A nationwide, cross-sectional survey on unusual sleep postures and sleep-disordered breathing-related symptoms in people with Down syndrome.

BACKGROUND: People with Down syndrome (DS) often have sleep-disordered breathing (SDB). Unusual sleep postures, such as leaning forward and sitting, are observed in people with DS. This study aimed to clarify the prevalence of unusual sleep postures and their relationships with SDB-related symptoms (SDB-RSs), such as snoring, witnessed apnoea, nocturnal awakening and excessive daytime sleepiness. METHODS: A questionnaire, including demographic characteristics and the presence of unusual sleep postures, as well as SDB-RSs, was completed by 1149 parents of people with DS from Japan. RESULTS: Unusual sleep postures were recorded in 483 (42.0%) people with DS. These participants were significantly younger and had a history of low muscle tone more frequently than people without unusual sleep postures. In all ages, the leaning forward posture was more frequent than sitting. People with DS with unusual sleep postures suffered from SDB-RSs. Those who slept in the sitting posture had more frequent SDB-RSs than did those who slept with the leaning forward posture. Snoring, witnessed apnoea and nocturnal awakening were observed in 73.6, 27.2 and 58.2% of participants, respectively. Snoring increased with aging. Witnessed apnoea was more common in males and in those with hypothyroidism than in females and in those without hypothyroidism. CONCLUSIONS: Our study shows that there is a close relationship between unusual sleep postures and SDB-RSs. We recommend that all people with DS with unusual sleep postures should be checked for the presence of SDB.

Effects of 6-h exposure to low relative humidity and low air pressure on body fluid loss and blood viscosity.

The purpose of this study was to investigate the effects of 6-h exposure to low relative humidity (RH) and low air pressure in a simulated air cabin environment on body fluid loss (BFL) and blood viscosity. Fourteen young healthy male subjects were exposed to four conditions, which combined RH (10% RH or 60% RH) and air pressure (NP: sea level or LP: equivalent to an altitude of 2000 m). Subjects remained seated on a chair in the chamber for 6 h. Their diet and water intake were restricted before and during the experiment. Insensible water loss (IWL) in LP10% condition was significantly greater than in NP60% condition; thus, combined 10%RH and LP conditions promoted a greater amount of IWL. The BFL under the LP condition was significantly greater than that under the NP condition. Blood viscosity significantly increased under LP conditions. Increases in red blood cell counts (RBCs) and BFL likely contributed to the increased blood viscosity. These findings suggest that hypobaric-induced hypoxia, similar to the conditions in the air cabin environment, may cause increased blood viscosity and that the combined low humidity and hypobaric hypoxia conditions increase IWL.

Correlation of immunologic status with high-resolution CT and distributions of pulmonary tuberculosis.

PURPOSE: To investigate the correlation of cluster of differentiation (CD)4 lymphocyte counts with high-resolution CT (HRCT) findings and distribution of pulmonary tuberculosis. MATERIAL AND METHODS: Thirty-seven bacteriologically proven pulmonary tuberculosis, clinically non-AIDS, patients underwent HRCT and CD4 lymphocyte counts in peripheral blood cells were obtained within 3 days after the CT examinations. Patients were categorized into four groups according to CD4 lymphocyte counts (A >800; B 800-500; C 500-200; D <200). HRCT findings analyzed were as follows: typical, atypical, and mixed findings of post-primary tuberculosis, common, uncommon, and mixed distribution, and number of lobes involved. RESULTS: CD4 lymphocyte counts correlated with the degree of the mixture of atypical CT findings (rho=0.565, p<0.001) and the degree of the mixture of uncommon distribution (rho=0.431, p<0.01). Number of involved lobes showed no statistically significant correlation (rho=0.209, p=0.21). CONCLUSION: In patients with low CD4 levels, atypical HRCT findings co-exist with typical findings, and uncommon sites are involved in addition to common sites.

Enhanced expression of heat shock proteins in activated polymorphonuclear leukocytes in patients with sepsis.

BACKGROUND: Heat shock proteins (HSPs) in cells, as molecular chaperons, have been reported to regulate cell functions. The objective of this study was to investigate the HSP expression in polymorphonuclear leukocytes (PMNLs) from severe septic patients and the relation between the expression of HSPs and PMNL function. METHODS: In blood samples from 21 patients with sepsis and serum C-reactive protein levels more than 10 mg/dL, we used flow cytometry to measure expressions of HSP27, HSP60, HSP70, and HSP90; oxidative activity; and levels of apoptosis in PMNLs during sepsis. In in vitro studies, we used cells from 14 healthy volunteers to examine the relation between the expression of HSP70 and PMNL function. Quercetin (30 microM), a suppressor of HSP, and sodium arsenite (100 microM), an inducer of HSP, were used to regulate the expression of HSP70 in PMNLs, and oxidative activity and apoptosis in these cells were measured. RESULTS: In patients with sepsis, the expressions of HSP27, HSP60, HSP70, and HSP90 and oxidative activity in PMNLs were significantly increased. Apoptosis of these PMNLs was markedly inhibited. In the in vitro studies, administration of sodium arsenite enhanced the expression of HSP70, significantly increased oxidative activity, and inhibited apoptosis. Administration of quercetin before sodium arsenite prevented the expression of HSP70, the increase in oxidative activity, and the inhibition of apoptosis. CONCLUSION: Sepsis causes the enhanced expression of HSPs in activated PMNLs. In PMNLs with enhanced expression of HSP70, oxidative activity is increased and apoptosis is inhibited. The enhanced expression of HSPs may play a role in regulating PMNL function in patients with sepsis.

Enhanced expression of heat shock proteins in leukocytes from trauma patients.

BACKGROUND: Heat shock proteins (HSPs) play essential roles as molecular chaperones in cells to assist in the repair of degenerated proteins. The expression of HSPs in polymorphonuclear leukocytes (PMNLs) following insult has not been delineated. The objective of this study was to clarify the serial changes in HSP expression in PMNLs from trauma patients. METHODS: Fifty severely injured patients (mean Injury Severity Score of 31.8 +/- 10.8) and 17 healthy volunteers were included as study subjects. Blood samples were serially obtained at three time points: days 0 to 1, days 2 to 5, and days 6 to 14 after the trauma event. We measured expressions of HSP27, HSP60, HSP70, and HSP90 in permeabilized PMNLs by flow cytometry using a monoclonal antibody generated against each HSP and fluorescein isothiocyanate-conjugated antimouse immunoglobulins as secondary reagents. We also evaluated the expression of HSP70 mRNA in PMNLs by Northern blot hybridization and the expression of HSP70 in PMNLs by fluorescence microscopy. RESULTS: Expressions of HSP27, HSP70, and HSP90 in PMNLs from trauma patients were significantly greater than in PMNLs from healthy volunteers in all three periods (days 0-1, days 2-5, and days 6-14). The expression of HSP60 in PMNLs from trauma patients was significantly greater than normal expression on days 2 to 5 and days 6 to 14. The values for HSP27, HSP60, and HSP70 on days 2 to 5 were significantly higher than those on days 0 to 1. The expression of HSP70 mRNA in PMNLs was significantly enhanced for as long as 2 weeks after trauma compared with that in normal volunteers. CONCLUSION: Severe trauma causes demonstrated enhanced expression of HSPs in PMNLs during the acute phase. This enhanced expression of HSPs may regulate PMNL functions.

A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan.

OBJECT: The criteria for the use of mild hypothermia (34 degrees C) in severely head injured patients have not been standardized. A prospective randomized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure (ICP). METHODS: At 11 medical centers, 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided randomly into two groups: the mild hypothermia group (HT group, 45 patients) and the normothermia group (NT group, 46 patients). Patients in the HT group were exposed to mild hypothermia (34 degrees C) for 48 hours, followed by rewarming at 1 degrees C per day for 3 days, whereas patients in the NT group were exposed to normothermia (37 degrees C) for 5 days. The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome at 3 months postinjury. During treatment, there was a significantly greater use of neuromuscular blocking agents in the HT group (p = 0.011). During the initial 2 weeks postinjury, the incidences of pneumonia, meningitis, leukocytopenia, thrombocytopenia, hypernatremia, hypokalemia, and hyperamylasemia were significantly higher in the HT than in the NT group (p < 0.05). CONCLUSIONS: Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients.

Toxicokinetics of intravenous fluoride in rats with renal damage caused by high-dose fluoride exposure.

Fluoride (F) complexes are used in some fields of industry and medicine. F excretion mainly depends on kidney function. Urinary F concentration is measured to monitor the health of workers exposed to F. The toxicokinetics of F were studied by analyzing plasma concentration of F after intravenous injection of 2.86, 5.71 and 8.57 mg/kg into male Wistar rats. A dose-response relationship was recognized between these F doses and renal tissue injury. Blood samples were removed at 0, 10, 20, and 30 min, and after 1, 2, 3, 4, 5, and 6 h after injection. Plasma concentration-vs-time profiles were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Results indicated that a two-compartment model could describe the elimination of F from plasma. The beta rate constant, total plasma clearance (C1) and first-order rate constants (K21, Kel) decreased, and the half-time of the beta-phase (t1/2beta) was significantly prolonged with increasing dose. The kidney is the main target organ for F toxicity. Acute exposure to high doses of F damages renal tissue and causes renal dysfunction. The C1 of F is mainly dependent on renal F excretion. Since severe kidney damage markedly affected the toxicokinetics of F and decreased its elimination, other nephrotoxic indicators and measurement of plasma F concentration are necessary for monitoring high-dose F exposure.

Interleukin-1beta alters the oxygen delivery-oxygen consumption relationship in rabbits by increasing the slope of the supply-independent line.

When systemic oxygen delivery (DO2) is reduced, oxygen consumption (VO2) is maintained until a critical level is reached (DO2crit). Sepsis is thought to shift DO2crit to the right and lengthen the supply-dependent portion. We tested the effect of interleukin (IL)-1beta, which is one of the key cytokines related to sepsis, on the DO2-VO2 relationship. Fifteen rabbits were subjected to stepwise cardiac tamponade to reduce DO2 to 10% by inflating a handmade balloon placed into the pericardial sac. Seven rabbits were given 10 microg/kg of IL-1beta intravenously (IL-1beta group) prior to the graded cardiac tamponade. The remainder received saline alone (control group). The DO2-VO2 relationship was analyzed by the dual-line method. IL-1beta significantly decreased mean arterial pressure (65 +/- 11 mmHg from baseline 85 +/- 7 mmHg) without altering cardiac output. The IL-1beta group showed significantly steeper supply-independent line slopes than did the control group (0.19 +/- 0.02 vs. 0.11 +/- 0.02, respectively), which resulted in a DO2crit shift to the left (IL-1beta group, 8.7 +/- 1.7 ml/kg x min vs. control, 11.7 +/- 0.7 ml/kg x min). The IL-1beta group also showed greater PO2 and plasma lactate levels in the portal vein than did the control group. These results indicate that IL-1beta impairs systemic oxygen uptake even before VO2 becomes supply-dependent, presumably due to maldistribution of the blood flow including the splanchnic circulation.

Catalase-less peroxisomes. Implication in the milder forms of peroxisome biogenesis disorder.

We established a Chinese hamster ovary cell line having a temperature-sensitive phenotype in peroxisome biogenesis. This mutant (65TS) was produced by transforming a PEX2-defective mutant, Z65, with a mutant PEX2 gene, PEX2(E55K), derived from a patient with infantile Refsum disease, a milder form of peroxisome biogenesis disorder. In 65TS, catalase was found in the cytosol at a nonpermissive temperature (39 degrees C), but upon the shift to a permissive temperature (33 degrees C), catalase gradually localized to the structures containing a 70-kDa peroxisomal membrane protein, PMP70. In contrast to catalase, other matrix proteins containing typical peroxisome targeting signals, acyl-CoA oxidase and peroxisomal 3-ketoacyl-CoA thiolase, were co-localized with PMP70 in most cells, even at 39 degrees C. We found that these structures are partially functional peroxisomes and named them "catalase-less peroxisomes." Catalase-less peroxisomes were also observed in human fibroblasts from patients with milder forms of peroxisome biogenesis disorder, including the one from which the mutant PEX2 gene was derived. We suggest that these structures are the causes of the milder phenotypes of the patients. Temperature-dependent restoration of the peroxisomes in 65TS occurred even in the presence of cycloheximide, a protein synthesis inhibitor. Thus, we conclude that in 65TS, catalase-less peroxisomes are the direct precursors of peroxisomes.

High-resolution CT characteristics of poorly differentiated adenocarcinoma of the peripheral lung: comparison with well differentiated adenocarcinoma.

OBJECTIVE: The purpose of this study was to elucidate the characteristic high-resolution CT (HRCT) findings of poorly differentiated adenocarcinoma (PDA) in comparison with those of well differentiated adenocarcinoma (WDA). MATERIALS AND METHODS: We investigated the HRCT features of surgically resected PDAs (n=21) and WDAs (n=31). We analyzed the margin, CT attenuation, and internal architecture of the tumor and findings in the surrounding lung field, comparing them with the corresponding pathologic findings. RESULTS: Smoothness of the greater part (full-1/2 round) of the tumor and solid appearance were more prevalent in PDAs than WDAs (81% vs. 32%, 100% vs. 35%) [p<0.01]. Air-bronchogram was prevalent in WDAs (58%), but was never seen in PDAs [p<0.01]. Ground-glass opacity in PDAs pathologically corresponded to inflammation and edema in the alveolar space. CONCLUSIONS: Smoothness of the tumor margin and solid appearance without air-bronchogram were more commonly found in PDA than in WDA. HRCT may predict the histological differentiation of adenocarcinoma in selected cases in which differentiation is inconclusive by sputum cytology and transbronchial or CT-guided biopsy.

Temperature sensitivity in peroxisome assembly processes characterizes milder forms of peroxisome biogenesis disorders.

Peroxisome biogenesis disorders (PBDs) contain various clinical phenotypes; Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), decreasing in the clinical severity in this order. We found that all IRD cell lines and some NALD lines belonging to several different complementation groups are temperature-sensitive in peroxisome assembly; that is, they lacked catalase-positive peroxisomes at 37 degrees C, but do gain the peroxisomes at 30 degrees C. We identified heterozygous mutations E55K/R119Stop in the PEX2 gene of an IRD patient of complementation group F. The E55K mutation was the direct cause of the temperature-sensitivity because similar phenotypes could be transferred to PEX2-defective CHO cells by transfecting the mutant gene. Thus, temperature-sensitive peroxisome assembly is representative of milder forms of PBDs.

Visualization of gene activity in living cells.

Chromatin structure is thought to play a critical role in gene expression. Using the lac operator/repressor system and two colour variants of green fluorescent protein (GFP), we developed a system to visualize a gene and its protein product directly in living cells, allowing us to examine the spatial organization and timing of gene expression in vivo. Dynamic morphological changes in chromatin structure, from a condensed to an open structure, were observed upon gene activation, and targeting of the gene product, cyan fluorescent protein (CFP) reporter to peroxisomes was visualized directly in living cells. We found that the integrated gene locus was surrounded by a promyelocytic leukaemia (PML) nuclear body. The association was transcription independent but was dependent upon the direct in vivo binding of specific proteins (EYFP/lac repressor, tetracycline receptor/VP16 transactivator) to the locus. The ability to visualize gene expression directly in living cells provides a powerful system with which to study the dynamics of nuclear events such as transcription, RNA processing and DNA repair.

Formation of peroxisomes from peroxisomal ghosts in a peroxisome-deficient mammalian cell mutant upon complementation by protein microinjection.

Most mammalian cell strains genetically deficient in peroxisome biogenesis have abnormal membrane structures called ghosts, containing integral peroxisomal membrane protein, PMP70, but lacking the peroxisomal matrix proteins. Upon genetic complementation, these mutants regain the ability of peroxisome biogenesis. It is postulated that, in this process, the ghosts act as the precursors of peroxisomes, but there has been no evidence to support this. In the present study, we investigated this issue by protein microinjection to a mutant Chinese hamster ovary cell line defective of PEX5, encoding a peroxisome-targeting signal receptor. When recombinant Pex5p and green fluorescent protein (GFP) carrying a peroxisome-targeting signal were co-injected into the mutant cells, the GFP fluorescence gathered over time to particulate structures where PMP70 was co-localized. This process was dependent on both Pex5p and the targeting signal, and, most importantly, occurred even in the presence of cycloheximide, a protein synthesis inhibitor. These findings suggest that the ghosts act as acceptors of matrix proteins in the peroxisome recovery process at least in the PEX5 mutant, and support the view that peroxisomes can grow by incorporating newly synthesized matrix proteins.

Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure.

OBJECT: This study was performed to determine whether mild hypothermia therapy is essential for the treatment of severely head injured patients in whom intracranial pressure (ICP) can be maintained below 20 mm Hg by using conventional therapies. METHODS: Sixteen consecutive severely head injured patients fulfilled the following criteria: the patient's ICP was maintained below 20 mm Hg by using fluid restriction, hyperventilation, and high-dose barbiturate therapy; and the patient had a Glasgow Coma Scale score of 8 or less on admission. After conventional therapies had been applied, the patients were divided randomly into two groups: the mild hypothermia group (HT group; eight patients) and the normothermia group (NT group; eight patients). The HT group received mild hypothermia (intracranial temperature 34 degrees C) therapy for 48 hours followed by rewarming at 1 degree C per day for 3 days, whereas the NT group received normothermia (intracranial temperature 37 degrees C) therapy for 5 days. Specimens of cerebrospinal fluid (CSF) taken from an intraventricular catheter every 24 hours were analyzed for the presence of excitatory amino acids ([EAAs] glutamate, aspartate, and glycine) and cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, IL-8, and IL-10). The two groups did not differ significantly in patient age, neurological status, or level of ICP. There were no significant differences in daily changes in CSF concentrations of EAAs and cytokines between the two groups. The incidence of pneumonia was slightly higher in the HT group compared with the NT group (p = 0.059). The incidence of diabetes insipidus associated with hypernatremia was significantly higher in the HT group compared with that in the NT group (p < 0.01). The two groups did not differ with respect to their clinical outcomes. CONCLUSIONS: The authors recommend normothermia therapy for the treatment of severely head injured patients in whom ICP can be maintained at lower than 20 mm Hg by using conventional therapies, because mild hypothermia therapy does not convey any advantage over normothermia therapy in such patients.

Priming, second-hit priming, and apoptosis in leukocytes from trauma patients.

BACKGROUND: Polymorphonuclear leukocytes (PMNL) play important roles in both host defenses and systemic inflammatory responses after insults. The objectives of this study are to examine the serial changes in PMNL priming and apoptosis in severely injured patients and to evaluate the impact of second hits on primed PMNL function and systemic vascular endothelial damage. METHODS: Twenty-four severely injured patients (mean Injury Severity Score, 31.1 +/- 9.7) were included. Infections were seen as second hits after trauma in seven patients. Oxidative activity, phagocytosis, and apoptosis of PMNL from serial blood samples were measured by flow cytometry. Oxidative activity with no stimulus and with formylmethionyl-leucyl-phenylalanine (FMLP) were analyzed as the priming index and FMLP response, respectively. Interleukin (IL)-6, IL-10, PMNL elastase, and thrombomodulin concentrations in blood were also measured before and after the second hit. RESULTS: The PMNL priming index was elevated from days 2 to 13, especially days 2 to 5 after injury. FMLP response was enhanced from days 2 to 21 after injury. Apoptosis of PMNL was inhibited for as long as 3 weeks after injury. Infections as second hits after trauma enhanced both the priming index and the FMLP response within 24 hours after diagnosis of infection and increased serum IL-6 concentrations. However, serum thrombomodulin levels were not affected by second hits. All patients with second hits survived. CONCLUSION: Severe trauma stimulated acute-phase priming in PMNL and inhibited apoptosis. Infections after trauma induced second-hit priming in PMNL, but the unchanged serum levels of thrombomodulin suggest that priming per se may not cause systemic vascular endothelial damage.

[Evaluation of mycobacteria growth indicator tube (MGIT), an automated culture system for detection of mycobacteria from clinical specimens].

We compared the Mycobacteria Growth Indicator Tube 960 (MGIT 960) and Ogawa medium (OM) for the detection of mycobacteria (acid fast bacteria: AFB) using 882 sputum specimens. Overall, 120 strains of AFB were isolated by the MGIT 960 system and 99 strains of AFB were isolated by using OM. As far as Mycobacterium tuberculosis is concerned, 88 and 71 isolates were achieved by the MGIT 960 and OM respectively. A total of 28 isolates (18 isolates of M. tuberculosis and 10 isolates of nontuberculous mycobacteria: NTM) were detected by the MGIT 960 only whereas only 2 isolates (1 M. tuberculosis and 1 NTM) were detected by OM only. Of these sputum specimens, 72 were smear positive for AFB. The rates of smear negative but culture positive specimens were 8.0% (65 out of 809) for the MGIT 960 system and 6.2% (50 out of 809) for OM. The contamination rate for MGIT 960 was only 1.2%. The average time required for detection of M. tuberculosis was 14.1 days by the MGIT 960 system and 24.6 days by OM. For the NTM, the average detection time were 8.3 days for the MGIT 960 system and 22.8 days for OM. These results indicate that the MGIT 960 system allows detection of mycobacteria significantly faster than OM.

Resected peripheral small cell carcinoma of the lung: computed tomographic-histologic correlation.

In order to clarify the characteristic computed tomographic findings of peripheral small cell lung cancer, the authors investigated 12 patients with surgically resected and histologically proven peripheral small cell lung cancer. Conventional computed tomography was performed on all, and additional high-resolution computed tomographic images were obtained for nine patients. Marginal, internal, and surrounding features of the tumors were analyzed, and these findings were correlated with histologic findings. All 12 tumors appeared as homogenous masses, and eight had well-defined margins. Lobulation was found in seven, marginal ground-glass opacity in three, fine spiculation in two, and both ground-glass opacity and spiculation in one. Cut specimens showed whitish medullary masses without large areas of necrosis, and microscopic specimens showed small areas of necrosis in 11 patients. Marginal ground-glass opacities corresponded to focal edema and hemorrhage in two patients and to intraalveolar invasion in one. Fine spiculation corresponded to vascular/lymphatic invasion in one patient and to irregular intraalveolar spread in another. The authors concluded that a homogenous mass without necrosis is the most characteristic feature of peripheral small cell carcinoma on computed tomography.

Adaptive spatial filtering technique for storage phosphor radiography in portable chest radiographs: parameter optimization.

PURPOSE: To investigate the optimal parameters of adaptive spatial filtering (ASF) in storage phosphor radiography for processing portable chest radiographs. MATERIALS AND METHODS: Two types of weighting factor curves starting at 383 digital pixel values (PV) (type B) and at 511 PV (type C) were selected for the optimization of ASF. The PV of 27 areas of apparent pulmonary lesions and seven retrocardiac areas were measured for original unprocessed and ASF-processed images. Three radiologists compared 30 ASF-processed portable chest radiographs with apparent pulmonary or pleural lesions with unprocessed images. RESULTS: PV measurements revealed no significant change in pulmonary densities in type B, and an increase in PV of lower pulmonary densities in type C. Densities of retrocardiac areas were more enhanced in type C than in type B. Observer testing showed that pulmonary densities were evaluated as unchanged in 90% of type B images and 76% of type C images. Changes in mediastinal densities were evaluated as adequate in 80% of type B and 90% of type C images. CONCLUSION: The starting point of the weighting factor curve of ASF in portable chest radiographs should be set the same as in chest radiographs in the upright posteroanterior position with high kVp.