Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

A surgical navigation system for aortic vascular surgery: a practical approach.

In aortic vascular surgery, a navigation system must represent the anatomical map of individual patient in order to detect the important artery. To provide a proper fit for positions along the dorsoventral axis, the spinous process was added to a currently used anatomical point set consisting of four anterior body landmarks. In addition, we attempted to reduce the registration error by compensating for alignment errors resulting from variations in tissue thickness at each landmark. The alignment values were examined using a human phantom consisting of a skeleton model with subcutaneous tissue in the semilateral position. Using this method, a phantom simulation and five clinical trials were performed. Target errors were evaluated at the orifice of the intercostal artery. In the phantom simulation, the error at the target point was 4.1 ± 2.7 mm. However, for one patient undergoing thoracoabdominal aortic aneurysm replacement surgery, the target error was 8.0 mm using the proposed method.

Diastereoselective tandem Michael-intramolecular Wittig reactions of a cyclic phosphonium ylide with 8-phenylmenthyl enoates.

The diastereoselective tandem Michael-intramolecular Wittig reactions of a five-membered cyclic phosphonium ylide 2 using 8-phenylmenthyl enoates were examined. The reaction of the phosphonium ylide with 8-phenylmenthyl cinnamate followed by the hydrolysis of the resulting enol ether 4a afforded (3R,4S)-4-(diphenylphosphinyl)-3-phenylcycloheptanone (3R,4S)-5a as the major isomer. The diastereoselectivity of the initial tandem reactions was estimated to be 94:6 from the 31P NMR of a mixture of the diastereomeric ketal derivatives 6a and 6'a which were obtained by the reaction of 5a with (2R,3R)-2,3-butanediol, and the absolute configuration of the major isomer was determined by the single-crystal X-ray analysis. Similar reactions using some 8-phenylmenthyl alkenoates were attempted. As a result, it was clarified that the corresponding trans-ketones 5b-d were obtained and that the diastereomer ratios of their ketal derivatives were 60:40-73:27.

Heterostructures of single-walled carbon nanotubes and carbide nanorods

A method based on a controlled solid-solid reaction was used to fabricate heterostructures between single-walled carbon nanotubes (SWCNTs) and nanorods or particles of silicon carbide and transition metal carbides. Characterization by high-resolution transmission electron microscopy and electron diffraction indicates that the heterostructures have well-defined crystalline interfaces. The SWCNT/carbide interface, with a nanometer-scale area defined by the cross section of a SWCNT bundle or of a single nanotube, represents the smallest heterojunction that can be achieved using carbon nanotubes, and it can be expected to play an important role in the future fabrication of hybrid nanodevices.

Epimerization of moxalactam by albumin and simulation of in vivo epimerization by a physiologically based pharmacokinetic model.

We investigated the mechanism of epimerization (R to S or S to R) of moxalactam in serum of rats, dogs, and humans. The epimerization of moxalactam occurred in the serum of these animals, but not in the serum filtrate. The albumin fraction of human serum purified by gel filtration catalysed the epimerization of moxalactam at an identical rate to serum, but other fractions (i.e., lipoproteins and globulins) showed slower epimerization. alpha 1-acid glycoprotein, which was eluted in the same fraction with albumin by G-200 gel filtration, did not epimerize moxalactam. The presence of 2 mM warfarin decreased the binding of R- and S-moxalactam and decreased the epimerization of moxalactam in human serum. These results demonstrate moxalactam was epimerized on the warfarin binding site on albumin in serum. Additionally, a physiologically based pharmacokinetic model shows that the epimerization of moxalactam after administration in dogs is simulated by the epimerization in serum.

Mechanism of hypocholesterolemic action of S-8921 in rats: S-8921 inhibits ileal bile acid absorption.

The mechanism of the hypocholesterolemic action of S-8921, methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)- 4-hydroxy-6,7,8-trimethoxy-2-naphthoate, was examined in rats. In diet-induced hypercholesterolemic rats, 2 weeks oral administration of S-8921 dose- and time-dependently decreased plasma cholesterol level in the daily dose range of 0.1 to 10 mg/kg. Results with the dual-isotope plasma ratio method indicated that S-8921 inhibits cholesterol absorption from the intestine and enhances its elimination from the body. The in situ loop method showed that S-8921 does not inhibit the absorption of cholesterol from rat jejunum, clearly inhibits active absorption of taurocholic acid (TCA) and glycocholic acid (GCA) from rat ileum and does not inhibit passive absorption of cholic acid (CA) from the rat jejunum. In rat ileal brush-border membrane vesicles, S-8921 inhibited the sodium-dependent uptake of TCA in a concentration-dependent manner with IC50 of 2.1 microM, not the Na(+)-dependent D-glucose and L-alanine uptake. These results suggest that S-8921 is a potent, selective inhibitor of the Na(+)-dependent bile acid transport system in the ileal mucosal cell brush-border membrane, and this inhibition is the mechanism by which this drug decreases intestinal bile acid reabsorption to result in a significant decrease of plasma cholesterol.

A novel myeloid cell line, Marimo, derived from therapy-related acute myeloid leukemia during treatment of essential thrombocythemia: consistent chromosomal abnormalities and temporary C-MYC gene amplification.

A novel myeloid leukemia cell line, Marimo, was established from bone marrow cells of a patient with secondary acute myeloid leukemia (AML) that had developed during the treatment of essential thrombocythemia (ET) with busulfan. Karyotype at the ET phase was 46,XX,der(15)t(1;15) (q23;p12-13), but at the blastic phase changed to 44,XX,-5,del(8)(q22), add(17)(p11),+18, psu dic(18;9) (q23;p21) x 2 lacking t(1;15). In Marimo cells, C-MYC gene was temporarily amplified by double-minutes (dmin) but disappeared at 33 months, whereas t(10;14;11)(q22;q32;q13) and t(10;14)(q22;q32) were added in vitro psu dic(18;9) x 2 and add(17)(p11) were consistently found throughout the culture. These results suggest that this AML clone is not derived from ET but rather is therapy-related.

Unusual feature of the T-cell receptor genes in T-lineage acute lymphoblastic leukemia.

We characterized the T-cell receptor (TCR) gene rearrangements and sequences in 15 T-lineage acute lymphoblastic leukemia (T-ALL) and seven adult T-cell leukemia (ATL) samples. Southern blot analysis showed that neither of the two TCR delta alleles was deleted in two T-ALL samples, suggesting that the TCR alpha loci have a germ line configuration. The TCR alpha and beta sequences were cloned and sequenced by reverse transcriptase-inverse polymerase chain reaction. Two T-ALL samples had a long complementarity determining region (CDR), three of the alpha chain and the other two T-ALL samples had long CDR3 of the beta chain, compared with normal peripheral blood lymphocytes (PBL). Thus, a total of six T-ALL samples had unusual TCR gene structure, which was unrelated to the immunophenotype. On the other hand, CDR3 length in ATL samples was similar to normal PBL. These data suggest that T-ALL is derived from an immature T-cell repertoire which undergoes TCR gene rearrangement or has not been negatively selected.

[A case of Morgagni hernia composed of hypertrophic adipose tissue in the falciform ligament].

We report our recent experience with an asymptomatic case of Morgagni hernia composed of hypertrophic adipose tissue in the falciform ligament. The patient was a 47-year-old obese para-II woman. A chest X-ray during a routine health checkup showed an abnormal shadow in the right cardiophrenic angle that was larger than one year previously. Computed tomograms revealed a fat-density mass in the right side of the chest in contact with the anterior chest wall, pericardium and sternum that continued into the abdominal cavity. Magnetic resonance imaging (MRI) showed that the intrathoracic mass lesion was continuous with the subphrenic tissue, and that the hilus of the hernia was 5 x 3 cm in size. A barium gastro-intestinal series revealed no abnormal findings. Surgical repair was achieved through the transabdominal approach. The omentum was found in its normal position. The herniated adipose tissue in the falciform ligament was repositioned on the peritoneal side, and excised. The hilus of the hernia was then closed with knotted sutures. Postoperatively, the abnormal shadow on the X-ray was no longer present, and the postoperative course was uneventful. Histological examination revealed the hernia to consist of mature adipose tissue 5 x 10 x 3 cm in size. This is the first case of Morgagni hernia composed of hypertrophic adipose tissue in the falciform ligament reported in Japan.

[A case report of pulmonary sequestration (Pryce I) associated with incomplete lobulation of the left lung].

A 28-year-old man was treated surgically for pulmonary sequestration of Pryce type I associated with incomplete lobulation of the left lung. His chief complaint was hemoptysis. His chest X-ray film showed a mass lesion behind the cardiac shadow. Aortogram revealed a large artery arising from the descending aorta and supplying the left basal segment, and venous blood returning into the left inferior pulmonary vein. The left basal segment had no pulmonary arteries. A bronchogram showed no defects in the bronchial tree. The left basal segment was resected successfully. Histological study showed the trunk of the aberrant artery to be elastic. Differences between histological types of aberrant arteries in pulmonary sequestration of Pryce type I and the pathogenesis of intralobar sequestration were discussed.

Familial macrothrombocytopenia with unusually elongated mitochondria.

We report a familial case of macrothrombocytopenia without inclusion bodies in polymorphonuclear cells or any congenital abnormalities. The results of the hemostatic and platelet function tests were all normal except for the platelet retention rate. The number of megakaryocytes increased slightly and some were relatively small. Electron microscopic studies revealed a unique morphological abnormality of the platelets' mitochondria.

[Familial occurrence of von Hippel-Lindau disease--a case report].

It is well known that von Hippel-Lindau disease is defined as the association of retinal angiomatosis and cerebellar hemangioblastomas. This disease is frequently associated with extra-neural vascular neoplasma, especially visceral angiomatous tumors. In this paper we report the familial occurrence of von Hippel-Lindau disease in a 55-year-old mother and her 24-year-old son. The mother had simultaneous multiple angiomas of the liver, stomach and head of the pancreas. The initial symptom was sudden onset of vertigo, possibly caused by a slow-growing cystic cerebellar lesion. An apparent genetic factor indicates that clinical settings begin in the early life of the patients.

[Bronchogenic cyst of the diaphragm: a case report].

A 30-year-old man was treated surgically for bronchogenic cyst originating from the diaphragm. An abnormal shadow was found on a routine chest roentgenogram. The tumor was located in the left vertebro-phrenic angle. CT scan showed a CT number of 34.2, which MRI examination revealed with low intensity on the T1 weighted image and high intensity on the T2 weighted image. A multilocular cystic tumor filled with viscid fluid, about 3 cm in size, was resected. This was diagnosed as a bronchogenic cyst, as microscopic examination showed bronchial epithelium, one layer of smooth muscle, bronchial glands, and cartilage. This is the 10th case of diaphragm-related bronchogenic cysts reported in Japan. Of these 10, 7 were located at the vertebro-phrenic angle.

A quantitative concept of the mechanism of intestinal lymphatic transfer of lipophilic molecules.

The partition of mepitiostane, testosterone, and some structurally related compounds between lymph and blood in rat jejunum (lymph-blood partition ratio; LBPR) was determined, and the quantitative relationship between LBPR and lipophilicity was examined. When the delta Rm values (hydrophobic parameter derived from the mobility) relative to testosterone were < 0.2, their logLBPRs remained approximately constant in the range of -2 to -3. When the delta Rm values of the compounds were > 0.2, a linear correlation (r = 0.986, n = 8) was observed between these values and the logLBPRs. The LBPR, but not the extent of lymphatic absorption, of lipophilic molecules was determined strictly by the superlipophilicity, and for high partitioning into the lymph (> 50% of the absorbed amount), the delta Rm value had to be > 0.50 (5.65 as the logP value). The relationship between LBPR and superlipophilicity could be explained on the basis of the theoretical equations derived from absorption kinetics based on a dynamic partitioning model.

Nucleotide sequences of the variable regions of a human monoclonal antibody against HLA-A1, A23, and A24.

Nucleotide sequences of the heavy and light chain variable (VH and VL) regions of a human monoclonal antibody (4-35-7), which recognized HLA-A1, A23 and A24, were determined by means of the reverse transcriptase-polymerase chain reaction. This antibody was generated by Epstein-Barr virus transformation of lymphocytes obtained from a multiparous donor, followed by fusion with mouse myeloma cells. The VH gene segment belonged to the VHIII gene family, and used the DXP4 and JH4 gene segments. This VH gene segment had 92.9% homology to the germline gene VH26, and contained 21 nucleotide substitutions. Fourteen of them generated the replacements of amino acids, while 7 failed to generate the replacement. The ratio of replacement to silent mutations in complementarity determining regions (CDRs) was 7.0. The VL gene segment belonged to the VkI gene family, and used Jk4. This VL gene segment showed 96.1% homology to the germline gene HK102, and contained 11 nucleotide substitutions. Seven of them generated the replacement of amino acids, while 4 failed to generate the replacement. The high ratio of replacement to silent mutations in CDRs of the VH gene segment suggested that the multiparity caused the processes of antigenic selection and somatic mutation, and generated this anti-HLA antibody.

Malignant nerve sheath tumor with rhabdomyoblastic differentiation arising from the acoustic nerve.

A case of a malignant nerve sheath tumor with rhabdomyoblastic differentiation arising from the acoustic nerve in a 38 year old man is reported. At autopsy, the tumor was found to be extensively involved in the right cerebellopontine angle of the brain stem. Histologically, the tumor was composed mainly of spindle-shaped tumor cells proliferating in hypercellular fascicles scattered with pleomorphic cells. The tumor cells were characterized by high mitotic activity and invasive growth. Occasional tumor cells had eosinophilic cytoplasm, which in a few cases was cross-striated. Cytoplasmic interdigitations and a thick basal lamina were confirmed ultrastructurally. Immunohistochemical analysis revealed that some tumor cells were positive for myoglobin and desmin, but weakly positive or negative for S-100 protein. The patient did not have von Recklinghausen's disease.