Biomedical subjects

A E Hubbard

Publications and source records attributed to A E Hubbard.

At least 19 recordsLinked to original sources

PubMed2000

Nonparametric survival estimation when death is reported with delay.

In disease registries there can be a delay between death of a subject and the reporting of this death to the data analyst. If researchers use the Kaplan-Meier estimator and implicitly assumed that subjects who have yet to have death reported are still alive, i.e. are censored at the time of analysis, the Kaplan-Meier estimator is typically inconsistent. Assuming censoring is independent of failure, we provide a simple estimator that is consistent and asymptotically efficient. We also provide estimates of the asymptotic variance of our estimator and simulations that demonstrate the favorable performance of these estimators. Finally, we demonstrate our methods by analyzing AIDS survival data. This analysis underscores the pitfalls of not accounting for delay when estimating the survival distribution and suggests a significant reduction in bias by using our estimator.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Effects of acoustic trauma on acoustic enhancement of electrically evoked otoacoustic emissions.

Moderate acoustic trauma results in decreased cochlear sensitivity and frequency selectivity. This decrease is believed to be caused by damage to the cochlear amplifier that is associated with outer hair cells (OHCs) and their nonlinear electromechanical characteristics. A consequence of OHC nonlinearity is the acoustic enhancement effect, in which low-frequency electrically evoked otoacoustic emissions are enhanced by a simultaneous tone. The present study found that acoustic trauma reduced the acoustic enhancement effect and this reduction is correlated with the N1 threshold at the electrode site. This result is consistent with the theory that trauma affects the mechanoelectric transduction process, thus affecting cochlear mechanical nonlinearity. Acoustic trauma also reduced the cochlear microphonic in a way that suggests that the number of functioning tension-gated channels and the stiffness of the gating springs were decreased. In some cases, the electromechanical transduction process was also found to be affected by acoustic trauma.

Animals↗

PubMed2000

Cerebrospinal fluid pharmacokinetics of cefpodoxime proxetil in piglets.

Cefpodoxime is an oral third-generation cephalosporin used for the treatment of acute upper-respiratory tract infections caused by susceptible bacteria in children. Although not indicated for the treatment of bacterial meningitis, it is used to treat other infections produced by organisms associated with meningitis and may obscure the result of cerebrospinal fluid (CSF) cultures in children who develop meningitis while receiving oral antibiotics if sufficient concentrations are achieved in the CSF. This study evaluated the disposition of cefpodoxime and penetration into CSF in piglets. Fifteen Landacre-Camborough cross piglets (10-20 days old) received cefpodoxime proxetil oral suspension (10 mg/kg). Repeated plasma and CSF samples were collected over 24 hours for quantitation of cefpodoxime by HPLC. Pharmacokinetic analysis was performed on both plasma and CSF data. The plasma concentration versus time data for cefpodoxime were best characterized using a one-compartment model with first-order absorption. The mean (+/- SD) pharmacokinetic parameters for Cmax, tmax, and AUC0-infinity were 23.3 +/- 12.9 mg/L, 3.9 +/- 1.4 h, and 237 +/- 129 mg/L.h, respectively. CSF/plasma ratios for AUC0-infinity demonstrated a mean cefpodoxime penetration of approximately 5%. CSF penetration of cefpodoxime was evident following a single oral dose of cefpodoxime proxetil suspension. Despite the small percentage of total cefpodoxime dose distributing into the CSF, the resultant concentrations approached or exceeded the MIC90 for many bacterial pathogens considered susceptible to cefpodoxime. Accordingly, clinicians should use caution in the interpretation of CSF cultures in patients who develop clinical signs and symptoms consistent with meningitis and who have been previously treated with cefpodoxime.

Animals↗

PubMed2000

Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells.

Benzene is an established human carcinogen, producing leukemia, hematotoxicity and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its conversion to phenol and hydroquinone, the latter being oxidized to the highly toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell lines to hydroquinone has previously been shown to cause various forms of genetic damage, including aneusomy and the loss and gain of chromosomes. However, the target cells for leukemogenesis are the pluripotent stem cells or early progenitor cells which carry the CD34 antigen (CD34(+) cells). In this study, human cord blood, which is particularly rich in CD34(+) cells, was exposed to hydroquinone for 72 h in a medium that favored CD34(+) cell survival and growth. CD34(+) and CD34(-) cells were then isolated. Fluorescence in situ hybridization was employed to determine the level of aneusomy of chromosomes 7 and 8 in both cell types. CD34(+) cells were generally more susceptible to aneusomy induction by hydroquinone than CD34(-) cells. Increased trisomy and monosomy of chromosomes 7 and 8 were observed in CD34(+) cells (P(trend) < 0.001), whereas in CD34(-) cells only an increased level of monosomy 7 was detected (P(trend) = 0.002). Particularly striking effects of hydroquinone were observed in CD34(+) cells on monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid leukemias, suggesting that these aneusomies produced by hydroquinone in CD34(+) cells play a role in benzene-induced leukemogenesis.

Aneuploidy↗

PubMed1999

Psychological stress in the workplace and menstrual function.

The relation between psychological stress at work and menstrual function was examined for 276 healthy, working, premenopausal women who participated in the California Women's Reproductive Health Study in 1990-1991. Subjects collected daily urine samples and completed a daily diary for an average of five menstrual cycles. Metabolites of estrogen and progesterone were measured in the urine, and computer algorithms were developed to characterize each cycle as ovulatory or anovulatory and to select a probable day of ovulation. A telephone interview collected information about psychological stress at work as well as other occupational, demographic, lifestyle, and environmental factors. Logistic regression was used to model stressful work and risk of anovulation (> or = 36 days without ovulating) and measures of within-woman cycle variability. Repeated measures analyses were performed on other menstrual cycle parameters. Stressful work (high demand in combination with low control) was not strongly related to an increased risk for anovulation or cycle variability or to any of the following cycle endpoints: short luteal phase (< or = 10 days), long follicular phase (> or = 24 days), long menses (> or = 8 days), or long cycle (> or = 36 days). However, women in stressful jobs had a more than doubled risk for short cycle length (< or = 24 days) compared with women not working in stressful jobs (adjusted odds ratio = 2.24, 95% confidence interval 1.09-4.59).

Adolescent↗

PubMed1998

Nonlinear characteristics of electrically evoked otoacoustic emissions.

To further our knowledge of outer hair cell nonlinearities, we measured the dependence of the electrically-evoked otoacoustic emissions (EEOEs) on current level for a wide range of electrical frequencies. Alternating electrical current was delivered into the scala media of the gerbil cochlea while the EEOE was measured with a probe-tube microphone. While the EEOE scaled linearly with current level for many frequencies and current levels, notable exceptions occurred. For frequencies below 300 Hz and currents above 20-30 microA(peak), the gain (primary EEOE magnitude divided by the current level) increased abruptly. For higher frequencies, the gain often increased slightly with increasing current of up to 30-50 microA(peak), but decreased at even higher current levels. We also investigated the enhancement of the EEOE due to simultaneous acoustic stimulation. The enhancement of the EEOE was relatively insensitive to current level with little change in enhancement for current levels up to 20 microA(peak). For current levels above approximately 40 microA(peak), the enhancement decreased slightly.

Acoustic Stimulation↗

PubMed1997

A prospective study of work-related physical exertion and spontaneous abortion.

We examined the relation of physical exertion to spontaneous abortion in a prospective study of 5,144 pregnant women. In a first trimester interview, we obtained data on employment and physical activity at work and at home, as well as other potential risk factors for spontaneous abortion. We measured exertion as follows: time spent working, standing and bending at work, hours between breaks, and hours spent doing housework or yardwork; shift worked; number of times lifted weights and more than 15 pounds at work or at home; number of children under age 5 years cared for at home. None of the exertion measures was appreciably associated with an increased risk of spontaneous abortion overall. In addition, physical activity at work and at home combined was not related to increased risk. For women with a history of two or more spontaneous abortions, standing at work more than 7 hours per day was associated with an adjusted odds ratio (OR) of 4.3 [95% confidence limits (CL) = 1.6, 11.7], whereas standing at work for 7 hours or less was associated with an adjusted OR of 1.7 (95% CL = 1.1, 2.6). Women without such a history who stood more than 7 hours at work had an adjusted OR near unity.

Abortion, Spontaneous↗

PubMed1997

Caffeinated beverages, decaffeinated coffee, and spontaneous abortion.

We examined the relations between spontaneous abortion and the consumption of caffeine, individual caffeine-containing beverages (coffee, tea, and soda), and decaffeinated coffee in a prospective study of 5,144 pregnant women. We collected information about potential risk factors for spontaneous abortion, including consumption of caffeinated beverages and decaffeinated coffee before and during pregnancy, by interview in the first trimester. Neither total estimated caffeine nor individual caffeinated beverage consumption during the first trimester was associated with an appreciable increase in risk for spontaneous abortion. The adjusted odds ratio for consumption of greater than 300 mg per day of caffeine was 1.3 [95% confidence interval (CI) = 0.8-2.1] after adjustment for maternal age, pregnancy history, cigarette and alcohol consumption, employment, race, gestational age at interview, and marital and socioeconomic status. The adjusted odds ratio for spontaneous abortion related to consumption of three or more cups of decaffeinated coffee during the first trimester was 2.4 (95% CI = 1.3-4.7) in the same model. Although we could not demonstrate this with available data, we suspect that this association was due to bias resulting from the relations among fetal viability, symptoms of pregnancy such as nausea, and consumption patterns during pregnancy.

Abortion, Spontaneous↗

PubMed1995

Psychologic stress in the workplace and spontaneous abortion.

The relation of work-related psychologic stress to spontaneous abortion was examined in a prospective study of 3,953 pregnant, employed members of a prepaid health plan in California, recruited between 1990 and 1991. Information on occupation, psychologic stress-related factors at work, social support at work, physical exertion at work, life events, pregnancy worries, and potential confounders was obtained by a telephone interview. Psychologic job stress and social support at work were assessed using an abbreviated version of the instrument developed by Karasek and colleagues (Los Angeles: University of Southern California, 1986). Results from the multivariate model indicated that, overall, stressful work was not associated with an increased risk of spontaneous abortion. However, interactions were observed between stressful work and maternal age over 32 years (p = 0.04), cigarette smoking (p = 0.02), and primigravidity (p = 0.06). Relative to the odds ratio for stressful work in young, nonsmoking, multigravid women without a history of two or more spontaneous abortions, the odds ratios for spontaneous abortion given stressful work were higher by 2.45 (95% confidence interval (CI) 1.03-5.81) for older women, 2.96 (95% CI 1.16-7.52) for smokers, and 2.27 (95% CI 0.97-5.27) for primigravid women.

Abortion, Spontaneous↗

PubMed1995

Acoustic enhancement of electrically evoked otoacoustic emissions reflects basilar membrane tuning: a model.

A simple model for the acoustic enhancement of electrically evoked otoacoustic emissions (EEOEs) is presented in this paper. The model is based on the assumption that the enhancement is a result of the local interaction between the electrical current spreading in the scala media and the basilar membrane (BM) response to acoustic input. The analytical, steady-state response of the 1-dimensional linear cable to sinusoidal current injection is derived and is used to predict the current spreading in the cochlea. Acoustic enhancement at an emission generator is modeled as a magnitude change that is a sigmoid function of the local BM motion. The model results are in good agreement with the experimental findings and support our interpretation that the acoustic enhancement of EEOEs reflects BM tuning.

Acoustic Stimulation↗

PubMed1995

Electrically evoked basilar membrane motion.

Electrically induced outer hair cell (OHC) motility, demonstrated by a number of investigators in isolated OHC preparations, has been considered to be a key mechanism in the active process which brings about the excellent sensitivity and frequency selectivity of the mammalian cochlea. In this study, electrical-to-mechanical transduction in the gerbil cochlea was demonstrated in vivo by direct measurement of basilar membrane motion evoked by sinusoidal electrical current injected into the scala media. The characteristic frequency (CF) of the measurement place was approximately 40 kHz as determined by the basilar membrane (BM) responses to acoustic stimulation. The results showed that basilar membrane motion could be evoked by electrical current of frequencies from below 10 Hz to exceeding 40 kHz. The magnitude and phase of the BM velocity response to constant current stimulation, from 100 Hz to 10,000 Hz, were similar to the acoustically driven BM velocity for constant umbo velocity. For frequencies in this range, the BM motion evoked by a current of 50 microA was comparable to the BM motion evoked by a 60 dB SPL acoustic stimulus. The phase of the electrically evoked BM motion indicates that positive current injected into the scala media caused the BM to move toward scala vestibuli for frequencies between 100 and 10 kHz. This result is consistent with the hypothesis that the electrically evoked BM motion is due to electrically evoked OHC length changes.

Animals↗

PubMed1994

Effects of electrical biasing on electrically-evoked otoacoustic emissions.

Electrically-evoked otoacoustic emissions were produced using a 10 microA, 750 Hz AC current plus a biasing DC current in the range of +/- 10 microA. Concurrently, a 1643 Hz tonal stimulation was delivered to the eardrum. At low sound levels, negative DC current increased the emission while positive DC current reduced the emission. Such findings are reasonably explained by a negative-feedback model of cochlear function. At high sound levels, negative DC current reduces the emission, while positive current has little effect. These data can be accounted for by voltage-dependent length changes shown to occur in isolated outer hair cells, with the additional requirement that voltage-dependent K+ channels in outer hair cells reduce the effectiveness of positive DC current in changing membrane potential.

Acoustic Stimulation↗

PubMed1994

A piezoelectric model of outer hair cell function.

Mammalian outer hair cells (OHC) are believed to increase cochlear sensitivity and frequency selectivity via electromechanical feedback. A simple piezoelectric model of outer hair cell function is presented which integrates existing data from isolated OHC experiments. The model predicts maximum OHC force production to equal 1.25 nN/mV. The model also predicts that the maximum velocity of OHC contraction in situ to be 800 microns/s. These predictions are compared to available experimental data and are found to be in good agreement. The good agreement between the predicted and experimental results suggests that, at the characteristic frequency of a given cochlear location, the OHC receptor current is very efficiently converted into basilar membrane motion.

Animals↗

PubMed1994

Electrically evoked otoacoustic emissions from the apical turns of the gerbil cochlea.

Electrically evoked otoacoustic emissions were measured with current delivered to the second and third turns of the gerbil cochlea. The emission magnitude and phase are dependent on the characteristic frequency (CF) of the stimulating microelectrode location. The death of the animal resulted in an initial increase in emission below the CF of the electrode location and a decrease in emission near the CF of the electrode location. The group delay of the electrically evoked emission phase data is twice as large as the acoustically evoked cochlear microphonic (CM) data obtained by Schmiedt and Zwislocki [J. Acoust. Soc. Am. 61, 133-149 (1977)]. This suggests the possibility of two separate propagation modes for the forward and reverse traveling waves.

Acoustic Stimulation↗

PubMed1993

Acoustic enhancement of electrically-evoked otoacoustic emissions reflects basilar membrane tuning: experiment results.

Acoustic enhancement of the electrically-evoked otoacoustic emissions (EEOEs) was investigated by systematically varying acoustic frequency and intensity. The results demonstrated that simultaneous acoustic stimulation at frequencies around the characteristic frequency of the electrical current injection place was most effective in enhancing low-frequency EEOEs. Moreover, it was demonstrated that the enhancement was tuned and graded. The enhancement threshold tuning curves (defined as sound pressure level needed to achieve 1 dB of enhancement) resembled basilar membrane tuning at high sound pressure levels. The data suggest that the emissions were generated from a cochlear region near the electrode place, and the magnitude of the enhancement depends on the magnitude of the basilar membrane response to the acoustic stimulus.

Acoustic Stimulation↗

PubMed1990

Haircell forward and reverse transduction: differential suppression and enhancement.

Cochlear outer haircells are believed to play a significant role in an amplification process which greatly enhances inner ear sensitivity. Haircell forward (mechanical-to-electrical) and reverse (electrical-to-mechanical) transduction may be involved. We have produced decreases in cochlear microphonic and increases in electrically-evoked cochlear emissions using the drug, furosemide. The data indicate forward and reverse transduction are not a simple bi-directional process and suggest that the outer haircells are part of a negative feedback system.

Animals↗

PubMed1989

Rapid force production in the cochlea.

Electrical stimulation of the mammalian cochlea causes a mechanical response which produces acoustic signals at the frequency of the electrical current. These electrically-evoked acoustic emissions can be as large as 34 dB SPL. Concurrent acoustic stimuli can enhance the emission response. Comparison of the enhancement effect with the cochlear microphonic (CM) suggests that the emissions originate from the outer hair cells (OHC). Frequency response measurements indicate a rate-limiting time constant for the force-generating process which is less than 35 microseconds.

Animals↗

PubMed1986

Cochlear emissions simulated using one-dimensional model of cochlear hydrodynamics.

Stapes velocity was computed using a nonlinear, one-dimensional model of cochlear hydromechanics. The model's compliances and damping coefficients were mechanically nonlinear and instantaneously varying in proportion to simulated current injected into the cochlea. Experimental data showing the spectral content of the pressure waveform near the eardrum during the delivery of sound and current to the cochlea were compared with model results.

Cochlea↗