Association between large aortic arch atheromas and high-intensity transient signals in elderly stroke patients

BACKGROUND AND PURPOSE: Aortic arch atheromas (AAs) have been shown to be a risk factor for ischemic stroke (IS) in the elderly because of their potential for cerebral embolization. However, the association between AAs and the presence of cerebral microemboli has not been clearly established. The aim of this study was to determine whether large AAs are associated with an increased frequency of high-intensity transient signals (HITS) in elderly patients with IS. METHODS: We performed bitemporal simultaneous HITS monitoring of both middle cerebral arteries in 62 consecutive elderly patients with acute IS (mean age 72.5+/-8.8 years, 65% men). In 16 patients, one or both temporal windows were inadequate; therefore, the analysis of HITS was performed in the remaining 46 patients. All patients underwent omniplane transesophageal echocardiography (TEE), and they had no significant extracranial or intracranial artery disease and no cardiac prosthetic valves. Large AA was defined as > or = 4 mm in thickness. Complex AA was defined as ulcerated or mobile, regardless of plaque thickness. HITS monitoring was performed within 24 hours of TEE and analyzed by an experienced neurologist-sonographer blinded to TEE findings. A 9-dB threshold was chosen to discriminate HITS from background Doppler signal. The HITS counts in the left and in the right middle cerebral arteries were added and reported as a total number of HITS in 30 minutes. RESULTS: HITS were detected in 14 (78%) of 18 patients with large AAs versus 8 (29%) of 28 patients with no or small AAs (odds ratio [OR] 8.8, 95% CI 2.2 to 34.8; P=0. 001). The association was also present in 27 patients with no other cardiac embolic sources, such as atrial fibrillation, patent foramen ovale, spontaneous echo contrast, and thrombus (7 of 10 patients with large AAs versus 3 of 17 patients with small or no AA; OR 10.9, 95% CI 1.7 to 68.5; P=0.013). Complex AAs were associated with a higher frequency of HITS than were noncomplex AAs (6 of 6 patients with complex AAs versus 15 of 39 patients with noncomplex AAs; OR 2. 6, 95% CI 1.7 to 3.9; P=0.005). CONCLUSIONS: HITS are significantly associated with large AAs in elderly stroke patients. This observation may support the causal role of large AAs in IS.     

The anti-ischemic effects of CP-060S during pacing-induced ischemia in anesthetized dogs

CP-060 S, (-)-( S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3 ,4-methylenedioxyphenoxy)ethyl]-amino]propyl]-1,3-thiazolidin++ +-4-one hydrogen fumarate, is a novel cardioprotective drug which prevents Na+-, Ca2+-overload and has Ca2+ channel blocking activity. We compared the anti-ischemic effects of CP-060S with those of diltiazem, a Ca2+ channel blocker, and R56865, N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine, a Na+-, Ca2+-overload inhibitor, in a canine pacing-induced ischemia model. CP-060S 100 microg kg(-1) significantly suppressed the pacing-induced ischemic epicardial ST-segment elevation by maximally 75%, while diltiazem 100 microg kg(-1) suppressed it by maximally 35%. R56865 100 microg kg(-1) significantly suppressed the ST-segment elevation by maximally 30%. In addition, diltiazem 100 microg kg(-1) caused synergistic suppression of ST-segment elevation by 70% when administered simultaneously with R56865 100 microg kg(-1). These results suggest that a Na+-, Ca2+-overload preventive action and a Ca2+ channel blocking action independently contribute to the suppression of the ST-segment elevation. Therefore, CP-060S may suppress pacing-induced ST-segment elevation by a dual action by preventing Na+-, Ca2+-overload and the Ca2+ channel blockade.     

Synergistic effects of a macrolide and a cell wall-affecting antibiotic on Pseudomonas aeruginosa in vitro and in vivo. 1. Combined effects of a macrolide and a peptide antibiotic

Synergistic effects of peptide and macrolide antibiotics against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals in the logarithmic growth phase. These bacteria were treated concurrently with polymyxin B (PL) at the final concentration of 1.56 U/ml and with 9,3"-di-O-acetylmidecamycin (MOM) at varying concentrations. Synergistic effect was observed when PL was used with MOM at 3.13 and 12.5 microgram/ml respectively. When MOM at 50 microgram/ml was used with PL, the viable bacterial count was reduced to below 1/300 of the control to which PL alone had been added. Thus, the synergistic effect was remarkable. Similar results were obtained when colistin methanesulfonate (CL) was used instead of PL. Subsequently, attempts were made to determine if this action could also be found in in vivo experiments using mice. PL or CL was injected intramuscularly and midecamycin (MDM) or MOM was administered once or repeatedly by the oral route. Simultaneously, Pseudomonas aeruginosa strain IFO 3455 was inoculated intraperitoneally to mice. In the case of treatment once or repeatedly using both PL and MDM or MOM, the survival rate of infected mice increased significantly compared to single treatment by PL alone. Thus, the synergistic effects were demonstrated in four experiments. (The significance levels for the experiments were P = 0.070, 0.015, 0.042 and 0.024). Similar results were obtained when strain No. 5 was used to infect mice (P = 0.0096, 0.0027). When CL and MOM were given to mice once prior to infection with strain No. 5, synergistic effects were obtained as well (P = 0.010, 0.034).     

Synergistic effects of a macrolide and a cell wall-affecting antibiotic on Pseudomonas aeruginosa in vitro and in vivo. 2. Combined effects of a macrolide with a fosfomycin and an aminoglycoside antibiotic

Synergistic effects of the cell wall-affecting antibiotics, dibekacin (DKB) and fosfomycin (FOM) and a macrolide antibiotic, midecamycin (MDM) or its derivative 9,3"-di-O-acetylmidecamycin (MOM) against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals after the two kinds of antibiotics were added to the logarithmic phase of the bacterial solution. Six hours after addition of antibiotic, the viable bacterial count of the culture treated with FOM and MOM underwent 2 log reduction compared to that which treated with FOM alone. Thus synergistic effect was significant. The number of viable bacteria treated with DKB and MDM showed slight reduction at 3 hours after addition of the two antibiotics and a marked reduction was noted after 20 hours compared with the control. Synergistic action was also demonstrated in in vivo experiments using mice. Three experimental mouse infection models, intraperitoneal infection, subcutaneous infection with carrageenan solution and burn infection were used. FOM was administered subcutaneously. DKB was administered intramuscularly. MDM or MOM was administered by the oral route. In all three experiments the survival rate of infected mice treated with FOM and MOM increased significantly compared to control mice. Similar synergistic effect was also obtained with DKB and MDM.     

MRI of orbital schwannomas

The literature on MRI of orbital schwannomas is limited. The appearances in three patients with an orbital schwannoma were reviewed. A superior orbitotomy through a subfrontal craniotomy revealed a schwannoma in all cases. MRI characteristics of very low signal on T 1-weighted images and homogeneous postcontrast enhancement may be helpful for differentiating schwannomas from other intraconal masses. Received: 21 June 1999/Accepted: 20 September 1999     

Plasticity of central monoaminergic systems during aging]

The locus coeruleus (LC), located within the caudal pontine central gray, is composed of noradrenaline-containing neurons. The axons of these neurons form extensive collateral branches that project widely to many brain sites. The function of the LC is still unclear at present, however, LC neurons are known to exhibit marked axonal regeneration and sprouting in response to brain damage. We investigated the age-related changes in noradrenergic innervations of the frontal cortex, using in vivo electrophysiological techniques and immunohistochemistry. While noradrenergic innervations gradually decreased with age in the frontal cortex, a high degree of sprouting occurred in the LC axon terminals in middle age. Neither the electrophysiological properties of LC neurons nor NA levels in the frontal cortex changed with age. These findings suggested that the LC neurons preserve a strong capacity to remodel their axon terminals even in the aging brain. Exogenous brain-derived neurotrophic factor (BDNF) infusion caused a marked increase in the density of noradrenergic axon in the aged brain, but no trophic action of BDNF was observed in the young or middle-aged brain. The result suggests that BDNF is necessary for the maintenance of noradrenergic innervations in the aged brain.     

Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2. I. Taxonomy, isolation, physico-chemical properties and biological activities

Tyropeptins A and B, new proteasome inhibitors, were isolated from the culture broth of Kitasatospora sp. MK993-dF2. They were purified using ethyl acetate extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and HPLC. Tyropeptin A inhibited the chymotrypsin-like (ChT-L) and trypsin-like (T-L) activities of 20S proteasome with IC50 values of 0.1 microg/ml and 1.5 microg/ml respectively, but did not inhibit the peptidylglutamyl-peptide hydrolyzing (PGPH) activity of 20S proteasome at a concentration of 100 microg/ml. The inhibitory activities of tyropeptin A were about two times as strong as that of tyropeptin B. Taxonomy of the producing strain is also described.     

The first recognized patient withLegionella pneumophila serogroup 9 pneumonia in Japan

A 77-year-old female was admitted because of high fever, cough and sputum. She had been receiving corticosteroid therapy for 4 years for multiple myeloma and was immunosuppressed. A physical examination on admission showed coarse crackles in the right lower lung field, a chest radiograph showed consolidation in the right middle and lower lung fields, and a blood gas analysis revealed marked hypoxemia. The patient was diagnosed as having refractory pneumonia associated with acute respiratory failure and treated with intravenous cefmetazole followed by imipenem. On hospital day 5, erythromycin therapy was started because of a poor response to the previous antibiotics. The patient became afebrile on the tenth day and was in good health on day 15. A sputum culture on day 4 revealed aLegionella organism on Wadowsky-Yee-Okuda medium, which was subsequently confirmed to beLegionella pneumophila by a DNA hybridization test. This strain was identified at the Centers for Disease Control (Atlanta, GA, USA) by slide agglutination asL. pneumophila serogroup 9. Although our patient's symptoms are not apparently different from those caused by other serogroup strains ofL. pneumophila, this is the first recognized patient with culture-provenL. pneumophila serogroup 9 pneumonia in Japan. The clinical course of the disease and the diagnostic difficulties in identifying this type of pneumonia are discussed.