Faculty Bibliography

BACKGROUND: In obstructive sleep apnea/hypopnea syndrome, immediate physiological consequences of events have a dual role: censoring artifacts and gauging physiological significance. Newer airflow monitors may have changed the relative importance of these functions. The purpose of this study was to determine the frequency and hierarchy of occurrence of oxygen desaturation, EEG arousal and heart rate changes as immediate consequences of respiratory events. METHODS: Thirty-nine sleep apnea patients underwent polysomnography with airflow detection by nasal cannula. Eighty events/subject were randomly selected and evaluated for 4% oxygen desaturation, EEG arousal and heart rate increase. RESULTS: Of apneas, 78% caused desaturation, 63% arousal, and 73% heart rate increase. Of hypopneas, 54% caused desaturation, 47% arousal, and 55% heart rate increase. Of events with mildest amplitude reduction 25% caused desaturation, 42% arousal, and 42% heart rate increase. Consequences overlapped but did not occur hierarchically: each occurred alone and in all combinations. CONCLUSION: No single consequence occurred after every event; thus none can be used to corroborate airflow reduction as non-artifactual without missing events corroborated by other consequences. As different consequences validate non-hierarchical sets of respiratory events, we propose there is need to capture all changes in breathing in obstructive sleep apnea/hypopnea syndrome before examining their role in clinical outcome.

Reports an error in the original article by Ana C. Krieger et al (Journal of Sleep Research, 2004[Dec], Vol 13[4], 407-441.) The manufacturer of the Oxford Sleep Resistance Test, OSLER was inadvertently omitted. The manufacturer is: Stowood Scientific Instruments, Oxford, UK. (The following abstract of this article originally appeared in record 2004-21174-013). The objectives were to evaluate the correlation between sleep onset as defined by the Oxford sleep resistance (OSLER) test and by simultaneous electroencephalography (EEG) and to determine the correlation between sleep latencies measured by the OSLER test and maintenance of wakefulness test (MWT) performed on the same day. This was a prospective, cross-sectional study carried out in a tertiary-care university-based sleep laboratory. Participants were 11 consecutive subjects presenting to the sleep center with clinical indications for nocturnal polysomnography and MWT. The interventions included MWT and OSLER test. Mean sleep latencies for the OSLER and MWT in each subject were closely correlated (ICC = 0.94, [Intra-class correlation] P < 0.05). Sleep latency by OSLER and simultaneous measurement of EEG also had excellent agreement (ICC = 0.91) with a bias of -0.97 min. The OSLER test is a practical and reliable tool for evaluating daytime sleepiness when compared with the MWT. No obvious systematic adaptation was seen during sequential OSLER test performance. Given its portability and minimal technical requirements, the OSLER test may be useful for largescale applications in the evaluation of daytime wakefulness and vigilance.

In this longitudinal study, quantitative and qualitative changes in responses of people with aphasia were examined on a phonemic fluency task. Eighteen patients were tested at 3-month intervals on the letters F-A-S while they received comprehensive, intensive treatment from 3 to 12 months post-stroke. They returned for a follow-up evaluation at an average of 10 months post-intervention. Mean group scores improved significantly from beginning to end of treatment, but declined post-intervention. Patients produced a significantly greater number and proportion of modifiers (adjectives and adverbs) between the beginning and end of treatment, with no decline afterwards, implying that they had access to a wider range of grammatical categories over time. Moreover, patients used significantly more phonemic clusters in generating word lists by the end of treatment. These gains may be attributed to the combined effects of time since onset and the linguistic and cognitive stimulation that patients received in therapy. LEARNING OUTCOMES: Readers of this paper should (1) gain a better understanding of verbal fluency performance in the assessment of aphasia, (2) recognize the importance of analyzing qualitative aspects of single word production in aphasia, and (3) contribute to their clinical judgment of long term improvement in aphasia.

STUDY OBJECTIVES: Current Medicare guidelines include an apnea-hypopnea index (AHI) > or = 15 events per hour, in which all hypopneas must be associated with 4% desaturation, to qualify for reimbursement for therapy with continuous positive airway pressure (CPAP). The present data demonstrate the effect of pulse oximeter differences on AHI. DESIGN: Prospective study, blinded analysis. SETTING: Academic sleep disorder center. PATIENTS: One hundred thirteen consecutive patients (84 men and 29 women) undergoing diagnostic sleep studies and being evaluated for CPAP based on the Medicare indications for reimbursement. INTERVENTIONS: Patients had two of four commonly used oximeters with signal averaging times of 4 to 6 s placed on different digits of the same hand during nocturnal polysomnography. MEASUREMENTS AND RESULTS: Apneas and candidate hypopneas (amplitude reduction, > 30%) were scored from the nasal cannula airflow signal without reference to oximetry. Candidate hypopneas then were reclassified as hypopneas by each oximeter if they were associated with a 4% desaturation. Although the use of three oximeters resulted in a similar AHI (bias, < 1 event per hour), the fourth oximeter showed an overall increase in AHI of 3.7 events per hour. This caused 7 of 113 patients to have an AHI of > or = 15 events per hour (meeting the Medicare criteria for treatment) by one oximeter but not when a different oximeter was used. More importantly, when our analysis was limited to those patients whose number of candidate hypopneas made them susceptible to the threshold value of 15 events per hour, 7 of 35 patients who did not meet the Medicare AHI standard for treatment by one oximeter were reclassified when a different oximeter was used. CONCLUSION: In the present study, oximeter choice affected whether the AHI reached the critical cutoff of 15 events per hour, particularly in those with disease severity that was neither very mild nor very severe. As oximetry is not a technique that produces a generic result, there are significant limitations to basing the definition of hypopnea on a fixed percentage of desaturation in determining the eligibility for CPAP therapy.

The objectives were to evaluate the correlation between sleep onset as defined by the Oxford sleep resistance (OSLER) test and by simultaneous electroencephalography (EEG) and to determine the correlation between sleep latencies measured by the OSLER test and maintenance of wakefulness test (MWT) performed on the same day. This was a prospective, cross-sectional study carried out in a tertiary-care university-based sleep laboratory. Participants were 11 consecutive subjects presenting to the sleep center with clinical indications for nocturnal polysomnography and MWT. The interventions included MWT and OSLER test. Mean sleep latencies for the OSLER and MWT in each subject were closely correlated (ICC = 0.94, [Intra-class correlation]P < 0.05). Sleep latency by OSLER and simultaneous measurement of EEG also had excellent agreement (ICC = 0.91) with a bias of -0.97 min. The OSLER test is a practical and reliable tool for evaluating daytime sleepiness when compared with the MWT. No obvious systematic adaptation was seen during sequential OSLER test performance. Given its portability and minimal technical requirements, the OSLER test may be useful for large-scale applications in the evaluation of daytime wakefulness and vigilance.

Replicating adenoviral vectors are capable of multiplying up to a thousandfold in the target cell, a property that might prove to be of tremendous potential for cancer therapy. However, restricting viral replication and toxicity to cancer cells is essential to optimize safety. It has been proposed that modifications of the E1a protein that impair binding to Rb or p300 will prevent S-phase induction in normal cells, resulting in selective viral replication in tumor cells. However, it remains uncertain which of the several possible E1a modifications would be most effective at protecting normal cells without compromising the oncolytic effect of the vector. In this study, we have expressed several E1a-deletion mutants at high levels using the CMV promoter and tested them for their ability to facilitate S-phase induction, viral replication, and cytotoxicity in both normal and cancer cells. Deletion of the Rb-binding domain within E1a only slightly decreased the ability of the virus to induce S phase in growth-arrested cells. The effect of this deletion on viral replication and cytotoxicity was variable. There was reduced cytotoxicity in normal bronchial epithelial cells; however, in some normal cell types there was equal viral replication and cytotoxicity compared with wild type. Deletions in both the N-terminus and the Rb-binding domain were required to block S-phase induction effectively in growth-arrested normal cells; in addition, this virus demonstrated reduced viral replication and cytotoxicity in normal cells. An equally favorable replication and cytotoxicity profile was induced by a virus expressing E1a that is incapable of binding to the transcriptional adapter motif (TRAM) of p300. All viruses were equally cytotoxic to cancer cells compared with wild-type virus. In conclusion, deletion of the Rb-binding site alone within E1a may not be the most efficacious means of targeting viral replication and toxicity. However, deletion within the N-terminus in conjunction with a deletion within the Rb-binding domain, or deletion of the p300-TRAM binding domain, induces a more favorable cytotoxicity profile.

STUDY OBJECTIVES: Evaluate the utility of overnight monitoring limited to nasal cannula airflow and oximetry in the diagnosis of obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: Prospective randomized study, blinded analysis. SETTING: Sleep disorder center, academic institution. PARTICIPANTS: 56 patients with suspected OSAHS, 10 normal volunteers. MEASUREMENTS AND RESULTS: In-laboratory full nocturnal polysomnography (NPSG) and unattended ambulatory study with monitoring of only airflow and oximetry performed in randomized order. Obstructive respiratory events were scored on the full NPSG while visualizing all signals and then rescored on the full NPSG and on the ambulatory study while visualizing only airflow and oximetry signals. Respiratory disturbance indexes (RDI) for the limited studies (RDIFlowNPSG and RDIFlowAmbulatory) were calculated as the sum of the apneas and hypopneas (defined using airflow amplitude and O2 desaturation) divided by the valid flow-signal time. The reference RDIFullNPSG was calculated from the sum of the apneas and hypopneas (defined using flow amplitude, O2 desaturation and electroencephalographic arousal) identified on the full NPSG divided by the total sleep time. RDIFullNPSG was greater than RDIFlowNPSG (bias = 5.6 events per hour) and RDIFlowAmbulatory (bias = 10.9 events per hour), but the differences were mainly in subjects with an RDI > 40 events per hour. The diagnostic sensitivity and specificity for the diagnosis of OSAHS using a cutoff of 18 events per hour were 96% and 93% using the flow signal from the NPSG and 88% and 92% using the flow signal from the ambulatory study performed on a separate night. CONCLUSIONS: In subjects with OSAHS, analysis of the flow signal from a nasal cannula can provide an RDI similar to that obtained in a full NPSG.

Bowhead whales, Balaena mysticetus, migrate west during fall approximately 10-75 km off the north coast of Alaska, passing the petroleum developments around Prudhoe Bay. Oil production operations on an artificial island 5 km offshore create sounds heard by some whales. As part of an effort to assess whether migrating whales deflect farther offshore at times with high industrial noise, an acoustical approach was selected for localizing calling whales. The technique incorporated DIFAR (directional frequency and recording) sonobuoy techniques. An array of 11 DASARs (directional autonomous seafloor acoustic recorders) was built and installed with unit-to-unit separation of 5 km. When two or more DASARs detected the same call, the whale location was determined from the bearing intersections. This article describes the acoustic methods used to determine the locations of the calling bowhead whales and shows the types and precision of the data acquired. Calibration transmissions at GPS-measured times and locations provided measures of the individual DASAR clock drift and directional orientation. The standard error of the bearing measurements at distances of 3-4 km was approximately 1.35 degrees after corrections for gain imbalance in the two directional sensors. During 23 days in 2002, 10,587 bowhead calls were detected and 8383 were localized