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Biomedical subjects

L Bruschini

Publications and source records attributed to L Bruschini.

17 recordsLinked to original sources

Responses of Purkinje-cells of the cerebellar anterior vermis to stimulation of vestibular and somatosensory receptors.

In decerebrate cats, sinusoidal rotation of the forepaw around the wrist modifies the activity of the ipsilateral forelimb extensor triceps brachii (TB) and leads to plastic changes of adaptive nature in the gain of vestibulospinal (VS) reflexes (VSRs). Both effects are depressed by functional inactivation of the cerebellar anterior vermis, which also decreases the gain of VSRs. In order to better understand the mechanisms of these phenomena, the simple spike activity of Purkinje (P-) cells was recorded from the vermal cortex of the cerebellar anterior lobe during individual and/or combined stimulation of somatosensory wrist, neck and vestibular receptors. About one third of the recorded units were affected by sinusoidal rotation of the ipsilateral forepaw around the wrist axis (0.16 Hz, +/-10 degrees ). Most of these neurons ( approximately 60%) increased their activity during ventral flexion of the wrist and decreased it during the oppositely directed movement, with an average phase lag of -141 degrees with respect to the position of maximal dorsiflexion. The remaining cells ( approximately 40%) were excited during dorsiflexion of the wrist, with an average phase lead of 59 degrees with respect to the extreme dorsal flexion. Both populations showed comparable response gains, with an average value of 0.42+/-0.52, S.D., imp/s/deg. About half of the recorded units were also tested during sinusoidal roll tilt of the animal around the longitudinal axis (0.16 Hz, +/-10 degrees ), leading to stimulation of labyrinthine receptors. When both stimuli were applied simultaneously, the responses to combined stimulation usually corresponded to the sum of individual responses. While the phase distribution of somatosensory responses was clearly bimodal, vestibular responses showed phase angle values uniformly scattered between +/-180 degrees and 0 degrees , so that, during combined stimulation, each neuron could be maximally activated by coupling the two stimuli with a particular phase relation. Finally, a proportion of the recorded neurons was also tested during sinusoidal rotation of the body around its longitudinal axis, with the head fixed in space, leading to stimulation of neck receptors. The proportion of neurons affected by individual stimulation of vestibular or neck receptors (81% and 72%, respectively) was larger than that of wrist-driven neurons. Convergence of signals from vestibular, somatosensory wrist and neck receptors was found in 18% of the neurons analyzed. In conclusion, the results of this study show that somatosensory signals from the forelimb: i) modulate the activity of a sizeable proportion of neurons located within the cerebellar anterior vermis and ii) interact widely with labyrinthine and neck signals at this level. Moreover, iii) this corticocerebellar region is largely dominated by vestibular and neck signals that may be utilized to build up a neuronal representation of the position of body in space. These findings suggest that: 1) the modulation of TB activity induced by rotation of the ipsilateral wrist may at least partially depend upon the simultaneous changes in P-cell activity and 2) the interaction of vestibular and somatosensory wrist signals at P-cell level may represent the substrate of the plastic changes that affect the VSR when animal tilt and wrist rotation are driven together. A preliminary report of these data has been presented [ Responses of cerebellar Purkinje cells to forepaw rotation in decerebrate cat. Pflügers Arch 440:R31].

Action Potentials↗

Drop attacks and vertical vertigo after transtympanic gentamicin: diagnosis and management.

Drop attacks represent a significant problem during the natural course of Meniere's disease. They are characterized by a sudden fall to the ground without loss of consciousness. Diagnosis is clinical and based on the typical description of the patient. Involvement of vertical canal is possible during Meniere's disease and also after gentamicin application. Treatment of drop attacks is still a matter of discussion; most cases have a benign course with spontaneous remission and no treatment is necessary. In severe cases, aggressive treatment (surgical or pharmacological) is necessary. A case of drop attack associated with vertical vertigo is presented. Vestibular tests were performed in order to assess the involvement of inner ear. Caloric test and ice water test reveal no response. Vestibular Evoked Myogenic Potentials are present even after high doses of gentamicin. Drop attacks and vertical vertigo can occur after transtympanic gentamicin and can be well managed with high doses of local gentamicin.

Administration, Topical↗

Coupling sensory inputs to the appropriate motor responses: new aspects of cerebellar function.

It is known that proprioceptive signals modify the spatial organization of the postural reflexes, thus leading to body stability. The neurophysiological basis of this phenomenon are at present unknown. The present report documents that, in decerebrate cat, body-to-head rotation in the horizontal plane modified the preferred response direction to labyrinthine stimulation of the forelimb extensor triceps brachii. Such direction resulted always perpendicular to the longitudinal body axis of the animal, whatever its relative position with respect to the head could be. The rotation of the preferred response direction of the triceps was greatly reduced by functional inactivation of the ipsilateral cerebellar vermis. On the other hand, following body-to-head displacement, the preferred response directions of the corresponding P-cells tended, on the average, to rotate in the same direction and by the same angle as the body. We propose that the neck input finely tunes parallel vestibular channels, endowed with different spatial and temporal properties, impinging upon P-cells, thus modifying their responses to animal tilt and, as a consequence, the spatial properties of VS reflexes. It is possible that, by a similar mechanism, the cerebellum may contribute to the changes in reference frame occurring in sensorimotor transformations of reflex and voluntary nature.

Afferent Pathways↗

Cranio-cervical necrotizing fascitiis: case report and review of the literature.

Necrotising fascitiis is a rapidly progressive bacterial infection of the soft tissues and generally attacks the walls of the abdomen, the perineum, the limbs or, to a lesser degree, the cranio-cervical area. In the latter region, the infection involves the soft tissues of the neck, in a more or less extensive manner, and causes diffuse necrosis. Crepitation, areas with linear infiltration and others with fluctuation are detected on manual examination. Systemic symptoms such as fever, tachycardia, tachypnoea and signs of septic shock are always present, at least during the more advanced stages of the disease. Computed tomography may prove fundamental since it reveals an increase in the thickness and degree of impregnation of the cervical soft tissues, as well as the presence of liquid or gaseous infiltration in the thoracic areas, especially in cases of mediastinitis. Personal experience in a case is described which led to a review of the literature. The best approach in the management of this devastating condition is early diagnosis, adequate antibiotic treatment and radical surgical procedures, which may often need to be repeated several times.

Anti-Bacterial Agents↗

Paroxysmal positional vertigo: short- and long-term clinical and methodological analyses of 794 patients.

Between 1995 and 2001, eight Italian clinical centres used the same diagnostic and therapeutic protocol in order to assess the clinical progress of paroxysmal positional vertigo and the benefits of an appropriate follow-up in prevention of relapse. The study population comprises 794 patients affected by paroxysmal positional vertigo. The study protocol comprised diagnostic staging including a complete otoneurological test, an anamnestic questionnaire aimed at identifying any possible risk factor, a blood test in basal conditions and monitoring of blood pressure. If necessary, more specific instrumental tests have been carried out. Appropriate rehabilitative manoeuvres were performed from 1 to 3 times within the same session. The patient was checked 3-5 days later: in the presence of a positive result, the treatment was repeated; if negative, patients were seen at clinical follow-up 7, 30, 180 and 365 days after recovery. Wherever possible, patients have been contacted 2 years after the first treatment and asked to answer a questionnaire and to attend for a clinical check-up. The incidence of paroxysmal positional vertigo appeared to be higher in females and in patients aged 50-70 years, being low in patients under 30. In 88.8% of cases posterior semicircular canals showed a significant involvement; in 6.8% of cases, only involvement of lateral semicircular canals; monolateral (2.7%) and bilateral (1.7%) multicanalar forms were rare. Paroxysmal positional vertigo forms involving posterior semicircular canals have been treated with Semont (simplified by Toupet), Epley, Parnes Price-Jones manoeuvres; those, involving lateral semicircular canals with Vannucchi-Vicini forced position and "barbecue" or Gufoni manoeuvre. Whilst all these manoeuvres were equally effective, longer recovery times have been observed in paroxysmal positional vertigo forms involving lateral semicircular canals when the Vannucchi-Vicini forced position was ineffective. Any relapses have been evaluated at least 15 days after a negative clinical pattern. Possible involvement of other semicircular canals (recurrence) some time after the first onset has been considered separately. Follow-up at 6 months showed recurrence in 12.4% of cases, while being chronic in 1.5% of cases. Only 9.3% of cases showed recurrence at 6 months, no statistically significant difference being observed between vertical (8.9%) and lateral canal (9.6%), forms. Relapses occurred in 3.1% of cases, in one third of which at least two risk factors were detected.

Aged↗

Giant neck neoplasm. Case report.

Giant latero-cervical neoplasias usually originate in the parotid gland, as slow-growing adenomas, in subjects who take little care of their personal health. Giant adenomas of submandibular gland are very rare. These neoplasias involve prevalently male sex (male/female ratio: 2/1) and usually occur between 20 and 40 years of age. Signs of malignant transformation may be observed in the adenomatous epithelial component in a percentage ranging from 1% to 10% of cases. The case is reported of a giant malignant latero-cervical neoplasia originating from a pleomorph adenoma of the submandibular gland. The diagnostic work-up and treatment protocol are described.

Adenoma, Pleomorphic↗

Positron emission tomography (PET) in the staging of head neck cancer: comparison between PET and CT.

Standard pre-treatment clinical staging (TNM) of head and neck squamous cell carcinoma includes clinical and instrumental objective examination of primary tumour and of the cervical lymph nodes (inspection, palpation of neck, panendoscopy, biopsy of tumour, fine needle aspiration of nodes) and computed tomography or magnetic resonance imaging. Albeit, this procedure presents diagnostic limitations in the identification of approximately 1/3 of T1, of small sized nodes and in the diagnosis of metastases. Positron emission tomography-fluorodesoxy-glucose imaging, in the diagnostic workup of these cases, appears to offer an important contribution, however, its use is limited due to poor availability of this equipment and the high cost of the examination. In the present study, a comparison is made of results of standard clinical staging and positron emission tomography-fluorodesoxy-glucose in 22 patients with head and neck carcinoma prior to surgical treatment, with the results of pathological staging (pTNM) carried out on surgical specimens. In the staging of the tumour, computed tomography shows a sensitivity of 71% and positron emission tomography of 81%. In the staging of nodes, computed tomography imaging shows a sensitivity of 73%, a specificity of 57% and an accuracy of 68%, whereas positron emission tomography shows a sensitivity of 93%, a specificity of 100% and an accuracy of 95%. Furthermore, positron emission tomography identified 1/5 occult tumours and one tumour revealed at objective endoscopic examination, but not by computed tomography. The risk of occult nodes following positron emission tomography was found to be 7%. Overall, these results are in keeping with those reported in the literature, thus confirming the usefulness of positron emission tomography-fluorodesoxy-glucose in identifying occult tumours and nodes, in which computed tomography appears to be limited. Indications of positron emission tomography-fluorodesoxy-glucose may play a role in the choice of therapeutic options for the clinically N0 neck.

Aged↗

Postural responses of forelimb extensors to somatosensory signals elicited during wrist rotation: interaction with vestibular reflexes.

The responses of the forelimb extensor triceps brachii (TB) to sinusoidal wrist rotation, at 0.156 Hz, +/-5 degrees, were investigated in decerebrate cats. In most of the tested muscles [12/15) the multiunit electromyographic (EMG) activity of the TB muscle increased during dorsiflexion and decreased during plantar flexion of the ipsilateral limb extremity, showing an average (+/-SD) gain of 1.38+/-0.64 impulses/s/ degrees and a phase lead of 33+/-19 degrees with respect to the extreme dorsiflexion of the forepaw. Both parameters remained unmodified by increasing the amplitude of stimulation from 5 degrees up to 10 degrees. Rotation of the contralateral wrist had no effect on TB activity. When the rotation of the ipsilateral wrist occurred during sinusoidal roll tilt of the whole animal, a stimulus that activates vestibular receptors, the TB response to combined stimulation closely corresponded to the vectorial sum of the individual responses. Dorsiflexion of the forepaw could drive the vestibulospinal system, which excites the ipsilateral TB motoneurons. In fact, functional inactivation of the cerebellar anterior vermis, which controls vestibulospinal neurons, significantly modified the TB response to wrist rotation. It appears, therefore, that the somatosensory signals elicited by wrist rotation utilize the spinocerebellum to modulate the activity of the TB. The TB responses to wrist rotation could play a role in stabilizing posture during stance and locomotion.

Animals↗

Prediction of recurrence by microsatellite analysis in head and neck cancer.

We examined the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in histopathologically negative surgical margins and cervical lymph nodes from head and neck cancer (HNC) patients. We used polymerase chain reaction (PCR)-based microsatellite analysis DNA to analyze primary tumors, paired surgical margins, and cervical lymph nodes from 41 HNC patients. Samples were scored for alterations as defined by the presence of new alleles (shifts) or loss of heterozygosity (LOH) at each of 10 markers. We identified 25 (61%) patients with primary HNC who appeared to have had a complete resection on the basis of the histopathological assessment and who were informative regarding microsatellite alterations in tumor tissue. In 11 of these 25 (44%) cases, PCR analysis of surgical margins showed the same microsatellite alterations as in the primary tumors. In 7 of these 11 patients, the carcinoma recurred locally, as compared with 1 out of 14 patients with negative margins (log rank test, P = 0.0049). Conversely, we were unable to detect clonal neoplastic cells in histopathologically negative lymph nodes examined by molecular analysis. Cox regression analysis showed that molecular positive margins were an independent prognostic factor (P = 0.04) for recurrence. This study demonstrates that microsatellite analysis may be a valuable tool for evaluating the risk of local recurrence.

Aged↗

Cumulative prognostic value of p53 mutations and bcl-2 protein expression in head-and-neck cancer treated by radiotherapy.

We investigated the prognostic significance of p53-gene mutation (exon 5-9) and bcl-2-protein expression in primary squamous-cell carcinoma of the head and neck (HNSCC) treated by curative radiotherapy (RT). Primary squamous-cell carcinomas for analysis were obtained from 85 consecutive head-and-neck-cancer patients, with complete follow-up data. We detected bcl-2 protein in 24% (20/85) of HNSCC studied; 38 (45%) of the 85 tumours had cells bearing p53 mutations. A strong association was observed between tobacco exposure and bcl-2-protein expression (p = 0.003), an association also evident in those patients who had a p53-mutated carcinoma (p = 0.049). Moreover, we found that most of the bcl-2-positive cancers (70%) were also mutated in the p53 gene (p = 0.010). In univariate and in multivariate analyses, the simultaneous detection of bcl-2 expression and a p53-gene mutation in a tumour biopsy specimen was associated with greater risk of locoregional failure (p = 0.002 and 0.001 respectively) and worse survival (p = 0. 045 and 0.033) within 5 years in HNSCC patients treated by RT. The present study shows a cumulative prognostic value of simultaneous detection of bcl-2 over-expression and p53-gene aberration in some primary HNSCC treated with conventional RT, and provides further evidence for cross-talk between p53 and bcl-2, suggesting that these genes are important determinants of radiation-induced apoptosis, thereby modulating resistance to RT. Int. J. Cancer (Pred. Oncol.) 84:573-579, 1999.

Adult↗

Neck input modifies the reference frame for coding labyrinthine signals in the cerebellar vermis: a cellular analysis.

The activity of 68 neurons, mainly Purkinje cells, was recorded from the cerebellar anterior vermis of decerebrate cats during wobble of the whole animal (at 0.156 Hz, 5 degrees), a mixture of tilt and rotation, leading to stimulation of labyrinth receptors. Most of the neurons (65/68) were affected by both clockwise and counterclockwise rotations. Twenty-four units showing responses of comparable amplitude to these stimuli (narrowly tuned cells) were represented by a single vector (Smax), whose preferred direction corresponded to the direction of stimulation giving rise to the maximal response. The remaining 41 units, however, showed different amplitude responses to these rotations (broadly tuned cells) and were characterized by two spatially and temporally orthogonal vectors (Smax and Smin), suggesting that labyrinthine signals with different spatial and temporal properties converged on these cells. All these units were tested while the body was aligned with the head (control position), as well as after static displacement of the body under a fixed head by 15 degrees and/or 30 degrees around a vertical axis passing through C1-C2, thus leading to stimulation of neck receptors. The orientation component of the response vector of the Purkinje cells to vestibular stimulation changed following body-to-head displacement. Moreover, the amplitude of vector rotation corresponded, on the average, to that of body rotation. Changes in temporal phase, gain and tuning ratio of the responses were also observed. We propose that information from neck receptors regulates the convergence of labyrinthine signals with different spatial and temporal properties on corticocerebellar units. Due to their strict relationship with the motor system, these units may give rise to appropriate responses in the limb musculature, by modifying the spatial organization of the vestibulospinal reflexes according to the requirements of body stability. The cerebellar vermis may thus represent an important structure, where frames of reference can be altered to account for changes in position of trunk, head and neck.

Animals↗

Perennial allergic rhinitis and chronic sinusitis: correlation with rhinologic risk factors.

BACKGROUND: The reported association of allergy and sinusitis varies greatly between study, and the exact role of allergy in predisposing to sinusitis is not clear. We attempted to determine whether patients with perennial allergic rhinitis are at greater risk of developing sinusitis with respect to a control group, and to determine whether there is a correlation between rhinomanometry, endoscopy, and nasal swab, and computed tomography (CT) findings. METHODS: Forty adult patients with perennial allergic rhinitis underwent CT scans of the paranasal sinuses, and the results were then compared to CTs of the paranasal sinuses of 30 control subjects. All allergic patients underwent nasal endoscopy, nasal swab, and active anterior rhinomanometry, and the results were studied in relation to the CT findings. RESULTS: We found sinusitis in 67.5% of the allergic patients and in 33.4% of the controls, with a statistically significant difference between the two groups (P = 0.017). Twenty-three patients had a positive nasal swab; 22 showed increased nasal resistance on rhinomanometry, and 36 had positive endoscopy, but the association of CT findings with endoscopy, rhinomanometry, or nasal swab was not statistically significant (P = 0.583, P = 1.00, P = 0.506, respectively). CONCLUSIONS: Allergic rhinitis is often associated with sinusitis, but the underlying mechanism has yet to be determined. Evidently, factors other than classical pathogen growth and mechanical factors, such as the association of the various factors and immunologic mechanisms, may contribute to the pathogenesis of chronic sinusitis in allergic patients.

Adolescent↗

Progressive sensorineural hearing impairment in systemic vasculitides.

OBJECTIVES: A large series of patients with various forms of systemic vasculitis were evaluated to analyze the prevalence of progressive sensorineural hearing loss (PSNHL), its characteristics and evolution, and the effects of different therapies. METHODS: A total of 673 patients were questioned about the presence of subjective audiovestibular disturbances. Of those, 80 subjects complained of subjective audiological disturbances and underwent oto-rhino-laryngological and audiovestibular evaluation. Those patients with progressive hearing impairment were selected and studied carefully. RESULTS: A PSNHL was observed in 14 patients. The hearing loss was bilateral and asymmetrical in most subjects. It was usually sensorineural, with a cochlear lesion. Unsteadiness was the most frequent vestibular symptom and canal paresis or palsy was noted in most patients. Systemic corticosteroids and cyclophosphamide were useful treatments; in unresponsive patients, satisfactory results were obtained with methotrexate and plasma exchange. CONCLUSIONS: PSNHL is a rare complication of systemic vasculitis, but occasionally is one of the presenting symptoms. Its clinical evolution is variable, but timely clinical assessment and treatment can positively affect prognosis.

Adrenal Cortex Hormones↗

[Progressive sensorineural hearing loss: immunologic etiology].

An auto-immune progressive sensorineural hearing loss (PSNHL) can occur as one of the clinical features of systemic immune-mediated disorders, such as Cogan's syndrome, Behçet's disease, Wegener's granulomatosis, mixed cryoglobulinaemia, systemic sclerosis, systemic lupus erythematosus, giant cell arteritis, panarteritis nodosa, relapsing polychondritis, unclassified systemic vasculitides, etc, or as a distinct clinical entity, the so-called auto-immune inner ear disease. The clinical evolution of the hearing loss during the course of the systemic disease is extremely variable (slowly progressive versus rapidly progressive), while the auto-immune inner ear disease is usually characterized by a rapidly developing (weeks or months) progressive hearing loss. In both cases a timely clinical assessment and treatment can positively affect the prognosis of the hypoacusia. To date, no laboratory test will give a sure diagnosis of autoimmune hearing loss and only a good response to corticosteroid and/or cytostatic treatment can indirectly confirm this diagnosis. The laboratory tests that are usually performed can be divided into aspecific and specific tests, the latter evaluating the immune-mediated response to the specific inner ear antigen. Evaluation of the aspecific parameters sometimes shows high values of erythrocyte sedimentation rate and C-reactive protein, but often no alteration of the inflammation parameters is observed. However, the specific tests seem to achieve higher sensibility and sensitivity but to date they are not available in clinical practice. In this study we examined a group of 13 patients affected with bilateral idiopathic PSNHL who underwent Western Blot, which is a specific test for the inner ear antigen. A positive result was found in 53.8% of the cases; in particular, all 3 patients who had an improvement of hearing loss with corticosteroid treatment, and therefore were probably suffering from auto-immune progressive hearing loss, had a positive result to the Western Blot test.

Adult↗

[Progressive sensorineural hearing loss: metabolic, hormonal and vascular etiology].

Metabolic, hormonal and vascular disorders are considered to cause hearing dysfunction such as progressive sensorineural hearing loss (PSNHL). The diseases most commonly associated with PSNHL are diabetes mellitus, congenital and acquired hypothyroidism, chronic renal failure, chronic labyrinthine ischemia determined by non-hematologic factors (tissue perfusion pressure, blood vessel diameter) or by hematologic factors (blood viscosity and/or rigidity of the red blood cells). In this study a review of data on the relationship between these clinical disorders and the presence and deterioration of the hearing function was carried out. PSNHL seems to be significantly associated with diabetes mellitus, in particular the mitochondrial type: a progressive deterioration of the hearing function is reported in 60% of the patients suffering from this type of disease with mitochondrial mutations. Regarding hypothyroid disorders, the data do not support a pathogenetic link between PSNHL and acquired hypothyroidism, whereas in subjects with congenital hypothyroidism both clinical and experimental results indicate a progressive damage of hearing function if the thyroid disorder is not treated early in life. Also, in patients with chronic renal failure the hearing thresholds seem to be significantly worse than in control subjects, particularly in patients undergoing dialysis, whereas the effect of kidney transplantation on auditory function is still not understood. Finally a relationship between PSNHL and chronic labyrinthine ischemia due to alterations of hematologic factors (increase of blood viscosity and/or increase of rigidity of the red blood cells) has been reported by several authors. However, data on high blood pressure and hyperlipoproteinemia as causes of deterioration of hearing acuity are controversial, and it is often difficult to understand whether the progressive hearing deficit is due only to these factors or also to the elderly age of patients.

Diabetes Mellitus, Type 1↗

[Progressive sensorineural hearing loss from infectious agents].

The progressive sensorineural hearing loss due to infectious causes can involve different etiological agents like bacteria, viruses, protozoons or mycetes. These infectious agents can act in various ways: directly through a labyrinthitis that may destroy the neuroepithelium; through an ischaemic process secondary to a septic embolus; or through a thrombus. In some cases the damage can occur in a meningitis context, because of the passage of the germ in the inner through the nerves, the vases or the labyrinthine liquids. Bacterial meningitis is one of the causes of progressive sensorinueral hearing loss. Among bacteria, the Mycobacterium Tuberculosis has nowadays acquired a remarkable importance which is also due to its considerable diffusion, despite modern therapy, and to its association with HIV infection. Bacteria can also cause a labyrinthitis acting directly on the inner ear: among these, Treponemas Pallidum, a spirochaete which causes syphilis and Borrelia Burgdorferi, a spirochaete that causes Lyme Disease, must be mentioned. The viruses that are certainly involved in the etiology of progressive sensorineural hearing loss are Cytomegalovirus and Rubella virus. The virus usually causes a labyrinthitis after the viraemia, wich may be due to the passage of the virus from the blood to the endolymph, through the stria vascularis with the consequent infection of the sensorial cells of the organ of Corti. Less frequently the viral damage to the inner ear can occur after a vasculitis, a meningitis or an alteration of the cell-mediated immunity. Progressive sensorineural hearing loss can also occur because of some congenital viral infections such as those caused by Cytomegalovirus and Rubella virus. More recently even the Human Parvovirus B19 seems to have been involved. This virus seems to act through autoimmune and/or immunologic processes, like that causing sudden hearing loss in Lassa fever. Another viral infection which can nowadays more frequently be considered among the cause of progressive hearing loss is HIV. In the HIV infection the neurological toxic lesions due to the administered ototoxic drugs are added up to the damages caused by the opportunistic infectious agents (virus, bacterium, protozoon mycete). However, in these patients HIV itself could be the cause of the auditory and vestibular lesions. More rarely, a progressive hearing loss may be due to the action of a protozoon or mycete only.

Disease Progression↗

Microsatellite instability as biomarker for risk of multiple primary malignancies of the upper aerodigestive tract.

Head and neck cancer (HNC) patients are at high risk of developing second primary tumors of the upper aerodigestive tract and this is a chief cause of death. Genomic instability reflecting the propensity and the susceptibility of the genome to acquire multiple alterations is considered a driving force behind multiple carcinogenesis and the alterations of the length of single repetitive genomic sequences or microsatellite instability (MI), implicating impaired DNA repair mechanisms, and could be a sensitive marker for assessing genomic instability in multiple HNC. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes a risk factor in patients with multiple head and neck cancer, we examined replication errors (RER) at 10 microsatellite loci in 21 primary and 5 second primary cancers in 21 patients with multiple malignancies of the upper aerodigestive tract, in comparison with match-paired primary HNC from patients without multiple malignancies. A RER+ phenotype (alterations at > or =2 loci) was observed at 10 microsatellite alterations on chromosomes 2, 3, 11, 17 in at least one tumor from 15 out of 21 (71.5%) patients with multiple primary cancers but only in 11 tumors from 40 (27.5%) HNC patients with single cancer (P=0.001). A RER+ phenotype was also associated with a positive familial cancer history (P=0.046). Our results suggest that a genetic instability may play an important role in the pathogenesis of multiple primary cancers and that testing for MI in a primary HNC may be useful in detecting patients with high risk for developing multiple malignancies of the upper aerodigestive tract.

Adult↗