurs to only a very limited extent. The lavage parameters which are unaffected by lung vitamin E content apparently appear in airways as a result of events not involving lipid peroxidation.

Detection of in vivo lipid peroxidation using the thiobarbituric acid assay for lipid hydroperoxides.

Thiobarbituric acid (TBA) assays which have been modified for detection of lipid hydroperoxides appear to be useful for demonstration of in vivo lipid peroxidation. Since these methods require heating tissue membranes with the buffered TBA, there is a possibility of interference from the detection of autoxidation that occurs during heating. These studies were undertaken to investigate conditions which favor TBA color production from hydroperoxide while limiting autoxidation during the assay. An acetic acid-sodium acetate buffered (pH 3.6) TBA assay was used. Heating linoleic acid hydroperoxide with 50 microM ferric iron or under nitrogen nearly doubled color production compared to heating it with no added iron or under air. The lipid antioxidant butylated hydroxytoluene inhibited color production from fatty acid hydroperoxides. When tissue fractions, including liver and lung microsomes and lung whole membranes, were heated in the assay, color production was greater under air than under nitrogen and was much greater under oxygen. When liver microsomes from carbon tetrachloride-exposed rats were used, color was increased only when oxygen was present in the heating atmosphere. The results with tissue fractions appear to demonstrate autoxidation during color development rather than the presence of preformed hydroperoxides. Finally, it was found that color production from membrane fractions was dependent on the vitamin E content of the membranes. It appears that autoxidation during heating should be limited by heating under nitrogen and not by adding antioxidants, which inhibit color production from hydroperoxides. As the vitamin E effect demonstrates, antioxidant status must be considered, since a change in color production could result from a change in antioxidant content without the accumulation of lipid hydroperoxides.

Sensitivity to perspective structure while walking without vision.

Experiments are reported of the nonvisual sensitivity of observers to their paths of locomotion and to the resulting changes in the structure of their perspectives, ie changes in the network of directions and distances spatially relating them to objects fixed in the surrounding environment. In the first experiment it was found that adults can keep up to date on the changing structure of their perspectives even in the absence of sights and sounds that specify changes in self-to-object relations. They do this rapidly, accurately, and, according to the subjects' reports, automatically, as if perceiving the new perspective structures. The second experiment was designed to investigate the role of visual experience in the development of sensitivity to occluded changes in perspective structure by comparing the judgments of sighted adults with those of late-blinded adults (who had extensive life histories of vision) and those of early-blinded adults (who had little or no history of vision). The three groups performed similarly when asked to judge perspective while imagining a new point of observation. However, locomoting to the new point greatly facilitated the judgments of the sighted and late-blinded subjects, but not those of the early-blinded subjects. The findings indicate that visual experience plays an important role in the development of sensitivity to changes in perspective structure when walking without vision.

Biochemical assessment of acute nitrogen dioxide toxicity in rat lung.

The early primary biochemical response of lung to NO2 was studied separately from the later secondary responses of inflammation and proliferation by measuring several biochemical parameters in lungs of rats immediately following a 4-hr exposure to nitrogen dioxide (NO2) at concentrations of 10, 20, 30, and 40 ppm. Cell-free lavage fluid contained elevated amounts of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), isocitrate dehydrogenase (IDH), glucose-6-phosphate dehydrogenase (GDH), acid phosphatase (AP), and aryl sulfatase (AS) after 30 or 40 ppm NO2. Total protein and sialic acid were increased in cell-free lavage after 20, 30, or 40 ppm NO2. The amounts of protein, sialic acid, and acid phosphatase recovered by airway lavage were equal to the amounts found in 0.7 ml of plasma, consistent with transudation of this volume of plasma into airways as a source of these parameters. The plasma activity of the other parameters measured was too low to account for their increase in lavage fluid by plasma leakage into airways. Decrease in the number and enzyme content of lavagable cells indicated damage to free cells in the airways. The amount of the decrease in enzyme content of the lavagable cell fraction was similar to the increase in the cell-free lavage for all of the measured enzymes except acid phosphatase, suggesting the release of these enzymes into airways as a result of damage to free cells. However, the LDH isoenzyme profile in cell-free lavage after exposure is inconsistent with free cells as the source of this enzyme. No changes were observed in the whole-lung homogenate content of protein, DNA, lipid, LDH, MDH, IDH, GDH, AP, AS, glutathione reductase, NADPH cytochrome c, or succinate cytochrome c reductase immediately after NO2 exposure. This study indicates that initial acute damage to lung by NO2 results in translocation of enzymes, proteins, and sialic acid into airways. Plasma is a likely source of translocated protein, sialic acid, and acid phosphatase. The sources of the other enzyme activities remain to be identified, with lung parenchyma and free cells as likely sources.