Protective effects of benidipine on arachidonic acid-induced acute cerebral ischemia in rats.

Acute cerebral ischemia was produced in rats by injection of arachidonic acid (AA) into the internal carotid artery. Evans blue (EB) was intravenously injected and its extravasation into the brain was determined as an indicator of disturbances in the blood-brain barrier and endothelial cells. Control animals showed severe cerebral edema and marked blue staining of the brain. Benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content and the extravasation of EB. Similarly nicardipine (100 micrograms/kg, i.p.) suppressed the elevation of water content and the extravasation of EB. Furthermore, both benidipine (30 micrograms/kg, i.p.) and nicardipine (100 micrograms/kg, i.p.) improved the neuronal injuries following AA-injection. An antiplatelet agent, ticlopidine (100 mg/kg, i.p.), and a thromboxane A2 synthetase inhibitor, OKY-1581 (3 mg/kg, i.p.), also suppressed the elevation of cerebral water content. A lipoxygenase inhibitor, AA-561 (200 mg/kg, p.o.), and a cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.p.), did not prevent the increase in cerebral water content. Neither benidipine (3-30 micrograms/kg, i.v.) nor nicardipine (100 micrograms/kg, i.v.) inhibited the AgNO3-induced thrombus formation of the abdominal aorta, whereas ticlopidine (100 mg/kg, p.o.) and OKY-1581 (3 mg/kg, i.v.) prevented the thrombus formation. From the present results, it is suggested that benidipine, as well as nicardipine, may protect against AA-induced acute cerebral infarction via a mechanism independent of antithrombotic action.     

A case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy

We present a case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy. The case was of a 78-year-old man with the complaint of sudden asymptomatic macrohematuria. An excretory urogram strongly suggested the presence of duplication of the right collecting system, and cystoscopy revealed a gross hematuria from the right ureteral orifice. A retrograde ureteropyelogram revealed incomplete duplication of the right renal pelvis and ureter fused at about the ureter crossing over the iliac vessels, and a polyp-like filling defect in the lower segment of duplicated ureter at about 4 cm from the fusion of the ureters. Transurethral uretero-renoscopy was employed to investigate the filling defect, and a papillary tumor extended into the lower segment of duplicated ureter was revealed. Tumor was resected by a rigid operating instrument under transurethral uretero-renoscopy. The pathological diagnosis was grade I-transitional cell carcinoma of the ureter, so that right total nephroureterectomy with partial cystectomy was carried out subsequently. Surgical specimen after right total nephroureterectomy with partial cystectomy showed no other tumor in the pelvis or ureter macroscopically, and histopathological studies of surgical specimens were no evidence of malignancy. We believe that transurethral uretero-renoscopy significantly increases the diagnostic accuracy in determining the nature of upper urinary tract lesions, and this procedure is indispensable in the diagnosis of ureteral tumors. The present case was the 7th case of primary ureteral carcinoma in the duplicated renal pelvis and ureter in the Japanese literature.     

Modification of the Na,K-pump of glial cells within cobalt-induced epileptogenic cortex of rat

The characteristics of a glial Na⁺,K⁺-pump dependent on extracellular K⁺ within epileptogenic cortex were studied electrophysiologically, biochemically and histochemically in vitro using slices from cobalt-induced epileptogenic cortex of rat. When the extracellular K⁺ concentration ([K⁺]_o) was varied between 4 and 40 mM, the mean slope of membrane potential plotted against [K⁺]_o was about 57 mV in glia from the normal cortex (tissue A) and about 44 mV in glia from the epileptogenic cortex (tissue B); whereas no significant difference in the resting membrane potential of these tissues was observed. In glia from tissue B, a marked transient hyperpolarization above control level was caused by replacement of elevated [K⁺]_o with the normal medium. Ouabain abolished these phenomena observed in glia from tissue B, but had no effect on the membrane potential during normal [K⁺]_o. Reduction of extracellular Na⁺, Ca²⁺ and Cl⁻ did not significantly affect the membrane potential of glia from either tissue. In tissue A, the cells marked by intracellular injection of horseradish peroxidase after intracellular recording were protoplasmic astrocytes; in tissue B, fibrous astrocytes with abnormal processes predominated. K⁺-dependent stimulation of Na⁺,K⁺-ATPase activity of the astrocyte-enriched fraction and its membrane preparation from tissue B was much larger than that from tissue A. A certain amount of the reaction product of K⁺-pNPPase activity was seen on glial plasma membrane within tissue B but not on that from tissue A. The above findings suggest that a glial Na⁺,K⁺-pump within actively firing epileptogenic cortex may be modified to increase in its activity.     

Low-molecular-weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers

Biodegradable copolymers of L -lactic acid (L -LA) and DL -α-hydroxy acids with relatively low molecular weights, for example L -LA/DL -lactic acid (DL -LA), L -LA/DL -α-hydroxybutyric acid (DL -HBA), L -LA/DL -α-hydroxyisovaleric acid (DL -HIVA), and L -LA/DL -α-hydroxyisocaproic acid (DL -HICA), were synthesized by quantitative direct copolycondensation without catalysts at 200°C. The in vitro degradation, which was evaluated by measuring the weight loss of these copolymers in M/15 phosphate buffer solution (pH 7,2) without enzymes at 37°C, is strongly dependent on the kind and molecular weight of these copolymers, resulting in the formation of different degradation patterns such as parabola type (L -LA/DL -HBA system), linear type (L -LA/DL -LA system), and S type (L -LA/DL -HIVA and L -LA/DL -HICA systems).     

Successful treatment of blunt trauma involving complete laceration of the pancreas and duodenum in a 7-year-old child: Report of a case

The acute onset of peritoneal signs and shock in a 7year-old boy who had been hit in the epigastrium by a log-seesaw mandated surgical treatment. Enhanced computed tomography (CT) demonstrated complete laceration of the pancreas as well as duodenal injury, and a duodenoduodenostomy with distal pancreaticogastrostomy was subsequently performed. Temporary external drainage of the stomach and distal pancreas led to an uneventful recovery in the early postoperative period. Although the patient's postoperative development was appropriate for his age, the orifice of the distal pancreas spontaneously closed 2.5 years following surgery. We present this report to stress the fact that every effort should be made to preserve the pancreas following abdominal injury in children.     

Late Effects of Childhood Acute Leukemia and Its Treatment

Late effects of childhood acute leukemia and its treatment were studied in 766 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.     

Pharmacokinetic analysis of antibody localization in human colon cancer: Comparison with immunoscintigraphy

The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study.     

Serum thymidine kinase,a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase

We measured serum thymidine kinase (TK) activity with a radioenzyme assay system employing [I-125]-iododeoxyuridine as the tracer on serial specimens from five bone marrow transplant (BMT) patients before and after transplantation. The serum level of TK activity in the 4 patients with effective BMT treatment ranged from 3.0 to 16.9 U/L (mean, 7.80 U/L) before transplantation and from 27.3 to 236.1 U/L (mean, 82.95 U/L) after the BMT treatment. Mean serum TK activity increased 13.17-fold (range, 1.68 to 29.14-fold). In contrast, the activity in the patient with ineffective BMT treatment was not significantly different during, before, or after BMT treatment. In addition, serum TK activity in BMT patients was well correlated with the change in the number of leukocytes before and after BMT treatment [r = +0.709 (p less than 0.01), y = 0.012 x +0.87]. We conclude that the determination of serum TK activity in BMT patients is very useful in monitoring the course of bone marrow transplantation in the early recovery phase.     

Intercostal hemangioma

This paper presents a case of intercostal hemangioma, in which a complete surgical resection was accomplished based upon a tentative diagnosis provided by magnetic resonance imaging (MRI). A 27-year-old man visited our hospital for the evaluation of chest pain and shortness of breath after exertion. Computed tomography showed a soft tissue mass, 5.5×3.5 cm in size, arising from the right lateral 7th intercostal space. Dynamic MRI showed that the mass was enhanced rapidly in the early phase and that this early enhancement was maintained during the delayed phase, which was compatible with a diagnosis of intercostal hemangioma. The patient underwent surgery, and a complete resection of the tumor with the right 7th and 8th ribs and their intercostal muscles was accomplished. Histopathological examination confirmed the diagnosis of intramuscular hemangioma of the large-vessel type. Presently, 6 months after the operation, the patient is doing well, without any evidence of local recurrence.     

Shifting of dural arteriovenous malformation from the cavernous sinus to the sigmoid sinus to the transverse sinus after transvenous embolization. A case of left spontaneous carotid-cavernous sinus fistula.

The angiographic features of left spontaneous carotid-cavernous sinus fistula and multiple dural arteriovenous malformations that developed after transvenous embolization are described. A dural arteriovenous malformation involving the left sigmoid sinus was demonstrated, along with a marked decrease in size of the left carotid-cavernous sinus fistula and the disappearance of venous drainage from the left cavernous to the right cavernous sinus after embolization with spring coils via the left superior ophthalmic vein. The dural arteriovenous malformation of the left sigmoid sinus subsequently extended to the transverse sinus after partial embolization of the sigmoid sinus. Finally, a dural arteriovenous malformation involving the left transverse sinus developed, with the disappearance of the arteriovenous malformation affecting the sigmoid sinus and left carotid-cavernous sinus fistula following complete embolization of the sigmoid sinus via the left transverse sinus.