Surgical treatment of liver injury with microwave tissue coagulation: an experimental study

OBJECTIVE: The purpose of this study was to examine whether microwave tissue coagulation (MTC) therapy is capable of stopping bleeding from severe liver injury in pigs. METHODS: Ten pigs (38 +/- 4 kg) underwent a 30-mL/kg isovolemic exchange transfusion with 3% low-molecular-weight dextran to produce dilutional coagulopathy, and then a through-and-through laceration injury measuring approximately 8 cm in length was induced in the right hepatic lobe. Immediately after inflicting the injury, the animals were randomly divided into two groups: Group A (n = 5, MTC was repeated along the liver laceration at intervals of 2.0 cm with manual compression) or Group B (n = 5, the injured lobe was manually compressed without MTC therapy for 1 minute). All animals received lactated Ringer's solution to maintain the mean arterial pressure at 75 mm Hg for 1 hour after the abdominal closure. The intraperitoneal blood loss, mean arterial pressure, volume of lactated Ringer's solution, and hematologic variables were compared between the groups. For further laboratory evaluation, three additional experimental animals were treated with the MTC therapy after inflicting the injury and then were allowed to survive for 14 days. RESULTS: Mean arterial pressure declined from a mean value of 88 +/- 10 mm Hg (range, 75-107 mm Hg) to 62 +/- 3 mm Hg (range, 50-75 mm Hg) after the induction of liver injury. The total blood loss in Group A was 192 +/- 58 g (range, 120-250 g), which was lower (p < 0.01) than that of 448 +/- 138 g (range, 260-650 g) in Group B. The resuscitation fluid volume of Group A animals was 304 +/- 204 mL (range, 100-600 mL), which was smaller (p < 0.01) than that of 1,320 +/- 654 mL (range, 900-2,250 mL) in Group B. At 14 days, all three animals that were treated in the additional study were found to be in good health. Their necropsies showed no evidence of an intrahepatic abscess, hematoma, or biloma. CONCLUSION: MTC therapy was thus found to provide simple, rapid, and definitive hemorrhage control in cases of severe liver injury without the need for reoperation.     

Glomerular calcification induced by bolus injection with dibasic sodium phosphate solution in Sprague-Dawley rats

To elucidate the nephrotoxicity of phosphate, dibasic sodium phosphate solution was given to Sprague-Dawley rats by daily bolus intravenous administration at concentrations of 0, 1, 25, 250, or 360 mM (0, 1, 28, 284, or 408 mg/kg Na2HPO4) for 14 days, and the kidneys were pathologically examined. There were no remarkable changes in blood chemistry values; however, urinalysis revealed mild to moderate proteinuria in the 250 and 360 mM groups. The kidneys from the 360 mM group were macroscopically pale. Histopathology revealed panglomerular deposition of basophilic dense granules, which were positive for von Kossa's staining, accompanied by dose-dependent degeneration of the glomerular epithelium and parietal epithelium in the 250 and 360 mM groups. Electron microscopic examination showed fusion of podocytes and increased microvilli, with large amounts of debris in the Bowman's space. Low-density lamellar structures were present not only in the glomerular epithelium, basement membrane, mesangial matrix and parietal epithelium but also within the Bowman's space depending on the severity of the glomerular lesion. Phosphorus and calcium were detected by X-ray microanalysis as fine particles admixed with lamellar structures. These results suggest that high-dose phosphate used in this study transiently overloads the glomerular epithelium during filtration through glomerular capillaries and produces insoluble calcium salt and glomerular lesions, resulting in proteinuria.     

Sensitive thyroid-stimulating antibody assay with high concentrations of polyethylene glycol for the diagnosis of Graves' disease

The aim of the present study was to determine the usefulness of a newly developed thyroid-stimulating antibody (TSAb) assay. We developed a highly sensitive TSAb (sTSAb) assay with 22.5% polyethylene glycol-precipitated crude IgG. The thyroid-stimulating hormone (TSH) receptor antibody (TRAb) causes Graves' disease and TRAb has been measured as TSH-binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb). The TSAb stimulates the thyroid glands and causes hyperthyroidism. In addition to investigating the usefulness of the newly developed sTSAb assay, we also investigated the frequencies of positive TRAb in thyrotoxic patients with subacute thyroiditis, painless thyroiditis or a solitary toxic nodule. We studied 700 untreated Graves' patients with hyperthyroidism and 923 normal controls. We also studied thyrotoxic patients with subacute thyroiditis, painless thyroiditis or a solitary toxic nodule. Conventional TSAb (cTSAb) and sTSAb were measured as TSAb, whereas porcine TBII (pTBII) and human recombinant TBII (hTBII) were measured as TBII. Levels of cTSAb and sTSAb were determined in 923 normal controls and 629 untreated Graves' patients and cTSAb and sTSAb were found to be normally distributed in normal controls, but not in untreated Graves' patients. Receiver operating characteristic (ROC) curve analysis demonstrated that cTSAb and sTSAb had high sensitivity and specificity for Graves' disease. Of the patients investigated, 96.5% of untreated Graves' patients were positive for sTSAb and/or pTBII. Some untreated Graves' patients who were negative for cTSAb were positive for sTSAb. Paired determinations of cTSAb and sTSAb were performed in 146 untreated Graves' patients. A positive correlation was found between cTSAb and sTSAb. Titres of sTSAb were higher than those of cTSAb and sTSAb had high sensitivity. Of the 35 untreated Graves' hyperthyroid patients who were negative for cTSAb, 18 (51%) were positive for sTSAb. Of the 36 untreated Graves' patients who were negative for hTBII, nine (25%) were positive for sTSAb. Some untreated Graves' patients who were negative for cTSAb were positive for sTSAb and some who were negative for hTBII and pTBII were positive for sTSAb. 5. Some thyrotoxic patients with subacute thyroiditis or painless thyroiditis were positive for TRAb. However, the frequency of TRAb-positive patients was low in this group. None of the patients with a solitary toxic nodule was positive for TRAb. In conclusion, sTSAb had higher sensitivity than cTSAb. Graves' patients who were cTSAb negative and hTBII negative could be sTSAb positive. The sTSAb indicates TSAb activity, but pTBII and hTBII do not necessarily do so. We recommended that the sTSAb is used in Graves' patients.     

Transposition of the anterior superior oblique insertion as a treatment for excyclotorsion induced from limited macular translocation

PURPOSE: To evaluate the transposition of the anterior superior oblique insertion as a treatment for cyclovertical diplopia accompanied by an awareness of tilted image perceived with the affected eye induced from limited macular translocation (LMT). DESIGN: Observational case series. METHODS: Transposition of the anterior part of the superior oblique tendon combined with or without vertical muscle surgery on the affected eye was retrospectively studied in seven patients. Clinical outcome was assessed for binocular and monocular vision. A successful result was defined as restoration of single binocular vision (SBV) at distance and near examined with the Bagolini test with disappearance of a tilted image perceived in the affected eye. RESULTS: Six of seven patients (86%) became unaware of tilted image, and three patients (43%) obtained successful results after the strabismus surgery. Of these three patients with successful results, one (33%) patient recognized metamorphopsia, whereas two (67%) of the three patients with unfavorable results reported metamorphopsia. Patients with successful results showed a visual acuity of 20/25 or better in the affected eye and a significantly smaller difference in visual acuity between the two eyes than those patients with unfavorable surgical results (0.133 logarithm of the minimal angle of resolution for SBV(+) vs 0.675 logarithm of the minimal angle of resolution for SBV(-); P =.0255). CONCLUSIONS: The relatively low success for restoration of SBV indicates that strabismus surgery is recommended for patients whose difference in visual acuity between the two eyes is small and who have a high level visual acuity of the affected eye.     

Improved generation of HLA class I/peptide tetramers

As a tetrameric major histocompatibility complex (MHC) class I-peptide complex (tetramer) is capable of detecting antigen-specific cytotoxic T lymphocyte (CTL) by flow cytometry, significant information about the generation of in vivo immunity can be obtained. It is, however, difficult to make a soluble wild type of MHC class I heavy chain by the prokaryotic expression system. Therefore, we developed a new method for making soluble mutant HLA-A*2402 heavy chain. In this method, signal sequences were deleted, and the codon was changed to silent mutated nucleotide sequences that bacteria could use as preferable codon. When purified mutant HLA-A*2402 molecules were examined for the protein generation by SDS-polyacrylamide gel electrophoresis (PAGE) and western blotting using anti-HLA class I monoclonal antibody (mAb) as compared with wild type, a large amount of mutant heavy chain could be detected. In contrast, the expression of wild-type stable HLA-A*2402 heavy chain molecule was not detected in this system. Consequently, by using mutant HLA-A*2402/peptide tetramers, CTL precursors (CTLp) that specifically recognize antigenic peptide derived from the X;18 chromosomal translocations of synovial sarcoma were detected in patients' PBL.     

Elimination kinetics of quinaprilat and perindoprilat in hypertensive patients with renal failure on haemodialysis

Objective of the present study was to investigate the elimination kinetics of quinaprilat and perindoprilat, the active metabolites of angiotensin-converting enzyme (ACE) inhibitors quinapril and perindopril, in hypertensive patients with renal failure under haemodialysis to evaluate the appropriate duration of off-dose of these drugs before starting of low-density lipoprotein (LDL) apheresis. The informed consent was received from 12 hypertensive patients with renal failure, who were under haemodialysis (42 to 62 years). The patients received oral administration of quinapril (10 mg) or perindopril (2 mg) once a day for four weeks. First, to evaluate the dialyzability of each metabolite, blood samples were collected before and after haemodialysis one week after the repeated doses. Second, to evaluate the elimination kinetics of quinaprilat or perindoprilat, blood samples were collected at 24, 72, 120, 192 and 240 h after the final administration. Plasma concentrations of quinaprilat and perindoprilat were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay, respectively. Pharmacokinetic parameters were determined by a model-dependent method. Values of haemodialysis clearance (CL(HD)) and extraction ratio (ER) were 51.5+/-30.2 ml/min and 0.35+/-0.21 for quinaprilat and 108.1+/-5.9 ml/min and 0.75+/-0.04 for perindoprilat, respectively. The terminal elimination half-lives of quinaprilat and perindoprilat were 60.7+/-2.1 and 79.9+/-14.0 h, respectively. The dialyzability of perindoprilat was much higher than that of quinaprilat probably due to low protein binding potency. The present study suggests that hypertensive patients receiving chronic therapy with quinapril or perindopril on haemodialysis should be withdrawn for at least 2 to 3 weeks before LDL apheresis.