ENDOSCOPIC OBSERVATION OF MUCOSAL SPREAD LESION OF CHOLANGIOCARCINOMA USING PERORAL CHOLANGIOSCOPY WITH NARROW BAND IMAGING

A 69‐year‐old man was admitted to Toho University Omori Medical Center complaining of icterus. Abdominal computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were suspicious of cholangioma of inferior bile duct. Peroral cholangioscopy using narrow band imaging (NBI) was performed and it was possible to diagnose the mucosal spread lesions of cholangioma. Histological findings reflected the endoscopic findings. Mucosal spread lesions of cholangiocarcinoma were successfully diagnosed using the CHF‐B260 for NBI.     

Reoperation for a patient with starr-edwards aortic valve malfunction due to pannus formation twenty-nine years after implantation

We report a re-do case of severe aortic valve stenosis due to pannus formation 29 years after an aortic Starr-Edwards caged-ball valve implantation. A huge shelf of calcified and thick pannus tissue below the valve had reduced the already small orifice by at least a third in surface area. The explanted Starr-Edwards valve revealed no mechanical or structural failure. Early detection and treatment of pannus outgrowth is essential in order to prevent life-threatening prosthetic valve malfunctions.     

Phase I study of E1040, a new parenteral cephem antibiotic

The safety and pharmacokinetics of E1040, a new injectable cephem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 125, 250, 500, 1000 and 2000 mg of E1040 were administered by I.V. infusion over 1 hour. Results of 5 minutes I.V. infusions of 500, 1000 and 2000 mg of the drug were also studied. Plasma concentration-time profiles were well suited to a two-compartment open model. The half-life of elimination from plasma was 1.85 +/- 0.16 hours, and the Cmax and AUC paralleled the doses given. The mean urinary recovery within the first 24 hours was 85.7 +/- 6.43% of the dose. In a multiple-dose study, 2000 mg of E1040 (I.V. over 1 hour) was administered every 12 hours (total 9 times) and no abnormal accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between single- and multiple-dose regimens. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject given 250 mg over 1 hour reported diarrhea, and another complained of nausea during the infusion of 2000 mg over 5 minutes. From these results E1040 was concluded to be safe and well tolerated.     

Incidence of renal cell carcinoma in Chiba Prefecture, Japan; ten years experience]

Many reports about the increase of renal cell carcinoma patients have been published in Japan recently, however, the real fluctuations in the total number of patients in relation to the change of population have not been reported yet. Most of the patients with renal cell carcinoma in the last 10 years were examined in Chiba prefecture, which has a population of about five million and 25 active urological offices. Histologically confirmed cases were investigated by sending questionnaire letters. The items were as follows; sex, age, address, occupation, family history, past history, symptoms, examination methods that first detected the tumor, operation date, tumor diameter and clinical stage. Twenty two offices returned answers and 560 cases who lived in Chiba were found to have renal cell carcinoma from 1980 to 1989. Yearly incidence rates per 100,000 persons demonstrated a significant increase from 0.32 to 2.07. Small, asymptomatic and low stage cancers have been increasing rapidly, however, the rate of metastatic disease has not shown any decrease. The main cause of rapid increase seems to be attributed to progress in diagnostic methods and increase of early detection, but the possibility of an increase in some carcinogenic factors can not be ruled out.     

Activation of phospholipase D by platelet-derived growth factor (PDGF) in rat C6 glioma cells: possible role in mitogenic signal transduction.

The effects of platelet-derived growth factor (PDGF) on phospholipase D (PLD) activity and deoxyribonucleic acid (DNA) synthesis in rat C6 glioma cells have been investigated. Pretreatment of serum-starved C6 cells with PDGF results in enhanced choline production and the phosphatidylethanol (PEt) formation in the presence of ethanol, indicating the activation of PLD acting on phosphatidylcholine (PC). The dose-response curve for choline generation and DNA synthesis were comparable. In addition, the effects of PDGF on both PEt formation and [3H]thymidine incorporation into acid-precipitable material was blocked by the potent protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) but not by N-(2-guanidinoethyl)-5-isoquinolinesulphonamide (HA1004), a relatively weak inhibitor of PKC, suggesting that PDGF plays an important role as a positive regulator of glioma cell growth via a PLD-mediated mitogenic signal transduction cascades, which depends largely on the activation of PKC.     

Acquisition of interleukin-3 independence in FDC-P2 cells after transfection with the activated c-H-ras gene using a bovine papillomavirus-based plasmid vector.

Since the ras family of proto-oncogenes is supposed to be involved in leukemogenesis by point-mutational activation, we studied the effect of the activated ras gene on the growth of a murine interleukin-3 (IL-3)-dependent cell line, FDC-P2. The human activated c-H-ras gene was transfected into FDC-P2 cells by electroporation using a high-level expression vector, BMGhph, which contains a partial DNA sequence from bovine papillomavirus (BPV) and a hygromycin B (hmB)-resistant gene as a selectable marker. The transformed FDC-P2 cells showed a high incidence of IL-3-independent growth and tumorigenicity in nude mice. These clones did not express or secrete IL-3, suggesting the acquisition of IL-3 independence by a nonautocrine mechanism. The high incidence of autonomous growth may be due to the use of the BMG vector, because (1) the activated ras gene in pBR322 vector (pHs-49) was not so efficient in the induction of IL-3 independence, (2) the c-H-ras genome copies per cell increased in number up to about 50 copies by using the BMG vector, and (3) cotransfection with the activated ras gene and the BPV gene in separate plasmids partly enhanced the incidence of autonomous growth without increasing the copy number of the ras gene compared with transfection with the activated ras gene alone. The present study supports the idea that the activation of ras gene is an important step in malignant transformation of hematopoietic cells and suggests that the BPV gene products may cooperate with ras gene activation probably by affecting the cellular genes that may be involved in multistep leukemogenesis. The BMG vector may be useful to test the transforming ability of oncogenes whose oncogenic potential is relatively low.     

Globus pallidus calcification in Down syndrome with progressive neurologic deficits.

We report a 10-year-old Down syndrome patient who developed dystonia, choreoathetosis, dysarthria, and dysphagia beginning with hemiparesis. Cranial computed tomography disclosed bilateral calcification in the globus pallidus which resembled a sign of premature aging. Conversely, the clinical course and magnetic resonance imaging findings resembled those of Hallervorden-Spatz syndrome.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.