Impact of enzyme activity assay on indication in liver transplantation for ornithine transcarbamylase deficiency

There are no objective and concrete guidelines for the management of Ornithine transcarbamylase deficiency (OTCD). Based on previous findings, we hypothesized that patients with OTCD have a low Ornithine transcarbamylase (OTC) activity in the liver, and therefore it would be better to determine the appropriate indications and optimal timing for liver transplantation (LT) based on the OTC activity. However, few data have so far been accumulated on the OTC activity in cases that are indicated for LT. The purpose of the present study was to clarify the OTC activity in cases that were indicated for LT. This study involved thirteen children with OTCD (8 males and 5 females) who underwent LT, and two females with OTCD who did not require LT. The OTC activity of the neonatal onset type ranged from 0% to 7.2%, while that of the late onset type who underwent LT ranged from 4.4% to 18.7%. The OTC activity of the late onset type which did not require LT was 33-38% based on a preoperative needle liver biopsy. Some late onset patients that underwent LT, showed an activity that was as low as that observed in the neonatal onset cases. This is the first report to show the results of measuring the OTC activity for serial OTCD cases indicated for LT. OTC activity might be an indicator to determine the indications for and the timing of LT in the late onset type, however, further investigations are necessary.     

Increased primary motor cortical excitability by a single-pulse transcranial magnetic stimulation over the supplementary motor area

The supplementary motor area (SMA) is a secondary motor area that is involved in various complex hand movements. In animal studies, short latency and probably direct excitatory inputs from SMA to the primary motor cortex (M1) have been established. Although human imaging studies revealed functional connectivity between SMA and M1, its electrophysiological nature has been less studied. This study explored the connection between SMA and M1 in humans using a single-pulse transcranial magnetic stimulation (TMS) over SMA. First, TMS over SMA did not alter the corticospinal tract excitability measured by the size of motor evoked potential elicited by single-pulse TMS over M1. Next, we measured short-interval intracortical facilitation (SICF), which reflects the function of a facilitatory circuit within M1, with or without a single-pulse TMS over SMA. When the intensity of the second pulse in the SICF paradigm (S2) was as weak as 1.0 active motor threshold for a hand muscle, SMA stimulation significantly enhanced the SICF. Furthermore, this enhancement by SMA stimulation was spatially confined and had a limited time window. On the other hand, SMA stimulation did not alter short-interval intracortical inhibition or contralateral silent period duration, which reflects the function of an inhibitory circuit mediated by gamma-aminobutyric acid A (GABA_A) or GABA_B receptors, respectively. We conclude that a single-pulse TMS over SMA modulates a facilitatory circuit within M1.     

Overexpression of MCM2 in myelodysplastic syndromes: association with bone marrow cell apoptosis and peripheral cytopenia

Myelodysplastic syndromes (MDS) are characterized by proliferation and apoptosis of bone marrow cells. Minichromosome maintenance protein (MCM) 2, which is known to be essential for regulating DNA replication, has proven to have a pro-apoptotic effect in our recent study. Thus, to determine the role of MCM2 in MDS, real-time PCR, immunohistochemistry and in vitro analysis were performed. Our results showed higher MCM2 expression in MDS than in control and AML. Notably, there was no correlation between MCM2 and Ki67-labeling indices (LIs) in MDS, while MCM2 LIs were significantly correlated with cleaved caspase 3 LIs in MDS. In vitro analysis revealed that MCM2 overexpression induced apoptosis in HL60 cells. Furthermore, MDS bone marrow exhibited higher ratio of MCM2 and cleaved caspase 3 double-positive cells and the ratio was correlated with the degree of leukocytopenia. These results suggest that the up-regulated expression of MCM2 is associated with frequent apoptosis in MDS and may have an important role in the pathogenesis of MDS.     

Laparoscopic-assisted tension-free vaginal mesh: an innovative approach to placing synthetic mesh: transvaginally for surgical correction of pelvic organ prolapse

Polypropylene mesh implants for the correction of pelvic organ prolapse (POP) are now available in Japan. We developed an innovative approach for correcting POP by placing polypropylene mesh transvaginally with laparoscopic assistance. From June 2007 through March 2010, sixteen consecutive patients with symptomatic stage 2 or 3 pelvic organ prolapse underwent the laparoscopic-assisted tension-free vaginal mesh procedure at Okayama University Hospital. All patients were evaluated before and at 1, 3, 6, and 12 months after surgery. Female sexual function was also evaluated with the Female Sexual Function Index (FSFI). The procedure was performed successfully without significant complications. Fifteen of 16 patients were considered anatomically cured (93.8%) at 12 months postoperatively. One patient with a recurrent stage 3 vaginal vault prolapse required sacral colpopexy six months postoperatively. Total FSFI scores improved significantly from 10.3 ± 1.3 at baseline to 18.0 ± 1.2 at 12 months after surgery. The laparoscopic-assisted trans-vaginal mesh is a safe, effective, and simple procedure for POP repairs. The procedure not only restores anatomic relationships but also improves sexual function.     

Antimicrobial-susceptible patterns of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> isolated from surgical infections: a new approach

Our goal was to analyze minimum inhibitory concentration (MIC) data for Staphylococcus aureus isolated from surgical infections (SIs) and to look for correlations among the clinically available antimicrobials that were tested. Clinical isolates from SIs were collected by a multicenter surveillance group involving 34 institutions in Japan. During the period April 1998 to March 2007, 312 strains of S. aureus [71 methicillin susceptible (MSSA) and 241 methicillin resistant (MRSA)] were consecutively obtained from these institutions. MIC data for 18 clinically available antimicrobial agents [ABPC, CEZ, CTM, CMX, CPR, FMOX, CFPM, CZOP, IPM, MEMP, GM, ABK, MINO, CLDM, FOM, LVFX, VCM, and TEIC (abbreviations defined in Tables 2 and 3)] against these isolates was analyzed using a principal component analysis (PCA). PCA revealed that four principal components explained 71.1% of the total variance. The first component consisted of major contributions from MEPM and IPM. The second component consisted of major contributions from MINO. These two-first axes, which were strong and explained 54.2% of the total variance, were able to classify the clinical isolates into four clusters. Furthermore, the proportion of the four clusters provided the characteristics of the S. aureus that were clinically isolated at each institute. PCA is a clinically applicable method for analyzing MIC patterns. Such analyses might contribute to the establishment of a practical classification of antimicrobial agents and to the identification of the characteristic antimicrobial resistance patterns at each institute.