Antinociceptive Interaction of Intrathecal alpha sub 2 -adrenergic Agonists, Tizanidine and Clonidine, with Lidocaine in Rats

Background: The intrathecal alpha2 -adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2 -adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine.

Methods: Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2 -adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored.

Results: Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in micro gram) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure.     

Congenital esophageal atresia successfully treated by early ligation of a tracheoesophageal fistula and delayed repair of the esophagus in a premature infant: Report of a case

We report herein the case of a premature infant with esophageal atresia (EA) and a tracheoesophageal fistula (TEF) associated with cardiac anomalies who was successfully treated by an early ligation of the TEF following gastrostomy, and delayed repair of the esophagus. A 1212-g male was born prematurely at 31 gestational weeks, at which time he was diagnosed as having EA with TEF and patent ductus arteriosus (PDA), ventricular septal defect (VSD), and atrial septal defect (ASD). A gastrostomy was initially performed but following extubation he gradually became tachypneic. A chest roentogenogram revealed atelectasis and ground-glass appearance, and reintubation was required. Ligation of the TEF was performed 53h after his birth. Following the improvement of his respiratory condition through ventilatory support and the intratracheal administration of pulmonary surfactant, he underwent repair of the esophagus on the 6th day of life. Postoperatively, he suffered from heart failure, but was treated with peritoneal dialysis and pharmacological closure of the PDA. Weaning the infant from the ventilator proved difficult, but it was finally achieved when he had reached a weight of 2268g at 3 months of age by enteral feeding. Our experience of this case demonstrates that early ligation of TEF should be performed for a premature infant with EA and TEF before respiratory distress syndrome (RDS) has developed. If a gastrostomy is required to prevent gastric distention, it should be followed by simultaneous or immediate ligation of the TEF.     

Giant infectious intracavernous carotid artery aneurysm presenting as intractable epistaxis

Infectious intracavernous carotid artery aneurysms usually present with ophthalmoplegia and/or signs of cavernous sinus thrombosis. We report an unusual case in which a patient with AIDS presented with intractable epistaxis secondary to rupture of a giant infectious intra-cavernous carotid artery aneurysm. Culture of the aneurysm grew mycobacterium avium intracellulare (MAI). The patient was treated successfully by excision of the aneurysm and reconstruction of the internal carotid artery with a saphenous vein interposition graft.     

A case of pregnancy in a woman with cloacal dysgenesis and a rudimentary uterine horn

Cloacal dysgenesis is frequently associated with uterine anomalies. We report a case of pregnancy which resulted in an abortion in a woman with a persistent cloaca. Presumptive diagnosis before operation was ectopic pregnancy of the left tube. Postoperatively, the site of implantation of the conceptus was found to be the cavity of a unicornuate uterus in association with a rudimentary horn, the presence of which misled us to diagnose an ectopic pregnancy.      

Anaplastic ganglioglioma with sarcomatous component: An immunohistochemical study and molecular analysis of p53 tumor suppressor gene

The present case report describes a case of ganglioglioma with a distinct sarcomatous component in the left temporal lobe of a 59‐year‐old Japanese man. Neoplastic neuroglial tissue contained both benign and anaplastic glial components with a MIB‐1 labeling index of 0.1% and 12.0%, respectively. Sarcomatous tissue adjacent to the anaplastic glial tissue was dominated by pleomorphic fibroblastic cells with a MIB‐1 labeling index of 10.8%. They were immunoreactive for smooth muscle actin, type IV collagen, and alpha 1 antitrypsin, but not for desmin and CD34. Interestingly, some of the sarcomatous cells were double‐positive for smooth muscle actin and GFAP. The p53 protein had accumulated in the anaplastic astrocytes and sarcomatous cells, but direct DNA sequencing of PCR products failed to detect any mutation in the p53 gene (from exon 4 to exon 10).     

Germ cell tumor in the hypothalamo-neurohypophysial region: clinical features and treatment

Twenty-one patients with germ cell tumors (17 germinomas and 4 teratomas) involving the hypothalamic-neurohypophysial (HN) region were reviewed retrospectively. Eleven patients were males and 10 females, and their ages ranged from 7 to 45 years (average 18.5 years). Diabetes insipidus was the initial and the most prominent symptom in most germinomas; in teratomas the most prominent symptom was visual disturbance. Fifteen patients with germinomas were treated by radiotherapy, and 4 with teratomas were treated by surgical resection alone. Two recent germinoma patients with extensive CSF dissemination were treated with systemic chemotherapy consisting of anticancer platinum drugs and etoposide, which resulted in a complete disappearance of the tumors. Patients with germinoma treated after the introduction of CT scanning had a greatly improved mortality rate, and their actual survival rate was 87.5% over 10 years. On the basis of this review, the authors consider that diagnosis at an early stage of the disease and chemotherapy, which can be an effective therapeuric alternative to radiation therapy, may improve not only the mortality rate but also the quality of life of patients with HN germ cell tumors.     

A Case of Postbulbar Duodenal Ulcer with Jaundice

Abstract: A 63-year-old man was hospitalized because of jaundice and anorexia. An upper gastrointestinal series and hypotonic duodenography revealed circumferential sclerosis and stenosis of the duodenal wall. Endoscopic examination disclosed an ulcer, the upper margin of which was located at the papilla of Vater. The papilla was situated in the base of the ulcer. Endoscopic retrograde cholangiopancreatography disclosed mild dilatation of the common bile, intrahepatic bile and pancreatic ducts, but with neither severe stenosis nor occlusion. Nevertheless, there was some degree of circumferential compression and mild stenosis of the terminal portions of the bile and pancreatic ducts, as potential causes of obstructive jaundice in this patient. Computed tomographic examination of the abdomen revealed a tumorous lesion at the duodenal bulb. Because malignancy in the duodenum could not be ruled out, a pancreatoduodenectomy was performed. Histopathological examination showed a postbulbar duodenal ulcer, associated with inflammation of the papillary orifice and fibrosis of the region near the papilla. There was no evidence of a tumorous lesion. In this case, a postbulbar duodenal ulcer may have caused obstructive jaundice.     

Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma

We report a case of a 15-year-old girl with new onset seizures, who had a mixed dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1 and a high T2 signal on magnetic resonance imaging. Architecturally it was in large part intracortical and multinodular, but also featured a leptomeningeal component. The former corresponded to DNT, a proliferation of oligodendroglia-like cells (OLCs) arranged in nodules, as well as comprising a diffuse internodular element featuring “floating neurons” in a mucoid matrix. The leptomeningeal portion of the lesion was a ganglioglioma consisting of large neurons and astrocytes in association with marked desmoplasia. Spacially, the two components abutted one another but appeared distinct. Immunohistochemistry showed the neurons of the ganglioglioma to be positive for class III β-tubulin, synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100 protein. This apparently mixed lesion suggests that a close histogenetic relationship exists between DNT and ganglioglioma. We postulate that the pluripotential progenitor cells residing in the subpial granular layer may have given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our knowledge, this is the first detailed histological, immunochemical and ultrastructural report of a mixed DNT and ganglioglioma. Received: 11 August 1997 / Revised, accepted: 24 November 1997