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.     

Secretion in yeast of human lysozymes with different specific activities created by replacing valine-110 with proline by site-directed mutagenesis.

Computer graphics indicate that a steric hindrance exists between valine-110 side chain of human lysozyme (EC 3.2.1.17) and an acetyl group of a modified substrate that contains N6,O-diacetylmuramic acid. To alter the substrate specificity of human lysozyme to be effective on the modified substrate, we replaced the valine-110 residue with various amino acids by site-directed mutagenesis. One of the mutant proteins (valine residue replaced with proline:P110) was secreted in Saccharomyces cerevisiae as at least four components (P110-A, P110-B, P110-C, and P110-D) with different specific activities. Two components, P110-B and P110-D, were isolated in a pure form and structurally characterized. The results suggest that this mutation lowered the lytic activity against Micrococcus lysodeikticus by changing a local conformation of the catalytic site while keeping almost the same substrate binding sites. Our results also indicate that cis/trans isomerization of prolyl peptide bonds probably occurs in vivo and that the conformational change of protein as well as point mutations in genes might influence the molecular evolution of the protein.     

Postoperative bronchial stump fistula responding well to occlusion with metallic coils and fibrin glue via a tracheostomy: a case report.

An 80-year-old man underwent middle and lower lobectomy of the right lung to treat squamous cell carcinoma (SCC) (4 cm in diameter) originating from the right B4 bronchus. On the 4th postoperative day, a massive air leak from the thoracic drain was noted. At that time, a diagnosis of bronchial stump fistula was made on the basis of the bronchoscopic findings. Continuous thoracic drainage, aspiration of sputum via a tracheostomy and intravenous administration of antibiotics were performed immediately after the diagnosis. However, the patient's condition was complicated by aspiration pneumonia. On the 11th postoperative day, bronchoscopic procedure to close the bronchial fistula was performed via the tracheostomy. During this procedure, metallic coils were first inserted into the fistula to serve as the core for occlusion. Then, instead of directly infusing fibrin glue, several small beans-sized pieces of Surgicell cotton (Johnson & Johnson Co., Cincinnati, OH) soaked in fluid A (concentrated fibrinogen) and the same number of Surgicell cotton pieces soaked in fluid B (thrombin) were alternately inserted into the fistula, to allow closure of the bronchial fistula. After this procedure, the embolus created remained in place without being expectorated, and the aspiration pneumonia entered remission, allowing the patient to be discharged from the hospital on the 24th postoperative day. At preset, 14 months after surgery, the patient is in good condition. This technique allows simple and reliable closure of a fistula if a tracheostomy is available. It should be selected as a therapy of first choice when dealing with patients with a postoperative bronchial stump fistula in poor general condition. Patients undergoing right pneumonectomy or middle and lower lobectomy of the right lung should be considered as belonging to a high risk group for bronchial fistula and as requiring preventable measures (e.g., covering the stump with an intercostal muscle flap).     

Study on local recurrence of squamous cell carcinoma of the lung on hilar lesion

The study population consisted of 62 patients with squamous cell carcinoma of the lung on hilar lesion who underwent curative or relative curative resection during the seven year period between January, 1980 and December, 1986. We studied the correlation between local recurrence and the distance from the surgical margin of the trachea or bronchus to the tumor. 1) As the classification of the T and N factors increased, the incidence of local recurrence became higher. 2) In order to prevent local relapse, we need to completely resect the hilar and mediastinal lymph nodes, and we must maintain a distance of 16 mm or more between the surgical margin of the trachea or bronchus and the tumor.     

A case of aberrant left pulmonary basal aneurysm arising from the descending aorta]

A 65-year-old man was referred to our hospital because of fever and abnormal shadow in the left lung. An aortogram revealed a large artery arising from the descending aorta supplying the left basal segment and, which then flowed into the pulmonary vein. This artery had an aneurysm and 30 mm in diameter. Bronchography showed compression of the left basal branch. A clinical diagnosis of an aberrant left pulmonary basal aneurysm arising from descending aorta was made, and left lower lobectomy was performed, because of the danger apprehension of the aneurysmal rupture. The procedure was successful. There are only 15 case reports of a systemic artery supplying the lung with normal bronchial branch in Japan. Differences of this anomaly from pulmonary sequestration were discussed.     

Prediction of spinal cord ischemia with a retrievable stent graft on endovascular treatment for a case of thoracic aortic aneurysm

Multiple aortic aneurysms in Behçet’s disease were repaired with transluminaly placed endovascular stent grafts. Before deploying the stent graft device for permanent implantation for the saccular aneurysm located in the descending thoracic arota, from which feeding arteries for the spinal cord possibly branched, a retrievable stent graft was inserted and evoked spinal cord potential (ESP) were monitored in order to predict spinal cord ischemia. The original retrievable stent graft, constructed of a self-expandable Z-shaped stainless steel stent covered with e-PTFE, can be easily withdrawn into a 18 Fr. sheath after deployment. Blood flow into intercostal arteries branching from that part of the descending aorta where the permanent stent graft is planned to be implanted, is intercepted by the retrievable stent graft. A change of ESP during the temporary implantation of the device indicates that spinal cord ischemia would be caused by permanent implantation of the stent graft. In this case, no change of ESP was observed and the patient showed no postoperative paraplegia.The retrievable stent graft was useful for prediction of spinal cord ischemia before endoluminal stent graft repair of the descending aortic aneurysm. However, the device is not flexible enough to fit a severely tortuous aorta, therefore we are obliged to select patients to some extent. Further improvement of the device is required to make prediction of spinal cord ischemia with the retrievable stent graft possible in all cases.     

Establishment of a human glioma cell line bearing a homogeneously staining chromosomal region and releasing α- and β-type transforming growth factors

Summary A human glioma cell line (YKG1), which was positively identified for glial fibrillary acidic (GFA) and S-100 proteins, was established from a surgical specimen of a patient with glioblastoma. Chromosome analysis of the cells revealed a homogeneously staining region (HSR) on a marker chromosome. The assay for transforming growth factors (TGFs) in the conditioned medium of the cell line revealed that it contained high levels of - and -type TGFs, which might regulate the growth of glioblastoma and influence on the peritumoral tissues.     

Advance in animal experiments with the undulation pump total artificial heart: 50 and 54 day survival periods with 1/R control

The undulation pump total artificial heart (UPTAH) is a unique, implantable, total artificial heart (TAH) that uses undulation pumps. To achieve long-term survival in animals with physiologic hemodynamic conditions, a control method based on conductance and arterial pressure was applied to UPTAH. With this control method, called 1/R control, survival periods of 50 days (No. 0016, 49.6 kg) and 54 days (No. 0030, 42.5 kg) were obtained in adult female goats. In No. 0016, 1/R control was applied to the left pump, whereas in No. 0030, it was applied to the right pump. Another pump was used for left-right balance control. The control stability was better in No. 0030 than in No. 0016. The sucking effect of the left atrium was remarkable in No. 0016, possibly because of a time delay when left-right balance control was performed with the right pump. In No. 0016, the cause of death was probably a thrombus flown from a panus in the left atrium. It is possible that the left atrial suction effect influenced the thrombus and panus formation in the left atrium. In No. 0030, the cause of death was a small rupture of the membrane in the right pump. The rupture may have been caused by excessive negative pressure inside the pump. This pressure resulted from suction of the right atrium because of an unexpected control excursion, which was probably caused by a software bug. It will be necessary to redesign the undulation pump and improve the software to achieve longer survival periods for animals with physiologic hemodynamic conditions.