The species-specific nature of the ototoxicity of dihydrostreptomycin in the patas monkey.

The remarkable susceptibility of the inner ear of the patas monkey (Erythrocebus patas) to the ototoxic action of dihydrostreptomycin (DHSM) (and streptomycin (SM)) is well established in this paper and affords a rare example of a species-specific reaction to a restricted class of compounds within the aminoglycoside group of antibiotics. In a series of experiments, behavioral and morphological observations together provided the following profile of DHSM ototoxicity in the patas monkey: Sudden onset of hearing loss beginning after 7-9 weeks of treatment; Substantial, though often partial, hearing impairment beginning at the high frequencies and progressing with or without continued treatment to the low frequencies; In the inner ear, a corresponding and selective loss of nerve fibers and of outer hair cells, relative to inner hair cells, beginning in the base of the cochlea and proceeding toward the apex; Continued and progressive loss of hearing for several months after cessation of drug treatment; and Non-auditory effects in some animals on the kidney and vestibular system. Results from control experiments confirmed this special relationship between the patas monkey and DHSM: Other nonhuman primates (macaques and vervet monkeys) were essentially unaffected by DHSM; The patas showed no equivalent sensitivity to other aminoglycosides such as kanamycin or to other forms of ototraumatic insult such as intense noise.

Effects of outer hair cell loss on the frequency selectivity of the patas monkey auditory system.

This report describes a study that took advantage of the unique reactivity of the patas monkey (Erythrocebus patas) to dihydrostreptomycin-sulfate (DHSM) to investigate the effects of selective outer hair cell (OHC) lesions on psychophysical tuning curves (PTC). Four patas monkeys were trained using operant reinforcement techniques to perform forward masking PTCs at frequencies of 500 Hz, 2, 4, and 8 kHz, at 10 dB SL. Steady and pulsed-tone thresholds were also measured from 63 Hz to 40 kHz in half-octave steps. The animals were given daily i.m. injections of DHSM at 20 mg/kg per day until shifts in absolute threshold at 16 kHz exceeded 10 dB, at which time the drug was discontinued. Initial changes in PTC shape included elevations in the tip region associated with the increase in threshold and no elevation or a hypersensitivity of the low-frequency tail region. In general, threshold and therefore PTC tip elevations of at least 40 dB were required before any increase in the low-frequency tail became evident. Following completion of psychophysical testing, animals were sacrificed and cytochochleograms were determined. At frequencies corresponding to regions of complete OHC loss and complete IHC retention a lack of selectivity was evident and PTCs closely resemble low-pass filters. This residual low-pass tuning is similar to that seen in VIIIth nerve fibers in ears devoid of OHCs and in basilar membrane transfer functions from traumatized ears. PTCs taken at frequencies corresponding to areas with no loss of receptors showed no systematic changes in sensitivity or selectivity. Because loss of normal OHC function results in greater than a 50-dB loss in sensitivity, as well as a detuned PTC, these findings strongly support the suggestion that the role of the OHC system is to increase the sensitivity and selectivity of the auditory system.

[Frequency of hereditary neurologic diseases. A clinical study]. / La frequenza delle malattie neurologiche ereditarie. Uno studio clinico.

INTRODUCTION: The nervous system is affected in 30% of hereditary monogenic disorders and as many as 500 single-gene disorders display major neurologic symptoms. We have studied the frequency of hereditary neurological diseases to assess their importance in daily hospital activity. Only single-gene hereditary diseases with central or peripheral nervous system involvement were considered; thus chromosomal diseases and diseases with multifactorial etiology were excluded. METHODS: We surveyed admission to in- and out-patient departments of Neurology, Pediatrics, and Dermatology of the Aosta Regional Hospital for the calendar years 1982-1991, collecting 229 cases, 95 women and 134 men. Out-patient departments held 126 patients, the others came from in-patient departments. Admission to the neurological in-patient department were 1.8% of total neurological admissions in the same period. Each diagnosis was assigned to the code number of the International Classification of Diseases (ICD-IX Revision, 1975). RESULTS: We found 33 different phenotypes. Most frequent diagnoses were: essential tremor (89 patients), hereditary sensory-motor neuropathy (HSMN) type I (28), Huntington's chorea (13), progressive muscular dystrophy limb-girdle type (8), neurofibromatosis type I (9), HSMN type II (9), spinocerebellar ataxia (9), hereditary spastic paraplegia (7), spinal muscular atrophy type IV (5), myotonic dystrophy (5), cerebellar ataxia (4), HSMN type III (4), spinal muscular atrophy type II and III (3), tuberous sclerosis (3). Essential tremor mostly affected persons in the over-50 age groups. On the contrary, the other neurologic monogenic diseases were diagnosed in all ages with the following age-group breakdown: 0-9, 11%; 10-19, 16%; 20-29, 15%; 30-39, 8%; 40-49, 11%; 50-59, 19%; 60-69, 14%, 70+, 7%. Consistently with the general rule, autosomic recessive diseases have the earliest onset and autosomic dominant ones the latest; HSMN, spinal muscular atrophy and Huntington's chorea were the disorders diagnosed in older age group. DISCUSSION: Although the frequency of the single neurologic monogenic disease is low (with the exception of essential tremor), their overall prevalence is higher than the prevalence of multiple sclerosis or the peripheral neuropathies. All age-groups are involved. We separated three groups of diseases: 1) two relatively benign diseases, essential tremor and the HSMN, affecting half of our patients; 2) five severe and more common diseases (Huntington's chorea, progressive muscular dystrophy limb-girdle type, neurofibromatosis type I, spinocerebellar ataxia, hereditary spastic paraplegia), affecting 1/4 of patients; and 3) a group of rare, mostly severe diseases, affecting the remaining 1/4 of patients.

[Results of a 7-year (1983-1989) retrospective analysis of syphilids in the Aosta Valley]. / Risultati di una analisi retrospettiva di 7 anni (1983-1989) di sifilide in Valle d'Aosta.

We have considered all patients with positivity in the serological tests for syphilis admitted in our hospital since 1983. After grouping them according to the department, we have tried to show a connection between syphilis and principal disease.

Sound localization of frequency-modulated sinusoids by Old World monkeys.

Directional hearing acuity, as measured by the minimum audible angle (MAA), was determined in four Old World monkeys, Macaca radiata. The acoustic stimuli were linear changes in frequency (sweeps) for different frequency ranges and sweep rates. The sweeps ranged between 0.5 and 1.3 kHz, at two durations, 100 and 200 ms. In upsweeps which began at 0.5 kHz and were 200 ms in duration, MAA decreased as sweep rate and frequency range increased. These thresholds were compared to MAAs of sweeps which traversed the same range of frequencies but at a different rate, to MAAs of sweeps with identical rates but over different frequency ranges, and to the MAAs of downsweeps. These comparisons indicated that range, and not sweep rate, exerts the greatest effect on the MAA. Interaural phase differences derived from the upper limits of the frequency range are discussed as potential FM localization cues.