Three cases of successful stenting for radiation-induced carotid arterial stenosis

We report three cases of radiation-induced carotid arterial stenosis that underwent successful angioplasty with stenting. The patients had received radiation therapy for tongue or laryngeal cancers and developed minor completed strokes 6 to 14 years after irradiation. All patients had multiple and bilateral stenosis, measuring more than 50%, of the carotid arteries. The stenosis was located in the internal, external, and common carotid arteries. We performed percutaneous transluminal angioplasty with stenting. All interventions were successful and carotid stenosis decreased to less than 28%. No permanent complications occurred. During follow-up periods of up to 26 months, all of these cases were free from ischemic symptoms. Neither carotid angiography nor ultrasound sonography showed evidence of restenosis. The present results suggest the usefulness of angioplasty with stenting for radiation-induced carotid arterial stenosis.     

The clinical evaluation of maxacalcitol on therapy for secondary hyperparathyroidism of chronic hemodialysis patients

The spectrum of bone disease in end-stage renal failure is changing, but secondary hyperparathyroidism is still a troublesome complication. The vitamin D3 analog, maxacalcitol, has reduced calcemic action compared to vitamin D3, but show equivalent suppression of parathyroid hormone(PTH) secretion. In the first step of the study, we investigated the severity of secondary hyperparathyroidism in 670 chronic hemodialysis patients, whose age, sex(male/female), and duration on dialysis were 63.5 +/- 12.4 years, 383/287, and 7.3 +/- 6.0 years, respectively. The number of patients with serum intact-PTH concentrations over 300 pg/ml was 118. Most patients in this group(87.3%) were already being prescribed oral vitamin D3 analog. In the second step, maxacalcitol was administered intravenously, instead of the oral vitamin D3 analog, to 92 patients selected from the above-described group. The age, sex(male/female), and duration of dialysis were 59.4 +/- 11.5 years, 56/36, and 7.3 +/- 6.0 years, respectively. Serum intact-PTH concentration and alkaline phosphatase activity decreased significantly, from 612.3 +/- 32.7 to 414.2 +/- 26.8 pg/ml, and from 329.3 +/- 17.3 to 277.0 +/- 12.5 IU/l, respectively. Serum calcium phosphorous concentration increased significantly, and maxacalcitol administration was interrupted because of hypercalcemia in 17 patients(18.5%). Serum intact-PTH concentration did not decrease in patients with serum Ca concentrations of 10.5 mg/dl or more before maxacalcitol therapy. In conclusion, maxacalcitol suppressed PTH secretion more effectively in hemodialysis patients with secondary hyperparathyroidism than did oral active vitamin D3 therapy, especially in patients with serum Ca concentrations lower than 10.5 mg/dl.     

Bilateral cervicomediastinal neurofibroma originating from the vagal nerve in a patient with von Recklinghausen's disease: report of a case

A 19-year-old woman with von Recklinghausen's disease was admitted with symptoms of hoarseness. A computed tomography scan showed a bilateral cervicomediastinal tumor. An extirpation of the left cervicomediastinal tumor was performed for the purpose of diagnosis and treatment. On thoracotomy, the tumor, which measured 9 × 8 × 4 cm in size, arose from the intrathoracic vagal nerve and the left tumor was resected with a segment of the vagal nerve and recurrent nerve. The pathological diagnosis of the tumor was a neurofibroma. The tumor on the right side was left untreated due to concerns about possibly causing palsy of the bilateral recurrent nerve and also because of the asymptomatic state of the right tumor. Mediastinal neuofibroma in a patient with von Recklinghausen's disease often arises from the intrathoracic vagal nerve. To our knowledge, this is the first report of bilateral cervicomediastinal neurofibroma originating from the vagal nerves. Received: November 15, 2001 / Accepted: May 7, 2002 Reprint requests to: M. Ohta     

Laparoscopic cholecystectomy after coronary artery bypass grafting using the right gastroepiploic artery: report of a case

A laparoscopic cholecystectomy (LC) was successfully performed on a 61-year-old man who had undergone coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). He complained of right hypochondralgia 20 days after CABG. Gallstones were diagnosed and a cholecystectomy was performed 9 months after CABG. Under general anesthesia, the operation was performed using a pneumoperitonium. When a laparoscope was inserted, the RGEA pedicle could be clearly recognized. The pedicle obstructed the operating field and made the working space narrower than usual. No ST changes on the electrocardiogram were seen during LC, especially during the initiation of pneumoperitonium, the insertion of the ports, or when retracting the gallbladder. The postoperative course was uneventful. To avoid complications, care should be taken not to stretch the RGEA pedicle during LC, and careful monitoring of the electrocardiogram is also necessary. It is difficult to view the operating field and the RGEA pedicle together. It is therefore better to insert another laparoscope for concomitant monitoring of the RGEA pedicle. Received: June 25, 2001 / Accepted: January 8, 2002     

Pharmacokinetic interaction between TAK-044, a new endothelin antagonist,and ciclosporin in rats

The pharmacokinetic interaction between TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-alanyl-L- alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium, CAS 157380-72-8) and ciclosporin (CAS 59865-13-3) was investigated after concomitant intravenous (i.v.) administration in rats. After i.v. administration of 14C-labeled TAK-044 ([14C]TAK-044 alone at a dose of 3 mg/kg, the radioactivity concentration in the plasma was 1.65 micrograms/ml at 5 min and decreased biphasically with half-lives of 0.09 h and 0.39 h. AUC0-1 h was 0.38 microgram.h/ml. The pharmacokinetics of [14C]TAK-044 were affected dose-dependently by coadministration with ciclosporin. The AUC value for [14C]TAK-044 was increased 5- and 14-fold by the coadministration with cyclosporin at doses of 3 and 10 mg/kg, respectively. On the other hand, TAK-044 (3 and 10 mg/kg) did not change the pharmacokinetic parameters for ciclosporin (3 mg/kg). Biliary excretion is the major elimination route for both TAK-044 and cyclosporin. Ciclosporin delayed biliary excretion of [14C]TAK-044 in a dose-dependent manner, which might be due to inhibition of process(es) of hepato-biliary excretion of TAK-044. In conclusion, the AUC values for TAK-044 in rats are increased dose-dependently by coadministration with ciclosporin. Therefore, it may be necessary to adjust the dosage of the TAK-044 in combination with ciclosporin in the course of the first clinical trials.     

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 4th communication: Effects on gastrointestinal,urinary and reproductive systems and other effects

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sj?gren's syndrome. The general pharmacological properties of this drug on the gastrointestinal, urinary and reproductive systems and other tissues were investigated in mice, rats guinea pigs, rabbits and dogs. 1. Gastrointestinal system: SNI-2011 did not cause any effects on the gastrointestinal system, i.e. the intestinal transport of charcoal meal in mice, the secretion of gastric and bile juices, and the formation of ulcer induced by water immersion restraint in rats. 2. Urinary and reproductive systems: SNI-2011 augmented the spontaneous movement of rat pregnant uterus in vivo at 0.3 mg/kg i.v. or higher, and this effect was not observed in the non-pregnant uterus. SNI-2011 increased the spontaneous movement of isolated guinea pig bladder (3 x 10(-6) mol/l or higher) and increased the in vivo spontaneous movement of rat bladder (0.3 mg/kg i.v. or higher). SNI-2011 caused increases in rat urine volume, pH and urinary excretion of Na+ and Cl- at 30 mg/kg p.o. 3. Others: SNI-2011 had no effect on the vascular permeability in mice, hematological parameters and blood coagulation in rats. SNI-2011 had neither hemolytic nor anti-inflammatory effect. These results suggest that SNI-2011 has muscarinic effects on the gastrointestinal, urinary and reproductive systems and other tissues at the doses approximately 10-fold higher than the doses needed for saliva secretion.     

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 2nd communication: effects on somatic nervous system and on autonomic nervous system and smooth muscle

A novel muscarinic receptor agonist SNI-2011 ((+/-)-cis-2-methylspirol[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sj?gren's syndrome. The general pharmacological properties of this drug on the somatic nervous system and on the autonomic nervous system and smooth muscle were investigated in mice, rats, guinea pigs, rabbits and cats. 1. Somatic nervous system: SNI-2011 had no effect on the neuromuscular junction in rats and no muscle relaxant effect in mice. No surface anesthetic effect was observed in guinea pigs, but infiltration anesthetic effect was found after intracutaneous injection of solution (1% or higher). 2. Autonomic nervous system and smooth muscle: SNI-2011 tended to cause mydriasis at 3 mg/kg i.v. or higher in rabbits and dose-dependently caused mydriasis at 10 mg/kg p.o. or higher in rats. Mydriasis in rats was also observed by ophthalmic instillation, caused via the peripheral muscarinic acetylcholine receptors. SNI-2011 elevated the base line tension of nictitating membrane in cats when it was injected intravenously at 3 mg/kg or higher. In the smooth muscle, SNI-2011 increased the spontaneous movement of isolated rabbit ileum (1 x 10(-6) mol/l or higher), contractions of isolated guinea pig ileum (1 x 10(-6) mol/l or higher) and isolated guinea pig trachea (3 x 10(-6) mol/l or higher). SNI-2011 relaxed the histamine- and noradrenaline-induced contractions of isolated guinea pig aorta and augmented noradrenaline- and phenylephrine-induced contractions of isolated rat vas deferens. These effects were induced by relatively higher concentrations only i.e. 1 x 10(-5) mol/l or higher. From these results, SNI-2011 has muscarinic side effects on the somatic nervous system and on the autonomic nervous system and smooth muscle, however, in the case of oral administration, that is clinical administration route, SNI-2011 caused no muscarinic side effect at the effective doses needed for saliva secretion.