IGF-I is a key factor in intrauterine development and postnatal growth and metabolism. The secretion of IGF-I in utero is not dependent on GH, whereas in childhood and adult life, IGF-I secretion seems to be mainly controlled by GH, as revealed from studies on patients with GHRH receptor and GH receptor mutations. In a 55-yr-old male, the first child of consanguineous parents, presenting with severe intrauterine and postnatal growth retardation, microcephaly, and sensorineural deafness, we found a homozygous G to A nucleotide substitution in the IGF-I gene changing valine 44 into methione. The inactivating nature of the mutation was proven by functional analysis demonstrating a 90-fold reduced affinity of recombinantly produced for the IGF-I receptor. Additional investigations revealed osteoporosis, a partial gonadal dysfunction, and a relatively well-preserved cardiac function. Nine of the 24 relatives studied carried the mutation. They had a significantly lower birth weight, final height, and head circumference than noncarriers. In conclusion, the phenotype of our patient consists of severe intrauterine growth retardation, deafness, and mental retardation, reflecting the GH-independent secretion of IGF-I in utero. The postnatal growth pattern, similar to growth of untreated GH-deficient or GH-insensitive children, is in agreement with the hypothesis that IGF-I secretion in childhood is mainly GH dependent. Remarkably, IGF-I deficiency is relatively well tolerated during the subsequent four decades of adulthood. IGF-I haploinsufficiency results in subtle inhibition of intrauterine and postnatal growth.

Objectives An investigation of the hearing status of musicians of professional symphony orchestras. Main questions are: (1) Should musicians be treated as a special group with regard to hearing, noise, and noise related hearing problems (2) Do patterns of hearing damage diVer for diVerent instrument types (3) Do OAE have an added value in the diagnosis of noise induced hearing loss (NIHL) in musicians. Methods 241 professional musicians, aged between 23-64 participated. A brief medical history and the subjective judgment of their hearing and hearing problems were assessed. Musicians were subjected to an extensive audiological test battery, which contained testing of audiometric thresholds, loudness perception, diplacusis, tinnitus, speech perception in noise, and otoacoustic emissions. Results Most musicians could be categorized as normal hearing, but their audiograms show notches at 6 kHz, a frequency that is associated with NIHL. Musicians often complained about tinnitus and hyperacusis, while diplacusis was generally not reported as a problem. Tinnitus was most often localized utmost left and this could not be related to the instrument. It was usually perceived in high frequency areas, associated with NIHL. In general, musicians scored very well on the speech-in-noise test. The results of the loudness perception test were within normal limits. Otoacoustic emissions were more intense with better pure-tone thresholds, but due to large individual diVerences it can still not be used as an objective test for early detection of NIHL.Conclusions Musicians show more noise induced hearing loss than could be expected on the basis of age and gender. Other indicators, such as complaints and prevalence of tinnitus, complaints about hyperacusis and prevalence of diplacusis suggest that musicians' ears are at risk. Continuing education about the risks of intensive sound exposure to musicians, with the emphasis on the possible development of tinnitus and hyperacusis and the need for good hearing protection is warranted.

The Clarion CII is a promising cochlear implant with which our first 10 patients have obtained excellent speech perception results. The NRI system yields high quality signals with a limited number of sweeps at a high sampling rate.

Chemotherapy-induced pulmonary toxicity is reversible, whereas nephrotoxicity and ototoxicity are not. However, the long-term effects of chemotherapy in testicular cancer patients were minor and not invalidating.

The use of low-pass filtered masking noise makes speech-in-noise tests more sensitive to detect NIHL in an early stage.