Association of subpleural ground-glass opacities with respiratory failure and RNAemia in COVID-19.

OBJECTIVES: To examine the radiological patterns specifically associated with hypoxemic respiratory failure in patients with coronavirus disease (COVID-19). METHODS: We enrolled patients with COVID-19 confirmed by qPCR in this prospective observational cohort study. We explored the association of clinical, radiological, and microbiological data with the development of hypoxemic respiratory failure after COVID-19 onset. Semi-quantitative CT scores and dominant CT patterns were retrospectively determined for each patient. The microbiological evaluation included checking the SARS-CoV-2 viral load by qPCR using nasal swab and serum specimens. RESULTS: Of the 214 eligible patients, 75 developed hypoxemic respiratory failure and 139 did not. The CT score was significantly higher in patients who developed hypoxemic respiratory failure than in those did not (median [interquartile range]: 9 [6-14] vs 0 [0-3]; p < 0.001). The dominant CT patterns were subpleural ground-glass opacities (GGOs) extending beyond the segmental area (n = 44); defined as "extended GGOs." Multivariable analysis showed that hypoxemic respiratory failure was significantly associated with extended GGOs (odds ratio [OR] 29.6; 95% confidence interval [CI], 9.3-120; p < 0.001), and a CT score > 4 (OR 12.7; 95% CI, 5.3-33; p < 0.001). The incidence of RNAemia was significantly higher in patients with extended GGOs (58.3%) than in those without any pulmonary lesion (14.7%; p < 0.001). CONCLUSIONS: Extended GGOs along the subpleural area were strongly associated with hypoxemia and viremia in patients with COVID-19. KEY POINTS: • Extended ground-glass opacities (GGOs) along the subpleural area and a CT score > 4, in the early phase of COVID-19, were independently associated with the development of hypoxemic respiratory failure. • The absence of pulmonary lesions on CT in the early phase of COVID-19 was associated with a lower risk of developing hypoxemic respiratory failure. • Compared to patients with other CT findings, the extended GGOs and a higher CT score were also associated with a higher incidence of RNAemia.

Contactless electrical conductivity measurement of metallic submicron-grain material: Application to the study of aluminum with severe plastic deformation.

We measured the electrical conductivity σ of aluminum specimen consisting of submicron-grains by observing the AC magnetic susceptibility resulting from the eddy current. By using a commercial platform for magnetic measurement, contactless measurement of the relative electrical conductivity σn of a nonmagnetic metal is possible over a wide temperature (T) range. By referring to σ at room temperature, obtained by the four-terminal method, σn(T) was transformed into σ(T). This approach is useful for cylinder specimens, in which the estimation of the radius and/or volume is difficult. An experiment in which aluminum underwent accumulative roll bonding, which is a severe plastic deformation process, validated this method of evaluating σ as a function of the fraction of high-angle grain boundaries.

Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Cultured stellate cells in human vocal fold mucosa.

OBJECTIVES: Stellate cells in the maculae flavae, located at both ends of the human vocal fold mucosa, have been considered an independent category of cells. We aimed to isolate and subculture these stellate cells, and to observe their morphological characteristics. METHODS: Stellate cells from the maculae flavae and fibroblasts from Reinke's space were cultured in three normal, adult human vocal fold mucosa preparations. RESULTS: The subcultured cells from Reinke's space were conventional fibroblasts. The subcultured cells from the maculae flavae were stellate in shape and had cytoplasmic processes. They were larger than conventional fibroblasts, and lipid droplets in the cytoplasm disappeared in the second culture. These stellate cells proliferated by attaching their cytoplasmic processes to each other. During the seven to 10 month subculture period, each cell type continued to exhibit its own morphological characteristics. CONCLUSION: This study demonstrated that such stellate cells form an independent cell category, which should be considered as a new category of cells within the human vocal fold.

Diffusion-weighted magnetic resonance imaging in infants with periventricular leukomalacia.

OBJECTIVE: We examined diffusion-weighted magnetic resonance imaging (DWI) findings in periventricular leukomalacia (PVL) and then evaluated the relationship between the mean apparent diffusion coefficient (ADC) values and the region and severity of PVL. METHODS: Between April 2006 and July 2007, 98 infants at gestational ages between 27 and 33 weeks were enrolled in the study. DWI was performed during the first week of life when electroencephalography indicated PVL. The mean ADC values were evaluated using regions of interest drawn manually in the periventricular white matter, posterior limbs of internal capsules (PLICs), and various regions of the brain. RESULTS: DWI was performed in three of four infants with PVL indicated on electroencephalography. All had decreased diffusivity in the anterior to posterior white matter despite a predominance in the posterior white matter. DWI abnormalities were also observed in the corpus callosum and PLICs and were more broadly distributed in the brain than those detected by later conventional MRI. In the PLICs, the changes in the ADC values were correlated with the severity of the PVL. CONCLUSION: The DWI findings provided additional information regarding PVL. Among the findings, the association of the presence of decreased diffusivity in the corticospinal tract with later motor impairment was the most interesting.

Tentorial papillary meningioma in a child: case report and review of the literature.

We report a usual case of papillary meningioma arising from tentorium cerebelli occurring in a 13-year-old boy. This patient presented a 3-month history of a mildly poor coordination of the left side of his body. Computed tomography showed a homogenous enhanced mass lesion in the left posterior fossa. At surgery, gross total resection of the tumor was accomplished. Upon microscopic examination, some tumor cells were arranged in the papillary pattern and a resulting diagnosis of papillary meningioma was made. Electron microscopic studies showed typical meningioma features such as interdigitations and desmosomes, which were, however, detectable in only few tumor cells. Cytological and ultrastructural features of pediatric papillary meningioma and of high-grade meningioma in general are sparse. Since papillary meningioma rarely presents in children, we report this case and review the literature.

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19.

Hypercalcemia is relatively rare but clinically important complication in childhood leukemic patients. To clarify the clinical characteristics, mechanisms of hypercalcemia, response to management for hypercalcemia, incidence of t(17;19) and final outcome of childhood acute lymphoblastic leukemia (ALL) accompanied by hypercalcemia, clinical data of 22 cases of childhood ALL accompanied by hypercalcemia (>12 mg/dl) reported in Japan from 1990 to 2005 were retrospectively analyzed. Eleven patients were 10 years and older. Twenty patients had low white blood cell count (<20 x 10(9)/l), 15 showed hemoglobin> or =8 g/dl and 14 showed platelet count > or =100 x 10(9)/l. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcemia was confirmed in 11 of the 16 patients in whom elevated-serum level or positive immunohistochemistry of PTHrP was observed. Hypercalcemia and accompanying renal insufficiency resolved quickly, particularly in patients treated with bisphosphonate. t(17;19) or add(19)(p13) was detected in five patients among 17 patients in whom karyotypic data were available, and the presence of E2A-HLF was confirmed in these five patients. All five patients with t(17;19)-ALL relapsed very early. Excluding the t(17;19)-ALL patients, the final outcome of ALL accompanied by hypercalcemia was similar to that of all childhood ALL patients, indicating that the development of hypercalcemia itself is not a poor prognostic factor.

The immunohistochemical expression of p21WAF1/Cip1 and Proliferating cell nuclear antigen in laryngeal squamous cell carcinomas.

The purpose of this study was to assess the significance of the expression of p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who had undergone operations between 1998 and 2003 were included in this study. The Envision immunohistochemistry method was utilized to stain these tissue specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show any correlation with differentiation, N stage, metastasis, survival, recurrence or the laryngeal site of involvement. A significant inverse correlation was detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of PCNA labelled cells showed a significant correlation with the T stage, but not with other clinicopathological parameters. There were differences in the expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may play an important role in the progression of carcinoma of the supraglottic larynx.

[Nonpenetrating traumatic injury of the thoracic aorta and left subclavian artery; report of a case].

Nonpenetrating traumatic injury of the thoracic aorta and/or its major branch is usually fatal and the treatment of this condition carries extremely high risk because of associated visceral organ injuries. Accurate diagnosis have been difficult. However, recently developed multi-slice helical computed tomography (CT) is highly sensitive in early detection of precise location of injury and associating injuries of other organs. Here we report our case with combined thoracic aortic and left subclavian artery injuries, diagnosed by 3-dimensional (3-D) CT and treated successfully.

Power Doppler sonography of hepatocellular carcinomas with portal-vein blood supply.

We report the power Doppler imaging (PDI) findings in 2 cases of hepatocellular carcinoma (HCC) with a portal-vein blood supply. Gray-scale sonography in both cases showed a well-circumscribed nodule, hypoechoic in case 1 and hyperechoic in case 2. PDI revealed an afferent tumor vessel with constant flow in both nodules, and CT during arterial portography demonstrated a portal-vein supply to both nodules. The nodules were diagnosed by percutaneous core biopsies as highly differentiated HCC. We also examined with PDI another 64 patients with 76 HCC nodules, and none of the nodules showed a constant-flow afferent tumor vessel. The presence of a constant-flow afferent tumor vessel indicates a supplying portal vein; but this is not diagnostic of HCC, and biopsy remains necessary to establish a final diagnosis.

Outcome prediction by molecular detection of minimal residual disease in bone marrow for advanced neuroblastoma.

BACKGROUND: We have determined whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB). PROCEDURE: Bone marrow samples from 19 patients over 12 months of age with stage 4 neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) mRNA using reverse transcription-polymerase chain reaction (RT-PCR). All patients received repetitive multi-drug chemotherapy including cisplatin, cyclophosphamide or ifosphamide, adriamycin, and etoposide or vincristine. Seventeen patients received myeloablative therapy with hematopoietic stem cell transplantation after achieving complete remission. RESULTS: All but one patient were histologically positive for tumor cells in BM samples at diagnosis, and they became negative for tumor cells within 3 months histologically. By the RT-PCR analysis, all patients were positive for TH mRNA in BM samples at diagnosis, and they became negative for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM samples became negative for TH mRNA within 4 months after the start of chemotherapy remained alive without evidence of disease (median 61 months, range 20-76). In contrast, 12 of 13 patients whose BM samples remained positive at that time developed relapse and 10 of them died of disease (median 24 months, range 13-43). There was a statistically significant difference in survival between the two groups (P < 0.05). No significant difference of clinical characteristics by the MRD positivity at 4 months after the start of chemotherapy. CONCLUSIONS: Persistence of MRD in BM at 4 months after the start of chemotherapy could predict poor prognosis in advanced neuroblastoma.

Disease outcome may be predicted by molecular detection of minimal residual disease in bone marrow in advanced neuroblastoma: a pilot study.

PURPOSE: This pilot study focussed on whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma. PATIENTS AND METHODS: Bone marrow samples from 21 patients older than age 12 months with stage IV neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) messenger ribonucleic acid (mRNA) using reverse transcription-polymerase chain reaction (RT-PCR). Twenty patients received myeloablative therapy with hematopoietic stem cell transplantation after achieving complete remission. RESULTS: All BM samples of patients except that of one patient was cytologically positive for neuroblastoma cells at diagnosis, and they became negative for neuroblastoma cells within 3 months by cytologic examination. By RT-PCR analysis, BM samples of all patients were positive for TH mRNA at diagnosis, and samples of 19 patients became negative for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM samples became negative for TH mRNA within 4 months after the start of chemotherapy remained alive without evidence of disease (median 76 mos, range 36-91). In contrast, out of 15 patients whose BM samples remained positive, 10 patients had relapse develop and 9 patients died from disease (median 15 mos, range 10-25). There was a statistically significant difference in disease-free survival between the two groups (P < 0.05). CONCLUSION: Persistence of MRD in BM may predict poor prognosis in advanced neuroblastoma.

The predictive value of p53, Ki-67 and angiogenetic factors in primary hypopharyngeal carcinoma.

To evaluate the predictive role of the oncogene p53, the proliferating marker Ki-67, angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/dThdPase) and vascular endothelial growth factor (VEGF) in primary hypopharyngeal carcinoma, we immunohistochemically studied a series of 84 primary hypopharyngeal carcinoma patients who were treated at the Department of Otolaryngology of Kurume University Hospital between 1990 and 1997. The correlation of each score according to the intensity and percentage of the labeled cells with the TNM stage, histological grade, metastasis and survival status was analyzed. The positive rate of p53 was 52.4%. The percentages of Ki-67 labeled cells in patients with or without metastasis showed a significant difference (p = 0.011). VEGF also showed a significant difference between the live and death groups (p < 0.05) and also among the differentiation group (p < 0.05). A statistically significant correlation was also seen between the score of Ki-67 and VEGF (r = 0.438, p < 0.001) or the score of Ki-67 and PD-ECGF (r = 0.259, p < 0.001), respectively. In conclusion, the present study suggests that a correlation exists between proliferating and angiogenesis, and VEGF and Ki-67 are thus considered to be possible prognostic discriminators in hypopharyngeal carcinoma.

Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions.

The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly (MHA), Sebastian syndrome (SBS), and Fechtner syndrome (FTNS), are rare platelet disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like leukocyte inclusions. The locus for these disorders was previously mapped on chromosome 22q12.3-q13.2 and the disease gene was recently identified as MYH9, the gene encoding the nonmuscle myosin heavy chain-A. To elucidate the spectrum of MYH9 mutations responsible for the disorders and to investigate genotypephenotype correlation, we examined MYH9 mutations in an additional 11 families and 3 sporadic patients with the disorders from Japan. Korea, and China. All 14 patients had heterozygous MYH9 mutations, including three known mutations and six novel mutations (three missense and three deletion mutations). Two cases had Alport manifestations including deafness, nephritis, and cataracts and had R1165C and E1841K mutations, respectively. However, taken together with three previous reports, including ours, the data do not show clear phenotype-genotype relationships. Thus, MHA, SBS, and FTNS appear to represent a class of allelic disorders with variable phenotypic diversity.

[Hemodynamics of the lower extremities in patients with decubitus ulcers using the ultrasonic Doppler method].

Our clinical experience indicates that decubitus ulcers with tissue loss/necrosis extending beyond the subcutaneous fat in aged patients are liable to become refractory and that most of these patients experience a cold feeling/cyanosis in the lower extremities. In order to determine the relationship between the severity of the decubitus ulcers and the hemodynamics in the lower extremities, we conducted a blood flow test using the ultrasonic Doppler method on the lower extremities in patients. Sixty-eight inpatients (38 men, 30 women, with an average age of 80.5 +/- 7.6 years old) were selected. B-mode tomographs were obtained with an ultrasonic diagnostic apparatus. The power Doppler method was used to measure blood flow rate, vascular lumen diameter, and intravascular blood flow at the dorsalis pedis artery, posterior tibial artery, peroneal artery furcation, and femoral artery. The subjects were divided into three groups: patients without decubitus ulcers; patients with mild to moderate decubitus ulcers of IAET Classification grade I-III; and patients with severe decubitus ulcers (IAET Classification grade IV), and the measurements were compared among the groups. The results revealed a tendency for the vascular lumen to become narrowed and intravascular blood flow to be reduced at all sites as decubitus ulcers increased in severity and showed the hemodynamics in the lower extremities to be particularly poor in the severe group. We measured the hemodynamics in the lower extremity with the ultrasonic Doppler method from the viewpoint of decubitus ulcer prevention and found differences in blood flow in the lower extremities according to the severity of decubitus ulcers. A reduction in blood flow in the lower extremities is considered to indirectly indicate a susceptibility to decubitus ulcers and to serve as a sign of its exacerbation. We consequently considered the test to be useful and concluded that deterioration of hemodynamics due to the progress of arteriosclerosis is one of the causes of decubitus ulcer exacerbation.

Effects of milrinone on platelet aggregation in swine with pulmonary hypertension.

PURPOSE: The purpose of this study was to investigate whether the effect of milrinone on platelet aggregation was related to the selectivity of vasodilation vasculature in a swine model with PH. MATERIALS AND METHODS: To induce pulmonary hypertension, we injected two sets of acid-washed glass beads in 15 swine, which were divided into two groups (those receiving milrinone or not) and compared with each other. RESULTS: The induction of pulmonary hypertension decreased the platelet count and increased the plasma levels of thromboxane B2 and 6-keto-prostaglandin F1alpha. CONCLUSION: A locally high concentration of prostaglandin I2, at least in part, may produce selectivity of vasodilation in the pulmonary vasculature.

Factors affecting water balance and fecal moisture content in suckling calves given dry feed.

Holstein bull calves were used to examine factors affecting water balance and fecal moisture content in suckling calves given dry feed for 2 wk from 1 wk of age. In Experiment 1 (n = 16), the shift of water balance (decreased urine volume, and increased water retention and fecal water excretion) and elevation of fecal moisture content were greatest when calf starter and Sudangrass hay were fed in addition to liquid milk replacer, compared with calves receiving only milk replacer. Intermediate changes occurred when calves were fed milk replacer and calf starter or milk replacer, calf starter, and rice straw. Water retention was correlated positively with digestible DMI and negatively with urine volume. Fecal water excretion was highly correlated with fecal DM excretion. In Experiment 2 (n = 18), water balance and fecal moisture content during wk 2 were affected by free access to calf starter and hay from wk 1. Urine volume of calves fed dry feed and milk replacer was lower than that of calves fed only milk replacer; however, when water was available in addition to dry feed, urine volume was similar to that of calves fed only milk replacer. Fecal water excretion was highly correlated with water retention rather than with fecal DM excretion, suggesting a close relationship to extracellular fluid volume. Ruminal fermentation would be an important factor affecting both water balance and fecal moisture content in suckling calves given dry feed.

[Epidemiological characteristics and virulence factor of verotoxin-producing Eschericia coli O121:H19 isolated in Akita Prefecture in July 1997].

Epidemiological characteristics and virulence factors of VTEC O121:H19 strains isolated in July 1997 from a 15 year old female and a 20 year old male patient suffering from bloody diarrhea and severe abdominal pain were examined. The 2 VTEC O121:H19 isolates showed identical antibiotic susceptibility patterns, biochemical characteristics and plasmid profile while slight differences were observed in their Xba I and Not I PFGE patterns, suggesting that closely related 2 VTEC O121:H19 strains evoked the sporadic infectious cases in July 1997. The 2 VTEC O121:H19 isolates, as well as VTEC O157:H7, possessed eaeA gene and a ca. 60 MDa plasmid which hybridised with CVD 419 probe and produced enterohemolysin. In addition, the VTEC O121:H19 isolates produced almost the same amount of VT-2 in vitro as VTEC O157:H7 did. These results suggested that VTEC O121:H19 possesed the virulence factor comparable to that of VTEC O157:H7. Incidence, molecular epidemiology and infectious source of VTEC O121:H19 in this country have not been sufficiently understood. Antiserum for E. coli serogroup O121 should be manufactured to clarify the epidemiology of the highly virulent VTEC strain.

Expression of transfected human Na+/H+ exchanger (NHE-1) in the the basolateral membrane of opossum kidney cells.

Some epithelial cells have Na+/H+ exchanger (NHE) activity in both apical and basolateral membranes. Amiloride-sensitive NHE-1 is generally identified in the basolateral membrane. The renal cell line, OK7a, targets amiloride-resistant NHE predominantly to the apical membrane. It is controversial whether the transfected NHE-1 is targeted preferentially to the basolateral membrane in OK7a cells, when human NHE-1 is chronically expressed under control of constitutively active promoters. We tried to identify the membranes in which the transfected human NHE-1 could be detected following acute expression in OK7a cells. We have always observed small Na(+)-dependent pH recovery in the basolateral membrane in OK7a cells. It is, however, controversial whether or not OK7a cells express NHE activity in the basolateral membrane. We also characterized Na(+)-dependent pH recovery in the basolateral membrane. It was not inhibited by [4,4'diisothiocyanatostilbene-2,2'-disulfonic acid] (DIDS), [4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid] (SITS), or contralateral amiloride. Li+ but not K+, chol+, or NMG+ could replace Na+. These results are consistent with the presence of the NHE in the basolateral membrane. NHE activities were predominant in the apical membrane and those in both membranes were resistant to amiloride analogs. After stable transfection with human NHE-1 in a vector utilizing the metallothionein promoter, overnight induction with Zn(2+)increased the NHE activity and its sensitivity to amiloride only in the basolateral membrane in OK7a cells. We conclude that the transfected human NHE-1 is exclusively targeted to the basolateral membrane of OK7a cells during acute induction.