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.

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.

Variable region gene analysis of 2 human monoclonal-antibodies to gd3.

We analyzed the genetic origins of anti-GD3 antibodies by comparing nucleotide sequences of the variable regions from the human monoclonal antibody (mAb), 27-26 (mu, k), established from a patient with leukemia, and another human anti-GD3 mAb, HJM-1 (mu, lambda) derived from a patient with melanoma. The variable regions of 27-26 and HJM-1 were remarkably similar to the germ-line genes. The mAb 27-26 was thought to be derived from germ-line repertoire expanded throughout our experiment. HJM-1 was derived from lymphocytes stimulated by GD3 abundantly expressed on melanoma cells.

Disappearance of minimal residual lymphoblastic leukemia cells 6 months after allogeneic bone marrow transplantation without GVHD.

The recent development of the polymerase chain reaction (PCR) has enabled us to determine the hypervariable sequence of immunoglobulin heavy chain known as complementarity determining region (CDR)-III. We amplified the leukemia-specific CDR-III from common acute lymphoblastic leukemia (cALL) cells using the PCR and determined its sequence. To detect minimal residual leukemia (MRL) cells, a second round PCR was performed with clone-specific primers corresponding to 5' and 3' ends of CDR-III to detect MRL cells. A million-fold diluted leukemia cells were clearly detected. Using stepwise diluted materials, the number of residual cells was semiquantitatively estimated. In one patient with cALL, induction chemotherapy resulted in a hematologically complete remission with only a 2-log reduction of the leukemia cells. MRL cells at a level of 10(-6) were also detected within 1 month after bone marrow transplantation (BMT), but leukemia cells were not detectable 6 months after BMT.

Studies on phospholipase A inhibitor in blood plasma. I. Purification and characterization of phospholipase A inhibitor in bovine plasma.

Phospholipase A inhibitor was found in bovine, human and porcine plasma. The inhibitor was purified about 300-fold from bovine plasma by ammonium sulfate fractionation, DEAE-cellulose chromatography, Sephadex G-200 gel filtration and anti-BSA antibody-agarose column chromatography to remove albumin. The purified material was homogeneous as judged by immunoelectrophoresis and 0.7% agarose-2% polyacrylamide gel electrophoresis. The inhibitor suppressed not only rat and human plasma phospholipase A2 activity, but also purified Mamushi (Agkistrodon halys blomhoffi) venom phospholipase A2-II. Bovine plasma inhibitor was shown to be a lipoprotein containing phosphatidylcholine, sphingomyelin, cholesterol ester, and triacyl glycerol as major lipid components. The molecular weight of the native inhibitor was nearly the same as that of bovine plasma high density lipoprotein (HDL) when determined by the gel filtration method. The molecular weights of two subunits of the inhibitor observed on polyacrylamide gel electrophoresis in the presence of SDS were about 10K and 42K. The anti-inhibitor antiserum obtained from rabbits immunized with the highly purified inhibitor cross-reacted with bovine plasma alpha-lipoprotein (HDL). The lipid composition of the inhibitor was similar to that of HDL, but apoinhibitor and apoHDL were different in molecular weight and solubility in various buffers.

Studies on phospholipase A inhibitor in blood plasma. II. Interaction of phospholipase A inhibitor with phospholipase A and its specificity.

Non-competitive inhibition of snake venom phospholipase A2 which has been exhibited by bovine plasma phospholipase A inhibitor, a kind of lipoprotein, was not observed unless the inhibitor was preincubated with the enzyme. The inhibition seemed to be due to the formation of the enzyme-inhibitor complex, which was identified by immunoelectrophoresis. The enzyme-inhibitor interaction was observed maximally on incubation at physiological pH, but not below pH 5. The inhibitor was inactivated by trypsin digestion and heat treatment. It suppressed the phospholipase A2 activities of rat blood plasma as well as of the snake venom and porcine pancreas, but not the enzyme activities such as those of phospholipase C of Bacillus cereus, lipase of porcine pancreas, trypsin, and papain. The inhibitor also showed the ability to decrease membrane-bound phospholipase A1 and A2 activities in intracellular organelles such as plasma membranes, mitochondria, lysosomes, and microsomes. In view of these facts, it was concluded that the plasma inhibitor is specific for phospholipase A.

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.

Studies on the absorption of practically water-insoluble drugs following injection V: Subcutaneous absorption in rats from solutions in water immiscible oils.

To elucidate the kinetics and mechanisms of subcutaneous absorption of practically water-insoluble drugs in oily solutions, the absorption behaviors of select azo dyes and other prototype agents were investigated by a local clearance method in the dorsum in intact rats. The absorption of the drug components appeared to be first-order. The first-order rate constant (k) was inversely proportional to the cube root of the injection volume. In more limited studies, essentially the same behavior was observed in the rat abdomen, and the difference in k between the dorsal and abdominal injections was slight. The comparison of k of a given compound from different oily vehicles showed that k was governed predominantly by the distribution coefficient (K) between the oily vehicle and the aqueous subcutaneous medium and depended little on the viscosity of the vehicle. This distributioning relationship was shown through correlation of the rate constants with in vitro distribution coefficients. A plot of log k versus log K for all the compounds tested was linear with a slope of approximately -0.7. This linear relationship allows adequate prediction of absorption rates of other drugs from oily vehicles. The observed subcutaneous absorption rates and behaviors are compared with previous results involving the intramuscular route.

Effect of oily vehicles on absorption of mepitiostane by the lymphatic system in rats.

[14C]Mepitiostane in various vehicles was administered to the small intestine of anaesthetized rats with cannulated thoracic ducts, and the effect of lipids on lymphatic absorption was examined. The extent of lymphatic absorption was greatest when administered in triolein and sesame oil, which are triglycerides of long-chain fatty acids. Absorption in the presence of other vehicles was in the order of 10% Tween 80 aqueous solution greater than monolein greater than oleic acid approximately oleic acid/monolein (2:1 mol/mol) greater than aqueous suspension. Differences between the extents of lymphatic absorption of mepitiostane in the various formulations were not due to variation in the lymph flow but to the increased secretion of chylomicron and very low density lipoproteins. During absorption of mepitiostane from the small intestine, oil affected not only the penetration into epithelium cells and the metabolism in them, but also the partition between blood and lymph.

Effect of bile on absorption of mepitiostane by the lymphatic system in rats.

The effects of bile and site of gastrointestinal absorption on the lymphatic absorption of the highly lipophilic drug, mepitiostane were examined using thoracic duct-cannulated rats. The lymphatic absorption from the small intestine was very small in the absence of bile compared with that when bile was present. The lymphatic absorption was greatest when drug was administered to the upper small intestine with bile, was smaller for the lower regions of the small intestine, and was negligible for the stomach and the large intestine. A correlation was observed between the extent of lymphatic absorption and the secretion of chylomicron and very low density lipoproteins after administration to various regions with or without bile. The portal absorption data of mepitiostane confirmed that site specificity occurs in the partition of drug between blood and lymph.

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.

[Acoustic neurinoma associated with facial neurinoma--a case report].

A 38-year-old man developing slowly progressive left facial paresis was admitted to our hospital. The clinical diagnosis of "adhesive arachnoiditis was made. The first operation was performed in December 1987, and his symptom disappeared postoperatively. Three years later, left facial paresis recurred together with trunkal ataxia. A computed tomography and magnetic resonance image revealed two tumors located at the left cerebellopontine angle region and in the left middle cerebral fossa. These two tumors were thought to arise in the different cranial nerve. Under the clinical diagnosis of acoustic neurinoma associated with facial nerve neurinoma, the two step-operation was designed for total removal of the tumor in December 1990 and January 1991. Intraoperative finding confirmed that these two tumors had the different origin. Pathologic diagnosis was compatible with neurinoma. This patient had no family history of "Neurofibromatosis".

[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.

[Cryosurgical treatment of atrial tachyarrhythmia with atrial flutter].

Two cases of atrial tachyarrhythmias with atrial flutter requiring cryosurgical treatment are reported. In two cases, preoperative electrophysiological studies revealed supraventricular reentrant tachyarrhythmias during atrial flutter and showed enhanced conduction through the AV node that conducted atrial impulses rapidly to the ventricle. Based on intraoperative endocardial mapping, the earliest excitation site was localized along the AV node and His bundle during supraventricular tachyarrhythmias in one case. The cryosurgical treatment was administered at Koch's triangles and in one case additionally at coronary sinus. After the operation, supraventricular tachyarrhythmias were not inducible and no clinical recurrences have occurred. Normal atrioventricular conduction was preserved in two cases. We concluded that cryosurgical treatment is useful for the treatment of the atrial tachyarrhythmias.

[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.

[Surgery and adjuvant therapy of non-small cell lung cancer].

Bronchial arterial infusion of chemotherapeutic agents (BAI), radiation therapy, chemotherapy and immunotherapy were used as surgical adjuvant therapy for non-small cell lung cancer, and the clinical effects of these treatment modalities on survival rates were evaluated. BAI brought about a decrease of tumor size, but no significant effect on survival rats was noted. Postoperative radiation therapy on P-N2 cases exerted no significant effect on the survival rate, but when immunotherapy was combined with radiation therapy, there was a significant prolongation of the survival rate. As for post-operative chemotherapy, three types of combination chemotherapy have been performed over the past twelve years: short-term chemotherapy (S-C), long-term intermittent chemotherapy (L-I-C), and long-term continuous chemotherapy (L-C-C). Retrospective comparison of survival rates between these three methods was carried out. The survival rate of the group which was treated by L-I-C showed better results than those obtained by S-C. The group treated by L-C-C showed a much better survival rate than that treated by L-C-C: Stage I + II cases that underwent curative resection and were treated by L-I-C showed a significantly better survival rate than those treated by S-C. Furthermore, the survival rate of stage III cases with curative resection was improved by L-C-C (CQ+CPA+ADM+5-FU) with statistical significance. To evaluate the clinical efficacy of OK-432, a streptococcal preparation, as an immunotherapeutic agent for lung cancer, patients admitted between 1975 and 1982 were randomized into two groups: (1) an immunochemotherapy group and (2) a chemotherapy group (control group). For both groups, the same L-I-C was administered in accordance with the cancer histological cell type. There were 119 resected cases in the immunochemotherapy group and 115 cases in the control group, that were eligible for evaluation of long-term survival after surgery. Overall, the cases in the immunochemotherapy group showed a better survival rate than the control group, and this difference was statistically significant. In addition, statistically significant improvements of survival rate by the immunotherapy were observed for the following items; resected stage I + II cases, resected stage III + IV cases, cases with curative resection, cases with non-curative resection and resected epidermoid carcinoma. On the other hand, there were no statistically significant differences between the two groups in cases of adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical value of postoperative chemotherapy for non-small cell lung cancer--with special reference to long-term combined chemotherapy combined with immunotherapy].

The main reason for unfavourable surgical outcome of lung cancer is latent distant metastases over looked during surgery, which ultimately cause recurrence, or death of the patients even in cases undergoing curative surgery. This fact necessitates the indispensable use of systemic adjuvant therapy in patients under going surgery for lung cancer. There have been mary reports concerning the clinical efficacy of surgical adjuvant chemotherapy for non-small cell lung cancer using various kinds of drugs in various treatment modalities, but the results have been controversial. During the past eleven years, we have used postoperative chemotherapy in three ways over three different periods: in the earliest period, short-term combined chemotherapy (STCC) was used, in the middle period, intermittent long-term combined chemotherapy (ILTCC) was used in combination with immunotherapy for a randomized group, and in the latest period, when continuous long-term combined chemotherapy (CLTCC) with immunotherapy was employed. A comparison was then made between these three kinds of treatment groups. In Comparing of the results obtained for the earliest and middle periods, ILTCC showed a significantly improved beneficial effect over STCC in terms of further increased survival rate. Furthermore, by randomized study, it was clarified that the favourable effect of ILTCC was further improved by concomitant use of immunotherapy. CLTCC with immunotherapy carried out in the latest period seemed to be prevent early recurrences in patients with stage I or II who underwent curative surgery, even though a short-term observation period of for 20 months was employed. It is conceivable that the latest treatment modality used will exerted best the most favourable beneficial effect in comparison with the two early treatments. A review of the literature was presented along with a discussion of the clinical value of chemotherapy and immunochemotherapy as a surgical adjuvant.

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.