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.

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.

An orphan nuclear receptor lacking a zinc-finger DNA-binding domain: interaction with several nuclear receptors.

The yeast two-hybrid screening was applied to cloning cDNAs of proteins that interact with peroxisome proliferator-activated receptor alpha (PPAR alpha). We obtained from a rat liver cDNA library a clone encoding a protein related to the ligand-binding domain of the members of nuclear hormone receptor superfamily, whereas apparently lacking the zinc-finger DNA-binding domain. This protein interacted with the activated forms of several nuclear receptors, and thus is a novel type of heterodimer-forming nuclear receptor.

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.

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.

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.

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.

Antitumour effect of fibrinogen microspheres containing doxorubicin on Ehrlich ascites carcinoma.

The antitumour activity of fibrinogen microspheres containing doxorubicin has been evaluated against Ehrlich ascites carcinoma in mice in terms of changes in body weight and survival. Tumour cell injections were made on day 0 and microsphere injections on day 1, both intraperitoneally. The suppressive effect of the drug-containing microspheres on increase in body weight was higher than that of the free drug, and tumour-bearing mice given the microspheres lived longer than those given the free drug.

Hemodialysis effect on serum boron level in the patients with long term hemodialysis.

Serum and dialysate boron levels in 17 patients with long term hemodialysis (HD) were determined by inductively coupled plasma emission spectrometry (ICPES). Serum boron level was compared with the value of age matched 467 healthy controls and the relationship between serum and dialysate boron level was analyzed. The results showed that serum boron level was significantly higher at the beginning of HD, and lower at the completion of HD in comparison with controls. Although the dialysate was contaminated with trace boron, HD resulted in an excessive decrease of serum boron, rather than boron exposure from the dialysate. Boron hemodialyzability was almost proportional to the gradient of the boron level at the beginning of HD and it could be controlled by the adjustment of the gradient. In conclusion, the serum boron level was very much disturbed in long term HD patients. If boron excess in serum at the beginning of HD, or deficiency at the completion of HD may contribute to the complications of HD patients, fine adjustment and close surveillance of the gradient should be taken into account.

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.

Neural network analysis of breast cancer from MRI findings.

PURPOSE: To evaluate how much the experience of radiologists affects the performance of an artificial neural network (ANN) trained by two highly experienced radiologists. MATERIALS AND METHODS: Before biopsy two experienced radiologists reviewed the MR images of 100 adult patients with suspicious breast lesions and evaluated their findings based on six features. This database was then used to train a three-layered feed-forward neural network. The network's generalizing ability was then tested to predict the outcome of biopsy in 56 new patients' records which were extracted by 10 participating radiologists. The MRI findings of each reader were presented to the ANN to evaluate the effect of various levels of experience on the output of the ANN. The performance of the ANN was then compared with that of attendant physicians in terms of sensitivity, specificity, and accuracy as well as ROC analysis. RESULTS: The best ANN outcome offered a correct diagnosis in 40 of 41 of the patients with malignant breast cancer and 10 of 15 with benign entity presented in the testing set. The output of the trained ANN outperformed the attendant radiologists with low levels of experience and showed comparable performance with radiologists with higher levels of experience. CONCLUSIONS: The ANN is able to work as a backup system to assist radiologists in the diagnosis of breast cancer.

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.

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.

Intra-arterial digital subtraction angiography with extra-large fields using a computed radiography system in evaluating peripheral vascular disease.

The authors evaluated the usefulness of intra-arterial digital subtraction angiography (DSA) with extra-large field sizes using a computed radiography (CR) system in evaluating peripheral vascular disease (PVD). Intra-arterial DSA using CR was performed in 55 patients with suspected PVD. A 4 F catheter was advanced into the abdominal aorta via the transbrachial approach and 90 ml of contrast medium was injected during six exposures using a long leg changer mounting a total of 18 imaging plates on six surfaces. Visualization of the superficial femoral and popliteal arteries was judged as diagnostic in all cases. The abdominal aorta, iliac arteries, and subtrifurcation were also visualized in most cases, but visualization was suboptimal in some cases. As a complication, median nerve palsy occurred in one case. This technique is thought to be a useful method for evaluating PVD because of the advantages of a large field of view and wide exposure latitude, in spite of its relatively long processing time.

[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.

[Study of diarrhea-inducing strains of Escherichia coli mainly isolated in Kanto area between June and September 1996].

A total of 21,609 faecal specimens obtained from patients with diarrhea mainly in Kanto area between June and September 1996 were investigated to identify the causative pathogens for diarrhea. One-hundred fifty-seven strains of Escherichia coli of 29 different O-serotypes were isolated as the causative pathogens, which were previously recognized to induce severe abdominal cramps and diarrhea. Of these, 114 strains, in which the possibility of enterohemorrhagic E. coli due to their O-serotypes was predicted, were examined for the producibility of Vero toxins. Twenty-six (76.5%) of the 34 strains of E. coli O157 produced the Vero toxins, and other 8 strains were the non-producers. Twenty of the 26 producers produced both VT1 and VT2, whereas the other 6 strains produced VT2 only. Furthermore, 4 strains of E. coli O26, and 1 strain each of E. coli O125 and O126 produced Vero toxins. Thirty-two of the 114 strains, isolated from the patients with diarrhea and selected as the enterohemorrhagic E. coli according to the specific O-serotypes, were actually confirmed produce Vero toxins. Thirty-four strains of E. coli O157 tested were susceptible to all antibiotics such as ampicillin, doxycylin, levofloxacin, fosfomycin, chloramphenicol and polymyxin B, and no strains resistant to levofloxacin, polymyxin B and fosfomycin were found.

Pathohistological study on changes observed in the temporomandibular joint after experimental mutilation and shortening of the mandibular process with special reference to the changes under abnormal mandibular movement.

Abnormal mandibular movement continues to occur when fracture of the mandibular process has resulted in abnormal occlusion or abnormal mandibular movement. However, what changes might occur in the temporomandibular joint have not yet been fully clarified. In the present study, a fracture of the condylar process was experimentally induced in rats, and the resulting bone ends were wired in place. That is to say, the resulting displacement was fixed permanently. Histological studies were made on the changes of the temporomandibular joint at the postoperative third month in those rats which demonstrated abnormal occlusion and abnormal mandibular movement. Lack of uniformity of the fibrous layer and a shallowing of the mandibular fossa; proliferation of the fibrous connective tissue and reduction in size of the superior and inferior articular cavity; tylosis and irregularity in the articular disc; deformation and tylosis of the fibrous layer of the articular cartilage, tendency of the layer structure in the articular cartilage to disappear, and some effect on cartilaginous ossification in the condyle; flattening of the condyle and thinning of the layer structure in the condylar articular cartilage in the unaffected side of the mandibular joint. These changes were observed to be more marked as the displacement and occlusal abnormality of the mandible intensified, showing no morphological adaptation of the temporomandibular joint.

Influence of copper on MRI of hepatocellular carcinoma.

The purpose of this paper is to clarify whether copper accumulation in hepatocellular carcinoma (HCC) is a cause of high intensity signal pattern on T1-weighted images (T1-WI) by comparing the histologically proven copper accumulation with MR images. Forty-five surgically resected HCCs were analyzed. Distribution patterns of divalent copper by a modified Timm's method on their maximum cut surfaces were compared with signal patterns on corresponding T1-WI. The degree of copper accumulation in tumor compared with surrounding liver tissue was higher in 6 lesions, equal in 17 lesions, and lower in 22 lesions. High intensity pattern on T1-WI were observed in 3 of 6 lesions (50%), 10 of 17 lesions (59%), and 10 of 22 lesions (45%). Distribution patterns of copper were not correlated with intensity patterns on T1-WI. We conclude that the paramagnetic effect of divalent copper accumulation in HCC is insufficient to influence the MRI.