Effects of Bepridil Versus E‐4031 on Transmural Ventricular Repolarization and Inducibility of Ventricular Tachyarrhythmias in the Dog

Background: Bepridil (a multiple channel blocker) may markedly prolong the QT interval and induce polymorphic ventricular tachyarrhythmias (VTA). We compared the transmural ventricular repolarization characteristics and inducibility of polymorphic VTA after administration of bepridil versus the pure I_Kr blocker, E‐4031, each administered to five open‐chest dogs. Methods: We used plunge needle electrode to record transmural left ventricular (LV) repolarization and activation‐recovery interval (ARI) to estimate local repolarization. The correlation between paced cycle length and ARI was separately examined in the LV endocardium, mid‐myocardium (Mid), and epicardium. Attempts to induce VTA were made during bradycardia and sympathetic stimulation. Results: Bepridil and E‐4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia. Compared with E‐4031, bepridil caused mild, reverse use‐dependent changes in ventricular repolarization, and less ARI dispersion than E‐4031 during slow ventricular pacing. Both drugs increased ARI_max and cycle length at 50% of ARI_max, though the changes were smaller after bepridil than after E‐4031 administration. Bradycardia after the administration of each drug induced no VTA; however, sympathetic stimulation induced sustained polymorphic VTA in two of five dogs treated with E‐4031 versus no dog treated with bepridil. Conclusions: Unlike the pure I_kr blocker, E‐4031, bepridil exhibited weak properties of reverse use‐dependency and protected against sympathetic stimulation‐induced VTA. It may be an effective supplemental treatment for recipients of implantable cardioverter defibrillator. (PACE 2010; 950–959)     

Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in transcatheter arterial embolization for urgent control of life-threatening massive bleeding from gastric or duodenal ulcer

We estimated the usefulness of a mixture of N-butyl-2-cyanoacrylate (NBCA) with lipiodol for transcatheter arterial embolization (TAE) used to control massive bleeding from gastric or duodenal ulcer. Thirty patients who had gastric or duodenal ulcers and massive bleeding that was uncontrollable by endoscopic procedures were included in this study. All patients were subjected to TAE (without NBCA in 23 and with NBCA in seven patients). Coils and/or gelfoam were also used. The achievement of haemostasis, occurrence of rebleeding and the time taken for TAE were compared between patients who received TAE without and with NBCA. Eighteen of 23 patients (78.3%) who received TAE without NBCA and six of seven patients (85.7%) who underwent TAE with NBCA achieved complete haemostasis without rebleeding. The time for TAE was significantly shorter in patients who received NBCA compared with those who did not (P= 0.0095). TAE using NBCA or a combination of NBCA and coils achieved a rapid, complete embolization regardless of vascular distribution or arterial diameter. Thus NBCA is considered to be useful as a secondary embolization material in TAE that is urgently conducted to control massive bleeding from gastric or duodenal ulcers.     

“Reverse” Bypass Using a Naturally Formed “Bonnet” Superficial Temporal Artery in Symptomatic Common Carotid Artery Occlusion: A Case Report

We herein describe a patient with symptomatic common carotid artery occlusion who underwent a reverse superficial temporal artery (STA)-middle cerebral artery (MCA) single bypass using a naturally formed “bonnet” STA. The surgical procedure was performed without difficulty, and no further neurological deterioration was observed after surgery. In practice, this case highlights that the reverse STA-MCA bypass can be achieved safely and less invasively using a naturally formed “bonnet” STA.     

Hypercalcemia Associated With Neoplastic Diseases

Hypercalcemia was observed most frequently in patients withadvanced breast cancer, following which the order of occurrencewas in lung, cervix, esophagus and tongue cancer patients, andmyeloma patients. The shortening of Q – aTc interval onthe electrocardiogram was remarkable and served as a usefulindicator in the early detection of hypercalcemia. The loweredserum phosphorus level was often observed in hypercalcemia inpatients with skeletal metastases. Metabolic alkalosis in hypercalcemiawas probably due to hypochloremia or hypopotassemia. The degreeof calcium deposition along the renal tubules was proportionalto the duration of hypercalcemia. Corticosteroid administrationwas effective in the treatment of hypercalcemia. However, patientsdied frequently of uremia when hypercalcemia persisted for morethan 20 days. The mechanism of hypercalcemia associated withneoplastic diseases is discussed.     

Primary pulmonary choriocarcinoma in a four month old boy complicated with precocious puberty

A four month old boy with pulmonary choriocarcinoma, showing iso-sexual precocious puberty is reported. His serum human chorionic gonadotropin (HCG) was highly elevated. A round isolated tumor in the right lung, found by chest X-ray, magnetic resonance imaging and gallium scintigraphy, was removed surgically a month and a half after clinical manifestations were noticed. It was determined to be choriocarcinoma on the basis of histological findings and positive HCG on histochemical examination. Skull irradiation and chemotherapy (cisplatinum, vinblastin and bleomycin) had only a transient effect on reducing tumor size and normalizing the serum level of HCG. This case suggests that a more effective treatment regimen needs to be established.     

PEPTIC ULCER: PATHOGENESIS,HEALING AND ANTI-ULCER DRUGS

Abstract At present, the evaluation of anti-ulcer drugs is generally accomplished simply by calculating the cumulative healing rate at a certain point of time during treatment, which does not implicate any analysis of the healing speed of the ulcer. If the cumulative healing rate of an ulcer is expressed as a function of drug administration time, t, then it will be possible to calculate parameters concerning the healing speed of ulcers and thus evaluate drug efficacy as the time series analysis of the cumulative healing rate. A new method of evaluating anti-ulcer drugs by a statistical analysis of healing speed is proposed. A non-linear regression analysis was performed between two variables, t (time of drug administration: week) and y (non-healing rate: %), to obtain the exponential function y = Ae^?kt. The theoretical values calculated from the exponential equation were in close proximity to the observed values. With this analysis, four parameters concerning the healing speed were defined, namely the healing rate constant, the initiation time of healing, the half-life of non-healing rate and the time necessary for 50% healing. With this method, the efficacy of drugs on peptic ulcer healing was dynamically analysed, the non-healing rate (y) being expressed as an exponential function of length of time (t) of treatment, thus obtaining digital parameters for healing speed.     

The Establishment of a Cell Strain (PC-1) from a Human Lung Cancer

A human lung cancer cell strain (PC-1) was established in vitroand maintained in continuous growth for more than two and ahalf years. The material used for explanation was a metastaticlymph node of a case of poorly differentiated epidermoid carcinomaconsisting predominantly of small anaplastic cells of a polygonalcell type. The cultured cell grew attached to a glass surfacein layered heaps and were epidermoid ultrastructurally. Chromosomal analysis of the cells at the 7th passage culturerevealed that all mitotic cells with the chromosome number of46 or more exhibited the karyotypic abnormality of Dp⁺. Tumorsdeveloped after hetcrotransplantation of the cultured cellsinto the hamster's cheek pouch showed features of epidermoidcarcinoma with keratinization indicating neoplastic cell originof the strain. Doubling time of the total cell population was72 hours. Histogenesis of the small cell anaplastic carcinoma was discussed.     

Morphometry of Bladder Cancer Cells in Tissue Sections According to Histological Grade of Malignancy

Morphometrical analysis was performed on cells of bladder carcinomastaken from patients who had undergone surgery at the NationalCancer Center Hospital. Ten cases each of the following groupswere compared as to the nuclear area, standard deviation ofnuclear areas, cytoplasmic area, and nuclear/cytoplasmic ratio:normal mucosa and grade I transitional cell carcinoma obtainedby transurethral resection (TUR), and normal mucosa, grade II,III and in situ transitional cell carcinomas obtained by totalcystectomy. There were significant differences in both nuclear area andnuclear/cytoplasmic ratio between normal epithelium obtainedby TUR and grade I carcinoma. There were also significant differencesin nuclear area and nuclear/cytoplasmic ratio among the fourtotal cystectomy groups. In this cytomorphometrical analysis, cells of carcinoma in situhad the characteristics of grade II or grade III carcinoma cells.The morphometrical features of the two advanced cases of gradeII carcinoma revealed that the nuclear area, the standard deviationof the nuclear area and the cytoplasmic area were rather small,whereas the nuclear/cytoplasmic ratio was almost average forthe grade II group. The results of this analysis, especially those for the nuclear/cytoplasmicratio, corresponded well with the histological grading of bladdercarcinoma.     

Effect of Local Anaesthetics on the Stimulus-secretion Coupling in Bovine Adrenal Chromaffin Cells*

Abstract— This study was carried out to determine the relative potencies of local anaesthetics to inhibit the cholinergic synaptic transmission using cultured bovine adrenal chromaffin cells, and to clarify if the inhibitory action would correlate with biophysical and pharmacological properties. Local anaesthetics (bupivacaine, etidocaine, tetracaine, lignocaine and procaine; 0·02–2 Mm ) inhibited carbachol-induced catecholamine release from the cells in a concentration-dependent manner. This inhibition was completely reversible. IC50 (concentration of 50% inhibition) of each anaesthetic showed no correlation with the lipid solubility. The local anaesthetics showed greater inhibitory potency at a higher extracellular pH. The results suggest that clinically relevant concentrations of local anaesthetics inhibit the stimulus-secretion coupling in the chromaffin cells. The un-ionized base form plays a major role, and the inhibitory potency does not depend on the lipid solubility of the anaesthetics.