Presence Of Hemosiderin-laden Macrophages Research Articles

An Uncommon Cause of Hemoptysis Presenting Like Hemolytic Anemia

Idiopathic pulmonary hemosiderosis (IPH) usually presents with hemoptysis and iron deficiency anemia. In this report, an unusual presentation of IPH is described. 11-year-old boy presented with clinical features suggestive of hemolytic anemia. However, on detailed evaluation, he was diagnosed to have IPH and confirmed by the presence of hemosiderinladen macrophages in bronchoalveolar lavage fluid (BALF). The child was managed with oral corticosteroids, and he was doing well on follow-up.

Multi-Organ Histopathological Changes in a Mouse Hepatitis Virus Model of COVID-19

Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7–8 exhibit severe lung inflammation, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions.

Peritoneal lavage cytology in the diagnosis of pelvic endometriosis.

We aimed to assess the sensibility, specificity, and predictive values of cytology of the fluid sediment in patients with pelvic endometriosis diagnosed based on laparoscopic-guided biopsy. Between January 2017 and September 2018, 71 specimens of peritoneal fluid collected by laparoscopy were evaluated. Fifty-three patients were diagnosed laparoscopically and histologically with endometriosis, and 18 were considered controls (without suspicious endometriosis lesions). We calculated the sensitivity, specificity, the positive and negative predictive value, and the accuracy of endometrial-like cells (ELC) and hemosiderin-laden macrophages (HLM) in the fluid sediment. Of the 50 patients with endometriosis, 32 (64%) had HLM, 9 (18%) had ELC, and 7 (14%) had both elements. Of the 18 patients without endometriosis, 3 (16%) had HLM, 2 (11%) had ELC, and 1 (5%) had both ELC and HLM. The sensitivity of the cytology of peritoneal fluid sediment for the diagnosis of endometriosis, based on the presence of ELC, was 18%, the specificity was 83%, the positive predictive value was 82%, the negative predictive value was 28.7%, and the accuracy was 36.8%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy based on the presence of HLM were 64%, 83%, 91%, 45.5%, and 69.1%, respectively. The study of peritoneal fluids obtained laparoscopically from women undergoing evaluation for endometriosis may identify patients with the disease.

Diffuse Alveolar Hemorrhage After Pediatric Hematopoietic Stem Cell Transplantation.

Pulmonary complications are common following hematopoietic cell transplantation (HCT) and contribute significantly to its morbidity and mortality. Diffuse alveolar hemorrhage is a devastating non-infectious complication that occurs in up to 5% of patients post-HCT. Historically, it carries a high mortality burden of 60–100%. The etiology remains ill-defined but is thought to be due to lung injury from conditioning regimens, total body irradiation, occult infections, and other comorbidities such as graft vs. host disease, thrombotic microangiopathy, and subsequent cytokine release and inflammation. Clinically, patients present with hypoxemia, dyspnea, and diffuse opacities consistent with an alveolar disease process on chest radiography. Diagnosis is most commonly confirmed with bronchoscopy findings of progressively bloodier bronchoalveolar lavage or the presence of hemosiderin-laden macrophages on microscopy. Treatment with glucocorticoids is common though dosing and duration of therapy remains variable. Other agents, such as aminocaproic acid, tranexamic acid, and activated recombinant factor VIIa have also been tried with mixed results. We present a review of diffuse alveolar hemorrhage with a focus on its pathogenesis and treatment options.

DIFFUSE ALVEOLAR HEMORRHAGE FOLLOWING DUAL CHECKPOINT INHIBITOR THERAPY

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Immune checkpoint inhibitors (ICIs) have emerged as new therapeutic agents with survival benefit for various cancers, but are associated with various complications (1,2). ICI related pulmonary toxicity usually manifests in the form of pneumonitis, but diffuse alveolar hemorrhage (DAH) caused by ICIs has not been previously described (3). CASE PRESENTATION: A 72-year-old man with history of Diabetes Mellitus, Asthma, Acute Myeloid Leukemia who failed three lines of chemotherapy and bone marrow transplant, was started on ICI therapy with ipilimumab and nivolumab. He was admitted to hospital for worsening night sweats, fatigue and recurrent falls. On day 2, he developed fever, dyspnea, minor hemoptysis (<5mL) and hypoxemia requiring supplemental oxygen (3L via nasal cannula). CT chest revealed bilateral ground-glass infiltrates. He was treated with diuresis and antimicrobials including meropenem and posaconazole. His course was complicated by increasing oxygen requirements (non-invasive ventilation). Extensive infectious workup was negative including blood, urine cultures, respiratory viral panel and fungal serologies. Bronchoalveolar lavage (BAL) performed on day 3 revealed grossly hemorrhagic fluid with no change on 3 sequential lavages. Hemosiderin laden macrophages were reported on the cytologic exam. Of note, he had thrombocytopenia from leukemia, and his platelet count was 13000/cu.mm on the day of bronchoscopy. Following BAL, he was started on IV methylprednisolone 1 mg/kg/day for suspected pneumonitis related to ICI therapy. Within 24 hours, he showed significant improvement in work of breathing and oxygen was weaned to 2L via nasal cannula. BAL culture grew Pseudomonas aeruginosa and vancomycin resistant Enterococcus faecium. He was transitioned to oral steroids was discharged in a stable condition on room air. DISCUSSION: Association of ICIs with pulmonary toxicity in the form of pneumonitis is well recognized. However, DAH has not been described in association with this therapy. We report a case of DAH that appeared after 3 months of ipilimumab and nivolumab treatment. DAH was confirmed through grossly hemorrhagic sequential lavages with the presence of hemosiderin-laden macrophages. Though BAL cultures in this patient showed growth, infection as a cause of DAH is extremely unlikely given progression of disease despite antibiotics and dramatic response to steroids. Further research is needed to elucidate the mechanism and association of DAH in setting of ICI therapy and prognostic and therapeutic implications of such presentation. CONCLUSIONS: Use of immunotherapy for cancer is rapidly expanding, and complications related to such therapy are being increasingly recognized. We describe a case of DAH manifesting with hemoptysis and hypoxic respiratory failure in a patient who was receiving ipilimumab and nivolumab. To our knowledge, this is the first description of such an association. Reference #1: Valadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities. Trans Lung Cancer Res. 2015;4(5):560-75 Reference #2: Suresh, Karthik et al. Pneumonitis in Non–Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors Journal of Thoracic Oncology , Volume 13 , Issue 12 , 1930 – 1939 Reference #3: Naidoo J, Wang X, Woo KM, et al. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2016;35(7):709-717. DISCLOSURES: No relevant relationships by Herbert Berger, source=Web Response No relevant relationships by Vikas Koppurapu, source=Web Response No relevant relationships by Roger Struble, source=Web Response

Idiopathic pulmonary hemosiderosis: A differential diagnosis of pulmonary tuberculosis in a young child

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease diagnosed primarily in children and young adults, characterized by recurrent diffuse alveolar hemorrhage which leads to the deposition of hemosiderin-laden macrophages in the lung. It is a diagnosis of exclusion and requires a high level of clinical suspicion. It may remain undiagnosed for years, hence often mistreated. Here, we describe such a case of IPH in a 15-year-old male who was initially mistreated twice as clinically diagnosed pulmonary tuberculosis first with Category 1 and then Category 2 antitubercular drugs. He had a history of two episodes of hemoptysis, recurrent episodes of paleness, persisting weakness, and shortness of breath. He also had bilateral reticulonodular opacities on chest skiagram. His history raised the suspicion, the presence of hemosiderin-laden macrophages in bronchoalveolar lavage, and transbronchial lung biopsy strongly suggested the diagnosis. However, the final diagnosis came out after ruling out all the probable causes.

Repeated infections of dengue (serotype DENV-2) in lung cells of BALB/c mice lead to severe histopathological consequences

ABSTRACTTo determine the effect of DENV (serotype 2) repeated infections on lung cells is the main goal of this study. From the result, lung histology of control BALB/c mice showed normal alveolar morphology, while vehicle control BALB/c mice highlighted a slight thickening of the alveolar septum. Lung histopathology of BALB/c mice infected twice by DENV-2 showed the presence of hemorrhage, plasma leakage and presence of hemosiderin-laden macrophages (HLMs). Notably, in the lung of BALB/c mice infected four times by DENV-2, we observed thickening and disruption of the alveolar septum, inflammatory cell infiltration, plasma leakage and increased cellularity. Megakaryocyte releasing platelets were also found into the lung alveolus. Overall, our findings showed severe histopathological damage in lungs repeatedly infected by DENV-2, allowing us to argue that they can be linked to pulmonary complication. Result also showed that the number of infections with similar total DENV-2 titer led to different histopathological changes.

Pneumothorax in Women of Child-Bearing Age: An Update Classification Based on Clinical and Pathologic Findings

A significant percentage of pneumothorax in women is due to thoracic endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic aspects are poorly known. Clinical and pathologic records of all consecutive women of reproductive age operated on for pneumothorax between 2000 and 2011 were retrospectively reviewed. Two hundred twenty-nine women (mean age, 33 years) underwent surgery. One hundred forty-four cases (63%) were right-sided, and pneumothoraces were catamenial for 80 women (35%). Diagnosed pelvic endometriosis was associated in 29 cases. At pathology, thoracic endometriosis was diagnosed in 54 cases (24%). Endometrial glands were observed in 33 of 54 cases and were often cystic (16 of 33). Stroma was observed in 51 of 54 cases and endometrial stroma without glands in 21 cases. Hemosiderin-laden macrophages were observed in 27 of 54 cases. All cases of thoracic endometriosis were positive for progesterone and/or estrogen receptors (intense and nuclear). Catamenial pneumothoraces (n = 80, 34.9%) were endometriosis related in 50% of cases (n = 40, 17% of the whole population). Pneumothoraces were noncatamenial but endometriosis related in 6% of cases (n = 14) and merely idiopathic in 60% of patients (n = 135). Multivariate analysis showed that right side, presence of diaphragmatic abnormalities, relapse after unilateral surgery, and presence of hemosiderin-laden macrophages were independent variables associated with thoracic endometriosis (all, P &lt; .02). Apical emphysema-like changes were found in 184 of the 213 patients (86%) with apical resection and were significantly associated with the absence of thoracic endometriosis (P &lt; .001). In women with surgically treated pneumothorax, prevalence of catamenial/endometriosis-related pneumothorax is high. Clinicians and pathologists must be aware to recognize such a difficult diagnosis.

New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare® cohort

BackgroundIdiopathic pulmonary hemosiderosis (IPH) is a rare cause of alveolar hemorrhage in children and its pathophysiology remains obscure. Classically, diagnosis is based on a triad including hemoptysis, diffuse parenchymal infiltrates on chest X-rays, and iron-deficiency anemia. We present the French pediatric cohort of IPH collected through the French Reference Center for Rare Lung Diseases (RespiRare®, http://www.respirare.fr).MethodsSince 2008, a national network/web-linked RespiRare® database has been set up in 12 French pediatric respiratory centres. It is structured as a medical recording tool with extended disease-specific datasets containing clinical information relevant to all forms of rare lung diseases including IPH.ResultsWe identified 25 reported cases of IPH in children from the database (20 females and 5 males). Among them, 5 presented with Down syndrome. Upon diagnosis, median age was 4.3 [0.8-14.0] yrs, and the main manifestations were: dyspnea (n = 17, 68%), anemia (n = 16, 64%), cough (n = 12, 48%), febrile pneumonia (n = 11, 44%) and hemoptysis (n = 11, 44%). Half of the patients demonstrated diffuse parenchymal infiltrates on chest imaging, and diagnosis was ascertained either by broncho-alveolar lavage indicating the presence of hemosiderin-laden macrophages (19/25 cases), or lung biopsy (6/25). In screened patients, initial auto-immune screening revealed positive antineutrophilic cytoplasmic antibodies (ANCA) (n = 6, 40%), antinuclear antibodies (ANA) (n = 5, 45%) and specific coeliac disease antibodies (n = 4, 28%). All the patients were initially treated by corticosteroids. In 13 cases, immunosuppressants were introduced due to corticoresistance and/or major side effects. Median length of follow-up was 5.5 yrs, with a satisfactory respiratory outcome in 23/25 patients. One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage.ConclusionThe present cohort provides substantial information on clinical expression and outcomes of pediatric IPH. Analysis of potential contributors supports a role of auto-immunity in disease development and highlights the importance of genetic factors.

Reduction of autofluorescence at the microelectrode–cortical tissue interface improves antibody detection

Immunohistochemistry (IHC) remains among the most utilized methods for detection of inflammatory events occurring at the microelectrode–cortical tissue interface. It has further become a standard protocol to quantify the intensity of this resulting fluorescent signal, normalized to “background”, as a measurement of the extent of inflammatory events. Unfortunately, several sources of autofluorescence could result in variations in this user-defined “background”. Notably, we found that the presence of hemosiderin-laden macrophages (HLMs) at the interface resulted in a variable source of background in both green and red fluorescent channels. The HLM-derived autofluorescence prevented the reproducible detection of presumably low-level antigens at the interface. Here we show that treatment of the native cortical tissue for no less than 10min, with a minimum of 0.5mM copper sulfate, resulted in at least a 70% reduction in native HLM autofluorescence in both green and red fluorescent channels. In the case of highly expressed antigens, such as glial fibrillar acidic protein (GFAP), treatment of immuno-labeled tissue with copper sulfate reduced tissue background, compared to standard IHC methodology, but did not result in significant differences in the quantification of normalized signal intensity. However, treatment with copper sulfate substantially enhanced the detection efficiency of weakly expressed antigens at the device–tissue interface. This study demonstrates that the inclusion of copper sulfate incubation during IHC tissue preparation significantly reduced HLM-derived autofluorescence, and allowed for more accurate detection and quantification of faintly expressed inflammatory markers at the device–tissue interface.

Ovarian hydrobursitis in female camels (Camelus dromedarius): Clinical findings, histopathology and fertility after unilateral surgical ablation

This study was undertaken to verify the clinical signs, incidence, location, etiology and pathology of ovarian hydrobursitis in infertile female camels and estimate the fertility after unilateral surgical ablation. Genital organs (n = 124) were examined in camels slaughtered at Makkah abattoir during Hajj of 2009. Infertile female camels (n = 142) presented for management to the Veterinary Teaching Hospital, Qassim University, Saudi Arabia, were clinically examined and ultrasound-scanned for the diagnosis of genital abnormalities. Twenty eight camels diagnosed with ovarian hydrobursitis were further investigated for the effect of unilateral surgical ablation on breeding outcomes. Surgical ablation was carried on 14 cases (treated group), the remaining 14 cases were followed as controls (control group). Both groups were observed for breeding results: 90 days non-return rate (90d NRR) and calving rate (CR). Removed bursae were sent to the laboratory for histopathological investigation. Results showed that the incidence of ovarian hydrobursitis was 6.5% in slaughtered camels and 33.8% in infertile females. Camels with hydrobursitis were concurrently affected with pyometra, uterine and vaginal adhesions or purulent endometritis. Histopathology reported degeneration and hyperplasia of the lining epithelium, mononuclear cells infiltration, focal aggregation of inflammatory cells, cystic dilatation of multi-acinal structures, tiny hemorrhages, and presence of hemosiderin-laden macrophages. The 90d NRR and CR of the surgically-treated cases were 64.3% and 50%, respectively. None of the untreated cases conceived. These results confirmed that ovarian hydrobursitis causes infertility in dromedary female camels and is associated with inflammatory genital conditions and surgical ablation in unilaterally affected animals presents a potential treatment.

Cytological diagnosis of peritoneal endometriosis

Sir, Endometriosis is a common disease characterized by ectopic growth of endometrial tissue that responds to hormonal stimulation. It primarily affects women in the reproductive age group with mixed symptomatology. Cytological features of endometrial cells in peritoneal fluid are not well described, which we wish to highlight. A 30-year-old woman presented with lower abdominal pain and dysmenorrhoea of 1 year duration. On examination, she had mild ascites. Bilateral cysts were seen near the fallopian tube on laparoscopy. Diagnostic considerations included neoplastic process or pelvic endometriosis. A peritoneal wash was performed and 100 mL of haemorrhagic fluid was sent for cytological examination. On microscopy, the fluid showed the presence of endometrial cells. The glandular epithelial cells were arranged in variably sized spheres in which the periphery showed epithelial cells, along the border and as a honeycombed sheet, with a cluster of stromal cells in the centre having hyperchromatic nuclei, scant cytoplasm and indistinct cytoplasmic borders [Figure 1]. There was no nuclear atypia and the nucleoli were inconspicuous. Some of the fragments were arranged in a small ball-like configuration in which there was cytoplasm resembling mesothelial cells [Figure 2]. Their three-dimensional nature and tight grouping set them apart from the loose sheets of mesothelial cells of the peritoneal wash. A few hemosiderin-laden macrophages were identified. A cytological diagnosis of endometriosis was made. Figure 1 Large endometrial fragment in peritoneal wash fluid showing epithelial lining on the outside, seen on the sides and as honeycombed cells as well as compact stromal cells within (PAP, ×400) Figure 2 Small spherule of endometrial cells in three-dimensional arrangement, which has to be differentiated from reactive mesothelial cells (PAP, ×400) The utility of peritoneal wash cytology for diagnosis of endometriosis has been reported.[1,2] In most cases, only hemosiderin-laden macrophages are identified.[2–5] The presence of endometrial cells is more specific but less sensitive than hemosiderin-laden macrophages for the diagnosis of endometriosis. The endometrial cells have been reported in 25%–52% of peritoneal washes done in endometriosis.[1,5] However, recognition of endometrial cells as well as hemosiderin-laden macrophages is essential for diagnosis on morphological basis alone.[6,7] The descriptions, diagnostic features and illustration of endometrial cell morphology in the peritoneal wash fluid is restricted to a few reports.[3,6] The distinction of endometrial cells from mesothelial cells and adenocarcinoma cells is important. Endometrial cells come in three-dimensional fragments that do not resemble mesothelial cells architecturally in washings which are arranged in sheets. However, endometriosis may elicit reactive mesothelial proliferation, which form three-dimensional fragments with calcific concretions, which are difficult to distinguish from endometrial cells.[5] Larger endometrial cell fragments may include stromal cells, which is a useful feature for differentiation as seen in the present case. Presence of hemosiderin-laden macrophages is indirect evidence of endometriosis. In the presence of an adnexal mass, a well-differentiated adenocarcinoma is always a diagnostic consideration and needs to be ruled out by the absence of atypia in the small cells and nuclei of endometrial cells. This distinction becomes difficult if there is reactive mesothelial proliferation in case of endometriosis.[2,5] The use of cell blocks and immunocytochemistry for epithelial and mesothelial cell markers can greatly aid diagnosis in distinction between reactive mesothelial fragments on one side and endometriosis and adenocarcinoma on the other.[2] Correlation with clinical and operative features is essential before cytological diagnosis.

Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages

Chronic obstructive pulmonary disease (COPD) is the 5(th) most prevalent disease worldwide leading to severe morbidity and mortality in developed countries. The disease is strongly associated with smoking, and can be characterized by progressive and irreversible deterioration in lung function and destruction of the lung parenchyma. We show here that infection with the hookworm Nippostrongylus brasiliensis results in deterioration in lung function, destruction of alveoli and long-term airways hyperresponsiveness, consistent with COPD and emphysema. N. brasiliensis infection leads to chronic low level hemorrhaging in the lung and the presence of hemosiderin-laden macrophages in the absence of an overt inflammatory infiltrate. Microarray analysis of gene expression in diseased lungs and quantitative RT-PCR analysis of purified macrophages revealed a state of prolonged tissue injury and the presence of alternatively activated macrophages producing MMP-12. Taken together, these data show that lung tissue damage caused by hookworm infection can result in the development of COPD and emphysema.

HISTOPATHOLOGICAL FEATURES OF TESTICULAR REGRESSION SYNDROME: RELATION TO PATIENT AGE AND IMPLICATIONS FOR MANAGEMENT

Testicular regression syndrome (TRS) represents a congenital condition in which no normal testicular tissue can be identified following exploration for a clinically impalpable testis. A spectrum of pathological findings may be present but there is little literature systematically examining these features. We searched a pediatric histopathology database to identify cases of TRS, and the histopathological findings were reviewed and pooled with those of all previously published smaller series. A total of 117 cases were identified during the period (1989–2004), median age 2 (range birth–12) years. In 52 (44%) a nodule was identified macroscopically, median maximum diameter 0.5 (range 0.1–2.0) cm. Microscopic hemosiderin-laden macrophages were present in 85 (73%), dystrophic calcification in 52 (44%), residual testicular tubules in 12 (10%), vas deferens in 71 (61%), and epididymal tissue in 39 (33%). The prevalence of hemosiderin laden macrophages and dystrophic calcification were significantly greater in cases ≤3 years (84% versus 64% and 55% versus 32%, respectively). But there was no significant difference in the frequency of other findings between the younger and older age groups; in particular, the presence of residual testicular tubules was similar (7% versus 13%, respectively). Furthermore, there was no significant correlation between identification of a macroscopically distinct nodule and presence of residual tubular structures, tubules being identified in 6 of the 65 cases in which no clearly identifiable nodule was seen macroscopically. The presence of hemosiderin-laden macrophages and foci of dystrophic calcification showed a positive association. TRS is associated with specific histopathological features, the findings being consistent with changes secondary to intrauterine testicular torsion. Residual testicular tubules are found in 10% of cases regardless of the presence or absence of a macroscopically identifiable nodule.

Time Course of Hemosiderin Production by Alveolar Macrophages in a Murine Model

The diagnosis of alveolar hemorrhage is assisted by the presence of hemosiderin-laden macrophages (HLMs) in the BAL fluid or lung tissue. Despite the importance of this diagnostic method in clinical settings, limited information is available on the formation and clearance of HLMs as a function of time. The objectives of this study are to determine the time course of HLMs within the BAL and lung tissue, and to evaluate the effect of a single blood aspiration on the recruitment of inflammatory cells within the BAL. Under light anesthesia, Balb/c mice received a single intranasal instillation of species-specific blood (50 microL). Control animals received heparinized sterile saline solution in a similar manner. At several time points after blood aspiration, BAL was recovered for cell differentials and determination of HLMs. The time course for HLMs was also established in the lung tissue. Hemosiderin staining within alveolar macrophages was first detected in the BAL and lung tissue at day 3, peaked at day 7, and persisted through 2 months. The analysis of the BAL revealed an increased number of total cells, with an acute inflammatory reaction that resolved within 2 weeks. Our findings demonstrate the validity of this model for the study of HLM production after blood aspiration. Additional work using animal models of lung hemorrhage is needed to further characterize the cellular events leading to clearance of erythrocytes within the lung.

Quantitative assessment of a change of hemosiderin deposition with age in splenic compartments of rats.

Hemosiderin deposition was quantitatively estimated in paraffin sections stained using Perls' iron reaction in the spleens of untreated male rats aged from 0 to 28 months. Hemosiderin was deposited in the periarteriolar lymphocyte sheath (PALS), lymph follicles, and marginal zone, as well as in the red pulp which was the main compartment of hemosiderin deposition. Special attention was paid to the PALS and marginal zone. Marked hemosiderin deposition was evident from 4 months, although only few hemosiderin-laden macrophages appeared in the first 3 months. Hemosiderin deposition peaked at 12 months in the red pulp and at 20 months in the white pulp and marginal zone. The deposition in the white pulp and marginal zone was about 1/9 to 1/4 of that in the red pulp. A few hemosiderin-laden macrophages were found in the lymph follicles after 2 months. In the periarterial region of the splenic hilus, deposition of hemosiderin granules was observed even at 1 month when there was little hemosiderin deposition elsewhere. Since no arteries open there, the presence of hemosiderin-laden macrophages in the PALS and lymph follicles suggested movement of some macrophages from the red pulp and/or the marginal zone. In addition, hemosiderin deposition in the PALS increased with age after it decreased in the other compartments.

SAM studies on high-temperature annealing of vanadium thin films on oxidized silicon wafers

The diagnosis of alveolar hemorrhage is assisted by the presence of hemosiderin-laden macrophages (HLMs) in the BAL fluid or lung tissue. Despite the importance of this diagnostic method in clinical settings, limited information is available on the formation and clearance of HLMs as a function of time. The objectives of this study are to determine the time course of HLMs within the BAL and lung tissue, and to evaluate the effect of a single blood aspiration on the recruitment of inflammatory cells within the BAL.Under light anesthesia, Balb/c mice received a single intranasal instillation of species-specific blood (50 μL). Control animals received heparinized sterile saline solution in a similar manner. At several time points after blood aspiration, BAL was recovered for cell differentials and determination of HLMs. The time course for HLMs was also established in the lung tissue.Hemosiderin staining within alveolar macrophages was first detected in the BAL and lung tissue at day 3, peaked at day 7, and persisted through 2 months. The analysis of the BAL revealed an increased number of total cells, with an acute inflammatory reaction that resolved within 2 weeks.Our findings demonstrate the validity of this model for the study of HLM production after blood aspiration. Additional work using animal models of lung hemorrhage is needed to further characterize the cellular events leading to clearance of erythrocytes within the lung.