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Biomedical subjects

O Michel

Publications and source records attributed to O Michel.

At least 91 records · Page 5Linked to original sources

In vitro expression of inducible nitric oxide synthase in the nasal mucosa of guinea pigs after incubation with lipopolysaccharides or cytokines.

In order to demonstrate the involvement of nitric oxide synthases (NOS)--in particular the inducible isoform (iNOS)--in inflammatory processes within the nasal airways, we used organ-bath incubation to study isolated inferior turbinates and mucosa of the maxillary sinus of guinea pigs. The pattern of the expression in various substructures of the nasal mucosa was of special interest. Mucosa was incubated for 6 h with lipopolysaccharides (LPS) produced by E. coli, interleukin II (IL-2) or tumor necrosis factor-alpha (TNF-alpha). Saline was used as the control solution. Following incubation the specimens were fixed in buffered 4% formaldehyde solution over a period of 4 h. Tissues were next exposed to nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase-reaction and immunostained with specific antibodies to iNOS. Results then showed a clearly increased or initiated expression of iNOS in epithelium, glands, leucocytes and blood vessels of treated tissues in comparison to the control specimens. The inflammatory mediator LPS and the cytokines Il-2 or TNF-alpha alone were found to be capable of increasing the expression of iNOS, although the effects of LPS clearly exceeded those of the cytokines. This finding implicates iNOS-generated nitric oxide as a key factor for causing nasal swelling, secretion and obstruction during nasal infections and allergic episodes.

Animals↗

Modulation of endothelial cell function by normal polyspecific human intravenous immunoglobulins: a possible mechanism of action in vascular diseases.

Intravenous immunoglobulin (IVIg) is increasingly used in the treatment of autoimmune and inflammatory diseases, including vasculitides and Kawasaki disease. However, the outcome of IVIg interaction with endothelial cells of the vascular bed is not clear as yet. We have investigated the effect of IVIg on the in vitro activation of human endothelial cells, as assessed by cell proliferation and reverse transcription-polymerase chain reaction-detected expression of mRNA coding for adhesion molecules (intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1), chemokines (monocyte chemoattractant protein-1, macrophage colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor), and proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6). IVIg inhibited proliferation of endothelial cells in a time-dependent manner. This effect was dependent on both Fc and F(ab')2 fragments of the immunoglobulin molecule and was fully reversible. Tumor necrosis factor-alpha and interleukin-1beta also inhibited thymidine incorporation, but to a lesser degree. IVIg had no effect on basal levels of mRNA coding for the adhesion molecules, chemokines, and proinflammatory cytokines. IVIg fully down-regulated the expression induced by tumor necrosis factor-alpha or interleukin-1beta of mRNA coding for these molecules. Thus, blockade of cellular proliferation and of cytokine-induced expression of adhesion molecules, chemokines, and cytokines may explain the therapeutic effect of IVIg in vascular and inflammatory disorders.

Cell Adhesion Molecules↗

[Rhabdomyosarcoma in the area of the head-neck. A synopsis of some cases, therapeutic possibilities and prognoses].

BACKGROUND: Soft tissue sarcoma represent approximately 7% of all neoplasms in children up to 14 years. The most common type (approx. 50%) among them is the rhabdomyosarcoma (RMS). Within the head and neck, which accounts for approx. 35% of all RMS, the tumor can be found ubiquitiously. Preferred localizations are the orbita, the paranasal sinuses, and the soft tissue of cheek and neck. The prognosis of RMS was formerly poor but has markedly improved since defined multimodal therapy was established in the Seventies (for example the Intergroup Rhabdomyosarcoma Study, IRS, in 1972; the International Society of Paediatric Oncology, SIOP, in 1975, or the German "Cooperative Weichteil-Sarkom-Studien", CWS, in 1981). The therapy of choice for RMS, according to the CWS, is chemotherapy because very often a good remission of the tumor is achieved. The main role of surgery is first to obtain biopsy specimens for histological diagnosis, and second aim is the complete resection of the primary and resectable metastases, for example by a neck dissection. Severe mutilation by radical surgery, especially in childhood, should be avoided in favor of multidrug chemotherapy and radiation in the interest of patient well-being. PATIENTS: Our retrospective study shows the treatment and results of 11 patients with a rhabdomyosarcoma of the head and neck within 25 years (1972-1997). RESULTS: Five of the 11 patients, who were treated in the years 1972-77, died (average 13 months, range 3-72 months). Five of the six patients, who were treated since 1991, have survived to date, one had a relapse of the tumor. Four special cases of patients are discussed in greater detail. CONCLUSION: Although the achieved mean survival time is encouraging nowadays (a 5-year survival rate of approx. 70% for all RMS is described) fatal cases are typical for this malignancy. Early diagnosis, localization, histological subtype, and prompt initiation of adequate treatment is decisive for a successful outcome.

Adolescent↗

Emergency stenting of malignant obstruction of the upper airways: long-term follow-up with two types of silicone prostheses.

We report on 10 patients with severe malignant "mixed-type" obstruction of the proximal trachea or distal trachea plus both main stem bronchi. They had far-advanced inoperable tumors (esophageal cancer in 4 patients, lung cancer in 3, and recurrent laryngeal, uvular, and thyroid cancers in 1 each). Emergency treatment consisted of a dilating bougie maneuver followed by the insertion of a large one-way (4 patients) or Y-shaped (6) silicone prosthesis. Subsequent to the intervention, there was long-lasting clinical improvement. The median survival from stent insertion was 8 months for all patients irrespective of tumor type; it was 5 months for lung carcinoma patients and 8 months for those with esophageal cancer. The results are in accordance with those of other studies using different therapeutic modalities. Stent exchange proved necessary in 5 patients. The main reasons were continuing tumor growth beyond the proximal and distal boundaries and recurrent productive bronchial infection. Patients died of pneumonia (4 patients), pulmonary lymphangitic spread (1), heart failure (2, one of whom also had pneumonia), and fatal hemorrhage (1). As of December 1995, 3 patients were still alive, 2, 5, and 8 months after stent implantation. As evidenced by clinical efficacy and length of palliation, endoscopic placement of silicone-based one-way and bifurcated prostheses in far-advanced tumor of the central airways is technically feasible and ethically justifiable.

Aged↗

[Diseases associated with organic dusts].

Organic dust is ubiquitous and is a mixture of both allergens and several pro-inflammatory agents. Exposure to organic dust elicits a very complex immune response leading to pulmonary and systemic symptoms, in some occupational settings as well as in domestic environment. In this later setting, identification of pathogenic components from the organic dust could improve our understanding of pathogenesis of asthma as well as chronic obstructive pulmonary diseases.

Allergens↗

Clinical and laboratory evaluation of a new thin-walled self-expanding tracheobronchial silicone stent: progress and pitfalls.

BACKGROUND: Although widely established in the management of malignant airway lesions, currently available tracheobronchial prostheses made of silicone have their drawbacks resulting from rigidity and wall thickness. Therefore we present clinical follow-up data obtained with a novel thin-walled expandable prototype silicone airway stent (Polyflex stent, Willy Rüsch AG, Kernen, Germany) in 19 patients. METHODS: Seventeen of 19 patients had tracheobronchial complications of infiltrating cancer: five had respiratory-digestive fistulas, 14 had mixed-type obstructions (mucosal infiltration plus extrinsic compression), and two had diffuse tracheal hemorrhages from the tumor surface (three patients had more than one complication). Two of 19 patients had benign postintubation stricture and malacia. Overall, 33 stents were implanted either simultaneously or in a consecutive manner. Scanning electron microscopy was performed both on prototype stents and on other available silicone stents for comparison. RESULTS: The treatment improved the patients' clinical condition substantially. The mechanical properties of the new prosthesis were excellent. Important stent-associated side effects were early mucus retention (n = 7), infolding of the inner silicone layer (n = 2), and stent dislodgment (n = 2). As of February 1997, 10 patients have died of causes unrelated to stent placement. Seven patients with malignant airway disease are still alive from 2 weeks up to 7 months after initial treatment. Scanning electron microscopy of explanted and unused prototypes suggested that an extremely ragged luminal microstructure may contribute to the firm adhesion of secretory material and that technical smoothing of the surface avoids such complications. CONCLUSIONS: The novel self-expandable silicone airway stent may be a promising addition to commonly used stent types. Short-term and medium-term management of fistulas, tumor surface bleeding, and strictures (malignant and benign) is satisfactory. Scanning electron microscopy of stents provides information on peculiar features of microstructure and material that may be of use in clinical research and technical innovation.

Adult↗

Reduction of insulin and triglycerides delays glomerulosclerosis in obese Zucker rats.

To evaluate the effect of insulin and/or triglycerides on the pathogenesis of glomerulosclerosis, acarbose (BAYg5421), an inhibitor of intestinal alpha-glucosidases, was administered as a dietary admix (40 mg/100 g chow) to Zucker obese rats (ZOA), from 1.5 months until sacrifice at 1.5, 5, 8, 10 and 15 months. Obese (ZO) and lean (ZL) rats served as controls. Despite a similar food intake, ZOA weighed less than ZO at all ages. Acarbose reduced serum triglycerides at all ages, and insulin until 10 months. Glycemia remained normal in all groups. Proteinuria developed with age and to a greater degree in ZO than in ZOA rats. In ZL, a faint proteinuria appeared only in the oldest animals. Glomerulosclerosis, tubular and interstitial lesions rapidly affected ZO kidneys. These lesions were reduced in ZOA until 10 months. Acarbose did not modify the hypertrophy of the glomeruli that developed after three months, but slowed down the expansion of the mesangial domain seen in ZO. Thus, by reducing the amount of ingested glucose, acarbose yielded a normal glycemia with a lesser production of insulin and reduced renal impairment. Therefore, insulin could be a key factor involved in the pathogenesis of glomerulosclerosis, either directly or through a control of triglyceride concentrations.

Acarbose↗

Dose-response relationship to inhaled endotoxin in normal subjects.

Exposure to endotoxin and to its purified derivative lipopolysaccharide (LPS) is related to several occupational pulmonary diseases and to severe domestic asthma. An inhalation of a given dose of pure LPS produces both a systemic and a bronchial inflammatory response. Information on the dose-response relationship to inhaled LPS in normal subjects is a prerequisite to define the safety threshold of exposure. In the present study, the clinical and inflammatory responses to rising doses of inhaled LPS was evaluated. Nine normal volunteers were challenged weekly by inhalation with saline, 0.5, 5, and 50 microg LPS (Escherichia coli). The response determinators are the clinical symptoms, fever, FEV1, blood polymorphonuclear neutrophils (PMNs) with their level of activation (measured by luminol enhanced-chemiluminescence), and both the blood and the urine concentrations of the C-reactive protein (CRP). To assess the bronchial inflammatory response, an induced sputum was obtained 6 h after each dose of LPS, and the total and differential cell counts as well as the MPO, ECP, and TNF-alpha concentrations were measured. Compared with the saline, an inhalation of 0.5 microg LPS induces a significant decrease in the PMN luminol-enhanced chemiluminescence (p < 0.01), which could reflect a process of margination and/or extravascular sequestration of activated PMN. Inhalation of 5 microg LPS is associated with a significant rise in blood CRP (p < 0.01) and PMNs (p < 0.001) and in sputum PMNs (p < 0.05), monocytes (p < 0.05), and MPO (p < 0.05). Inhalation of 50 microg LPS was characterized by a significant increase in temperature (p < 0.01), blood PMNs (p < 0.001), blood and urine CRP (p < 0.01 and < 0.01), and sputum PMNs (p < 0.001), monocytes (p < 0.05), lymphocytes (p < 0.05), MPO (p < 0.01), TNF-alpha (p < 0.01), and ECP (p < 0.01) while five subjects develop symptoms. In normal subjects, the response to inhaled LPS is dose-related, the most sensitive markers of LPS-induced inflammation being the blood PMNs count with their level of activation, the blood CRP concentration, and the sputum PMNs count. The no-response threshold to an acute inhalation of LPS is less than 0.5 microg.

Administration, Inhalation↗

Biotin and digoxigenin as labels for light and electron microscopy in situ hybridization probes: where do we stand?

Biotin was recently applied to detect cellular DNA or RNA. In combination with avidin, streptavidin or antibody, it can be conjugated with fluorescent dye, enzyme, ferritin, or gold. However, emphasis has recently been placed on the false-positive results that are obtained when this probe is used, because endogenous biotin may sometimes interfere with specific signals. Digoxigenin appears to be an interesting alternative because it is present exclusively in Digitalis plants as a secondary metabolite. We discuss in this review the efficiency and the respective advantages and disavantages of these two probes for in situ hybridization, mainly at the electron microscopic level.

Biotin↗

Mite allergy is associated with a specific profile of IgG epitopes recognized on antigen p1 of Dermatophagoides pteronyssinus.

BACKGROUND: Immune response to inhaled antigens differs in allergic patients and healthy individuals, mostly in the quality of T cell help provided (i.e. Th2 or Th1 dominant subset). However, while different in many functional aspects, both groups of T cells shared the capacity to support the synthesis of antigen-specific immunoglobulin G (IgG) antibodies detected in different amounts in the serum of atopic and healthy individuals. OBJECTIVE: The present study investigates whether these IgG responses display similar or different epitopic dominance in the mite sensitization model. METHODS: Antibody specificity was evaluated by comparing the IgG binding to native Der p1 (nDer p1) and its products of pepsin hydrolysis (dDer p1) in 56 mite-allergic patients and 148 healthy individuals, including 24 mite-sensitized individuals in a solid enzyme linked immunosorbent assay (ELISA). Antibody specificity was also studied in competitive ELISA using streptavidin biotin technology. RESULTS: Mite-allergic sera showed a higher degree of binding to nDer p1 than to dDer p1, whereas control sera and mite-sensitized sera bound at a similar level to the two forms of the antigen. Allergic sera and control sera, including mite-sensitized sera, showed distinct capacities to prevent the binding to nDer p1 of pooled IgG from each group as well as murine monoclonal antibodies specific to Der p1. CONCLUSION: The IgG response to Der p1 of mite-allergic patients differs from that of healthy controls and mite-sensitized subjects, not only in its increased titres but also in its consistant pattern of modified specificity, displaying a marked preference for conformational epitopes. Cross-competition experiments confirm the clinically associated, restricted specificity, allowing almost complete discrimination between groups, particularly between mite-sensitized and mite-allergic subjects, which is currently impossible with routinely available assays.

Adult↗

Human keratinocyte culture from the peritonsillar mucosa.

Tonsillectomy tissue can be used as a routine source for cultures of oropharyngeal keratinocytes. In so doing, a peritonsillar strip of unaltered mucosa was dissected in the upper submucosa. Subsequent trypsinization yielded 7.0 +/- 3.4 x 10(6) keratinocytes per bilateral tonsillectomy. Keratinocyte attachment and growth in primary culture were promoted by sublethally irradiated 3T3 murine fibroblasts. Three subcultures could be performed without a feeder layer and were characterized by a population doubling time of 4.5 days during log growth phase. Electrophoretic and immunoblot analysis of the third subculture revealed a strong expression of keratin pairs 5/14 and 6/16 as well as keratins 7 and 19, whereas keratins 8/18 were expressed less intensely. The lowest intensity, was found for keratin 13, which is known to be indicative of the differentiated mucosa. The culture technique thus provides an easily available in vitro model for morphological and functional studies on the epithelial compartment of human oropharyngeal mucosa.

3T3 Cells↗

[Self-induced illness in ENT medical practice. Artefacts as a contribution to differential diagnosis of unusual illness courses].

Until now reports of factitious disease have not been found in the ENT literature. In contrast, the dermatologic literature estimates an incidence from 0.01 to 0.26%. In order to achieve effective treatment for these patients, knowledge of the characteristic symptoms is fundamental. The present paper describes the variety of disease possible, using three cases treated between 1992 and 1994 in the ENT Department of Cologne. According to the literature, females are involved in a ratio of 9:1, with the majority working in medically related professions. Depression and anorexia are typical symptoms. When a factitious disease is suspected, psychiatric consultation is essential. Confrontation of a suspect patient by the otolaryngologist is not often considered because several reports quote suicidal behavior in up to 25% of self-manipulating patients and tendencies to refuse to follow psychiatric treatment are considerable.

Adult↗

Emergency stenting of malignant obstruction of the upper airways: long-term follow-up with two types of silicone prostheses.

OBJECTIVE: We evaluated the long-term prognosis of stents placed on an emergency basis in the trachea and its bifurcation for malignant stenosis. METHODS: We retrospectively analyzed all bronchologic treatments of obstructing airway lesions from January 1993 to December 1995. RESULTS: We report on 10 patients with severe malignant "mixed-type" obstruction of the proximal trachea or distal trachea plus both main-stem bronchi. They had far-advanced inoperable tumor (esophageal cancer: n = 4; lung cancer: n = 3; recurrent laryngeal, uvula, and thyroid cancer: n = 1 each). Emergency treatment consisted of a dilating bougie maneuver followed by the insertion of a large one-way (n = 4) or Y-shaped silicone prosthesis (n = 6). After the intervention, there was a long-lasting clinical improvement. Median survival from stent insertion was 8 months for all patients irrespective of tumor type; it was 5 months for patients with lung carcinoma and 8 months for those with esophageal cancer. The results are in accordance with other studies using different therapeutic modalities. Stent exchange was necessary in five patients. Main reasons were continuing tumor growth beyond the proximal and distal boundaries and recurrent productive bronchial infection. Patients died of pneumonia (n = 4), pulmonary lymphatic spread (n = 1), cardiac failure (n = 2), and fatal hemorrhage (n = 1). As of December 1995, three patients were still alive 2, 5, and 8 months after implantation. CONCLUSIONS: As evidenced by clinical efficiency and length of palliation, endoscopic placement of silicone-based one-way and bifurcational prostheses in far-advanced tumor of the central airways is technically feasible and ethically justifiable.

Aged↗

Effects of bilateral orbital decompression by an endoscopic endonasal approach in dysthyroid orbitopathy.

AIMS: The efficacy of endoscopic endonasal orbital decompression in dysthyroid orbitopathy was analysed. METHODS: In 21 consecutive cases of bilateral operation short term (10 (SD 6) days after operation) and long term (156 (12) days after operation) results were recorded. RESULTS: Short term results showed that vision of the more affected eye improved from a mean of 0.35 to 0.59; vision improved in all but one eye which remained unchanged. In the fellow eyes mean visual acuity improved from 0.6 to 0.7; three of these eyes showed a decrease. Mean proptosis returned from 23.0 mm to 20.0 mm. As to motility the mean abductive capacity decreased from 5.5 mm to 4.0 mm of monocular excursion, whereas adduction increased from 7.5 mm to 8.5 mm. Upgaze and downgaze did not show any major change. The mean angle of horizontal squint shifted from 7.5 degrees of convergence to 15.5 degrees while no significant vertical or cyclorotational deviation was induced. These immediate postoperative results proved to be stable for the period of long term follow up with only slight changes. No significant bleeding or specific otorhinolaryngological complication without resolve occurred intraoperatively or perioperatively. CONCLUSION: This method is believed to be superior to non-endoscopic techniques because it avoids external scars and antral pain. With regard to the relief of intraorbital pressure, the technique gives good results for visual acuity improvement, but in proptosis reduction the method is not as efficient as external or combined procedures. There seems to be no difference when compared with other approaches in induction of horizontal squint. The method has a protective long term effect against the recurrence of compressive optic neuropathy.

Adult↗

Hyperthermia occurring with paradoxical development of cerebral tuberculomas.

A 59-year-old male Moroccan who had been mechanically ventilated for extensive pulmonary tuberculosis, suddenly developed a generalized seizure with hyperthermia. He had been receiving adequate antituberculosis treatment for 2 weeks. Brain CT scan demonstrated the development of multiple cerebral tuberculomas. The brain CT scan that had been performed at the initiation of antituberculosis therapy was normal. Corticosteroids resulted in rapid improvement of the patient's clinical condition. The pathogenic mechanisms of the development of such lesions as well as their therapy and CT appearance are discussed.

Adrenal Cortex Hormones↗

Severity of asthma is related to endotoxin in house dust.

In sensitized subjects, exposure to the mite allergen appears to be only one of several factors leading to asthma. We hypothesized that in association with allergen exposure, endotoxin, a proinflammatory agent present in house dust (HD), influences the severity of asthma. Using a cross-sectional study design, we investigated a group of 69 consecutive dust mite (HDM)-sensitized subjects defined as having rhinitis (n = 20) or asthma (n = 49); the latter were evaluated functionally and clinically by three different scores and by their need for daily medication. Concentrations of Dermatophagoides pteronyssinus p I allergen (Der p I) (by two-site monoclonal antibody enzyme-linked immunosorbent assay [ELISA]), guanine (by high-pressure liquid chromatography [HPLC]), and endotoxin (by modified Limulus. amebocyte lysate assay) were measured in HD collected in duplicate from the mattresses and floors in each subject's home. The concentrations of Der p I and of guanine in HD collected from mattresses were significantly higher in asthmatic subjects than in those with rhinitis (p < 0.05 and < 0.04, respectively). In subjects (n = 37) exposed to a high level of HDM allergen (i.e., Der p I > or = 10 micrograms/g HD and/or guanine > or = 0.10 mg/100 mg HD), the severity of asthma was unrelated to mite allergen concentration in HD. On the contrary, the severity of asthma was related to concomitant exposure to endotoxin in HD, since the concentration of HD endotoxin was significantly and inversely correlated with FEV1 (p < 0.05), FEV1/FVC (p < 0.02), daily need for oral (p < 0.01) and inhaled (p < 0.01) corticosteroids, daily need for beta 2 agonists (p < 0.001) and xanthines (p < 0.01), and clinical scores such as the modified Aas score (p < 0.01). In HDM-sensitized subjects exposed to a high level of allergen, the concentration of endotoxin measured in HD is an important determinant of asthma severity.

Adult↗