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.     

Validity of Electrode Placement at Fpz to Detect Alpha Wave

Abstract: The possibility on placing electrodes at Fpz-A₂ instead of C₃-A₂ was investigated to obtain a more stable configuration avoiding obstruction by the hair. Our original system of alpha wave detection by a microcomputer was used, and a total of 22 all-night hypnograms of five healthy young students waa recorded. Pearson's moment correlation coefficients of alpha wave % between the two positions were 0.780–0.948. Except for one subject, alpha wave % taken at Fpz-A₂ tended to be 3–5% lower than that at C₃-A₂. The above analysis indicates that using EEG electrode position of Fpz-A₂ is valid and useful as a stable electrode configuration for a long-time monitoring.     

Effects of ethanol feeding on collagen synthesizing and degrading enzymes in rat pancreas

Collagen metabolism in the pancreas was investigated in male Wistar strain rats after 7 weeks of ethanol feeding. Compared with control rats, the ethanol-fed rats had a normal hydroxyproline content in the pancreas. However, prolyl hydroxylase activity and collagenolytic cathepsin activity were increased, though collagenase activity did not change. Both prolyl hydroxylase activity and collagenolytic cathepsin activity were inversely correlated with amylase activities. These findings were also confirmed in ethanol-pyrazole treated rats. These results suggest that the ethanol-induced pancreatic injury, even at an early stage, accelerates the collagen metabolism in the pancreas.     

Antibodies against saline-soluble components of skeletal muscle in myasthenia gravis

Summary Antibodies against phosphate-buffered-saline extracts (SE) of non-acetylcholine receptor (AChR) skeletal muscle antigens were found in patients with myasthenia gravis (MG). The antigenicity of SE was distributed in three fractions with molecular masses of over 200 kDa, 90–150 kDa and 7–14 kDa on gel filtration. These fractions shared common antigenicities. Further analysis of 90–150 kDa fractions on sodium dodecyl sulphate polyacrylamide gel electrophoresis showed five major bands, ranging from 105 kDa to 275 kDa. The antibodies against SE were detected in 52% (58/112) of the MG patients; incidence and titres were higher in the thymoma group (n=21; 90% and 0.872 respectively) than in the non-thymoma group (n=91; 43% and 0.200, P<0.001). In patients without a thymoma, these antibodies were frequently observed in late-onset disease and the severe generalized form (P<0.01). In 4 of 7 ocular MG patients without anti-AChR antibodies, low but appreciable levels of anti-SE antibodies were found. In 73% (11/15) of generalized MG patients treated with prednisolone and thymectomy, anti-SE antibody titres changed in association with those of anti-AChR antibodies and with the clinical course. Both antibody titres increased synchronously in patients who developed crises.     

Polycationic biocides with pendant active groups: molecular weight dependence of antibacterial activity.

Two types of polycations with pendant active groups were synthesized: one is polymethacrylate containing pendant biguanide units, and the other is poly(vinylbenzyl ammonium chloride). The two polycations were found to exhibit higher bactericidal activity against Staphylococcus aureus than the corresponding monomers. Fractionation of the polycations was successfully performed on gel filtration chromatography, and examination of the antibacterial activity against S. aureus of the well-characterized polymer samples with various molecular weights (MW) revealed that the activity was strongly dependent on the MW of the polycations and that there existed an optimal MW range for the cidal action of the polymeric biocides. Experiments on the lysis of protoplasts of Bacillus subtilis in contact with the polycations have shown that target sites of the polycationic biocides are cytoplasmic membranes of bacteria.     

When is total thyroidectomy indicated as a treatment of “follicular carcinoma”?

Clinicopathologic studies were performed to establish rational criteria for total thyroidectomy as a treatment of follicular carcinoma. During the 4-year period from 1981 to 1984, total thyroidectomy was carried out on 23 patients in whom unequivocal vascular invasion and/or obvious extracapsular extension were disclosed on pathological study of the primary thyroid lesion. Although occult metastatic lesions were detected postoperatively in 5 patients, no distant metastases have been found in 12. Distant metastasis was clinically manifest on admission in the other 6 patients. The degree of vascular invasion at the primary lesion was not correlated with the occurrence of distant metastasis. However, 10 of the 15 patients with tumors characterized by a thick fibrous capsule had distant metastases, while all but 1 of 8 patients with a thin capsule showed no metastasis. Apparent capsular invasion seemed to increase the relative risk of distant metastasis. On the other hand, solid clusters of tumor cells containing a variable number of small follicles, which characterize Langhans' wuchernde Struma, were found in 6 patients, and 5 of them showed distant metastases. Thus, total thyroidectomy should be considered when (a) distant metastases are clinically apparent, (b) the primary lesion has a thick fibrous capsule with or without obvious capsular invasion, or (c) solid clusters of tumor cells are demonstrated microscopically.

---

Resumen Se realizaron estudios clinicopatológicos con el propósito de establecer criterios racionales para la tiroidectomía total en el tratamiento del carcinoma folicular. En el curso de un perfodo de 4 anos entre 1981 y 1984, se realizó tiroidectomía total en 23 pacientes en quienes se halló inequívoca invasión vascular y/o obvia extension extracapsular en el examen histopatológico de la lesión tiroidea primaria. Aunque postoperatoriamente se detectaron lesiones metastáticas ocultas en 5 pacientes, no se encontraron metástasis distantes en 12. Metástasis distantes eran clínicamente manifiestas en el momenta de la admisión en los otros 6 pacientes. El grado de invasión vascular en la lesión primaria no apareció correlacionado con la ocurrencia de metástasis distantes. Sin embargo, 10 de los 15 pacientes con tumores caracterizados por una cápsula gruesa y fibrosa tenían metástasis distantes, mientras solo 1 de 8 pacientes con tumores de cápsula fina mostró metástasis. La invasión capsular aparente parece incrementar el riesgo relativo de metástasis distantes. Por otra parte, agrupaciones sólidas de células tumorales con presencia de números variables de folículos pequeños, que caracterizan al wuchernde Struma de Langhans, fueron encontrados en 6 pacientes, 5 de los cuales mostraron metastasis distantes. Por lo tanto, se debe considerar la tiroidectomía total cuando: (a) haya metástasis distantes clínicamente aparentes, (b) la lesión primaria tenga una gruesa cápsula fibrosa con o sin invasión capsular obvia, y (c) se demuestren microscópicamente agrupaciones sólidas de células tumorales.

---

Résumé Une étude clinicopathologique a été menée pour déterminer les critères de thyroïdectomie totale comme traitement dans le cancer folliculaire de la thyroïde. Pendant 4 ans, de 1981 à 1984, 23 patients ont subi une thyroïdectomie totale pour envahissement vasculaire non équivoque et/ou extension extracapsulaire évidente découverte sur la pièce d'exérèse initiale. Cinq patients avaient des métastases occultes découvertes dans la période postopératoire, 6 avaient des métastases cliniquement évidentes, alors que 12 ne présentaient aucun signe de métastase à distance. Le degré d'envahissement vasculaire de la lésion primitive n'était pas corrélé avec la survenue de métastases à distance. Cependant, 10 des 15 patients à tumeurs caractérisées par un épaississement de la capsule fibreuse avaient des métastases à distance, alors que 7 des 8 patients avec une capsule mince n'avaient pas de métastases. L'envahissement capsulaire était associé à un plus grand risque de métastases à distance. Des amas solides de cellules tumorales contenant de petits follicules, le wuckernde struma de Langhans, étaient retrouvés dans 6 cas, dont 5 avaient des métastases à distance. Ainsi, la thyroïdectomie totale est préconisée lorsque (a) des métastases à distance sont cliniquement évidentes, (b) la lésion primitive possède une capsule fibreuse épaisse avec ou sans envahissement évident, et (c) on met en évidence des cellules tumorales en amas microscopiquement.

---

---

Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.     

Juvenile parkinsonism with marked diurnal fluctuation

We presented a report on four cases of juvenile parkinsonism with a marked diurnal fluctuation of symptoms and dystonia. Among parkinsonian signs, rigidity fluctuated the most and increasing rigidity by passive or active movements or emotional stress was observed. When we analyzed patients previously reported, in addition to our own new patients, apart from the diurnal fluctuation and predominant occurrence in females, many similarities to Yokochi's third group of juvenile parkinsonism were found. In the previous reports, the patients with the marked fluctuation of parkinsonian symptoms have not always shown dystonia. The changes of symptoms in relation to menstruation and pregnancy were other characteristic features in our three female patients. Here we proposed that for the present, it is preferable to call this disorder "juvenile parkinsonism with a marked diurnal fluctuation."