Mapping-guided focal cryoablation and endoaneurysmorrhaphy for a case of ischemic ventricular tachycardia with left ventricular aneurysm

A 74-year-old woman admitted with exertional dyspnea. Echocardiography revealed the giant left ventricular aneurysm. In the hospital course, she fell into sustained monomorphic ventricular tachycardia. Coronary angiogram showed complete obstruction of the LAD. Left ventricular ejection fraction was 20%. The origin of tachycardia seems to be at infero-apicallateral area of LV by electrophysiology study. Because of the failure of RF energy ablation, we planned mapping-guided cryoablation, CABG and endoaneurysmorrhaphy. To prevent air embolism and myocardial ischemic damage for long aortic cross clamp, intraoperative endocardial mapping was carried out on beating heart due to continuous normothermic coronary blood perfusion (300 ml/min) from the aortic root cannula under aortic clamping. Cold crystalloid cardioplegia changed into the root cannula after EPS, focal cryoablation (-100 degrees C) was performed 3 times on cardiac arrest. Sustained VT was not inducible in the following study. CABG and endoaneurysmorrhaphy was performed on repeated cardiac arrest during single aortic clamp. Postoperative course was uneventful, and she discharged 8 weeks after the operation.     

Neurological prognosis correlated with variations over time in the number of subependymal nodules in tuberous sclerosis

In tuberous sclerosis (TS), brain CT reveals subependymal nodules, cortical tubers and white matter lesions. This study is a retrospective analysis of the relationship between the variations over time in the number of subependymal nodules and the clinical course in cases of tuberous sclerosis. Twenty-four children with tuberous sclerosis, who attended the National Children's Hospital as outpatients, were followed by means of brain CT examinations for 7 years and 1 month on average. Cranial MRI was also performed in 22 cases. Brain CT disclosed subependymal nodules already in early infancy. In almost all cases, the number of subependymal nodules gradually increased with age, especially around the frontal horn of the lateral ventricle. The increase stopped at around age 10. The cases with five or more subependymal nodules at the initial or subsequent CT examination (17 patients; Group A) exhibited a significantly greater number of cortical tubers than those with less than five (five patients; Group B) and had white matter lesions unlike Group B. In addition, the number of cases with either infantile spasms or mental retardation was significantly higher in Group A than Group B (P<0.005). In conclusion, the number of ventricular subependymal nodules may allow prediction of the severity of the cerebral dysfunction in TS. Our results suggest that its variation may reflect the degree of the embryologic disorder when neuronal cells grow in the early gestational period.     

The antigen 85 complex vaccine against experimental Mycobacterium leprae infection in mice

The proteins in culture filtrate derived from Bacillus Calmette-Guérin (BCG) were examined for protection against infection by Mycobacterium leprae. Immunization with the major secreted proteins, antigen 85 complex (Ag 85) A, B and C, induced effective protective immunity against multiplication of M. leprae in the foot pads of mice. The most effective protection was observed when mice were immunized with Ag 85A. A single immunization with Ag 85 could induce antigen-specific interferon gamma (IFNgamma) synthesis and more effective protection than live BCG vaccine. This study demonstrates that Ag 85 is an important immunoprotective molecule against leprosy infection.     

Factors relate to participation in medical checkups in a rural community an analysis including social network scores]

Since 1969, community-based stroke prevention programs have been conducted in N town, Kochi prefecture. To clarify factors related to participation in medical checkups including social networks, a cross-sectional questionnaire survey was performed on 6,704 residents aged 40 and over in N town in 1996. 1. Location of the workplace, types of medical insurance and interest in health were significantly associated with participation in medical checkups. 2. Participation in medical examinations provided at the workplace was significantly, inversely related with participation rates in community checkups in the group aged 40 to 59 years. 3. Low independence level in daily activities was inversely associated with participation rates for medical checkups in groups aged 60 years and older. 4. Visiting medical facilities was inversely associated with the participation rate for medical checkups in female groups. 5. The group with the highest social networks score (5 points) had the highest participation rate for medical checkups. After adjusting for other participation related factors, social networks scores had a significantly positive association with the participation rate for medical checkups provided by the Health Services for the Elderly Act.     

Induction of genes into the rabbit eye by iontophoresis

PURPOSE: After inducing 6-carboxyfluorescein (6-FAM)-labeled phosphorothioate oligonucleotides (S-ODNs) noninvasively into albino rabbit eyes by iontophoresis, we assessed the transfer of S-ODNs into the ocular tissues, their stability, and the possible presence of injury to the ocular tissues. METHODS: The iontophoresis group consisted of 12 eyes of 6 rabbits and the control group consisted of 4 eyes of 2 rabbits given eye drops containing S-ODNs. Aqueous humor and vitreous humor were collected after iontophoresis, subjected to electrophoresis with a fluorescent DNA sequencer and analyzed by the Gene Scan program. Frozen sections at 10 microns were prepared for observations under a fluorescent microscope. A plasmid 4.7 kbp in size that expresses green fluorescent protein (GFP) was induced into 18 eyes of 9 rabbits by the same procedure. RESULTS: In the iontophoresis group, S-ODNs were detected in the anterior chamber 5 minutes after electrophoresis and in the vitreous 10 minutes after. These S-ODNs maintained the same length as at the initial synthesis. S-ODNs could also be detected in the posterior retina 20 minutes after electrophoresis. No evidence of degeneration or inflammation due to the above procedure was found in the ocular tissues. Fluorescence showing GFP gene expressions were found in the cornea, the anterior chamber angle, and the ciliary subepithelial tissues. CONCLUSIONS: These findings show that iontophoresis is an effective method to induce gene into rabbit eyes.     

Contribution of P-glycoprotein to bunitrolol efflux across blood-brain barrier

In this study, we investigated the mechanism of the blood-brain barrier (BBB) transport of bunitrolol (BTL), as a model of beta-blocker, in vivo and in vitro. In order to define the contribution of P-glycoprotein (P-gp) to the active efflux of BTL from brain to blood, we examined the in vivo brain distribution of BTL in mdr1a(-/-) mice with a disrupted mdr1a gene. After intravenous administration of BTL to mdr1a(-/-) mice, the brain concentration and Kp value of BTL were significantly increased as compared with those in mdr1a(+/+) mice. Next, the contribution of the mdr1a P-gp to in vitro uptake of BTL was compared in LV500 cells and L cells (mouse mdr1a-expressing cells and host cells, respectively). The intracellular accumulations of [3H]vinblastine and BTL by LV500 cells were lower than those by L cells, but were significantly increased by verapamil, a P-gp inhibitor. Furthermore, the BTL uptake by KB-VJ300 cells, which express human P-gp, was also significantly lower than that by KB host cells, and was increased by verapamil. The steady-state uptake of BTL by LLC-GA5-COL300 cells, expressing human P-gp, was significantly increased in the presence of 20 microM cyclosporin A (another P-gp inhibitor), which had no effect in the LLC-PK1 host cells. On the other hand, the steady-state intracellular accumulation of BTL by MBEC4 cells, which express mdr1b P-gp instead of mdr1a P-gp, was not significantly changed in the presence of verapamil. This finding suggested that BTL is not a good substrate for mdr1b P-gp. In conclusion, our results suggest that BTL is transported from brain to blood by mdr1a P-gp in mice and by MDR1 in humans, and this presumably accounts for the low brain distribution of BTL.     

Morphine-induced changes in cyclic AMP metabolism and protein kinase activity in the brain.

The effects of consecutive oral administration of morphine on the cyclic AMP synthesizing system and cyclic AMP dependent protein kinase activity in the cerebral cortex of mice were examined. The administration of morphine (2--4 weeks) induced an increase of the cyclic AMP formation by activating adenylate cyclase, whereas responses of the cyclic AMP synthesizing system to biogenic amines (norepinephrine, dopamine and histamine) added in vitro was found to be significantly attenuated in these animals. Cyclic AMP dependent protein kinase activity in the cerebral cortex was also increased following a consecutive oral administration of morphine. These changes in the activities of adenylate cyclase and protein kinase were found mainly in crude mitochondrial and/or synaptosomal fractions. Morphine induced decrease in the response of the cyclic AMP synthesizing system to biogenic amines was rapidly reversed, and a significant increase of the cyclic AMP formation in the presence of added norepinephrine compared with that found in morphinized animals was observed following the administration of levallorphan, a narcotic antagonist. On the other hand, the changes in adenylate cyclase and cyclic AMP dependent protein kinase activities were not affected significantly by levallorphan administration. These results suggest that alterations in activities of cyclic AMP synthesizing system and of cyclic AMP dependent protein kinase may be involved in processes of the formation of morphine dependence. Possible involvement of abrupt increments in the sensitivity of "norepinephrine receptor-adenylate cyclase" system and a subsequent increase in cerebral cyclic AMP is also suggested as a cause of morphine withdrawal syndrome.     

Synthesis and biological activity of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B

The synthesis and biological properties of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B are described. Reaction of 3,3",6'-tri-N-tert-butoxycarbonyl-amikacin with an appropriate amidinating or guanidinating reagent and subsequent deblocking gave a series of amikacin derivatives having an amidino or guanidino group on the 4"'-position. The corresponding kanamycin B analogs were also prepared by a similar procedure. Among these derivatives, 1-N-(4-formamidino- and guanidino-2-hydroxybutyryl)kanamycins A (7a and 7k) and B (11 and 14) exhibited antibacterial activity similar to the corresponding 4-amino analogs. The nephrotoxic potential of selected compounds is also briefly discussed.     

Artificial ventilation-induced diffuse alveolar damage in rabbits: preliminary study of early detection on expiratory high-resolution computed tomography

RATIONALE AND OBJECTIVES: To investigate whether expiratory high-resolution computed tomography (HRCT) is more useful than inspiratory HRCT for the detection of early-phase diffuse alveolar damage. METHODS: Eleven anesthetized rabbits were scanned with both inspiratory and expiratory HRCT every 30 minutes during mechanical ventilation. Ten rabbits were killed after the detection of pulmonary abnormalities on both inspiratory and expiratory HRCT. The remaining rabbit was killed when the pulmonary abnormalities appeared only on expiratory HRCT. RESULTS: In four cases (36%), the abnormal findings were detected earlier on expiratory HRCT than on inspiratory HRCT. In seven cases (64%), the abnormalities appeared simultaneously on inspiratory and expiratory HRCT. In all 11 cases, the histopathological changes of areas with abnormal CT findings corresponded to the exudative or proliferative phase of diffuse alveolar damage. CONCLUSIONS: Expiratory HRCT has the potential to detect the abnormalities of diffuse alveolar damage earlier than inspiratory HRCT.