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.

Limitations of successive transradial approach in the same arm: the Japanese experience.

The transradial approach (TRA) has been used for diagnostic and interventional cardiology. It has not previously been determined how many times the same radial artery can be cannulated without complications. A total of 812 patients (502 men and 310 women) underwent angiography or angioplasty via the TRA between 1997 and 1999 at our institution with a total of 1,438 procedures. Sheaths were 5 (55%) or 6 Fr (45%). Dropout rates of 3.5% and 7.9% were found at the second TRA attempt in the men and the women, respectively. Of the 62 TRA failures, 56 (90%) were due to narrowing or occlusion of the radial artery after the previous TRA procedure. A third TRA procedure was possible in 90% of the men and 80% of the women. A fifth TRA procedure was possible in 70% of the men and 50% of the women. The dropout rates for TRA increased as successive punctures were performed. This was primarily due to vessel narrowing and occlusion occurring as a function of multiple punctures.

Efficacy of a new hemostatic device, Adapty , after transradial coronary angiography and intervention.

A novel hemostatic device, Adapty (Medikit, Tokyo, Japan), was developed to achieve effective and comfortable hemostasis following transradial procedures. The device consists of a pad fixed to a transparent plastic plate and a self-adhesive strap. The catheter sheath is removed from the radial artery after the pad has been positioned precisely over the puncture site, with the strap attached to the plate. Compression pressure then is adjusted with the self-adhesive strap, as is required with occlusive clamps. Patients do not need to maintain hyperextension of the wrist after the procedure. The wrist can be mobilized immediately after application. The efficacy of Adapty was evaluated in prospective observations of 200 patients. The device was successfully applied in all patients immediately after sheath removal. No patient required interruption of compression because of pain, congestion or ischemia. Complete hemostasis was obtained in 199 patients (99.5%), and the device caused no vascular complications. This study demonstrates that Adapty is highly effective for achieving hemostasis after transradial procedures.

Tumor necrosis factor-alpha (TNF-alpha)-induced and interleukin-1 beta (IL-1 beta)-induced shedding of TNF receptors from gingival fibroblasts.

Tumor necrosis factor-alpha (TNF-alpha) exerts its functions by binding two different receptors (TNFR55 and TNFR75). Both TNFR55 and TNFR75 exist in cell-associated and soluble forms. Soluble TNF receptors (sTNFR), sTNFR55 and sTNFR75, are proteolytically shed upon inflammatory stimuli and then modulate various TNF-alpha bioactivities. As human gingival fibroblasts (HGF) can be potential targets for TNF-alpha in inflamed gingiva, we hypothesized that HGF partially modulate the cellular responses to TNF-alpha by regulating their own TNFR. In this study, the kinetics of expression of cell-associated and soluble forms of both receptors from cultured HGF in response to proinflammatory cytokines TNF-alpha and interleukin-1 beta (IL-1 beta) were investigated in vitro. Both TNF-alpha and IL-1 beta upregulated the gene expression of TNFR75 and did not affect that of TNFR55. TNF-alpha and IL-1 beta decreased binding of [(125)I]TNF-alpha to HGF. Moreover, TNF-alpha and IL-1 beta upregulated the release of sTNFR75 from HGF but not that of sTNFR55. These results suggest that HGF under inflammatory conditions may contribute to the inactivation of circulating TNF-alpha through the preferential induction and shedding of TNFR75.

A case in which stent insertion is considered to have triggered contrast medium-induced coronary vasospasm.

A Gianturco-Roubin II (GR-II) stent was inserted in a 75-year-old man who developed restenosis of the right coronary artery (RCA) after percutaneous transluminal coronary angioplasty (PTCA). Although the vessel became partially occluded after 7 months, it was redilated by PTCA. Follow-up angiography of the RCA and left coronary artery (LCA) was performed 3 months later. Chest pain with bradycardia and hypotension occurred immediately after this examination, and ST elevation appeared in ECG leads II, III, and aVF. Repeat angiography of the RCA confirmed complete occlusion due to a spasm at a site proximal to the GR-II stent. The spasm was resolved by intracoronary infusion of isosorbide dinitrate (ISDN), and PTCA was carried out for extensive recurrent restenosis of the RCA; however, vascular dissection developed at the distal end of the GR-II stent. Therefore, a Palmaz-Schatz (P-S) stent was placed such that its proximal end overlapped the distal end of the GR-II stent. Follow-up angiography 3 months later showed no restenosis, but an episode of vasospasm similar to the previous one occurred immediately after left ventriculography. The RCA was completely occluded proximal to the GR-II stent because of spasm. Although this spasm was gradually relieved by intracoronary infusion of ISDN, marked spasm was also observed distal to the P-S stent; complete relief was achieved by infusion of additional ISDN.

Expression of truncated pro-opiomelanocortin gene transcript in human leukemia cell lines.

Although previous studies have suggested that human peripheral blood mononuclear cells (PBMCs) may express pro-opiomelanocortin (POMC) mRNA and synthesize its related peptides, the patho-physiological role of POMC expressed in peripheral cells is not known. In this study, we investigated the POMC gene expression in various types of human leukemia cell lines by Northern blot analysis and the reverse transcribed-polymerase chain reaction (RT-PCR) method. The POMC mRNA was not detected by Northern blot analysis in all cell lines tested except the Jurkat cell line which is derived from T-lymphoblastic leukemia. The POMC mRNA expressed in the Jurkat cells was smaller than that in the human anterior pituitary gland. The RT-PCR method revealed that a truncated-POMC transcript could be detected not only in lymphoblastic leukemia cells but also in erythroid and myeloid cells. Interestingly, two cell lines of monocytic leukemia, J-111 and U937, did not express the truncated-POMC mRNA. Treatment with concanavalin-A stimulated truncated POMC mRNA expression and ACTH-like immunoreactivity in lymphoblastic leukemia cells with T-(Jurkat) and B-(BALL-1) lymphocyte phenotypes. These results confirm that human leukemia cells except for monocytic cells express a truncated-POMC mRNA as well as in the human normal PBMC.

Structural analysis of N-linked carbohydrate chains of funnel web spider (Agelenopsis aperta) venom peptide isomerase.

The structure of the N-linked carbohydrate chains of peptide isomerase from the venom of the funnel web spider (Agelenopsis aperta) has been analyzed. Carbohydrates were released from peptide isomerase by hydrazinolysis and reductively aminated with 2-aminopyridine. The fluorescent derivatives were purified by phenol/chloroform extraction, followed by size-exclusion HPLC. The structure of the purified pyridylamino (PA-) carbohydrate chains were analyzed by a combination of two-dimensional HPLC mapping, sugar composition analysis, sequential exoglycosidase digestions, and mass spectrometry. The peptide isomerase contains six kinds of N-linked carbohydrate chains of truncated high-mannose type, with a fucose alpha 1-6 linked to the reducing N-acetylglucosamine in approximately 80% of them.

Species differences and mechanism of the epimerization of a new MAO-A inhibitor.

1. (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl-2-oxazolidinone (E2011) has two chiral centers in its structure. In vivo optical inversion of the hydroxy group at one of the chiral centers converts E2011 to a diastereoisomer (ER-20593). Pharmacokinetic parameters of E2011 and ER-20593 were determined after administration of E2011 to rat at 10 mg/kg, and the plasma concentration ratios of E2011 to ER-20593 were almost constant after Tmax of the plasma concentrations. 2. E2011 and ER-20593 were separately administered orally to six species in addition to rat, and the species differences in both directions of epimerization (i.e. from E2011 to ER-20593 and from ER-20593 to E2011) were studied by measuring the plasma concentrations of both compounds. In mouse, guinea pig, dog, and squirrel monkey, the epimerization of E2011 to ER-20593 did not occur, but the epimerization of ER-20593 to E2011 did. In rat, pig and rhesus monkey, the inversion of E2011 to ER-20593 occurred, but the ratios of this inversion were smaller than those for the inversion in the opposite direction. E2011 underwent about 15% inversion to ER-20593 in rat, which was the largest inversion in the seven species examined. 3. To study the mechanism of the epimerization, deuterium-labelled E2011 and ER-20593 (created by substituting the proton at the chiral center of the parent compounds for deuterium) were orally administered (separately) to rat and dog, and the concentration ratios and molecular weights of E2011 and ER-20593 in the plasma were determined by hplc and FAB(+)-mass spectrometry respectively. The results indicated that the major mechanism of the epimerization was oxidation to the carbonyl form followed by reduction to the original epimer and/or the other epimer. 4. The carbonyl form of E2011 (CO-E2011) was reduced to E2011 and ER-20593 (alcohol forms) by liver cytosol and microsomes from rat and dog in vitro with NADH or NADPH. The resultant epimeric ratios (E2011:ER-20593) were consistent with the in vivo results in rat and dog. 5. In conclusion, species differences in the epimerization of E2011 would result from product stereoselectivity of the reductase activity with the carbonyl intermediate.

[Repair of intrathoracic visceral damage using video-assisted thoracoscopic surgery for blunt chest trauma and rib fixation at the site of mini-thoracotomy].

We treated three patients with intrathoracic visceral damage caused by severely dislocated fractured ribs resulting from blunt trauma by using video-assisted thoracoscopic surgery (VATS) and rib fixation through a mini-thoracotomy. Under general anesthesia and unilateral respiration, the thoracic cavity was inspected with a thoracic video scope through the port inserted through the thoracic drainage opening which was made upon arrival at hospital. As the visceral damage seemed restorable under VATS, a mini-thoracotomy was positioned just above the rib fracture. Two thoracic ports were inserted through the site of rib fracture or through the intercostal space and then VATS was performed using three ports. After the restoration of intrathoracic visceral damage, the fractured rib was fixated using a bioabsorbable poly-L-lactide rib fixation pin or a marlex mesh. Lung injuries were sutured and ligated under VATS in two of our cases and a spur of the fractured rib was shaved in one case. Only severely dislocated ribs were fixated through the mini-thoracotomy in all cases. Air leakage stopped just after this procedure and there were no complications. The rib fixation and bone regeneration were excellent after this procedure. The advantages of this method are the visceral restoration under VATS through a mini-thoracotomy and the ability to perform rib fixation without injuries to the intercostal muscle, artery, vein or nerve. This operative procedure is recommended for intrathoracic visceral damage caused by severely dislocated rib fracture.

Portal-hepatic venous shunt through a portal aneurysm complicated by hepatic encephalopathy and pulmonary hypertension.

We report a rare case of portal-hepatic venous shunt through an enormous portal aneurysm complicated by pulmonary hypertension. A 66-year-old woman was admitted to our hospital for hepatic encephalopathy. Chest roentgenography revealed pulmonary hypertension. Computed tomography and ultrasound examination demonstrated a shunt between the portal and hepatic veins through an enormous portal aneurysm. The diagnoses of portal-hepatic venous shunt and pulmonary hypertension were confirmed by hepatic venous catheterization and cardiac catheterization. Pulmonary hypertension might result from the effects of vasoconstrictive agents, which should be metabolized by the liver in normal subjects, passing through the intrahepatic shunt into the lung.

GM-CSF- and IL-3-dependent CD34 expressing myeloid cell line (SAS-1) established from CD7 and CD34 expressing acute myeloblastic leukemic cells.

A novel factor-dependent human myeloid leukemia cell line (SAS-1) was established from a 69-year-old Japanese male suffering from CD7 and CD34 expressing acute myeloblastic leukemia (AML M2 in FAB classification). Morphological and cytochemical staining showed that SAS-1 cells were round with basophilic cytoplasm which is positive for peroxidase. Analysis of surface markers revealed that SAS-1 cells were myeloblasts derived from an immature progenitor origin, which express CD34. The consensus karyotype of the cell line was 41 XY 5q-, -7, 11p-, 12p+, -13, -14, -16, -17, -19, -22, with two markers. The proliferation of SAS-1 cells was dependent on the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and GM-CSF- and IL-3-induced proliferation was dose dependent. Neither, stem cell factor (SCF) nor granulocyte colony-stimulating factor (G-CSF) alone supported the growth of SAS-1 cells, but supported their viability for more than 4 days and arrested them in the G0/G1 phase. SCF also enhanced GM-CSF- or IL-3-induced growth, but other cytokines did not have this synergistic effect. Clonogenic assays revealed that SAS-1 cells formed 36.0 +/- 5.7 or 41.5 +/- 0.7 colonies/1000 cells in the presence of GM-CSF or IL-3, respectively. SCF also increased the number of colonies formed by GM-CSF or IL-3 treatment, while SAS-1 cells did not form colonies in the presence of SCF alone. SAS-1 cells may prove to be a useful tool for studying the regulation of the cell cycle, myeloid proliferation, and differentiation.

[Esophago-bronchial fistula which developed after the insertion of an expandable metallic stent for corrosive esophageal stenosis].

A 69-year-old man attempted suicide by abdominal penetrating injury and taking sulfonyl acid. After a laparotomic drainage operation, corrosive esophageal stenosis occurred. Esophageal bougienage was not effective. An expandable metallic stent (GIANTURCO-ROCHE Z stent, Cook Bloomington U.S.A.) was inserted aiming to achieve temporary oral diet and nutritional improvement. But diet did not improve sufficiently because of the awareness of the prosthesis, severe hiccup, uncontrolled regurgitation esophagitis and restenosis caused by intraluminal mucosal growth. After 4 months of insertion, an esophago-bronchial fistula was produced by the wire of EMS. An operation became necessary for this complication. No data exist on the long-term use of the EMS and it is not suitable for benign esophageal stenosis. Unavoidably if the palliative treatment of endoprosthesis is necessary for benign esophageal stenosis such as corrosive esophageal stenosis, a removable esophageal tube prosthesis is preferable.

[Administration method and recurrence-preventing effect of medroxyprogesterone acetate (MPA) as a postoperative adjuvant endocrine therapy for stage III breast cancer. Kitakyushu Collaborative Study Group for Breast Cancer].

By a collaborative study undertaken by 11 medical institutions in the Kita-Kyushu area, we evaluated the clinical efficacy of the combination of medroxyprogesterone acetate (MPA) and Tamoxifen (TAM) as a postoperative adjuvant endocrine therapy for Stage III breast cancer. First, 1 course of CAF therapy was administered; then, in combination with the basic therapy of 5-FU 200 mg/day p. o. for 3 years, ER (+) patients were treated with either 2-week sequential therapy of TAM (30 mg/day) and MPA (800 mg/day) or TAM (30 mg/day), and ER (-) patients received either MPA (800 mg/day) or 5-FU alone. Neither survival nor disease-free rates of the 92 analyzable patients were different between these treatment groups. Furthermore, the blood levels of MPA and cortisol had no correlation with survival and disease-free periods. We studied the effect of MPA on the natural inhibitors of blood coagulation, but found no difference from the result in healthy adults. It was, however, shown that MPA had a bone marrow-protecting effect.

Cardiogenic shock following recombinant alpha-2b interferon therapy for chronic hepatitis C. A case report.

A 57-year-old woman with chronic hepatitis C was treated with alpha-2b interferon (IFN). Forty-five days after the initiation of IFN therapy, she developed cardiogenic shock. Acute perimyocarditis as a cause of cardiogenic shock was clinically suspected by the findings of complete atrioventricular block, regional wall motion abnormality and pericardial effusion. Since IFN therapy may induce cardiogenic shock in some patients, it is important to carefully monitor patients under treatment with IFN for abnormal cardiac signs.

Sarcoidosis after interferon therapy for chronic active hepatitis C.

Sarcoidosis is characterized by multisystemic granulomatous lesions of unknown etiology. A 62-year-old woman developed sarcoidosis after treatment with alpha-2a interferon (IFN) for 24 weeks (total dose: 522 million units) for chronic hepatitis C. She developed complete atrioventricular block and multiple noncaseating granulomatous lesions in the lung. IFN therapy, which may disturb cellular immune activation in some patients, may have contributed to the onset and progression of sarcoidosis.

[Preoperative plasmapheresis for lung cancer with multiple myeloma].

A 66-old-male admitted to our hospital was diagnosed multiple myeloma (IgA kappa type, Durie & Salmon stage IIIA) and squamous cell lung cancer (c-T2N0M0 stage I). The function of platelets was within a normal range (11.7 x 10(4)/mm3 and the bleeding time of two minutes), but the function of coagulation was reduced (prothrombin time, 13.1 seconds; activating prothrombin time, 45.1 seconds; and antithrombin III, 65%). The hyperviscosity syndrome was anticipated because of high IgA M protein (6,551 mg/dl). Plasmapheresis with 800 ml of fresh frozen plasma was performed before the left lower pulmonary lobectomy and R1 lymph node dissection. Then the function of coagulation was improved (prothrombin time, 12.6 seconds; activating prothrombin time, 31.3 seconds; and antithrombin III, 75%). IgA M protein was also decreased to 4,696 mg/dl. Postoperative bleeding necessitated a second thoracotomy. The cause of postoperative bleeding was the ablasion of the pleural adhesion due to tuberculous pleuritis as well as bleeding tendency of multiple myeloma. The plasmapheresis performed in this case did not fully improve the bleeding tendency. Cases of cancer complicated with multiple myeloma have been increasing and if an operation is needed, plasmapheresis should be considered. The indication and the extent of hematologic restoration to be achieved should be further investigated.

PSA assay of dried blood samples from the ear lobe on a filter paper with special reference to prostatic mass screening.

To eliminate complicated procedures for taking blood samples in the field work for prostatic mass screening, we developed a method for PSA testing using blood samples taken from the ear lobe and dried on a filter paper. The stability, the diagnostic efficacy, and the cost-benefit effect of the method were confirmed in hospitalized patients, as well as in subjects from our mass screening program.

Kinetic analysis of prostatic volume in patients with stage D prostatic cancer treated with LHRH analogues in relation to prognosis.

OBJECTIVE: To evaluate the clinical usefulness of the kinetic analysis of prostatic volume in the prognosis of patients with Stage D prostatic cancer treated using luteinizing hormone-releasing hormone (LHRH) analogues. PATIENTS AND METHODS: The reduction of prostatic volume was monitored in 12 patients with Stage D prostatic cancer using transrectal ultrasonography (TRUS) after treatment with LHRH analogues. Data obtained from the kinetic analysis of prostatic volume were compared with the prognosis. RESULTS: All the patients having a reduction time, tau (derived from the kinetic analysis of prostatic volume change with time), of less than 41 days had neither clinical progression within 15 months nor death caused by prostatic cancer during the 5-year follow-up, while the disease-specific 5-year survival rate in patients having a tau of greater than 42 days was as low as 17%. The difference in both the progression and disease-specific survival between these groups was statistically significant (P < 0.05) despite the limited number of patients. In contrast, conventional prognostic parameters showed no significant predictability for prognosis with the exception of prostatic acid phosphatase, which correlated strongly with the occurrence of progression within 15 months. CONCLUSION: The kinetic analysis of the change of prostatic volume using TRUS shows promise in the prognosis of the patients with Stage D prostatic cancer.

Direct determination of E2020 enantiomers in plasma by liquid chromatography-mass spectrometry and column-switching techniques.

High-performance liquid chromatography with column switching and mass spectrometry (MS) was applied to the on-line determination and resolution of the enantiomers of E2020 (acetylcholinesterase inhibitor) in plasma. This system employs two avidin columns and fast atom bombardment (FAB)-MS. A plasma sample was injected directly into an avidin trapping column (10 mm x 4.0 mm I.D.). The plasma protein was washed out from the trapping column immediately while E2020 was retained. After the column-switching procedure, E2020 was separated enantioselectivity in an avidin analytical column. The separated E2020 enantiomers were specifically detected by FAB-MS without interference from metabolites of E2020 and plasma constituents. The limit of quantification for each enantiomer of E2020 in plasma was 1.0 ng/ml and the intra- and inter-assay relative standard deviations for the method were less than 5.2%. The assay was validated for enantioselective pharmacokinetic studies in the dog.

[The historic study on the health drink-especially on the origin of health drink and the formation of its market-].

The health drink is oral liquids which are classified as elixirs or limonades and so on, which are peculiar to Japan and differ from other liquids to glass a dose of drug. It has mainly been divided into two classes by glassed volume (dosage) in the bottle. One class is the drink tonic which is the capacity of 100 ml and another is the mini-drink tonic which is 50 ml and less. In addition, oral liquid glassed with an ampule is called the ampule tonic. Such drugs were thought to appear after World War II and have been widely known since 1960. However, tonics which had consisted of recipies like the present health drink were shown to exist before World War II. Thus, it was considerable that such prescription formulas were also applied to the ampule tonic and drink tonic. On the other hand, one of the important problems with health drugs was how to make their taking easy in its development. Further, it was necessary to add to acid antiseptic and high content of sugar etc., because the liquids generally had been putrescible. It might be one of the reason for their appearances that it was allowed to produced a liquid which was stabler and made its taking easier to be released from the above limit by the introduction of a dose-glassed liquid. In 1960, the ampule tonic quickly became popular and the drink tonic followed. It was probably caused by changes on the standard and style of living involved the enhancements of the labor time, purchasing power and sense on the health and active propaganda of the manufacturers. In this way, the market has satisfactorily expanded. However, because such medicines liked beverages appeared, it was difficult to distinguish their differences since 1965. Therefore, the Ministry of Health and Welfare has performed some administrative guidances. In 1978, it regulated new approval of the production of 100 ml drink tonics, which led to the appearance of the mini-drink tonic. Its market rapidly expanded since 1985. In 1991, its scale reached about 200 billion yen on both drink tonics and the sale volume was 20% at drug stores in Japan. The health drink is supporting the economic foundation of drug stores at present.