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The relevance of the research is caused by the need to improve the accuracy of mathematical models of nonlinear dynamic processes of iron ore raw materials enrichment. This direction of improving the modeling tools for complex systems will make better the control of enrichment and the quality of the final products. The main aim of the research is to increase the accuracy of dynamic spatiotemporal mathematical models of interrelated processes for control systems of the technological enrichment line of ore represented by mineral-technological varieties. Objects: dynamic spatiotemporal mathematical models of interrelated processes for control systems of the technological ore enrichment line. Methods: systematization and analysis of the developed methods of mathematical modeling of distributed interrelated processes, methods of mathematical statistics and probability theory for processing experimental results, computer information and software technologies for implementing the developed approaches. Results. The authors have proposed the improved approach for modeling iron ore raw material enrichment as spatio-temporal structures with distributed parameters, taking into account the indices of individual technological stages throughout the spectrum of the granulometric characteristics of the processed ore. To reduce the dimensionality of the models represented as distributed structures of control objects, which transform the content and yield of the useful component over the entire spectrum of ore granulometric characteristics, it is advisable to use the method of diffusion maps, in this case the Sammon's error was 2,6 %. more...

The relevance of the research is caused by the need to improve the accuracy of the means for ultrasonic operational monitoring of the characteristics of iron ore pulp solid phase in enrichment process. This area of means for improving will allow increasing the efficiency of controlling the enrichment and the quality of the final products. The main aim of the research is to increase the accuracy when measuring the particles density in pulp solid phase based on the laws of gamma radiation propagation in randomly non-uniform heterogeneous environments, as well as Lamb waves along the surfaces in contact with these fluids, in their natural or specially organized movement. Objects: processes of gamma radiation propagation in randomly inhomogeneous heterogeneous media, as well as Lamb waves on surfaces contacting these media. Methods: systematization and analysis of the methods developed for ultrasonic controlling the characteristics of solid phase of heterogeneous environments, methods of mathematical statistics and probability theory for processing the results of experiments, computer information technologies and software technologies designed to implement the techniques developed. Results. Investigated distribution patterns of gamma radiation in randomly non-uniform heterogeneous environments, as well as Lamb waves along the surfaces in contact with these fluids, in their natural or specially organized movement allow determining particle density of solid phase, which characterizes the degree of disclosure of a useful component (mineral) at known particle size and concentration in the test volume. The authors have developed the scheme for monitoring the suspensions solid phase density based on the obtained regularities. The error in measuring particle density in pulp solid phase by this method is 1–3 %. more...

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs). In this study, 20 expert melanoma pathologists rendered a diagnosis on 47 DMNs based on hematoxylin and eosin sections with demographic information. After submitting their diagnosis, the experts were given the same cases, but this time with comprehensive genomic sequencing results, and asked to render a diagnosis again. Identification of desmoplastic melanoma (DM) improved by 7%, and this difference was statistically significant ( P <0.05). In addition, among the 15 melanoma cases, in the pregenomic assessment, only 12 were favored to be DM by the experts, while after genomics, this improved to 14 of the cases being favored to be DM. In fact, some cases resulting in metastatic disease had a substantial increase in the number of experts recognizing them as DM after genomics. The impact of the genomic findings was less dramatic among benign and intermediate-grade desmoplastic tumors (BIDTs). Interobserver agreement also improved, with the Fleiss multirater Kappa being 0.36 before genomics to 0.4 after genomics. NGS has the potential to improve diagnostic accuracy in the assessment of desmoplastic melanocytic tumors. The degree of improvement will be most substantial among pathologists with some background and experience in bioinformatics and melanoma genetics., Competing Interests: Conflicts of Interest and Source of Funding: P.G. has served as a consultant for Castle Biosciences and has received an honorarium for this, he has also received royalties for textbooks from Elsevier. For the remaining authors, none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) more...

Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that most commonly occurs in ultraviolet-exposed body sites. The epidemiology of MCC in different geographies and populations is not well characterized., Objectives: The objective of this systematic review is to summarize evidence on the incidence, mortality and survival rates of MCC from population-based studies., Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from database inception to 6 June 2023. No geographic, age or date exclusions were applied. We included population-based studies of MCC that reported the incidence, survival or mortality rate, and also considered systematic reviews. A data-charting form was created and validated to identify variables to extract. Two reviewers then independently charted the data for each included study with patient characteristics, and estimates of incidence rate, mortality rate, and survival rate and assessed the quality of included studies using the Joanna Briggs Institute Checklist for Prevalence studies, Newcastle-Ottawa Scale and Assessment of Multiple Systematic Reviews. We abstracted age-, sex-, stage- and race-stratified outcomes, and synthesized comparisons between strata narratively and using vote counting. We assessed the certainty of evidence for those comparisons using the Grading of Recommendations, Assessments, Developments and Evaluations framework., Results: We identified 11 472 citations, of which 52 studies from 24 countries met our inclusion criteria. Stage I and the head and neck were the most frequently reported stage and location at diagnosis. The incidence of MCC is increasing over time (high certainty), with the highest reported incidences reported in southern hemisphere countries [Australia (2.5 per 100 000); New Zealand (0.96 per 100 000) (high certainty)]. Male patients generally had higher incidence rates compared with female patients (high certainty), although there were some variations over time periods. Survival rates varied, with lower survival and/or higher mortality associated with male sex (moderate certainty), higher stage at diagnosis (moderate-to-high certainty), older age (moderate certainty), and immunosuppression (low-to-moderate certainty)., Conclusions: MCC is increasing in incidence and may increase further given the ageing population of many countries. The prognosis of MCC is poor, particularly for male patients, those who are immunosuppressed, and patients diagnosed at higher stages or at an older age., Competing Interests: Conflicts of interest A.M.D. has received compensation from the British Journal of Dermatology (Section Editor), American Academy of Dermatology (guidelines writer), National Eczema Association (grant reviewer) and Canadian Agency for Drugs and Technologies in Health (consultant). A.M.D. has received research grants to his institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes for Health Research, National Institutes of Health and Physicians Services Incorporated Foundation. J.J.L. is a consultant for Feldan Bio, Inc., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.) more...

Deregulation of miRNAs contributes to the development of distinct cancer types, including melanoma, an aggressive form of skin cancer characterized by high metastatic potential and poor prognosis. The expression of a set of 580 miRNAs was investigated in a model of murine melanoma progression, comprising non-metastatic (4C11-) and metastatic melanoma (4C11+) cells. A significant increase in miR-138-5p expression was found in the metastatic 4C11+ melanoma cells compared to 4C11-, which prompted us to investigate its role in melanoma aggressiveness. Functional assays, including anoikis resistance, colony formation, collective migration, serum-deprived growth capacity, as well as in vivo tumor growth and experimental metastasis were performed in 4C11- cells stably overexpressing miR-138-5p. miR-138-5p induced an aggressive phenotype in mouse melanoma cell lines leading to increased proliferation, migration and cell viability under stress conditions. Moreover, by overexpressing miR-138-5p, low-growing and non-metastatic 4C11- cells became highly proliferative and metastatic in vivo, similar to the metastatic 4C11+ cells. Luciferase reporter analysis identified the tumor suppressor Trp53 as a direct target of miR-138-5p. Using data sets from independent melanoma cohorts, miR-138-5p and P53 expression were also found deregulated in human melanoma samples, with their levels negatively and positively correlated with prognosis, respectively. Our data shows that the overexpression of miR-138-5p contributes to melanoma metastasis through the direct suppression of Trp53., (Copyright © 2021. Published by Elsevier Inc.) more...

Purpose: We report a multicenter phase II study of patients with metastatic melanoma (MM), evaluating the efficacy, toxicity, progression-free survival (PFS), immunogenicity, and biomarker profile of interleukin-21 (IL-21)., Patients and Methods: Patients with no prior systemic therapy and with limited-disease MM were treated with IL-21 by using three different dosing regimens. Cohort 1 received 50 μg/kg per day by outpatient intravenous bolus injection for 5 days of each week during weeks 1, 3, and 5 of an 8-week cycle. Cohort 2 received 30 μg/kg per day on the same schedule, and cohort 3 received 50 μg/kg per day for 5 days of each week during weeks 1 and 3 of a 6-week cycle., Results: Forty patients were enrolled: three in cohort 1, 30 in cohort 2, and seven in cohort 3. Two patients in cohort 1 and four in cohort 3 had dose-limiting toxicities; all other patients were treated with a dose of 30 μg/kg per day. Common adverse events were fatigue, rash, diarrhea, nausea, and myalgia. Overall response rate (ORR) was 22.5%, with nine confirmed partial responses (median response duration, 5.3 months); 16 had stable disease (median response duration, 5.3 months). ORR did not appear to depended on IL-21 receptor expression or BRAF mutation status. The median PFS was 4.3 months and median overall survival (OS) was 12.4 months (95% CI, 10.09 to 17.81 months)., Conclusion: The ORR to IL-21 is 22.5% for first-line MM and warrants further investigation. The favorable PFS and OS suggest that this is an active agent in comparison to both historical NCIC Clinical Trials Group data and data from meta-analysis of Cooperative Group phase II trials. more...

Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology. more...

To the authors' knowledge, there is a paucity of published accounts of radiotherapy-induced ID reaction. We report a case of generalized dermatitis pathologically defined as an ID reaction after a course of local radiotherapy. more...

Split-thickness skin grafts remain central to the strategy of burn wound treatment. The dressing used to cover the donor wound site has a significant effect on healing parameters. The purpose of this study was to compare split-thickness skin graft donor site reepithelialization under Xeroform and Jelonet dressings. A dermatome was used to cut two consecutive strips of skin from 25 paired donor sites on the thigh, calf, or back of 19 participants. Standardization of the harvest method was achieved by using the same surgeon to harvest the compared skin graft strips, with attention to consistency of dermatome skin-thickness setting, downward pressure, and angle of dermatome approach. A strip of Xeroform or Jelonet was applied to one of each pair of wounds. Epidermal and dermal thickness was measured from biopsy specimens cut at the midpoint of each split-thickness graft strip. The day of final dressing separation was declared the day of complete donor reepithelialization (healing). The mean healing time for Xeroform and Jelonet was 10.4 +/- 2.6 days (n = 25) and 10.6 +/- 2.8 days (n = 25) (p = 0.76) at sites cut to a mean depth of 0.23 +/- 0.08 mm and 0.23 +/- 0.09 mm (p = 0.89), respectively. There was no correlation between graft thickness and healing time for sites dressed with Xeroform (r = 0.17) or Jelonet (r = 0.02). Donors sites reharvested 10 to 21 days after a prior harvest healed an average of 3.1 days earlier than virgin sites (8.4 +/- 1.6 versus 11.5 +/- 2.6 days, p < 0.001), although reharvested grafts were on average 0.05 mm thicker (p = 0.10). The mean thickness of reepithelialized donor-site epidermis (0.13 +/- 0.04 mm, n = 30) was found to be twice the thickness of virgin epidermis from the same sites (0.06 +/- 0.02 mm, n = 38, p < 0.001). Thirty-six grafts harvested with dermatomes set to cut 8/1000 inch (0.20 mm) deep ranged from 0.12 to 0.42 mm thick, with only eight of these grafts measuring within +/-10 percent of the desired thickness setting. Before donor dressing separation, Xeroform and Jelonet dressings were judged to be more comfortable by nine patients and one patient, respectively, whereas no difference was detected by six patients. The authors now use Xeroform as the preferred donor dressing. more...

Metastatic melanomas are often resistant to chemotherapy. To study whether the p53 mutational status affects chemosensitivity, we compared the responses to chemotherapy of four melanoma cell lines containing the wild-type p53 and four cell lines carrying the mutant p53. Cisplatin, at 10 microM, virtually killed all the cells in the wild-type p53 cell lines, while 57-95% of the cells in the mutant p53 cell lines survived (P = 0.005). After treatment with 100 nM of vincristine, on average 18% of the wild-type p53 melanoma cells survived compared with 55% of the mutant p53 cells (P = 0.04). After treatment with 40 nM, 200 nM or 1 microM of camptothecin the survival rates were, on average, 16%, 8% and 4% for the wild-type p53 melanoma cells, compared with 89%, 67% and 38% for the mutant p53 cells, respectively (P = 0.00004, P = 0.003 and P = 0.04, respectively). The anticancer agents were not toxic to normal melanocytes at doses inducing cytotoxicity in wild-type p53 melanoma cells. The main mechanism of cytotoxicity appears to be drug-induced apoptosis. Cisplatin, camptothecin and vincristine all induced apoptosis in wild-type p53 melanoma cells, but not in mutant p53 cells. Our results suggest that chemotherapy-induced apoptosis in melanoma cells is p53 dependent, and mutation of the p53 gene is an indicator of drug resistance in melanoma. more...

Mutations of the p53 gene have been implicated as an important factor in the pathogenesis of ultraviolet light induced skin cancers. To examine the role of p53 in skin carcinogenesis, we observed the development of skin cancers in homozygous p53-deficient (-/-) mice and wild-type p53 (+/+) mice, after chronic ultraviolet B (290-320 nm) exposure. At a dose of 2 J per m2 per s of ultraviolet B for 30 min three times per week, all p53-/- mice developed skin tumors by week 12. All the p53-/- mice developed multiple tumors by week 16. The majority of the tumors occurred on the ears. None of the p53+/+ mice developed skin tumors after 17 wk of UV exposure. Ten p53-/- tumors were examined histologically: five invasive squamous cell carcinomas, four squamous cell carcinomas in situ, and one actinic keratosis. p53-/- mice have a short life-span due to internal tumors or a deficiency in the immune system; however, ultraviolet B exposure did not significantly reduce the life-span of p53-/- mice. These results demonstrate that loss of wild-type p53 function shortens the latent period and predisposes the animals to the development of squamous cell carcinomas after ultraviolet irradiation. more...

We report a severe case of Wells' syndrome, or eosinophilic cellulitis, after a bee sting in a 4-year-old girl. The patient had a widespread, painful, blistering eruption that was subsequently complicated by Pseudomonas aeruginosa superinfection and septicemia, hypoalbuminemia, anemia, and neutropenia. The skin lesions responded to systemic steroid therapy. There was residual scarring alopecia of the scalp. There have been 17 previous reports of childhood Wells' syndrome. We believe that this disorder is a distinct entity that should be considered in the differential diagnosis of blistering diseases in children. more...

Background: Topical diphenylcyclopropenone (DPCP) and minoxidil have been used in the treatment of alopecia areata with variable results., Objective: This study was designed to evaluate the efficacy of DPCP alone or in combination with topical 5% minoxidil for the treatment of chronic severe alopecia areata. The effect of therapy on cutaneous T-cell and Langerhans cell subpopulations and intercellular adhesion molecule-1 (ICAM-1) expression was also examined., Methods: Fifteen patients with chronic (more than 2 years), severe (more than 50% scalp involvement) alopecia areata participated in a 24-week trial. Half of the scalp was treated with DPCP once weekly and with either 5% minoxidil solution or a vehicle solution twice daily in a randomized double-blind design. Skin biopsy specimens from each half of the scalp were obtained before therapy and after 12 and 24 weeks of therapy for histologic and immunophenotypic analysis., Results: Thirteen patients completed the study. Five of 13 patients (38%) showed marked regrowth of coarse terminal hair after 24 weeks of treatment with DPCP. The addition of topical 5% minoxidil did not produce any significant clinical benefit in this 24-week trial. Immunophenotypic analysis showed no differences between responders and nonresponders at baseline. During treatment, Leu-4, Leu-2, Leu-3, and keratinocyte ICAM-1 expression were significantly reduced in biopsy specimens of responders versus nonresponders., Conclusion: DPCP treatment showed a 38% success rate in producing cosmetically acceptable regrowth in patients with chronic severe alopecia areata. more...

Recent evidence suggests that pharmacological treatment may alter the rate of progression of cartilage damage in osteoarthritis (OA). However, a lack of accurate and precise noninvasive assessments of cartilage structure makes it difficult to answer this question directly with prospective clinical trials, prevents early diagnosis of OA and restricts assessment of treatment to evaluation of symptoms or joint function. It is important, therefore, to develop precise, noninvasive methods both for diagnosis of early OA before damage is extensive and irreversible and for evaluation of therapeutic effectiveness. Magnetic resonance imaging (MRI) allows for noninvasive, multiplanar body imaging which depends on proton density, flow, and the T1 and T2 relaxation times. Because these variables differ markedly among joint tissues, cartilage erosions are visible with MRI and it should be possible to quantify them. Our objective was to compare MRI with arthroscopy for assessing the depth of lesions in the articular cartilage of human knees to help develop and validate MRI for use in clinical trials designed to assess the effect of therapy on cartilage structure. In the first part of our study, the effect of the MRI pulse sequence variables on the images was evaluated by varying them systematically and comparing the anatomy seen with MRI with that seen at arthroscopy or arthrotomy and with the histology. In the second part, 31 patients were assessed with MRI before arthroscopy. The MRI were graded on a 4-point ordinal scale by 2 observers who were unaware of the clinical diagnosis and compared with findings at arthroscopy which were graded using the same scale.(ABSTRACT TRUNCATED AT 250 WORDS) more...

Immunohistologic markers have been of considerable value in differentiating malignant mesothelioma from adenocarcinoma. Recently, staining for milk-fat globule (MFG) protein has been suggested as a useful diagnostic test for this separation, but subsequent reports have been conflicting, with some authors finding clearcut differences, while others showed similar marking of both tumor types. To examine this technique further, we studied lung carcinomas and mesotheliomas with commercially available anti-MFG, and compared these results with those obtained with anticarcinoembryonic antigen (CEA), a commonly used immunomarker of carcinoma. We found that carcinomas showed strong cytoplasmic staining for MFG and CEA; however, a greater percentage of carcinomas were more strongly positive for CEA than for MFG. Mesotheliomas did not, for the most part, stain strongly with either antibody. In addition, carcinomas from different hospitals stained differently for MFG, but not for CEA. We conclude that although strong cytoplasmic staining for MFG is a reasonably reliable indicator of carcinoma, CEA staining provides a better separation and is considerably easier to interpret in lung cancer specimens. more...

It has been suggested that exposure to both asbestos and cigarette smoke can produce worse parenchymal lung disease than exposure to asbestos alone. Using a guinea pig model of asbestos administration that produces primarily airway disease and associated airflow abnormalities, we showed previously that the combination of asbestos and smoke acts synergistically to produce more marked increases in tissue collagen, fibrosis of airway walls, and early interstitial fibrosis than are seen with asbestos alone. To investigate the functional effects of these morphological and biochemical abnormalities, pulmonary function tests for volumes and flows, including lung volumes, pressure-volume curves, and flow-volume curves, were performed. By themselves, both smoke and asbestos produced increases in total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC); the two agents together made all these changes worse than either one alone. Both smoking and asbestos moved the pressure-volume curve upward, and the effects of the two agents together were again greater than either alone. Similarly, both smoke and asbestos decreased flows, and the two agents produced more severe impairment than either one by itself. The changes in volumes, pressure-volume curve, and flows correlated with both increased thickness of small airway walls and increases in airspace size. These observations indicate that, at least in this guinea pig model, cigarette smoke can potentiate the functional consequences of asbestos exposure. more...

For investigation of mechanisms whereby smoking might potentiate asbestos-related disease, guinea pigs were given 0.5 mg UICC amosite by intratracheal instillation. Half the animals were subsequently exposed to cigarette smoke. Animals were sacrificed at 1 day, 7 days, and 1 month after exposure. Lungs were lavaged and macrophages separated from the lavage fluid. Lung fiber concentration, numbers of fibers in macrophages, and fiber sizes from tissue (TFs), macrophages (MFs), and macrophage-free lavagate (FFs) were determined by electron microscopy. Smoke-exposed animals retained greater numbers of fibers in lung tissue by 1 month but had greater total numbers of fibers in macrophages at all time periods. In both smokers and nonsmokers, fibers in the three morphologic compartments had distinctly different lengths: the longest fibers were found associated with the lung tissue; the macrophages always contained the shortest fibers; and the macrophage-free lavagate had fibers of intermediate size. However, fiber widths and aspect ratios did not show the same clear separation by anatomic compartment, suggesting that in both smoking and nonsmoking animals length is the size parameter which is most important in determining fiber clearance. Smoking did not affect the lengths of MFs but did produce a progressive reduction in the lengths of FFs and TFs with time. These data indicate that smoking causes a marked increase in the number of fibers retained in the lung within macrophages and suggest that either macrophage removal via the mucociliary escalator or macrophage mobility is impaired by cigarette smoke. However, smoking does not change the sizes of fibers in macrophages and does not appear to depress phagocytic capacity. These observations imply that failure of macrophage clearance and subsequent re-release of fibers into the medium may at least partially explain the changes in fiber sizes and eventual increases in tissue fiber concentrations in smoke-exposed animals. more...

To determine whether asbestos-induced changes in the structure of the walls of small airways might be associated with abnormalities of pulmonary function, guinea pigs were given 10 mg of amosite asbestos (test group) or saline (control group) by intratracheal instillation. Pulmonary function tests performed 6 months later revealed significant increases in FRC, RV, and TLC in the test group. Measurement of airway wall thickness showed that both membranous and respiratory bronchioles were significantly thickened in the test group; this group also had airways of smaller internal diameter than the controls. Analysis for lung collagen content as hydroxyproline showed a 50% increase in the asbestos exposed animals. There was, however, only minimal and very focal interstitial fibrosis (asbestosis) in the lung parenchyma. Analysis of fiber size indicated that the fibers obtained by digestion of the tissue or from the lavage fluid were significantly longer and wider than those in the original asbestos sample; however, the tissue contained considerably larger fibers than the lavage fluid. We conclude that: Asbestos can produce airway fibrosis and narrowing causing air trapping on pulmonary function examination; this process occurs in the absence of significant interstitial fibrosis of the parenchyma (asbestosis), implying that abnormalities of pulmonary function which are consistent with airflow obstruction in asbestos exposed animals can be caused by pathologic changes in the small airways alone; long asbestos fibers are preferentially retained in the lung, and the longest fibers appear to be in a compartment inaccessible to lavage, presumably, in this model, in airway walls. Enhanced penetration of long fibers into tissue may be one reason why long fibers are more pathogenic than short ones. more...

The authors used immunohistochemical staining for S-100 protein to search for Langerhans cells in 7 cases of pulmonary eosinophilic granuloma (EGL) and in 18 cases of other pulmonary processes (including reactive eosinophilic pleuritis, chronic interstitial pneumonias, eosinophilic pneumonia, and nonspecific scars), which can produce diagnostic confusion with EGL. Qualitatively, Langerhans cells were found in almost every disease. However, cases of active or resolving EGL showed greater than 75 such cells/10 high-power fields (hpf), often appearing as densely packed aggregates (a virtually diagnostic feature), while all other conditions, including completely scarred EGL, showed fewer than 35 Langerhans cells/10 hpf, and the cells were scattered through the parenchyma. The authors conclude the following: (1) Langerhans cells participate in many types of inflammatory process in the lung, and hence the mere presence of Langerhans cells is not diagnostic of EGL; (2) S-100 staining with quantitation of Langerhans cells is a useful adjunct in the diagnosis of active and resolving EGL. more...

In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS) more...

We present a case of slowly progressive Aspergillus infection occurring in a partially immunocompromised host. The histologic pattern mimicked bronchocentric granulomatosis as seen in allergic bronchopulmonary aspergillosis, but the clinical history, spread of disease in the face of steroid therapy, peculiar granulomatous response to the organisms, and large numbers of organisms present suggest that this was really a case of chronic necrotizing pulmonary aspergillosis. These entities must be distinguished because their therapy, prognosis, and clinical significance are totally different. more...