Relationship between clinical characteristics of narcolepsy and CSF orexin-A levels.

Although an abnormally low cerebrospinal fluid (CSF)-orexin level is well known to be a specific finding in narcoleptic patients, the relationships between the severity of the core symptoms of narcolepsy [i.e. daytime sleepiness and increased rapid eye movement (REM) propensity], as well as levels of obesity, and CSF-orexin levels have not been well elucidated. The aim of this study was to examine the relationship between these characteristic symptoms of narcolepsy and CSF-orexin level. Fifty-three patients with narcolepsy with cataplexy (NA/CA) and 17 without cataplexy (NA w/o CA) were enrolled. Sleep latency and sleep onset REM latency were measured using the multiple sleep latency test (MSLT). Multiple linear regression analysis was used to determine factors associated with both mean sleep latency and mean sleep onset REM latency on MSLT, with %body mass index (BMI), gender, onset age, length of excessive daytime sleepiness (EDS) morbidity, diagnostic subgroup and CSF-orexin levels being used as independent variables. The NA/CA group included a significantly higher number of patients with undetectable CSF-orexin levels and shorter sleep onset and rapid eye movement (SOREM) latency, as well as a higher %BMI, versus NA w/o CA. Multiple linear regression analysis revealed that sleep latency was associated significantly with CSF-orexin levels and gender. With regard to sleep onset REM latency and %BMI, only CSF-orexin levels appeared to be a significantly associated factor. In narcoleptic patients, the severity of both excessive daytime sleepiness and increased REM propensity, as well as the level of obesity, could be associated with CSF-orexin deficiency, rather than with subcategories of the disorder.

Cloning and transcriptional analysis of the gene encoding 5-aminolevulinic acid synthase of the white-rot fungus Phanerochaete sordida YK-624.

In this study, we cloned the gene encoding 5-aminolevulinic acid synthase (ALAS) from the hyper-lignin-degrading fungus Phanerochaete sordida YK-624. The deduced amino acid sequence showed highest identity (93.0%) to ALAS of P. chrysosporium. Expression of the gene encoding ALAS, which we named aas, corresponded temporally with the expression and activity of manganese peroxidase.

Exploring the daily activities associated with delayed bedtime of Japanese university students.

University students show delayed sleep-wake patterns, i.e., later bed- and rise-times, and this pattern is known to be associated with various malfunctions. There may be a variety of daily activities associated with their delayed sleep patterns, such as watching TV. However, it is unclear to what extent each activity possesses an impact on their sleep patterns. The purpose of this study was to determine the daily activities associated with delayed bedtime in Japanese university students who live with or without their families. Three hundred and thirty-one participants were required to record the timing and duration of their sleep and daily activities, and the data from the 275 students (160 men and 115 women; 19.01 +/- 1.66 years) who completely filled forms were used for analysis. The results of multiple regression analyses suggested that interpersonal communication late at night is one of the major factors leading to the delayed bedtime of students living away from home. Among those living with their families, indoor activities such as watching TV and using the Internet were related to their delayed bedtimes. Attending classes and having a morning meal were related to the earlier bedtimes of the students living away from home, but there were no activities associated with those of the students living with their families. These results suggest that ensuring attendance at morning classes and having appropriate mealtimes, as well as restricting the use of visual media and socializing activities at night, are necessary for preventing late bedtimes in university students.

Cloning and homologous expression of novel lignin peroxidase genes in the white-rot fungus Phanerochaete sordida YK-624.

Two genes, encoding YK-LiP1 and YK-LiP2, were cloned from the white-rot fungus Phanerochaete sordida YK-624, and a homologous expression system for the gene was constructed. Two full-length cDNAs (ylpA and ylpB) were isolated by degenerate RT-PCR and RACE-PCR. The results of N-terminal amino acid sequence analysis of native YK-LiP1 and YK-LiP2 showed that ylpA and ylpB coded for YK-LiP2 and YK-LiP1 respectively. The promoter of glyceraldehyde-3-phosphate dehydrogenase cloned from P. sordida YK-624 (PsGPD) was used to drive the expression of ylpA. Expression vector pGPD-g-ylpA was transformed into a P. sordida YK-624 uracil auxotrophic mutant, UV-64. The YlpA protein was secreted in active form by the transformants after 4 d of growth in a medium containing an excessive nitrogen source, whereas endogenous YK-LiP1 and YK-LiP2 were not produced. The physical and catalytic properties of the purified YlpA protein were very similar to those of YK-LiP2. These results suggest that homologous expression of recombinant YK-LiP2 was successful.

Impact of microarousal associated with increased negative esophageal pressure in sleep-disordered breathing.

PURPOSE: "Microarousals" during sleep have not been analyzed systematically. We investigated the importance of "microarousals" (lasting 1.5-3 s). METHODS: Standard polysomnography including esophageal pressure (Pes) assessment was performed on ten patients (aged 54.0 +/- 5.0 years) with respiratory effort-related arousal > or =5/h. We measured the number of arousals per hour (American Sleep Disorders Association (ASDA) arousal index) and the number of microarousals lasting 1.5-3 s per hour (mASDA arousal index). On the night after the baseline sleep study, we performed overnight continuous positive airway pressure (CPAP) titration. RESULTS: mASDA arousals, characterized by lower Pes values, were observed more frequently in patients with sleep-disordered breathing. The Pes results did not differ significantly between ASDA and mASDA arousals (-15.6 +/- -5.0 vs -15.0 +/- -4.4 cmH(2)O). mASDA arousals were significantly improved by CPAP treatment (mASDA arousals, 82.6 +/- 60.1 vs 6.0 +/- 1.4/h). CONCLUSIONS: mASDA arousals were characterized by an increase in Pes. mASDA arousals are thus key to our understanding of clinical manifestations in patients with sleep-disordered breathing.

Efficient expression of laccase gene from white-rot fungus Schizophyllum commune in a transgenic tobacco plant.

Ligninolytic enzymes produced by white-rot fungi are effective degraders of recalcitrant aromatic environmental pollutants. However, gene sequences of these enzymes are rich in CpG dinucleotides, which are particularly unfavorable to efficient expression in plants. In order to develop a phytoremediation technique with a ligninolytic enzyme-producing transgenic plant, laccase cDNA (scL) from white-rot fungus Schizophyllum commune was used as a model ligninolytic enzyme, and we attempted to obtain the efficient expression of scL in a transgenic tobacco plant by decreasing the CpG-dinucleotide motif content. We constructed a mutagenized scL sequence, scL12, decreasing the CpG-dinucleotide motif content by 12%, and scL12 was introduced into the tobacco plant. Much higher laccase activity was detected in transgenic scL12 plants than in transgenic scL plants and wild-type plants. Using reverse transcriptase-PCR analysis, scL12 was translated in transgenic scL12 plants whereas mRNA of scL was not detected in the transgenic scL plants, and scL, which is the product of the scL12 gene, was produced in the transgenic scL12 plants using native-polyacrylamide gel electrophoresis analysis. Moreover, transgenic scL12 plants were able to remove trichlorophenol more effectively than transgenic scL plants and wild-type plants. These results suggest that decreasing CpG-dinucleotide motif content in fungal target genes is a useful method for efficient expression of these genes in transgenic plants.

Developing PCR primers using a new computer program for detection of multiple animal-derived materials in feed.

To reduce the risk of the bovine spongiform encephalopathy agent being recycled to cattle through animal feed, in October 2001 Japan introduced a feed ban prohibiting the use of animal proteins in feed. PCR identification of feed ingredients is part of the audit program to ensure the proper implementation of the feed ban. For efficient analysis, screening of feed products for materials from multiple species is essential. In our study, we developed a computer program GSPRIMER (http://www. famic.go.jp/ffis/feed/gsprimer/) that facilitates development of PCR primers specific to multiple species. The most important feature of GSPRIMER is its ability to estimate the specificity and homology of a potential primer in incremental steps from the 3' terminal. We analyzed all regions of mitochondrial DNA from the target and nontarget species using GSPRIMER. We designed species-specific primer sets for three animal species (sheep, goats, and swine) and group-specific primer sets for ruminants and animals susceptible to transmissible spongiform encephalopathy. The primers were efficiently screened by the PCR protocol using a mixture of mitochondrial DNA from nontarget species as a template. As a result, one primer set each for sheep and goats, two for swine, and three for a group of ruminant species were developed. The detection limit of one of the ruminant primer sets ranged from 0.05 to 0.01% bovine meat and bone meal and 0.1 pg of bovine DNA. We also successfully applied the primer set to 17 commercial feed samples that were known to be free from ruminant-derived materials. No false-positive results were found.

Assessment of continuous positive airway pressure treatment in obstructive sleep apnea syndrome using 24-hour urinary catecholamines.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is related to diurnal sympathetic hyperactivity and increased blood pressure, both factors that are likely to lead to the development of cardiovascular disease. HYPOTHESIS: The study investigated whether 24-h urinary catecholamines would reflect the effect of obstructive sleep apnea on autonomic activity. METHODS: Standard polysomnography was performed in 17 patients with OSAS (age 53.7 +/- 13.5 years, mean +/- standard deviation). The number of apnea/hypopnea episodes per hour of sleep (apnea/hypopnea index [AHI]); number of oxygen desaturation episodes per hour (desaturation index [DSI]); arousals per hour (arousal index); lowest oxygen saturation (lowest SpO2); and percentages of stages 1, 2, 3/4, and rapid eye movement sleep (% stage 1, -2, and -3/4, and % REM, respectively) were measured. Overnight continuous positive airway pressure (CPAP) titration was performed the night after the baseline sleep measurements had been taken. Twenty-four-hour urinary adrenaline and noradrenaline were also examined. RESULTS: During the CPAP treatment, both 24-h urinary adrenaline and noradrenaline were significantly lower compared with natural sleep. Continuous positive airway pressure significantly decreased the AHI, DSI, % stage 1, and arousal index and significantly increased the lowest SpO2. There were no significant differences in % stage 2, % stage 3/4, and % REM between before and during CPAP treatment. Multiple analysis of covariance tests revealed that lowest SpO2 was the most important factor for increasing 24-h urinary noradrenaline levels (F = 4.75, p = 0.048). CONCLUSIONS: One night CPAP treatment could improve autonomic dysfunction. The assessment of 24-h urinary noradrenaline would provide important information for evaluating the effect of CPAP treatment.

Is nocturnal panic a distinct disease category? Comparison of clinical characteristics among patients with primary nocturnal panic, daytime panic, and coexistence of nocturnal and daytime panic.

OBJECTIVE: Many patients with panic disorder (PD) experience nocturnal panic attacks. We investigated the differences in demographic variables and symptom characteristics as well as response to treatment among patients with primary day panic (DP), primary nocturnal panic (NP), and the coexistence of DP and NP (DP/NP), and discuss whether NP is a distinct disease category. METHOD: One hundred one consecutive untreated patients with PD were enrolled and subsequently divided into the NP, DP, and DP/NP groups. The presence of 13 panic attack symptom items as well as scores on the Panic Disorder Severity Scale (PDSS) and the Pittsburgh Sleep Quality Index (PSQI) were compared among the groups. After 3 months of regular treatment, PDSS scores were assessed again to evaluate treatment response. RESULTS: Nocturnal panic attacks of the participants were mostly reported to occur in the first tertile of nocturnal sleep. The number of males, onset age, and presence of choking sensation were significantly higher, and the PDSS score was significantly lower in the NP group compared with the other groups. The DP/NP group showed the highest PDSS score, and participants in this group were prescribed the highest doses of medication among all groups. Only diagnostic sub-category was significantly associated with treatment response. The total score for PDSS and PSQI correlated significantly only in the NP group. CONCLUSIONS: DP/NP could be a severe form of PD, while primary NP could be a relatively mild subcategory that may partially share common pathophysiology with adult type night terror.

Improvement of ligninolytic properties in the hyper lignin-degrading fungus Phanerochaete sordida YK-624 using a novel gene promoter.

We identified a highly expressed protein (BUNA2) by two-dimensional gel electrophoresis from the hyper lignin-degrading fungus Phanerochaete sordida YK-624 under wood-rotting conditions. Partial amino acid sequences of BUNA2 were determined by LC-MS/MS analysis, and BUNA2 gene (bee2) and promoter region were PCR-cloned and sequenced. The bee2 promoter was used to drive the expression of the manganese peroxidase gene (mnp4) in P. sordida YK-624. Eighteen mnp4-expressing clones were obtained, with most showing higher ligninolytic activity and selectivity than wild-type YK-624. Examination of the ligninolytic properties of the most effective lignin-degrading transformant, BM-65, cultured on wood meal revealed that this strain exhibited higher lignin degradation and MnP activities than those of wild type. Transcriptional analysis confirmed the increased expression of recombinant mnp4 in the transformant. These results indicate that use of the bee2 promoter to drive the expression of ligninolytic enzymes may be an effective approach for improving the lignin-degrading properties of white-rot fungi.

Differences in findings of nocturnal polysomnography and multiple sleep latency test between narcolepsy and idiopathic hypersomnia.

OBJECTIVES: To compare differences in nocturnal and daytime polysomnographic findings between narcolepsy (NA) with and without cataplexy (CA) and idiopathic hypersomnia without long sleep time (IHS w/o LST). METHODS: Nocturnal polysomnography (n-PSG) and multiple sleep latency test (MSLT) findings were compared among subjects with NA with CA (n=52), NA without CA (n=62), and IHS w/o LST (n=50). RESULTS: The NA with CA group had significantly more disrupted and shallower nocturnal sleep than the other groups. On MSLT, the IHS w/o LST group had significantly longer sleep latency (SL) compared with the two NA groups. The latter two groups did not show statistical differences in diurnal variation of SL. CONCLUSIONS: The IHS w/o LST group had milder objective daytime sleepiness compared with the NA groups. In patients with NA, nocturnal sleep disturbances appeared only in cases with CA, despite a similar trend in diurnal changes in sleep propensity between the two NA groups. SIGNIFICANCE: Objective nocturnal sleep disturbances are specific to NA patients with CA, whereas diurnal variations of sleep propensity are observed irrespective of the presence of CA among NA patients. These findings could be helpful for choosing optimal treatment plans for patients with these disorders.

Clinical characteristics in two subgroups of obstructive sleep apnea syndrome in the elderly: comparison between cases with elderly and middle-age onset.

BACKGROUND: Morbidity due to obstructive sleep apnea syndrome (OSAS) is increased in the elderly population. However, the clinical characteristics of OSAS in elderly patients have not been characterized conclusively. The aim of this study was to clarify differences in clinical characteristics of OSAS between patients with middle-age onset and elderly onset of OSAS. METHODS: Patients with OSAS aged > or = 65 years were classified into groups according to age at first identification of respiratory pauses during sleep: a middle-age onset group (n = 32) where onset was at age < 50 years and an elderly onset group (n = 31) where onset was at age > or = 60 years. We compared demographic variables; polysomnographic variables; daytime sleepiness measures, including the multiple sleep latency test (MSLT) and the Epworth sleepiness scale (ESS); and adequate level of nasal continuous positive airway pressure (CPAP) between groups. RESULTS: BMI and frequency of underlying cardiovascular disorder were lower in the elderly onset group than in the middle-age onset group. No significant differences in apnea-hypopnea index or percentage of the period showing O(2) desaturation were seen between groups. However, arousal index, maximal negative esophageal pressure value, and adequate nasal CPAP level were significantly smaller in the elderly onset group. Mean sleep latency on MSLT was longer, and ESS score was lower in the elderly onset group. CONCLUSIONS: Compared with the middle-age onset group, the clinical significance of OSAS in the elderly onset group seemed to remain milder. This finding is possibly because of the smaller physiologic response to respiratory events.

Comparison of clinical characteristics among narcolepsy with and without cataplexy and idiopathic hypersomnia without long sleep time, focusing on HLA-DRB1( *)1501/DQB1( *)0602 finding.

BACKGROUND: Clinical characteristics of narcolepsy without cataplexy (NA w/o CA) and its relation to positivity of HLA-DRB1( *)1501/DQB1( *)0602 remain unclarified. We investigated clinical features of NA w/o CA, particularly addressing HLA-DRB1( *)1501/DQB1( *)0602. METHODS: Comparisons of the Epworth Sleepiness Scale (ESS), multiple sleep latency test (MSLT) variables, rapid eye movement (REM)-related symptoms, and treatment response to psychostimulant medication were made for four patient groups (narcolepsy with cataplexy; NA-CA, NA w/o CA HLA-positive, NA w/o CA HLA-negative, and idiopathic hypersomnia without long sleep time; IHS w/o LST). RESULTS: Mean sleep latency was significantly shorter and the rate of reduction of ESS after medication was lower in both NA-CA and NA w/o CA HLA-positive groups than those in the IHS w/o LST group. Among the three narcoleptic groups, the NA w/o CA HLA-negative group showed the lowest REM latency and the highest reduction rate of ESS after treatment. Neither these subjective and objective sleepiness measures nor the treatment response measure was significantly different between this group and the IHS w/o LST group. CONCLUSIONS: In NA w/o CA, HLA-positivity might affect hypersomnia severity and REM propensity. The NA w/o CA HLA-negative group and the IHS w/o LST group exhibit equivalent hypersomnia severity.

Upper airway morphology in patients with obstructive sleep apnea syndrome: effects of lateral positioning.

OBJECTIVES: The aim of this study was to clarify the interaction of lateral and supine sleeping positions with upper airway morphology in patients with obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: Thirty-one patients with OSAS, whose apnea/hypopnea index (AHI: number of episodes of apnea or hypopnea per hour) was over 15, were enrolled in this study. Subjects were divided in two groups according to positional effects on their AHI. In six patients, a lateral posture decreased the AHI by 50% and more (responders); in the remaining 25, lateral positioning decreased the AHI by less than 50% or even increased the AHI (nonresponders). AHI and body mass index (BMI) of the responders tended to be lower and their mean age was younger than those of nonresponders, but these differences were not statistically significant. We compared the upper airway morphology between the responders and the nonresponders regarding the tonsil size, tongue position (modified Mallanpati grade, reflecting the space between the tongue and soft palate) and the width of the fauces and retroglossal space. In addition, we compared nasal resistance between the groups using active rhinomanometry. RESULTS: The width of the fauces was significantly greater (P=0.041) among the responders than among the nonresponders. However, the other parameters were not consistently different between the two, and these differences were not statistically significant either. CONCLUSIONS: The distance between the fauces was the sole morphological feature to distinguish the responders and the nonresponders to the positional therapy in patients with OSAS. Lateral positioning during sleep might be a recommended sleep hygiene for OSAS patients with wide fauces.

Transformation by complementation of a uracil auxotroph of the hyper lignin-degrading basidiomycete Phanerochaete sordida YK-624.

Phanerochaete sordida YK-624 is a hyper lignin-degrading basidiomycete possessing greater ligninolytic selectivity than either P. chrysosporium or Trametes versicolor. To construct a gene transformation system for P. sordida YK-624, uracil auxotrophic mutants were generated using a combination of ultraviolet (UV) radiation and 5-fluoroorotate resistance as a selection scheme. An uracil auxotrophic strain (UV-64) was transformed into a uracil prototroph using the marker plasmid pPsURA5 containing the orotate phosphoribosyltransferase gene from P. sordida YK-624. This system generated approximately 50 stable transformants using 2 x 10(7) protoplasts. Southern blot analysis demonstrated that the transformed pPsURA5 was ectopically integrated into the chromosomal DNA of all transformants. The enhanced green fluorescent protein (EGFP) gene was also introduced into UV-64. The transformed EGFP was expressed in the co-transformants driven by P. sordida glyceraldehyde-3-phosphate dehydrogenase gene promoter and terminator regions.

Influence of nasal resistance on initial acceptance of continuous positive airway pressure in treatment for obstructive sleep apnea syndrome.

BACKGROUND: Continuous positive airway pressure (CPAP) is considered as the standard therapy for obstructive sleep apnea syndrome (OSAS), but some patients with OSAS are unable to accept CPAP due to nasal obstruction and poor nasal airflow. OBJECTIVES: We assessed the influence of nasal resistance before beginning CPAP treatment on the initial acceptance of CPAP in OSAS patients. METHODS: The study subjects comprised 77 patients (74 males, 3 females) with primary OSAS, all of whom received CPAP treatment with nasal masks. Before trials, all subjects underwent overnight polysomnography, and nasal resistance was measured with active anterior rhinomanometry in the seated position on the first day of CPAP trial. RESULTS: The CPAP treatment was accepted by 56 patients after the initial trials with overnight polysomnography. Body mass index, the number of apnea/hypopnea episodes per hour (apnea/hypopnea index; AHI), and the number of episodes per hour with an oxygen desaturation of >3% (oxygen desaturation index) were significantly higher (p<0.01) and nasal resistance was lower (p=0.003) in patients who accepted CPAP than in those who did not. Logistic regression analysis, with patient age, body mass index, Epworth sleepiness scale score, AHI, oxygen desaturation index, and nasal resistance before CPAP treatment as explanatory variables, showed that nasal resistance (OR+0.1 Pa/cm3/s: 1.48; p=0.002) and AHI (OR+1 event/h: 0.93; p=0.003) were significant factors for CPAP non-acceptance. CONCLUSIONS: Nasal resistance before the beginning of CPAP treatment has a significant effect on the acceptance of CPAP in OSAS patients, and hence, could be a predictive parameter for the initial acceptance of CPAP.

Daytime polysomnography for early diagnosis and treatment of patients with suspected sleep-disordered breathing.

Excessive daytime sleepiness (EDS) is a common complaint among patients with sleep-disordered breathing (SDB). Population-based studies on traffic and industrial accidents suggest a relationship between EDS and life-threatening events, and adults with EDS have cognitive and memory problems. Nocturnal polysomnography (nPSG) is essential for diagnosing SDB but it is time and energy consuming. We examined the usefulness of daytime polysomnography (dPSG) for the early diagnosis and treatment of patients with suspected SDB. We studied 108 consecutive patients aged 51.9 +/- 13.5 years (mean+/-SD). All patients underwent dPSG and nPSG. The number of apnea/hypopnea episodes per hour (apnea/hypopnea index: AHI) and the number of 3% desaturation episodes per hour (desaturation index: DSI) were calculated. All patients were classified into two groups. The REM group consisted of subjects who had an AHI < or = 25/h, AHI(REM)/AHI(NREM) > 2, and AHI(NREM) < 15/h. Those who did not satisfy these criteria were placed in the NREM group. Continuous positive airway pressure (CPAP) titration was performed for patients whose AHI was > or =20/h on dPSG. Using the international classification of sleep disorders, 96 patients were diagnosed as obstructive sleep apnea [including five upper airway resistance syndrome (UARS) patients], six patients were snoring, four had idiopathic hypersomnia due to a medical condition, and two had circadian rhythm sleep disorders. The sensitivity of dPSG for AHI was 81.0%, specificity was 100%, and accuracy was 83.5%. The sensitivity and accuracy of dPSG for AHI in the REM group were considerably lower than in the NREM group. There was no significant difference for optimal CPAP between dPSG and nPSG. In the five patients with UARS, their AHI, DSI, and arousal index on dPSG were 0.92 +/- 1.2/h, 2.9 +/- 3.4/h, and 29.3 +/- 3.5/h, respectively, and their AHI and DSI on nPSG were 3.2 +/- 2.5/h and 2.8 +/- 2.4/h, respectively. However, their respiratory effort-related arousals were 37.9 +/- 7.4/h, and their arousal index was 33.2 +/- 6.3/h. The five patients with UARS were also treated with CPAP, and their daytime sleepiness was improved. Although dPSG has limitations, these results indicate that dPSG recording is clinically useful for the diagnosis of and determination of types of treatment in patients with suspected SDB.

Reduced nasal resistance after simple tonsillectomy in patients with obstructive sleep apnea.

BACKGROUND: The aim of this study was to investigate the effects of simple tonsillectomy on nasal resistance in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Conventional tonsillectomy was performed in 20 patients who were refractory to treatment with continuous positive airway pressure. The subjects consisted of 17 men and 3 women (mean age, 32.9 +/-6.3 years). The effects of tonsillectomy were evaluated with preoperative and postoperative polysomnography and nasal resistance. RESULTS: After tonsillectomy, nasal resistance decreased significantly from 0.39+/-0.30 Pa/cm(3) per second to 0.27 +/-0.16 Pa/cm(3) per second (p < 0.05). Simultaneously, the apnea-hypopnea index decreased significantly from 55.7 +/-22.5 to 21.2 +/-14.2 (p < 0.05). There was no significant correlation between tonsillar weight and percentage of change in bilateral nasal resistance (p > 0.05). CONCLUSION: The reduction in nasal resistance induced by simple tonsillectomy could play an important role in improving OSAS, as does nasal surgery or adenotomy.

Factors contributing to sleep disturbance and hypnotic drug use in hemodialysis patients.

OBJECTIVE: Sleep disturbance and the use of hypnotic medications are common in patients on hemodialysis. Factors that contribute to sleep disturbance and the use of hypnotic medications in hemodialysis patients were investigated. METHODS: With the use of a questionnaire-based survey, we examined the prevalence of symptoms that reflect sleep disorders such as insomnia, restless legs syndrome (RLS), and snoring and use of hypnotic medications in 252 hemodialysis patients. RESULTS: The overall prevalence of insomnia was 59.1%, with the prevalence of difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), and early morning awakening (EMA) being 47.6, 24.2, and 28.2%, respectively. Daytime sleepiness and habitual snoring were reported by 42.5 and 33.7%, respectively. The prevalence of routine use of hypnotic drugs was 25.8%. Both RLS and age were significantly associated with insomnia [odds ratio (OR), 3.75; p 0.001, OR, 1.03; p < 0.01]. RLS was a significant factor for DIS, DMS, and EMA (OR, 2.26; p < 0.05, OR, 3.44; p < 0.0005, OR, 4.25; p < 0.0005) and age was a significant factor for DMS and EMA (OR, 1.03; p = 0.053, OR, 1.05; p < 0.005). Both insomnia and snoring were associated with the use of hypnotic drugs (OR, 2.97; p < 0.001, 1.59; p=0.13). CONCLUSION: Both RLS and sleep-disordered breathing may contribute to sleep disturbance in hemodialysis patients. RLS in particular may be an important factor in insomnia, which in turn is likely responsible for the high prevalence of hypnotic drug use in hemodialysis patients.

Platelet GPIIb/IIIa is activated and platelet-leukocyte coaggregates formed in vivo during hemodialysis.

BACKGROUND/AIM: During hemodialysis, platelets and leukocytes are activated and form platelet-leukocyte coaggregates in which GPIIb/IIIa (CD41/CD61) and CD62P (P-selectin) are involved. However, it is still controversial whether platelet activation and platelet-leukocyte coaggregate formation are dependent on the dialyzer membrane material. METHOD: We examined the appearance of activation-dependent antibody on platelets as an index of platelet activation, and the appearance of platelet-specific antigen on leukocytes as an index of platelet-leukocyte coaggregation, during hemodialysis in 7 patients treated using regenerated cellulose (RC) membrane and next using polysulfone (PS) membrane. In order to reduce the influence of factors other than dialyzer membrane material, this study was conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate. Moreover, flow cytometric techniques with whole blood were employed, which reduce artificial cell activation during the cell or plasma separation procedure. The platelet-specific monoclonal antibodies used in this study were anti-CD61, PAC-1 (which recognizes only the conformationally activated GPIIb/IIIa) and anti-CD62P. RESULTS: Changes in the percentage of PAC-1-positive platelets were significantly greater during hemodialysis with RC than with PS. However, changes in the percentage of CD62P-positive platelets were not significantly different between hemodialysis with RC and PS. Changes in the percentage of CD61- or CD62P-positive leukocytes were significantly greater during hemodialysis with RC than with PS. Although changes in percentage of PAC-1-positive platelets did not parallel those of CD62P-positive platelets during hemodialysis, there was a significant positive correlation between the percentage of CD61-positive leukocytes and the percentage of CD62P-positive leukocytes. CONCLUSION: This study, conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate in order to reduce the influence of factors other than the dialyzer membrane material, demonstrated that both the degrees of GPIIb/IIIa activation and platelet-leukocyte coaggregation were greater during hemodialysis with RC than PS.