Biomedical subjects
Publications and source records attributed to M H Sanders.
The use of continuous positive airway pressure (CPAP) in treating symptoms associated with OSAHS is reviewed. Although it is an imperfect intervention, it continues to evolve and improve in such a way that patients who would not have been able to use this treatment even in the recent past can benefit from it today.
Repair of cyclobutane pyrimidine dimers (CPDs) in cultured neonatal human fibroblasts and in Mus spretus x M. castaneus F1 neonatal skin fibroblasts was analyzed after UVC-irradiation by cleavage with T4 endonuclease V cyclopyrimidine dimer glycosylase, alkaline-agarose gel electrophoresis, and Southern blotting. The blots were sequentially probed with 32P-labeled Alu, or B2, to preferentially illuminate R-band DNA, by L1 to preferentially illuminate G-band DNA, and by satellite DNA to illuminate C-band DNA. These three different DNA populations showed slightly different global nucleotide excision repair rates that are in the order of speed, R-band DNA > G-band DNA > C-band DNA. Fibroblasts from out-bred neonatal mice and humans showed similar band-specific repair rate ratios and the global repair rate of murine fibroblasts was almost as rapid as that of the human fibroblasts. The mass distribution of the human Alu-probed signal was further analyzed. Gel mobility data was fitted to a logistic equation to include all M(r) values. Hypothetical distributions of DNA randomly cleaved to a particular number-average molecular weight were fit to the logistic gel mobility function to determine how such a randomly cleaved distribution of a particular cleavage frequency would be displayed along the experimental gel. This revealed a rapidly repaired kinetic fraction that represented 17% of the Alu-probed signal (R-band DNA), almost none of the L1 probed signal (G-band DNA), and reflects transcription coupled repair of active genes. The remaining Alu-probed DNA showed a random distribution of UVC-induced CPDs throughout all stages of global nucleotide excision repair. The Alu-probed CPDs disappeared with an excellent fit to first order kinetics and with a half-life of seven hours.
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Chiari Malformation (CM) encompasses several patterns of congenital or acquired cerebellar herniation through the foramen magnum. This may result in brain-stem compression that impacts control of breathing and is associated with obstructive and central apneas. A high clinical suspicion for sleep-disordered breathing is needed in the care of such patients after as well as before corrective surgery. To introduce a review of CM with a focus on the relevance to sleep medicine, we present a case of a 13-year-old female who was diagnosed with CM Type 1 in the course of an evaluation of symptomatic central sleep apnea. After initial improvement following surgery there was recurrence of brain-stem compression. The only clinical expression of which was polysomnographically evident recurrence of sleep apnea.
OBJECTIVES: To evaluate study failure and sensor loss in unattended home polysomnography and their relationship to age, gender, obesity, and severity of sleep-disordered breathing (SDB). DESIGN: A cross-sectional analysis of data gathered prospectively for the Sleep Heart Health Study (SHHS). SETTING: Unattended polysomnography was performed in participants' homes by the staff of the sites that are involved in SHHS. PARTICIPANTS: 6,802 individuals who met the inclusion criteria (age >40 years, no history of treatment of sleep apnea, no tracheostomy, no current home oxygen therapy) for SHHS. RESULTS: A total of 6802 participants had 7151 studies performed. 6161 of 6802 initial studies (90.6%) were acceptable. Obesity was associated with a decreased likelihood of a successful initial study. After one or more attempts, 6440 participants (94.7%) had studies that were judged as acceptable. The mean duration of scorable signals for specific channels ranged from 5.7 to 6.8 hours. The magnitudes of the effects of age, gender, BMI, and RDI on specific signal durations were not clinically significant. CONCLUSION: Unattended home PSG as performed for SHHS was usually successful. Participant characteristics had very weak associations with duration of scorable signal. This study suggests that unattended home PSG, when performed with proper protocols and quality controls, has reasonable success rates and signal quality for the evaluation of SDB in clinical and research settings.
Varying approaches to measuring the respiratory disturbance index (RDI) may lead to discrepant estimates of the severity of sleep-disordered breathing (SDB). In this study, we assessed the impact of varying the use of corroborative data (presence and degree of desaturation and/or arousal) to identify hypopneas and apneas. The relationships among 10 RDIs defined by various definitions of apneas and hypopneas were assessed in 5,046 participants in the Sleep Heart Health Study (SHHS) who underwent overnight unattended 12-channel polysomnography (PSG). The magnitude of the median RDI varied 10-fold (i.e., 29.3 when the RDI was based on events identified on the basis of flow or volume amplitude criteria alone to 2.0 for an RDI that required an associated 5% desaturation with events). The correlation between RDIs based on different definitions ranged from 0.99 to 0.68. The highest correlations were among RDIs that required apneas and hypopneas to be associated with some level of desaturation. Lower correlations were observed between RDIs that required desaturation as compared with RDIs defined on the basis of amplitude criteria alone or associated arousal. These data suggest that different approaches for measuring the RDI may contribute to substantial variability in identification and classification of the disorder.
We compared noninvasive positive-pressure ventilation (NPPV), using bilevel positive airway pressure, with usual medical care (UMC) in the therapy of patients with acute respiratory failure (ARF) in a prospective, randomized trial. Patients were subgrouped according to the disease leading to ARF (chronic obstructive pulmonary disease [COPD], a non-COPD-related pulmonary process, neuromuscular disease, and status postextubation), and were then randomized to NPPV or UMC. Thirty-two patients were evaluated in the NPPV group and 29 in the UMC group. The rate of endotracheal intubation (ETI) was significantly lower in the NPPV than in the UMC group (6.38 intubations versus 21.25 intubations per 100 ICU days, p = 0.002). Mortality rates in the intensive care unit (ICU) were similar for the two treatment groups (2.39 deaths versus 4.27 deaths per 100 ICU days, p = 0.21, NPPV versus UMC, respectively). Patients with hypoxemic ARF in the NPPV group had a significantly lower ETI rate than those in the UMC group (7.46 intubations versus 22.64 intubations per 100 ICU days, p = 0.026); a similar trend was noted for patients with hypercapnic ARF (5.41 intubations versus 18.52 intubations per 100 ICU days, p = 0.064, NPPV versus UMC, respectively). Patients with ARF in the non-COPD category had a lower rate of ETI with NPPV than with UMC (8.45 intubations versus 30.30 intubations per 100 ICU days, p = 0.01). Although the rate of ETI was lower among COPD patients receiving NPPV, this trend did not reach statistical significance (5.26 intubations versus 15.63 intubations per 100 ICU days, p = 0.12, NPPV versus UMC, respectively). In conclusion, NPPV with bilevel positive airway pressure reduces the rate of ETI in patients with ARF of various etiologies.
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This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.
Positive airway pressure in the treatment of obstructive sleep-disordered breathing (OSDB) is reviewed. Continuous positive airway pressure (CPAP), bilevel positive airway pressure, and variable (auto-CPAP) pressure, their mechanisms of action, benefits, and complications are examined. A perspective on the future of positive airway pressure therapy for OSDB is provided.
We examined the effect of split-night polysomnography on compliance with positive pressure via a mask for the treatment of obstructive sleep-disordered breathing. A comparison of objective compliance (hours/day) at the first meter read from the positive-pressure device (4-6 weeks after set-up) in patients who had a successful split-night positive-pressure titration vs. patients who had traditional full-night positive-pressure titration was performed. Patients were matched for age, sex, and severity of the obstructive sleep-disordered breathing. Twelve patients were matched with controls who underwent full-night polysomnography. There were no significant differences between the split-night patients and the full-night patients with regard to age, sex, body mass index, and pretreatment Epworth Sleepiness Score. In addition, there was no significant difference between apnea-hypopnea index and the desaturation-event frequency for both groups pre- and post-treatment. The average daily use of continuous positive airway pressure (CPAP) at the time of the first meter reading in the group that underwent full-night positive-pressure titrations as opposed to split-night titrations was 5.2 hours/day +/- 2.2 vs. 3.8 hours/day +/- 2.9, respectively (p = 0.29). The Epworth Sleepiness Scale on the initial clinic visit (as an index of patient-perceived impairment) did not predict compliance at 4-6 weeks. The time at the final positive pressure did not correlate with compliance. Acceptance of positive pressure in the split-night patients ranged from 62 to 67%.
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Chronic alveolar hypoventilation may present in an insidious fashion with nonspecific manifestations. The clinician should be aware of the potential for developing this condition in patients with certain thoracic and systemic diseases. Once chronic alveolar hypoventilation is confirmed with arterial blood gas analysis, a systematic evaluation can often point to the underlying etiology. As sleep in affected individuals is often associated with marked worsening of gas exchange and may also contribute to worsening daytime cardiopulmonary dysfunction, polysomnography is often indicated to determine the severity of nocturnal aberrations and to look for coexistent obstructive sleep apnea. Therapy of chronic alveolar hypoventilation often focuses on elimination of the nocturnal deterioration in gas exchange, and recent applications of noninvasive positive pressure ventilation during sleep have proven useful in the management of individuals with obesity-hypoventilation syndrome, restrictive thoracic disorders, neuromuscular diseases and central causes for hypoventilation. It is unclear whether wide-spread application of nocturnal ventilatory support to patients with chronic ventilatory failure due to chronic obstructive pulmonary disease is of long-term benefit.
Factors that determine a successful outcome following uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea (OSA) are not well defined. This study was undertaken to determine if prior tonsillectomy is predictive of a lower response rate to UPPP. A retrospective review of a cohort undergoing UPPP alone or in combination with nasal septoplasty for OSA was undertaken. Preoperative and postoperative polysomnograms were obtained to evaluate the severity of the OSA. The sample was a consecutive series of 79 patients with OSA. Clinical evaluation was performed by both an otolaryngologist and a pulmonologist. Surgical treatment in this group of 79 patients included 52 UPPP and 27 UPPP in patients with prior tonsillectomy. Concurrent septoplasty was undertaken in 17 patients. Criteria for outcome were based on comparison of preoperative and postoperative polysomnograms (i.e., apnea index, respiratory disturbance index change, and lowest saturation). A response to therapy was defined as a reduction in apnea index greater than 50%. A success was defined as apnea index less than 5, reduction of respiratory disturbance index greater than 50%, and nadir saturation greater than 82%. In 79 patients with OSA, 78% responded and 37% reflected therapeutic successes. Patients with history of prior tonsillectomy were less likely to have therapeutic improvement following UPPP. In 52 patients without previous tonsillectomy, 88% responded and 52% had a successful outcome. Of those with previous tonsillectomy, 59% responded and 7% had a successful outcome. The status of previous tonsillectomy is an important prognostic indicator in the success of UPPP for the treatment of OSA. We speculate that the presence of palatine tonsils allows the removal of an extra measure of oropharyngeal tissue, thereby improving the likelihood of success for UPPP.
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STUDY OBJECTIVE: Although it is intuitively desirable, the measurement of arterial carbon dioxide tension (PaCO2) during diagnostic polysomnography and nocturnal trials of positive pressure therapy is invasive and potentially expensive. The accuracy of end-tidal carbon dioxide tension (PETCO2) and transcutaneous carbon dioxide (tcPCO2) monitoring in these contexts has not been systematically evaluated. This investigation was undertaken to evaluate the accuracy of PETCO2 and tcPCO2 in patients undergoing polysomnography. METHODS AND PROCEDURES: Values of PETCO2 were compared with PaCO2 in 19 patients spontaneously breathing room air (condition 1), in 13 patients receiving supplemental oxygen via nasal cannula (condition 2), and in 22 patients receiving nocturnal positive pressure ventilatory assistance (all but one with continuous positive airway pressure or bilevel positive airway pressure) (condition 3). The accuracy of tcPCO2 monitoring during sleep was also examined by comparing tcPCO2 values with simultaneously recorded PaCO2 values obtained during sleep in patients undergoing nocturnal polysomnography. Data were collected using three commercially available brands of tcPCO2 monitors (capnograph R, n = 17 patients; capnograph S, n = 17; and capnograph N, n = 15). RESULTS: Accuracy of PETCO2--There was significant scatter in the PaCO2 vs PETCO2 relationship such that only 23 percent of the variability in PaCO2 was explained by variation of PETCO2 during condition 1 and only 15 percent and 20 percent of the variability in PaCO2 was explained by variation of PETCO2 during conditions 2 and 3, respectively. 21.3 percent of patients had average PETCO2 values in error by > 10 mm Hg during condition 1, while during conditions 2 and 3, 46.2 and 63.7 percent of patients had average values in error by > 10 mm Hg, respectively. Accuracy of tcPCO2--While capnographs S and N generally overestimated PaCO2 with a wide scatter, capnograph R tended to have offsetting overestimations and underestimations of PaCO2 with a wide scatter. With each capnograph, a relatively small portion of the variability of the PaCO2 was explained by variability of the tcPCO2 (r2 = 0.2, 0.45 and 0.64 for capnographs S, N, and R, respectively). Across the three capnographs, 43.1 to 66.7 percent of measurements were in error by > 10 mm Hg, and 5 to 20 percent of measurements reflected errors > 20 mm Hg. There was no consistent relationship between the tcPCO2 error and the level of PaCO2, nor was the tcPCO2 error consistent in individual patients. There was no relationship between tcPCO2 accuracy and body mass index. CONCLUSION: Neither PETCO2, measured within a face mask, nor tcPCO2 is a consistently accurate reflection of PaCO2. This limits the utility of these variables in monitoring patients during diagnostic and therapeutic sleep studies, and in particular, during trials of nocturnal ventilatory assistance where adequate levels of support are to be established and unacceptable hyperventilation and respiratory alkalosis must be recognized.
STUDY OBJECTIVE: To determine the effectiveness of oronasal masks for positive pressure therapy in alleviating obstructive sleep apnea (OSA). METHODS AND PROCEDURES: Polysomnographic records of all 245 patients with OSA who underwent therapeutic trials of either continuous positive airway pressure (CPAP) or bilevel positive airway pressure between January 1991 and December 1992 were reviewed. Thirty patients who had been prescribed positive pressure therapy employing an oronasal mask were identified. Two patients known to be successfully treated with CPAP via oronasal mask underwent repeat polysomnography. The initial portion of the study was a diagnostic evaluation during which the patients were untreated. During the second portion of the study, both patients used CPAP via an oronasal mask while wearing a mouthpiece designed to maintain oral patency. RESULTS: The 30 patients with OSA who were identified in this study had significant amelioration of OSA while receiving positive pressure therapy via oronasal mask compared with the baseline, diagnostic polysomnogram (apnea index: 55.3 +/- 36.9-->1.6 +/- 3.7, p < 0.001; hypopnea index: 21.2 +/- 20-->2.7 +/- 4.9, p < 0.001; nadir of SaO2: 72.5 +/- 13.9-->87.1 +/- 4.3, p < 0.001, mean +/- SD). Improvement of OSA did not depend on maintenance of a closed mouth, as evidenced by elimination of sleep-disordered breathing in the two patients receiving positive pressure via oronasal mask while wearing a mouthpiece to keep the mouth open. CONCLUSION: Oronasal masks are a viable alternative interface for alleviating OSA with positive pressure therapy in those patients who are unwilling or unable to tolerate conventional nasal interfaces. Although there were no adverse consequences associated with the use of oronasal masks in our patients, appropriate safety precautions should be taken to minimize the possibility of aspiration of gastric contents and avoid untoward sequelae due to positive pressure device failure.
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