Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.

AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. RESULTS: The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.     

Fecoflowmetric Analysis of Anorectal Motor Function in Postoperative Anal-Preserving Surgery Patients With Low Rectal Cancer Comparison With the Wexner Score and Anorectal Manometry

The aim of this study was to elucidate whether fecoflowmetry (FFM) could evaluate more detailed evacuative function than anorectal manometry by comparing between FFM or anorectal manometric findings and the clinical questionnaires and the types of surgical procedure in the patients who received anal-preserving surgery. Fifty-three patients who underwent anal-preserving surgery for low rectal cancer were enrolled. The relationships between FFM or the manometric findings and the clinical questionnaires and the types of procedure of anal-preserving surgery were evaluated. There were significant differences between FFM markers and the clinical questionnaire and the types of the surgical procedure, whereas no significant relationship was observed between the manometric findings and the clinical questionnaire and the types of the surgical procedure. FFM might be feasible and useful for the objective assessment of evacuative function and may be superior to manometry for patients undergoing anal-preserving surgery.Key words: Anorectal manometry, Anal-preserving surgery, Fecoflowmetry, Incontinence, Rectal cancerSphincter preservation has been one of the key issues of rectal cancer surgery. Low anterior resection (LAR)¹ and internal and external sphincter resection (ISR and ESR) are anal-preserving surgeries.^2,3 The aim of these procedures is to restore the normal process of defecation, along with its function, and to improve the quality of life of patients by avoiding permanent colostomy. However, anal-preserving surgery is often associated with evacuative dysfunction and various degrees of incontinence.^4–7Most studies that have assessed the evacuation function have used clinical questionnaires, which are subjective and may vary according to the patient perception.⁷ There are many factors that can affect the evacuative function, such as the stool consistency, rectal capacity, anal sphincters, pelvic floor muscles, and intra-abdominal pressure. Although manometry with or without the clinical score has also commonly been used, fecoflowmetry (FFM) has been reported to be more accurate and useful for assessing the postoperative anorectal motor function.^8–13 FFM was first introduced by Shafik and is a dynamic method for examining the anorectal motor activity that simulates the natural act of defecation.¹⁴ Some studies have shown its usefulness in postoperative patients with anorectal disease,^8–11 but only a few studies have been performed to examine the evacuative function following anal-preserving surgery.^12,13 The aim of this study was to evaluate the evacuative function in the postoperative period following anal-preserving surgery in patients with low rectal cancer using FFM, and to compare the results with the Wexner score and anorectal manometry.¹⁵     

Steroidogenic acute regulatory protein (StAR) retains activity in the absence of its mitochondrial import sequence: Implications for the mechanism of StAR action

Steroidogenic acute regulatory protein (StAR) plays a critical role in steroid hormone biosynthesis, presumably by facilitating the delivery of cholesterol to P450scc in the inner mitochondrial membranes. StAR is synthesized as a 37-kDa preprotein that is processed to a 30-kDa mature form by cleavage of an N-terminal mitochondrial import sequence. To identify structural features required for StAR biological activity, we mutated the human StAR cDNA, including the deletion of N- and C-terminal sequences, and examined the ability of the mutants to promote steroidogenesis and enter the mitochondria of transfected COS-1 cells. Deletion of up to 62 residues from the N terminus (N-62) did not significantly affect steroidogenesis-enhancing activity. The N-terminal deletion mutants were associated with mitochondria-enriched fractions, but import and processing were progressively impaired with increasing length of the deletion. Immunogold electron microscopy and in vitro import assays showed that the active N-62 mutant was not imported into the mitochondria. Removal of the 28 C-terminal amino acids (C-28) inactivated StAR. Deletion of the C-terminal 10 amino acids (C-10) reduced steroidogenic activity by 53%, while truncation of the last 4 amino acids had no effect. The C-28 mutant StAR was not efficiently imported into mitochondria or processed, whereas some of the C-10 mutant was processed, indicating that import had occurred. We conclude that in the COS-1 cell system used, StAR does not need to enter into mitochondria to stimulate steroidogenesis and that residues in the C terminus are essential for steroidogenesis-enhancing activity. These findings imply that StAR acts via C-terminal domains on the outside of the mitochondria.     

Identification of a Novel NDM Variant,NDM-13, from a Multidrug-Resistant Escherichia coli Clinical Isolate in Nepal

A novel New Delhi metallo-β-lactamase, NDM-13, was identified in a carbapenem-resistant Escherichia coli clinical isolate obtained from the urine of a patient in Nepal. The enzymatic activity of NDM-13 against β-lactams was similar to that of NDM-1. However, NDM-13 displayed significantly higher k_cat/K_m ratios for cefotaxime. The genetic environment of bla_NDM-13 was determined to be tnpA-IS30-bla_NDM-13-ble_MBL-trpF-dsbC-cutA-groES-groL, with bla_NDM-13 located within the chromosome.     

Therapeutic Potential of Monteplase in Acute Myocardial Infarction as a Powerful Thrombolytic Agent for Pretreatment of Coronary Intervention

Thrombolysis with conventional thrombolytic agents followed by percutaneous coronary intervention (PCI) had no impact on the treatment of acute myocardial infarction (AMI). However, the development of mutant type plasminogen activator (mt‐PA) has prompted us to reassess the combination of thrombolysis and PCI. Monteplase (Eisai, Co. Ltd., Tokyo, Japan) is a newly developed mt‐PA that can be administrated as a single intravenous bolus injection. We initiated a clinical trial [Combining Monteplase with Angioplasty (COMA)] to evaluate the effectiveness of monteplase followed by PCI. The AMI patients were randomly assigned to receive PCI following pretreatment with a single bolus intravenous injection of monteplase or direct PCI without monteplase. The initial coronary angiography prior to PCI showed that 36.2% of patients in the monteplase group achieved Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct‐related artery, compared with in only 7.9% of patients in the direct PCI group (P < 0.0001). During 24 months following PCI, major cardiac events occurred in 27.7% of patients in the monteplase + PCI group, and in 46.7% of patients in the direct PCI group without monteplase (P < 0.05). Thus, the ideal strategy for the treatment of AMI is the administration of monteplase upon arrival at a community hospital with a prompt transfer to a tertiary center for PCI.     

Brief episode of myocardial ischemia before prolonged ischemia attenuates cardiac sympathetic nerve injury.

BACKGROUND: The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. METHODS AND RESULTS: Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1 +/- 4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05) compared with rats without the pretreatment. CONCLUSION: A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.     

Multistage bone-charged distraction osteogenesis for aesthetic reconstruction of an extensive bone deficiency in the mandible

Alveolar and mandibular bone defects impair occlusion and affect the aesthetics of facial contouring, making it difficult to obtain a satisfactory outcome. Treatment with distraction osteogenesis (DO) is particularly difficult in cases in which the defective region extends to close to the inferior margin of the mandible. To overcome the limits of current DO, we developed a method as follows. In the first stage, a submucosal space necessary for bone grafting was prepared by soft tissue expansion through DO. In the second stage, an iliac corticocancellous bone was transplanted with its cancellous side in close contact with the new bone in the space formed on the labial side into this new space. In the third stage, the grafted bone was distracted. This technique requires time, but each surgery is of minimum invasiveness and does not leave a visible scar; use of this technique may expand the limited indication of current DO and dental implants.     

Inhibitory effects of carbon dioxide insufflation on pneumoperitoneum and bowel distension after percutaneous endoscopic gastrostomy

AIM: To evaluate the inhibitory effects of carbon dioxide (CO₂) insufflation on pneumoperitoneum and bowel distension after percutaneous endoscopic gastrostomy (PEG).METHODS: A total of 73 consecutive patients who were undergoing PEG were enrolled in our study. After eliminating 13 patients who fitted our exclusion criteria, 60 patients were randomly assigned to either CO₂ (30 patients) or air insufflation (30 patients) groups. PEG was performed by pull-through technique after three-point fixation of the gastric wall to the abdominal wall using a gastropexy device. Arterial blood gas analysis was performed immediately before and after the procedure. Abdominal X-ray was performed at 10 min and at 24 h after PEG to assess the extent of bowel distension. Abdominal computed tomography was performed at 24 h after the procedure to detect the presence of pneumoperitoneum. The outcomes of PEG for 7 d post-procedure were also investigated.RESULTS: Among 30 patients each for the air and the CO₂ groups, PEG could not be conducted in 2 patients of the CO₂ group, thus they were excluded. Analyses of the remaining 58 patients showed that the patients’ backgrounds were not significantly different between the two groups. The elevation values of arterial partial pressure of CO₂ in the air group and the CO₂ group were 2.67 mmHg and 3.32 mmHg, respectively (P = 0.408). The evaluation of bowel distension on abdominal X ray revealed a significant decrease of small bowel distension in the CO₂ group compared to the air group (P < 0.001) at 10 min and 24 h after PEG, whereas there was no significant difference in large bowel distension between the two groups. Pneumoperitoneum was observed only in the air group but not in the CO₂ group (P = 0.003). There were no obvious differences in the laboratory data and clinical outcomes after PEG between the two groups.CONCLUSION: There was no adverse event associated with CO₂ insufflation. CO₂ insufflation is considered to be safer and more comfortable for PEG patients because of the lower incidence of pneumoperitoneum and less distension of the small bowel.