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Lung cancer and exposure to man-made vitreous fibers: results from a pooled case-control study in Germany.

BACKGROUND: To investigate the association between lung cancer and occupational exposure to man-made vitreous fibers (MMVF), a pooled analysis of two case-control studies was conducted in the years 1988-1994. METHODS: The case series consisted of 3498 males who were histologically or cytologically verified primary lung cancer cases. 3541 male population controls were drawn at random from the general population and matched to cases by sex, age, and place of residence. To examine the relationship between MMVF and lung cancer we asked all study subjects who worked for at least 6 months as construction and installation workers whether they ever installed or removed insulations and what kind of insulation material they used. RESULTS: Some 304 (8.7%) cases and 170 (4.8%) controls reported to have insulated with glass wool or mineral wool mats. Coded as ever/never exposed, the odds ratio was 1.48 (95% CI: 1.17-1.88), adjusted for smoking and asbestos. To be sure to exclude any confounding effect of asbestos, we tried to identify those cases and controls who insulated with glass wool or mineral wool mats only and never reported any asbestos exposure. For this group we calculated an odds ratio of 1.56 (95% CI: 0.92-2.65), after adjustment for smoking. An elevated risk was also estimated on the basis of an expert rating which was done for a subgroup of cases and controls. Ever exposure to MMVF (but not to asbestos) in this subgroup yielded an odds ratio of 1.30 (95% CI: 0.82-2.07). CONCLUSIONS: Our study provides some indication for an excess risk of man-made vitreous fibers. This result also persists after adjustment for smoking and asbestos.

Asbestos↗

Cell-mediated cytotoxicity of sensitized spleen cells against target liver cells--in vivo and in vitro study with a mouse model of experimental autoimmune hepatitis.

Spleen cells obtained from C57BL/6 (B6) mice with an experimental autoimmune hepatitis were transferred to normal C57BL/6 recipient mice. Most prominent liver damages occurred in the recipient mice injected with sensitized nylon wool column-adherent spleen cells from the donor mice. Production of such liver damage was blocked by treatment of the sensitized adherent spleen cells with anti-Thy 1,2 monoclonal antibody and complement before injection. Based on these in vivo results, a microcytotoxicity assay was performed using isolated C57BL/6 hepatocytes as target cells and sensitized spleen cells obtained from hepatitis donor mice as effector cells. The fraction of sensitized nylon wool-adherent spleen cells demonstrated a high cytotoxic activity against isolated syngeneic hepatocytes, although the other fractions and spleen cells of control animals showed no such effect. The cytotoxic activity of sensitized-adherent spleen cells against target hepatocytes was significantly reduced after treatment with anti-Thy 1,2 antibody and complement, but it increased after depletion of B cells and Fc receptor-bearing T-cells. Although these sensitized nylon wool-adherent spleen cells showed high cytotoxic activities against syngeneic hepatocytes, their cytotoxicity against allogeneic hepatocytes was lower. They exerted no cytotoxic activity against syngeneic renal glomerular cells and EL-4 thymoma cells. These results suggest that sensitized T-cells in the nylon wool column-adherent fraction play the role of cytotoxic killer cells against target liver cells in vitro.

Animals↗

Preparation of leukocyte-poor platelets by filtration.

There is evidence that leukocyte contaminating red blood cells and platelet concentrates are responsible for refractoriness to platelet transfusions. The efficacy of a cotton-wool filter to remove leukocytes from red blood cells has been documented previously. The present study was designed to evaluate whether the cotton-wool filters can effectively remove leukocytes from platelet concentrates. Sixty pools of random-donor platelets and single-donor plateletpheresis products were filtered through a cotton-wool filter. The efficacy of filtration was determined by measuring the absolute numbers of leukocytes and platelets and subpopulations of mononuclear cells. The average platelet loss was 8% per pool of random platelets and 10% per plateletpheresis product. The average leukocyte removal was 99% from a pool of random platelets and plateletpheresis concentrates collected by CS-3000 and 90% from plateletpheresis concentrates harvested by single-stage COBE/IBM-2997. The filtration removed 100% of granulocytes, 95% of monocytes, 90% of B-lymphocytes, and 85% of T-lymphocytes. We conclude that filtration through a cotton-wool filter is an efficient and cost-effective method for preparation of leukocyte-poor platelets.

Blood Component Removal↗

Lymphocyte isolation from chronically inflamed synovial membranes.

A simple two-step procedure was developed for isolation of lymphocytes from chronically inflamed human synovial membranes. In the first step minced inflamed synovial tissues are disrupted enzymatically by deoxyribonuclease and collagenase. The second step consists of nylon-wool column filtration of the isolated cells. 7 min of preincubation of up to 37.4 X 10(6) cells in a column packed with 600 mg nylon-wool in 6 ml prior to filtration did not result in significant selective losses of either T or B cells, whereas 45 min of preincubation did. Recovery of lymphocytes after nylon-wool column filtration ranged from 68 to 95% (mean 80%) and viability was always higher than 90%. Nylon-wool column filtration increased the proportion of lymphocytes by a mean 73%. The method allows rapid identification of synovial tissue lymphocyte subpopulations as well as characterization of their function.

Adult↗

Relationship between large granular lymphocytes and NK-1.2+ cells from normal and poly(inosinic:cytidylic acid) (poly(I:C]-treated mice.

The present work analyzes the relationship between large granular lymphocytes (LGL), NK-1.2+ cells, and natural killer (NK) activity of C3H/HeN mice. Different hematic cell fractions were obtained according to their nylon-wool adherence and density on Percoll gradients. NK-1.2+ cells (8% of nucleated cells) were more numerous than LGL (3% of nucleated cells) in the input blood population. Eighty-five percent of LGL were recovered from the sorted NK-1.2+ cell fraction. After incubation on nylon-wool column, 63% of LGL and 36% of NK-1.2+ were eluted in the nonadherent fraction. Eighteen percent of NK-1.2+ cells were recovered from the most adherent elutable cell fraction. After the discontinuous Percoll gradient most LGL were present in the low-density fractions while 20% of NK-1.2+ cells were recovered from the highest-density fraction. NK activity was significant both in the nylon-wool-nonadherent and -adherent fractions. After the Percoll gradient most NK activity was present in the low-density fractions. In the present experimental conditions treatment poly(inosinic:cytidylic acid) (poly(I:C] did not increase the numbers of LGL and NK-1.2+ cells either in the blood or in the spleen. However it increased significantly the NK activity of the input cell populations and of the nonadherent and low-density fractions. Similarly, exposure of specific pathogen-free (SPF) mice to non-SPF conditions stimulated NK cytotoxicity but did not alter the percentage of LGL in the blood or in the spleen. Poly(I:C) treatment induced a shift of LGL and NK-1.2+ cells toward the low-density fractions. In poly(I:C)-treated mice images of granule secretion from LGL were detected. Taken together, the present results indicate that LGL and NK-1.2+ cell populations do not totally overlap. Moreover subpopulations of LGL and NK-1.2+ cells can differ in NK activity, morphology, density, adherence to nylon wool, and response to poly(I:C).

Animals↗

Effects of various vehicles on the penetration of flufenamic acid into human skin.

The effect of various vehicles (polyacrylate gels and wool alcohol ointments) on the penetration of flufenamic acid into excised human skin was investigated. Physico-chemical properties of the formulations were examined and discussed. Penetration data was gathered using two different in vitro test systems: the Saarbruecken penetration model (SB-M) and the Franz diffusion cell (FD-C). With wool alcohol ointments, drug concentration in the formulation was the decisive parameter for drug liberation and penetration. The incorporation of water into wool alcohol ointment led to increased drug amounts within the deeper skin layers (DSL), especially after longer incubation times. The drug concentration within the stratum corneum (SC) was not influenced by the bleeding effect of lipophilic, liquid components of the various wool alcohol ointments. With polyacrylate gels different results for liberation and penetration were observed. These results could be related to the effects of the drug concentration within the formulation and the penetration enhancers incorporated into the gels. Especially the effects of penetration enhancers clearly illustrated that liberation experiments do not predict the situation in the skin, but make experiments with a biological barrier essential. The high water content of the gels led to hydration of the skin specimen for the SB-M and the FD-C and therefore, in contrast to previous findings, comparable data were obtained in the penetration studies with both models. Furthermore, the quasi steady-state drug amount in the SC could be calculated for all formulations using an equation derived from a Michaelis-Menten kinetics. The data from both test systems were linearly correlated to each other. In addition, a direct linear relationship between the SC drug amount and the drug amount in the DSL was found as long as the quasi steady-state drug amount in the SC was not reached. A combination of all results might offer the chance to reduce the costs and to simplify the development of a new drug formulation.

Chemistry, Pharmaceutical↗

The persistence of human scalp hair on clothing fabrics.

This study reports the persistence behaviour of human scalp hairs under a number of different circumstances. The effects of artificial dyeing of hairs, the presence or absence of roots and different types of fabrics on the persistence of hair on a variety of garments were investigated. The garments were made from cotton, polycotton, cotton/acrylic, polyester and wool. The results indicated that neither artificial dyes nor the presence or absence of roots had statistically significant effects on the persistence of hair. In contrast, the type of fabric had a major impact and it was found that, generally, hairs persist longer on rougher fabrics. The rate of loss of hairs from non-woollen fabrics during normal wear was found to follow an exponential decay curve. In contrast, the rate of loss from the woollen garments was quite linear, indicating a constant, even loss, and thus suggests that a different process is involved in the persistence of hairs on woollen garments from that on non-woollen garments. The speed at which hair was lost from fabrics decreased in the order polyester, cotton/acrylic, polycotton, cotton, smooth wool, rough wool, so that wool gives the best chance of recovering samples of hair. Due to the uniqueness of each case, it is advised that caution be used when making any interpretations and before drawing any conclusions.

Clothing↗

Removal of heavy metal ions from aqueous solutions using various low-cost adsorbents.

The removal of single heavy metals Co and Zn from aqueous solutions using various low-cost adsorbents (Fe(2)O(3), Fe(3)O(4), FeS, steel wool, Mg pellets, Cu pellets, Zn pellets, Al pellets, Fe pellets, coal, and GAC) was investigated. Experiments were performed at different solution pH values (1.5-9) and metal concentrations (0.67-333 mg/l). The effect of solution pH on metal adsorption using Fe(2)O(3) and Fe(3)O(4) was significant, but was negligibly small using steel wool, Mg pellets, Fe pellets, and Al pellets over the entire pH range. Steel wool and Mg pellets were the most excellent adsorbents; for example, the removal of Zn and Co from dilute solutions (<35 mg/l) was greater than 94% at an adsorbent dose of 1.7 g/l. A mass transfer model, which involves two parameters tau (50% breakthrough time) and k (proportionality constant), was proposed to describe breakthrough data of Co in the fixed beds packed with steel wool and Mg pellets. The calculated breakthrough curves agreed well with the measured data (standard deviation < 6%). The value of tau decreased with increasing the flow rate. The effects of flow rates on the value of k and adsorption capacity are discussed.

Adsorption↗

Silica, asbestos, man-made mineral fibers, and cancer.

Approximately three million workers in the United States are estimated to be exposed to silica, man-made mineral fibers, and asbestos. The lung is the primary target organ of concern. Each of these substances is composed predominantly of silicon and oxygen; asbestos and silica are crystalline, and asbestos and man-made mineral fibers are fibers. Man-made mineral fibers and asbestos are used as insulating agents, with the former having generally replaced the latter in recent years. Silica is used in foundries, pottery, and brick making, and is encountered by miners. A meta-analysis of 16 of the largest studies with well-documented silica exposure and low probability of confounding by other occupational exposures, indicates a relative risk (RR) of 1.3 (95 percent confidence interval [CI] = 1.2-1.4). Lung cancer risks are highest and most consistent for silicotics, who have received the highest doses (RR = 2.3, CI = 2.2-2.4, across 19 studies). The data for mineral fibers continue to support the International Association for Research on Cancer's 1988 judgment that mineral fibers are a possible human carcinogen (Group 2B). Recent epidemiologic studies provide little evidence for lung carcinogenicity for either glass wool or rock/slag wool. Ceramic fibers, a much less common exposure than glass wool and rock/slag wool, are of concern because of positive animal studies, but there are insufficient human data. Regarding asbestos, its carcinogenicity for the lung and mesothelium is well established. With regard to the controversy over chrysotile and mesothelioma, the data suggest chrysotile does cause mesothelioma, although it may be less potent than amphibole asbestos.

Animals↗

Differences in inflammatory responses and cytotoxicity in RAW264.7 macrophages induced by Streptomyces Anulatus grown on different building materials.

Streptomyces anulatus, an indicator microbe of mold in buildings, was grown on different building materials in order to study the impact of growth conditions on the ability of the spores of this microbe to induce toxicity and inflammatory responses. The microbes were grown for 2 months on sterilized and unsterilized wood, chipboard, concrete, plaster board and mineral wool in tight glass vessels under humid conditions. The highest microbial spore concentration was detected on the sterilized mineral wool followed by the sterilized plaster board and the unsterilized mineral wool. Mouse RAW264.7 macrophages were exposed in vitro for 24 h to the spores of S. anulatus and the production of the inflammatory mediators, nitric oxide (NO), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-10 (IL-10) and cytotoxicity, were measured. The dose equivalent to 5 x 10(5) spores/ml of medium was used to compare the different materials. The most intense production of NO (11.6 microM), TNF alpha (560 pg/ml) and IL-6 (2800 pg/ml) in macrophages was induced by the spores grown on sterilized plaster board. They also caused the greatest loss of cell viability (39%). The spores grown on sterilized concrete induced significant production of NO (1.5 microM) and decreased cell viability (22%), and the spores grown on unsterilized and sterilized mineral wool increased production of NO (4.1 microM and 0.8 microM, respectively). The spores did not stimulate production of the anti-inflammatory cytokine IL-10. These results indicate that the ability of S. anulatus to induce inflammatory responses and cytotoxicity in macrophages is dependent on the growth conditions provided by different building materials.

Air Pollution, Indoor↗

[Ocular microangiopathy syndrome in patients with AIDS is associated with increased plasma levels of the vasoconstrictor endothelin-1].

OBJECTIVE: Ocular microangiopathic syndrome is the most frequent ophthalmic finding in patients suffering from the acquired immunodeficiency syndrome (AIDS). Ocular microvascular changes including cotton-wool spots are closely associated with neuroretinal and cognitive deficits in patients infected with the human immunodeficiency virus type 1 (HIV-1). Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving vascular structures. METHODS: We studied 29 patients with AIDS by indirect ophthalmoscopy and by slit lamp biomicroscopy, and endothelin-1 immunoreactivity (IR) was measured in plasma by radioimmunoassay. Cotton-wool spots were counted as indicator of retinal microvasculopathy. Conjunctival bloodflow sludging in conjunctival vessels was measured by a standardized rating scale as indicator of conjunctival microvasculopathy. Parameters of immunosystemic damage were determined as covariates. RESULTS: Endothelin-1 IR was closely associated with the number of cotton-wool spots (Spearman r = 0.53, p < 0.01) and with the extent of conjunctival blood-flow sludging (r = 0.61, p < 0.001). The level of significance became stronger applying analysis of covariance with Endothelin-1 IR as dependent variable and number of cotton-wool spots (p < 0.0001) or extent of conjunctival blood-flow sludging (p < 0.0001) as independent variables. CONCLUSION: Our data are consistent with the hypothesis that the vasoconstrictor endothelin-1 has an important role in the pathogenesis of HIV-1-related ocular microangiopathic syndrome. As HIV-1-related ocular microangiopathic syndrome is associated with neuroretinal and cognitive deficits in patients with HIV-1 disease the therapeutic use of endothelin antagonists currently under investigation should be discussed.

Acquired Immunodeficiency Syndrome↗

Undernutrition in sheep. The effect of supplementation with protein on protein accretion.

In a comparative-slaughter experiment, individually rationed wether lambs initially of 42 kg were given 235, 362 or 456 kJ metabolizable energy (ME)/kg live weight (LW)0.75 per d as sodium hydroxide-treated barley straw with urea (six lambs per treatment), or NaOH-treated barley straw with urea plus 125 g/d white-fish meal to give 307 or 488 kJ ME/kg LW0.75 per d (seven lambs per treatment) for 92 d. All unsupplemented lambs lost both fat and body protein. The changes in fat were -3.53, -2.75 and -1.40 (SE 0.59) kg (initial value 8.6 kg), and the changes in body protein were -0.47, -0.09 and -0.14 (SE 0.13) kg (initial value 4.9 kg) for the three unsupplemented groups respectively. When supplemented with fish meal, fat was again lost as -1.53 and -0.93 (SE 0.55) kg, but wool-free body protein was increased, and gains were 0.48 and 0.89 (SE 0.12) kg for the two supplemented groups respectively. All animals lost wool-free body energy, total changes being -150, -111, -59 and -49 and -16 MJ respectively. When corrected to an equal ME intake the supplemented lambs, when compared with the unsupplemented lambs, gained (instead of losing) body protein (P less than 0.001) and lost less fat (P less than 0.05). Wool growth did not respond to supplemental protein, but was related to ME intake with an increase of 0.78 g wool fibre for each additional MJ ME. The maintenance requirements of the unsupplemented and supplemented groups respectively were estimated by regression analysis to be 554 and 496 kJ ME/kg LW0.75 per d. The apparent utilization of ME below energy equilibrium (km) was 0.31 (SE 0.08) for the unsupplemented animals, and 0.12 (SE 0.10) for the supplemented animals, well below a km of 0.70 which current UK standards (Agricultural Research Council, 1980) would predict. Most of these differences could be reconciled if basal metabolism was assumed not to be constant. It is concluded that lambs in negative energy balance can continue lean body growth at the expense of body fat, provided sufficient dietary protein is available. It is also concluded that since the animals at the lowest ME intakes required less ME than predicted by current feeding standards, the effect was that it would have been difficult to distinguish between the apparent utilization of ME for maintenance (km) and for fattening (kf).

Animals↗

Synthetic vitreous fibers: a review of toxicology research and its impact on hazard classification.

Because the inhalation of asbestos, a naturally occurring, inorganic fibrous material, is associated with lung fibrosis and thoracic cancers, concerns have been raised about the possible health effects of synthetic vitreous fibers (SVFs). SVFs include a very broad variety of inorganic fibrous materials with an amorphous molecular structure. Traditionally, SVFs have been divided into three subcategories based on composition: fiberglass, mineral wool (rock, stone, and slag wools), and refractory ceramic fiber. For more than 50 years, the toxicologic potential of SVFs has been researched extensively using human epidemiology and a variety of laboratory studies. Here we review the research and its impact on hazard classification and regulation of SVFs. Large, ongoing epidemiology studies of SVF manufacturing workers have provided very little evidence of harmful effects in humans. Several decades of research using rodents exposed by inhalation have confirmed that SVF pulmonary effects are determined by the "Three D's", fiber dose (lung), dimension, and durability. Lung dose over time is determined by fiber deposition and biopersistence in the lung. Deposition is inversely related to fiber diameter. Biopersistence is directly related to fiber length and inversely related to fiber dissolution and fragmentation rates. Inhaled short fibers are cleared from the lung relatively quickly by mobile phagocytic cells, but long fibers persist until they dissolve or fragment. In contrast to asbestos, most of the SVFs tested in rodent inhalation studies cleared rapidly from the lung (were nonbiopersistent) and were innocuous. However, several relativley biopersistent SVFs induced chronic inflammation, lung scarring (fibrosis), and thoracic neoplasms. Thus, biopersistence of fibers is now generally recognized as a key determinant of the toxicologic potential of SVFs. In vitro dissolution of fibers in simulated extracellular fluid correlates fairly well with fiber biopersistence in the lung and pulmonary toxicity, but several exceptions suggest that biopersistence involves more than dissolution rate. Research demonstrating the relationship between biopersistence and SVF toxicity has provided a scientific basis for hazard classification and regulation of SVFs. For a nonhazardous classification, legislation recently passed by the European Union requires a respirable insulation wool to have a low lung-biopersistence or be noncarcinogenic in laboratory rats. U.S. fiberglass and mineral wool industries and the Occupational Health and Safety Administration (OSHA) have formed a voluntary Health and Safety Partnership Program (HSPP) that include: a voluntary permissible exposure level (PEL) in the workplace of 1 fiber/cc, a respiratory protection program for specified tasks, continued workplace air monitoring, and, where possible, the development of fiber formulations that do not persist in the lung. RCF manufacturers have implemented a Product Stewardship Program that includes: a recommended exposure guideline of 0.5 fibers/cc; a 5-year workplace air monitoring program; and research into the development of high-temperature-resistant, biosoluble fibers.

Animals↗

Mechanisms of genetic resistance to Friend virus leukemia. III. Susceptibility of mitogen-responsive lymphocytes mediated by T cells.

Friend leukemia virus (FV) suppressed the proliferative responses of spleen, lymph node, marrow, and thymus cell populations to various T- and B-cell mitogens. Cells taken from mice, e.g. BALB/c genetically susceptible to leukemogenesis in vivo were much more susceptible to suppression of mitogenesis in vitro than similar cells from genetically resistant mice, e.g., C57BL/6. Nylon wool-purified splenic T cells from BALB/c and C3H mice lost susceptibility to FV-induced suppression of mitogenesis but became suppressible by addition of 10% unfiltered spleen cell. Thus, FV mediates in vitro suppression of lymphocyte proliferation indirectly by "activating" a suppressor cell. The suppressor cell adhered to nylon wool but not to glass wool or rayon wool columns. Pretreatment of spleen cells with carbonyl iron and a magnet did not abrogate the suppressor cell function. Suppressor cells were not eliminated by treatment with rabbit antimouse immunoglobulin (7S) and complement (C). However, high concentrations of anti-Thy-1 plus C destroyed suppressor cells of the spleen; thymic suppressor cells were much more susceptible to anti-Thy-1 serum. Nude athymic mice were devoid of suppressor cells and their B-cell proliferation was relatively resistant to FV-induced suppression in vitro. The suppressor cells in the thymus (but not in the spleen) were eliminated by treatment of mice with cortisol. Thus, FV appears to mediate its suppressive effect on mitogen-responsive lymphocytes by affecting "T-suppressor cells." Spleen cells from C57BL/6 mice treated with 89Sr to destroy marrow-dependent (M) cells were much more suppressible by FV in virto than normal C57BL/6 spleen cells. However, nylon-filtered spleen cells of 89Sr-treated C57BL/6 mice were resistant to FV-induced suppression in vitro, indicating that the susceptibility of spleen cells from 89Sr-treated B6 mice is also mediated by suppressor cells. Normal B6 splenic T cells were rendered susceptible to FV-induced suppression of mitogenesis by addition of 10% spleen cells from 89Sr-treated B6 mice. Thus, M cells appear to regulate the numbers and/or functions of T-suppressor cells which in turn mediate the immunosuppressive effects of FV in vitro. Neither mitogen-responsive lymphocytes nor T-suppressor cells are genetically resistant or susceptible to FV. The genetic resistance to FV is apparently a function of M cells, both in vitro as well as in vivo.

Animals↗

Pyrolysis and volatilization of cocaine.

The increasing popularity of inhaling cocaine vapor prompted the present study, to determine cocaine's fate during this process. The free base of [3H]cocaine (1 microCi/50 mg) was added to a glass pipe, which was then heated in a furnace to simulate freebasing. Negative pressure was used to draw the vapor through a series of glass wool, ethanol, acidic, and basic traps. Air flow rate and temperature were found to have profound effects on the volatilization and pyrolysis of cocaine. At a temperature of 260 degrees C and a flow rate of 400 mL/min, 37% of the radioactivity remained in the pipe, 39% was found in the glass wool trap, and less than 1% in the remainder of the volatilization apparatus after a 10-min volatilization. Reducing the air flow rate to 100 mL/min reduced the amount of radioactivity collected in the glass wool trap to less than 10% of the starting material and increased the amount that remained in the pipe to 58%. GC/MS analysis of the contents of the glass wool trap after volatilization at 260 degrees C and a flow rate of 400 mL/min revealed that 60% of the cocaine remained intact, while approximately 6 and 2% of the starting material was recovered as benzoic acid and methylecgonidine, respectively. As the temperature was increased to 650 degrees C, benzoic acid and methylecgonidine accounted for 83 and 89% of the starting material, respectively, whereas only 2% of the cocaine remained intact. Quantitation of cocaine in the vapor during the course of volatilization revealed high concentrations during the first two min and low concentrations for the remaining time.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoates↗

Historical cohort study of US man-made vitreous fiber production workers: VI. Respiratory system cancer standardized mortality ratios adjusted for the confounding effect of cigarette smoking.

To date, the US cohort study of man-made vitreous fiber workers has provided no consistent evidence of a relationship between man-made vitreous fiber exposure and mortality from malignant or non-malignant respiratory disease. Nevertheless, there have been small, overall excesses in respiratory system cancer (RSC) among workers from the fiberglass and rock/slag wool production plants included in the study that were unexplained by estimated worker exposures to respirable fiber or other agents present in the plants. The present investigation was designed to provide a quantitative estimate of the extent to which the overall excess in RSC mortality observed at the total cohort level among male fiberglass and rock/slag wool workers is a result of the positive confounding effects of cigarette smoking. Because cigarette-smoking data were neither available nor obtainable at the individual level for all members of the fiberglass and rock/slag wool cohorts, we used the "indirect" method to adjust RSC standardized mortality ratios (SMRs) at the group (cohort and plant) level. Our adjustment suggested that cigarette smoking accounts for all of the 7% and 24% excesses in RSC observed, respectively, for the male fiberglass and rock/slag wool cohorts in the latest mortality updates. The same conclusion was reached regardless of which of several alternative formulations were used to adjust local rate-based RSC SMRs. We found that our smoking adjustments were robust with respect to several alternative characterizations and (with the exception of one fiberglass plant) produced adjusted RSC SMRs that were lower than their unadjusted counterparts. Further, all statistically significantly elevated unadjusted SMRs were reduced to not statistically significant levels. These results reaffirm that RSC SMRs based on US and local rates must take into account the potential confounding effects of cigarette smoking. They also suggest that the use of local county mortality rate-based SMRs may not help to adjust for cigarette smoking to the degree suggested by some investigators.

Adolescent↗

Retinal lesions as clues to disseminated bacterial and candidal infections: frequency, natural history, and etiology.

Invasive bacterial and candidal infections are known to involve the retina, but the natural history of the retinal lesions and the utility of ophthalmologic consultation in the critical care setting as a diagnostic tool are not well understood. We 1) performed weekly funduscopic examinations on 77 medical and surgical patients in intensive care units (ICUs), 2) analyzed results of serial ocular examinations in 180 non-neutropenic patients with candidemia, and 3) reviewed the English literature on the association of retinal lesions with disseminated bacterial or candidal infection (DBCI). We found that 15 (19%) of the ICU patients had retinal lesions consistent with DBCI. Of these 15, 1 had clearly sepsis-related retinal lesions, while 13 (87%) had 1 or more systemic disease that could have explained their retinal findings (6 diabetic retinopathy; 2 human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) retinopathy; 2 hypertensive retinopathy; 1 hemolytic uremic syndrome, and 1 leukemia). Multivariate analysis revealed that systemic disease (odds ratio 8.37, 95% confidence intervals: 3.24-21.56) independently correlated with the presence of retinal lesions while DBCI, trauma, hyperalimentation, and transfusion of blood products were not independently predictive in any analysis. Twenty of the 180 (15%) candidemic patients had retinal lesions. Two (1%) had classic 3-dimensional white lesions with vitreal extension, and 5 (2.7%) had chorioretinal lesions without vitreal haziness. Notably, 10% of patients had superficial retinal hemorrhages and/or cotton wool spots that could have been due to either candidemia or a systemic disease (diabetes, hypertension, renal failure, closed head trauma). Concurrent bacteremia occurred in 3 of the 27 patients with eye lesions. Retinal lesions resolved in a mean of 33 days. None of the patients had symptoms at the time of the retinal finding. We found 3 studies that prospectively assessed retinal lesions in bacteremic patients. The frequency of retinal lesions in these series varied from 12% to 26%, with the most common lesions being cotton wool spots followed by superficial retinal hemorrhages. White-centered hemorrhages were seen in about 15% +/- 2 of bacteremic patients. Five studies prospectively evaluated candidemic patients for Candida endophthalmitis. These studies observed rates from 0% to 78% for lesions consistent with candidal endophthalmitis. Most studies performed recently found that nonspecific lesions such as cotton wool spots or superficial retinal hemorrhages occurred with a frequency of 11% to 20%. The availability of less toxic antifungal agents, more frequent use of empirical therapy, and the trend to early treatment may be altering the frequency of this complication. Observation of a classic 3-dimensional retina-based vitreal inflammatory process is virtually diagnostic of endogenous endophthalmitis due to Candida spp., but such lesions are relatively uncommon. Conversely, nonspecific lesions that could be due to bacterial or candidal endophthalmitis (cotton wool spots, retinal hemorrhages, and Roth spots) are seen frequently. These lesions are most often due to an underlying systemic disease rather than an infection. Serial examinations provide the best evidence that a given lesion is due to an intercurrent infection. The current low rate of vitreal extension of retinal process appears to be due to the high rate of empirical or therapeutic use of antifungal agents in high-risk patient groups. Ophthalmoscopy should be performed in patients with known candidemia. However, ophthalmoscopic examination seems to have little value in assisting with the discovery of occult disseminated candidiasis or bacterial infection.

Adult↗

The isolation of Streptococcus pyogenes from throat swabs.

Simulated throat swabs were prepared with known numbers of Streptococcus pyogenes; some were suspended in pasteurised human saliva and an equal number in saline. Two types of commercially available swabs were tested; these were composed of (1) plain, buffered, cotton wool, and (2) albumen-coated cotton wool. The mean recovery rates of first platings on solid media from albumen-coated and plain cotton-wool swabs were similar (8-2% and 8-3%) and the mean recovery rates from platings 1-4 were also similar (6-6% and 6-5%). The greater the delay in plating, the less were the chances of recovery of streptococci, although the viability of these was significantly prolonged on swabs held at 4 degrees C. Similar results were again produced by both types of swabs; processing swabs in saliva, however, produced by both types of swabs; processing swabs in saliva, however, produced a recovery rate that was 1-2% greater than the rate for the saline series. Swabs were also agitated or squeezed by forceps in nutrient broth to release any organisms they contained, and standard samples of the broth were then plated on solid media. Counts thus obtained indicated that about 50% of the original inoculum was still viable and could be recovered from the broth; in comparison, recoveries from initial direct plating of the swabs were low. No demonstrable toxic effect was produced by the cotton wool in these experiments.

Albumins↗