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.     

Arterial conduit shear stress following bypass grafting for intermediate coronary artery stenosis: a comparative study with saphenous vein grafts.

OBJECTIVES: Graft failure has been reported when the arterial conduit, such as the internal thoracic artery (ITA) or the right gastroepiploic artery (GEA), is grafted to a lower grade coronary artery stenosis. The shear stress as a significant factor affecting graft patency was compared between the arterial conduit and the saphenous vein graft (SVG) after surgery. METHODS: In 101 patients, 40 ITAs, 27 GEAs and 34 SVGs were examined using a Doppler-tipped guide wire during postoperative angiography. The graft flow volume and shear stress were calculated from velocity and diameter data. The study grafts were classified according to the grade of native coronary artery stenosis: group L had more than 50 up to 75% stenosis, and group H had more than 75% stenosis. Group H consisted of 25 ITAs, 17 GEAs and 21 SVGs, while group L consisted of 15 ITAs, 10 GEAs and 13 SVGs. RESULTS: In group H, graft flow volume did not significantly differ among the ITA (34+/-11 ml/min), GEA (36+/-16 ml/min) and SVG (41+/-15 ml/min), and graft shear stress significantly (ITA vs. GEA P<0.0001; GEA vs. SVG P<0.01) differed among the ITA (16.0+/-4.8dyn/cm(2)), GEA (9.1+/-3.2dyn/cm(2)) and SVG (4.8+/-1.6dyn/cm(2)). In group L, flow volume was lower (P<0.001) in the ITA (18+/-6 ml/min) and GEA (13+/-8 ml/min) than in the SVG (35+/-16 ml/min), and shear stress was significantly (P<0.001) greater in the ITA (13.7+/-4.9dyn/cm(2)) than the GEA (5.6+/-2.0dyn/cm(2)) or SVG (4.6+/-2.0dyn/cm(2)). CONCLUSIONS: These data suggest that shear stress of the ITA is superior and maintained despite the flow volume being reduced by flow competition. Lower shear stress of the GEA for intermediate stenosis may be associated with the development of conduit failure.     

UFT for head and neck cancers: its tissue concentrations and effects on lymphocyte subpopulations

Summary UFT, a combination of the masked compound of 5-fluorouracil (FT-207) and uracil, was given to head and neck cancer patients for 1 week preoperatively and for 8 weeks postoperatively. Drug concentrations were examined in the surgically removed tissues. The concentrations of FT-207, 5-fluorouracil, and uracil were higher in tumor tissues than in normal tissues. The lymphocyte subpopulations were assessed by cytofluorometry with monoclonal antibodies. There was no evidence that adjuvant chemotherapy with UFT specifically suppresses immunocompetent cells. We therefore conclude that further clinical evaluation of adjuvant chemotherapy with UFT would be worthwhile.     

A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis]

A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.     

Improvement of Cardiac Function by Dry Weight Optimization Based on Interdialysis Inferior Vena Caval Diameter(3)

The nonimprovement group was characterized by the following: ① a high incidence of diabetes (4 of 6 patients) ,② a high incidence of preexisting cardiac dysfunction documented prior to or at the time of induction of     

Gene therapy for gastrointestinal tract cancer: Prospects for combination treatment consisting of surgery and molecular surgery

Progress in understanding carcinogenesis has shown cancer to be a disease caused by gene abnormalities, and a variety of oncogenes and tumor suppressor genes have thus been identified. Advances in molecular biology have given us new tools for diagnosing, staging and predicting the outcome for cancer patients and gene therapy could therefore potentially revolutionize the treatment of gastrointestinal (GI) tract cancer. Progress has been made in several approaches related to genetic modification: (1) antisense oncogene and the restoration of tumor suppresor gene therapy; (2) suicide gene therapy; and (3) cancer immunotherapy. In situ in vivo gene transfer is a practical method of gene therapy for GI tract cancer. Although many hurdles need to be overcome to achieve effective gene transfer and targeting, our early results of in situ in vivo suicide gene therapy for canine gastric cancer are promising. The era of combined treatment consisting of surgery and molecular surgery for GI tract cancer is thus considered to soon be possible.     

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase

Summary Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.