A Novel Modification of the Retrograde Approach for the Recanalization of Chronic Total Occlusion of the Coronary Arteries Intravascular Ultrasound-Guided Reverse Controlled Antegrade and Retrograde Tracking

ObjectivesThe study evaluates the feasibility and efficacy of the novel modification of the retrograde recanalization of the chronic total occlusion (CTO) of the coronary arteries by using intravascular ultrasound (IVUS)-guided reverse controlled antegrade and retrograde tracking (CART).BackgroundDespite improvement in the techniques and materials, CTO recanalization is still suboptimal. The CART procedure has improved success rates, but there are certain inherent technical uncertainties and risk with this procedure.MethodsThis first series involves 31 patients, with 22 patients having previous failed attempts at CTO recanalization. All patients were treated with bilateral approach and using IVUS-guided reverse CART concept.ResultsSuccessful recanalization of the CTO was achieved in all cases (100%). The access route was septal collateral in 20 (70%) cases and epicardial collateral in 11 (30%) cases. IVUS guidance was used successfully in 30 cases, and the channel dilator (microcatheter) was used in 27 cases. Guidewire injury and grade 1 perforation was seen in 3 (9%) cases, which were managed conservatively. There was no death, coronary artery bypass surgery, or pericardiocentesis in this group of patients. Mean fluoroscopy time was 65.84 ± 23.16 min, ranging from 31 to 106 min and total contrast volume used 321.32 ± 137.77 ml (range 115 to 650 ml).ConclusionsThis first series describes a high success rate of CTO recanalization with IVUS-guided reverse CART in selected patients performed by an experienced operator

Investigation of the Therapeutic Effect of Tobramycin in Mice with Experimental Pneumonia in One-shot Versus Divided-dose Schedules

We measured the plasma levels of tobramycin administered by different methods and evaluated the therapeutic effects of tobramycin in mice with experimental pneumonia in various methods and dose schedules. (1) Mice were dosed with tobramycin intramuscular, intravenous oneshot injection and drip infusion, and intramuscular injection in divided doses at intervals of 15 minutes. The plasma concentration of the drug was determined at timed intervals after administration in each instance. Intramuscular and one-shot intravenous injections resulted in substantially parallel time courses of plasma concentration and plasma concentration with drip infusion was similar to that after divided intramuscular injection. (2) A therapeutic experiment was conducted in mice with Klebsiella pneumoniae pneumonia using one-shot and divided intramuscular injection methods of tobramycin. The one-shot injection group showed a satisfactory result at the dose level of 2 mg/kg, but the injection in four divided doses yielded better results at 1 mg/kg. Therefore, in cases where high doses are not feasible or are undesirable, the time of contact of the bacteria and the drug should be prolonged, rather than trying to increase the peak plasma concentration of the drug

Damage of the Mouse Testis by Tritiated Water and <137>^Cs-γ-Rays

Tritiated water at 23.2, 46.3 or 92.5 MBq/animal and ^Cs-γ-rays at 9.5 Gy (equivalent 370 MBq) or lower doses were administered to 6-week old male C3H/HeNCrj and C57BL/6NCrj mice, as well as FI Crj: B6C3F1 (C3H × C57BL) progeny. Each set of six to ten animals were autopsied 30 days after the first irradiation. Testis weights were decreased dose dependently, relative values being highest in the C3H and lowest in the C57BL case, with B6C3F1 intermediate. Vacuolization in seminiferous tubules appeared in the 23.2 MBq group and increased with the dose. Focal pyknosis and karyomegaly were found at 46.3 MBq, while primary and secondary spermatocytes and spermatids disappeared with 92.5 MBq. Only a few spermatogonia and Sertoli cells remained after exposure to 9.5 Gy ^Cs-γ-rays. Sizes of seminiferous tubules were decreased dose dependently, with no strain differences. When male B6C3F1 mice were irradiated with Cs-γ-rays at 0.119 (equivalent 4.63 MBq tritiated water) or 2.38 Gy (equivalent 92.5 MBq tritiated water), body weights and size of the seminiferous tubules were decreased at both doses, and the larger dose also caused reduction of testis weight and abnormal sperm. However, all changes except for the alteration in weights had disappeared 1 month after the final irradiation. It is considered that the size of seminiferous tubules may be a good parameter for radiation damage in the testis

Effects of Weaning by Surrogate Mothers (ACI) on Tumor Development in SD Rats Treatedwith Methylnitrosourea (MNU) and/or N-Methyl-N-nitro-N-nitrosoguanidine (MNNG)

In this experiment, MNU was administered, followed by MNNG, to assess effects ofsurrogate mothering on tumor. One or two day old male SD pups were treated with or without30mg/kg body weight of methylnitrosourea (MNU) and nursed by SD or ACI surrogate mothersfor 5 weeks. When 6-weeks-old they were then treated with 100ppmN-methyl-N-nitro-N-nitrosoguanidine (MNNG) or tap water for 16 weeks. The tumor incidencein the MNNG alone group was significantly lower than with MNU alone or MNU+MNNG (p<0.01).Kidney or nerve tumors mainly developed in the MNU group, gastric tumors in the MNNG group,and the two combined in the MNU+MNNG group. The incidence and mean number of tumors didnot significantly differ between the two weaning groups. However, mean survival time withthe ACI surrogate mothers after treatment with MNU was increased as compared with the SDmother group. Cumulative development of tumors in the ACI surrogate mother group was alsodelayed (p<0.05). Similar results were obtained with MNU+MNNG and MNNG alone. The presentexperiment suggested that tumor induction might be effected by components of the mother'smilk

Defects of Granulopoiesis in Patients with Severe Congenital Neutropenia

To confirm the abnormalities of primitive myeloid progenitor cells in patients withsevere congenital neutropenia (SCN), we studied their responsiveness to hematopoieticfactors including granulocyte colony-stimulating factor (G-CSF). In all SCN patientsstudied no abnormalities of granulocyte colony-stimulating factor receptor (G-CSFR) genewere detected by polymerase chain reaction-single-strand conformation polymorphism analysisand sequence analysis. A flow cytometric analysis of bone marrow cells based on theexpression of CD34, Kit receptor, and G-CSFR demonstrated a reduced frequency ofCD34+/Kit+/G-CSFR+ cells in patients with SCN. The granulocyte/macrophage (GM)-colonyformation of CD34+/Kit+/G-CSFR+ cells in patients was markedly decreased at allconcentrations of G-CSF in serum-deprived semisolid culture. The responsiveness ofCD34+/Kit+/G-CSFR+ cells in patients showed a reduced response to the combination of stemcell factor, the ligand for flk2/flt3, and interleukin-3 with or without G-CSF inserum-deprived semisolid and liquid suspension cultures. In contrast, no difference in theresponsiveness of CD34+/Kit+/G-CSFR- cells was noted between SCN patients and normalsubjects. The bone marrow cells from a patient who underwent bone marrow transplantationshowed a restoration of both the reduced frequency and the decreased level of GM-colonyformation of CD34+/Kit+/G-CSFR+ cells. These results demonstrate that the presence ofqualitative and quantitative abnormalities of primitive myeloid progenitor cells expressingG-CSFR may play an important role in the impairment of granulopoiesis in patients with SCN

Different Patterns of Vascular Response Between Patients With or Without Diabetes Mellitus After Drug-Eluting Stent Implantation Optical Coherence Tomographic Analysis

ObjectivesWe performed this study to investigate with optical coherence tomography (OCT) the vascular response after sirolimus-eluting stent (SES) implantation between patients with and those without diabetes mellitus (DM).BackgroundThe difference in vascular response after SES implantation between patients with and those without DM has not been fully evaluated with OCT.MethodsOptical coherence tomography was performed to examine 74 nonrestenotic SES implanted in 63 patients (32 with DM and 31 without DM) at 9 months after SES implantation. For struts showing neointimal coverage, the neointimal thickness on the luminal side of each strut section was measured, and neointimal characteristics were classified into high, low, and layered signal pattern.ResultsBaseline patient characteristics and lesion and procedural characteristics data were similar between the 2 groups. In total, 11,422 struts were analyzed. High signal neointima was observed in 90.2 ± 13.9%, low signal neointima in 7.3 ± 10.0%, and layered neointima in 2.7 ± 5.8%/stents. There was higher incidence of low signal neointima (10.5 ± 10.3% vs. 4.5 ± 5.6%, p = 0.003), neointimal thickness was larger (median: 106.8 μm, interquartile range: 79.3 to 130.4 μm vs. median: 83.5 μm, interquartile range: 62.3 to 89.3 μm; p < 0.0001), and neointimal coverage of stent struts was higher (92.1 ± 6.2% vs. 87.2 ± 11.9%; p = 0.03) in DM patients.ConclusionsHigh signal neointimal pattern was predominantly observed, and low or layered signal pattern was observed in some cases. In DM patients, low signal neointima was observed with high frequency. Neointimal coverage and neointimal thickness was also higher in DM patients as compared with non-DM patients

Improvement in accuracy of multiple sequence alignment using novel group-to-group sequence alignment algorithm with piecewise linear gap cost

BACKGROUND: Multiple sequence alignment (MSA) is a useful tool in bioinformatics. Although many MSA algorithms have been developed, there is still room for improvement in accuracy and speed. In the alignment of a family of protein sequences, global MSA algorithms perform better than local ones in many cases, while local ones perform better than global ones when some sequences have long insertions or deletions (indels) relative to others. Many recent leading MSA algorithms have incorporated pairwise alignment information obtained from a mixture of sources into their scoring system to improve accuracy of alignment containing long indels. RESULTS: We propose a novel group-to-group sequence alignment algorithm that uses a piecewise linear gap cost. We developed a program called PRIME, which employs our proposed algorithm to optimize the well-defined sum-of-pairs score. PRIME stands for Profile-based Randomized Iteration MEthod. We evaluated PRIME and some recent MSA programs using BAliBASE version 3.0 and PREFAB version 4.0 benchmarks. The results of benchmark tests showed that PRIME can construct accurate alignments comparable to the most accurate programs currently available, including L-INS-i of MAFFT, ProbCons, and T-Coffee. CONCLUSION: PRIME enables users to construct accurate alignments without having to employ pairwise alignment information. PRIME is available at