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Biomedical subjects

M Delos

Publications and source records attributed to M Delos.

At least 19 recordsLinked to original sources

Biodistribution of ultrasmall iron oxide particles in the rat liver.

Ferumoxtran, an ultrasmall superparamagnetic iron oxide particle, can be located in several tissue compartments in the liver, namely the extracellular space (blood and interstitium), reticuloendothelial cells, and possibly hepatocytes. To better understand the compartmental distribution of ferumoxtran in the liver, we performed a longitudinal study in the rat using microscopy and magnetic resonance imaging. At light microscopy, no substantial cellular uptake of ferumoxtran was observed before one hour after injection. With a dose of 15 micromol Fe/kg, the number of ferumoxtran particles in the reticuloendothelial cells peaked between one and four hours and with a 150 micromol Fe/kg dose, it peaked between eight and 24 hours. Within hepatocytes, only sparse particles were observed with electron microscopy, at a dose of 150 micromol Fe/kg. Imaging performed up until one hour after ferumoxtran injection showed a significant increase in liver signal intensity on T1-weighted images. These results suggest that ferumoxtran mainly acts as an extracellular agent for at least one hour in the rat and that reticuloendothelial accumulation peaks at later time points. Substantial uptake within hepatocytes did not occur.

Animals↗

Reduced epithelial expression of secretory component in small airways correlates with airflow obstruction in chronic obstructive pulmonary disease.

The epithelial polymeric immunoglobulin receptor/transmembrane secretory component (pIgR/SC) transports into secretions polymeric immunoglobulin A (pIgA), which is considered the first line of defense of the respiratory tract. The present study, done with quantitative immunohistochemistry, evaluated epithelial expression of secretory component (SC) and Clara cell protein (CC16) and neutrophil infiltration into the airways of eight patients with severe chronic obstructive pulmonary disease (COPD) who were undergoing lung transplantation, as compared with these processes in six nonsmoking patients with pulmonary hypertension who were used as controls and in lung specimens from five smokers without chronic bronchitis. Staining for SC was significantly decreased in the COPD patients as compared with the controls, both in large (mean optical density [MOD]: 23.4 [range: 21.1 to 27.8] versus 42.2 [range: 28.2 to 49.3], p = 0.003) and in small airways (MOD: 30.8 [range: 20.3 to 39.4] versus 41.5 [range: 39.2 to 46.2], p = 0.003). SC expression in small airways correlated strongly with functional parameters such as FEV1 (Kendall's tau (K) = 0.76, p = 0.008), FVC (K = 0.64, p = 0.03), and midexpiratory flow at 50% of VC (MEF50) (K = 0.74, p = 0.01). The reduced expression of SC in large airways correlated with neutrophil infiltration in submucosal glands (K = -0.47, p = 0.03). Expression of CC16 in the bronchial epithelium of COPD patients was also significantly decreased as compared with that of controls, especially in small airways (MOD: 28.3 [range: 26.8 to 32.4] versus 45.8 [range: 40.7 to 56.0], p = 0.002), but no correlation was observed with lung function tests. In conclusion, this study shows that reduced expression of SC in airway epithelium is associated with airflow obstruction and neutrophil infiltration in severe COPD.

Adolescent↗

Interleukin-9 reduces lung fibrosis and type 2 immune polarization induced by silica particles in a murine model.

We examined the effect of interleukin (IL)-9, a cytokine active on B and T lymphocytes and associated with bronchial asthma, on the development of lung fibrosis induced by crystalline silica particles. Therefore, we compared the response to silica (1 and 5 mg/animal, intratracheally) in transgenic mice that constitutively express high levels of IL-9 (Tg5) and their wild-type counterparts (FVB). At 2 and 4 mo after treatment with silica, histologic examination and measurement of lung hydroxyproline content showed that the severity of fibrosis was significantly less important in Tg5 mice than in their wild-type counterparts. Intraperitoneal injection of IL-9 in C57BL/6 mice also reduced the amplitude of silica-induced lung fibrosis. The reduction of lung fibrosis by IL-9 was associated with a significant expansion of the B-lymphocyte population, both in bronchoalveolar lavage (BAL) and in the pulmonary parenchyma. In wild-type animals, silica-induced fibrosis correlated with markers of a T helper 2-like response such as upregulation of IL-4 levels in lung tissue and an increased immunoglobulin (Ig) G1/IgG2a ratio in BAL. Immunohistochemical studies demonstrated that the upregulation of IL-4 associated with the development of fibrosis was mainly localized in inflammatory alveolar macrophages. In transgenic mice, the level of IL-4 in lung homogenates was not significantly affected by silica treatment, and a reduced IgG1/IgG2a ratio was observed upon treatment with silica. The levels of interferon-gamma were significantly decreased after silica treatment in both strains. Together, these observations point to an antifibrotic effect of IL-9 in pulmonary fibrosis associated with a limitation of the type 2 polarization which accompanies lung fibrosis.

Animals↗

Lobular capillary haemangioma of the nasal cavity: observation of three specific cases.

Lobular Capillary Haemangioma of the nasal cavity: Observation of three specific cases. Lobular Capillary Haemangioma, unproperly called "Pyogenic granuloma", is a benign vascular tumour pedunculated on the skin and on mucous membranes of the oral and nasal cavities. Microtrauma and pregnancy are the most often evocated aetiologic factors. Epistaxis and nasal obstruction are the most marked symptoms of this irregular and friable mass. We report three cases (two adult and one paediatric) of this pathology. Two have as trigger factor a nasal microtrauma, the third an oestro-progestative impregnation. A clinical, radiological and histological description allows us to expose the characteristics of this lesion that remains obscure to many rhinologists. Lobular Capillary Haemangioma has to be evocated in the differential diagnosis of each haemorrhagic endonasal mass.

Adult↗

[Cutaneous acanthamoebiasis in a lung transplant patient].

BACKGROUND: Cutaneous acanthamoebiasis is a rare opportunistic infection in immunocompromised patients, particularly in HIV infected patients. We report a case of a primary cutaneous Acanthamoeba infection, in a patient with a double lung transplant not infected by the HIV. CASE REPORT: A 38 year-old white man, with a double lung transplant 3 years ago, developed a painful fibrinous ulceration of the right foot, with cellulitis. A few days later, two purplish nodules were observed, surrounded by an inflammatory reaction. Histologic examination revealed trophozoite and cyst forms. Therapy was begun with intravenous pentamidine and itraconazole along with topical ketoconazole and chlorhexidine, but was ineffective. Because of the renal toxicity of pentamidine, the patient was treated by dialysis. He died six months after diagnosis of Acanthamoeba infection. DISCUSSION: Acanthamoeba, a free-living amoeba is the causative organism of few human diseases. In immunocompromised hosts (particularly HIV infected), besides granulomatous amebic encephalitis, it can provoke some cutaneous lesions such as nodules, pustules, ulcerations... Skin biopsy is diagnostic: numerous amebic trophozoites and cysts are visualized. Recommended treatments are pentamidine, itraconazole and flucytosine. Due to the morbidity and mortality of acanthamoeba infection optimal therapy must be defined.

Acanthamoeba↗

Sinonasal lymphomas. Case report.

In the field of Otorhinolaryngology sinonasal lymphomas are relatively uncommon and represent less than 1% of all head and neck malignancies. Nowadays, they are regarded as consisting of two distinct subgroups, characterised by phenotype, location, prognosis and treatment. Lymphomas of the B-Cell phenotype are the most frequent type found in the paranasal sinuses. They are less aggressive and carry a relatively better prognosis. T/NK-Cell lymphomas are mostly found in the nasal cavity. They are more aggressive and carry a relatively worse prognosis. We present a case of a 65-year-old patient, who complained with unilateral right-sided nasal obstruction associated with a sensation of right aural fullness. CT scan demonstrated opacity of the posterior ethmoid and sphenoid sinuses on the right side, with evidence of erosion of the anterior wall of the sphenoid. Nasal endoscopy revealed a smooth purple mass, arising from the right superior meatus, which bled on contact, and which was subsequently shown to be, on histological assessment, a malignant high grade lymphoma, non-Hodgkin's B-cell phenotype. Following a discussion of the case we will present a review of these tumours, which have a poor overall prognosis, focusing on epidemiology, sites of origin, symptoms, investigation and management.

Aged↗

Coal fly ash- and copper smelter dust-induced modulation of ex vivo production of tumor necrosis factor-alpha by murine macrophages: effects of metals and overload.

The objective of this study was to assess the effect of two arsenic-containing particles, coal fly ash (FA) and copper smelter dust (CU), on lung integrity and on the ex vivo release of tumor necrosis factor alpha (TNF-alpha) by alveolar phagocytes. Particle effects were compared in nonoverload condition on the basis of a low but identical volume load and arsenic content intratracheally instilled in the mouse lung (273 nl/mouse and 186 ng arsenic/mouse; FAL and CUL groups). Other mice received 600 ng arsenic/mouse in amounts of particles leading to different volume loads (FAH and CUH groups: 880 and 273 nl/mouse, respectively). Animals were sacrificed at 1, 6, 30, or 120 d (FAL and CUL groups) or at 6 and 120 d posttreatment (FAH and CUH groups). Biochemical markers and inflammatory cell number and type were analyzed in bronchoalveolar lavage, ex vivo TNF-alpha production by alveolar phagocytes was assessed, and measurement of arsenic lung content and histopathological examinations were performed. Our results show that coal fly ash and copper smelter dust bear distinct inflammatory properties. At the end of the observation period (d 120), the high CU dose (CUH) produced a fibrotic reaction whereas the high dose of FA particles (FAH) generated a delayed and persistent lung inflammatory reaction associated with lymphoid noduli. Marked differences in TNF-alpha production were observed within the CU and FA groups. CU particles, conceivably through their metal content, decreased TNF-alpha production by alveolar phagocytes. Due to their low arsenic content, considerably higher FA particle doses needed to be administered to produce an inhibition of TNF-alpha production. Since high doses of FA (FAH) caused an overload condition, our results do not allow us to decide whether FA-mediated TNF-alpha reduction is due to the load administered or to the metallic content.

Animals↗

Limp as unusual presentation of Langerhans' cell histiocytosis.

UNLABELLED: An isolated eosinophilic granuloma involving the posterior elements of a lumbar vertebra is reported in a 3-year-old boy presenting with progressive limp. Radiological investigations revealed osteolysis of the L5 right pedicle. MRI showed a well-defined homogeneous mass with nonspecific signal intensity. An unusual feature was the paravertebral muscular location of the largest part of the tumour indicating a possible soft tissue origin. Immunohistochemical studies were typical for Langerhans' cell histiocytosis. CONCLUSION: A limp can be due to lumbar and paravertebral muscular location of Langerhans' cell histiocytosis.

Child, Preschool↗

Adult onset of multifocal eosinophilic granuloma of bone: a long-term follow-up with evaluation of various treatment options and spontaneous healing.

We report a case of multifocal-monosystemic Langerhans cell histiocytosis (LCH), formerly usually referred to as eosinophilic granuloma (EG) of bone. The condition developed in a 36-year-old man. A notable infrequent thoracic spine location and two successive distinct costal lesions were observed. Both the first costal site and the vertebral location healed spontaneously; the second costal lesion underwent biopsy resection. The patient's disease course with an 8-year follow-up is discussed with reference to various treatment options, emphasising in selected cases a watchful conservative approach, in view of the widely documented potential for spontaneous healing.

Adult↗

Derivation of tumor-specific cytolytic T-cell clones from two lung cancer patients with long survival.

We derived lung carcinoma cell lines from tumor material resected from a patient with small-cell lung cancer (SCLC) and from a patient with non-small-cell lung cancer (NSCLC). The patient with NSCLC was vaccinated with irradiated autologous tumor cells. The two patients enjoyed an exceptionally favorable clinical evolution and are currently without signs of cancer 10 and 8 yr after their diagnoses, respectively. Autologous mixed lymphocyte-tumor cell cultures (MLTC) were produced with blood lymphocytes stimulated with irradiated autologous tumor cells. The first patient's SCLC cells, which carried a small amount of human leukocyte antigen (HLA) class I molecules, were incubated with interferon-gamma (IFN-gamma) before being used as stimulator cells. A cytolytic T-lymphocyte (CTL) clone was derived that specifically lysed the IFN-gamma-treated SCLC cells but did not lyse untreated tumor cells or autologous lymphoblasts. Clones of autologous tumor-specific CTL, directed against the NSCLC cells of the other patient, were also obtained. These tumor cells carried a higher level of HLA class I molecules and were lysed by the CTL without incubation with IFN-gamma. Altogether, these results indicate that SCLC and NSCLC cancer cells can be recognized by autologous CTL, and might therefore be susceptible to specific immunotherapy.

Carcinoma, Non-Small-Cell Lung↗

Lung fibrosis induced by silica particles in NMRI mice is associated with an upregulation of the p40 subunit of interleukin-12 and Th-2 manifestations.

Interleukin (IL)-12 is a cytokine produced principally by activated macrophages which is involved in control of the T-helper 1/T-helper 2 cell (Th1/Th2) polarization of immune responses. To examine its potential involvement in the development of lung fibrosis, we examined the expression (protein, messenger RNA [mRNA]) of IL-12 (p70) and of its subunits (p40 and p35) in lung homogenates, bronchoalveolar lavage fluid (BALF), and bronchoalveolar lavage (BAL) cell cultures in mouse models of resolutive alveolitis (RA) and fibrosing alveolitis (FA) induced by inorganic particles (manganese dioxide [MnO2] and crystalline silica, respectively). The administration of tungsten carbide (WC), which behaved as an innocuous dust for the lung, served as a negative control condition. The FA was specifically accompanied by a Th2-like polarization characterized by high levels of immunoglobulin (Ig)G1 in BALF and by a protracted overproduction of both p40 protein and mRNA, but not by the biologically active form of IL-12 (p70). In the RA model, the p40 response was only transient, and a Th1-like response was reflected by increased levels of interferon (IFN)-gamma and dominant levels of IgG2a in BALF. Taken together, these findings suggest that production of the p40 subunit of IL-12 and Th2 polarization play important roles in lung inflammatory and fibrotic responses to inhaled inorganic particles.

Animals↗

Correcting vocal fold immobility by autologous collagen injection for voice rehabilitation. A short-term study.

We report on a short-term clinical study of injectable autologous collagen (Vocalogen) used to correct dysphonias arising from vocal fold immobility. The collagen is extracted from skin taken from the lower abdominal quadrant area or from just above the bikini line. About 30 cm2 of skin are required to provide 2 mL of injectable collagen. The histologic examination of the preparation before injection disclosed the presence of elastin fibers and some clusters of epithelial cells, beside the collagen fibers. The collagen is naturally reticulated, and the molecule is preserved in its entirety. The technique is exactly the same as that reported for bovine collagen: injection into Reinke's space, under general anesthesia, monitored by direct microlaryngoscopy. The amount injected is also similar: 1.5 mL for correction of glottic insufficiency in which the immobile vocal fold is in the intermediate position. Eight patients were injected, and the average follow-up was 4.5 months. Voice assessments made before and after the treatment included stroboscopy, subjective and perceptual judgments, and aerodynamic and acoustic measurements. The functional results were similar to those obtained with bovine collagen. No complications arose. The probability of any hypersensitivity reaction, always a possibility to be feared with bovine collagen, is negligible with the autologous collagen. Long-term results are as yet unknown, but from the fact that the collagen molecular structure is intact and there is little risk of foreign body response, it would be expected that autologous preparations would be more stable than bovine collagen; this appears to be the case in cosmetic applications. Autologous collagen could be employed for the same indications as bovine collagen, provided that a delay of 45 days (the time required to prepare the injectable collagen) is acceptable. The amount of collagen required is also a limiting factor, since the patient's own skin is the starting donor material.

Aged↗

Prognostic factors in squamous cell carcinomas of the head and neck.

This review will focus on prognostic factors that can be disclosed by the pathological and molecular analysis of squamous cell carcinomas of the head and neck. The following pathological prognostic factors are considered and discussed: location, histopathology, lymph node metastasis. In addition, a number of molecular genetic markers have been identified such as: DNA content, chromosomal abnormalities, cell proliferation, RAS gene family, epidermal growth factor and its receptor, tumor-suppressor genes, cell adhesion molecules and proteinases.

Biomarkers, Tumor↗

Angiosarcoma of the thyroid and concurrent hyperthyroidism.

We describe the exceptional association of an angiosarcoma of the thyroid and hyperthyroidism in a 74-year-old woman who presented with a toxic multinodular goiter of recent growth. This association reported in two other cases may not be fortuitous but due a vascular effect of the angiosarcoma contributing to the development of thyrotoxicosis. This case also illustrates the diagnostic difficulties and the poor prognosis of this tumor.

Aged↗

Mechanisms of acute eosinophilic inflammation in a case of acute eosinophilic pneumonia in a 14-year-old girl.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is characterized by respiratory distress, eosinophilic infiltration in the lung, acute onset, resolution of symptoms with corticosteroids and the absence of relapse. Studies to identify the pathophysiology of AEP in adults have demonstrated eosinophil activation in the BAL fluid, and the presence of high levels of interleukin 5 (IL-5) in the BAL. OBJECTIVE: To investigate the pathophysiology of AEP with pleural effusion in a paediatric patient. METHODS: ECP levels in the BALand pleural fluid was determined by radioimmunoassay. IL-5 and GM-CSF concentrations in the BAL and pleural fluid were measured by Elisa. Immunohistochemistry studies performed on open lung biopsy included a specific ICAM-1 immunostaining and a ECP specific immunostaining (EG2+). RESULTS: High levels of ECP were found in the BAL (5 microg/L) and pleural fluid (750 microg/L) demonstrating eosinophil activation at these sites. Immunohistochemistry illustrated activated (EG2+) eosinophils in the interalveolar septa and alveolar space and detected increased expression of ICAM-1 on alveolar epithelial cells. High levels of IL-5 were measured in the BAL (1334 pg/mL) and pleural fluid (7014 pg/mL), while elevated concentrations of GM-CSF (150 pg/mL) were found in the BAL. CONCLUSION: We conclude that in this paediatric patient with AEP activated eosinophils were present in the BAL fluid, in the interalveolar septa and in the pleural space while increased ICAM-1 expression was detected on alveolar epithelial cells, contributing, at least partly, for their adhesive interactions. IL-5 and GM-CSF are likely important to the massive eosinophil recruitment and activation in the lung, while IL-5 is probably related to eosinophil accumulation and activation in the pleural space. Thus, lung generation of eosinophil-active cytokines is central to the pathophysiology of AEP in paediatric patients.

Acute Disease↗

Comparison of unenhanced and gadoxetate disodium-enhanced spin-echo magnetic resonance imaging for the detection of experimental hepatocellular carcinoma in the rat.

RATIONALE AND OBJECTIVES: The authors compare the potential value of unenhanced and gadoxetate disodium-enhanced spin-echo images for the detection of hepatocellular carcinoma in a rat model. METHODS: Eleven rats with chemically induced hepatocellular carcinoma underwent unenhanced T2-weighted fast spin-echo imaging followed by T1-weighted spin-echo imaging before and at 5 minutes, 30 minutes, 3 hours, 1 day, and 3 days after intravenous administration of 60 micromol/kg gadoxetate disodium at 4.7 tesla. Tumor and liver enhancement, and tumor-to-liver contrast-to-noise (C/N) ratio were calculated. RESULTS: After gadoxetate disodium administration, the tumors showed less enhancement than the liver. Tumor-to-liver C/N ratio increased from 5.5 +/- 0.8% on unenhanced T1-weighted images to 12.9 +/- 2.4% on gadoxetate-enhanced T1-weighted images (P = 0.02). However, the C/N ratio on unenhanced T2-weighted images (23.5 +/- 3.6%) remained higher than that on gadoxetate-enhanced T1-weighted images, a difference that is statistically significant (P < 0.01). CONCLUSIONS: In the experimental setting of our study, the higher tumor-to-liver C/N ratio on unenhanced T2-weighted spin-echo images suggests that unenhanced T2-weighted spin-echo images are superior to gadoxetate disodium-enhanced T1-weighted spin-echo images for the detection of hepatocellular carcinoma.

Animals↗