Exposures from chrysotile-containing joint compound: evaluation of new model relating respirable dust to fiber concentrations.

The potential for fiber exposure during historical use of chrysotile-containing joint compounds (JCC) has been documented, but the published data are of limited use for reconstructing exposures and assessing worker risk. Consequently, fiber concentration distributions for workers sanding JCC were independently derived by applying a recently developed model based on published dust measurements from sanding modern-day (asbestos-free) joint compound and compared to fiber concentration distributions based on limited historical measurements. This new procedure relies on factors that account for (i) differences in emission rates between modern-day and JCC and (ii) the number of fibers (quantified by phase contrast microscopy [PCM]) per mass of dust generated by sanding JCC, as determined in a bench-scale chamber study using a recreated JCC, that convert respirable dust concentrations to fiber concentrations. Airborne respirable PCM-fiber concentration medians (and 95% confidence intervals) derived for output variables using the new procedure were 0.26 (0.039, 1.7) f/cm(3) and 0.078 (0.013, 0.47) f/cm(3) , and corresponding total fiber concentrations were 1.2 (0.17, 9.2) f/cm(3) and 0.37 (0.056, 2.5) f/cm(3) , in enclosed and nonenclosed environments, respectively. Corresponding estimates of respirable and total PCM fiber concentrations measured historically during sanding of asbestos-containing joint compound-adjusted for differences between peak and time-weighted average (TWA) concentrations and documented analytical preparation and sampling artifacts-were 0.15 (0.019, 0.95) f/cm(3) and 0.86 (0.11, 5.4) f/cm(3) , respectively. The PCM-fiber concentration distributions estimated using the new procedure bound the distribution estimated from adjusted TWA historical fiber measurements, suggesting reasonable consistency of these estimates taking into account uncertainties addressed in this study.

Pre-stroke socioeconomic status predicts upper limb motor recovery after inpatient neurorehabilitation.

BACKGROUND: Lower socioeconomic status (SES) is associated with higher mortality rates and the likelihood of receiving less evidence-based treatment after stroke. In contrast, little is known about the impact of SES on recovery after discharge from inpatient rehabilitation. The aim of this study was to investigate the influence of SES on long-term recovery after stroke. PATIENTS AND METHODS: In a prospective, observational, multicentre study, inpatients were recruited towards the end of rehabilitation. The 12-month follow-up focussed on upper limb motor recovery, measured by the Fugl-Meyer score. A clinically relevant improvement of ≥5.25 points was considered recovery. Patient-centric measures such as the Patient-reported Outcomes Measurement Information System-Physical Health (PROMIS-10 PH) provided secondary outcomes. Information on schooling, vocational training, income and occupational status pre-stroke entered a multidimensional SES index. Multivariate logistic regression models calculating odds ratios (ORs) and corresponding confidence intervals (CIs) were applied. SES was added to an initial model including age, sex and baseline neurological deficit. Additional exploratory analyses examined the association between SES and outpatient treatment. RESULTS: One hundred and seventy-six patients were enrolled of whom 98 had SES and long-term recovery data. Model comparisons showed the SES-model superior to the initial model (Akaike information criterion (AIC): 123 vs. 120, Pseudo R2: 0.09 vs. 0.13). The likelihood of motor recovery (OR = 17.12, 95%CI = 1.31; 224.18) and PROMIS-10 PH improvement (OR = 20.76, 95%CI = 1.28; 337.11) were significantly increased with higher SES, along with more frequent use of outpatient therapy (p = .02). CONCLUSIONS: Higher pre-stroke SES is associated with better long-term recovery after discharge from rehabilitation. Understanding these factors can improve outpatient long-term stroke care and lead to better recovery.KEY MESSAGEHigher pre-stroke socioeconomic status (SES) is associated with better long-term recovery after discharge from rehabilitation both in terms of motor function and self-reported health status.Higher SES is associated with significantly higher utilization of outpatient therapies.Discharge management of rehabilitation clinics should identify and address socioeconomic factors in order to detect individual needs and to improve outpatient recovery. Article registration: clinicaltrials.gov NCT04119479.

Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure.

The marked difference in biopersistence and pathological response between chrysotile and amphibole asbestos has been well documented. This study is unique in that it has examined a commercial chrysotile product that was used as a joint compound. The pathological response was quantified in the lung and translocation of fibers to and pathological response in the pleural cavity determined. This paper presents the final results from the study. Rats were exposed by inhalation 6 h/day for 5 days to a well-defined fiber aerosol. Subgroups were examined through 1 year. The translocation to and pathological response in the pleura was examined by scanning electron microscopy and confocal microscopy (CM) using noninvasive methods. The number and size of fibers was quantified using transmission electron microscopy and CM. This is the first study to use such techniques to characterize fiber translocation to and the response of the pleural cavity. Amosite fibers were found to remain partly or fully imbedded in the interstitial space through 1 year and quickly produced granulomas (0 days) and interstitial fibrosis (28 days). Amosite fibers were observed penetrating the visceral pleural wall and were found on the parietal pleural within 7 days postexposure with a concomitant inflammatory response seen by 14 days. Pleural fibrin deposition, fibrosis, and adhesions were observed, similar to that reported in humans in response to amphibole asbestos. No cellular or inflammatory response was observed in the lung or the pleural cavity in response to the chrysotile and sanded particles (CSP) exposure. These results provide confirmation of the important differences between CSP and amphibole asbestos.

Potential artifacts associated with historical preparation of joint compound samples and reported airborne asbestos concentrations.

Airborne samples collected in the 1970s for drywall workers using asbestos-containing joint compounds were likely prepared and analyzed according to National Institute of Occupational Safety and Health Method P&CAM 239, the historical precursor to current Method 7400. Experimentation with a re-created, chrysotile-containing, carbonate-based joint compound suggested that analysis following sample preparation by the historical vs. current method produces different fiber counts, likely because of an interaction between the different clearing and mounting chemicals used and the carbonate-based joint compound matrix. Differences were also observed during analysis using Method 7402, depending on whether acetic acid/dimethylformamide or acetone was used during preparation to collapse the filter. Specifically, air samples of sanded chrysotile-containing joint compound prepared by the historical method yielded fiber counts significantly greater (average of 1.7-fold, 95% confidence interval: 1.5- to 2.0-fold) than those obtained by the current method. In addition, air samples prepared by Method 7402 using acetic acid/dimethylformamide yielded fiber counts that were greater (2.8-fold, 95% confidence interval: 2.5- to 3.2-fold) than those prepared by this method using acetone. These results indicated (1) there is an interaction between Method P&CAM 239 preparation chemicals and the carbonate-based joint compound matrix that reveals fibers that were previously bound in the matrix, and (2) the same appeared to be true for Method 7402 preparation chemicals acetic acid/dimethylformamide. This difference in fiber counts is the opposite of what has been reported historically for samples of relatively pure chrysotile dusts prepared using the same chemicals. This preparation artifact should be considered when interpreting historical air samples for drywall workers prepared by Method P&CAM 239.

Cardiac autoantibodies. I. Immunodiffusion analysis of multiple responses evoked homologously and heterologously.

1. A high proportion of rabbits immunized with pooled rabbit heart homogenates in complete Freund's adjuvant responded with the production of multiple precipitating antibodies to soluble rabbit heart antigens. The most potent antisera revealed at least five distinct antigens. 2. Rabbit anti-rabbit heart antibodies reacted with similar antigens in other mammalian hearts, (human, rat, guinea pig, and bovine) with apparent "reactions of identity" by immunodiffusion. 3. Rabbits immunized with human, rat, or guinea pig heart homogenates also responded with multiple precipitating antibodies directed against rabbit cardiac antigens, although somewhat less intensively than animals immunized homologously. The specificities of these antibodies appeared to be the same as those evoked homologously. 4. The autoantibody nature of the homologously and heterologously induced responses was unequivocally demonstrated in several instances by reactions between the sera from immunized rabbits and their own hearts. 5. Many of the autoantibodies appeared to be directed against antigens restricted to the heart, judging by comparative immunodiffusion tests with other rabbit tissue extracts. This was convincingly confirmed by multiple absorption of potent antisera with several rabbit tissues. The cardiac-restricted antigens were also present in heart extracts of other mammalian species. In those instances where some of the cardiac-evoked autoantibodies reacted with other rabbit tissues, the tissue cross-reactions were quite variable. 6. Rabbits immunized with guinea pig heart homogenate suffered a high early mortality of undetermined cause, compared to animals immunized with rabbit, human, or rat hearts. 7. A small proportion of the anti-heart sera revealed immunodiffusion reactions with Group A streptococcal products, derived from organisms grown in antigen-free media. In these few instances, the reactions appeared unrelated to cardiac autoantibody responses.

The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results.

The pathological response and translocation of a commercial chrysotile product similar to that which was used through the mid-1970s in a joint compound intended for sealing the interface between adjacent wall boards was evaluated in comparison to amosite asbestos. This study was unique in that it presents a combined real-world exposure and was the first study to investigate whether there were differences between chrysotile and amosite asbestos fibers in time course, size distribution, and pathological response in the pleural cavity. Rats were exposed by inhalation 6 h/day for 5 days to either sanded joint compound consisting of both chrysotile fibers and sanded joint compound particles (CSP) or amosite asbestos. Subgroups were examined through 1-year postexposure. No pathological response was observed at any time point in the CSP-exposure group. The long chrysotile fibers (L > 20 microm) cleared rapidly (T(1/2) of 4.5 days) and were not observed in the pleural cavity. In contrast, a rapid inflammatory response occurred in the lung following exposure to amosite resulting in Wagner grade 4 interstitial fibrosis within 28 days. Long amosite fibers had a T(1/2) > 1000 days and were observed in the pleural cavity within 7 days postexposure. By 90 days the long amosite fibers were associated with a marked inflammatory response on the parietal pleural. This study provides support that CSP following inhalation would not initiate an inflammatory response in the lung, and that the chrysotile fibers present do not migrate to, or cause an inflammatory response in the pleural cavity, the site of mesothelioma formation.

A biopersistence study following exposure to chrysotile asbestos alone or in combination with fine particles.

In designing a study to evaluate the inhalation biopersistence of a chrysotile asbestos that was used as a component of a joint-compound, a feasibility study was initiated to evaluate the short-term biopersistence of the chrysotile alone and of the chrysotile in combination with the sanded reformulated joint-compound. Two groups of Wistar rats were exposed to either 7RF3 chrysotile (Group 2) or to 7RF3 chrysotile combined with aerosolized sanded joint-compound (Group 3). In addition, a control group was exposed to filtered-air. The chrysotile used in the Ready Mix joint compound is rapidly removed from the lung. The chrysotile alone exposure group had a clearance half-time of fibers L > 20 microm of 2.2 days; in the chrysotile plus sanded exposure group the clearance half-time of fibers L > 20 microm was 2.8 days. However, across all size ranges there was approximately an order of magnitude decrease in the mean number of fibers remaining in the lungs of Group 3 as compared to Group 2 despite similiar aerosol exposures. Histopathological examination showed that the chrysotile exposed lungs had the same appearance as the filtered-air controls. This study uniquely illustrates that additional concurrent exposure to an aerosol of the sanded joint-compound, with large numbers of fine-particles depositing in the lungs, accelerates the recruitment of macrophages, resulting in a tenfold decrease in the number of fibers remaining in the lung. The increased number of macrophages in the chrysotile/sanded joint exposure group was confirmed histologically, with this being the only exposure-related histological finding reported.

Re-creation of historical chrysotile-containing joint compounds.

Chrysotile-containing joint compound was commonly used in construction of residential and commercial buildings through the mid 1970s; however, these products have not been manufactured in the United States for more than 30 years. Little is known about actual human exposures to chrysotile fibers that may have resulted from use of chrysotile-containing joint compounds, because few exposure and no health-effects studies have been conducted specifically with these products. Because limited amounts of historical joint compounds are available (and the stability or representativeness of aged products is suspect), it is currently impossible to conduct meaningful studies to better understand the nature and magnitude of potential exposures to chrysotile that may have been associated with historical use of these products. Therefore, to support specific exposure and toxicology research activities, two types of chrysotile-containing joint compounds were produced according to original formulations from the late 1960s. To the extent possible, ingredients were the same as those used originally, with many obtained from the original suppliers. The chrysotile used historically in these products was primarily Grade 7RF9 from the Philip Carey mine. Because this mine is closed, a suitable alternate was identified by comparing the sizes and mineral composition of asbestos structures in a sample of what has been represented to be historical joint compound (all of which were chrysotile) to those in samples of three currently commercially available Grade 7 chrysotile products. The re-created materials generally conformed to original product specifications (e.g. viscosity, workability, crack resistance), indicating that these materials are sufficiently representative of the original products to support research activities.

A simple and sensitive enzyme immunoassay for determination of soluble type-specific polysaccharide from group B streptococci.

A method was developed for the determination of soluble group B streptococcal type-specific polysaccharide in diluted culture supernatant. The type-specific antigen was immobilized to the solid phase of an enzyme immunoassay using wheat germ agglutinin as a link between the plastic surface and the polysaccharide. The binding of monovalent rabbit antiserum to the type-specific polysaccharide was quantitated by an anti-rabbit IgG-enzyme conjugate. Antisera against each of the polysaccharide types Ia, Ib. II and III gave strong and specific reactions against the respective antigen. The ultimate sensitivity of the assay was 70 pg/ml, as determined for type III polysaccharide. Using this technique, it was found that the concentration of soluble type-specific antigen in a GBS, type III culture supernatant reached a steady-state approximately 3 h after the beginning of the stationary growth phase of the bacteria. Ten type III strains were investigated for synthesis of type-specific polysaccharide, and a positive correlation between the production of capsular and soluble type III antigen was found. There was also an inverse correlation between soluble antigen production and the buoyant densities of these strains. The method described may be used for the serotyping of encapsulated GBS and/or determination of soluble type-specific antigen synthesis.

Tissue cages for study of experimental streptococcal infection in rabbits. I. Production of erythrogenic toxins in vivo.

Tissue cages implanted subcutaneously were used to infect rabbits with erythrogenic toxin (ET) producing streptococci. The in-vivo production of ET was followed during the infection by immunoprecipitation analyses of the tissue cage fluid (TCF). ET types A and C were mainly detected during the first week of infection, but, as late as 4 weeks after the inoculation, ET was occasionally found in TCF. The nonspecific mitogenic activity of ET on human lymphocytes was also used as a biological marker to recognize ET in TCF. Mitogenic activity was detected in 90% of samples during the first week. In order to characterize the mitogenic material released by growing streptococci, TCF was electrofocused in polyacrylamide gel. The eluates of sliced gels were checked for mitogenic activity and compared with a purified ET preparation containing ET types A and C. It could be verified that ET type A was produced under in-vivo conditions by strains NY-5 and SF130, while ET type C was produced by strain T18. Differences between production of toxins in vitro and in vivo might be of significance for the understanding of the pathogenetic mechanisms in streptococcal infection.

Tissue cages for study of experimental streptococcal infection in rabbits. II. Humoral and cell-mediated immune response to erythrogenic toxins.

Infection of rabbits with erythrogenic toxin producing streptococcal strains caused a marked increase of humoral antibodies, which was detected by immunoprecipitation and ELISA. An antibody response directed towards the erythrogenic toxin type A was demonstrated by fused rocket immunoelectrophoresis. All toxinogenic reference strains produced ET type A under in vivo conditions despite that this toxin was not always demonstrated under in vitro conditions. The infection resulted in an increase of mitogenic response of peripheral lymphocytes to the initial nonspecific mitogenic erythrogenic toxins, whereas the Con A stimulation was depressed starting 14 days after infection and lasting during a period of 90 days. Since a normal antibody response was evoked, it seems likely that the T helper cell function was not affected.

Bacterial interference in vitro. Comparison between a quantitative kinetic and a cocultivation blood agar test method.

The aim of the present study was to compare two methods for estimation of bacterial growth interference between various bacteria using a Bioscreen robot analyzer, allowing kinetic documentation, and a cocultivation test on blood agar plates. Six laboratory strains with different virulence and growth requirements were used: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mitis, Staphylococcus aureus, and Staphylococcus epidermidis. The interference activity was correlated with a reference system of Streptococcus sanguis (strain alpha 89) and Streptococcus pyogenes (group A streptococci, GAS serotypes T 9 and T 22). The methods used and results obtained were as follows: 1. Estimation of synergistic and antagonistic bacterial interferences using a Bioscreen robot analyzer. Suspensions of viable bacteria were added to microtiter plates with different concentrations of UV light-killed bacteria in liquid media. The Bioscreen analyzer monitored bacterial growth every 10 min for 24 h giving kinetic data during the growth period. Synergisms as well as antagonisms were demonstrated between the tested bacterial strains which have not earlier been reported in the literature. However, the antagonistic effect observed between the six strains was less than that induced by the S. sanguis strain on the two strains of S. pyogenes. 2. Cocultivation of bacterial strains on blood agar surface with precultivated or simultaneously stamped interfering bacteria indicated no detectable interference between the six tested bacterial strains, while the S. sanguis strain inhibited the growth of S. pyogenes strains as well as the hemolysis around the colonies. The Bioscreen method was found more sensitive for testing bacterial interference compared to the commonly used blood agar test.

An experimental model for acute poststreptococcal glomerulonephritis in mice.

A number of factors have been implicated in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN). The lack of a reliable animal model has made it difficult to further examine the role of these factors in the pathogenetic process. In this report, we present a tissue cage model in mice for the study of APSGN. Morphological and immunohistological changes in the kidney, resembling those of APSGN in man, were induced at high frequency in the experimental model after infection with group A streptococcal nephritis isolates. Nephritis-associated strain induced hypercellularity, occlusion of capillaries, and C3 deposition at high frequencies compared to the changes induced in animals infected with a non-nephritis-associated strain and non-infected controls. In animals infected with a nephritis isolate, hematuria and proteinuria were also detected. If penicillin treatment was initiated on the third day of infection, the development of the nephritis process was prevented. Streptokinase, as well as preabsorbing antigen and streptococcal pyrogenic exotoxin B (SpeB), have been implicated in the pathogenesis of APSGN. These proteins, as well as SpeA and SpeF, were detected in the fluids of the infectious focus, regardless of the origin of the strains and whether or not glomerulonephritis was seen. Antibodies to streptokinase were evoked in the majority of the infected animals. This immune response did not correlate with the nephritic process since hypercellularity was also seen in animals which lacked detectable streptokinase antibodies. The results show that the mouse tissue cage model can be used to study APSGN and to evaluate factors involved in the pathogenesis of the disease.

The interference of gingival cell cultures with growth of selected bacteria.

The aim of the present study was to analyze the interference of oral tissue cells or cell lines (effector cells) with growth of reference bacteria, and furthermore to investigate whether cells derived from different individuals differ in such activity. The reference bacteria were Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum. The effector cells used were gingival fibroblasts (GF) from 21 periodontally involved persons, gingival epithelial cells (E) from 2 such persons, HeLa cells (HeLa), and an amnion cell line (Amnion). The cells were cultivated and their supernatants tested for antibacterial activity in a Bioscreen robot analyzer (Labsystems, Finland). Results suggest that the antibacterial activity of each tested primary cell line of tissue had its own profile depending on cell type and donor, and that the composition of oral microbiota was influenced by oral cells, which might, in turn, contribute to the variations in the pathogenesis of periodontal diseases.

A streptococcal plasminogen activator in the focus of infection and in the kidneys during the initial phase of experimental streptococcal glomerulonephritis.

Strains of group A streptococci known to secrete the nephritis strain-associated protein (NSAP), a plasminogen activator, were studied for their ability to produce APSGN in rabbits. A tissue cage model was used to monitor the secretion of NSAP at the focus of infection and histopathological examination of kidney tissue was used to determine glomerular pathology. Animals infected with NSAP positive strains exhibited NSAP deposits in the glomerular tissue by day 7 in the absence of antibody to this molecule with progressive pathology indicative of APSGN three weeks later. Animals infected with the NSAP negative streptococcal strain exhibited no abnormal pathology. The ability of NSAP to bind to kidney tissue suggested that it has unique nephrotropic properties; and its ability to activate plasminogen to plasmin, possibly in situ, suggests that much of the pathological events associated with APSGN may be initiated by plasmin activity.

Antimicrobial screening of zinc in the absence or presence of oleoresins and various resin acids.

Zinc and oleoresins are the main components of several wound dressings, and are also frequently used in root canal treatment. The in vitro antibacterial effects of zinc, six highly purified resin acids and two commercial oleoresins alone or combined in varying proportions were analysed. Oleoresins are composed of approximately 90% resin acids and the most common acids were included in this study. The antibacterial activity of the various chemicals was estimated using a Bioscreen robot analyser, which allowed 24 h kinetic documentation of bacterial growth. The bacteria employed were reference species commonly occurring on human skin or of oral origin. Zinc as well as the oleoresins and the pure resin acids all showed antibacterial activity when present in growth media, but the sensitivity of the bacteria varied. The presence of resin acids and oleoresins increased the antibacterial effect of zinc to varying degrees depending on the combination and the bacterial species tested. The results of the present study indicate that zinc, resin acids, or oleoresins alone, as well as combined, show antibacterial activity against selected aerobic Gram-positive and anaerobic Gram-negative bacteria.

Synchronous occurrence of carcinoid tumour of the appendix and T-cell lymphoma of the ileum. A case report with review of the literature.

Carcinoid tumours of the gastrointestinal tract are often associated with other tumour types at various sites. However, only rarely has a lymphoma constituted the second tumour. In the present paper, we report the case of a 62-year-old woman who was operated on for a perforated T-cell lymphoma of the ileum and in whom an appendicular carcinoid tumour was incidentally discovered at surgery. It was possible to completely remove both tumours and postoperatively the patient underwent CHOP treatment. Ten months after surgery the patient is well, with no tumour manifestations. We also discuss problems concerning classification of the lymphoma on account of loss of the T-cell antigen CD45RO (UCHL-1).

Estimation of type-specific anti-streptococcal M-protein antibodies with biotinylated peptides in human sera.

The design of a novel enzyme-linked immunosorbent assay for the estimation of antibodies directed against the N-terminus of the M-protein of Streptococcus pyogenes is described. The ELISA employs biotinylated peptide antigens of the types 1, 4, 12 and 19 immobilized by (strept-)avidin on the surface of polystyrene microtiter wells. In rabbit hyperimmune sera and in human serum samples, antibodies against the corresponding serotype could be detected with high sensitivity and specificity.

Accumulation of penicillin in vaginal fluid.

The excretion of phenoxymethylpenicillin in vaginal fluid was determined in five women after intake of a single dose of 1 g phenoxymethylpenicillin and in five women on a 10-day medication scheme with 1 g twice daily. After the single dose, there was a steady increase of penicillin in vaginal secretion during the following 3 hours. During the same period, the concentrations in serum and saliva peaked and started to decline. Fifteen hours after intake, vaginal fluid contained more than 1 mg/L, whereas no activity was found in serum or saliva. During the 10-day course of treatment, vaginal concentrations ranged between 2-3 mg/L. The drug was not eliminated from the vagina until the second day after ceasing medication. The accumulation and slow pharmacokinetics of phenoxymethylpenicillin in the vagina may be explained by the countercurrent vascular system supplying the internal genitalia and upper vagina. The effect of the high concentrations of penicillin on the vaginal microflora is discussed.

A sialic-acid-specific lectin from Cepaea hortensis that promotes phagocytosis of a group-B, type-Ia, streptococcal strain.

Group-B streptococci that possess a type-specific surface polysaccharide undergo phagocytosis only in the presence of antibodies to this, and complement. The snail Cepaea hortensis forms a lectin that is specific for sialic acid; treatment with this promoted the phagocytosis of a group-B streptococcus of serotype Ia (strain O90) in the absence of opsonic antibodies. The effect of the lectin was dose-dependent and required the presence of complement. The specificity of the lectin reaction for sialic acid was proved by the inhibition of phagocytosis by bovine submaxillary mucin. The participation of complement in the reaction was confirmed by demonstrating that C3 was bound to the surface of lectin-treated cells.