Evaluation of vascular anatomy for colon cancer located in the splenic flexure using the preoperative three-dimensional computed tomography angiography with colonography.

PURPOSE: The aim of this study is to reveal the vascular branching variation in SFC (splenic flexure cancer) patients using the preoperative three-dimensional computed tomography angiography with colonography (3D-CTAC). METHODS: We retrospectively analyzed patients with SFC who underwent preoperative 3D-CTAC between January 2014 and December 2019. RESULTS: Among 1256 colorectal cancer (CRC) patients, 96 (7.6%) manifested SFC. The arterial branching from the superior mesenteric artery (SMA) was classified into five patterns, as follows: (type 1A) the left branch of middle colic artery (LMCA) diverged from middle colic artery (MCA) (N = 47, 49.0%); (2A) the LMCA diverged from the MCA and the accessory middle colic artery (AMCA) (N = 26, 27.1%); (3A) the LMCA independently diverged from the SMA (N = 16, 16.7%); (4A) the LMCA independently diverged from the SMA and AMCA (N = 3, 3.1%); (5A) only the AMCA and the LMCA was absent (N = 4, 4.1%). Venous drainage was classified into four patterns, as follows: (type 1V) the SFV flows into the inferior mesenteric vein (IMV) then back to the splenic vein (N = 50, 52.1%); (2V) the SFV flows into the IMV then back to the superior mesenteric vein (SMV) (N = 19, 19.8%); (type 3V) the SFV independently flows into the splenic vein (N = 3, 3.1%); (type 4V) the SFV is absent (N = 24, 25.0%). CONCLUSION: 3D-CTAC could reveal accurate preoperative tumor localization and vascular branching. These classifications should be helpful in performing accurate complete mesocolic excision and central vessel ligation for SFC.

Serum milk fat globule epidermal growth factor 8 elevation may subdivide systemic lupus erythematosus into two pathophysiologically distinct subsets.

OBJECTIVE: Impaired clearance of apoptotic cells is a potential trigger of systemic lupus erythematosus (SLE). Milk fat globule epidermal growth factor 8 (MFG-E8) plays an important role in the clearance of dying cells. Previously, we reported serum MFG-E8 was elevated in some SLE patients. Here we further investigated the prevalence of MFG-E8 in active SLE and other autoimmune diseases and also tried to clarify the characteristics of MFG-E8-positive and -negative SLE. METHODS: Serum MFG-E8 was measured in 40 active non-treated SLE patients, 104 disease controls and 104 healthy controls by ELISA. Clinical characteristics and serum cytokine profiles were compared between MFG-E8-positive and MFG-E8-negative SLE patients. RESULTS: Prevalence of MFG-E8 was significantly higher in SLE patients (40%) than in various controls (p < 0.05). MFG-E8 level became negative after treatment, and increased again upon relapse. When compared, MFG-E8-positive SLE patients showed higher immune complex (p = 0.021) and lower complement (p = 0.004 for CH50). In contrast, MFG-E8-negative SLE patients tended to show higher CRP (p = 0.094). There was a positive correlation between MFG-E8 level and immune complex level (r s = 0.49, p = 0.049). TNF-α (p = 0.019), IFN-γ (p = 0.031) and IL-10 (p = 0.013) were significantly higher in MFG-E8-positive SLE. CONCLUSION: MFG-E8-positive SLE and -negative SLE may have different clinical features, the one with stronger immunological response and the other with stronger inflammatory response, and those two groups may be two distinct subtypes of SLE driven by different mechanisms. Further, MFG-E8 could be used as a biomarker for diagnosis and monitoring of disease activity in certain SLE patients.

Association between anti-U1 ribonucleoprotein antibodies and inflammatory mediators in cerebrospinal fluid of patients with neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: We investigated possible associations between neurotoxic inflammatory mediators (IMs) and anti-U1RNP antibodies (Abs) in cerebrospinal fluid (CSF) of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Serum and CSF anti-U1RNP Abs were detected using an RNA-immunoprecipitation assay and CSF anti-U1RNP Ab levels were measured by ELISA. IFN-α, MCP-1 and IL-8 levels in CSF were determined by quantitative multiplex cytokine analysis. IM levels were compared among anti-U1RNP-positive and anti-U1RNP-negative NPSLE as well as other rheumatic disease controls (controls). RESULTS: Anti-U1RNP Abs were detected in serum (58%) and in CSF (18%) of 82 NPSLE patients. CSF MCP-1 levels were higher in NPSLE than in controls. CSF IFN-α level was higher in CSF anti-U1RNP Ab-positive than in -negative patients or controls. When limited to serum anti-U1RNP Ab-positive patients, however, levels of all three IMs in CSF were higher in CSF anti-U1RNP Ab-positive than in -negative patients. Anti-U1RNP Ab levels in CSF correlated with CSF MCP-1, but not IFN-α and IL-8 levels. CONCLUSIONS: CSF anti-U1RNP Ab positivity is associated with increased level of CSF IFN-α. MCP-1 levels correlated with CSF anti-U1RNP Ab levels, whereas the increased CSF MCP-1 was not specific to CSF anti-U1RNP Ab-positive NPSLE.

Type I interferon induces CX3CL1 (fractalkine) and CCL5 (RANTES) production in human pulmonary vascular endothelial cells.

Type I interferon (IFN) medications cause various adverse reactions, including vascular diseases. Although an association between chemokines and vascular diseases has also been reported, the relationship between type I IFN and chemokines in vascular endothelial cells (VEC) remains unclear. To provide clues to pathogenesis of the diseases, we analysed the effects of type I IFN on chemokine production in human VEC. Type I IFN induced higher CX3CL1 (fractalkine) mRNA expression and protein secretion in pulmonary arterial VEC than in umbilical vein VEC. Type I IFN also induced CCL5 [regulated upon activation normal T cell expressed and secreted (RANTES)] production in VEC, especially in lung micro-VEC. IFN-ß induced much higher chemokine production than IFN-α, and Janus protein tyrosine kinase (JAK) inhibitor I prevented type I IFN-induced chemokine secretion. Type I IFN-induced chemokines may be involved in the pathophysiology of pulmonary vascular diseases, and the JAK inhibitor may serve as a therapeutic option for these diseases.

Interferon-gamma release assay for diagnosing Mycobacterium tuberculosis infections in patients with systemic lupus erythematosus.

Our aim was to analyze the performance of an interferon-gamma release assay, QuantiFERON-TB Gold (QFT-2G), for diagnosing Mycobacterium tuberculosis (MTB) infection in patients with systemic lupus erythematosus (SLE). We performed the QFT-2G and tuberculin skin test (TST) in 71 SLE patients. The QFT-2G results of 279 patients with other connective tissue diseases (CTD) and 35 healthy controls were analyzed. Of the 71 SLE patients, two (2.8%) were positive and 46 (64.8%) were negative by QFT-2G. All SLE patients had no evidence of active MTB infection, apart from one. QFT-2G produced a significantly higher number of indeterminate results in patients with SLE (23/71, 32.4%) compared with those with other CTD (5.7%) or healthy controls (0%) (p < 0.0001 and p < 0.0001). Decreased lymphocyte counts and high SLEDAI scores in SLE patients were shown to be risk factors for indeterminate results by multivariate analysis (p = 0.02 and p = 0.04). Among all patients with CTD, SLE itself and lymphocytopenia were found to be independent risks for indeterminate results (p = 0.00000625 and p = 0.000107). In conclusion, QFT-2G may have more potential to assist in the diagnosis of active and latent MTB infection than TST in SLE patients. However, because of the high frequency of indeterminate results, caution must be used when interpreting the results of QFT-2G among SLE patients, especially those who have parallel or subsequent flares.

[Surgical treatment for pulmonary aspergillosis with hyper immunoglobulin-E syndrome; report of a case].

A 6-year-old girl who had been diagnosed as hyper immunoglobulin-E syndrome, was admitted to the department of pediatrics of our institute in May 2006, because of pulmonary aspergillosis. The chest X-ray showed bilateral cavities with niveau and fungus ball in the left middle lung field. In spite of medical treatment by antibiotics and antimycotics, the lesions did not improve. Therefore, bilateral lobectomy was done. After surgery, she needed re-operation twice, because of prolonged air leakage. There are few reports of lung surgery for the patient with the hyper immunoglobulin-E syndrome, and we present our case and review previous 2 case reports in the Japanese literature.

Technique and assessment of sentinel lymph node biopsy usefulness in laparoscopy-assisted distal gastrectomy.

BACKGROUND: Recently, some studies have suggested that sentinel node biopsy also can be applied to gastric cancer. The authors apply sentinel lymph node biopsy in laparoscopy assisted distal gastrectomy to perform it as safe limited surgery. Limited surgery is a procedure in which the extent of lesion resection and lymph node dissection is reduced. The authors demonstrate that intraoperative diagnosis of lymph node metastasis is useful in this respect. METHODS: The study was conducted with 38 patients (29 men and 9 women) who had a preoperative diagnosis of T1 tumor invasion. The patients had a mean age of 66.2 years. Patent blue (1%) was injected submucosally into four or five different sites around the primary tumor at 1 ml per site. Blue-stained lymphatics and lymph nodes could be seen by turning over the greater omentum and the lesser omentum extraperitoneally. If blue nodes were found, biopsy was performed. RESULTS: The mean number of blue nodes dissected was 2.5 +/- 1.9. Intraoperative identification and biopsy of blue nodes could be performed for 35 (92.1%) of the 38 patients. Of the 35 patients in whom blue nodes were identified, 4 (9.7%) had metastases in blue nodes confirmed by intraoperative frozen-section diagnosis. Intraoperative frozen-section diagnosis was negative for blue node metastasis in 31 patients. Postoperative permanent section diagnosis also showed no evidence of lymph node metastasis in these 31 patients (100% accuracy, 0% false-negative rates). CONCLUSION: The reported method allows observation of blue-stained lymphatics up to 2 h after patent blue injection. Sentinel node biopsy was performed in laparoscopy assisted distal gastrectomy, making it technically equivalent to open gastrectomy. Sentinel node biopsy can serve as a method to determine the appropriate use of laparoscopy assisted distal gastrectomy for management of T1 gastric cancer.

Structure of the gene encoding human alpha 2-HS glycoprotein (AHSG).

Alpha 2-HS glycoprotein (AHSG) is a human plasma glycoprotein and fetuin is the homologue in the calf. In this report, we present the structure and organization of the AHSG gene. Introns and the 5' and 3'-flanking regions were obtained by polymerase chain reaction (PCR) and the inverted PCR, respectively, from genomic DNA using AHSG cDNA-specific oligonucleotide primers. The sequence of the PCR products shows that the coding region spans approximately 8.2 kb and is composed of seven exons interrupted by six introns. The exon-intron splice junctions agree with the consensus sequence, and the positions interrupted by introns are precisely identical to those of the rat insulin receptor tyrosine kinase inhibitor (fetuin) gene. The 5'-promoter region contains several characteristic sequences such as an A + T-rich sequence of TAAATAA, C/EBP-binding site, and hepatocyte nuclear factor-5 (HNF-5) and serum response factor (SRF) sites.

Association of plasma triglyceride-rich lipoprotein remnants with coronary atherosclerosis in cases of sudden cardiac death.

Among the risk factors for coronary atherosclerosis, elevated LDL-C level is best known. The action of lipoprotein lipase on triglyceride-rich lipoproteins produces remnant lipoprotein particles enriched in cholesterol and apolipoprotein E (apo E). Apo E serves as the ligand for uptake of remnant lipoproteins via the LDL-receptor or the remnant receptor. In this study, postmortem plasma total cholesterol, triglycerides (TG), VLDL-C, HDL-C, lipoprotein (a) [Lp(a)] and remnant-like lipoprotein particles (RLP)-cholesterol, RLP-TG, apolipoproteins B, C III and E were measured, together with LDL-C to assess their potential contribution to the severity of coronary and aortic atherosclerosis of the 197 cases of sudden death (132 cardiac death and 65 non-cardiac death). In all cases, the severity of coronary atherosclerosis was determined at postmortem pathological examination. RLP-cholesterol (RLP-C) and LDL-C concentrations were significantly higher in cases with advanced coronary atherosclerosis compared with those without coronary atherosclerosis; respective median values were 13.5 vs 8.4 mg/dl (P < 0.001) and 140 vs 115 mg/dl (P < 0.05). RLP-C levels were more strongly correlated with the severity score of coronary atherosclerosis than LDL-C.

Intra-alveolar haemorrhage in sudden infant death syndrome: a cause for concern?

BACKGROUND: The "Back to Sleep" campaign in 1991 resulted in a dramatic decrease in the incidence of sudden infant death syndrome (SIDS). The proportion of presumed SIDS deaths being actually suspicious deaths from airway obstruction is likely to have become relatively greater. There is usually little pathological evidence to suggest smothering, but intra-alveolar haemorrhage appears to be more prominent in cases where interference with the airway is suspected. AIM: To attempt to quantify intra-alveolar haemorrhage to see whether it could be used as a marker to distinguish between smothering/overlaying and SIDS. METHODS: Intra-alveolar haemorrhage was quantified using digital image analysis on haematoxylin/eosin stained sections taken from the lungs of 62 consecutive infants who had died suddenly and unexpectedly. Cases were initially classified according to the original cause of death. After quantitation, the case histories were critically reviewed. Three pathologists independently made microscopic assessments of the degree of intra-alveolar haemorrhage in the first 24 cases to see whether these accurately reflected the quantitative results. RESULTS: 73% of those infants with a history suggesting possible involuntary overlaying and 45% of those with a history suspicious of smothering had significant intra-alveolar haemorrhage (> 5% of total lung surface area assessed). From the history, the cause of death in 11 cases initially classified as SIDS would better have been given as "Unascertained." Simple microscopic assessments underestimated the true extent of the haemorrhage in 33% (8/24). CONCLUSIONS: If a moderate degree (at least 5%) of pulmonary parenchymal haemorrhage is observed, this may be an indicator of airway obstruction for a significant period, either from overlaying or possibly smothering. The diagnosis of SIDS may be being used inappropriately in such cases.

A sensitive sandwich enzyme immunoassay for gamma-seminoprotein and its application to sex discrimination of blood and bloodstains.

A sensitive sandwich enzyme immunoassay for gamma-seminoprotein (p30, prostate-specific antigen) is described for sex discrimination of blood and bloodstains. A polystyrene ball coated with rabbit anti-gamma-seminoprotein IgG was incubated with gamma-seminoprotein and, after washing, with affinity-purified rabbit anti-gamma-seminoprotein Fab'-horseradish peroxidase conjugate. Peroxidase activity bound to the polystyrene ball was assayed by fluorometry using 3-(4-hydroxyphenyl)propionic acid as hydrogen donor. The detection limit of gamma-seminoprotein was 0.15 pg per assay. Blood levels of gamma-seminoprotein, measured using 1-10 microliters of blood, were at least 3.3-fold higher in male adults than in female adults. The ratio of gamma-seminoprotein in terms of pg to hemoglobin in terms of mg was significantly higher in male adults than in female adults. Thus, the measurement of gamma-seminoprotein or both gamma-seminoprotein and hemoglobin was useful for the discrimination of blood and bloodstains of male and female adults, although with some limitations.

A highly specific and sensitive sandwich enzyme immunoassay for human hemoglobin A.

A highly specific and sensitive sandwich enzyme immunoassay for human hemoglobin A (Hb A) is described. A rabbit anti-human Hb A IgG-coated polystyrene ball was incubated with human Hb A and subsequently with affinity-purified anti-human Hb A Fab'-horseradish peroxidase conjugates, which had been prepared before and after absorption with Japanese monkey Hb-Sepharose 4B and dog Hb-Sepharose 4B. Bound peroxidase activity was measured by fluorimetry using 3-(4-hydroxyphenyl)propionic acid as a substrate. The detection limits of human Hb A using the conjugate before and after the absorption were 0.65 pg/tube (3 X 10(10)-fold dilution of whole blood) and 2.0 pg/tube (1 X 10(10)-fold dilution of whole blood), respectively. Human Hb A could be discriminated from Hb of animals such as Japanese monkey, dog, cat, pig, horse, sheep, chicken and cow by measuring bound peroxidase activity in the presence and absence of the conjugates prepared before and after the absorption. Human Hb A in bloodstains on cotton gauze could be discriminated from Hb of animals described above even after seven washings. Human Hb A in 220,000-fold diluted bloodstains on cotton gauze could also be discriminated from Hb of animals described above.

Determination of chronic methamphetamine abuse by hair analysis.

A 30-year-old male truck driver, known to be asthmatic, was found dead at the roadside lying near his car. A nebulizer bottle of Berotec (fenoterol hydrobromide) was found near his hand. The anatomic cause of death was suspected to be asthma. Toxicological screening of urine using Triage demonstrated the presence of methamphetamine. The blood concentration of methamphetamine was 0.4 microg/ml, and fenoterol was not detected. Hair analysis clearly indicated chronic methamphetamine abuse and medium dependency during the 2 months before death. We conclude that death might have been induced by the interaction of fenoterol and methamphetamine.

Increased complex formation of Gc globulin with actin in plasma from human cadavers.

Gc globulin binds actin at an equimolar ratio with a high affinity. It has been revealed that complexes of Gc with actin are present in the plasma of human cadavers. In the present study, an immunoassay which we developed using a specific anti-Gc monoclonal antibody was applied to evaluate the complexed Gc in cadaver plasma. The percentage of Gc in the complexed form was found to be 38.3 +/- 19.8% (n = 45), and a significantly higher percentage was observed in the plasma of cadavers from burn death. However, the plot of the complex percentage against the time since death showed a relatively low correlation, with a coefficient (r) of 0.51. This was supposed to be due to different environmental conditions after death. Since the complex formation represents the release of cytoplasmic actin into plasma from collapsed cells, the phenomenon should be noted in forensic postmortem chemistry.

A case of homicidal poisoning involving several drugs.

Accidental or suicidal poisonings due to benzodiazepines have been previously reported. A case of fatal, homicidal poisoning with benzodiazepines, antipyretic analgesics (anti-inflammatory drugs), and beer is described here. In this homicidal poisoning, the drugs and beer were given to the decedent by his wife. Autopsy findings showed no clinically significant macroscopic findings except for slight postmortem change. Capillary gas chromatography coupled to mass spectrometry was employed to quantitate the drugs in biological fluids and stomach contents. Six drugs (brotizolam, triazolam, ibuprofen, dihydrocodeine, phenylpropanolamine, and chlorpheniramine) were identified and quantitated in blood, urine, and stomach contents. Although each drug was present in a very small quantity, the cause of death was determined to be the combination of these drugs and alcohol poisoning.

Plasma triglyceride-rich lipoprotein remnants as a risk factor of 'Pokkuri disease'.

In our recent report, it remained unclear whether or not triglyceride-rich lipoprotein remnants (RLP) were associated with the risk of sudden coronary death in younger cases without coronary atherosclerosis that were detected in about 10% of all sudden coronary death cases in Japan. These cases were categorized as 'origin unknown, but suspected to be due to coronary spasm', the so called 'pokkuri disease' in Japan. The present study population consisted of 108 sudden death cases without coronary atherosclerosis [(pokkuri disease n=57) and non-cardiac sudden death (control n=51)] aged 20-69 years from Kanagawa prefecture in Japan. All individuals had died suddenly and unexpectedly, most had no significant history of medical conditions including cardiac symptoms and had not taken medications prior to death according to their medical records. All the autopsies were performed within 12 h after death. Plasma total cholesterol (TC), triglycerides (TG), phospholipids, RLP-C and RLP-TG, VLDL-C, LDL-C, HDL-C, apolipoproteins A-I, A-II, B, C-II, C-III, E, Lp (a) and homocysteine were measured in postmortem plasma samples. The TG-rich lipoprotein remnants measured as RLP-C and RLP-TG were significantly higher in pokkuri disease compared with controls both in fasting and postprandial states (P<0.05 and P<0.001), indicating that RLP-C and RLP-TG were the most significant risk factor in pokkuri disease among the parameters tested in this study. In conclusion the TG level in RLP (RLP-TG) appeared to be strongly associated with the risk of sudden death in the absence of coronary atherosclerosis (pokkuri disease).

Effects of muscle relaxants on EEG, ABR and EMG in rabbits.

The effects of baclofen and pancuronium bromide on evoked electromyogram (EMG), cortical electroencephalogram (EEG) and auditory brainstem responses (ABR) were studied in pentobarbital anesthetized normal rabbits. Evoked EMG was measured in the gastrocnemius muscle by electrical stimulation of the sciatic nerve. Intravenous injection of baclofen decreased EEG and arterial blood pressure and light reflex, however, it had no significant influence on EMG or ABR at doses of 10 and 20 mg/kg/h. Pancuronium bromide immediately inhibited respiration, decreased EEG and EMG, however, it had no significant influence on arterial blood pressure, ABR, or light reflex, at doses of 0.4 and 1.0 mg/kg/h in anesthetized rabbits. ABR waves were observed until just before cardiac arrest with both of the muscle relaxants. It is suggested that ABR are not influenced by central or peripheral muscle relaxants, or by pentobarbital.

Fatal methemoglobinemia caused by liniment solutions containing sodium nitrite.

We describe a case of fatal methemoglobinemia (MetHb-emia) resulting from application of liniment solution containing large quantities of sodium nitrite. As a remedial treatment of atopic dermatitis, the liniment solution was applied all over the boy's body. Autopsy findings showed no significant macroscopic or microscopic findings except blood tinted chocolate brown color and chronic atopic dermatitis over the whole surface of the body. Quantitation of the methemoglobin (MetHb) in the blood was performed using spectrophotometer; MetHb concentration of the blood was 76%. Ion chromatographic determination revealed a nitrite concentration of 1 mg/L in the serum. Such a liniment solution is not authorized by the Ministry of Public Welfare.