David M. Claman

A bifunctional thymidylate synthetase-dihydrofolate reductase in protozoa

Thymidylate synthetase and dihydrofolate reductase exist as a bifunctional protein in a number of species of protozoa which span diverse groups of the subkingdom. The enzymes copurify upon gel filtration and on affinity chromatography columns specific for dihydrofolate reductase. The bifunctional protein has been found in species of Crithidia, Leishmania, Trypanosoma, Plasmodium, Eimeria, Tetrahymena and Euglena. For reasons unknown, neither enzyme could be detected in Entamoeba histolytica or E. invadens. Since neither enzyme has yet been found as a separate protein in protozoa, it is likely that the bifunctional protein is widespread among these primitive eukaryotes. In most cases, the apparent size of the native protein is approximately twice that of the subunit possessing thymidylate synthetase. Further, with one exception, the subunit sizes are close to the sum of the subunit sizes of the separate enzymes found in other sources.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS®; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty‐one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single‐arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea–hypopnea index, from in‐laboratory polysomnogram) and sleep‐related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea–hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h−1) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device‐related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Disturbed sleep among COPD patients is longitudinally associated with mortality and adverse COPD outcomes

OBJECTIVE To investigate the cross-sectional association between COPD severity and disturbed sleep and the longitudinal association between disturbed sleep and poor health outcomes. METHODS Ninety eight adults with spirometrically-confirmed COPD were recruited through population-based, random-digit telephone dialing. Sleep disturbance was evaluated using a 4-item scale assessing insomnia symptoms as: difficulty falling asleep, nocturnal awakening, morning tiredness, and sleep duration adequacy. COPD severity was quantified by: FEV(1) and COPD Severity Score, which incorporates COPD symptoms, requirement for COPD medications and oxygen, and hospital-based utilization. Subjects were assessed one year after baseline to determine longitudinal COPD exacerbations and emergency utilization and were followed for a median 2.4 years to assess all-cause mortality. RESULTS Sleep disturbance was cross-sectionally associated with cough, dyspnea, and COPD Severity Score, but not FEV(1). In multivariable logistic regression, controlling for sociodemographics and body-mass index, sleep disturbance longitudinally predicted both incident COPD exacerbations (OR=4.7; p=0.018) and respiratory-related emergency utilization (OR=11.5; p=0.004). In Cox proportional hazards analysis, controlling for the same covariates, sleep disturbance predicted poorer survival (HR=5.0; p=0.013). For all outcomes, these relationships persisted after also controlling for baseline FEV(1) and COPD Severity Score. CONCLUSIONS Disturbed sleep is cross-sectionally associated with worse COPD and is longitudinally predictive of COPD exacerbations, emergency health care utilization, and mortality.

Use of Selective Serotonin Reuptake Inhibitors and Sleep Disturbances in Community-Dwelling Older Women

OBJECTIVES: To determine the association between use of selective serotonin reuptake inhibitors (SSRIs) and objective measures of sleep disturbances in older community‐dwelling women, including women without evidence of depression.

HIV infection is associated with diffusing capacity impairment in women

Abstract:Respiratory dysfunction is common with HIV infection, but few studies have directly assessed whether HIV remains an independent risk factor for pulmonary function abnormalities in the antiretroviral therapy era. Additionally, few studies have focused on pulmonary outcomes in HIV+ women. We tested associations between risk factors for respiratory dysfunction and pulmonary outcomes in 63 HIV+ and 36 HIV-uninfected women enrolled in the Womens Interagency HIV Study. Diffusing capacity (DLCO) was significantly lower in HIV+ women (65.5% predicted vs. 72.7% predicted, P = 0.01), and self-reported dyspnea in HIV+ participants was associated with both DLCO impairment and airflow obstruction. Providers should be aware that DLCO impairment is common in HIV infection, and that either DLCO impairment or airflow obstruction may cause respiratory symptoms in this population.

Clinical Validation of the Bedbugg™ in Detection of Obstructive Sleep Apnea

OBJECTIVE: To validate the accuracy of the Bedbugg™, a new home monitoring device for diagnosis of obstructive sleep apnea. STUDY DESIGN AND SETTING: Simultaneous sleep monitoring was performed by formal polysomnography and by Bedbugg. Monitoring was performed in a university sleep center in 42 subjects who had previously been scheduled for polysomnography. RESULTS: The correlation for the apnea-hypopnea index (AHI) between polysomnography and Bedbugg was r = 0.96. The sensitivity of Bedbugg for detecting an AHI > 15 was 85.7%. The specificity of Bedbugg for detecting an AHI < 15 was 95.2%. CONCLUSION: The Bedbugg device provides an accurate assessment of the apnea-hypopnea index. SIGNIFICANCE: Accurate home monitoring for sleep apnea may provide access to care for a higher proportion of undiagnosed sleep apnea patients.

Periodic leg movements are associated with reduced sleep quality in older men: the MrOS Sleep Study.

STUDY OBJECTIVES Periodic limb movements in sleep (PLMS) are common in the elderly. A previous large polysomnographic (PSG) study examining the relationship of PLMS to sleep architecture and arousals from sleep in women found that leg movements were common in elderly women, and PLMS which were associated with EEG arousals had a strong and consistent association with markers of disturbed sleep. Since sleep differs in men and women, we now investigate the association between PLMS and PSG indices of sleep quality in a large community-based sample of older men. DESIGN Observational study, cross-sectional analyses. SETTING Six clinical sites participating in the Osteoporotic Fractures in Men (MrOS) Study. PARTICIPANTS 2,872 older community-dwelling men (mean age 76.4 years) who completed in-home PSG from 2003-2005. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS In-home PSG was performed which included bilateral measurement of leg movements. The total number of leg movements per hour of sleep (PLMI) and the number of leg movements causing EEG-documented arousals per hour of sleep (PLMA) were computed. A PLMI ≥ 5 (70.8%) and PLMA ≥ 5 (27.4%) were both prevalent. Linear regression models were used to examine the relationship between PLMS as predictors and sleep architecture, arousal index, and sleep efficiency as outcomes. The highest quintiles of PLMI (≥ 65.1) and PLMA (≥ 6.8) showed the largest association with indices of sleep architecture; PLMA showed a larger magnitude of effect. After multivariate adjustment, participants with a higher PLMA had a small but significantly higher arousal index, lower sleep efficiency, higher percentages of stages 1 and 2 sleep, and lower percentages of stage 3-4 and REM sleep (p < 0.01). An increased PLMI was similarly associated with a higher arousal index, higher percentage of stage 2 sleep, and lower percentage of stage 3-4 (p < 0.0001), but not with an increase in stage 1, REM sleep, or sleep efficiency. Neither PLMI nor PMLA was associated with subjective sleepiness measured by the Epworth Sleepiness Scale. CONCLUSIONS This study demonstrated that periodic leg movements are very common in older community-dwelling men and regardless of associated arousals, are associated with evidence of lighter and more fragmented sleep.

HYPOTHERMIA FROM PROLONGED IMMERSION: BIOPHYSICAL PARAMETERS OF A SURVIVOR

We report a case of survival following prolonged immersion and hypothermia. The patient survived for over 9 h in open water, after his vessel capsized and sank in the Pacific Ocean off the coast of Northern California. Water temperature on the day of the sinking was 14.4 degrees C (58.0 degrees F). Although he did have adequate flotation, the patient did not wear a survival suit. On initial physical examination in the Emergency Department (ED), the patients rectal temperature was 30.0 degrees C (86.0 degrees F). With active rewarming, his temperature returned to normal (37.0 degrees C (98.6 degrees F)) within 5 h. Body fat of the patient was 19.6%, near the 50th percentile for his age (19.0%). Surface/volume ratio of the patient (.0228 m(2)/L) was 19% smaller than a predicted average (.0282 m(2)/L). We believe that the patients large body habitus contributed to survival and that surface/volume ratio was likely the biophysical variable most closely associated with decreased cooling.

INCREASING SLEEP DURATION IS ASSOCIATED WITH GEOGRAPHIC ATROPHY AND AGE-RELATED MACULAR DEGENERATION.

Purpose: Sleeping too much or too little has been associated with adverse health outcomes including total mortality, cardiovascular disease, Type 2 diabetes, and hypertension. This study explored the relationship between sleep patterns and age-related macular degeneration (AMD). Methods: One thousand and three consecutive patients in a retina practice were prospectively surveyed regarding sleep histories. Each patient then had a masked ophthalmic examination and was graded on the modified Wisconsin Age-Related Maculopathy System. The relationship between AMD grade and sleep hours was analyzed in a logistic regression model. Multivariable analysis was performed after adjustment for age, gender, and smoking history. Results: In multivariable analysis, controlling for age, gender, and smoking history, sleep hours are not associated with neovascular AMD (P = 0.97) but are associated with geographic atrophy (P = 0.02). Sleeping >8 hours is associated with geographic atrophy (age-adjusted odds ratio, 7.09; 95% confidence interval, 1.59–31.6) compared with patients without AMD. Conclusion: Longer sleep duration is associated with geographic atrophy secondary to AMD. These altered sleep patterns may be another morbidity of AMD, but further study is necessary.

The Patient With Suspected Obstructive Sleep Apnea Guidelines for Perioperative Management and ICU Care

Obstructive sleep apnea is a commonly encountered problem in the perioperative period. In this article, guidelines are proposed to help physicians identify at-risk patients preoperatively and to guide subsequent intraoperative and postoperative monitoring and management.