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.

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.

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.

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.

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.

[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.

Establishment of enzyme immunoassay of human thrombomodulin in plasma and urine using monoclonal antibodies.

Thrombomodulin, TM, is an endothelial cell membrane protein acting as a cofactor for the activation of plasma protein C. Soluble TM is present in plasma and urine of normal subjects. Enzyme immunoassay, EIA, for human TM was developed using mouse monoclonal antibodies against human placental TM in this paper. We obtained four types of the monoclonal antibodies against human placental TM. EIA sandwich method using three types of the monoclonal antibodies enabled us to measure almost all of 6 and 7 TM subspecies in plasma and urine, respectively, except 1 subspecies, 31 kDa TM. There was no interference from other components of plasma and urine in the assay conditions. Titration curves of purified TM in buffer or in normal plasma were linear within the range from 0.08 to 10 ng/ml. The coefficient of variation at 0.08 ng/ml TM was 4.7%. TM titer with buffer, assayed by this method, was reduced by the addition of thrombin at the final concentration of 20 U/ml, but the titer with plasma was not reduced even at 100 U/ml. These concentrations of thrombin are far larger than those which would be formed in circulation. TM levels in plasma and urine of normal subjects collected in the morning were 35.2 +/- 8.32 ng/ml (n = 346) and 111 +/- 31.6 ng/ml (n = 33), respectively. TM level in plasma did not differ from the level in serum. Circadian fluctuation of plasma TM was not significant in 10 normal adults, although a tendency of increase in TM excretion to urine was found rather in the day time than the other times.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of matrix metalloproteinase-2 (mmp-2) in cervical neoplasia - immunohistochemical and in-situ hybridization studies.

The expression of matrix metalloproteinase-2 (MMP-2, type IV collagenase, 72 kDa) in 47 cervical precancerous and cancerous lesions were localised by in situ hybridization and immunohistochemical studies. MMP-2 mRNA was present in the stromal cells surrounding invasive cells in the majority of squamous cell carcinomas and adenocarcinomas. In contrast, MMP-2 immunoreactivity was found in the epithelial cells. Our results indicate that there may be some interaction between carcinoma cells and stromal cells to produce MMP-2 which may contribute to the destruction of the extracellular matrix in invasive cervical carcinomas.

Prostaglandin F2 alpha and indomethacin in hepatogenic pulmonary angiodysplasia. Effects on pulmonary hemodynamics and gas exchange.

We treated a 68-year-old man with cirrhosis of the liver associated with moderate hypoxemia. Contrast-enhanced echocardiography revealed late opacification of the left ventricle, and pulmonary perfusion imaging with 99mTc macroaggregated albumin showed evidence of a significant uptake in both lungs and in the liver, spleen, and kidneys. Right cardiac catheterization revealed pulmonary hypotension, low pulmonary vascular resistance, and high cardiac output. We administered prostaglandin F2 alpha intravenously (0.2 microgram/kg/min for 30 minutes) and indomethacin orally (75 mg/day for three days). There was some degree of resolution of the hypoxemia and increases in both pulmonary arterial pressure and pulmonary vascular resistance. These findings suggest that the pathophysiology of hepatogenic pulmonary angiodysplasia is a reversible intrapulmonary vascular dilatation. These conditions can to some extent be modulated by vasoactive substances such as prostaglandins or other eicosanoids.

Long-range effect of mutation of calcium binding aspartates [correction of asparates] on the catalytic activity of alkaline protease from Pseudomonas aeruginosa.

Apart from a catalytic domain, the alkaline protease of Pseudomonas aeruginosa has a novel parallel beta-helix domain stabilized through Ca2+ binding. In order to clarify the importance of the beta-helix structure in maturation of the enzyme, aspartic residue D-356 or D-365 in the Ca2+ binding sequence motif was replaced with L-alanine, and the catalytic activity of each mutant was assayed. These mutants did not show any proteolytic activity, although the composition of their polypeptide chains was the same as that of the wild type except for the mutated alanine residue. These results suggest that D-356 and D-365 are important in control of the beta-helix folding induced by Ca2+ binding and that incomplete beta-helix folding due to the lack of their side-chains affects the maturation of the enzyme in the long-range order.

Neural cell adhesion molecule expression in thyroid cancer.

Neural cell adhesion molecule (NCAM) is an integral membrane glycoprotein that participates in cell-cell interactions. We examined the expression of neural cell adhesion molecule (NCAM) by immunohistochemistry in 65 cases of thyroid disease. In the majority of thyroid tumors, NCAM expression was detected in tumor cells. In chronic thyroiditis, Hurthle cells demonstrated expression of NCAM. In normal thyroid gland, neither follicular nor parafollicular cells expressed NCAM at detectable levels. All papillary carcinomas and most poorly differentiated follicular carcinomas and some follicular adenomas demonstrated NCAM expression. In thyroid carcinoma, clinical stage and recurrent laryngeal nerve paralysis did not correlate significantly with expression of NCAM. Papillary carcinomas with strong expression of NCAM were more likely to have extra capsular invasion. It is supposed that immunohistochemical detection of NCAM expression supports histologic diagnosis and offers prognostic information.

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.

Analysis of expression of matrix metalloproteinases-2 and -9 in hypopharyngeal squamous cell carcinoma by in situ hybridization.

The gene expression of two type IV collagenases (matrix metalloproteinase [MMP]-2, a 72 kd type IV collagenase, and MMP-9, a 92 kd type IV collagenase) was investigated in carcinomas of the hypopharynx. We examined 27 cases operated on in our hospital by an in situ hybridization technique to detect their messenger RNA signals in cancer cells and surrounding stroma. Both signals were detected in all cancer nests and in stromal cells in the same specimens. Clinicopathologic studies showed a significant relationship between MMP-2 expression in the primary cancer and the outcome of treatment. Our present study suggests that hypopharyngeal squamous cell carcinoma producing MMP-2 has a high potential for invasion and metastasis and a poor outcome. The analysis of MMPs will be useful for treatment planning in hypopharyngeal carcinoma and for prognosis.

Fine needle aspiration cytology of glycogen-rich clear cell carcinoma of the breast. A case report.

BACKGROUND: Glycogen-rich clear cell carcinoma (GRCC) is a rare variant of breast carcinoma that was first described by Hull et al in 1981. The histologic findings have been described; however, the cytologic characteristics have not been well described. CASE: A 44-year-old female exhibited a palpable mass in her right breast. The fine needle aspirate contained cell clusters in a necrotic background. In addition to carcinoma cells with increased degrees of nuclear atypia, carcinoma cells with less atypia were identified. The tumor cells contained small round or ovoid nuclei and abundant, clear cytoplasm. The tumor, resected by modified radical mastectomy, was diagnosed as GRCC with detection of glycogen accumulation in the cytoplasm. CONCLUSION: Although rare, glycogen-rich clear cell carcinoma should be considered in the differential diagnosis of breast cancer in fine needle aspiration cytology to prevent misdiagnosis because of its varied morphologic patterns and less atypical cytologic features.

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.

[A familial outbreak of verotoxin-producing Escherichia coli O103:H2 infection in which a calf was the suspected infectious source].

A familial outbreak of Verotoxin-producing Escherichia coli (VTEC) infection occurred in July 1996 in AKITA prefecture. Four VTEC strains harboring VT-1 and eaeA genes were isolated from three patients and a calf, breeding farm for which was located as close as 4 meters from the house where the patients lived in. All of the 4 VTEC isolates were serotyped as O63:H2 using commercially available sera kits. However, a patient isolate, EC-281, was serotyped as 0103:H2 at the International Escherichia and Klebsiella Centre. Titration and absorption tests using rabbit antisera raised against EC-281 confirmed that the serogroup of the remaining 3-VTEC isolates was also O103. Epidemiological characteristics including plasmid profile, antibiotic susceptibility patterns and pulsed-field gel electrophoresis patterns of the 4 VTEC isolates were completely the same, indicating that these isolates originated from a common source. These findings in conjunction with the results of epidemiological survey conducted by the Health Center suggested that a possible infectious source for this outbreak is the calf. Our present results strengthen the significance of calf as an infectious source of VTEC infection.

Sertoli-stromal cell tumor containing metastatic lung cancer tissue.

A patient with a Sertoli-stromal cell tumor (SSCT) that contained metastatic lung cancer tissue is described, the first such report. The left ovarian tumor, which developed in a patient known to have lung cancer, mainly exhibited the histology of SSCT with a retiform pattern, and included a component of well-differentiated adenocarcinoma. Immunohistochemical specific stain for surfactant distinguished the adenocarcinoma from the primary ovarian tumor.

[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.

[Bacteriological and clinical studies of flomoxef in the field of pediatrics].

Bacteriological and clinical studies with flomoxef (FMOX, 6315-S), a new oxacephem antibiotic, were carried out in the field of pediatrics and the results obtained are summarized as follows: 1. The antimicrobial activity of FMOX against clinically isolated organisms was determined. FMOX had a good antimicrobial activity against Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae and especially against Staphylococcus aureus (including methicillin resistant S. aureus). 2. Mean serum concentrations of FMOX following intravenous bolus injection of 20 and 40 mg/kg (in 7 and 4 cases, respectively) were 35.3 and 77.7 micrograms/ml at 15 minutes after administration with mean serum half-lives (T1/2) of 0.75 and 0.95 hours and mean urinary recovery rates up to 6 hours after administration were 71.9 and 65.1%, respectively. 3. Twenty-five pediatric patients (19 cases of pneumonia, 1 case of pyothorax and 5 cases of urinary tract infection) were treated with FMOX in doses ranging from 50 to 138 mg/kg divided into 3 or 4 times a day. The rate of clinical effectiveness was 100% and the bacterial elimination rate was 90.6%. 4. No adverse reactions were observed. Abnormal laboratory findings were eosinophilia in 1, thrombocytosis in 2 and slight elevations of GOT and GPT in 3 patients. These results indicate the usefulness and the safety of FMOX in the treatment of bacterial infections in the pediatric field.

[Fundamental and clinical studies on cefuzonam in the field of pediatrics].

Fundamental and clinical studies on cefuzonam (L-105, CZON), a newly semisynthesized cephem antibiotic, were carried out in the field of pediatrics and the following results were obtained. Antibacterial activities of CZON against clinically isolated strains of Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, S. pyogenes, Escherichia coli, Klebsiella pneumoniae, Haemophilus parainfluenzae and H. influenzae were compared with those of cefmenoxime (CMX), latamoxef (LMOX), cefoperazone (CPZ), cefmetazole (CMZ), cefotiam (CTM) and cefazolin (CEZ). CZON was nearly as active as CEZ against S. aureus and S. epidermidis and superior to other antibiotics against other Gram-positive cocci. Against Gram-negative rods, CZON was as active as CMX and superior to other 5 antibiotics compared. Serum concentrations and urinary excretion rates after intravenous bolus injection of CZON at doses of 10 mg/kg, 20 mg/kg and 40 mg/kg for 5 minutes in 1, 5 and 4 cases, respectively, were determined. Mean serum concentrations of CZON at these dose levels were 11.0, 43.8 and 111.5 micrograms/ml at 15 minutes, 2.4, 10.3 and 30.3 micrograms/ml at 1 hour and 0.17, 0.72 and 1.28 micrograms/ml at 4 hours, with serum half-lives of 1.79, 0.88 and 1.19 hours, respectively. Mean cumulative urinary excretion rates within 6 hours after administration were 47.9, 56.3 and 40.3%, respectively. Thirty-four pediatric patients with various bacterial infections (tonsillitis 2, acute bronchitis 1, pneumonia 14, pyothorax 1, sepsis 1, suppurative lymphadenitis 1, UTI 13 and enteritis 1) were treated with CZON at a daily dose of 40-94 mg/kg t.i.d. or q.i.d.. The overall clinical efficacy rate was 94.1%. No adverse reactions were observed except 2 cases with mild diarrhea. Abnormal laboratory findings were also mild; slight elevation of GOT and GPT in 2, eosinophilia in 1 and thrombocytosis in 1. These results clearly indicate the usefulness of CZON in the treatment of bacterial infections in children.