Analgesic action of loperamide,an opioid agonist,and its blocking action on voltage-dependent Ca2+ channels

We investigated the relationship between the antinociceptive effect of the opiate agonist loperamide at the spinal level and its inhibitory effect on calcium influx. Intrathecal administration of loperamide showed a significant antinociceptive effect in the formalin test, which was not prevented by naloxone. On the other hand, no significant effects were observed by nicardipine, an L-type specific blocker, or by BAY K8644, an L-type specific agonist, suggesting no significant role of L-type calcium channels in nociceptive signal transduction. Loperamide suppressed the calcium influx in dorsal root ganglion neurons. As the antinociceptive effect of loperamide was not affected by naloxone or other calcium channel blocking toxins, and loperamide showed a direct inhibitory effect on calcium-influx, the analgesic effect of intrathecally injected loperamide might be due to its blockade of the voltage-dependent calcium channels at the terminals of the primary afferent fibers.     

Relation between yawning behavior and central serotonergic neuronal system in rats

Summary Subcutaneously (s.c.) administered apomorphine (0.0125–0.4 mg/kg) or physostigmine (0.025–0.4 mg/kg) to rats elicited yawning. The dose-response curves were bellshaped. The peak effects of apomorphine and physostigmine were observed with a dose of 0.1 mg/kg of each drug. Yawning elicited by apomorphine (0.1 mg/kg) or physostigmine (0.1 mg/kg) was reduced by intraperitoneally (i.p.) administered 5-hydroxytryptophan (5-HTP, 50–200 mg/kg, given 30 min before). Yawning elicited by apomorphine but not by physostigmine was enhanced by p-chlorophenylalanine (p-CPA, 25–400 mg/kg i.p., given 24 h before). Apomorphine elicited but not physostigmine-elicited yawning was enhanced by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 8 g/rat, given 14 days before into the dorsal raphe). This treatment led to a 35% depletion of serotonin (5-HT) in the striatum. 5-HTP, p-CPA or 5,7-DHT given alone did not elicit yawning. Bilateral, intrastriatal microinjection of apomorphine (1.5 –50 g/site) but not physostigmine (5–50 g/site) elicited yawning. The dose-response curve was also bell-shaped. These results indicate that central serotonergic pathways play an important role in modulating drug-elicited yawning in rats. Send offprint requests to S. Okuyama at the above address     

A new method of primary engineering of esophagus using orthotopic in-body tissue architecture

PurposeTissue engineering of esophagus is required for management of long-gap esophageal atresia (LGEA). Collagenous connective tissue membranes fabricated by in-body tissue architecture (iBTA), called biosheets, can repair esophageal defects and generate tissues similar to native esophagus. However, iBTA requires second-stage surgery because of heterotopic preparation of biosheets. Our aim was to develop orthotopic iBTA for primary engineering of the esophagus by interposing a tubular mold to the esophageal defect.MethodThe cervical esophagus of six rats was transected. An acrylic tube (internal diameter 2.6 mm, length 7.0 mm) was inserted and fixed between the ends of the upper and lower esophagus, and a 3 mm-long esophageal defect was created. Four weeks later, the rats were sacrificed for histological analysis.ResultsPostoperatively the rats could intake liquid food. After four weeks, the esophageal defects were filled with regenerated tissues. Histologically the new esophageal walls stained positive for collagen type I. The inner surfaces were covered with stratified squamous epithelium that expressed pan-cytokeratin. In only one of six rats, regeneration of muscular-like tissue was suggested by positive immunohistochemical staining for desmin.ConclusionOrthotopic iBTA can regenerate a substitute esophagus with esophageal epithelium and collagenous wall. This technique may be a novel treatment for esophageal atresia with gaps of various lengths including LGEA.     

Evaluation of conventional weaning criteria in patients with acute respiratory failure

We evaluated the reliability of conventional weaning criteria from a ventilator during 33 weaning trials on 25 patients with acute respiratory failure (ARF). Of 13 criteria, a ratio of maximal voluntary ventilation to minute ventilation (MV) 2, a vital capacity 12ml·kg^–1, a spontaneous respiratory rate 25 breaths·min^–1, and a MV 10l·min^–1 appeared to be useful for predicting successful weaning outcome. However, even using those criteria, there were many falsely-negative cases. The alveolar-arterial P_{O 2} gradient 350mmHg at an Fi _{O 2} 1.0 was not useful as a predictor of weaning outcome. The present study demonstrates that conventional criteria are frequently inaccurate for predicting weaning outcomes and suggests that the use of some of these criteria may unnecessarily prolong the length of ventilator support. Since ventilation of most patients with poor oxygenation can be successfully discontinued by placing them on a continuous positive airway pressure system, these results suggest that the improvement of oxygenation is not an indispensable prerequisite for weaning from mechanical ventilators.(Okamoto K, Iwamasa H, Dogomori H, et al.: Evaluation of conventional weaning criteria in patients with acute respiratory failure. J Anesth 4: 213–218, 1990)     

Nutrient-induced thermogenesis (NIT) following amino acid infusion

Nutrient-induced thermogenesis (NIT) induced by parenteral infusion of amino acid (AA) mixtures of different composition and of the same AA mixtures given via different routes (parenteral or intraportal infusion) were investigated in rats using a small animal indirect calorimeter. When 8 different AA solutions of differing composition but with the same total concentration were infused parenterally, both standard NIT (each AA is assumed to generate 3.28 kcal/g) and specific NIT (heat energy of each AA is calculated assuming that it is oxidized to carbon dioxide and water, and metabolised to urea and sulphuric acid) values of the leucine (Leu)-rich and the glycine (Gly)-rich solutions were significantly greater than those of the control solution. Removal of Leu or Gly from the respective AA solutions reversed the increase of both NIT values down to control levels. When the parenteral and portal infusion routes were used in one rat, both NIT values for parenteral infusion of the Leu-rich solution were again significantly greater than those of the control. Likewise, both NIT values for intrportal infusion of the Leu-rich solution were also significantly greater than those of the control. However, no difference in NIT values was found between parenteral and portal infusion of either solution. The result of this study indicated that Leu and Gly may be thermogenic AAs, and the thermogenic effect of Leu is not dependent upon the route of infusion.     

Recurrent breast cancer at 21 years after resection detected by serum tumor markers and manifested as dermatomyositis

A 52-year-old Japanese woman developed dermatomyositis. She had undergone a standard radical mastectomy for left breast cancer 21 years earlier. Though no physical sign of recurrent breast cancer appeared clinically, levels of tumor markers were abnormally elevated. Therefore, tamoxifen and CAF therapy were given. Further, the clinical course of dermatomyositis almost paralleled the level of serum tumor markers and the clinical course of her recurrent breast cancer. These markers were useful for detecting the recurrence, following the metastatic disease, and monitoring her response to therapy.     

Ocular findings in Japanese women with nevus of Ota

Background: Nevus of Ota is common in Japanese women, but most patients are not examined ophthalmologically. Methods: We performed ophthalmologic examinations on 16 Japanese women who had had bluish pigmentation in the periorbital region, sclera, and conjunctiva since birth. Results: Fifteen patients had unilateral involvement, and one had bilateral lesions. The visual acuities were good, and the intraocular pressures were within normal range. All patients had a negative family history. Three patients had light pigmentation in the optic disc in the affected eye. Conclusion: We believe that optic disc pigmentation associated with nevus of Ota, as found in these three patients, may be common but have been rarely described.     

Mapping-guided focal cryoablation and endoaneurysmorrhaphy for a case of ischemic ventricular tachycardia with left ventricular aneurysm

A 74-year-old woman admitted with exertional dyspnea. Echocardiography revealed the giant left ventricular aneurysm. In the hospital course, she fell into sustained monomorphic ventricular tachycardia. Coronary angiogram showed complete obstruction of the LAD. Left ventricular ejection fraction was 20%. The origin of tachycardia seems to be at infero-apicallateral area of LV by electrophysiology study. Because of the failure of RF energy ablation, we planned mapping-guided cryoablation, CABG and endoaneurysmorrhaphy. To prevent air embolism and myocardial ischemic damage for long aortic cross clamp, intraoperative endocardial mapping was carried out on beating heart due to continuous normothermic coronary blood perfusion (300 ml/min) from the aortic root cannula under aortic clamping. Cold crystalloid cardioplegia changed into the root cannula after EPS, focal cryoablation (-100 degrees C) was performed 3 times on cardiac arrest. Sustained VT was not inducible in the following study. CABG and endoaneurysmorrhaphy was performed on repeated cardiac arrest during single aortic clamp. Postoperative course was uneventful, and she discharged 8 weeks after the operation.