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Biomedical subjects

O Michel

Publications and source records attributed to O Michel.

At least 73 records · Page 4Linked to original sources

Nitric oxide synthase inhibitor suppresses the ototoxic side effect of cisplatin in guinea pigs.

Cisplatin is known to cause inner ear damage (ototoxicity). The role of inducible nitric oxide synthase (iNOS) in the cochlea of guinea pigs after injections of cisplatin or a combination of cisplatin and NOS inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) i.p. was examined electro-and immunohistochemically. The auditory brain stem responses (ABR) were measured prior to injection and 3 days after the injection. Three days after injection, the cochleas were examined immunohistochemically for iNOS. We found that iNOS was expressed in the cisplatin- and L-NAME/ cisplatin-treated cochlea. The threshold shift of ABR was significant in the cisplatin group, whereas it was decreased in the L-NAME/cisplatin group. iNOS catalyzed high NO levels lead to inner ear dysfunction. Our results indicate that iNOS mediates the ototoxicity of cisplatin.

Animals↗

Nitric oxide synthase inhibitor reduces the apoptotic change in the cisplatin-treated cochlea of guinea pigs.

Cisplatin is known to cause inner ear damage. The role of nitric oxide (NO) in the cochlea of the guinea pigs after injections of cisplatin or a combination of cisplatin and NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine methyl ester (L-NAME)] i.p. was examined by means of immunohistochemistry. Three days after injection, the cochleas were examined immunohistochemically for single-stranded DNA (ssDNA). We found that ssDNA was expressed in the stria vascularis and spiral ganglion cells of the cisplatin-treated cochlea. In the L-NAME/cisplatin-treated cochlea, the number of cells that exhibited positive staining for ssDNA was markedly reduced. High NO levels lead to inner ear dysfunction under pathological conditions. Our results indicate that NO mediates the ototoxicity of cisplatin.

Animals↗

Clinical experience with beta-trace protein as a marker for cerebrospinal fluid.

beta-Trace protein is an immunological marker for the detection of cerebrospinal fluid traces. The aim of the study was to evaluate the predictive value of the beta-trace protein test. We investigated 145 specimens for cerebrospinal fluid using beta-trace protein. All case notes were retrospectively reviewed and tabulated for indication and procedure with focus on outcome. The specimens were analyzed by immunoelectrophoresis. beta-Trace protein was detected in 62 specimens and was absent in 83. In correlation with the clinical course, the clinical findings, the results of high-resolution computed tomography of the paranasal sinuses or petrous bone, computed tomographic cisternography, magnetic resonance imaging, indium 111-pentetic acid radionuclide cisternography, intraoperative findings, and visualization using sodium-fluorescein, there were no false-positive results. In 6 cases, a false-negative result occurred. The overall accuracy was 95.68%. The beta-trace test has a specificity of near 100% and a sensitivity of 91.17%. Analysis of beta-trace protein is a valuable test and has some advantages in comparison with the beta2-transferrin assay.

Adolescent↗

Early glomerular macrophage recruitment in streptozotocin-induced diabetic rats.

Diabetic glomerulosclerosis is defined by increased glomerular extracellular matrix (ECM) that is mainly synthesized by mesangial cells that underwent an activation mediated by cytokines and growth factors from various cellular origins. In this study, we tested whether macrophages could infiltrate the glomeruli and influence ECM synthesis in experimental diabetes. To test our hypothesis, we initially studied the dynamics of glomerular macrophage recruitment in streptozotocin-induced diabetic rats at days 1, 2, 4, 8, 15, and 30 by using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on isolated glomeruli and immunohistochemistry and morphometry. We then assessed the role of macrophages on the basis of the pharmacological modulation of their recruitment by insulin or ACE inhibitor treatments and by X-irradiation-induced macrophage depletion at days 8 and 30. Macrophages were recruited within the glomeruli at the very early phase of hyperglycemia by using RT-PCR CD14 detection from day 2 and by using ED1 immunohistochemistry from day 8. This glomerular macrophage infiltration was associated with an increase in alpha1-chain type IV collagen mRNA. In parallel, the diabetic glomeruli became hypertrophic with an increase in the mesangial area. Macrophage recruitment was preceded by or associated with an increased glomerular expression of vascular cell adhesion molecule 1, intracellular adhesion molecule 1, and monocyte chemoattractant protein 1, which contributes to monocyte diapedesis. Glomerular interleukin-1beta mRNA synthesis was also enhanced as early as day 1 and could be involved in the increase in ECM and adhesion molecule gene expressions. Insulin treatment and irradiation-induced macrophage depletion completely prevented the glomerular macrophage recruitment and decreased alpha1-chain type IV collagen mRNA and mesangial area in diabetic rats, whereas ACE inhibitor treatment had an incomplete effect. It can be concluded that in the streptozotocin model, hyperglycemia is followed by an early macrophage recruitment that contributes to the molecular and structural events that could lead to glomerulosclerosis. Therefore, besides direct stimulation of mesangial cells by hyperglycemia, macrophages recruited in the glomeruli during the early phase of hyperglycemia could secondarily act on mesangial cells.

Animals↗

Preliminary report: long-term results of transnasal orbital decompression in malignant Graves' ophthalmopathy.

In order to demonstrate the safety and efficacy of transnasal orbital decompression for malignant Graves' ophthalmopathy, we carried out a retrospective chart review and clinical follow-up examination of 78 consecutive patients who were operated on for compressive optic neuropathy (CON) with loss of visual acuity or visual field defects. The intervention - strictly transnasal, endoscopically controlled, bilateral decompression of the medial and inferomedial wall of the orbit - was performed when medical and radiation therapy had failed. A total of 145 endonasal decompressions were performed on 78 patients (63 female, 15 male, 52. 2 +/- 10.5 yrs.) over 9 years. Of these, 65 were operated bilaterally, 15 required only unilateral decompression; 4 had repeated surgery. Visual acuity increased from an average of 0.50 +/- 0.27 (range, 0.01 - 1.25) to 0.75 +/- 0.21 (range, 0.01 - 1.25). Proptosis decreased by an average of 3.94 +/- 2.73 mm (range, -1.0 - 11.0 mm), from a mean preoperative Hertel measurement of 22.19 +/- 3. 13 mm (range, 15 - 34 mm) to a mean postoperative Hertel measurement of 18.3 +/- 2.65 mm (range, 10 - 26 mm). Ocular motility was corrected by recession of the medial rectus muscle in 58 cases, in 26 cases immediately after decompression in the same surgical session. The transnasal orbital decompression procedure improved vision, decreased proptosis in a range comparable to more invasive techniques and had favorable cosmetic results without additional disfiguring by scars. Post-decompression strabismus was successfully managed by recession of both medial orbital muscles in the same surgical session.

Decompression, Surgical↗

Expression of inducible nitric oxide synthase (iNOS/NOS II) in the cochlea of guinea pigs after intratympanical endotoxin-treatment.

Since NO is believed to be involved in cochlear physiology, presence of the constitutive isoforms of nitric oxide synthase (NOS), and the target enzyme of NO, soluble guanylyl cyclase (sGC) in structures of the mammalian cochlea have been demonstrated. To date, no reports have been published regarding the detection of the inducible isoform (NOS II) in the cochlea. In order to show the capability of iNOS expression in cochlear tissue, a mixture of proinflammatory bacterial lipopolysaccharides (LPS) and tumor necrosis factor alpha (TNF-alpha) was injected into the tympanic cavity of guinea pigs, vs. saline-solution as control. Paraffin sections of LPS/TNF-alpha treated and saline-treated cochleae (6 h) were examined immunohistochemically with specific antibodies to neuronal, endothelial and inducible NOS and to sGC. Initiated expression of iNOS in the cochlea was observed in the wall of blood vessels of the spiral ligament (SL) and the modiolus, in supporting cells of the organ of Corti, in the limbus, in nerve fibers and in a part of the perikarya of the spiral ganglion after LPS/TNFalpha-treatment. iNOS was not detected in saline-treated control tissue. Expression of both constitutive NOS-isoforms (endothelial and neuronal NOS) and of sGC showed no significant differences in both experimental groups. Endothelial eNOS and neuronal bNOS were detected co-localized in ganglion cells, in nerve fibers, in cells of the SL and in supporting cells of the organ of Corti, but not in sensory cells. Strong labeling for bNOS became evident in the endosteum of the cochlea, while in the endothelium of blood vessels and in the epithelium of the limbus only eNOS could be labeled. sGC could be detected in SL, in supporting and sensory cells of the organ of Corti, in nerve fibers, ganglion cells, in the wall of blood vessels and in the limbus-epithelium. While small amounts of NO, generated by bNOS and eNOS, seem to support the cochlear blood flow and auditory function as well as neurotransmission, high amounts of iNOS-generated NO could have dysregulative and neurotoxic effects on the inner ear during bacterial and viral infections of the middle and inner ear.

Animals↗

Expression of inducible nitric oxide-synthase in the vestibular system of hydropic guinea pigs.

Immunohistochemical investigations of the guinea pig vestibular system, using a specific antibody to the inducible isoform of NO-synthase (iNOS/NOS II), have been performed 3 weeks after surgical closure of the right endolymphatic duct (n = 7). Endolymphatic hydrops (ELH) of the right temporal bone became evident by excavation of the Reissner's membrane in all seven animals. Those animals revealed iNOS-expression in ganglion cells, in the wall of blood vessels and in nerve fibers of the right vestibular system, while the corresponding left temporal bones and temporal bones of non-operated controls (n = 6) as well as of sham-operated animals (n = 3) did not show any iNOS-positive structures. iNOS-generated NO could be involved in the pathophysiology of vestibular dysfunction in Meniere's disease.

Animals↗

[Neurinoma of the major petrosus nerve].

Facial nerve schwannomas are rare benign tumors, when occurring, they are located most frequently in the distal fallopian canal and present as extracranial masses. The predominant symptom is a progressive facial nerve paralysis. We report a 20-year-old woman with an intracranial schwannoma originating from the greater superficial petrosal nerve that had wide extension into the pterygopalatine fossa. The motor facial nerve including the geniculate ganglion was not affected. The patient presented with vertigo, progressive hearing loss and mild facial nerve synkinesis but without a lacrimation deficit. The tumor was detected by computed tomography and magnetic resonance imaging. The schwannoma was completely removed using an intracranial, extradural middle fossa approach during which complete preservation of the motor facial nerve was possible. To our knowledge this is the first reported case of an isolated schwannoma of the greater superficial petrosal nerve without involvement of the motor facial nerve.

Adult↗

[Sjögren syndrome and bilateral MALT lymphoma of the parotid gland].

Sjögren's syndrome is an important autoimmune disease in the head and neck. Patients have an increased arrival risk of up to 6% per year for developing B-cell lymphomas, including mucosa-associated lymphoid tissue (MALT) lymphomas. The following case report shows this relation and the difficulty of differentiating clinically recurrent swelling of the parotid gland in Sjögren's syndrome from malignant lymphoma. A 64-year-old woman had a 2-year history of indolent, recurrent swelling of both parotid glands. Blood examination showed elevated ESR and a hypergammaglobulinemia. Immunosuppressive therapy produced no improvement. Two years after the diagnosis of Sjögren's syndrome, swelling of the left parotid gland persisted. Superficial parotidectomy of the left side was performed and histopathological examination revealed a MALT-related lymphoma. Subsequent parotidectomy of the right side also showed infiltration of the gland by a MALT lymphoma. Postoperative radiation therapy was given. During the follow-up period no recurrence or systemic disease was detected. Patients with Sjögren's syndrome should be examined regularly by the otolaryngologist. If a lymphoma cannot be ruled out, open biopsy must be considered for histological diagnosis. Prognostic factors for developing a lymphoma are possibly a high ESR and hypergammaglobulinemia. Further prognostic factors have to be evaluated.

Blood Sedimentation↗

Localization of the NO/cGMP-pathway in the cochlea of guinea pigs.

The presence of nitric oxide synthase (NOS) in substructures of the cochlea of guinea pigs is an issue of current focus. Moreover, information concerning the localization of cells effected by the NO/cGMP-pathway are rare. Paraffin sections of guinea pig cochlea were incubated with specific antibodies to the three known NOS isoforms, soluble guanylyl cyclase (sGC) and cyclic guanosine-monophosphate (cGMP), the second messenger system of NO. While detection of inducible iNOS failed in all cochlear structures, expression of endothelial eNOS was found in the spiral ligament, in the stria vascularis, in cells of the organ of Corti, in nerve fibers and in some perikaryia of the spiral ganglion. The cochlear nerve showed an accentuated affinity for immunostaining in distal, basal segments of the cochlea. Neuronal bNOS was found predominantly in the endosteum of the modiolus and cochlea and was less intensively present in all perikaryia of the spiral ganglion and in the spiral ligament. Supporting cells of the organ of Corti and cells in the limbus spiralis displayed only modest immunostaining, while bNOS was not found in outer and inner hair cells. NOS detection was accompanied by immunoreactivity to sGC and to cGMP. The presence of NOS and its second messenger system gives evidence for a possible involvement in neurotransmission, regulation of the cochlear amplifier and in homeostasis.

Animals↗

Homeopathic effect on heart rate variability.

We record ECGs from healthy human subjects during 24-h long intervals, using ambulatory equipment. We calculate from the data various parameters, searching for those that change in a clear and systematic way under a homeopathic stimulus, (Strophantus hispidus 30c). The energy fraction at high frequencies in the power spectrum of heart rate variability fulfills this condition, and we are able to interpret our results in a way consistent with the information on this medicine in the homeopathic Materia Medica.

Adolescent↗

LMR spectroscopy: a new sensitive method for on-line recording of nitric oxide in breath.

Laser magnetic resonance spectroscopy (LMRS) is a sensitive and isotope-selective technique for determining low concentrations of gaseous free radicals with high time resolution. We used this technique to analyze the nitric oxide (NO) concentration profile while simultaneously measuring the flow and expired volume during several single breathing cycles. Eight healthy, nonallergic volunteers were investigated. An initial NO peak was found in all breathing cycles before the NO concentration dropped to a relatively stable plateau in the late phase of expiration. The nasal NO peak was significantly higher than the oral NO peak. The nasal NO plateau was always higher than the oral NO plateau. The height of the initial nasal and oral NO peak rose with increasing duration of breath hold, whereas the late expiratory NO plateau changed only little for either the nasal or the oral breathing cycles. Our findings demonstrate, in line with other reports using other techniques, that the nose is the primary source for NO within the airways.

Adult↗

Nitric oxide synthase in the vestibulocochlear system of mice.

The exact distribution of nitric oxide-synthases (NOS) and the NO-target enzyme soluble guanylyl cyclase (sGC) in the cochlea and vestibular organ is an issue of current discussion. The existence of NOS-isoforms in the cochlea of the guinea pig has been described recently, while information about the vestibular system are still rare and non-satisfying. In order to gain more information, immunostaining was performed, using specific antibodies to NOS I-III and to sGC, on paraffin sections of complete temporal bones from mice. NOS III could be detected in cochlea and vestibular ganglion cells, in nerve fibres, in outer hair cells of the cochlear and in the sensory epithelium of the maculae. Also, the spiral ligament and the limbus epithelium was positive to NOS III. NOS I was found in the sensory epithelium of the maculae and cristae ampullares, outer and inner hair cells of the cochlea, in nerve fibres and in ganglion cells. In contrast to that NOS II could not be detected at all. Furthermore, a strong NOS I immunoreaction was displayed on the endosteum of the bone, while the periosteum was lacking of NOS. NOS detection was accompanied by immunoreactivity to sGC. The findings imply that NOS I and III-generated NO is involved in neurotransmission and other regulative processes in the vestibulocochlear system.

Animals↗

Localisation of the nitric oxide (NO)/cGMP-pathway in the vestibular system of guinea pigs.

The exact distribution of nitric oxide-synthases (NOS) in the vestibular system has not been described satisfying yet. Immunostaining, using specific antibodies to the three known NOS-isoforms, to cyclic guanosine monophosphate (cGMP) and soluble guanylyl-cyclase (sGC), the second messenger system of nitric oxide (NO), was performed on paraffin sections of temporal bone from guinea pigs. eNOS could be detected in vestibular ganglion cells and in nerve fibres, including the calyces, surrounding the type 1 hair cells (HC). bNOS was found in the sensory epithelium, ganglion cells and in bone, while iNOS could not be found. NOS-detection was accompanied by reactivity to sGC and to cGMP. This finding implies that b- and eNOS-generated NO is involved in regulative processes in neurotransmission and regulation of blood flow.

Animals↗

Hyoid bone malformation confirmed by 3-dimensional computed tomography.

We describe the case of a young woman with pain on turning her head attributable to a malformation of the hyoid bone. Diagnosis was established using spiral computed tomography with the patient's neck in the position of greatest discomfort and with 3-dimensional reconstruction of the hyoid bone. Prior conventional radiography and magnetic resonance imaging did not aid in finding a diagnosis. After surgical removal of both greater cornua of the hyoid bone there was a complete relief of symptoms.

Adult↗