As liposomes containing ferromagnetic particles may be applicable for hyperthermia therapy against cancer, a convenient method for their preparation was studied; factors affecting the characteristics of liposomes were also examined. The procedures are as follows: Phosphatidylcholine (PC), cholesterol and hematoporphyrin were dissolved in a mixture of chloroform and methanol (9: 1) . The resultant solution was evaporated by a decompression rotary evaporator so that lipid film was formed on the inner wall of the round-bottom flask. Distilled water was added to the flask and the lipid film was suspended. After adding ferromagnetic Fe₃O₄ particles to the suspension, the preparation was ultrasonicated under a N₂ atmosphere. After centrifugation of the liposomal suspension, the supernatant was concentrated to 30% of the initial volume by ultrafiltration. Thereafter, the concentrated suspension of liposomes containing the ferromagnetic particles was filtered through a Millipore filter with 0.65μm pore size of make the particle size of the liposomes homogeneous. Results of the temperature rise of liposomes when heated with a high frequency induction heater indicated the following: as a main component of liposomes, egg-yolk PC was more preferable than dipalmitoyl Phosphatidylcholine, 30min was sufficient ultrasonication time, addition of rich cholesterol improved the liposomal stability, 15 nm diameter of the ferromagnetic magnetite was more preferable than 150 nm. This liposomal suspension was stable for about two months when kept at 4°C. Based on these findings, these liposomes can be considered beneficial for the study of cancer therapy.

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Pretreatment with Curdlan, a water-insoluble (1-3) -β-D-glucan prepared from Alcaligenes f aecalis var. myxogenes, IFO 13140, via an intraperitoneal route, significantly protected mice from lethal infection by various microorganisms. Introduction of a carboxymethyl group to Curdlan significantly increased its water-solubility, but almost completely eliminated its activity. Curdlan induced polymorphonuclear cell accumulation in the peritoneal cavity and generation of luminol-dependent chemiluminescence by peritoneal exudate cells. The chemiluminescence generated by macrophages was only 7% of that of total peritoneal exudate cells. The data suggest that the water-insolubility is an additional important factor that might affect antimicrobial activity induction.

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Cause and effect relations between Intravascular coagulation and increased vascular endothelial permeability have recently been recognized. The purpose of this study was to investigate the effect of high dose methylprednisolone on tissue edema formation and coagulation in canine legs subjected to venous occlusion. Eight mongrel dogs received 30mg/kg methylprednisolone administration intravenously. Eight additional days received normal saline as controls. Hind leg venous pressure was raised to 75mmHg continuously for 5 hours by a tourniquet around the thigh. Venous blood was sampled before tourniquet inflation, six times during tourniquet inflation, and 60 min after tourniquet ination. The sample blood was used for measurement of Sonoclot coagulation analysis, prothrombin time, and activated partial thromboplastin time. At each time of venous blood sampling, circumferences of 3 points of the distal part of the hind leg were measured to assess edema. Coagulation studies indicated initial hypercoagulability, and later hypocoagulability during venous occlusion in the control group. In the methylprednisolone-treated group, coagulation parameters remained unchanged throughout the study. Percent increases in circumferences as indices of edema formation were significantly less in the methylprednisolone-treated group than in the control group. The results suggest that inhibitory action of methylprednisolone on activation of the coagulation system secondary to venous occlusion may be a key factor in maintaining the integrity of endothelial permeability, resulting in less edema formation.

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Diltiazem and verapamil, calcium channel blocking agents, are reported to elevate plasma concentrations of some clinically used drugs in humans. In the present study, the effect of diltiazem and verapamil on the hepatic mixed function-monoxygenase system was investigated in Sprague-Dawley rats. Diltiazem and verapamil significantly increased cytochrome P-450 content by 60.8% (p<0.01) and 51.3% (p<0.01), respectively, after 5 days of treatment compared to the control value. Content of cytochrome b⁵ was significantly increased by verapamil (45.3%, p<0.01) but not by diltiazem. Activity of aminopyrine-N-demethylase was significantly increased by 5 days of treatment with diltiazem (61.9%, p<0.01) and verapamil (47.8%, p<0.01) . Aniline hydroxylase activity was gradually increased by verapamil treatment with significance on day 5 (33.8%, p<0.05) . The serum ratio of dimethadione to trimethadione (DMO/TMO) was significantly increased by diltiazem (from 0.40 to 0.87, p<0.05), but not by verapamil treatment. Diltiazem significantly enhanced the amount of 4-hydroxyantipyrine excreted into urine from 8.8% to 24.5% (p<0.01) . There was no significant change of any antipyrine metabolite by verapamil treatment. Both diltiazem and verapamil significantly increased the debrisoquine/4-OH debrisoquine ratio indicating inhibition of debrisoquine metabolism. These results suggest that both diltiazem and verapamil induce cytochrome P-450 but have different effects on the activity of P-450 isozyme in rats. Inhibition of hepatic drug-oxidizing enzymes by diltiazem and verapamil reported in humans was observed in this study of the metabolism of debrisoquine in rats.

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Ultrasound is being used extensively during craniotomy for monitoring. In recent years, color Doppler flow imaging has gradually been established, but this technique has been mainly used in conjunction with heart disease. In the present study, the authors used color Doppler flow imaging during surgery for cerebral arteriovenous malformation (AVM) . Differentiation of AVM from surrounding tissue is possible by color Doppler flow imaging, and this intraoperative imaging provides the safest route toward the AVM for the operating neurosurgeons. If further development work could yield improved equipment with a higher-resolution image, color Doppler flow imaging would facilitate the resection of the AVM without the need for a preoperative angiogram.

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This retrospective study of 59 patients with fractures of the mandible was undertaken to evaluate maxillomandibular fixation. Of the patients treated by rigid fixation, 63.3% achieved clinical union within 4 weeks. Fractures with no mobility were treated by semirigid fixation. Neither of these experienced any complication. It was concluded that most uncomplicated mandibular fractures need no more than 4 weeks of rigid fixation for clinical union, and semirigid fixation is indicated when there is no mobility at the fracture site.

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Cyanide concentrations in plasma and red blood cells during hypotension induced by sodium nitroprusside and a nitroprusside-trimetaphan mixture were studied in 29 male rabbits under halothane anesthesia. The rabbits were randomly divided into three groups: nitroprusside (group S; n=10) ; nitroprusside-trimetaphan mixture (group M; n=10) ; Controls (group C; n=9) . Group C received no vasodilator therapy and served as controls. Group S received an infusion of 0.05% nitroprusside solution, and group M received an infusion of a nitroprusside-trimetaphan mixture (0.02% nitroprusside and 0.2% trimetaphan) . Mean arterial pressure was decreased and was maintained at 60 mmHg for 60 minutes in groups S and M. No change was noted in plasma or red blood cell cyanide concentration in group C throughout the experiment. During and after induced hypotension in group S, plasma cyanide concentration was significantly higher than that of control value. The maximum increase occurred 60 min after induction of hypotension and the highest concentration of plasma cyanide was six times the control value. In group M, plasma cyanide concentration was unchanged from the control value. However, during and after induced hypotension, cyanide concentrations in red blood cells of group S and group M were significantly higher than those in control values. Concentrations of cyanide in red blood cells increased for 30 and 60 min during induced hypotension in group S (27.11±3.9μg/ml, P<0.001, 46.73±4.7μg/ml, P<0.001, respectively) and in group M (0.31±0.05μg/ml, P<0.05, 0.29±0.03μg/ ml, P<0.01, respectively) . In conclusion, the data suggest that a nitroprussidetrimetaphan mixture is a safe method to prevent cyanide toxicity for hypotensive anesthesia.

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A simple assay method for selective, highly sensitive, simultaneous determination of catecholamines, indoleamines and related metabolites in the central nervous system by high-performance liquid chromatography with a series of multiple coulometric detectors (HPLC-multiple coulometric detector) was investigated. For good separation of the analysanda (eleven compounds) and internal standards, aμ BONDAPAC C¹⁸ reversed-phase column and a mobile phase consisting of a 0.04M phosphate-0.04M citrate mixed buffer (pH3.0) containing 7.5mM sodium 1-heptanesulphonate, 0.08mM ethylenediaminetetraacetic acid, 11.7% methanol and 4.7% acetonitrile were used. Also, the selective, highly sensitive and simultaneous detection of these neurochemical substances was performed with the redox-reductive screen mode using a series of three coulometric working electrodes (CWE) . In this detection system, the first and second CWE were set at +0.35V and +0.05V, respectively, for the prereaction and to prevent interference; the third CWE was used as an electrode for actual measurement, with its potential set at -0.35V against a palladium reference electrode. The assay limit was 0.5-5.0pg. Excellent chromatograms of catecholamines, indoleamines and related metabolites were obtained within 25 min. The usefulness of the HPLC-multiple coulometric detector system with the redox-reductive screen detection mode was confirmed by application to the determination of concentration levels of catecholamines, indoleamines and related metabolites in crude perchloric acid extracts of rat brain and spinal cord regions. These findings suggest that the HPLC-multiple coulometric detector system with the redox-reductive screen detection mode is useful for the study of neurochemical functions of active substances in the central noradrenergic, dopaminergic and serotonergic nervous systems.

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Maternal exposure to potential teratogens constitutes an area of great concern to pregnant women. Several authors reported increased risk of malformation (particularity cleft lip and palate, and congenital heart disease) to offspring of epileptic mothers on anticonvulsants as one of the teratogens. However, there are few experimental studies of this problem. The purpose of our experiment was to show hemodynamic changes by Laserflo after injecting these agents into chick embryo. A Laserflo perfusion monitor, used for continuous monitoring of local microvascular blood circulation, was used in this experiment. Early on day 4 of incubation, the eggs were prepared for measuring flow, volume and velocity. Three agents (0.05 mg/ml diazepam, 0.3 mg/ml phenobarbital sodium, and 0.5 mg/ml sodium valproate) were introduced through the chorio-allantoic membrane. The three parameters were measured 15 min and 30 min after injection. All three agents induced a remarkable decrease in volume, velocity and flow. This phenomenon may be related to the etiology of induced cardiovascular anomalies.

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The importance of monitoring of spinal cord function in spinal surgery or neurosurgery has recently been emphasized. A decrease in spinal cord evoked potentials is considered to be a warning sign, but in upper cervical or medulla oblongata lesions, the typical means of spinal cord monitoring induces considerable disturbance to the operating procedure due to the presence of electrodes in the epidural space of the upper cervix. Measurement of motor potentials evoked by stimulating electrodes placed at the parietal and the hard palate showed very sensitive alterations consistent with surgical stress, and was thought to effectively monitor the cervical cord and medulla oblongata functions.

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The lever arm (L) and power arm (P) lengths in the two dimensional saggital plane of the human gastrocnemius and soleus muscles were estimated from the measurements of 10 male cadavers. The L/P values, defined as the ratio of these two lengths, were then calculated to determine functional characteristics of the architecture of these two muscles. Analysis of the L/P values suggested the following characteristics of the triceps surae muscle: 1. The gastrocnemius, which was morphologically considered a two joint muscle, had greater effectiveness on the speed of contraction for ankle joint plantar flexion than for knee joint flexion. 2. The soleus, which was morphologically considered a one joint muscle, was more effective on the production of muscular force than the gastrocnemius. Thus, the soleus is specialized for muscular force generation and the gastrocnemius is specialized for the speed of the joint excursion. 3. The distal expansion of the origin of the soleus did not reflect on its functional characteristics. These results agree with the accumulated data of the histological and biochemical features of this muscle, and could be correlated with the human bipedal habit.

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A 38-year-old housewife with hereditary thyroxine-binding globulin (TBG) excess complicated by hyperthyroidism was followed up over 16 years. This clinical entity is extremely rare and only 6 cases have been reported in Japan. Hyperthyroidism in this case developed initially as T³ toxicosis and a transient rise in TRAb was observed following recovery of thyroid function after antithyroid therapy. A pedigree survey revealed that her mother had a high level of blood TBG, comparable to that of the patient. It required more than 10 years for complete remission of her hyperthyroidism by antithyroid therapy. It was concluded from this fact that the TBG excess has no beneficial effect on the hyperthyroidism.

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