Validity of autism diagnoses using administrative health data.

It is necessary to monitor autism prevalence in order to plan education support and health services for affected children. This study was conducted to assess the accuracy of administrative health databases for autism diagnoses. Three administrative health databases from the province of Nova Scotia were used to identify diagnoses of autism spectrum disorders (ASD): the Hospital Discharge Abstract Database, the Medical Services Insurance Physician Billings Database and the Mental Health Outpatient Information System database. Seven algorithms were derived from combinations of requirements for single or multiple ASD claims from one or more of the three administrative databases. Diagnoses made by the Autism Team of the IWK Health Centre, using state-of-the-art autism diagnostic schedules, were compared with each algorithm, and the sensitivity, specificity and C-statistic (i.e. a measure of the discrimination ability of the model) were calculated. The algorithm with the best test characteristics was based on one ASD code in any of the three databases (sensitivity=69.3%). Sensitivity based on an ASD code in either the hospital or the physician billing databases was 62.5%. Administrative health databases are potentially a cost efficient source for conducting autism surveillance, especially when compared to methods involving the collection of new data. However, additional data sources are needed to improve the sensitivity and accuracy of identifying autism in Canada.

Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study.

Prenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) - the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (ß=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: ß=0.338, P=0.031; 2D:4D - right: ß=-0.207, P=0.040; left: ß=-0.276, P=0.006; AGD-fourchette - ß=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (ß=0.290, P=0.048), as well as right arm circumference (ß=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones.

Diabetes mellitus following gestational diabetes: role of subsequent pregnancy.

OBJECTIVE: This study was designed to determine the rate of diabetes up to 13 years after pregnancies complicated by gestational diabetes and to identify risk factors for developing diabetes. The role of a subsequent pregnancy, with and without gestational diabetes, was also examined. DESIGN: This was a retrospective cohort study of women with gestational diabetes. POPULATION AND SETTING: Women who had gestational diabetes in their first pregnancy between 1989 and 2002 were identified through a population-based perinatal database in Nova Scotia, Canada. METHODS: Subsequent diagnoses of diabetes, up to 13 years after the first pregnancy, were obtained from physician billing and hospital discharge databases. Cox proportional hazards regression models were used to estimate adjusted relative risks (RR) and 95% confidence intervals. MAIN OUTCOME MEASURES: Diagnosis of diabetes after pregnancy. RESULTS: Of the 1401 nulliparous women with gestational diabetes, 251 women (17.9%) developed diabetes in the follow-up period. The cumulative incidence at 1, 5, and 10 years was 5.9, 14.8, and 22.2%, respectively. Factors significantly associated with an increased risk of developing diabetes mellitus included a pre-pregnancy weight of > or = 86 kg (RR = 1.8, 95% CI 1.2-2.9), insulin therapy during the index pregnancy (RR = 4.1, 95% CI 2.1-7.9), neonatal hypoglycaemia (RR = 2.6, 95% CI 1.6-4.2), and a subsequent pregnancy with gestational diabetes (RR = 2.3, 95% CI 1.6-3.4). CONCLUSION: Indicators of the severity of gestational diabetes, defined by insulin use, neonatal hypoglycaemia, and recurrent gestational diabetes in a subsequent pregnancy, are important in predicting a subsequent diagnosis of diabetes. Our findings do not support the theory that subsequent pregnancy, per se, increases the risk of developing diabetes.

A population-based study of lung cancer incidence trends by histologic type, 1974-81.

All incident cases of microscopically confirmed lung cancer diagnosed between 1974 and 1981 in western Washington State were identified through the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, Bethesda, MD. The incidence of lung cancer by histologic type was studied in relation to time, with age, sex, and stage of disease at diagnosis being taken into account. Overall and within each sex, the incidence of adenocarcinoma has increased significantly since 1974. The rate of increase has been higher among females (86% increase) than among males (54% increase), with most of the increase in both sexes being among those over age 65 years with distant or unstaged disease at diagnosis. Similar patterns were not observed for squamous cell carcinoma. The potential effects of changes in diagnostic and pathology practice during the study period in producing these results were explored, and etiologic implications of the observed increase in adenocarcinoma were discussed.

Haloacetic acids in drinking water and risk for stillbirth.

BACKGROUND: Trihalomethanes (THMs) occurring in public drinking water sources have been investigated in several epidemiological studies of fetal death and results support a modest association. Other classes of disinfection by-products found in drinking water have not been investigated. AIMS: To investigate the effects of haloacetic acid (HAA) compounds in drinking water on stillbirth risk. METHODS: A population based case-control study was conducted in Nova Scotia and Eastern Ontario, Canada. Estimates of daily exposure to total and specific HAAs were based on household water samples and questionnaire information on water consumption at home and work. RESULTS: The analysis included 112 stillbirth cases and 398 live birth controls. In analysis without adjustment for total THM exposure, a relative risk greater than 2 was observed for an intermediate exposure category for total HAA and dichloroacetic acid measures. After adjustment for total THM exposure, the risk estimates for intermediate exposure categories were diminished, the relative risk associated with the highest category was in the direction of a protective effect, and all confidence intervals included the null value. CONCLUSIONS: No association was observed between HAA exposures and stillbirth risk after controlling for THM exposures.

Rates and risk factors for recurrence of gestational diabetes.

OBJECTIVE: To determine the recurrence rate of gestational diabetes (GDM) during a subsequent pregnancy among women who had GDM during an index pregnancy and to identify factors associated with the probability of recurrence RESEARCH DESIGN AND METHODS: A retrospective longitudinal study was performed in Nova Scotia, Canada, of women who were diagnosed as having GDM during a pregnancy between the years of 1980 and 1996 and who had at least one subsequent pregnancy during this time period. When only the index and first subsequent pregnancy were analyzed, the cohort included 651 women. The recurrence rate of GDM in the pregnancy after the pregnancy with the initial diagnosis of GDM was determined. Multivariate regression models were constructed to model the recurrence of GDM in a subsequent pregnancy as functions of potential predictors to estimate RRs and CIs. RESULTS: The rate of recurrence of GDM in the pregnancy subsequent to the index pregnancy was found to the 35.6% (95% CI = 31.9-39.3%). Multivariate regression models showed that infant birth weight in the index pregnancy and maternal prepregnancy weight before the subsequent pregnancy were predictive of recurrent GDM. CONCLUSIONS: In this large cohort of women, slightly more than one-third of the subjects had diabetes in a subsequent pregnancy, which is consistent with recurrence rates in other predominately white populations. Strategies to reduce the occurrence of neonatal macrosomia and maternal prepregnancy obesity may help lower the rate of recurrence of GDM.

Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study.

BACKGROUND: Studies from several countries report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Exposure to environmental chemicals could contribute to this trend. OBJECTIVES: To determine the associations between plasticisers and metals measured in early pregnancy with impaired glucose tolerance (IGT) and GDM in a Canadian pregnancy cohort. METHODS: Women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Eleven phthalate metabolites and total bisphenol A (BPA) were measured in first-trimester urine samples, and four metals (lead, cadmium, mercury and arsenic) were measured in first-trimester blood samples. IGT and GDM were assessed in accordance with standard guidelines by chart review. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for maternal age, race, pre-pregnancy BMI, and education. Restricted cubic spline analysis was performed to help assess linearity and nature of any dose-response relationships. RESULTS: Of 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome data and biomonitoring data measured for at least one of the chemicals we examined. Elevated odds of GDM were observed in the highest quartile of arsenic exposure (OR = 3.7, 95% CI = 1.4-9.6) in the adjusted analyses. A significant dose-response relationship was observed in a cubic spline model between arsenic and odds of GDM (p < 0.01). No statistically significant associations were observed between phthalates or BPA or other metals with IGT or GDM. CONCLUSIONS: Our findings add to the growing body of evidence supporting the role of maternal arsenic exposure as a risk factor for gestational diabetes.

Afferent and efferent innervation of the cat cochlea: quantitative analysis with light and electron microscopy.

The purpose of the present study was to describe the longitudinal and radial gradients of cochlear innervation in the cat. To this end, afferent and efferent terminals of both the inner (IHC) and outer hair cell (OHC) regions were reconstructed from serial ultrathin sections at six and eight cochlear locations, respectively, corresponding to roughly octave intervals of characteristic frequency (CF). Analysis of the afferent innervation of the IHCs showed 1) the number of radial fibers per IHC rises from 10 per IHC at the 0.25 kHz region to a maximum of 30 per IHC at the 10 kHz locus; 2) branching of radial fibers is essentially restricted to regions apical to the 1.0 kHz point; and 3) there are significant differences in synaptic-body morphology for synapses on different sides of the IHC, corresponding to known differences in afferent threshold and rate of spontaneous activity. With respect to efferent innervation in the IHC area, we found 1) that there were numerous vesicle-filled terminals contacting every IHC examined; however, those with obvious synaptic specialization were confined to the most apical regions; and 2) there were roughly the same numbers of efferent synapses per radial fiber at all cochlear locations; however, at each location, radial fibers contacting the modiolar side of the hair cell (corresponding to high-threshold afferents) showed significantly more efferent synapses than radial fibers contacting the pillar side. Analysis of the OHC afferent innervation showed 1) a clear rise in numbers of terminals per OHC from roughly 3 per cell in the base to 15 per cell in the apex, 2) no systematic differences in the numbers of terminals as a function of OHC row, and 3) that synaptic bodies at the OHC afferent synapse are common only apical to the 1.0 kHz locus. Counts of efferent terminals on OHCs revealed 1) maximal numbers (9 per OHC) between the 6 and 24 kHz regions and 2) striking decrease in terminal counts from first- to third-row OHCs. Ultrastructural data on efferent innervation were compared quantitatively with light-microscopic analysis of cochleas immunostained (with antibody to synaptophysin) to reveal all vesiculated terminals.

Unmyelinated axons of the auditory nerve in cats.

This paper describes some central terminations of type II spiral ganglion neurons as labeled by extracellular injections of horseradish peroxidase (HRP) into the auditory nerve of cats. After histological processing with diaminobenzidine, both thick (2-4 microns) and thin (0.5 microns) fibers of the auditory nerve were stained. Whenever traced, thick fibers always originated from type I spiral ganglion neurons and thin fibers always from type II ganglion neurons. Because the labeling of type II axons faded as fibers projected into the cochlear nucleus, this report is limited to regions of the ventral cochlear nucleus near the auditory nerve root. The central axons of type II neurons are unmyelinated, have simple yet variable branching patterns in the cochlear nucleus, and form both en passant and terminal swellings. Under the light microscope, most swellings are located in the neuropil but they are also found in the vicinity of cell bodies, nodes of Ranvier of type I axons, and blood vessels. Eighteen en passant swellings in the neuropil were located by light microscopy and resectioned for electron microscopy; two of these swellings exhibited ultrastructural features characteristic of chemical synapses. The data indicate that inputs from outer hair cells might be able to influence auditory processing in the cochlear nucleus through type II primary neurons.

Afferent innervation of outer and inner hair cells is normal in neonatally de-efferented cats.

It has been hypothesized that normal pruning of exuberant branching of afferent neurons in the developing cochlea is caused by the arrival of the olivocochlear efferent neurons and the resulting competition for synaptic sites on hair cells. This hypothesis was supported by a report that afferent innervation density on mature outer hair cells (OHCs) is elevated in animals deefferented at birth, before the olivocochlear system reaches the outer hair cell area (Pujol and Carlier [1982] Dev. Brain Res. 3:151-154). In the current study, this claim was evaluated quantitatively at the electron microscopic level in four cats that were de-efferented at birth and allowed to survive for 6-11 months. A semiserial section analysis of 156 OHCs from de-efferented and normal ears showed that, although de-efferentation essentially was complete in all four cases, the number and distribution of afferent terminals on OHCs was indistinguishable from normal, and the morphology of afferent synapses was normal in both the inner hair cell area and the OHC area. Thus, the postnatal presence of an efferent system is not required for the normal development of cochlear afferent innervation, and the synaptic competition hypothesis is not supported.

The effect on response rates of offering a small incentive with a mailed questionnaire.

To determine whether response rates to a mailed questionnaire sent to population control subjects could be increased through offer of a small incentive, half of the control subjects (n = 477) in a case-control study of renal cell carcinoma were randomly selected to receive a contact letter offering a lottery ticket if a completed questionnaire was returned; the remaining subjects (n = 477) received the same letter but with no mention of a lottery ticket. Overall response rates did not differ between the two groups (72.6% versus 74.4%), although a higher percentage of those offered a lottery ticket responded without follow-up (24.4% versus 18.5%). Binomial regression modeling of the effect of the lottery ticket offer, sex, age, and percent of urban dwellers on response indicated a significant effect only for percent of urban dwellers, the rate of response increasing with a decreasing percentage of urban dwellers. The effect of sex was of borderline significance (P = 0.05), with females having the higher rate of response.

Relation between stillbirth and specific chlorination by-products in public water supplies.

During water treatment, chlorine reacts with naturally occurring organic matter in surface water to produce a number of by-products. Of the by-products formed, trihalomethanes (THMs) are among the highest in concentration. We conducted a retrospective cohort study to evaluate the relationship between the level of total THM and specific THMs in public water supplies and risk for stillbirth. The cohort was assembled from a population-based perinatal database in the Canadian province of Nova Scotia and consisted of almost 50,000 singleton deliveries between 1988 and 1995. Individual exposures were assigned by linking mother's residence at the time of delivery to the levels of specific THMs monitored in public water supplies. Analysis was conducted for all stillbirths and for cause-of-death categories based on the physiologic process responsible for the fetal death. Total THMs and the specific THMs were each associated with increased stillbirth risk. The strongest association was observed for bromodichloromethane exposure, where risk doubled for those exposed to a level of [greater and equal to] 20 microg/L compared to those exposed to a level < 5 microg/L (relative risk = 1. 98, 95% confidence interval, 1.23-3.49). Relative risk estimates associated with THM exposures were larger for asphyxia-related deaths than for unexplained deaths or for stillbirths overall. These findings suggest a need to consider specific chlorination by-products in relation to stillbirth risk, in particular bromodichloromethane and other by-product correlates. The finding of a stronger effect for asphyxia deaths requires confirmation and research into possible mechanisms.

Peripheral hepatic arterial embolization with crosslinked collagen fibers.

Hepatic artery embolization with a nonimmunogenic, crosslinked microfibrillar collagen preparation (Angiostat, Collagen for Embolization, Target Therapeutics, Los Angeles, CA) was studied in mongrel dogs. Flow-directed technique was used to achieve complete distal arterial occlusion. Serial liver function evaluation demonstrated marked alterations at 48 to 72 hours, partial correction at one week, and resolution of abnormalities by one month. Restoration of large vessel blood flow was angiographically demonstrable at one week. Follow-up arteriograms showed no persistent arterial occlusion. Collagen was demonstrated in vessels of 20 to 250 micron. Recanalization was achieved by migration of endothelial cells around the collagen, development of a new vascular channel within an endothelial cell cleft, and subsequent complete removal of the collagen over a three- to four-month period. Three months after embolization with a single dose, normal hepatic vascular and tissue anatomy and hepatic function were restored completely. Repeated embolization at two weekly intervals was well tolerated.

Perinatal outcomes in women with asthma during pregnancy.

OBJECTIVE: To determine whether adverse perinatal outcome is associated with asthma or asthma medication use during pregnancy. METHODS: A retrospective cohort study was conducted of women who resided in Halifax County, Nova Scotia, and delivered between 1991 and 1993. Asthmatic women were classified into three groups, according to medication usage: no medications, beta agonists only, and steroids with or without other asthma medications. Outcomes compared among asthmatic and nonasthmatic women included maternal complications (pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, and antepartum and postpartum hemorrhage) and neonatal outcomes (low birth weight, congenital malformations, hyperbilirubinemia, and respiratory distress syndrome). RESULTS: The cohort included 817 asthmatic women and 13,709 nonasthmatic women. Overall, the prevalence of pregnancies complicated by asthma increased from 4.8% in 1991 to 6.9% in 1993. Asthmatic women were at increased risk for antepartum and postpartum hemorrhage, independent of medication usage. Asthmatic women taking steroids were at increased risk for pregnancy-induced hypertension (odds ratio [OR] 1.7; 95% confidence interval [CI] 1.0, 2.9). The only significant difference in neonatal outcome between asthma medication groups and nonasthmatic women was of an increased risk of hyperbilirubinemia in infants of women taking steroids (OR 1.9; 95% CI 1.1, 3.4). CONCLUSION: Risk of antepartum and postpartum hemorrhage is increased in asthmatic women, independent of medication usage. The increased incidence of neonatal hyperbilirubinemia and the borderline increased risk of pregnancy-induced hypertension may be complications of steroid use or may be related to poorly controlled asthma.

Risk scoring, fetal fibronectin, and bacterial vaginosis to predict preterm delivery.

OBJECTIVE: To determine the value of markers for predicting spontaneous preterm birth. METHODS: One hundred forty asymptomatic gravidas were recruited from 20-24 weeks' gestation. Risk score was assessed, vaginal swabs were analyzed for bacterial vaginosis, and cervical and vaginal swab were tested for fetal fibronectin FDC-6, X18A4, and CAF. Univariate analysis was used to determine potential predictors (and combinations of predictors) of outcome. Multiple logistic regression was done to identify independent predictors of spontaneous preterm birth. Sensitivity, specificity, positive and negative predictive values; and odds and likelihood ratios were calculated for significant predictors. RESULTS: Predictors significantly associated with the primary outcome were preterm birth-risk score and vaginal fetal fibronection FDC-6 (logistic regression odds ratio [OR] 16.9 [95% confidence interval (CI) 3.1, 92.8]) and 8.0 ([95% CI 1.6, 38.2], respectively). Bacterial vaginosis, fetal fibronectin X18A4, fibronectin CAF, and cervical fetal fibronectin FDC-6 were not associated with spontaneous preterm birth; however, the statistical power to assess these variables was limited. The combination of positive preterm birth-risk score and vaginal fetal fibronectin FDC-6 had a sensitivity of 44.4%, specificity of 97.7%, positive predictive value of 57.1%, negative predictive value of 96.2%, and a significant likelihood ratio for a positive test of 19.4 (95% CI 5.1, 73.8). CONCLUSION: The combination of preterm birth-risk score and vaginal fetal fibronectin FDC-6 predicted spontaneous preterm birth. Intervention trials are required to determine whether a combination of screening tests will reduce rates of spontaneous preterm birth.

Neonatal outcomes with placenta previa.

OBJECTIVE: To identify neonatal complications associated with placenta previa. METHODS: This was a population-based, retrospective cohort study involving all singleton deliveries in Nova Scotia from 1988 to 1995. The study group consisted of all completed singleton pregnancies complicated by placenta previa; all other singleton pregnancies were considered controls. Patient information was collected from the Nova Scotia Atlee perinatal database. Neonatal complications were evaluated while controlling for potential confounders. The data were analyzed using chi2, Fisher exact test, and multiple logistic regression. RESULTS: Among 92,983 pregnancies delivered during the study period, 305 cases of placenta previa were identified (0.33%). After controlling for potential confounders, neonatal complications significantly associated with placenta previa included major congenital anomalies (odds ratio [OR] 2.48), respiratory distress syndrome (OR 4.94), and anemia (OR 2.65). The perinatal mortality rate associated with placenta previa was 2.30% (compared with 0.78% in controls) and was explained by gestational age at delivery, occurrence of congenital anomalies, and maternal age. Although there was a higher rate of preterm births in the placenta previa group (46.56% versus 7.27%), there was no difference in birth weights between groups after controlling for gestational age at delivery. CONCLUSION: Neonatal complications of placenta previa included preterm birth, congenital anomalies, respiratory distress syndrome, and anemia. There was no increased occurrence of fetal growth restriction.

Causes and consequences of recent increases in preterm birth among twins.

OBJECTIVE: To examine the causes and consequences of the recent increase in preterm birth among twins. METHODS: We studied all twin births among residents of the province of Nova Scotia, Canada, between 1988 and 1997. Rates of preterm birth, preterm labor induction, preterm cesarean, small-for-gestational age (SGA), respiratory distress syndrome (RDS), stillbirth, perinatal mortality, and infant mortality were compared between past and more recent years. Changes in perinatal mortality were examined using logistic regression to adjust for the effects of other determinants. RESULTS: The study included 2516 twin births (73 stillbirths and 2443 live births). The rate of preterm birth increased from 42.3% in 1988-1992 to 48.2% of twin live births in 1993-1997 (14% increase, P =.04). Twin live births born after preterm labor induction increased from 3.5% in 1988-1989 to 8.6% in 1996-1997 (P for trend =.007). Of live births between 34 and 36 weeks' gestation, the proportion born SGA decreased from 17.5% in 1988-1992 to 9.2% in 1993-1997 (P =.005). Over the same period, rates of prophylactic maternal steroid therapy increased substantially and rates of RDS declined. Perinatal mortality rates among pregnancies reaching 34 weeks decreased from 12.9 per 1000 total births in 1988-1992 to 4.2 per 1000 total births in 1993-1997 (P =.05). CONCLUSION: Increases in preterm labor induction appear to be responsible for the recent increase in preterm birth among twins. These changes have been accompanied by decreases in perinatal morbidity and mortality among twin pregnancies that reach 34 weeks' gestation.

Assessment of coercive and noncoercive pressures to enter drug abuse treatment.

This paper reports preliminary data derived from a standardized interview scoring procedure for detecting and characterizing coercive and noncoercive pressures to enter substance abuse treatment. Coercive and noncoercive pressures stemming from multiple psychosocial domains are operationalized through recourse to established behavioral principles. Inter-rater reliability for the scoring procedure was exceptional over numerous rater trials. Substantive analyses indicate that, among clients in outpatient cocaine treatment, 'coercion' is operative in multiple psychosocial domains, and that subjects perceive legal pressures as exerting substantially less influence over their decisions to enter treatment than informal psychosocial pressures. Implications for drug treatment planning, legal and ethical issues, and directions for future research are proposed.

Acute ultrastructural changes in acoustic trauma: serial-section reconstruction of stereocilia and cuticular plates.

Single-unit recordings were made from populations of auditory-nerve fibers in 12 cats before and after acoustic overstimulation. Cats were killed 4 to 16 h after exposure, and the cochleas were analyzed at the light- and electron-microscopic levels. The exposures were designed to create 40 to 60 dB of acute threshold shift. Physiological changes were similar to those seen in cases of permanent threshold shift: tuning curves with elevation of 'tips' and 'tails' were associated with significant decreases in the mean spontaneous discharge rates; tuning curves with elevated tips but hypersensitive tails were associated with clear elevation of the mean spontaneous rates. At the light-microscopic level, none of the ears showed any significant stereociliary pathology. Some of the ears showed no light-microscopic pathology whatsoever, while others showed signs of swelling and vacuolization in both inner and outer hair cell areas in cochlear regions appropriate to the CF regions showing threshold shifts. The presence or absence of these light-microscopic changes was, to some extent, dependent on the nature of the exposure stimulus. At the electron-microscopic level, in addition to apparent swelling of radial afferent terminals, the inner hair cells themselves were swollen. In two cochlear regions (from two ears) which showed acute threshold shifts of 20 to 40 dB, but no light-microscopic changes, serial-section ultrastructural analysis of stereocilia and cuticular plates was performed. In contrast to the situation in ears with permanent threshold shifts [(1986) Hear Res. 26, 65-88], there was no pathology in the intracuticular portion of the stereocilia rootlets. There were, however, significant changes in the lengths of the supracuticular portion of the rootlets. It is suggested that this attenuation of the supracuticular rootlet could decrease the stiffness of the stereocilia tufts and thereby change the tuning properties and sensitivity of the cochlear partition.

Single-neuron labeling and chronic cochlear pathology. II. Stereocilia damage and alterations of spontaneous discharge rates.

The spontaneous discharge rates (SRs) sampled from auditory-nerve fibers in cases of chronic cochlear pathology are often abnormally low [17]. The application of intracellular labeling techniques to noise-exposed ears makes it possible to accurately correlate fiber populations showing SR abnormalities with the cochlear locations from which these responses originate. The correlations reveal that a decrease in the mean rates of spontaneous discharge is typically associated with selective loss of the tallest row of stereocilia from the inner hair cells. In cochlear regions where virtually all of the tall stereocilia are missing from the inner hair cells, the maximum rates of spontaneous discharge are less than 1/3 normal values. We suggest that the loss of tall stereocilia causes the decrease in SR because much of the resting current in the inner hair cell normally flows through the stereocilia membrane. Thus, the loss of that membrane leads to a hyperpolarization of the inner hair cell which, in turn, decreases the spontaneous release of vesicles at the synapse. An interpretation is also suggested for the "compression" of the SR distribution commonly seen among high-frequency neurons in normal animals [9].