A sheep survived for 48 days with the biventricular bypass type total artificial heart

A biventricular bypass type total artificial heart (BVB-TAH) utilizing two pusher-plate pumps was developed and implanted in a sheep for 48 days with excellent results. A Hall effect sensor was utilized to operate each pump independently with a full stroke at variable rates (VR). With this system, the animal's hemodynamics was kept physiologically, and all metabolic parameters except hemoglobin and hematocrit returned to normal three weeks after implantation. However, signs of infection appeared on the forty-second day, and consequently the animal fell into a state of shock. Even at that time the BVB-TAH maintained circulation by increasing pumping rate automatically. On the forty-eighth day, the animal could not stand and suffered from anuria; the experiment was then terminated after 1,140 h pumping. At autopsy, there was an enlarged heart with an atrophic change, 1,900 ml of pleural effusion, and 3,100ml of ascites fluid. Blood culture taken on the forty-seventh day yielded Acinetobacter calcoaceticus. The BVB-TAH operated in an independent VR mode maintained entire circulation, and has a capability of substituting the native heart function in any situation.     

Aortic arch replacement with proximal first technique.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) without retrograde cerebral perfusion (RCP) has a strict time limit. We modified a surgical technique for anastomosis to shorten the period of DHCA and unilateral cerebral perfusion (UCP). METHODS: Between March 1993 and August 2001, retrospective analysis was done on 23 consecutive patients, who underwent aortic arch replacement with branches. The patients were divided into two groups: DHCA group and UCP group. The DHCA group, in which DHCA alone and without additional cerebral perfusion was performed, comprised of nine patients. Proximal aortic anastomosis was performed first during systemic cooling; then both the brachiocephalic artery and left carotid artery were reconstructed with the branches of the artificial graft during circulatory arrest; thereafter, cerebral and coronary perfusions were resumed. The UCP group, in which DHCA was not used but right hemisphere perfusion during deep hypothermia was performed when the origin of brachiocephalic artery was safely clamped, consisted of 14 patients. RESULTS: Mean time of DHCA was 18.8+/-4.2 minutes and that of right hemisphere perfusion time was 11.0+/-3.8 minutes, respectively. Twenty-one patients survived the surgery (91.3%), and two (8.7%) died during hospitalization. Transient cerebral complication occurred in four patients in the DHCA group and all recovered. Logistic regression analysis revealed that DHCA was the only parameter to significantly influence temporary neurological dysfunction. There was no other significant difference between the two groups. CONCLUSION: With our modified and simple surgical technique for aortic arch repair, we were able to successfully shorten the DHCA time and right hemisphere perfusion time. However, because DHCA was the only parameter to significantly influence temporary neurological dysfunction, some form of continuous cerebral perfusion at deep hypothermia may be a safer method to preserve cerebral function.     

Outcomes in patients with interrupted aortic arch and associated anomalies: a 20-year experience.

OBJECTIVE: The surgical results for the repair of interrupted aortic arch (IAA) have evolved in recent years. We report our results for staged repair of this complex congenital malformation. METHODS: Sixty-five patients (mean age, 16.9+/-41.7 days) were diagnosed with IAA and referred for surgical therapy. The surgical management strategy at our institution between 1982 and 2005 has been one-stage complete repair (n=13) or staged repair (n=52) in selected patients. Non-complex patients (group I, n=51) had a ventricular septal defect (87%), aortopulmonary window (8%), and left ventricular outflow tract obstruction (27%). Group II (n=14) were patients with Taussig-Bing double outlet right ventricle (n=6) or truncus arteriosus (n=8). Method of staged repair of IAA was to transect and turn down the left carotid artery and anastomosis it to the descending aorta (n=41) or graft interposition (n=2) combined with a pulmonary artery (PA) banding followed in a few months by delayed ventricular septal defect (VSD) closure and PA de-banding. RESULTS: There were 5 early and 10 late deaths. The actuarial survival including early mortality was 92% at 1 year, 81% at 5 years, and 76% at 10 and 15 years. There was an 81% 15-year survival for children in group I compared with a 54% for children in group II (p<0.001). Risk factors for increased mortality by univariate analysis were as follows: (1) primary aortic anastomosis (p=0.03), (2) presence of complex anomalies (p=0.05), and (3) initial IAA repair performed before 1994 (p=0.05). Actuarial freedom from any type of aortic reoperation or intervention was 86% at 1 year, 69% at 5 years, and 60% at 10 and 15 years. Univariate and multivariate analyses identified no tested variables as risk factors for reoperation. The majority (86%) was in New York Heart Association (NYHA) class I, and 14% remained in NYHA class II. During the postoperative course there were no neurologic deficits, seizures, and growth disturbances in any patient. CONCLUSION: Staged repair of IAA using a left carotid artery turn down can be safely applied in IAA patients with and without other intracardiac anomalies with good results. Use of the left carotid artery for arch reconstruction did not result in any detectable neurological events or growth disturbances later in life. Associated anomalies played an important role in outcomes. The long-term probability for reoperation and/or reintervention remains high regardless of operative technique.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.     

Neurotized nevi of the oral mucosa: an immunohistochemical and ultrastructural analysis of nevic corpuscles

BACKGROUND: Nevic corpuscle (NC), a stacked lamellar structure reminiscent of Meissner corpuscle, is frequently observed in dermal melanocytic nevi. Although the heading 'neurotized' is classically used for these nevi, the exact neural nature of NC has been a topic of considerable debate. Neurotized nevi have received little attention in the dental literature, and there was no information on NC in oral melanocytic nevi. METHODS: Six cases of oral intramucosal nevi with a significant number of NC (two completely and four partially neurotized nevi) were examined immunohistochemically and ultrastructurally. RESULTS: NC was composed of closely piled laminar cells devoid of visible melanin. NC and associated spindle nevus cells were immunopositive for S-100 protein but negative for HMB-45, myelin basic protein and epithelial membrane antigen. Within NC, no reactivity for neurofilament protein, protein gene product 9.5 or peripherin was evident. Numerous CD34-positive dendritic cells were located between nevus cells and often encircled NC. Ultrastructurally, NC consisted of concentrically layered elongated cells with a slender lamellated cytoplasm rich in thin filaments and pinocytotic vesicles. Their cytoplasmic processes were focally covered by external basal lamina and continuous to spindle nevus cells. Occasional NC cells contained a few melanosomes. There was no interposed axon in NC. CONCLUSIONS: Despite the close resemblance to Meissner corpuscle, NC showed no axonal supply. NC cells lacked terminal Schwannian differentiation and appeared to be modified melanocytes with some perineurial ultrastructural characteristics. The presence of CD34-positive cells, presumably corresponding to endoneurial fibroblasts, further supports an organizational relationship of NC and peripheral nerve sheath elements.     

Axonal dystrophy in the posterior column nuclei of young adult epileptics with chronic phenytoin intoxication

Axonal spheroids in the posterior column nuclei of phenytoin-intoxicated epileptics were classified according to their predominant subcellular components into six types, and their incidences were compared with those in controls. Spheroids from phenytoin-intoxicated epileptics showed significantly higher proportions of the tubulomembranous (TM) and layered membrane loop (LML) types in the gracile nucleus, appearance of the same types in the cuneate nucleus, and a significant decrease of the neurofilamentous (NF) type in both nuclei. The incidences of the complex body (CB) and granular material types and of the homogeneous dense-body (HDB) type, which appeared only in the gracile nucleus, showed no difference between the intoxicated patients and the controls. The NF, CB and HDB types were therefore considered to be nonspecific. It was thought that chronic phenytoin intoxication might induce dystrophic changes, such as those characterized by the presence of the TM and LML types, in the axon terminals of the gracile and cuneate nuclei, possibly due to some abnormalities of the axoplasmic transport system.