These guidelines are designed to assist the pediatrician in caring for the child in whom a diagnosis of Down syndrome has been confirmed by chromosome analysis. Although a pediatrician's initial contact with the child is usually during infancy, occasionally the pregnant woman who has been given a prenatal diagnosis of Down syndrome will be referred for review of the condition and the genetic counseling provided. Therefore, this report offers guidance for this situation as well.

Health Supervision for Children With Down Syndrome

Nasal mucociliary clearance as a factor in nasal drug delivery

Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the temporal precision of the auditory system. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (18–30 years old) and older (60–67 years old) adult humans. Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Together, our results support the theory that older adults have a loss of temporal precision in the subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception.

https://www.jneurosci.org/content/jneuro/32/41/14156.full.pdf

Aging Affects Neural Precision of Speech Encoding

Tinnitus, the perception of sound in the absence of external stimuli, is a common and often disturbing symptom that is not understood physiologically. This paper presents an approach for using func...

Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation.

Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent) were toxic for both central nervous system (CNS) progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

/pdf/systemic-5-fluorouracil-treatment-causes-a-syndrome-of-1ts8g6wjm0.pdf

Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

Pulmonary function of 31 heavy smokers with laryngeal cancer was evaluated before and during the 1st year after total (n = 21) and conservative (n = 10) laryngectomy. 2 of them died because of recurrences, 1 for bronchopulmonary complications. Long-lasting hoarseness was the only presenting symptom in all patients. Preoperative lung function data and mucociliary clearance were consistent with a coexisting chronic obstructive lung disease in most subjects and was probably due to smoking. No differences were observed comparing pre- and postoperative data in the 10 conservative laryngectomy patients. On the contrary, the total-laryngectomy patients showed a progressive impairment of bronchial obstruction and bacteriological infection of the trachea during the 1st year after the operation. An impressive increase in mucociliary clearance rates has been observed 2 months after total laryngectomy during the postoperative hypersecretory phase. The obtained data allow us to hypothesize that when clinical conditions of laryngectomized patients in whom local or distant recurrences have been excluded deteriorate, this is related to a progressive bronchial obstruction at any level of the bronchial tree due to descending bacterial infection of the airways. To our knowledge this is the only work demonstrating that total laryngectomized patients need a complete pre- and postoperative evaluation of lung function, airway dynamics, mucociliary function and tracheal bacteriology for long-term prognosis and treatment.

Laryngeal cancer: long-term follow-up of respiratory functions after laryngectomy

Forty heavy smokers, all males aged between 40 and 70 and affected by laryngeal cancer underwent mucociliary clearance evaluation the day before total laryngectomy, 60 days after and, in 6 of them, 5 years later. Specimens of nasal and tracheal mucosa were obtained during laryngectomy and other subsequent operations. Before total laryngectomy, no significant changes in nasal mucociliary clearance were observed in smokers and controls, and the nasal ciliary carpet was fairly well preserved. Bronchial mucociliary clearance was impaired in all patients, owing to the coexistent chronic obstructive bronchitis. 60 days after the operation, nasal mucociliary clearance was significantly improved when compared with the preoperative data and controls, owing to the increase in the endonasal temperature and humidity, and to the reduction of the nasal blood flow and disappearance of the nasal cycle, which follow tracheostomy. Surface morphologic studies show a change in the squamous epithelium of the anterior third of the nasal fossa into a columnar ciliated one. During the first 3 months after the operation, tracheobronchial mucociliary clearance increased of 50% vis-a-vis the preoperative data. During this period a clinically evident bronchial hypersecretion was observed. The reduction in nasal and tracheobronchial mucociliary clearance function which became evident 6 years after the operation, is probably due to secondary chronic infections.

Mucociliary Clearance and Mucosal Surface Characteristics before and after Total Laryngectomy

86 male subjects, aged between 60 and 86 years (M = 69.5), underwent pure-tone audiometry, impedance tests and brainstem response audiometry (BRA). Subjects have been classified into four age-related groups: 1) 34 subjects, aged between 60 and 65; 2) 22, aged between 66 and 70; 3) 22 aged between 71 and 75; 4) 8, aged between 76 and 86. They have also been classified into four groups on the basis of their mean auditory threshold at 0.5, 1, 2, 4 and 8 kHz: 1) 14 subjects with mean auditory threshold less than or equal to 30 dB HL; 2) 16, between 31 and 40; 3) 24, between 41 and 50; 4) 32, with mean auditory threshold greater than or equal to 51 dB HL. 19 normally hearing adults, aged between 28 and 42, were chosen as controls. Statistically significant correlations have been found between age and mean auditory threshold (P less than or equal to 0.001), between wave latency V and age (P less than or equal to 0.001), between wave latency V and the mean pure-tone auditory threshold at 0.5, 1, 2, 4 and 8 kHz (P less than or equal to 0.001) and between the V-I interval and age (P less than or equal to 0.001). The discrepancy between the mean auditory threshold and the ABR waveform, the overall amplitude's reduction of ABR waves and the progressive lengthening of V-I interval values, seem to indicate that age-related changes involve not only the end organ but also the brainstem auditory structures.

Auditory brainstem responses (ABR) in the aged.

Auditory brain stem response (ABR) parameters were evaluated in 54 subjects with unilateral idiopathic subjective tinnitus in order to verify the possibility of detecting its site of origin. All the subjects had normal hearing or a symmetrical bilateral sensorineural hearing loss. All the cases in whom middle or inner ear disease had been diagnosed, were excluded. Subjects, classified on the basis of their mean auditory threshold and masking curves according to Feldmann, underwent a residual inhibition (RI) test and ipsilateral narrow-band noise masking before a second ABR test was performed. Patients with positive RI made up the A+ group, while those with negative RI made up the A-group. The main characteristics observed were an increase of the mean latency values of wave I in the tinnitus ear in the A+ group while, after masking, the values of the affected and unaffected ears almost overlapped. An increase in the latency values of wave V, unaffected by the masking procedure, could be observed in A- pati...

Contribution to the differentiation of peripheral versus central tinnitus via auditory brain stem response evaluation.

Auditory brainstem responses (ABR) evoked by clicks allow a threshold evaluation for the high-frequency range (2-4 kHz) but not for middle and low frequencies (0.5-1 kHz). In 19 normally hearing subjects aged between 24 and 40 years. ABRs have been recorded using clicks and 0.5- and 1-kHz tone pips, with durations of 6 and 3 ms, respectively, and rise-decay times of 3 and 1.5 ms. The input signal was filtered by a passband filter of 20-5 000 Hz. Parameters of tracings elicited by the different kinds of stimuli are compared. Tone-pip ABR morphology does not show the conventional seven peaks but a single large vertex-positive wave. On the ascending branch high-frequency potentials, probably corresponding to the I, II, III and IV-V click-evoked peaks, were visible in some cases, but they rapidly disappeared as the stimulus intensity was decreased. Their 2.3-3 ms greater mean latency values are presumably related to the rise times of the stimuli employed. In terms of bioelectric generators, this large vertex-positive peak probably corresponds to the Jewett V wave. It probably represents a generalized asynchronous dendritic activity. Thus it is possible to obtain ABRs to middle- and low-frequency stimuli. Mean amplitude values of the slow wave are considerably higher than those of the Jewett V wave, but standard deviations are also larger. The positive wave has been identified in response to 1-kHz tone pips in 100% of cases at 30 dB nHL and in 52% of cases at 20 dB, while for 0.5-kHz tone pips in 73.7% of cases at 30 dB and in 57% at 20 dB. On the whole the threshold is located between 15 and 30 dB nHL.

M. Maurizi

Papers

Laryngeal cancer: long-term follow-up of respiratory functions after laryngectomy

Mucociliary Clearance and Mucosal Surface Characteristics before and after Total Laryngectomy

Auditory brainstem responses (ABR) in the aged.

Contribution to the differentiation of peripheral versus central tinnitus via auditory brain stem response evaluation.

Auditory Brainstem Responses to Middle- and Low-Frequency Tone Pips