Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 +/- 0.56 ml/m2/L/min and 38.72 +/- 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 +/- 0.5 ml/m2/L/min and 24.7 +/- 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.     

Polyethylene/phospholipid polymer alloy as an alternative to poly(vinylchloride)-based materials

To develop new biomaterials for making medical devices, polymer alloys composed of a phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and polyethylene (PE) were prepared. The PE/PMPC alloy membrane could be obtained by a combination of solution mixing and solvent evaporation methods using xylene and n-butanol mixture as a solvent. Moreover, thermal treatment was applied to improve the mechanical properties of the PE/PMPC alloy membrane. In the PE/PMPC alloy membrane, the PMPC domains were located not only inside the membrane but also at the surface. Surface analysis of the PE/PMPC alloy membrane with X-ray photoelectron spectroscopy, wettability evaluation, and dynamic contact angle measurements revealed that the phospholipid polar groups in the PMPC covered the surface even after thermal treatment. Blood compatibility tests with attention to platelet adhesion and change in morphology of adhered platelets showed that the PE/PMPC alloy membrane had excellent platelet adhesion resistance. We finally concluded that the PE/PMPC alloy could be used as biomaterials instead of poly(vinyl chloride)-based materials.     

Dependence of the anterior olfactory area self-stimulation upon the lateral hypothalamic area

The functional relation between the anterior olfactory area (AO) and the lateral hypothalamic area (LH) was examined in a self-stimulation situation. Bar-pressing responses for AO sitmulation were suppressed by unilateral injection of procaine, and enhanced by glutamate, into LH. Neither procaine nor glutamate injected into AO had any influence upon LH self-stimulation. It is unlikely that the procaine effect was due to motor disturbance because similar injection of procaine into LH did not disturb the performance of a one-way avoidance task. It appears that the rewarding effect of AO stimulation is dependent upon the excitation of the more caudal structures including LH.     

INFANTILE DIGITAL FIBROMATOSIS HISTOPATHOLOGICAL and ELECTRON MICROSCOPIC STUDY WITH A REVIEW OF THE LITERATURE

Five cases of Infantile digital fibromatosis were described. Three were male and two were female. Multiple lesions were noted in two cases. The lesions were Intradermal and had a peculiar histologic pattern with intracytoplasmic inclusions. By electron microscopy, the inclusions were composed of a meshwork of both fibrils and fine granules and have no limiting membrane. No virus-like particle could be identified in the proliferating cells. Follow-up information was available in all five cases; one had recurring tumors.     

Deficits in radial-arm maze learning in aged rats

The present study was designed to investigate the possible deficits in the place learning on the 8-arm radial maze in aged rats. In this task, reward was given in the 4 predetermined arms. Aged rats (27 months old, N = 7) acquired this task more slowly than young rats (12 months old, N = 11), and didn't reach to the performance level of the young rats within 80 training trials. Analysis of error choices revealed that the aged animals first entered in the unbaited arms more often than the young rats, whereas there was no difference in the number of re-entered choices to the baited and unbaited arms between the aged and young animals. Therefore, it was concluded that learning deficits in aged rats were attributed to deficits in the reference memory but not in the working memory.     

High Frequency of Antibiotic-Associated Diarrhea due to Toxin A-Negative, Toxin B-Positive Clostridium difficile in a Hospital in Japan and Risk Factors for Infection

Patients hospitalized in a hospital with a high incidence of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive (A–/B+) Clostridium difficile were retrospectively investigated to determine the clinical manifestations and risk factors for infection. Of 77 Clostridium difficile isolates obtained from 77 patients during the 1-year investigation period, 30 were A–/B+ and 47 were toxin A-positive, toxin B-positive (A+/B+). By pulsed-field gel electrophoresis analysis, 23 of the 30 A–/B+ strains were outbreak-related, suggesting nosocomial spread of a single type of bacterium, which mainly affected patients in the wards of respiratory medicine, hematology and neurology. Using regression analysis, three factors were found to be associated with infection by A–/B+ isolates: (i) exposure to antineoplastic agents (P=0.01, odds ratio [OR]=5.1), (ii) the use of nasal feeding tubes (P=0.008, OR=5.2), and (iii) assignment to a certain internal medicine ward (P=0.05, OR=3.0). Between patients with Clostridium difficile-associated diarrhea caused by A–/B+ strains and those with A+/B+ strains, no statistically significant difference was found in body temperature, serum concentration of C-reactive protein, leukocyte count in whole blood, frequency of diarrhea, or type of underlying disease. These results indicate that A–/B+ strains of Clostridium difficile can cause intestinal infection in humans and they spread nosocomially in the same manner as A+/B+ strains.     

CT myelography with intramedullary enhancement in cervical spondylosis

The authors describe seven cases of cervical spondylosis in which small high-density areas were detected in the spinal cord on delayed computerized tomographic (CT) myelography. These high-density areas are believed to represent cavities or areas of cystic necrosis. In all seven cases the cervical spinal canal was narrow, and the spondylosis was located at multiple levels, causing a so-called "pincer effect." On the CT scans the high-density areas resembled fried eggs in the gray matter. These areas were localized near the abnormal cervical discs. In two cases in which the Brown-Séquard syndrome was noted, the symptoms could be attributed to the morphology of the high-density area on the affected side of the cord. Following decompressive surgery, most of the symptoms improved except for numbness of the upper extremities and motor weakness of hands.     

CYTOMEGALOVIRUS OOPHORITIS WITH CORTICAL NECROSIS DURING REMISSION OF ACUTE LYMPHOCYTIC LEUKEMIA

Ovarian involvement of cytomegalovirus (CMV) is rarely observed in autopsy and biopsy materials. Cortical necrosis of the ovaries was found in an autopsy case with generalized CMV infection. The patient was an 11-year-old girl in a remission state of acute lymphocytic leukemia. Autopsy revealed several areas showing necrotic change up to 2 mm in size in the cortex of both ovaries. Many cytomegalic cells were found in both the necrotic and intact areas of the cortex. CMV had infected the granulosa, thecal and stromal cells as well as vascular endothelial cells. Oocytes of neither primary nor graafian follicles showed cytomegalic changes, although they were destroyed due to the necrosis. CMV antigen was immunohistologically detected in these cytomegalic cells. Ultrastructurally, herpesvirus-type particles were revealed in the nuclei and cytoplasm of the cytomegalic cells. This case demonstrated that ovarian infection with CMV can potentially induce cortical necrosis and decrease the number of oocytes. ACTA PATHOL JPN 38 : 1069 ∼ 1076, 1988.     

Hypoxia-ischemic insult in neonatal rats induced slowly progressive brain damage related to memory impairment

The present study was designed to determine potential associations between the brain damage induced by hypoxic-ischemic (HI) insult and spatial learning impairment in an eight-arm radial maze task. We first determined the pathological outcomes after 2, 5, 9, and 17 weeks of recovery following the HI insult. The results show that the brain damage progressed from 2 up to 17 weeks of recovery. To clarify the time course of the brain damage changes, we investigated the histological changes of the same individual with magnetic resonance imaging (MRI) after 5, 9, and 57 weeks of recovery following the HI insult. The MRI changes were similar to the histological changes, and the brain damages were exacerbated in the contralateral hemisphere after 57 weeks of recovery following the HI insult. To investigate whether alteration in brain function was correlated with MRI and histological changes, the rats were made to find their way through an eight-arm radial maze was performed at either 7th or 16th weeks of recovery. According to the results, the spatial learning impairments of rats in the maze starting at 16 weeks of recovery were more severe than those at 7 weeks of recovery, indicating that the impairments were progressive and depended on the degree of brain damage. The results of the present study are the first demonstration that the evolutional and specific brain damage following the HI insult is slowly and progressively exacerbated to the contralateral hemisphere and rats who experience the HI are at risk for showing a late impairment of brain function.