Phase II Study of Mitoxantrone in Patients With Non-Small Cell Lung Cancer

A phase II study of mitoxantrone was performed in 24 patientswith non-small cell lung cancer (NSCLC). Mitoxantrone was administeredby intravenous drip infusion of 12 mg/m² every three weeks.There were no responders among the 21 evaluable patients includingfive patients without prior therapy. The major hematologicaltoxic effect was leukocytopenia. Thrombocytopenia and decreasein hemoglobin were slight. A change in the electrocardiogramwas observed in one patient and one patient experienced cardiogenicshock. Mitoxantrone is not acceptable for the treatment of NSCLC becauseof its low antitumor activity, and careful observation is neededfor administration of this agent to patients with pre-existingrisk factors, such as prior anthracycline exposure, mediastinalradiation or underlying cardiovascular disease.     

Bioavailability of Bropirimine 250 mg Tablet in Dogs: Effect of Food

The postprandial effect on the bioavailability of bropirimine in dogs after oral administration of bropirimine tablets (Bropirimine 250 mg Tablet) was investigated. At a dose of 500 mg bropirimine (two tablets of bropirimine 250 mg), the maximum plasma concentration under the postprandial condition was about twice that observed under the fasting condition, and the area under the plasma concentration vs time curve under the postprandial condition was also twice that under the fasting condition. The absolute oral bioavailabilities of bropirimine were 41.1% under the fasting condition and 83.5% under the postprandial condition. It is considered that the longer gastric residence time and larger volume of the gastric fluid induced by food-intake caused the increase in dissolution of bropirimine which increased the bioavailability after oral dosing of bropirimine 250-mg tablets.     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

A Case of Pneumocytoma (So-Called Sclerosing Hemangioma) With Lymph Node Metastasis

A case of "sclerosing hemangionia" (pneumocytoma) of the lungwith lymph node metastasis is reported. A 22-year-old Japaneseman was found to have a well-defined round lesion in the rightlung (S⁷), which increased in size slightly during a 2-yearfollow-up period. He underwent right lower lobectomy with a preoperative diagnosisof a benign lung tumor. The pulmonary tumor revealed histologicalfeatures characteristic of "sclerosing hemangioma" of the lung,in addition to which there were many large polygonal foamy cells,forming tubular or papillary structures. These cells were foundby electron microscopy to contain numerous cytoplasmic lamellarbodies and showed a positive reaction with anti-surfactant apoproteinantibody immunohistochemically. Therefore, they were consideredto be cells differentiating toward type II pneumocytes. Reviewof 21 typical "sclerosing hemangionia" disclosed a few or somesuch foamy cells in 10 cases. A single hilar lymph node wasthe site of microscopic metastases, which consisted of "largeclear foamy cells" and smaller polygonal or round cells withslightly eosinophilic cytoplasm, both of which were componentsof the pulmonary "sclerosing hemangioma" This case supportsthe theory that "sclerosing hemangioma" is a neoplasm of typeII pneumocyte lineage. Although it is said to be benign, rarecases apparently show metastatic potential.     

Benign Tumors and Tumor-Like Lesions (Excluding Adenomas) of the Lung: Radiological and Clinicopathological Analysis of 48 Cases

Forty-eight cases of surgically resected benign tumors and tumor-likelesions of the lung were analyzed, with the following results:1) Hamartoma and sclerosing hemangioma have well defined borders,compressing bronchi and blood vessels, and are loosely boundto the surrounding lung parenchyma. 2) Hamartomas, in 90% ofthe cases, showed "nodularity" on film tomograms. Histologically,nodularity at the edge was produced by lobules of cartilage.3) Fifty-three percent of the patients with sclerosing hemangiomawere middle-aged females and asymptomatic. Only two patientscomplained of hemosputum. Routine roentgenograms showed a roundshadow with homogeneous density. Cut surfaces were solid withvarious degrees of hasemorrhage. 4) Roentgenograms of benignmesothelioma showed large tumors more than 4 cm in diameter,in which extrapleural signs could be observed. 5) "Calcification"was seen on the roentgenograms of seven out of 27 hamartomasand one out of 15 sclerosing hemangiomas. Pleural retractioncould not be seen in our series. Xerotomography was superiorto film tomography in showing calcification. 6) One of the sclerosinghemangiomas was double, and the other 47 benign tumors and tumor-likelesions were solitary; the lesions were peripheral in 45 casesand central in three. All of the patients were free of localrecurrence and distant metastasis.     

Atrial Electrograms and Activation Sequences in the Transition Between Atrial Fibrillation and Atrial Flutter

Transition Between Atrial Fibrillation and Flutter. Introduction: The eletrophysiologic mechanism of atrial fibrillation (AF) has a wide spectrum, and it seems that some atrial regions are essential for the occurrence of a particular type of AF. We focused on one type of AF: AF associated with typical atrial flutter (AFI), which was right atrial (RA) arrhythmia, and sought to investigate intra-atrial electrograms and activation sequences in the transition between AF and AFL.
Methods and Results: Intra-atrial electrograms and activation sequences in the R.A free wall and the septum were evaluated in the transition between AF and AFL in seven patients without organic heart disease (all men; mean age 57 ± 11 years). In five episodes of the conversion of AFL into AF, the AFL cycle length was shortened (from 211 ± 6 msec in stable AFL to 190 ± 15 msec before the conversion, P, 0.001). Interruption of the AFL wavefront and an abrupt activation sequential change induced by a premature atrial impulse resulted in fractionation and disorganization of the septal electrograms. During sustained AF, septal electrograms were persistently fractionated with disorganized activation sequences. However, the RA free-wall electrograms were organized, and the activation sequence was predominantly craniocaudal rather than caudocranial throughout AF. In 12 episodes of the conversion of AF into AFL, the AF cycle length measured in the RA free wall increased (from 165 ± 26 msec at the onset of AF to 180 ± 24 msec before the conversion, P, 0.001). AFL resumed when fractionated septal electrograms were separated and organized to the caudocranial direction, despite the RA free-wall electrograms remaining discrete and sharp with an isoelectric line.
Conclusion: Changes of the electrogram and activation sequence in the atrial septum played an important role in the transition between AF and AFL.     

Medium-term results of percutaneous transluminal balloon aortic valvuloplasty with Inoue balloon catheter for congenital aortic stenosis

Although percutaneous transluminal balloon aortic valvuloplasty (PTAV) has been performed for congenital aortic stenosis in infants and children for several years, its efficacy and the associated aortic regurgitation (AR) have not been widely discussed. Percutaneous transluminal balloon aortic valvuloplasty using an Inoue balloon catheter was performed for congenital aortic stenosis in 12 patients (4–16 years old) in this study. The systolic aortic valve pressure gradient ranged from 42 to 111 mmHg before PTAV and became < 50 mmHg immediately after PTAV in 10 cases (83%). Eight of these 10 patients had no increase in the gradient during subsequent observation for a period of 9–40 months. Aortic regurgitation increased immediately after PTAV in nine cases (75%). It increased from grade 1 to grade 2 in eight cases and from grade 1 to grade 3 in one patient; no significant enlargement of the left ventricular end-diastolic diameter and no significant change in the left ventricular end-diastolic pressure (LVEDP) or the cardiac index was observed during follow-up in these patients. There was a correlation between the diameter of the balloon and efficacy; an appropriate diameter was considered to be about 90% of the aortic annular diameter. Changes in the hemodynamic parameter after PTAV with an Inoue balloon were small in most patients and this procedure is considered to be a treatment that should be attempted prior to surgery for congenital aortic stenosis.     

Biophysical properties of protein-free,totally synthetic pulmonary surfactants,ALEC and Exosurf,in comparison with surfactant TA

An artificial pulmonary surfactant prepared from chloroform-methanol extract of bovine pulmonary surfactant (surfactant TA) has been shown to be effective in both the prevention and the treatment of respiratory distress syndrome in premature babies. Recently, two types of protein-free totally synthetic surfactants, artificial lung expanding compound (ALEC) and Exosurf, have been evaluated in clinical trials of surfactant therapy. Artificial lung expanding compound was used initially as a dry powder, but is now prepared as a crystalline suspension in saline at 4°C. In this study we compared the biophysical properties of three different forms of ALEC (dry powder, crystalline suspension at 4°C and 37°C), Exosurf and surfactant TA (Surfacten) using a modified Wilhelmy surface balance and a pulsating bubble surfactometer. Surface activity of a crystalline suspension of ALEC in cold saline was no better than the dry powder of ALEC. Surfactant activity of ALEC was improved by addition of hydrophobic surfactant protein B and C (SP-B, SP-C) which are important constituents of surfactant TA. Surface properties of ALEC in any form and Exosurf were not superior to those of surfactant TA. These results suggest that a surfactant which contains SP-B and SP-C does not necessarily have to be dry or crystalline for an effective exogenous surfactant.     

Ureteral obstruction due to retroperitoneal fibrosis secondary to a solitary internal iliac aneurysm

We report a case of ureteral obstruction due to retroperitoneal fibrosis secondary to a solitary left internal iliac aneurysm. It has been reported that as a cause of ureteral obstruction, an internal iliac aneurysm without aortic and/or common iliac aneurysms is very rare. In the present case, magnetic resonance imaging was a useful modality to diagnose retroperitoneal fibrosis secondary to an internal iliac aneurysm as a direct cause of ureteral obstruction.     

Resetting of Tachycardia Cycle by Single and Double Ventricular Extrastimuli in Recurrent Sustained Ventricular Tachycardia

In two cases with recurrent sustained ventricular tachycardia (VT) due to re-entry, the response pattern to extrastimuli during the tachycardia was studied. In each case, right ventricular extrastimuli with longer coupling intervals during VT were followed by fully compensatory pauses and with shorter coupling intervals reset the tachycardia cycle. In one case, a plateau was produced by a single extrastimulus, resembling that seen in the response curve of sinus node automaticity as well as ectopic atrial tachycardia. Two successive stimuli produced three definite zones, i.e., fully compensatory, reset producing a plateau, and progressive prolongation zones with shortening of the coupling intervals between the two stimuli, and terminated the tachycardia with further shortening of the coupling intervals. In conclusion, resetting phenomenon was confirmed on two cases with re-entrant VT. This phenomenon cannot be used as a criterion to determine the mechanism responsible for VT.