Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

New hepatic vein reconstruction in left liver graft.

The incidence of hepatic venous stenosis is higher in partial liver transplantation. New methods for hepatic venous reconstruction in left liver transplantation, which secure wide anastomosis, were devised and are reported here. In the graft, the right side of the middle hepatic vein or the left side of the left hepatic vein was cut longitudinally and a rectangular-shaped vein patch was attached for venoplasty. In the recipient, after the left and middle hepatic veins were joined, the right side of the middle hepatic vein was cut toward the closed right hepatic vein, making a horizontal cavotomy for anastomosis. Of 92 patients who underwent conventional hepatic vein reconstruction, 3 were complicated by hepatic venous stenosis (median follow-up 43 months). By contrast, there were no hepatic vein complications in the 20 patients who underwent the new technique (7 months). The current method appears to be technically feasible for outflow reconstruction in left liver graft transplantation.     

Direct determination of benzalkonium chloride in ophthalmic systems by reversed-phase high-performance liquid chromatography

High-performance liquid chromatography has been used to quantitate benzalkonium chloride (alkylbenzyldimethylammonium chloride) in complex ophthalmic formulations at or below concentration levels of 50 ppm. The method involves a one-step dilution for sample preparation and direct injection; therefore, recovery and/or conversion problems are nonexistent. The assay is quick, specific, reproducible, and simple. This new approach makes routine determinations far simpler than previous methods and is especially useful for product stability studies and quality control procedures.     

Factor VIII lability, protein C and other vitamin K-dependent proteins

The stability of factor VIII was studied in plasmas from patients on long-term warfarin therapy. The percent residual factor VIII activity (F.VIII:C) after incubation at 37 degrees C for 4 hr was higher in warfarinized patients than in normal subjects; 76.9 +/- 10.8% (mean +/- SD) of the initial F.VIII:C in the patients versus 61.6 +/- 5.8% in normal subjects (p less than 0.001). On the whole, neither protein C nor vitamin K-dependent coagulation factors except factor VII activity (F.VII:C) correlated with the residual F.VIII:C. There was a negative and weak correlation between the residual F.VIII:C at 4 hr and either the initial F.VIII:C or F.VII:C. Another experiment using protein C depleted plasma showed a relatively enhanced stability of F.VIII:C in the protein C deficiency. These results indicate that factor VIII is more stable in warfarinized plasma, and that protein C and vitamin K-dependent coagulation factors are not the sole, main factor responsible for such a phenomenon.     

Lp(a) lipoprotein in cerebrovascular disease and dementia

Lp(a) lipoprotein has been considered an independent risk factor in the development of coronary heart disease (CHD). We examined the role of Lp(a) in patients with cerebrovascular disease (CVD) and those with dementia. The Lp(a) concentration in patients with CHD, those with cerebral infarction due to a large artery occlusion and those with vascular dementia (VD) was significantly higher than that of age-matched control subjects. However, the Lp(a) concentration was not high in cerebral infarction due to a small artery occlusion, intracerebral hemorrhage and dementia of the Alzheimer type (DAT). The present results suggest that Lp(a) should cause VD as well as CVD, and that Lp(a) should be one of the indicators that distinguish VD from DAT.     

Oxygen-assisted breath-holding in computed tomography

To achieve prolonged breath-holding, oxygen was administered just before dynamic CT and high resolution lung CT. Oxygen administration has proved to be a supportive means to improve the quality of CT studies.