Effects of moderate alcohol consumption and hypobaric hypoxia: implications for passengers' sleep, oxygen saturation and heart rate on long-haul flights.

BACKGROUND: Passengers on long-haul flights frequently consume alcohol. Inflight sleep exacerbates the fall in blood oxygen saturation (SpO2) caused by the decreased oxygen partial pressure in the cabin. We investigated the combined influence of alcohol and hypobaric hypoxia on sleep, SpO2 and heart rate. METHODS: Two groups of healthy individuals spent either two nights with a 4-hour sleep opportunity (00:00-04:00 hours) in the sleep laboratory (n=23; 53 m above sea level) or in the altitude chamber (n=17; 753 hPa corresponding to 2438 m above sea level, hypobaric condition). Participants consumed alcohol before one of the nights (mean±SE blood alcohol concentration 0.043±0.003%). The order of the nights was counterbalanced. Two 8-hour recovery nights (23:00-07:00 hours) were scheduled between conditions. Polysomnography, SpO2 and heart rate were recorded. RESULTS: The combined exposure to alcohol and hypobaric condition decreased SpO2 to a median (25th/75th percentile) of 85.32% (82.86/85.93) and increased heart rate to a median (25th/75th percentile) of 87.73 bpm (85.89/93.86) during sleep compared with 88.07% (86.50/88.49) and 72.90 bpm (70.90/78.17), respectively, in the non-alcohol hypobaric condition, 94.97% (94.59/95.33) and 76.97 bpm (65.17/79.52), respectively, in the alcohol condition and 95.88% (95.72/96.36) and 63.74 bpm (55.55/70.98), respectively, in the non-alcohol condition of the sleep laboratory group (all p<0.0001). Under the combined exposure SpO2 was 201.18 min (188.08/214.42) below the clinical hypoxia threshold of 90% SpO2 compared with 173.28 min (133.25/199.03) in the hypobaric condition and 0 min (0/0) in both sleep laboratory conditions. Deep sleep (N3) was reduced to 46.50 min (39.00/57.00) under the combined exposure compared with both sleep laboratory conditions (alcohol: 84.00 min (62.25/92.75); non-alcohol: 67.50 min (58.50/87.75); both p<0.003). CONCLUSIONS: The combination of alcohol and inflight hypobaric hypoxia reduced sleep quality, challenged the cardiovascular system and led to extended duration of hypoxaemia (SpO2 <90%).

Ribavirin treatment of acute and chronic hepatitis E: a single-centre experience.

BACKGROUND: The role of ribavirin for treatment of severe acute or chronic hepatitis E virus (HEV) infection is not well defined. AIMS: To investigate the applicability and efficacy of ribavirin therapy in acute and chronic HEV infections within a large single-centre cohort. MATERIALS & METHODS: Clinical courses of forty-four German HEV-infected individuals were analysed. RESULTS: In a prospective case series, we observed spontaneous recovery from acute symptomatic HEV-infection in 10/11 immunocompetent individuals. Ribavirin therapy was initiated in one patient with severe acute HEV-genotype-1e infection who rapidly improved liver function and cleared HEV. Of 15 organ transplant recipients with prolonged HEV viraemia, reduction in immunosuppression led to HEV-clearance in three patients, while ribavirin therapy was initiated in 11 subjects. A rapid response with undetectable HEV-RNA occurred in nine subjects. One patient died after experiencing a virological breakthrough associated with ribavirin dose reduction because of severe anaemia. DISCUSSION: Ribavirin is a safe treatment option for HEV infections. However, the optimal dose of ribavirin for the treatment of chronic hepatitis E remains to be determined as treatment failure may occur.

The effect of sudden depressurization on pilots at cruising altitude.

The standard flight level for commercial airliners is ∼12 km (40 kft; air pressure: ∼ 200 hPa), the maximum certification altitude of modern airliners may be as high as 43-45 kft. Loss of structural integrity of an airplane may result in sudden depressurization of the cabin potentially leading to hypoxia with loss of consciousness of the pilots. Specialized breathing masks supply the pilots with oxygen. The aim of this study was to experimentally simulate such sudden depressurization to maximum design altitude in a pressure chamber while measuring the arterial and brain oxygenation saturation (SaO(2) and StO(2)) of the pilots. Ten healthy subjects with a median age of 50 (range 29-70) years were placed in a pressure chamber, breathing air from a cockpit mask. Pressure was reduced from 753 to 148 hPa within 20 s, and the test mask was switched to pure O(2) within 2 s after initiation of depressurization. During the whole procedure SaO(2) and StO(2) were measured by pulse oximetry, respectively near-infrared spectroscopy (NIRS; in-house built prototype) of the left frontal cortex. During the depressurization the SaO(2) dropped from median 93% (range 91-98%) to 78% (62-92%) by 16% (6-30%), while StO(2) decreased from 62% (47-67%) to 57% (43-62%) by 5% (3-14%). Considerable drops in oxygenation were observed during sudden depressurization. The inter-subject variability was high, for SaO(2) depending on the subjects' ability to preoxygenate before the depressurization. The drop in StO(2) was lower than the one in SaO(2) maybe due to compensation in blood flow.

Sleep-Induced Hypoxia under Flight Conditions: Implications and Countermeasures for Long-Haul Flight Crews and Passengers.

PURPOSE: Recuperation during sleep on board of commercial long-haul flights is a safety issue of utmost importance for flight crews working extended duty periods. We intended to explore how sleep and blood oxygenation (in wake versus sleep) are affected by the conditions in an airliner at cruising altitude. METHODS: Healthy participants' sleep was compared between 4-h sleep opportunities in the sleep laboratory (n = 23; sleep lab, ie, 53 m above sea level) and in an altitude chamber (n = 20; flight level, ie, 753 hPa, corresponding to 2438 m above sea level). A subgroup of 12 participants underwent three additional conditions in the altitude chamber: 1) 4-h sleep at ground level, 2) 4-h sleep at flight level with oxygen partial pressure equivalent to ground level, 3) 4-h monitored wakefulness at flight level. Sleep structure and blood oxygenation were analysed with mixed ANOVAs. RESULTS: Total sleep time at flight level compared to in the sleep laboratory was shorter (Δ mean ± standard error -11.1 ± 4.2 min) and included less N3 sleep (Δ -17.6 ± 5.4 min), while blood oxygenation was decreased. Participants spent 69.7% (± 8.3%) of the sleep period time but only 13.2% (± 3.0%) of monitored wakefulness in a hypoxic state (<90% oxygen saturation). Oxygen enrichment of the chamber prevented oxygen desaturation. CONCLUSION: Sleep - but not wakefulness - under flight conditions induces hypobaric hypoxia which may contribute to impaired sleep. The results caution against the assumption of equivalent crew recovery in-flight and on the ground but hold promise for oxygen enrichment as a countermeasure. The present results have implications for flight safety and possible long-term consequences for health in crews.

Effects of nocturnal aircraft noise on cognitive performance in the following morning: dose-response relationships in laboratory and field.

OBJECTIVE: Nocturnal aircraft noise disturbs sleep and impairs recuperation. We investigated in laboratory and field studies whether noise-induced sleep fragmentation is associated with performance impairments in a psychomotor vigilance task (PVT) and a memory search task. METHODS: In the laboratory, 112 participants were exposed to aircraft noise during 9 consecutive nights. In the field, 64 participants were examined during 9 consecutive nights in the vicinity of Cologne/Bonn airport. Reaction time, signal detection performance and subjective task load were recorded. RESULTS: Dose-response relationships showed significant, linear impairments in reaction times. In the laboratory, reaction time in PVT increased with 0.13 ms/dB equivalent noise level (LAeq) plus 0.02 ms/noise event. In the field study, reaction time increased with 0.3 ms/dB LAeq. Participants worked significantly less accurate after nocturnal noise exposure. CONCLUSION: Influences of LAeq and number of noise events on daytime performance were small but consistent and significant, stressing the potential public health impact of nocturnal noise exposure.

Prevalence of parvovirus B19 and human bocavirus DNA in the heart of patients with no evidence of dilated cardiomyopathy or myocarditis.

BACKGROUND: Although the DNA of parvovirus B19 (B19V) is frequently detected in patients with dilated cardiomyopathy or myocarditis, whether the parvovirus causes disease is questionable, since even in healthy individuals the virus persists in various tissues. The same question applies to human bocavirus (HBoV). We have determined the prevalence and quantity of B19V and HBoV DNA in heart tissue of patients who were not experiencing virus-related heart diseases and analyzed whether the seroprevalence corresponded to DNA prevalence in the heart. METHODS: Samples of left-atrium heart tissue and serum were obtained from 100 patients who underwent open-heart surgery. Serum immunoglobulin (Ig) G and IgM against proteins encoded by B19V and HBoV were detected by enzyme-linked immunoabsorption assay and immunoblotting. B19V and HBoV DNA concentrations were determined by quantitative real-time polymerase chain reaction (PCR) in heart tissue and serum samples. Nested PCRs for VP1, K71, and GT3 identified the B19V genotypes. RESULTS: The prevalences of serum IgG specific for B19V and HBoV were 85% and 96%, respectively. Of all the patients, 85% had B19V DNA detected in heart tissues, and 4% displayed low-level B19V viremia, whereas only 5% of heart tissue samples and none of the serum samples demonstrated HBoV DNA. The sensitivity of B19V serological testing for B19V DNA in heart samples was 0.96 (95% confidence interval, 0.92-1.0). Specificity was 0.8 (95% confidence interval, 0.6-1.0), and the positive predictive value was 0.96 (95% confidence interval, 0.92-1.0). B19V genotypes 1 and 2 were present in 11% and 89% of heart tissues samples, respectively. B19V genotype 3 was not detected in any of the samples. CONCLUSIONS: Our data suggest that B19V but not HBoV demonstrates a lifelong persistence in the heart. The detection of B19V DNA in heart tissue showed no correlation with clinical symptoms. We strongly recommend that serological testing become a standardized procedure for future studies, to obtain representative data concerning the prevalence of B19V in the heart.

Performance impairment during four days partial sleep deprivation compared with the acute effects of alcohol and hypoxia.

OBJECTIVE: Subjects were exposed to cumulated partial sleep deprivation (psd), alcohol intake and hypoxia in a sequential design to examine the impact on neurobehavioral performance. METHODS: Sixteen healthy male volunteers were enrolled in this study and were exposed in turn, after adaptation and baseline measurements, to one day of periods of hypoxia, one day of alcohol intake and one day for recovering (with 8h time in bed TIB). Subsequently the exposition of those conditions is that the subjects spent 5h night restriction daily for four consecutive days, followed by two recovery days. Performance was tested five (or six) times per day with reaction time task (SRT) and unstable tracking task (UTT). RESULTS: The performance impairment showed to be cumulative in both tests over the four sleep deprivation days and differed significantly from baseline. Corresponding performance deficits under the influence of the stressors were for SRT: four days psd, 13% O(2) concentration and a blood alcohol concentration (BAC) of around 0.4-0.6 per thousand for UTT: four days psd, 13% O(2) concentration and a BAC of around 0.6 per thousand. One night of 8h sleep restored performance nearly to baseline level. CONCLUSIONS: A sleeping time of 5h per night for four consecutive days impairs performance in such a way that traffic safety may be compromised.

Lack of association of genetic variants in the LRP8 gene with familial and sporadic myocardial infarction.

Coronary artery disease (CAD) and myocardial infarction (MI) have a genetic basis, but the precise genetic underpinning remains controversial. Recently, an association of the LRP8 R952Q polymorphism (rs5174) with familial premature CAD/MI was reported. We analysed rs5174 (or the perfect proxy rs5177) in 1,210 patients with familial MI and 1,015 controls from the German MI Family study, in 1,926 familial CAD (1,377 with MI) patients and 2,938 controls from the Wellcome Trust Case Control Consortium (WTCCC) MI/CAD cohort, in 346 CAD patients and 351 controls from the AtheroGene study and in 295 men with incident CAD and 301 controls from the Prospective Epidemiological Study of MI study and found no evidence for association in any of the populations studied. In the WTCCC and the German MI Family studies, additional single-nucleotide polymorphisms in the LRP8 gene were analysed and displayed no evidence for association either.

Hepatitis E Seroprevalence and Genotyping in a Cohort of Wild Boars in Southern Germany and Eastern Alsace.

In the last few years it has been realized that the hepatitis E virus (HEV) is endemic in most industrialized countries and that it is a zoonotic disease. Potential reservoirs for HEV have been identified to be wild boars and deers, but HEV has also been found in domestic pigs and other animals. Due to the probable spread of the virus via contaminated food or contact to infected animals, HEV antibodies are present in more than 16% of the German adult population and rates are increasing with age. We collected blood from 104 wild boars in southern Germany and the border region of Alsace. We found an anti-HEV seroprevalence of 11.5% in our cohort, using ELISA. Furthermore, we observed active infection in 3.85% of the animals by positive HEV PCR in the sera of the boars. In our cohort, no regional differences of seroprevalence or active infection were seen. Sequencing revealed rather close homology of some detected HEV sequences to genotypes isolated from patients in Germany. Hence wild boars are a potential source of HEV infection in Middle Europe and the rate of infectious animals is quite high.

ABC A-subclass proteins: gatekeepers of cellular phospho- and sphingolipid transport.

During the past years, available evidence suggests that members of a novel family of structurally highly related multispan proteins, designated ABC A-subclass transporters, exert critical functions in the control of cellular lipid transport processes. Loss-of-function scenarios, thus far, have revealed pivotal roles of individual ABC A-transporters in specialized lipid secretory pathways of the cell including HDL biogenesis (ABCA1), lung surfactant production (ABCA3), retinal integrity (ABCA4/ABCR) and skin lipid barrier formation (ABCA12). Although the specific transporter activities of many members of this novel protein family have not yet been established in detail, available evidence indicates that ABC A-subclass transporters function as key components of highly specialized cellular phospho- and sphingolipid export machineries in major physiologic systems.

Chronobiotic effects of the melatonin agonist LY 156735 following a simulated 9h time shift: results of a placebo-controlled trial.

INTRODUCTION: The melatonin agonist LY 156735 (LY) is a new investigational drug under development to treat circadian rhythm disorders. The present study assessed the efficacy of LY to alleviate the symptoms of shift lag and to enhance readaptation of desynchronized circadian rhythms to a new time zone. SUBJECTS AND METHODS: Eight healthy male volunteers of age 25-35 yr participated in three identical trials of 13d duration in a temporal isolation unit separated by washout intervals. A high dose (HD) of 5 mg and a low dose (LD) of 0.5 mg of LY and placebo (PL) were administered double-blinded in a three-period cross-over design. Each trial consisted of an adaptation period, a pre-shift period for baseline measurements, a simulated 9h phase-advance shift, and a post-shift period for follow-up. The time shift was performed at 23:00h of day 6 by advancing the laboratory time to 08:00h of day 7. Double-blind study medication was administered at 14:30h on day 6, and at 22:30h on days 7-10. Subjective ratings of jet lag, alertness, tenseness, and daytime fatigue were assessed using visual analog scales (VAS) and standardized questionnaires. The objective markers of readaptation included core body temperature, wrist actigraphy, cortisol and electrolyte excretion, and a battery of computerized performance tests. RESULTS: HD but not LD enhanced the readaptation speed of all physiological rhythms investigated, as demonstrated by a significantly faster movement of acrophases towards the post-shift target time. HD (p = 0.05) significantly blunted the post-shift deterioration of performance in those tests that were sensitive to shift lag. Parameters of subjective well-being were not significantly affected by either dose. CONCLUSION: This pilot study demonstrates the chronobiotic efficacy of LY when taken at a dose of 5 mg/d.

Chronic hepatitis E virus infection in a patient with leukemia and elevated transaminases: a case report.

INTRODUCTION: Acute hepatitis E virus infection may cause mild, self-limiting hepatitis, either as epidemic outbreaks or sporadic cases, the latter of which have been reported in industrialized countries. Chronic infections are uncommon and have been reported in immunosuppressed patients, patients with human immunodeficiency virus infection, and patients with hematological malignancies. CASE PRESENTATION: A 46-year-old Caucasian man was admitted to the gastroenterology clinic with a history of increasing transaminases, persistent exhaustion, and occasional right-side abdominal pain over the course of a 6-month period. B-cell chronic lymphocytic leukemia had been diagnosed several years earlier, and the patient was treated with rituximab, pentostatin, and cyclophosphamide. A diagnostic workup ruled out autoimmune and metabolic liver disease, hepatitis A-C, and herpes virus infection. A physical examination revealed enlarged axillary lymph nodes. The results of an abdominal ultrasound examination were otherwise unremarkable. Hepatitis E virus infection was diagnosed by detection of hepatitis E virus-specific antibodies. Blood samples were positive for hepatitis E virus ribonucleic acid with high viral loads for at least 8 months, demonstrating a rare chronic hepatitis E virus infection. Sequencing and phylogenetic analysis revealed hepatitis E virus genotype 3c with homologies to other European isolates from humans and swine, indicating an autochthonous infection. CONCLUSIONS: Usually, hepatitis E virus infection appears as an acute infection; rare chronic infections have been reported for transplant patients, patients with human immunodeficiency virus, and patients with hematological malignancies. The chronic nature of hepatitis E infection in our patient was most likely induced by the immunosuppressive B-cell chronic lymphocytic leukemia treatment. The differential diagnosis in patients with unexplained hepatitis should include hepatitis E virus infection, and appropriate laboratory analyses should be considered.