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A Starr

Publications and source records attributed to A Starr.

At least 19 recordsLinked to original sources
PubMed2005

OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.

INTRODUCTION: The majority of hearing loss in children can be accounted for by genetic causes. Non-syndromic hearing loss accounts for 80% of genetic hearing loss in children, with mutations in DFNB1/GJB2 being by far the most common cause. Among the second tier genetic causes of hearing loss in children are mutations in the DFNB9/OTOF gene. METHODS: In total, 65 recessive non-syndromic hearing loss families were screened by genotyping for association with the DFNB9/OTOF gene. Families with genotypes consistent with linkage or uninformative for linkage to this gene region were further screened for mutations in the 48 known coding exons of otoferlin. RESULTS: Eight OTOF pathological variants were discovered in six families. Of these, Q829X was found in two families. We also noted 23 other coding variant, believed to have no pathology. A previously published missense allele I515T was found in the heterozygous state in an individual who was observed to be temperature sensitive for the auditory neuropathy phenotype. CONCLUSIONS: Mutations in OTOF cause both profound hearing loss and a type of hearing loss where otoacoustic emissions are spared called auditory neuropathy.

Child↗
PubMed2005

Auditory brain-stem, middle- and long-latency evoked potentials in mild cognitive impairment.

OBJECTIVE: Mild cognitive impairment (MCI) is a selective episodic memory deficit in the elderly with a high risk of Alzheimer's disease. The amplitudes of a long-latency auditory evoked potential (P50) are larger in MCI compared to age-matched controls. We tested whether increased P50 amplitudes in MCI were accompanied by changes of middle-latency potentials occurring around 50 ms and/or auditory brain-stem potentials. METHODS: Auditory evoked potentials were recorded from age-matched controls (n = 16) and MCI (n = 17) in a passive listening paradigm at two stimulus presentation rates (2/s, 1/1.5 s). A subset of subjects also received stimuli at a rate of 1/3 s. RESULTS: Relative to controls, MCI subjects had larger long-latency P50 amplitudes at all stimulus rates. Significant group differences in N100 amplitude were dependent on stimulus rate. Amplitudes of the middle-latency components (Pa, Nb, P1 peaking at approximately 30, 40, and 50 ms, respectively) did not differ between groups, but a slow wave between 30 and 49 ms on which the middle-latency components arose was significantly increased in MCI. ABR Wave V latency and amplitude did not differ significantly between groups. CONCLUSIONS: The increase of long-latency P50 amplitudes in MCI reflects changes of a middle-latency slow wave, but not of transient middle-latency components. There was no evidence of group difference at the brain-stem level. SIGNIFICANCE: Increased slow wave occurring as early as 50 ms may reflect neurophysiological consequences of neuropathology in MCI.

Aged↗
PubMed2005

Curcumin synergistically potentiates the growth inhibitory and pro-apoptotic effects of celecoxib in pancreatic adenocarcinoma cells.

BACKGROUND AND AIM: Adenocarcinoma of the Pancreas is a leading cause of cancer-related mortality, accounting for an estimated 30,000 deaths per year in the United States. Multiple studies have indicated that specific cyclooxygenase-2 (COX-2) inhibitors may serve in the prevention and treatment of a variety of malignancies including pancreatic adenocarcinoma. Recent studies had shown that the long-term use of high concentration of COX-2 inhibitors is not toxic free and may be limited due to serious gastrointestinal and cardiovascular side effects. The chemopreventive efficacy of the phytochemical, curcumin has been demonstrated in several in vitro and animal models. In this study we investigated whether curcumin potentiates the growth inhibition effect of a COX-2 inhibitor (celecoxib, Pfizer, NY, USA) in human pancreatic cancer cells. METHODS: P-34 (expressing high levels of COX-2), and MIAPaCa (expressing low levels of COX-2) and Panc-1 (no expression of COX-2) evaluated cell lines were exposed to different concentrations of celecoxib (0-40 microM), curcumin (0-20 microM) and their combination. Cell viability was by XTT assay. Apoptosis was assessed by flow cytometry and COX-2 expression was measured by Western blotting analysis. RESULTS: In P-34 cells, curcumin synergistically potentiated the inhibitory effect of celecoxib on cell growth. The growth inhibition was associated with inhibition of proliferation and induction of apoptosis. Western blot analysis showed that COX-2 expression was down-regulated by the combination therapy. CONCLUSION: Curcumin synergistically augments the growth inhibition inserted by celecoxib in pancreatic cancer cells expressing COX-2. The synergistic effect was mediated through inhibition of COX-2. This may enable the use of celecoxib at lower and safer concentrations and may pave the way for a more effective treatment in this devastating disease.

Adenocarcinoma↗
PubMed2003

Time course of motor excitability before and after a task-related movement.

AIMS OF THE STUDY: The time course of motor excitability during a task-related unilateral right thumb movement was studied using sub-threshold transcranial magnetic stimulation (TMS) to the contralateral left motor cortex. The level of stimulation evoked a motor evoked potential (MEP) in the thumb when the subject was at rest in approximately 10% of the trials. METHODS: Subjects made a brief right thumb movement to the predictable omission of regularly presented tone bursts allowing experimental definition of TMS relative to the cue to move. Motor cortical excitability was characterized by amplitude and/or probability of eliciting MEPs. RESULTS: There were four periods of altered motor excitability during task performance compared to a control resting state: a first period of weak facilitation before movement between -500 to -200 ms, a second period without increased excitability approximately 150 ms before movement onset when MEPs amplitude was below that seen in rest, a third period of strong facilitation between -100 ms before movement and +200 ms after facilitation and a fourth period of weak facilitation between +200 to +500 ms. CONCLUSION: These results show that during performance of a task requiring a motor response, motor cortical excitability is increased above resting for hundreds of millisecond before and after the response, except for a transient period between 75 and 150 ms prior to movement onset. The temporal pattern of these excitability changes is compatible with multiple excitatory and inhibitory inputs interacting on motor cortex.

Acoustic Stimulation↗
PubMed2002

Auditory event-related potentials during target detection are abnormal in mild cognitive impairment.

OBJECTIVE: To define brain activity and behavioral changes in mild cognitive impairment (MCI), an isolated memory deficit in the elderly that is a major risk factor for Alzheimer's disease. METHODS: Brain potentials and reaction time were examined in elderly controls (n=12) and MCI (n=15) using a target detection paradigm. Subjects listened to a sequence of tones and responded to high-pitched target tones (P=0.20) that were randomly mixed with low-pitched tones (P=0.80). Measures were a pre-stimulus readiness potential (RP), post-stimulus potentials (P50, N100, P200, N200, P300), and reaction time. RESULTS: Accuracy was equivalent between groups, but there was a trend for longer reaction times in MCI (P=0.08). Two potentials differed between groups: (1) P50 amplitude and latency were significantly increased in MCI, and (2) P300 latency was significantly longer in MCI. Results from two MCI subjects that converted to Alzheimer's disease are also discussed. CONCLUSIONS: Brain potentials in MCI subjects during target detection have certain features similar to healthy aging (RP, N100, P200, N200), and other features similar to Alzheimer's disease (delayed P300 latency, slower reaction time). P50 differences in MCI may reflect pathophysiological changes in the modulation of auditory cortex by association cortical regions having neuropathological changes in early Alzheimer's disease.

Acoustic Stimulation↗
PubMed2002

Preparatory slow potentials and event-related potentials in an auditory cued attention task.

OBJECTIVES: To examine reaction times and event-related potentials (ERPs) in an auditory cued attention task varying motor requirements, cue validity, and cue location. METHODS: Subjects (n=13) listened to cue-target stimulus pairs. Verbal cues (monaural, binaural) indicated the ear to receive a target tone 1.5s later. Cues correctly (valid) or incorrectly (invalid) predicted target ear, or were uninformative (neutral). In separate conditions subjects either responded by pressing one of two buttons, or did not respond to targets. ERPs for cues and targets (P50, N100, P200, late slow wave), and negative slow potentials between cues and targets were assessed. RESULTS: Target reaction times for valid cues were significantly shorter than for invalid cues, with intermediate values for neutral cues. When no motor response was required larger ERPs were seen to both cues and targets. Negative slow potentials had larger amplitudes before target presentation when subjects responded to targets; and were larger following neutral, vs. valid/invalid, cues. ERPs (N100, P200) to invalidly cued targets were significantly larger and a subsequent late slow wave was more positive, relative to validly cued targets. CONCLUSIONS: Expectancy for targets begins shortly after cue presentation, and is affected by both motor requirements and the information content of the cue. ERP amplitudes to targets are modulated by the correspondence between cue information and actual target location.

Acoustic Stimulation↗
PubMed2001

Orthotopic liver transplantation for autoimmune hepatitis and cryptogenic chronic hepatitis in children.

BACKGROUND: Autoimmune hepatitis (AIH) and cryptogenic chronic hepatitis (CCH) are important causes of liver failure in children, frequently necessitating orthotopic liver transplantation (OLT). The aim of this study is to review disease progression and potential differences between subgroups of children with AIH and CCH. METHODS: The medical records of 65 children diagnosed with AIH or CCH between 1980 and 1998 were evaluated. RESULTS: The median age at presentation was 9 years, 8 months (range 4 months-19 years), and the median follow-up period was 8 years (range 3 months-18 years, 10 months). Forty-one patients (63%) were female. Twenty-eight patients were Hispanic, 28 were Caucasian, 8 were African-American, and 1 was Asian. Forty-three patients (66%) were diagnosed with type 1 AIH, 8 (12%) with type 2 AIH, and 14 (22%) with CCH. Forty patients (62%) underwent OLT (51% of those with type 1 AIH, 75% of those with type 2 AIH, and 86% of those with CCH). Thirteen (33%) of the transplanted patients experienced disease recurrence. African-American patients experienced a significantly higher rate of disease recurrence post-OLT than did Hispanic patients. Seven patients (11%) died, two without OLT, and five posttransplantation. CONCLUSIONS: AIH and CCH frequently necessitate OLT in children. CCH is a more aggressive disease than Type 1 AIH among children with these disorders. Ethnicity influences the rate of disease recurrence after liver transplantation.

Adolescent↗
PubMed2001

Actuarial and actual analysis of surgical results: empirical validation.

This report validates the use of the Kaplan-Meier (actuarial) method of computing survival curves by comparing 12-year estimates published in 1978 with current assessments. It also contrasts cumulative incidence curves, referred to as "actual" analysis in the cardiac-related literature with Kaplan-Meier curves for thromboembolism and demonstrates that with the former estimate the percentage of events that will actually occur.

Actuarial Analysis↗
PubMed2001

Influence of task-related ipsilateral hand movement on motor cortex excitability.

OBJECTIVE: The time course of the right motor cortex excitability in relation to a task-related voluntary right thumb twitch was studied using sub-threshold transcranial magnetic stimulation (TMS) to the right motor cortex. METHODS: Motor excitability was studied in 8 adult subjects who made a brief right thumb twitch to the predictable omission of every fifth tone in a series of tones 2.5 s apart. This paradigm avoided an overt sensory cue, while allowing experimental control of TMS timing relative to both movement and the cue to move. Motor excitability was characterized by several measures of motor evoked potentials (MEPs) recorded from the left thenar eminence in response to TMS over the right scalp with a 9 cm coil: probability of eliciting MEPs, incidence of MEPs and amplitude of MEPs. RESULTS: All subjects showed suppression of motor excitability immediately following a voluntary right thumb twitch (ipsilateral response), and up to 1 s after it. However, two distinctly different effects on motor excitability were observed before the response: two subjects showed excitation, beginning about 500 ms before response until 300 ms after it, followed by the post-movement suppression; 6 subjects displayed pre-movement suppression, beginning about 600 ms before the response and persisting for the duration. CONCLUSIONS: The net effect of an ipsilateral response on motor cortex can be either inhibitory or excitatory, changing with time relative to the response. These findings are compatible with two separate processes, inhibitory and excitatory, which interact to determine motor excitability ipsilateral to the responding hand.

Adult↗
PubMed2001

Hemodynamic effects of S-nitrosocysteine, an intravenous regional vasodilator.

BACKGROUND: S-nitrosocysteine is a carrier form of nitric oxide that can be delivered intravenously. S-nitrosocysteine is rapidly metabolized by plasma (half-life = 2-3 seconds), forming nitric oxide and cysteine. With its short half-life and potent vasodilatory properties, S-nitrosocysteine may be useful as a pulmonary vasodilating agent in cases of postoperative and chronic pulmonary hypertension. OBJECTIVE: Our objective was to determine the hemodynamic properties of S-nitrosocysteine on the pulmonary and systemic circulations to assess its potential utility as a pulmonary vasodilatory agent. METHODS: Eleven adult swine were anesthetized. Thermodilution (Swan-Ganz; Baxter International, Inc, Deerfield, Ill) and arterial catheters were inserted. Flow probes were placed around the coronary, renal, superior mesenteric, and iliac arteries. Incremental infusion doses of S-nitrosocysteine (5-80 nmol. kg(-1). min(-1)) were delivered into the right atrium. Cardiac output, right and left heart pressures, heart rate, Pao(2), and iliac, renal, coronary, and mesenteric blood flow rates were recorded at baseline and at each infusion dose of S-nitrosocysteine. RESULTS: Low-dose S-nitrosocysteine infusion decreased mean pulmonary artery pressure (15%, P =.013) without a significant reduction in mean systemic artery pressure. Higher dose infusions produced further dose-dependent declines in pulmonary vascular resistance and measurable reductions in systemic vascular resistance (P =.01). At an S-nitrosocysteine dosage of 40 nmol. kg(-1). min(-1), there was a significant reduction in renal (P <.001) and mesenteric (P =.003) blood flow but no change in iliac (P >.2) or coronary (P >.2) blood flow. Cardiac output remained constant up to infusion rates of 40 nmol. kg(-1). min(-1) (P >.2). Doses higher than 5 nmol. kg(-1). min(-1) resulted in a substantial dose-dependent reduction in Pao(2) (P <.001), suggesting dilation of atelectatic areas of the lung. CONCLUSION: S-nitrosocysteine is a potent vasodilatory agent capable of overcoming the hypoxic vasoconstrictive response of the lung. Our results suggest it may prove useful as a pulmonary vasodilatory agent at low doses. Higher dose infusions reduce mean systemic pressure and lead to compensatory reductions in renal and mesenteric blood flow without a decrease in cardiac output.

Analysis of Variance↗
PubMed2001

Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy.

OBJECTIVE: To define both auditory nerve and cochlear receptor functions in subjects with auditory neuropathy (AN). DESIGN: We tested 33 AN subjects (66 ears) and compared them with 21 healthy subjects (28 ears). In AN subjects, the average pure-tone (1, 2, and 4 kHz) threshold loss was 57 dB HL. Click stimuli were used to elicit transient evoked otoacoustic emissions (TEOAEs), cochlear microphonics (CMs), and auditory brain stem responses (ABRs). Both cochlear and ABR potentials were recorded from surface electrodes (vertex-ipsilateral mastoid) using averaging procedures. The amplitudes and latencies of CMs and ABRs and the amplitude of the TEOAEs were analyzed. RESULTS: CM amplitudes recorded from normal ears decreased as a function of subject age. CMs recorded from AN subjects fell within the normal age-adjusted range in 60% of the subjects and were >2 SEEs (standard error of estimate) above the age-adjusted normal regression in 40% of the subjects. TEOAEs were absent in 19 (30%) AN ears (bilaterally in eight, and unilaterally in three subjects) and were present in 44 ears. In AN subjects, correlations among CM amplitude, TEOAE amplitude, and pure-tone average thresholds were not significantly related. CM amplitudes were not significantly different whether TEOAEs or ABRs were present or absent. The ABR was present in 21% of AN subjects and consisted of a low-amplitude Wave V without a preceding Wave I. Measures of CM amplitude and PTA hearing loss were not significantly different in those AN ears with a preserved ABR compared with ears with absent ABRs. Summating potentials to transient click stimuli were of small amplitude (<0.1 microV) and detectable in approximately 50% of the AN and healthy control subjects limiting formal analysis of summating potentials. CONCLUSIONS: In a significant proportion of AN subjects, we found abnormalities of cochlear receptor function, including elevated CM amplitudes and absence of TEOAEs. These two abnormalities occurred independently of each other. A low amplitude Wave V of the ABR was found in approximately one-fifth of AN subjects, evidence that neural synchrony can be partially preserved in some subjects with this disorder.

Adolescent↗
PubMed2000

Vestibular neuropathy accompanying auditory and peripheral neuropathies.

OBJECTIVE: To define the incidence of measurable vestibular disorders in patients with auditory and peripheral neuropathies. DESIGN: Descriptive study of the case features of auditory neuropathy in 14 patients, 8 of whom had concomitant peripheral neuropathies. SETTING: University referral center. PATIENTS: Fourteen patients aged from 10 to 75 years and diagnosed as having auditory neuropathy, 8 of whom had concomitant peripheral neuropathies. MAIN OUTCOME MEASURES: Incidence of abnormal vestibular caloric test results and the relationship of such incidence to clinical variables including the ages of the subjects, the presence of a concomitant peripheral neuropathy, vestibular symptoms, and audiological findings. RESULTS: Abnormal vestibular caloric test results occurred in 9 of the 14 patients. These 9 patients were on average older (35.6 years) than patients with normal caloric responses (17.8 years). Seven of the 9 patients with abnormal caloric responses had concomitant peripheral neuropathies compared with only 1 of the 5 patients with normal caloric responses. None of the 14 patients experienced symptoms of vestibular disorder. CONCLUSIONS: Asymptomatic vestibular disorders are common in patients with auditory neuropathy when a peripheral neuropathy is also present. The reason for the abnormal vestibular test results is likely a neuropathy of the vestibular nerves. Arch Otolaryngol Head Neck Surg. 2000;126:1453-1456

Adolescent↗
PubMed2000

Hereditary motor and sensory neuropathy--Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries.

Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb.

Adolescent↗
PubMed2000

Effects of stimulus sequence on event-related potentials and reaction time during target detection in Alzheimer's disease.

OBJECTIVES: To examine evoked potentials and behavior as a function of stimulus sequence in an auditory target detection paradigm in Alzheimer's disease (AD). METHODS: Evoked potentials and reaction times were collected from 12 healthy elderly controls and 10 patients with mild AD. Subjects pressed a response button to high-pitched target tones (P=0.20) that were randomly intermixed with low-pitched frequent tones. We measured pre-stimulus readiness potential (RP), event-related potentials (P50, N100, P200, N200 and P300), and reaction time as a function of the stimulus sequence. RESULTS: AD subjects performed at comparable levels of accuracy as controls, but had significantly increased reaction times. Grand averaged potentials in AD showed a significant reduction of the amplitude of the RP, and an increase of P300 latency. Both controls and AD showed speeding of reaction time, increases in RP amplitude, and decreases in P300 latency as a function of the number of frequents preceding the target. Sequential changes of other components (P200 and N200) were found in controls but not AD. CONCLUSIONS: AD patients have systematic changes of both RT and certain of the evoked potential components as a function of stimulus sequence. Moment-by-moment changes in target expectancy are largely preserved in AD, even though overall performance and evoked potential measures of expectancy (RP) and stimulus classification (P300 latency) are abnormal.

Acoustic Stimulation↗
PubMed2000

Delayed facilitation of motor cortical excitability following repetitive finger movements.

OBJECTIVES: To define motor cortical excitability changes occurring at various times after non-fatiguing bimanual exercise of the index fingers. METHODS: Twenty healthy right-handed subjects were studied with transcranial magnetic stimulation (TMS) of the right non-dominant hemisphere. They performed regular (3-4/s) repetitive opening-closing bilateral movements of the index finger onto the thumb. Motor evoked potentials (MEPs) of the left first dorsal interosseus (FDI) and rate of the repetitive finger movements were determined (1) before exercise, (2) immediately following 3 exercise periods of 30, 60 and 90 s, and (3) over a subsequent 30 min rest period. RESULTS: Rate of movement did not show significant change during any of the exercise periods but did increase significantly when tested after 15 min of rest. MEPs immediately after 30 and 60 s of exercise were facilitated whereas MEPs after 90 s of exercise did not differ from baseline measures. MEP amplitudes were significantly increased after rest of approximately 15 min compared to the baseline MEPs. In contrast, motor potentials evoked by peripheral nerve stimulation were unchanged throughout the experimental test periods. CONCLUSIONS: Motor cortical excitability relating to an intrinsic finger muscle (FDI) was facilitated beginning 15 min after a brief period of non-forceful, repetitive activity of that muscle. This delayed facilitation of motor cortex after exercise may represent a form of short-term potentiation of motor cortical excitability.

Adolescent↗
PubMed2000

Motor cortex excitability in chronic fatigue syndrome.

OBJECTIVE: To use transcranial magnetic stimulation (TMS) to define motor cortical excitability in chronic fatigue syndrome (CFS) subjects during a repetitive, bilateral finger movement task. METHODS: A total of 14 CFS patients were tested and compared with 14 age-matched healthy control subjects. TMS of the motor cortex (5% above threshold) was used to elicit motor evoked potentials (MEPs). Subjects performed regular (3-4/s) repetitive bilateral opening-closing movements of the index finger onto the thumb. MEPs of the first dorsal interosseus (FDI) were measured before, immediately following exercise periods of 30, 60 and 90 s, and after 15 min of rest. RESULTS: Performance, defined by rate of movement, was significantly slower in CFS subjects (3.5/s) than in controls (4. 0/s) independent of the hand measured. The rate, however, was not significantly affected by the exercise duration for either group. The threshold of TMS to evoke MEPs from the FDI muscle was significantly higher in CFS than in control subjects, independent of the hemisphere tested. A transient post-exercise facilitation of MEP amplitudes immediately after the exercise periods was present in controls independent of the hemisphere tested, but was absent in CFS subjects. A delayed facilitation of MEPs after 15-30 min of rest was restricted to the non-dominant hemisphere in controls; delayed facilitation was absent in CFS subjects. CONCLUSIONS: Individuals with CFS do not show the normal fluctuations of motor cortical excitability that accompany and follow non-fatiguing repetitive bimanual finger movements.

Adult↗