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Biomedical subjects

R Laskawi

Publications and source records attributed to R Laskawi.

At least 19 recordsLinked to original sources

[Solitary intraparotid neurofibroma of the facial nerve. Symptomatology, biology and management].

Neurogenic neoplasms of the parotid gland are extremely uncommon. We present the case of a solitary intraparotid neurofibroma of the N. facialis occurring in a 55-year-old female who noted a painless left-side enlargement in the region of the parotid gland over a period of 2 years. Facial function was normal. Magnetic resonance imaging revealed a well-demarcated round mass within the left parotid. At surgery, a tumor was found involving the main trunk of the facial nerve, histopathologically representing a neurofibroma. Since solitary intraparotid neurofibromas are characterized by a very slow growth lacking the propensity for malignant transformation, the tumor was left to preserve facial nerve function. The clinical course over months or even years and the non-specific symptomatology are characteristic of intraparotid facial neurofibromas. Surgical management depends on the clinical setting in the individual case. Conservative treatment based on facial nerve preservation and leaving the tumor in situ is recommended, rather than radical tumor removal with resection of the segment of the N. facialis involved.

Biomarkers, Tumor↗

Inflammatory diseases of the salivary glands in infants and adolescents.

OBJECTIVE: To determine retrospectively the localization, etiology and treatment of inflammatory diseases of the salivary glands in infants and children and to evaluate treatment outcome. PATIENTS AND METHODS: Forty-five patients were treated in our institution in the period 1966-2000. The patients' records were evaluated and the results and side-effects of therapy were documented by a controlled follow-up study. RESULTS: Twenty-five of our patients were females (55.6%) and 20 males (44.4%). Inflammatory disorders figured most prominently in the group of patients between 12 and 16 years (n=14). Inflammation of the submandibular glands was the most common disease with 53.3% (n=24). The most frequent underlying cause in this subgroup of acute and chronic sialadenitis was sialolithiasis of the submandibular gland (40%). All patients were symptom-free in the long-term follow-up and all were symptom-free after surgical intervention. CONCLUSIONS: The present study shows that diseases of the salivary glands are rare among infants and children. Acute and chronic sialadenitis not responding to conservative treatment requires an appropriate surgical approach.

Acute Disease↗

Autoantibodies to human manganese superoxide dismutase (MnSOD) in children with facial palsy due to neuroborreliosis.

AIM: Acute peripheral facial palsy due to neuroborreliosis is associated with a distal neuritis. In patients with Lyme disease the activity of antioxidant enzymes is decreased. With respect to the pathogenesis of neuroborreliosis, sera of children with acute peripheral facial palsy were investigated for autoantibodies against human manganese superoxide dismutase (MnSOD), which were suspected of raising the oxidative injury of infected tissues. METHODS: Sera of 20 children with acute peripheral palsy with neuroborreliosis, sera of 20 children with facial palsy without reference to Lyme disease and sera of 14 blood donors were tested for antibodies against human MnSOD using an ELISA. RESULTS: The concentrations of IgM autoantibodies to MnSOD of the children with neuroborreliosis were significantly increased, compared with the two control groups. CONCLUSIONS: We propose that the antibodies detected block the protective effects of MnSOD resulting in an increased oxidative inflammation.

Autoantibodies↗

[Botulinum toxin in otorhinolaryngology].

BACKGROUND AND OBJECTIVES: Through its anticholinergic effect, botulinum toxin is a suitable therapeutic option for dysfunctions of the muscular and the autonomic nervous system. PATIENTS/METHODS: Beside the classical indications like facial hyperkinesis (i.e. blepharospasm, hemifacial spasm), the treatment of complex dystonias (oromandibular dystonia, spasmodic dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful. Botulinum toxin is an alternative treatment of tension type headache and migraine. A new indication of botulinum toxin application may involve the treatment of nasal hypersecretion through the effect on the nasal glands. RESULTS: The positive therapeutic effect starts a few days after treatment and lasts longer in disorders of the autonomic nervous system. Because of its temporally limited therapeutic effect, the patients need further treatment. Side-effects are rare. CONCLUSIONS: Botulinum toxin is an effective treatment for a variety disorders with different etiologies and has very few side effects.

Autonomic Nervous System Diseases↗

Acute peripheral facial palsy in Lyme disease -- a distal neuritis at the infection site.

AIM: Children with acute peripheral facial palsy have often suffered tick bites and/or erythema migrans in the head/neck region on the same side. With respect to the pathogenesis of neuroborreliosis this topographical association was investigated in an animal model. METHODS: A Borrelia garinii strain, isolated from the CSF of a child with acute facial palsy, was injected in 9 rats intracutaneously in the right subauricular region. Infected rats were examined for clinical symptoms of Lyme disease, the spread of the spirochetes was investigated by PCR of necropsies (facial nerves, trigeminus nerves, heart, brain, skin) up to 47 days after infection. The nerve tissues were investigated by histology, immunohistochemistry and electron microscopy. RESULTS: None of the rats developed a facial palsy or other symptoms of Lyme disease. Borrelia DNA was found in the heart after 5 days and in the brain after 7 days of infection up to the end of investigation (47 days), as well as in the ipsilateral peripheral nerves after 7 to 33 days. Borrelia was detected by electron microscopy near endoneural vessels of the facial nerve. Peri-, epi-, and endoneural infiltrations of macrophages, plasma cells and B cells characterized an inflammation of the facial and trigeminus nerves ipsilateral to the infection site. CONCLUSION: An infection with Borrelia garinii in the subauricular region induces an ipsilateral neuritis of peripheral nerves. The particular vulnerability of the human facial nerve may be a result of its long intraosseus course. Thus, an inflammatory edema may injure the nerve in the canalis facialis.

Acute Disease↗

Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1, -2, and -3 in benign and malignant tumours of the salivary gland.

AIMS: The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of the normal salivary gland as well as in mechanisms of tumour invasion and metastasis. Our aim was to analyse protein and mRNA expression of MMPs and TIMPs in normal salivary gland tissue and in various salivary gland neoplasms. METHODS AND RESULTS: Immunohistochemistry for MMP-2, MMP-9, TIMP-1, -2 and -3 was performed in 20 malignant and six benign salivary gland tumours. The immunoscores of MMP-2 were significantly higher in carcinomas compared with adenomas (P = 0.0028). The MMP/TIMP ratio was significantly higher in carcinomas than in adenomas (P = 0.0097). In mucoepidermoid carcinomas MMP-2 expression was preferentially observed in the intermediate cell type. Neoplastic acinar cells of acinic cell carcinoma demonstrated de novo expression of MMP-2, MMP-9, TIMP-1, and TIMP-2. Immunoscores of TIMP-3 were not decreased in malignant tumours compared with adenomas. In accordance with the immunostaining of MMP-2 and -9, gelatinolytic activity could be demonstrated by in-situ zymography. The mRNA expression of MMPs and TIMPs analysed by real-time reverse transcriptase-polymerase chain reaction in three malignant and two benign tumours and their corresponding normal tissue did not generally correlate with their protein expression. CONCLUSIONS: Our findings suggest a disturbed balance between MMP and TIMP in malignant salivary gland tumours. MMP-2 expression in particular seems to be related to the invasive properties and the malignant potential of these tumours.

Adenoma↗

[The Levy-Hollister syndrome: a syndrome of dysplasias with ENT-manifestations].

The Levy-Hollister syndrome is characterized by a highly variable expression of dysplasia in different organ systems. Autosomal-dominant inheritance is recognised, but most cases are sporadic. In the field of otorhinolaryngology, xerostomia can be found due to aplasia of the major salivary glands, as well as congenital sensorineural, conductive or combined hearing loss and dysplasia of the auricles, mostly appearing as cup-shaped ears. Here we report on a 2-year-old boy with severe xerostomia. The disease was found to be caused by bilateral aplasia of the parotid and submandibular glands. There were also slight dysplasias of both auricles and a bilateral inner ear malformation as the origin of sensorineural hearing loss. Due to its highly variable expression, Levy-Hollister syndrome is often difficult to distinguish from other diseases and syndromes, so that the cooperation of different departments is necessary for an accurate diagnosis. Because of its dominant inheritance, a genetic consultation should be recommended to the patient. Auricular dysplasia and conductive hearing loss can possibly be treated surgically.

Abnormalities, Multiple↗

[Botulinum toxin in ENT medicine].

In otorhinolaryngology, botulinum toxin is a suitable therapeutic option in the muscular and the autonomic nervous system concerning dysfunctions. Respecting some special aspects, it is an effective treatment for disorders of different etiology with very few side-effects. The positive therapeutic effect is temporarily limited, so that the patients need further treatment. Beside the classical indications like the facial hyperkinesias (i.e. blepharospasms, hemifacial spasm) the treatment of complex dystonias (oromandibular dystonia, laryngeal dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful. Botulinum toxin is an alternative treatment of tension type headache and migraine. A new indication of botulinum toxin application may lay in the treatment of nasal hypersecretion through the effect on the nasal glands.

Acetylcholine↗

Analysis of the tumour suppressor genes, FHIT and WT-1, and the tumour rejection genes, BAGE, GAGE-1/2, HAGE, MAGE-1, and MAGE-3, in benign and malignant neoplasms of the salivary glands.

AIMS: Molecular genetic changes involved in tumorigenesis and malignant transformation of human tumours are novel targets of cancer diagnosis and treatment. This study aimed to analyse the expression of putative tumour suppressor genes, FHIT and WT-1, and tumour rejection genes, BAGE, GAGE-1/2, MAGE-1, MAGE-3, and HAGE (which are reported to be important in human cancers), in salivary gland neoplasms. METHODS: Gene expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) in normal salivary gland tissue and 44 benign and malignant salivary gland tumours. RESULTS: Aberrant FHIT transcripts were found in one of 38 normal salivary glands, three of 28 adenomas, and two of 16 carcinomas. WT-1 mRNA was detectable in two adenomas and five carcinomas. Immunoblotting showed that WT-1 mRNA expression was associated with raised WT-1 protein concentrations. RT-PCR for detection of BAGE, GAGE, and MAGE gene expression was positive in two adenomas and nine carcinomas, but negative in normal salivary gland tissue. HAGE mRNA was found in two normal salivary glands, 11 benign, and eight malignant tumours. CONCLUSIONS: FHIT mRNA splicing does not appear to be involved in the genesis of salivary gland neoplasms. The upregulation of WT-1 mRNA in tumours of epithelial/myoepithelial phenotype may imply a potential role of WT-1 in the genesis and/or cellular differentiation of these salivary gland tumours. The tumour rejection genes were more frequently, but not exclusively, expressed in malignant salivary gland tumours than in benign neoplasms, although none was suitable as a diagnostic marker of malignancy in salivary gland neoplasms.

Acid Anhydride Hydrolases↗

Successful management of drooling with botulinum toxin A in neurologically disabled children.

OBJECTIVES: The present study investigates the effect of topical injections of botulinum toxin A into the cephalic salivary glands of children with chronic hypersalivation due to neurodegenerative diseases. METHODS: Five children with hypersalivation due to severe neurological diseases received, under ultrasound guidance, a total of 50-65 units of botulinum toxin A (Botox) into the parotid and submandibular glands on both sides. All injections were tolerated without local anaesthesia. Before and 1, 2, 4, 8 and 12 weeks after toxin injection, salivary flow rates and the concentrations of total protein, alpha-amylase, acid phosphatase, kallikrein, and immunoglobulin A were measured in the secretions; simultaneously, the patients were clinically examined with regard to severity of symptoms, and their salivary glands were subjected to ultrasound study. RESULTS: A distinct improvement of symptoms within the first 2 weeks following toxin administration were reported by the parents. Sialometry revealed considerably reduced flow rates but sialochemistry showed an increase of amylase activity. Ultrasound examination did not reveal any changes of the salivary parenchyma, and side-effects were absent. CONCLUSION: Treatment of drooling by topical injection of botulinum toxin A into the salivary glands is a reliable and also side-effect-free therapeutic option for children with neurological disorders. All children involved in our study experienced a distinct improvement of their quality of life.

Adolescent↗

[Blocking secretion of exocrine glands in the head-neck area by administration of botulinum toxin A. Therapy of a rare disease picture].

BACKGROUND: Hypersecretion disorders of the exocrine glands of the head and neck area are a therapeutic problem in the field of otorhinolaryngology. In the present study, we demonstrate the effectiveness of local injections of botulinum toxin A to block secretions of exocrine glands of the head and neck area. PATIENTS AND METHODS: Four patients suffering from hypersecretion disorders received local injections of botulinum toxin A. Two patients suffered from disorders of the salivary glands: one presented an idiopathic hypersialorrhea and another a salivary fistula after parotidectomy. A third patient suffered from epiphora and a further patient presented severe hyperhidrosis on the pilose head region. In a retrospective clinical study, the outcome of therapy was evaluated by clinical examination and chemical parameters. RESULTS: Clear blocking of secretion in the treated glands could be demonstrated in all four cases. Possible side effects of the treatment could not be observed. CONCLUSIONS: The present study was able to demonstrate a clear blocking of secretion of the exocrine glands of the head and neck region through botulinum toxin A, offering an improvement in therapy especially for the innovative indication of blocking the salivary glands of the head.

Adult↗

[Oromandibular dystonia. Clinical forms, diagnosis and examples of therapy with botulinum toxin].

BACKGROUND: The present study reports on our experience with clinical aspects and therapy of oromandibular dystonia (OMD) with botulinum toxin A. OMD is a very rare form of focal dystonias. The clinical symptoms can vary considerably, depending on the musculature affected. PATIENTS: The various clinical forms are described. The description of the diagnostic analysis and the therapy with botulinum toxin A is explained with reference to the patients. In these cases, injections are made into the musculature of the base of the mouth, the muscles involved in chewing, the extrinsic muscles of the tongue and the caudal facial musculature. RESULTS: Most of the patients showed an improvement of their symptoms. The average dose of Botox(R) used was 35.4+/-23.6 units. The duration of the effect was 14+/-9.2 weeks on average. CONCLUSION: The therapy for OMD using botulinum toxin A has proved to be successful, the amount of improvement in this form of dystonia is, however, lower in comparison to other forms of mobility disorders in the head and neck region.

Adult↗

Cortical representation of the orbicularis oculi muscle as assessed by transcranial magnetic stimulation (TMS).

OBJECTIVES: To analyze characteristic features and details on motor-evoked potentials (MEPs) of the orbicularis oculi muscle resulting from cortical transcranial magnetic stimulation (TMS) in normal subjects as a basis for further investigations on motorcortical representation in patients presenting with facial nerve diseases. STUDY DESIGN: MEPs of the orbicularis oculi muscle resulting from focal cortical TMS with a figure-8-shaped coil were investigated in 17 healthy subjects with special regard to amplitude and onset latency as a function of the coil position on the head surface along the interaural line and in the anterior-posterior direction. The results were then compared with our data on lower-lip mimetic muscles and on the frontalis muscle obtained in previous studies. RESULTS: Bilateral reproducible responses could be observed at coil positions varying from 1 to 13 cm lateral to the vertex. During moderate muscle activation, maximum responses (mean amplitude 0.75 +/- 0.44 mV contralateral, 0.74 +/- 0.36 mV ipsilateral) were obtained at a mean stimulus position of 8.6 +/- 1.6 cm lateral and 2.0 +/- 2.2 cm anterior to the vertex for contralateral responses, and of 8.6 +/- 2.0 cm lateral and 2.8 +/- 2.4 cm anterior to the vertex for ipsilateral responses, respectively. Voluntary muscle activation by forced eye-closure was associated with a further increase in mean amplitudes. At rest, bilateral responses could be elicited in 15 subjects (88.2%). During moderate muscle activation, the shortest mean onset latencies were obtained at the optimum stimulus position on the interaural line, both for contralateral (10.2 +/- 1.3 ms) and ipsilateral (10.6 +/- 1.5 ms) MEPs. Comparing our data on the orbicularis oculi muscle with those obtained on lower-lip muscles and on the frontalis muscle, there was a considerable overlap of coil positions from which reproducible MEPs could be elicited in all three groups of mimetic muscles, but with the orbicularis oculi area being placed between forehead and lower-lip motorcortical areas. CONCLUSIONS: A statistically significant separation of the cortical representation areas of forehead, orbicularis oris, and lower-lip mimetic muscles is possible by focal cortical TMS reflecting a kind of somatotopic organization of the face-associated motorcortex. Compared with the results on lower-lip and forehead muscles, orbicularis oculi muscle responses show characteristics of both.

Adult↗

Genetic analysis of the human oncoprotein MDM2 in benign and malignant tumors of the salivary gland.

INTRODUCTION: Genetic alterations of oncogene MDM2 promote malignant transformation of several human tumors. In tumors of the salivary gland, however, the genetic status of MDM2 has not been evaluated so far. METHODS AND RESULTS: Benign and malignant tumors of the salivary gland (6 pleomorphic adenomas, 3 Warthin's tumors, 1 adenocarcinoma, 1 basal cell adenocarcinoma, 1 mucoepidermoid carcinoma, 3 acinic cell carcinomas, 2 adenoid cystic carcinoma, 1 squamous cell carcinoma) were analyzed by fluorescence-based PCR techniques and immunochemistry for MDM2 gene amplification, MDM2 gene expression, MDM2 gene mutation, MDM2 RNA splicing and MDM2 accumulation. Data show that all samples contained nonamplified MDM2 genes with nonmutant zinc finger regions. However, in two benign and two malignant samples, novel MDM2 mRNA splicing variant types 1 and 2 were detected. Furthermore, three malignant tumors revealed significant nuclear MDM2 accumulation. Correlation between levels of MDM2 mRNA and MDM2 protein could not be detected in the specimens. CONCLUSION: The present study suggests that MDM2 gene mutation and gene amplification do not contribute to MDM2 accumulation detected in malignant tumors of the salivary gland. However, the role of novel MDM2 splicing variants in MDM2 expression and malignant transformation must be elucidated further.

Adenoma↗

Botulinum toxin type A induces apoptosis in nasal glands of guinea pigs.

Nasal hypersecretion is predominantly caused by overaction of nasal glands, which are mainly under cholinergic control. In this work, we investigated the influence of botulinum toxin A (BTA) on the nasal mucosal tissue of the maxillary sinus turbinates of guinea pigs (n = 10) that were painlessly sacrificed 10 days (short-term group) or 3 months (long-term group) after local treatment with 20 units of BTA (Botox) or 0.2 mL of 0.9% sodium chloride (control). Histologic investigation of the nasal mucosal tissue of the BTA-treated animals (short-term group) showed degeneration of glands and ducts and apoptotic nuclei on TUNEL staining of these structures. The control animals revealed normal glandular tissue and no apoptosis. The animals of the long-term group showed almost normal glandular tissue and only a few apoptotic nuclei. In conclusion, BTA induces temporary apoptosis in the nasal glandular compartment of guinea pigs.

Animals↗